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March 1, 2024

Is Marijuana Bad for Health? Here’s What We Know So Far

Marijuana’s health impacts—good and bad—are coming into focus

By Jesse Greenspan

Cappi Thompson/Getty Images

With decades of legal and social opprobrium fading fast, marijuana has become an extremely popular commercial product with more than 48 million users across the U.S. Health concerns, once exaggerated, now often seem to be downplayed or overlooked. For example, pregnant patients “often tell me they had no idea there's any risk,” says University of Utah obstetrician Torri Metz, lead author of a recent paper in the Journal of the American Medical Association on cannabis and adverse pregnancy outcomes.

Fortunately, legal reforms are also gradually making it easier to study marijuana's health effects by giving U.S. scientists more access to the drug and a wider population of users to study. Although much research remains in “early stages,” the number of studies has finally been increasing, says Tiffany Sanchez, an environmental health scientist at Columbia University. As new results accumulate, they offer a long-overdue update on what science really knows about the drug.

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In addition to minor side effects that many users joke about—such as short-term memory loss—recent studies have linked marijuana to adverse health outcomes involving the lungs, heart, brain and gonads. For example, heavy marijuana consumption seems to increase the risk of clogged arteries and heart failure , and it may impact male fertility . Smoking weed likewise can lead to chronic bronchitis and other respiratory ailments (although, unlike tobacco, it hasn't been definitively tied to lung cancer). And cannabis plants hyperaccumulate metal pollutants, such as lead, which Sanchez found can enter users' bloodstreams .

Developing adolescent brains, particularly those predisposed to mental illness, may be most at risk from overconsumption. Although psychiatric effects are hotly debated , studies suggest that heavy weed use exacerbates—or may trigger— schizophrenia , psychosis and depression in youths and that it affects behavior and academic performance. “From a safety viewpoint, young people should definitely stay away from it,” says University of Ottawa psychiatrist Marco Solmi, lead author of a recent review of cannabis and health in the British Medical Journal .

24 states have legalized recreational marijuana, with 38 allowing medical use

Moreover, the drug can cross over to fetuses during pregnancy. Several studies have linked it to low birth weights , and researchers suspect it raises the likelihood of neonatal intensive care unit admissions and stillbirths . Some cannabis dispensaries have advertised their products as a cure for morning sickness, but Metz emphasizes that safer alternatives exist.

Of course, many adults use marijuana responsibly for pleasure and relaxation. Unlike with, say, opioids, there's effectively zero risk of life-threatening overdose. Plus, “people get addicted with tobacco way faster,” says Columbia University epidemiologist Silvia Martins, who studies substance use and related laws.

Cannabis, and its derivatives, also may help alleviate pain—although some researchers contend that it performs little better than a placebo . It may also decrease chemotherapy-induced nausea, calm epileptic seizures , ease the symptoms of multiple sclerosis and serve as a sleep aid .

Recent studies have hinted that the drug might slightly reduce opioid dependency rates, although this, too, is disputed . There's some evidence that weed users tend to be more empathetic , and researchers found that elderly mice get a mental boost from the drug. Still, experts caution against self-medicating: “You should ask your doctor,” Solmi says.

Some of the recent research into marijuana is more lighthearted. One study, for instance, found that, just like people, nematode worms dosed with cannabis get the munchies .

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After 50 Years, U.S. Opens The Door To More Cannabis Crops For Scientists

More than 30 states have medical marijuana programs — yet scientists are only allowed to use cannabis plants from one U.S. source for their research. That's set to change, as the federal government begins to add more growers to the mix. Drew Angerer/Getty Images hide caption

More than 30 states have medical marijuana programs — yet scientists are only allowed to use cannabis plants from one U.S. source for their research. That's set to change, as the federal government begins to add more growers to the mix.

After more than 50 years, the federal government is lifting a roadblock to cannabis research that scientists and advocates say has hindered rigorous studies of the plant and possible drug development.

Since 1968, U.S. researchers have been allowed to use cannabis from only one domestic source : a facility based at the University of Mississippi, through a contract with the National Institute on Drug Abuse (NIDA).

That changed earlier this month, when the Drug Enforcement Administration announced it's in the process of registering several additional American companies to produce cannabis for medical and scientific purposes.

It's a move that promises to accelerate understanding of the plant's health effects and possible therapies for treating conditions — chronic pain, the side effects of chemotherapy, multiple sclerosis and mental illness, among many others — that are yet to be well studied .

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"This is a momentous decision," says Rick Doblin, executive director of the Multidisciplinary Association for Psychedelic Studies (MAPS), which has spearheaded research into other Schedule 1 drugs — the most restrictive class of controlled substance, which the federal government defines as "drugs with no currently accepted medical use."

"This is the last political obstruction of research with Schedule 1 drugs," he says.

About one-third of Americans currently live in a state where recreational marijuana is legal — and more than 30 states have medical marijuana programs . Yet scientists still aren't allowed to simply use the cannabis sold at state-licensed dispensaries for their clinical research because cannabis remains illegal under federal law.

Medical Marijuana's 'Catch-22': Limits On Research Hinder Patient Relief

"It is a big disconnect," says Dr. Igor Grant , a psychiatry professor and director of the Center for Medicinal Cannabis Research at University of California, San Diego.

The new DEA decision doesn't resolve the conflict between federal and state laws, but it does offer researchers a new, federally sanctioned pipeline for more products and strains of cannabis.

"We'll see a decade or more of explosive cannabis research and potential new therapies," says Dr. Steve Groff, founder and chairman of Groff North America , one of three companies that has publicly announced it has preliminary approval from the federal government to cultivate cannabis for research.

A long-running fight to overturn federal "monopoly"

Despite their efforts, scientists have encountered administrative and legal hurdles to growing pharmaceutical-grade cannabis for decades.

In 2001, Dr. Lyle Craker, a prominent plant biologist, first applied for a license to cultivate marijuana for research — only to encounter years of delay that kicked off a prolonged court battle with the DEA, which has to greenlight research into Schedule 1 drugs like cannabis.

"There's thousands of different cannabis varieties that all have unique chemical profiles and produce unique clinical effects, but we didn't have access to that normal diversity," says Dr. Sue Sisley , a cannabis researcher and president of the Scottsdale Research Institute, which also received preliminary DEA approval to produce cannabis for research.

Only in 2016 did the federal government signal a change in policy that would open the door for new growers, but applications to do so languished for years. Craker and others ended up suing the federal government over the delay.

Psychiatrist Explores Possible Benefits Of Treating PTSD With Ecstasy Or Cannabis

Sisley has long taken issue with the supply of cannabis coming from the NIDA facility in Mississippi — in particular, how it's processed. She used cannabis produced there in her recently published clinical trial on treating PTSD in military veterans.

She describes the product as an "anemic" greenish powder.

"It's very difficult to overcome the placebo effect when you have something that diluted," she says.

The 76-person study, which took 10 years to complete, concluded that smoked cannabis was generally well tolerated and did not lead to deleterious effects in this group. But it also did not find any statistically significant difference in abating the symptoms of PTSD when compared to a placebo.

For Grant of UCSD, the problem with the long-standing supply of cannabis isn't so much the quality, but the lack of different products like edibles and oils and of cannabis strains with varying concentrations of CBD and THC, the plant's main psychoactive ingredient.

"We don't have enough research on the kind of marijuana products that people in the real world are using," he says.

As CBD Oils Become More Popular, The FDA Considers Whether To Set New Rules

Because of the limited domestic supply, some researchers have resorted to importing cannabis from outside the U.S. — a legal but wildly counterintuitive arrangement that is "arduous" and prone to hiccups, says Sisley.

The constraints on research cannabis also has impeded the pathway to drug development because the NIDA facility's cannabis could only be used for academic research, not for prescription drug development . A drug studied in phase 3 clinical trials — what's required before submitting for approval from the Food and Drug Administration — must be the same as what's later marketed.

"The NIDA monopoly has primarily been why we have medical marijuana in the states, but we don't have medical marijuana through the FDA," says Doblin of MAPS. "It's a fundamental change that we can now have drug development with domestic supplies."

A few barriers still remain

The few companies that will soon land DEA spots to cultivate cannabis have an eager marketplace of researchers who are "clamoring" for the chance to study the scientific properties and medical potential of the plant, says Groff, whose company is up for DEA approval and who also has an FDA project to study the antimicrobial properties of cannabis for killing dangerous bacteria like MRSA .

By the end of next year, Groff anticipates his company will be producing up to 5,000 pounds of marijuana per year, offering researchers a "full menu of customizable options."

Biopharmaceutical Research Company — a third company that will soon cultivate cannabis with a DEA license — already has dozens of agreements in place with U.S. researchers and is hearing from more academic institutions, drugmakers and biotech companies in the wake of the change in policy, says CEO George Hodgin.

"Now there's a very clear, approved and legal path for them to legally enter the cannabis space in the United States," says Hodgin.

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'illegal to essential': how the coronavirus is boosting the legal cannabis industry.

Washington State University's Center for Cannabis Policy, Research and Outreach is one of the places that expects to eventually procure cannabis from Hodgin's business.

"It's definitely a big step in the right direction because the industry is moving much faster than we are in research," says Michael McDonell , an associate professor of medicine and director of the university's cannabis center.

But he also points out that even with more growers coming online, it's still by no means easy to study cannabis, because researchers need a special license when working with a Schedule 1 drug and grants to conduct these studies are hard to come by.

Despite the widespread use of marijuana in the U.S., research into the medical potential of other Schedule 1 drugs like MDMA (ecstasy) is much further along than cannabis .

UCSD's Grant says the biggest leap forward for research would come from moving cannabis out of the Schedule 1 drug classification. "If that were to happen," he says, "that would solve a lot of these problems that we've been talking about."

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FDA and Cannabis: Research and Drug Approval Process

On this page:, fda supports sound scientific research.

• Cannabis Study Drugs Controlled Under Schedule I of the CSA
• Cannabis Study Drugs Containing Hemp

Additional Resources

The FDA understands that there is increasing interest in the potential utility of cannabis for a variety of medical conditions, as well as research on the potential adverse health effects from use of cannabis.

To date, the FDA has not approved a marketing application for cannabis for the treatment of any disease or condition. The agency has, however, approved one cannabis-derived drug product: Epidiolex (cannabidiol), and three synthetic cannabis-related drug products: Marinol (dronabinol), Syndros (dronabinol), and Cesamet (nabilone). These approved drug products are only available with a prescription from a licensed healthcare provider. Importantly, the FDA has not approved any other cannabis, cannabis-derived, or cannabidiol (CBD) products currently available on the market.

• Cannabis sativa L. is a plant that contains over 80 different naturally occurring compounds called “cannabinoids”
• Cannabidiol (CBD)
• Tetrahydrocannabinol (THC)
• Plants are grown to produce varying concentrations of cannabinoids – THC or CBD
• These plant variations are called cultivars

Cannabis-derived compounds

• Compounds occurring naturally in the plant – like CBD and THC
• These compounds are extracted directly from the plant
• Can be used to manufacture drug products
• Example: highly-purified CBD extracted from the plant

Cannabis-related compounds

• These synthetic compounds are created in a laboratory
• Can be used to manufacture drug products 
• Some synthetic compounds may also occur naturally in the plant and some may not
• Examples: synthetically-derived dronabinol (also naturally occurring) and nabilone (not naturally occurring) 

FDA has approved Epidiolex, which contains a purified form of the drug substance cannabidiol (CBD) for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older. That means FDA has concluded that this particular drug product is safe and effective for its intended use.

The agency also has approved Marinol and Syndros for therapeutic uses in the United States, including for nausea associated with cancer chemotherapy and for the treatment of anorexia associated with weight loss in AIDS patients. Marinol and Syndros include the active ingredient dronabinol, a synthetic delta-9- tetrahydrocannabinol (THC) which is considered the psychoactive intoxicating component of cannabis (i.e., the component responsible for the “high” people may experience from using cannabis). Another FDA-approved drug, Cesamet, contains the active ingredient nabilone, which has a chemical structure similar to THC and is synthetically derived. Cesamet, like dronabinol-containing products, is indicated for nausea associated with cancer chemotherapy.

FDA is aware that unapproved cannabis and/or unapproved cannabis-derived products are being used to treat a number of medical conditions including, AIDS wasting, epilepsy, neuropathic pain, spasticity associated with multiple sclerosis, and cancer and chemotherapy-induced nausea. Caregivers and patients can be confident that FDA-approved drugs have been carefully evaluated for safety, efficacy, and quality, and are monitored by the FDA once they are on the market. However, the use of unapproved cannabis and cannabis-derived products can have unpredictable and unintended consequences, including serious safety risks. Also, there has been no FDA review of data from rigorous clinical trials to support that these unapproved products are safe and efficacious for the various therapeutic uses for which they are being used.

FDA understands the need to develop therapies for patients with unmet medical needs, and does everything it can to facilitate this process. FDA has programs such as Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review that are designed to facilitate the development of and expedite the approval of drug products. In addition, the FDA’s expanded access (sometimes called “compassionate use”) statutory and regulatory provisions are designed to facilitate the availability of investigational products to patients with serious diseases or conditions when there is no comparable or satisfactory alternative therapy available, either because the patients have exhausted treatment with or are intolerant of approved therapies, or when the patients are not eligible for an ongoing clinical trial. Through these programs and the drug approval process, FDA supports sound, scientifically-based research into the medicinal uses of drug products containing cannabis or cannabis-derived compounds and will continue to work with companies interested in bringing safe, effective, and quality products to market.

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The FDA has an important role to play in supporting scientific research into the medical uses of cannabis and its constituents in scientifically valid investigations as part of the agency’s drug review and approval process. As a part of this role, the FDA supports those in the medical research community who intend to study cannabis by:

• Providing information on the process needed to conduct clinical research using cannabis.
• Providing information on the specific requirements needed to develop a human drug that is derived from a plant such as cannabis. In December 2016, the FDA updated its Guidance for Industry: Botanical Drug Development , which provides sponsors with guidance on submitting investigational new drug (IND) applications for botanical drug products. The FDA also has issued “ Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research, Draft Guidance for Industry .”
• Providing specific support for investigators interested in conducting clinical research using cannabis and its constituents as a part of the IND or investigational new animal drug (INAD) process through meetings and regular interactions throughout the drug development process.
• Providing general support to investigators to help them understand and follow the procedures to conduct clinical research through the FDA Center for Drug Evaluation and Research (CDER) Small Business and Industry Assistance group .

To conduct clinical research that can lead to an approved new drug, including research using materials from plants such as cannabis, researchers need to work with the FDA and submit an IND application to CDER. The IND application process gives researchers a path to follow that includes regular interactions with the FDA to support efficient drug development while protecting the patients who are enrolled in the trials. An IND includes protocols describing proposed studies, the qualifications of the investigators who will conduct the clinical studies, and assurances of informed consent and protection of the rights, safety, and welfare of the human subjects. The FDA reviews the IND to ensure that the proposed studies, generally referred to as “clinical trials,” do not place human subjects at an unreasonable risk of harm. The FDA also requires obtaining the informed consent of trial subjects and human subject protection in the conduct of the clinical trials. For research intending to develop an animal drug product, researchers would establish an INAD file with the Center for Veterinary Medicine (CVM) to conduct their research, rather than an IND with CDER.

FDA is committed to encouraging the development of cannabis-related drug products, including CBD. Those interested in cannabis-derived and cannabis-related drug development are encouraged to contact the relevant CDER review division and CDER’s Botanical Review Team (BRT) to answer questions related to their specific drug development program. The BRT serves as an expert resource on botanical issues and has developed the Botanical Drug Development Guidance for Industry to assist those pursuing drug development in this area. FDA encourages researchers to request a Pre-Investigational New Drug application (PIND) meeting to discuss questions related to the development of a specific cannabis-derived and cannabis-related drug product.

Please note that certain cultivars and parts of the Cannabis sativa L. plant are controlled under the Controlled Substances Act (CSA) since 1970 under the drug class "Marihuana" (commonly referred to as "marijuana") [21 U.S.C. 802(16)]. "Marihuana" is listed in Schedule I of the CSA due to its high potential for abuse, which is attributable in large part to the psychoactive intoxicating effects of THC, and the absence of a currently accepted medical use in the United States. From 1970 until December of 2018, the definition of “marihuana” included all types of Cannabis Sativa L. , regardless of THC content.  However, in December 2018, the Agriculture Improvement Act of 2018 (also known as the Farm Bill) removed hemp, a type of cannabis that is very low in THC (cannabis or cannabis derivatives containing no more than 0.3% THC on a dry weight basis), from controls under the CSA. This change in the law may result in a more streamlined process for researchers to study cannabis and its derivatives, including CBD, that fall under the definition of hemp, a result which could speed the development of new drugs containing hemp. 

Conducting clinical research using cannabis-derived substances that are considered controlled substances under the CSA often involves interactions with several federal agencies. For example:

• Protocols to conduct research with controlled substances listed in Schedule I are required to be conducted under a site-specific DEA investigator registration. For more information, see 21 CFR 1301.18 .
• National Institute on Drug Abuse (NIDA) Drug Supply Program provides research-grade marijuana for scientific study. Through registration issued by DEA, NIDA is responsible for overseeing the cultivation of marijuana for medical research and has contracted with the University of Mississippi to grow marijuana for research at a secure facility. Marijuana of varying potencies and compositions along with marijuana-derived compounds are available. DEA also may allow additional growers to register with the DEA to produce and distribute marijuana for research purposes. DEA that, as the result of a recent amendment to federal law, certain forms of cannabis no longer require DEA registration to grow or manufacture.
• Researchers work with the FDA and submit an IND or INAD application to the appropriate CDER divisions or other center offices depending on the therapeutic indication or population. If the research is intended to support the approval of an animal drug product, an INAD file should be established with CVM. Based on the results obtained in studies conducted at the IND or INAD stage, sponsors may submit a marketing application for formal approval of the drug.

Cannabis Study Drugs Controlled Under Schedule I of the CSA (greater than 0.3% THC on a dry weight basis)

Sponsor obtains pre-IND number through CDER review division to request a pre-IND meeting. For new animal drug research, a sponsor may engage with CVM to establish an INAD file. A pre-IND meeting with CDER is optional, and an opportunity to obtain FDA guidance on sponsor research plans and required content for an IND submission .

The sponsor contacts NIDA or another DEA-registered source of cannabis and/or cannabis-derived substances to obtain information on the specific cultivars available, so that all necessary chemistry, manufacturing, and controls (CMC) and botanical raw material (BRM) information can be included in the IND. Importation of products controlled under the CSA are subject to DEA authorization.

The sponsor may contact DEA to discuss Schedule I drug research plans that may require DEA inspection for an investigator and study site Schedule I license.

Step 4: If the selected BRM or drug substance manufacturer holds a Drug Master File (DMF) , the sponsor must obtain a Letter of Authorization (LOA) to reference CMC and BRM information. Alternatively, an IND submission would need to contain all necessary CMC data characterizing their study drug and ensuring it is safe for use in humans.

The sponsor sends a copy of the IND and clinical protocol, including a LOA (if applicable), to FDA.

FDA reviews the submitted IND. The sponsor must wait 30 calendar days following IND submission before initiating any clinical trials, unless FDA notifies the sponsor that the trials may proceed sooner. During this time, FDA has an opportunity to review the submission for safety to assure that research subjects will not be subjected to unreasonable risk.

If the IND is authorized by FDA as “safe to proceed” the sponsor may then submit their clinical protocol registration application, including referenced IND number, to DEA to obtain the protocol registration. Once this is received, the sponsor contacts NIDA or another DEA-registered source to obtain the cannabis and/or cannabis-derived substances and they can then begin the study.

For nonclinical research, including research conducted under an INAD file submitted established with CVM, there is no requirement of prior authorization of the protocol by FDA before the investigators may proceed with a protocol registration application submitted to DEA. For these nonclinical protocols, investigators may immediately pursue investigator and study site licensure, and protocol registration with DEA, so they may then obtain their Schedule I cannabis-derived study drug from supplier.

Cannabis Study Drugs Containing Hemp (no more than 0.3% THC on a dry weight basis)

Sponsor provides all applicable chemistry, manufacturing, and controls (CMC) and botanical raw material (BRM) information in the IND for review by FDA, including hemp cultivars.

If the selected hemp manufacturer holds a Drug Master File (DMF) , the sponsor must obtain a Letter of Authorization (LOA) to reference CMC and BRM information. Alternatively, an IND submission would need to contain all necessary CMC data characterizing their study drug and ensuring it is safe for use in humans.

FDA’s Role in the Drug Approval Process

The FDA’s role in the regulation of drugs, including cannabis and cannabis-derived products, also includes review of applications to market drugs to determine whether proposed drug products are safe and effective for their intended indications. The FDA’s drug approval process requires that clinical trials be designed and conducted in a way that provides the agency with the necessary scientific data upon which the FDA can make its approval decisions. Without this review, the FDA cannot determine whether a drug product is safe and effective. It also cannot ensure that a drug product meets appropriate quality standards. For certain drugs that have not been approved by the FDA, the lack of FDA approval and oversight means the safety, effectiveness, and quality of the drug – including how potent it is, how pure it is, and whether the labeling is accurate or false – may vary considerably.

• Product-Specific Guidance for Generic Drug Development: Draft Guidance on Cannabidiol Oral Solution (PDF - 42KB)
• Cannabis Clinical Research: Drug Master Files (DMFs) & Quality Considerations Webinar
• Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research, Draft Guidance for Industry
• FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD): Questions and Answers
• Development & Approval Process (Drugs)
• From an Idea to the Marketplace: The Journey of an Animal Drug through the Approval Process
• FDA Center for Drug Evaluation and Research Small Business and Industry Assistance group
• CVM Small Business Assistance
• National Institutes of Health (NIH): Guidance on Procedures for Provision of Marijuana for Medical Research
• National Institute on Drug Abuse's (NIDA) Role in Providing Marijuana for Research
• Drug Enforcement Administration - Registration of Manufacturers, Distributors, and Dispensers of Controlled Substances
• International Narcotics Control Board: Single Convention on Narcotic Drugs (1961)
• National Institute on Drug Abuse (NIDA): Ordering Guidelines for Marijuana and Marijuana Cigarettes

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The 7 most important cannabis research studies of 2023

2023 saw tons of new research come out related to cannabis. Below is a selection of some of the studies that caught my attention, with brief summaries of each. The first two studies are in the realm of public health. After that, three studies on commercial cannabis followed by two basic research studies on the endocannabinoid system.

This year, we saw a nice review of the public health research done over the past few years, finding little evidence that legalization promotes marijuana consumption among teens, together with evidence that does promote lower teen alcohol consumption. There was also interesting research done on the Cannabis plant itself, including non-terpene volatiles that drive its aroma and its susceptibility to Hop Latent Viroid , a devastating infection that’s spreading across North America. There was also interesting basic research, shedding new light on how the endocannabinoid system works.

Here’s a brief summary of a selection of studies from 2023.

The Public Health Effects of Legalizing Marijuana

As of the publication of this paper, 36 states had legalized medical marijuana and 18 had legalized recreational adult-use cannabis. This review paper summarizes studies that have come out to do with public health consequences of legalization. The major outcomes they reviewed the literature on included: youth marijuana use, alcohol consumption, the abuse of prescription opioids, traffic fatalities, and crime.

• “Little credible evidence to suggest that legalization promotes marijuana use among teenagers.”

Topics with a strong level of agreement across studies included:

• “Convincing evidence that young adults consume less alcohol when medical marijuana is legalized.”

For other topics, the authors found a lower level of agreement across studies preventing firm conclusions from being drawn. Those included:

• “For other public health outcomes such as mortality involving prescription opioids, the effect of legalizing medical marijuana has proven more difficult to gauge and, as a consequence, we are less comfortable drawing firm conclusions.”

For more detail on the literature they reviewed, check out the paper itself .

State Cannabis Legalization and Psychosis-Related Health Care Utilization

The question this study sought to address was whether state cannabis legalization was associated with increased rates of psychosis-related health care claims. This cohort study looked at claims data from over 63 million beneficiaries between 2003-2017. They found no statistically significant differences in the rates of psychosis-related diagnoses or prescribed antipsychotics in states with legal medical or adult-use cannabis compared to those without legal cannabis.

Minor, Nonterpenoid Volatile Compounds Drive the Aroma Differences of Exotic Cannabis

Following up on previous work showing that the “skunky” aroma of some strains comes not from terpenes, but from a class of compounds called, “volatile sulfur compounds,” a team from Abstrax dug deeper into the chemistry of cannabis aroma. They found that a variety of nonterpene volatile compounds are the main drivers of many of the “exotic” aromas that give strains various sweet or savory scents. 

To learn more about this particular study, check out this Leafly article and listen to the video lecture by Abstrax chemist Dr. Iain Oswald.

Symptomology, prevalence, and impact of Hop latent viroid on greenhouse-grown cannabis (Cannabis sativa L.) plants in Canada

Hop latent viroid is a virus-like infection that’s been devastating cannabis crops throughout North America. We have previously written about what HLV is and how it affects marijuana growers. This was a key study from 2023 showing what HLV does to Cannabis plants and how prevalent it already is in some locations. Given the enormous impact HLV is already having, expect to hear more about this bug in 2024.

Comparison of the Cannabinoid and Terpene Profiles in Commercial Cannabis from Natural and Artificial Cultivation

Some cannabis is grown indoors, some outdoors. Many consumers have strong opinions on which is better. In this 2023 study , researchers did a head-to-head comparison of two genetically identical cultivars grown indoors vs. outdoors, looking at their cannabinoid and terpene content. Main findings included:

• Significantly higher levels of oxidized and degraded cannabinoids in indoor-grown samples.
• Significantly more “unusual cannabinoids” such as C4- and C6-THCA in outdoor-grown samples.
• Significant differences in terpene profiles for outdoor- vs. indoor-grown samples, with outdoor-grown samples generally showing higher levels of sesquiterpenes like caryophyllene, humulene, etc.

Disruption of tonic endocannabinoid signaling triggers cellular, behavioral and neuroendocrine responses consistent with a stress response

The endocannabinoid system regulates many different systems in the brain and body. As we covered in this article , endocannabinoids play an important role in regulating pain perception, fear, and anxiety. At any given moment, there is a certain level of “endocannabinoid tone” in your brain. As this rodent study showed, endocannabinoid tone “gates” the stress response generated in the hypothalamus of the brain. In general, endocannabinoids restrict activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is the key brain system regulating stress levels. Higher endocannabinoid tone had the effect of lessening stress levels in rodents. 

Cannabinoid CB1 Receptors Are Expressed in a Subset of Dopamine Neurons and Underlie Cannabinoid-Induced Aversion, Hypoactivity, and Anxiolytic Effects in Mice

Endocannabinoid receptors are one of the most abundant proteins in the brain, found in many different brain regions and types of neurons. This is one reason why the effects of THC can be so diverse. Depending on the dose of THC consumed, different neurons and brain regions can be affected to different degrees, generating different effects. In this rodent study , neuroscientists studied the effects of a specific subset of dopamine neurons in the brain which express CB1 receptors. They found that this particular subset of neurons has some of the negative side effects that cannabinoids like THC can induce (especially at high doses), including anxiety. This highlights how specific subsets of neurons in the brain can control specific effects that cannabinoids generate.

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• National Institutes of Health

NIH-Supported Research on Cannabis, Cannabinoids, and Related Compounds

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The National Institutes of Health (NIH) supports a broad portfolio of research on cannabis and cannabis constituents and related compounds, as well as the endocannabinoid system. Specific topics of interest vary among Institutes, Centers, and Offices, but overall the research portfolio includes studies investigating the whole or parts of the Cannabis sativa plant, cannabis extracts or enriched extracts, cannabinoid compounds extracted and derived from cannabis extracts, non-cannabinoid constituents of cannabis, synthetic cannabinoids, and the components of the endocannabinoid system (the signaling pathways in the body activated by cannabinoids).

There is considerable interest in the possible therapeutic uses of cannabis and its constituent compounds. In 2015, NIH developed three reporting categories to describe and account for the research efforts underway to examine the chemical, physiological, and therapeutic properties of cannabinoids and the physiological systems they affect.

View examples of NIH research grants in each of the categories below.

• Cannabinoid Research – This category reports the total NIH investment in all cannabinoid research including basic research, animal and human preclinical studies, and clinical research. Studies examine cannabis use disorder as well as the societal and/or health impacts of changing cannabis laws and policies; all classes of cannabinoids (purified, synthetic, endocannabinoids, or phytocannabinoids); compounds that modify the activity of consumed cannabis (e.g., cannabinoid receptor allosteric modulators); as well as the physiological systems affected by cannabis (e.g., endocannabinoid system) and modulators thereof (e.g., fatty acid amide hydrolase [FAAH] inhibitors). 
• Cannabidiol Research – This subset of the Cannabinoid Research category (above) reports all NIH projects examining basic, preclinical, and therapeutic properties of cannabidiol (CBD).
• Therapeutic Cannabinoid Research – This subset of the Cannabinoid Research category (above) reports all NIH projects examining the therapeutic properties of all classes of cannabinoids (endocannabinoids, phytocannabinoids, and synthetic).

These categories are publicly accessible on the NIH categorical spending website ( NIH RePORTER ) and will be updated annually.

Marijuana and Your Health: What 20 Years of Research Reveals

People who drive under the influence of marijuana double their risk of being in a car crash, and about one in 10 daily marijuana users becomes dependent on the drug, according to a new review.

Marijuana use has become increasingly prevalent over the years, and the review of marijuana studies summarizes what researchers have learned about the drug's effects on human health and general well-being over the past two decades.

In the review, author Wayne Hall, a professor and director of the Center for Youth Substance Abuse Research at the University of Queensland in Australia, examined scientific evidence on marijuana's health effects between 1993 and 2013.

He found that adolescents who use cannabis regularly are about twice as likely as their nonuser peers to drop out of school, as well as experience cognitive impairment and psychoses as adults. Moreover, studies have also linked regular cannabis use in adolescence with the use of other illicit drugs, according to the review, published today (Oct. 6) in the journal Addiction.

Researchers in the studies still debated whether regular marijuana use might actually lead to the use of other drugs, Hall wrote in the study. However, he pointed to longer-term studies and studies of twins in which one used marijuana and the other did not as particularly strong evidence that regular cannabis use may lead to the use of other illicit drugs. [ Marijuana vs. Alcohol: Which Is Worse for Your Health? ]

The risk of a person suffering a fatal overdose from marijuana is "extremely small," and there are no reports of fatal overdoses in the scientific literature, according to the review. However, there have been case reports of deaths from heart problems in seemingly otherwise healthy young men after they smoked marijuana, the report said.

"The perception that cannabis is a safe drug is a mistaken reaction to a past history of exaggeration of its health risks," Hall told Live Science.

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However, he added that marijuana "is not as harmful as other illicit drugs such as amphetamine, cocaine and heroin, with which it is classified under the law in many countries, including the USA."

The risks of using marijuana

Marijuana use carries some of the same risks as alcohol use, such as an increased risk of accidents, dependence and psychosis, he said.

It's likely that middle-age people who smoke marijuana regularly are at an increased risk of experiencing a heart attack , according to the report. However, the drug's "effects on respiratory function and respiratory cancer remain unclear, because most cannabis smokers have smoked or still smoke tobacco," Hall wrote in the review.

Regular cannabis users also double their risk of experiencing psychotic symptoms and disorders such as disordered thinking, hallucinations and delusions — from about seven in 1,000 cases among nonusers to 14 in 1,000 among regular marijuana users, the review said. And, in a study of more than 50,000 young men in Sweden, those who had used marijuana 10 or more times by age 18 were about two times more likely to be diagnosed with schizophrenia within the next 15 years than those who had not used the drug.

Critics argue that other variables besides marijuana use may be at work in the increased risk of mental health problems, and that it's possible that people with mental health problems are more likely to use marijuana to begin with, Hall wrote in the review.

However, other studies have since attempted to sort out the findings, he wrote, citing a 27-year follow-up of the Swedish cohort, in which researchers found "a dose–response relationship between frequency of cannabis use at age 18 and risk of schizophrenia during the whole follow-up period."

In the same study, the investigators estimated that 13 percent of schizophrenia cases diagnosed in the study "could be averted if all cannabis use had been prevented in the cohort," Hall reported.

As for the effects of cannabis use in pregnant women, the drug may slightly reduce the birth weight of the baby, according to the review.

The effects of euphoria that cannabis users seek from the drug come primarily from its psychoactive ingredient, called delta-9-tetrahydrocannabinol, better known as THC , Hall wrote in the review. During the past 30 years, the THC content of marijuana in the United States has jumped from less than 2 percent in 1980 to 8.5 percent in 2006.

The THC content of the drug has also likely increased in other developed countries, Hall wrote in the report.

It is not clear, however, whether increased THC content may have an effect on users' health, the report said. [ The Drug Talk: 7 New Tips for Today's Parents ]

Some argue that there would be no increase in harm, if users adjusted their doses of the drug and used less of the more potent cannabis products to get the same psychological effects they seek, Hall said.

However, "the limited evidence suggests that users do not completely adjust dose for potency, and so probably get larger doses of THC than used to be the case," Hall said.

Studies on the use of alcohol — and, to a lesser extent, other drugs such as opioids — have also shown that more potent forms of these substances increase users' level of intoxication, as well as their risk of accidents and developing dependence, he added.

Follow Agata Blaszczak-Boxe on  Twitter .   Follow Live Science @livescience , Facebook   & Google+ . Originally published on Live Science .

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National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington (DC): National Academies Press (US); 2017 Jan 12.

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research.

• Hardcopy Version at National Academies Press

15 Challenges and Barriers in Conducting Cannabis Research

Several states have legalized cannabis for medical or recreational use since the release of the 1999 Institute of Medicine (IOM) 1 report Marijuana and Medicine: Assessing the Science Base ( IOM, 1999 ). As of October 2016, 25 states and the District of Columbia had legalized the medical use of cannabis, while 4 states and the District of Columbia had also legalized recreational cannabis use ( NCSL, 2016 ; NORML, 2016a ). 2 In November 2016, voters in California, Maine, Massachusetts, and Nevada approved ballot initiatives to legalize recreational cannabis, while voters in Arkansas, Florida, Montana, and North Dakota approved ballot initiatives to permit or expand the use of cannabis for medical purposes ( NORML, 2016b ).

Policy changes are associated with marked changes in patterns of cannabis use. In recent years, the number of U.S. adolescents and adults ages 12 and older who reported using cannabis increased by 35.0 percent and 20.0 percent for use in the past month and in the past year, respectively ( Azofeifa et al., 2016 ). Revenue from the sale and taxation of cannabis can serve as a proxy measure for cannabis use and suggests that the scope of cannabis use in the United States is considerable. For example, the total estimated value of legal cannabis sales in the United States was $5.7 billion in 2015 and $7.1 billion in 2016 ( Arcview Market Research and New Frontier Data, 2016 ). At the state level, the Colorado Department of Revenue reported that sales and excise taxes on recreational and medical cannabis sales totaled $88,239,323 in fiscal year 2015 ( CDOR, 2016a, p. 29 ), 3 and in Washington, state and local sales taxes and state business and occupation taxes on recreational and medical cannabis totaled $53,410,661 in fiscal year 2016 ( WDOR, 2016a , b ). 4

Despite these changes in state policy and the increasing prevalence of cannabis use and its implications for population health, the federal government has not legalized cannabis and continues to enforce restrictive policies and regulations on research into the health harms or benefits of cannabis products that are available to consumers in a majority of states. As a result, research on the health effects of cannabis and cannabinoids has been limited in the United States, leaving patients, health care professionals, and policy makers without the evidence they need to make sound decisions regarding the use of cannabis and cannabinoids. This lack of evidence-based information on the health effects of cannabis and cannabinoids poses a public health risk.

In order to promote research on cannabis and cannabinoids, the barriers to such research must first be identified and addressed. The committee identified several barriers to conducting basic, clinical, and population health research on cannabis and cannabinoids, including regulations and policies that restrict access to the cannabis products that are used by an increasing number of consumers and patients in state-regulated markets, funding limitations, and numerous methodological challenges. The following sections discuss these barriers in detail.

• REGULATORY AND SUPPLY BARRIERS

Regulatory Barriers

Investigators seeking to conduct research on cannabis or cannabinoids must navigate a series of review processes that may involve the National Institute on Drug Abuse (NIDA), the U.S. Food and Drug Administration (FDA), the U.S. Drug Enforcement Administration (DEA), institutional review boards, offices or departments in state government, state boards of medical examiners, the researcher's home institution, and potential funders. A brief overview of some of these review processes is discussed.

Researchers conducting clinical research on biological products such as cannabis must submit an investigational new drug (IND) application to the FDA. As a next step, the investigator may contact NIDA, an important source of research-grade cannabis, to obtain an administrative letter of authorization (LOA). An LOA describes the manufacturer's facilities, as well as the availability and pertinent characteristics of the desired cannabis product (e.g., strains, quality, strength, pharmacology, toxicology). To safeguard against the acquisition of cannabis or cannabinoids for non-research purposes, investigators must also apply for a DEA registration and site licensure before conducting studies involving cannabis or any of its cannabinoid constituents, irrespective of their pharmacologic activity. 5 The investigator must submit the IND and LOA to the FDA and the DEA for review ( FDA, 2015 ).

After submitting an IND application, researchers must wait at least 30 days before initiating research, during which period the FDA reviews the application to ensure that research participants will not be exposed to unreasonable risk ( FDA, 2016a ). If the FDA determines that the proposed research would expose study participants to unreasonable risk or that the IND application is in some other way deficient, a clinical hold postponing the research may be imposed. This hold is not lifted until and unless the sponsoring researchers have resolved the deficiencies ( FDA, 2016b ).

It is important to note that the Controlled Substances Act of 1970 classified cannabis as a Schedule I substance, the highest level of drug restriction. 6 As defined by the Act, Schedule I substances are those that (1) have a high potential for abuse; (2) have no currently accepted medical use in treatment in the United States; and (3) have a lack of accepted safety for their use under medical supervision. 7 Other substances classified in Schedule I include heroin, LSD, mescaline, hallucinogenic amphetamine derivatives, fentanyl derivatives (synthetic opioid analgesics), and gammahydroxybutyrate (GHB). 8 By contrast, Schedule II substances—though they also have a high potential for abuse and may lead to severe psychological or physical dependence—are defined as having a currently accepted medical use and can be prescribed with a controlled substance prescription ( DEA, 2006 ). 9

In some states, researchers conducting clinical research on cannabis or cannabinoid products must also apply for and receive a controlled substance certificate from a state board of medical examiners or a controlled substance registration from a department of the state government in order to conduct clinical trials or any other activity involving Schedule I substances ( Alabama Board of Medical Examiners, 2013 ; MDHSS, n.d .). Some state governments require additional approvals. For example, California requires that all trials involving Schedule I or II controlled substances be registered with and approved by the Research Advisory Panel of California ( CADOJ/OAG, 2016 ). When the necessary approvals are secured, only then can the investigator apply for a DEA registration and site licensure to conduct research on a Schedule I controlled substance (see Box 15-1 for examples of research barriers).

Illustrative Examples of the Current Research Barriers to Colorado Researchers.

Researchers conducting trials of Schedule I substances must additionally submit a research protocol to the DEA that includes details regarding the security provisions for storing and dispensing the substance. 10 Previously, nonfederally funded studies on cannabis were also required to undergo an additional review process conducted by the Public Health Service. This review process was determined to unnecessarily duplicate the FDA's IND application process in several ways and, as of June 2015, is no longer required. 11

To ensure that controlled substances obtained for research purposes will be stored and accessed in accordance with DEA security requirements, local DEA officials may perform a preregistration inspection of the facility where the proposed research will take place ( University of Colorado, 2016 ). DEA security requirements include storing cannabis in a safe, a steel cabinet, or a vault, and limiting access to the storage facility to “an absolute minimum number of specifically authorized employees. 12 The extent of the security measures required by DEA varies with the amount of cannabis being stored, 13 and among local DEA jurisdictions ( Woodworth, 2011 ). Funders must bear the costs of meeting the necessary security requirements.

Additionally, as with any human clinical trial, approval from an institutional review board must be sought. 14 Obtaining this approval confirms that an appropriate plan to protect the rights and welfare of human research subjects has been outlined in the proposed research efforts. If a study is being conducted in a clinical research center, a separate review may be required by this entity's medical or research advisory committee.

In summary, basic and clinical researchers seeking to obtain cannabis or cannabinoids from NIDA for research purposes—including efforts to determine the value of cannabis or cannabinoids for treating a medical condition or achieving a therapeutic end need—must obtain a number of approvals from a range of federal, state, or local agencies, institutions, or organizations. This process can be a daunting experience for researchers. The substantial layers of bureaucracy that emerge from cannabis's Schedule I categorization is reported to have discouraged a number of cannabis researchers from applying for grant funding or pursuing additional research efforts ( Nutt et al., 2013 ). Given the many gaps in the research of the health effects of cannabis and cannabinoids, there is a need to address these regulatory barriers so that researchers will be better able to address key public health questions about the therapeutic and adverse effects of cannabis and cannabinoid use.

CONCLUSION 15-1 There are specific regulatory barriers, including the classification of cannabis as a Schedule I substance, that impede the advancement of cannabis and cannabinoid research. 15

Barriers to Cannabis Supply

In the United States, cannabis for research purposes is available only through the NIDA Drug Supply Program ( NIDA, 2016a ). The mission of NIDA is to “advance science on the causes and consequences of drug use and addiction and to apply that knowledge to improve individual and public health,” rather than to pursue or support research into the potential therapeutic uses of cannabis or any other drugs ( NIDA, 2016b ). As a result of this emphasis, less than one-fifth of cannabinoid research funded by NIDA in fiscal year 2015 concerns the therapeutic properties of cannabinoids ( NIDA, 2016c ). 16 Because NIDA funded the majority of all the National Institutes of Health (NIH)-sponsored cannabinoid research in fiscal year 2015 ( NIDA, 2016c ), 17 its focus on the consequences of drug use and addiction constitutes an impediment to research on the potential beneficial health effects of cannabis and cannabinoids.

All of the cannabis that NIDA provides to investigators is sourced from the University of Mississippi, which is currently the sole cultivator of the plant material and has been since 1968 ( NIDA, 1998 , 2016a ). 18 In the past, the varieties of cannabis that were available to investigators through NIDA were limited in scope and were not of comparable potency to what patients could obtain at their dispensaries ( Stith and Vigil, 2016 ). Because of restrictions on production and vicissitudes in supply and demand, federally produced cannabis may have been harvested years earlier, is stored in a freezer (a process that may affect the quality of the product) ( Taschwer and Schmid, 2015 ; Thomas and Pollard, 2016 ), and often has a lower potency than cannabis sold in state-regulated markets ( Reardon, 2015 ; Stith and Vigil, 2016 ). In addition, many products available in state-regulated markets (e.g., edibles, concentrates, oils, wax, topicals) are not commonly available through federal sources ( NIDA, 2016d ). Since the products available through the federal system do not sufficiently reflect the variety of products used by consumers, research conducted using cannabis provided by NIDA may lack external validity. In July 2016, NIDA posted a formal request for information on the varieties of cannabis and cannabis products of interest to researchers ( NIDA, 2016e ). Reflecting the perceived shortcomings of cannabis and cannabis products currently provided by NIDA, a summary of the comments received in response to this request states that “the most consistent recommendation was to provide marijuana strains and products that reflect the diversity of products available in state dispensaries” ( NIDA, 2016e ).

Naturally, it is difficult for a single facility at the University of Mississippi to replicate the array and potency of products available in dispensaries across the country. It is worth noting, however, that NIDA has been increasingly responsive to the needs of clinical investigators. For example, NIDA has contracted with the University of Mississippi to produce cannabis strains with varying concentrations of Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) ( NIDA, 2016d ), and NIDA has previously authorized development of cannabis extracts, tinctures, and other dosage formulations for research purposes ( Thomas and Pollard, 2016 ). As mentioned above, NIDA has sought public comment on the needs of cannabis researchers in order to inform efforts to “expand access to diverse marijuana strains and products for research purposes” ( NIDA, 2016e ). In addition, cannabis is made available to research investigators funded by NIH at no cost. 19 Finally, the DEA has adopted a new policy that increases the number of entities that may be registered under the Controlled Substances Act (CSA) to grow (manufacture) marijuana to supply legitimate researchers in the United States. 20 Under this new policy, the DEA will facilitate cannabis research by increasing the number of private entities allowed to cultivate and distribute research-grade cannabis. As of December 2016, the University of Mississippi remains the sole cultivator of cannabis provided to researchers by NIDA ( NIDA, 2016a ).

Although new plans are being made to provide a wider array of more clinically relevant cannabis products for research, at present this issue is still a significant barrier for conducting comprehensive research on the health effects of cannabis use. How the proposed changes will affect cannabis research in the future remains to be seen.

CONCLUSION 15-2 It is often difficult for researchers to gain access to the quantity, quality, and type of cannabis product necessary to address specific research questions on the health effects of cannabis use.

Funding Limitations

Funding for research is another key barrier; without adequate financial support, cannabis research will be unable to inform health care or public health practice or to keep pace with changes in cannabis policy and patterns of cannabis use. NIH is responsible for funding research across a number of health domains. In 2015, NIH spending on all cannabinoid research totaled $111,275,219 ( NIDA, 2016c ). NIDA, a member institute of NIH, has as its mission to study factors related to substance abuse and dependence and conducts research on the negative health effects and behavioral consequences associated with the abuse of cannabis and other drugs ( NIDA, 2016b ). Because cannabis was historically perceived to have only negative effects, the majority of cannabis research has been conducted under the auspices of NIDA.

In fiscal year 2015, studies supported by NIDA accounted for 59.3 percent ($66,078,314) of all NIH spending on cannabinoid research; however, only 16.5 percent ($10,923,472) of NIDA's spending on cannabinoid research supported studies investigating therapeutic properties of cannabinoids ( NIDA, 2016c ). 21 , 22 As demonstrated in Chapter 4 of this report, a growing body of evidence suggests that cannabis and cannabinoids also have therapeutic health effects. In light of these findings, a comprehensive research agenda that investigates both the potential adverse and the potential therapeutic health effects of cannabis use is needed.

However, it may be unrealistic to expect NIDA to have the resources or interest to fund this broader research agenda, which could involve investigating the health effects of cannabis use on a diverse range of conditions (e.g., metabolic syndrome, cardiovascular disease, cancer, obesity and sedentary behavior, Alzheimer's disease) that are targeted by other institutes and centers of NIH. While it is not clear how these studies might be funded, almost assuredly the changing norms and the changing legal status of cannabis will have an impact on conditions that are targeted by institutes other than NIDA, and it will become increasingly important to have a funding mechanism to better understand the comprehensive health effects of cannabis so that consumers and policy makers can respond to changing trends accordingly.

CONCLUSION 15-3 A diverse network of funders is needed to support cannabis and cannabinoid research that explores the harmful and beneficial health effects of cannabis use.

• METHODOLOGICAL CHALLENGES

Drug Delivery Challenges

Another challenge in investigating the potential health effects of cannabis and cannabinoids is the identification of a method of administering the drug that is accepted by study participants, that can be performed at most research sites, and that ensures standardized dosing. Smoking as a route of administration is particularly challenging, as some study participants may not view it as an acceptable method of drug administration, and academic medical centers or other locations where cannabis or cannabinoid research takes place may lack facilities where study participants can smoke under controlled conditions. Furthermore, variations among individuals in terms of their cannabis smoking techniques make it difficult to ensure that study participants reliably receive the targeted dose of the drug. Devices for providing a metered dose of cannabis via inhalation exist ( Eisenberg et al., 2014 ), but the FDA has not approved such devices for use. Standardized smoking techniques have also been developed ( Foltin et al., 1988 ) but can be difficult to perform correctly. These difficulties are due, in part, to differences among individuals in their tolerance of the potential psychoactive effects of the drug ( D'Souza et al., 2008 ; Ramaekers et al., 2009 ), which may prevent the receipt of equal doses by all study participants.

Researchers have also explored vaporization as a method for administering cannabis ( Abrams et al., 2007 ). Cannabinoids vaporize at lower temperatures than the temperature at which pyrolytic toxic compounds are created through combustion; as a result, levels of some carcinogenic compounds are lower in cannabis vapor than in cannabis smoke ( Eisenberg et al., 2014 ). However, there is a paucity of research on the effectiveness of these devices as a mode of drug administration. For example, data on the plasma concentrations of cannabinoids achieved through use of vaporizers exists, but they are limited ( Abrams et al., 2007 ; Zuurman et al., 2008 ). In addition, even less is known about the long-term pulmonary effects of inhaling a vaporized liquid than about the effect of inhaling plant material. As vaporizing devices proliferate and evolve, researchers may benefit from advances in their portability and usability, but they will also have to account for clinically relevant differences in the functioning and the effectiveness of an increasingly wide range of models.

To circumvent the practical and methodological challenges involved in administration of cannabis through smoking or vaporization, investigators may choose to study the health effects of orally administered dronabinol or nabilone, which offer a more controlled method of drug delivery. However, the effects generated by these isolated cannabinoids might, at least in part, be different from those produced by the use of the whole cannabis plant, which also contains CBD and other cannabinoids, as well as terpenoids and flavonoids. As a result, extrapolating from the observed health effects associated with use of an isolated cannabinoid such as dronabinol or nabilone in order to predict the health effects associated with the use of cannabis may lead to erroneous conclusions.

The Placebo Issue

The gold standard of drug development is the prospective, randomized, double-blind, placebo-controlled clinical trial. Placebo cannabis produced by solvent extraction is available from NIDA and has a potency of 0.002 percent THC by weight and 0.001 percent CBD by weight ( NIDA, 2016d ). 23 The extraction process seems to retain the terpenoids and flavonoids so that the combusted placebo material smells similar to the true cannabis, thus helping to preserve the blinding to some extent. However, the psychoactive and vasoactive effects of cannabis pose a considerable challenge for effective blinding, since study participants who feel such effects will surmise that they are receiving cannabis or cannabinoids, and not a placebo.

Strategies to promote the effectiveness of blinding exist. For example, if the cannabis being studied has a very low THC content, study participants—especially those who, through regular use of more potent cannabis strains, are inured to the psychoactive effects of cannabis with low THC content—may not notice the psychoactive effects of the cannabis and therefore be unable to reliably determine whether they are using cannabis or a placebo. There is also a possibility that cannabis products with a lower ratio of the concentration of THC to the concentration of CBD may have less psychoactivity than products with a comparatively higher ratio of the concentration of THC to the concentration of CBD ( Hindocha et al., 2015 ; Jacobs et al., 2016 ). Using these strains with diminished psychoactive effects could promote more effective blinding. Researchers may also try treating both study arms in a placebo-controlled cannabis trial with a mildly psychoactive or sedating drug, the effects of which may help to ensure that study participants are unable to determine whether they are receiving a placebo or cannabis. However, by introducing another active agent, the investigators risk obfuscating the results of their study.

A potential method for assessing the effectiveness of blinding in a cannabis trial is to ask study participants to guess whether they are receiving true cannabis or a placebo. If most or all of the participants correctly guess their assignment, it can be inferred that the blinding was ineffective. Whether or not such methods are employed, investigators risk undermining their study results. On the one hand, conducting the test carries the risk of discovering that attempts at blinding were ineffective, thereby rendering the study results invalid. On the other hand, not conducting the test may lead journal reviewers aware of the challenges of blinding in cannabis trials to assume that blinding was ineffective and to discount the study results accordingly. Thus, research to address the challenge of achieving reliably effective blinding in a cannabis trial is of marked importance.

Exposure Assessment

In order to arrive at valid and meaningful results, population studies on the health effects of cannabis require as detailed an ascertainment of exposure to cannabis as possible. However, obtaining such a detailed exposure history can be difficult. This is especially true for recreational cannabis use due to the lack of a standardized dose and the existence of diverse routes of administration, including multiple modes of inhalation ( Schauer et al., 2016 ). In addition, known pharmacological biomarkers of cannabis use may be unreliable in some circumstances, while population studies to identify novel pharmacological biomarkers of cannabis exposure are limited ( Hartman et al., 2016 ; Schwope et al., 2011 ). Furthermore, the wide variety of different cannabis strains developed through a long and ongoing process of cultivation and the associated variation in the concentration of active substances in cannabis further complicate the characterization of cannabis exposure ( ElSohly and Gul, 2014 ; Elsohly et al., 2016 ; Mehmedic et al., 2010 ). Finally, recreational cannabis may contain chemical contaminants or adulterants ( Busse et al., 2008 ). Cannabis users may be unaware of the presence of these chemicals, making it unlikely that such chemicals would be identified through toxicological evaluation unless the user became involved in a forensic investigation.

Most observational studies, particularly case-control and cohort studies, depend on self-report in order to assess cannabis exposure. These reports may be incomplete, inaccurate, or imprecise due to failure on the part of investigators to ask cannabis users detailed questions about their cannabis exposure history, including the source of their cannabis exposure (e.g., smoking, edibles, vaping), or because users themselves may have limited knowledge of some aspects of their exposure or may be resistant to reporting some information. Personal recall of substance use may also be affected by other factors. For example, memory problems have been identified as a cause of inaccuracies in reporting drug use ( Johnson and Fendrich, 2005 ; Pedersen, 1990 ). In other cases, study participants may not report illicit substance use in an attempt to conform to perceived social norms ( Johnson and Fendrich, 2005 ). Similarly, individuals with substance dependency syndromes may have psychiatric comorbidity that affects the accuracy of reporting.

Finally, important information often missing from cannabis exposure histories is the extent of other substance use. As noted in Chapter 14 , there is limited evidence that cannabis use is associated with the use of other licit or illicit substances. Despite this association and the confounding effect of polysubstance use on evaluations of the health effects of cannabis use, surveys used to characterize cannabis exposure histories do not always assess for the presence of other substance use. Since secondhand exposure to cannabis smoke can have minor health effects, there may also be value in assessing for such exposure as part of larger assessments of cannabis exposure ( Herrmann et al., 2015 ).

Cannabis-Related Study Designs

In researching the health outcomes of cannabis use, the committee identified a number of studies, particularly cohort studies, of general health outcomes such as all-cause mortality or important chronic illnesses such as cancers or cardiovascular diseases. For both cohort and case-control studies, a better assessment of cannabis use would offer more valuable information, such as years of use and age at first use. Particularly for cohort studies, this would offer better ascertainment of the duration and net burden of use as well as more insight into period and age effects. As discussed in the proceeding health outcomes chapters of the report, in many of the existing cohort studies cannabis use was often queried only at baseline, and thus there was little information on interval use over time or on the variation or cessation in that use. There was also very limited information on interval health events as the cohorts progressed, impeding a summarization of long-term use and the consequent health effects. Attention to these issues will likely improve the precision of study findings.

CONCLUSION 15-4 To develop conclusive evidence for the effects of cannabis use on short- and long-term health outcomes, improvements and standardization in research methodology (including those used in controlled trials and observational studies) are needed.

The methodological challenges and the regulatory, financial, and access barriers described above markedly affect the ability to conduct comprehensive basic, clinical, and public health research on the health effects of cannabis use, with further consequences for the many potential beneficiaries of such research. In the absence of an appropriately funded and supported cannabis research agenda, patients may be unaware of viable treatment options, providers may be unable to prescribe effective treatments, policy makers may be hindered from developing evidence-based policies, and health care organizations and insurance providers lack a basis on which to revise their care and coverage policies. In short, such barriers represent a public health problem. See Box 15-2 for a summary of the chapter conclusions.

Summary of Chapter Conclusions .

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As of March 2016, the Health and Medicine Division continues the task of producing consensus studies and convening activities previously undertaken by the Institute of Medicine (IOM).

The count of states where cannabis is legalized for medical use includes Ohio and Pennsylvania, where medical cannabis laws were not operational as of October 2016 ( NCSL, 2016 ).

$22,225,750 (Marijuana Sales Tax [2.9%]) + $42,017,798 (Retail Marijuana Sales Tax [10%]) + $23,995,775 (Retail Marijuana Excise Tax [15%]) = $88,239,323.

Medical Cannabis: $5,236,536 (State Retail Sales Tax) + $792,906 (State Business and Occupation Tax) + $ 2,084,323 (Local Retail Sales Tax) = $8,113,765. Recreational Cannabis: $30,017,823 (State Retail Sales Tax) + $4,050,212 (State Business & Occupation Tax) + $11,228,861 (Local Retail Sales Tax) = $45,296,896. $8,113,765 (Total Medical Cannabis Taxes) + $45,296,896 (Total Recreational Cannabis Taxes) = $53,410,661.

Code of Federal Regulations, Registration of Manufacturers, Distributors, and Dispensers of Controlled Substances, Title 21, § 1301.11 and Code of Federal Regulations, Schedules of Controlled Substances, Title 21, § 1308.11.

Code of Federal Regulations, Schedules of Controlled Substances, Title 21, § 1308.11; United States Code, Schedules of Controlled Substances, Title 21, § 812.

United States Code, Schedules of Controlled Substances, Title 21, § 812(b)(1).

Code of Federal Regulations, Schedules of Controlled Substances, Title 21, § 1308.11.

United States Code, Schedules of Controlled Substances, Title 21, § 812(b)(2).

Code of Federal Regulations, Registration of Manufacturers, Distributors, and Dispensers of Controlled Substances, Title 21, § 1301.18.

Office of the Secretary, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services. Notice. “Announcement of Revision to the Department of Health and Human Services Guidance on Procedures for the Provision of Marijuana for Medical Research as Published on May 21, 1999,” Federal Register , 80, no. 120 (June 23, 2015): 35960, https://www ​.gpo.gov/fdsys ​/pkg/FR-2015-06-23/pdf/2015-15479 ​.pdf (accessed November 25, 2016).

Code of Federal Regulations, Registration of Manufacturers, Distributors, and Dispensers of Controlled Substances, Title 21, § 1301.72 (a) and (d).

Code of Federal Regulations, Registration of Manufacturers, Distributors, and Dispensers of Controlled Substances, Title 21, § 1301.71 (c).

Code of Federal Regulations, Institutional Review Boards, Title 21, § 56.103.

The committee was specifically directed in its statement of task not to comment on cannabis policy issues, such as regulatory options for legalization, taxation, or distribution. While the committee has identified the Schedule 1 classification of cannabis as posing a significant barrier to the conduct of scientific research on the health effects of cannabis, the committee is aware that any decision on the regulation of cannabis involves many factors far outside the committee's remit and expertise. Specifically, the committee did not comment on the abuse or dependency liability or accepted medical use of cannabis compared to other scheduled drugs.

In fiscal year 2015, NIDA's investment in cannabinoid research totaled $66,078,314, of which $10,923,472 was allocated for therapeutic cannabinoid research ( NIDA, 2016c ).

In fiscal year 2015, NIH's investment in cannabinoid research totaled $ $111,275,219, of which $66,078,314 was allocated to NIDA ( NIDA, 2016c ).

NIDA contracts with the University of Mississippi through an open solicitation process. Although the University of Mississippi is currently NIDA's only supplier of research-grade cannabis, other groups can compete for the contract ( NIDA, 2015 , 2016a ).

In December 2016, cannabis provided by NIDA was generally free for NIH-sponsored research. For research not funded by the federal government, the cost of non-placebo cannabis was $10.96 per cigarette and $1,133 per pound ($2,497 per kilogram) ( NIDA, 2016d ).

DEA, U.S. Department of Justice. Policy Statement. “Applications to Become Registered Under the Controlled Substances Act to Manufacture Marijuana to Supply Researchers in the United States,” Federal Register , 81, no. 156 (August 12, 2016): 53846, https://www ​.gpo.gov/fdsys ​/pkg/FR-2016-08-12/pdf/2016-17955 ​.pdf (accessed January 7, 2017).

$66,078,314 (Total NIDA spending on cannabinoid research in fiscal year 2015)/$111,275,219 (Total NIH spending on cannabinoid research in fiscal year 2015) = 0.593. $10,923,472 (Total NIDA spending on therapeutic cannabinoid research in fiscal year 2015)/$66,078,314 (Total NIDA spending on cannabinoid research in fiscal year 2015) = 0.165.

By contrast, NIH spending on tobacco research totaled $300 million in 2015, and spending on research related to the harms and benefits of alcohol use totaled $473 million in 2015 ( NIH, 2016 ).

In December 2016, placebo cannabis provided by NIDA was generally free for NIH-sponsored research. For research not funded by the federal government, the cost of placebo cannabis was $13.94 per cigarette and $1,133 per pound ($2,497 per kilogram) ( NIDA, 2016d ).

• Cite this Page National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington (DC): National Academies Press (US); 2017 Jan 12. 15, Challenges and Barriers in Conducting Cannabis Research.
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Center for Cannabis Policy, Research, and Outreach

The Center for Cannabis Policy, Research, and Outreach (CCPRO) at Washington State University (WSU) consists of more than 70 researchers across the WSU system. Four specific themes have been identified to establish WSU as a global leader in cannabis research, policy, and outreach:

• Improving health and well being.  WSU faculty conduct translational science related to the impact of cannabis on health, ranging from animal studies of the impact of cannabis on brain development, the impact of THC and CBD on pain, the impact of cannabis on mental health and stress, and the prevention of problematic cannabis use.
• Public policy and safety.  WSU faculty conduct research on roadside detection and work place safety and cannabis use, the impacts of de-criminalization on crime and the justice system, and federal and state cannabis policy.
• Economics.  WSU faculty conduct research on issues relevant to the cannabis industry, such as industry taxation and banking, economic impact, and cannabis work place issues.
• Agricultural Research. WSU faculty conduct agricultural research on industrial hemp grown for CBD extract, textiles, food, and fiber in compliance with state and federal law. Key to product development and sales is a strong crop production and pest management practices optimized for industrial hemp grown in Washington state.

Donations will help support current work on the cannabis policy landscape, determining short and long term health effects of cannabis use, including addiction, impact on the opioid crisis, pain, stress, anxiety, depression, and other public health issues, plus public safety and criminal justice issues, and agricultural issues. Your donation today will help continue this important research.

Conditional Note:  WSU currently does not accept money from marijuana related businesses that manufacture, distribute, or dispense marijuana (Controlled Substances Act-CSA, 21 U.S.C. § 801, et seq.), but private individuals and companies not subject to the CSA can donate. For more information please email us at [email protected] . 

Here is a sample of WSU researchers who take part in CCPRO activities or have been funded through WSU’s Alcohol and Drug Abuse Research Program or other sources:

To contact CCPRO, please e-mail us:

Contact CCPRO

Dr. Gang’s research focuses on how plants, like Cannabis sativa , produce important medicinally active compounds. To support those and other research efforts, he directs WSU’s TIMPL and LCME metabolomics/proteomics core facilities. He is also leading WSU’s contributions to national field trials for industrial hemp (for fiber, grain and cannabinoid/terpenoid production) and is developing partnerships with other research institution and Tribal communities for hemp research and economic development.

Dr. Klein’s research focuses on the interface between public policy and prescribing practices as they relate to practitioner, patient, and institutional factors. Her interprofessional collaborations include research on health professional communication and knowledge regarding cannabis, interventions to enhance shared decision-making about cannabis, the impact of policy change on use of cannabis and synthetic cannabinoids, and development and evaluation of continuing education specific to cannabis and cannabis use disorder for health professionals. In 2023 Dr. Klein completed a post-doctoral master’s degree at the University of Maryland College of Pharmacy focusing on medical cannabis pharmacology and therapeutics.

Dr. Clayton’s research focuses is on American political institutions and policy making, and Washington State politics.

Dr. Clowers’ research focuses on the development of trace detection of cannabinoids using mass spectrometry and ion mobility spectrometry. In addition to serving the needs of the fundamental cannabinoid research community, efforts are ongoing to realize a portable, sensitive instrument capable of assessing recent consumption marijuana. This latter research endeavor will fill a needed gap in law enforcement assessment protocols, workplace compliance, and rapid point-of-care diagnostics.

The Craft lab studies sex differences in the pain-relieving effects of cannabinoid drugs.

Dr. Cuttler’s research focuses on examining acute and chronic effects of cannabis on mental health (e.g., depression, anxiety, OCD, ADHD, PTSD), physical health (e.g., pain), stress, and cognition (e.g., memory, decision-making, executive functioning, creativity).

Dr. Delevich studies how adolescent cannabis use influences the maturation of neural circuits underlying motivated behavior. She is also interested in how the interplay of sex, pubertal hormones, and cannabis use impacts brain development.

Dr. Dhingra’s research focuses on the use of genomics, genetics, and breeding in food crops, and utilizing DNA-based knowledge during plant propagation to ensure ‘true to typeness’ of the plant material. The methods developed in his program are already being offered commercially and can be utilized by the cannabis industry to ensure end-user safety, and by the regulatory agencies for quality control.

Dr. Fales conducts research in the areas of pediatric pain. Her projects related to cannabis have focused on recreational use and its links to pain, physical activity, sleep, and quality of life in young people.

Dr. Fortenbery’s research related to cannabis has focused on the economic feasibility of industrial hemp production and processing, potential market size, and challenges in developing a stable hemp industry. He has published several studies on the potential markets for industrial hemp, consulted with potential processors and farmers, and been interviewed extensively on the risks and opportunities associated with hemp market development.

Dr. Fuchs studies the neurobiological mechanisms of cocaine, heroin, and cannabis use disorders.  Her most recent research explores the role of endocannabinoids in drug-memory maintenance and drug relapse using animal models.

Dr. Gartstein’s primary interest has to do with how cannabis use during pregnancy affects maternal-child health. Specifically, she is interested in the effects on child reactivity and self-regulation, and the mechanisms involved in the intergenerational transmission of risk.

Dr. Graves conducts research on population health impacts of cannabis legalization and use, including unintentional exposures to children and youth and parental cannabis use and storage behaviors. 

Dr. Hayashi studies the transgenerational effects of in utero cannabis exposure on male and female reproductive functions and mechanisms in germ cells.

Dr. Hemmens studies the effects of marijuana legalization on law enforcement and crime in Washington. This collaborative work with several WSU faculty, graduate students, undergraduate students, and numerous agency partners in the state and in Idaho, involves the use of focus groups, interviews and the analysis of state and federal data. He was also the PI on several grants from the Washington State Traffic Safety Commission to study nine years of traffic fatalities as they are affected by the presence of THC.

Individuals with mental illness often misuse cannabis, which has negative effects on subsequent mental and physical health, increasing rates of hospitalization and mortality. Work in my lab focuses on understanding the neurobiological underpinnings of substance misuse and co-occurring mental illness using use translationally relevant rodent models. Our ultimate goal is to contribute to the development of personalized, effective therapies for cannabis and other substance use disorders in clinical populations.

The Jiang laboratory is interested in genomic complexity of neuronal activities in response to cannabis exposure and development of efficient programs to combat the cannabis use disorders in humans.

Dr. Ladd’s research interests focus on improving prevention and early intervention techniques for promoting and motivating health behavior change. He is interested in understanding the risks and/or benefits of cannabis use. This includes refining the measurement of cannabis consumption and problems and investigating the role of cannabis in specific populations (e.g., chronic pain). Additionally, Dr. Ladd conducts process research with the goal of better understanding and identifying effective elements of therapeutic interventions, particularly Motivational Interviewing, in order to reduce the impact of substance use and problems.

Dr. Lovrich has extensive experience with the political dynamics of marijuana legalization and assessing the impact of marijuana law liberalization on crime and law enforcement. He has been working for several years on addressing the problem of the rapid field documentation of cannabis exposure and associated impairment in driving, boating and workplace settings.

Dr. Magnan studies the perceptions of risks and benefits of cannabis use, accuracy of these perceptions, and associations with use and related problems, as well as event-level experiences and correlates with other behaviors and affective experiences.

Dr. Makin is studying the effects of marijuana legalization on law enforcement and crime in Washington. Specific to this research, he is working on several studies examining the relationship between legalization and police effectiveness, distribution of calls, mental health, and to what extent legalization has influenced police community relationship. Additionally, he and Dr. Willits are developing a process to improve the detection of impairment through analytical solutions.

Dr. McDonell conducts research on the impact of cannabis on mental illness, especially on the mental health of youth experiencing psychosis. His other research focuses on testing treatments for co-occurring substance use disorders and severe mental illness. He also partners with American Indian and Alaska Native communities to test the new treatments for alcohol and drug problems.

Researchers in the McLaughlin Lab use translational animal models to investigate the long-term effects of developmental cannabis exposure on cognitive, emotional, and neural endpoints. Additionally, we explore how endogenous cannabinoid signaling in the brain contributes to alterations in the neuroendocrine and behavioral response to stress.

The Analytics and PsychoPharmaoclogy Laboratory (APPL) conducts research on 1) co-use of cannabis and tobacco among adolescents, and 2) cannabis use impact on substance or alcohol use disorder treatment outcomes.

Dr. Courtney Meehan’s research is focused on cannabis use during lactation. She is leading an interdisciplinary team to assess cannabinoid concentrations in human milk and potential relationships to infant development. This research will provide critically needed data on the effects of cannabis use while breastfeeding for healthcare providers and mothers.

Dr. Morgan’s research focuses on the ability of cannabinoids to treat chronic pain conditions.

Our work focuses on the effects of cannabis on vagal afferent signaling in the control of key autonomic reflexes that regulate the heart, lungs, and gastrointestinal tract.

Kawkab Shishani College of Nursing

Dr. Shishani’s research area is tobacco use and cessation with particular focus on waterpipe (hookah) tobacco smoking. Dr. Shishani is also interested in looking at the initiation and dual use of waterpipe tobacco smoking and marijuana.

Crystal Smith Elson S Floyd College of Medicine

Dr. Smith’s research addresses substance use broadly, but is heavily focused on the areas of cannabis and opioids, particularly as they impact youth and families, pain, and relate to genetics and genomics.

Dr. Snyder primarily studies the impacts of the legalization of marijuana on law enforcement after 30 years of being in the trenches of the war on drugs, where his approach resulted in working with both those criminally accused and representation of police officers in noncriminal matters.

Dr. Stohr studies the effects of marijuana legalization on law enforcement and crime in Washington. This collaborative work with several WSU faculty, graduate and undergraduate students and numerous agency partners in the state and in Idaho, involves the use of focus groups, interviews and the analysis of state and federal data. She was also the PI on a few smaller grants from the Washington State Traffic Safety Commission to study nine years of traffic fatalities as they are affected by the presence of THC.

Dr. Weybright broadly conducts research to understand and prevent adolescent risk behavior. Specific to cannabis, she has looked at patterns and correlates of use among youth of color (e.g., American Indian) and effectiveness of prevention programs in a legalized cannabis context.

Dr. Willits studies the effects of marijuana legalization on law enforcement and crime in Washington and examines the effects of marijuana on driving behavior/safety. In addition to examining the effects of legalization on crime and public safety, he is currently conducting work examining the effect of legalization on racial disparities in the criminal justice system.

Dr. Jessica Willoughby conducts research that examines the ways in which media is associated with attitudes toward cannabis among adolescents and young adults. She also does work on campaigns, communication strategies, and interventions that use media for risk reduction efforts.

Dr. Wilson’s research focuses on cannabis use among people prescribed opioids for chronic pain or opioid use disorder. Her team has published studies investigating the relationships between cannabis use frequency and distressing symptoms such as pain, depression, anxiety, and sleep disorders.

Cannabis Research Highlights from WSU’s Student Researchers

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What marijuana reclassification means for the United States

The U.S. Drug Enforcement Administration will move to reclassify marijuana as a less dangerous drug, a historic shift to generations of American drug policy that could have wide ripple effects across the country.

FILE - Marijuana plants are seen at a secured growing facility in Washington County, N.Y., May 12, 2023. The U.S. Drug Enforcement Administration will move to reclassify marijuana as a less dangerous drug, a historic shift to generations of American drug policy that could have wide ripple effects across the country. (AP Photo/Hans Pennink, File)

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Budtender Rey Cruz weighs cannabis for a customer at the Marijuana Paradise on Friday, April 19, 2024, in Portland, Ore. (AP Photo/Jenny Kane)

Cloud 9 Cannabis employee Beau McQueen, right, helps a customer, Saturday, April 13, 2024, in Arlington, Wash. The shop is one of the first dispensaries to open under the Washington Liquor and Cannabis Board’s social equity program, established in efforts to remedy some of the disproportionate effects marijuana prohibition had on communities of color. (AP Photo/Lindsey Wasson)

WASHINGTON (AP) — The U.S. Drug Enforcement Administration is moving toward reclassifying marijuana as a less dangerous drug. The Justice Department proposal would recognize the medical uses of cannabis , but wouldn’t legalize it for recreational use.

The proposal would move marijuana from the “Schedule I” group to the less tightly regulated “Schedule III.”

So what does that mean, and what are the implications?

WHAT HAS ACTUALLY CHANGED? WHAT HAPPENS NEXT?

Technically, nothing yet. The proposal must be reviewed by the White House Office of Management and Budget, and then undergo a public-comment period and review from an administrative judge, a potentially lengthy process.

Still, the switch is considered “paradigm-shifting, and it’s very exciting,” Vince Sliwoski, a Portland, Oregon-based cannabis and psychedelics attorney who runs well-known legal blogs on those topics, told The Associated Press when the federal Health and Human Services Department recommended the change.

“I can’t emphasize enough how big of news it is,” he said.

It came after President Joe Biden asked both HHS and the attorney general, who oversees the DEA, last year to review how marijuana was classified. Schedule I put it on par, legally, with heroin, LSD, quaaludes and ecstasy, among others.

Biden, a Democrat, supports legalizing medical marijuana for use “where appropriate, consistent with medical and scientific evidence,” White House press secretary Karine Jean-Pierre said Thursday. “That is why it is important for this independent review to go through.”

Cloud 9 Cannabis employee Beau McQueen, right, helps a customer, Saturday, April 13, 2024, in Arlington, Wash. (AP Photo/Lindsey Wasson)

IF MARIJUANA GETS RECLASSIFIED, WOULD IT LEGALIZE RECREATIONAL CANNABIS NATIONWIDE?

Ap audio: what marijuana reclassification means for the united states.

AP correspondent Haya Panjwani reports on a proposal for the federal government to reclassify marijuana in what would be a historic shift that could have wide ripple effects across the country.

No. Schedule III drugs — which include ketamine, anabolic steroids and some acetaminophen-codeine combinations — are still controlled substances.

They’re subject to various rules that allow for some medical uses, and for federal criminal prosecution of anyone who traffics in the drugs without permission.

No changes are expected to the medical marijuana programs now licensed in 38 states or the legal recreational cannabis markets in 23 states, but it’s unlikely they would meet the federal production, record-keeping, prescribing and other requirements for Schedule III drugs.

There haven’t been many federal prosecutions for simply possessing marijuana in recent years, even under marijuana’s current Schedule I status, but the reclassification wouldn’t have an immediate impact on people already in the criminal justice system.

“Put simple, this move from Schedule I to Schedule III is not getting people out of jail,” said David Culver, senior vice president of public affairs at the U.S. Cannabis Council.

But rescheduling in itself would have some impact, particularly on research and marijuana business taxes.

WHAT WOULD THIS MEAN FOR RESEARCH?

Because marijuana is on Schedule I, it’s been very difficult to conduct authorized clinical studies that involve administering the drug. That has created something of a Catch-22: calls for more research, but barriers to doing it. (Scientists sometimes rely instead on people’s own reports of their marijuana use.)

Marijuana plants are seen at a secured growing facility in Washington County, N.Y., May 12, 2023. (AP Photo/Hans Pennink, File)

Schedule III drugs are easier to study, though the reclassification wouldn’t immediately reverse all barriers to study.

“It’s going to be really confusing for a long time,” said Ziva Cooper, director of the University of California, Los Angeles Center for Cannabis and Cannabinoids. “When the dust has settled, I don’t know how many years from now, research will be easier.”

Among the unknowns: whether researchers will be able to study marijuana from state-licensed dispensaries and how the federal Food and Drug Administration might oversee that.

Some researchers are optimistic.

“Reducing the schedule to schedule 3 will open up the door for us to be able to conduct research with human subjects with cannabis,” said Susan Ferguson, director of University of Washington’s Addictions, Drug & Alcohol Institute in Seattle.

WHAT ABOUT TAXES (AND BANKING)?

Under the federal tax code, businesses involved in “trafficking” in marijuana or any other Schedule I or II drug can’t deduct rent, payroll or various other expenses that other businesses can write off. (Yes, at least some cannabis businesses, particularly state-licensed ones, do pay taxes to the federal government, despite its prohibition on marijuana.) Industry groups say the tax rate often ends up at 70% or more.

The deduction rule doesn’t apply to Schedule III drugs, so the proposed change would cut cannabis companies’ taxes substantially.

They say it would treat them like other industries and help them compete against illegal competitors that are frustrating licensees and officials in places such as New York .

“You’re going to make these state-legal programs stronger,” says Adam Goers, of The Cannabist Company, formerly Columbia Care. He co-chairs a coalition of corporate and other players that’s pushing for rescheduling.

It could also mean more cannabis promotion and advertising if those costs could be deducted, according to Beau Kilmer, co-director of the RAND Drug Policy Center.

Rescheduling wouldn’t directly affect another marijuana business problem: difficulty accessing banks, particularly for loans, because the federally regulated institutions are wary of the drug’s legal status. The industry has been looking instead to a measure called the SAFE Banking Act . It has repeatedly passed the House but stalled in the Senate.

ARE THERE CRITICS? WHAT DO THEY SAY?

Indeed, there are, including the national anti-legalization group Smart Approaches to Marijuana. President Kevin Sabet, a former Obama administration drug policy official, said the HHS recommendation “flies in the face of science, reeks of politics” and gives a regrettable nod to an industry “desperately looking for legitimacy.”

Some legalization advocates say rescheduling weed is too incremental. They want to keep the focus on removing it completely from the controlled substances list, which doesn’t include such items as alcohol or tobacco (they’re regulated, but that’s not the same).

Paul Armentano, the deputy director of the National Organization for the Reform of Marijuana Laws, said that simply reclassifying marijuana would be “perpetuating the existing divide between state and federal marijuana policies.” Kaliko Castille, a past president of the Minority Cannabis Business Association, said rescheduling just “re-brands prohibition,” rather than giving an all-clear to state licensees and putting a definitive close to decades of arrests that disproportionately pulled in people of color.

“Schedule III is going to leave it in this kind of amorphous, mucky middle where people are not going to understand the danger of it still being federally illegal,” he said.

This story has been corrected to show that Kaliko Castille is a past president, not president, of the Minority Cannabis Business Association and that Columbia Care is now The Cannabist Company.

___ Peltz reported from New York. Associated Press writers Colleen Long in Washington and Carla K. Johnson in Seattle contributed to this report.

Cannabis (Marijuana) Research Report What are marijuana's long-term effects on the brain?

Substantial evidence from animal research and a growing number of studies in humans indicate that marijuana exposure during development can cause long-term or possibly permanent adverse changes in the brain. Rats exposed to THC before birth, soon after birth, or during adolescence show notable problems with specific learning and memory tasks later in life. 32–34 Cognitive impairments in adult rats exposed to THC during adolescence are associated with structural and functional changes in the hippocampus. 35–37 Studies in rats also show that adolescent exposure to THC is associated with an altered reward system, increasing the likelihood that an animal will self-administer other drugs (e.g., heroin) when given an opportunity (see " Is marijuana a gateway drug? ").

Imaging studies of marijuana’s impact on brain structure in humans have shown conflicting results. Some studies suggest regular marijuana use in adolescence is associated with altered connectivity and reduced volume of specific brain regions involved in a broad range of executive functions such as memory, learning, and impulse control compared to people who do not use. 38,39 Other studies have not found significant structural differences between the brains of people who do and do not use the drug. 40

Several studies, including two large longitudinal studies, suggest that marijuana use can cause functional impairment in cognitive abilities but that the degree and/or duration of the impairment depends on the age when a person began using and how much and how long he or she used. 41

Among nearly 4,000 young adults in the Coronary Artery Risk Development in Young Adults study tracked over a 25-year period until mid-adulthood, cumulative lifetime exposure to marijuana was associated with lower scores on a test of verbal memory but did not affect other cognitive abilities such as processing speed or executive function. The effect was sizable and significant even after eliminating those involved with current use and after adjusting for confounding factors such as demographic factors, other drug and alcohol use, and other psychiatric conditions such as depression. 42

Some studies have also linked marijuana use to declines in IQ, especially when use starts in adolescence and leads to persistent cannabis use disorder into adulthood. However, not all of the studies on the link between marijuana and IQ have reached the same conclusion, and it is difficult to prove that marijuana causes a decline in IQ when there are multiple factors that can influence the results of such studies, such as genetics, family environment, age of first use, frequency of use, having a cannabis use disorder, duration of use, and duration of the study. Key research in this area to date is described below.

A large longitudinal study in New Zealand found that persistent marijuana use disorder with frequent use starting in adolescence was associated with a loss of an average of 6 or up to 8 IQ points measured in mid-adulthood. 43 Those who used marijuana heavily as teenagers and quit using as adults did not recover the lost IQ points. People who only began using marijuana heavily in adulthood did not lose IQ points. Two shorter-duration prospective longitudinal twin studies found that  youth who used marijuana showed significant declines in verbal ability (equivalent to 4 IQ points) and general knowledge between the preteen years (ages 9 to 12, before use) and late adolescence/early adulthood (ages 17 to 20); however those who went on to use marijuana at older ages already had lower scores on these measures at the start of the study, before they started using the drug. Also, no predictable difference was found between twins when one used marijuana and one did not. 44

More research will be needed to answer definitively whether marijuana use causes long-term IQ losses and whether factors that weren’t measured in the prior research, such as the increasing amounts of THC in cannabis and the emergence of new cannabis products, are relevant.

Also, the ability to draw definitive conclusions about marijuana’s long-term impact on the human brain from past studies is often limited by the fact that study participants use multiple substances, and there is often limited data about the participants’ health or mental functioning prior to the study. Over the next decade, the National Institutes of Health is funding the Adolescent Brain Cognitive Development (ABCD) study —a major longitudinal study that will track a large sample of young Americans from late childhood (before first use of drugs) to early adulthood. The study will use neuroimaging and other advanced tools to clarify precisely how and to what extent marijuana and other substances, alone and in combination, affect adolescent brain development.

Marijuana, Memory, and the Hippocampus

Distribution of cannabinoid receptors in the rat brain. Brain image reveals high levels (shown in orange and yellow) of cannabinoid receptors in many areas, including the cortex, hippocampus, cerebellum, and nucleus accumbens (ventral striatum).

Memory impairment from marijuana use occurs because THC alters how the hippocampus, a brain area responsible for memory formation, processes information. Most of the evidence supporting this assertion comes from animal studies. For example, rats exposed to THC in utero , soon after birth, or during adolescence, show notable problems with specific learning/memory tasks later in life. Moreover, cognitive impairment in adult rats is associated with structural and functional changes in the hippocampus from THC exposure during adolescence.

As people age, they lose neurons in the hippocampus, which decreases their ability to learn new information. Chronic THC exposure may hasten age-related loss of hippocampal neurons. In one study, rats exposed to THC every day for 8 months (approximately 30% of their lifespan) showed a level of nerve cell loss at 11 to 12 months of age that equaled that of unexposed animals twice their age.

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• Published: 06 May 2024

Ecological weed management and square planting influenced the weed management, and crop productivity in direct-seeded rice

• Mona Nagargade 1 , 2   na1 ,
• Manoj Kumar Singh 2   na1 ,
• Vishal Tyagi 1   na1 ,
• Prabhu Govindasamy 1 , 3   na1 ,
• Anil K. Choudhary 1 , 4 ,
• Kuldeep Rajpoot 2 ,
• Adarsh Kumar 5 ,
• Preeti Singh 6 &
• Debalin Sarangi 7  

Scientific Reports volume  14 , Article number:  10356 ( 2024 ) Cite this article

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• Plant sciences

Herbicide use may pose a risk of environmental pollution or evolution of resistant weeds. As a result, an experiment was carried out to assess the influence of different non-chemical weed management tactics (one hoeing (HH) at 12 DAS followed by ( fb ) one hand weeding at 30 DAS, one HH at 12 DAS fb Sesbania co-culture and its mulching, one HH at 12 DAS fb rice straw mulching @ 4t ha −1 , one HH at 12 DAS fb rice straw mulching @ 6 t ha −1 ) on weed control, crop growth and yield, and economic returns in direct-seeded rice (DSR). Experiment was conducted during kharif season in a split-plot design and replicated thrice. Zero-till seed drill-sown crop (PN) had the lowest weed density at 25 days after sowing (DAS), while square planting geometry (PS) had the lowest weed density at 60 DAS. PS also resulted in a lower weed management index (WMI), agronomic management index (AMI), and integrated weed management index (IWMI), as well as higher growth attributes, grain yield (4.19 t ha –1 ), and net return (620.98 US$ ha –1 ). The cultivar Arize 6444 significantly reduced weed density and recorded higher growth attributes, yield, and economic return. In the case of weed management treatments, one HH at 12 DAS fb Sesbania co-culture and its mulching had the lowest weed density, Shannon-weinner index and eveness at 25 DAS. However, one hoeing at 12 DAS fb one hand weeding at 30 DAS (HH + WH) achieved the highest grain yield (4.85 t ha –1 ) and net returns (851.03 US$ ha –1 ) as well as the lowest weed density at 60 DAS. PS × HH + WH treatment combination had the lowest weed persistent index (WPI), WMI, AMI, and IWMI, and the highest growth attributes, production efficiency, and economic return.

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Introduction.

On a global scale, rice is one of the stable food crops cultivated on around 165.25 million hectares, with a production of 787.29 million tonnes 1 . India is a major producer and consumer of rice, accounting for 27.27% of the global rice cultivated area (45.07 million hectares) and 15.79% of production 2 . Global rice demand is expected to rise by more than 40% by 2050 to fulfil the needs of the world's growing population 3 . Transplanted rice is still the most common and traditional planting method in India, requiring a large amount of natural resources and nonrenewable energy sources. As a consequence, meeting the ever-increasing demand for rice in the context of dwindling natural resources is a big concern 4 . Direct Seeded Rice (DSR) is an alternative choice for rice growers around the globe in the face of limited water and energy resources 5 . However, weed infestation is a major hurdle to the successful deployment of DSR. Weed competition throughout the season results in 100% yield reduction in DSR 6 . In general, the critical weed-free period for DSR goes from 11 to 83 DAS, which is longer than for transplanted rice 7 . Effective weed management in direct-seeded rice necessitates a multifaceted strategy. Many authors suggested that it is challenging to effectively manage weeds in DSR with a single strategy 8 , 9 . In this context, adopting the Integrated Weed Management (IWM) strategy, which involves the synergistic integration of at least two components, emerges as a successful approach capable of addressing this challenge comprehensively 10 . A more competitive crop has an edge over weeds and lowers weed-related yield losses 11 , 12 , 13 .

Adoption of short-duration, highly competitive, and high-yielding rice hybrids would be more cost-effective in northern India's productive Gangetic plains, where the rice–wheat cropping system (RWCS) persists. The early vigor and phenotypic flexibility of short-duration high-yielding rice hybrids demand the right geometry for a better DSR establishment. It is widely acknowledged that wider spacing and single rice transplanting in the system of rice intensification (SRI) result in profuse tillering and higher yield 14 . Wider spacing in hybrids reduces seed rate and production cost 12 , 15 . The wider spacing also facilitates mechanical weed control in the spaces between rows; however, it takes a long time for the canopy to close compared to the narrower rows 16 , 17 , this leads to a longer crucial period for weed management. However, weed-competitive hybrids quickly close the canopy, provide shade, and prevent weed growth 18 . Hybrids are more vigorous than inbred; therefore, the weed suppression ability of hybrids may be utilized in DSR rice. In general, the recommended seed rate for inbred varieties shown in zero-till seeders or dry direct-seeded method is 25–30 kg ha –1 in the DSR system 5 . The seed rate, like inbred lines, increases production costs and reduces the net return in hybrids. Therefore, DSR uses square planting geometry to provide identical growing conditions and better weed management like SRI in rice. There are opportunities to use cultural practices for better weed management in DSR 19 . There is a clear association between weed emergence time and crop yield loss 13 . Yield losses are greater when weeds emerge earlier or simultaneously with the crop 20 . Despite chemical weed control methods achieved distinctive successes for weed management in field crops, herbicide use could pose hazards in the environment. Therefore, mechanical and manual weed control methods are still preferred. A hoe at crop emergence may suppress weeds that germinate early, providing a competitive edge to rice seedlings. Manual weeding is the most common technique in rice; however, it is tedious and not economically feasible 21 . The combination of hoe and hand weeding is most appropriate, especially for small farms and places where laborers are cheap 22 . Also, the integration between mechanical and cultural or chemical methods exhibited better weed control efficiency than the use of individual practice 23 .

The soil organic carbon loss is a major concern in tropical regions due to rapid mineralization 24 . The inclusion of fast-growing nitrogen-fixing crops as cover crops or co-cultures might enhance the organic carbon content of the soil and improve the available nutrient status 25 . Co-cultivation of fast-growing crops like Sesabnia aculeata will suppress the weeds and add nitro-gen to the soil. According to Gill and Walia 26 , the use of S. aculeate residues conserves soil moisture and adds roughly 15 kg N ha –1 . The S. aculeata intercropping greatly reduce the weed density and biomass in DSR due to the low light transmission 27 . Residue retention enhances soil health by restoring the soil's physical characteristics 28 , and enhancing microbial activity and nutrient cycling 29 .

Mulching crop residue is a promising practice to suppress weed emergence and conserve moisture; however, this is almost impossible for large farms. The amount of rice straw is plentiful in the RWCS of northern India, and generally farmers burn the residues for easier and faster wheat planting 30 . The burning of residues pollutes the environment by emitting gases that are hazardous to human and environmental health 5 . There are several advantages in retaining rice residue. Rice straw can last longer in the field due to its higher lignin and silica content, which can help in managing weeds 31 . Furthermore, rice straw contains nutrients that can be recycled and utilized as organic fertilizer 32 , 33 , to improve soil fertility 34 , 35 . Retaining rice residue mulch provide an environmentally sound solution for managing weeds 13 , 24 . However, research on the effect of rice cultivars, planting geometry, and non-chemical weed management on weed density, diversity, and performance of hybrid rice cultivars is sparse.

Knowledge in these areas would make ecological weed management easier. To accomplish this, we hypothesise that the integration of cultivars, crop geometry, and non-chemical weed management approaches will result in sustainable rice production and weed management as well as healthy environment. The outcomes of this research can significantly contribute to the advancement of sustainable and economically viable agricultural practices. Therefore, a study was conducted with the following objectives: (1) to assess the influence of planting geometry, cultivars, and non-chemical weed management on crop performance, weed density and diversity of hybrid rice production (2) to analyze the economic implications of implementing these approaches in hybrid rice production. These objectives aim to offer valuable insights that can guide the development of economically viable and sustainable weed management practices in DSR.

Results and discussion

During the two-year study period, fourteen weed species from six different families were recorded at the experimental site. Among these, six species were grasses [i.e., bermudagrass ( Cynodon dactylon (L.) Pers . ), large crabgrass ( Digitaria sanguinalis (L.) Scop) , jungle rice ( Echinochloa colona (L.) Link), barnyardgrass ( Echinochloa crus-galli (L.) P. Beauv), goosegrass ( Eleusine indica (L.) Gaertn.) , and torpedograss ( Panicum repens L.), five species were broadleaves [ i.e., blistering ammannia ( Ammannia baccifera L.), pink node flower ( Caesulia axillaris Roxb .) , eclipta ( Eclipta alba (L.) Hassk.), water primrose ( Ludwigia parviflora Roxb.), and gulf leafflower ( Phyllanthus fraternus G.L.Webster), and three species were sedges [i.e., smallflower umbrella ( Cyperus difformis L.), flatsedge (Cyperus iria L.) and grasslike fimbry ( Fimbristylis miliacea (L.) Vahl)]. The grasslike fimbry, blistering ammannia , jungle rice and bermuda grass were the dominant weed species and had the highest relative densities of 12.15%, 11.66%, 11.14%, and 11.12%, respectively (Fig. S1 ).

Weed density

Grasses, broadleaf, sedges, and total weed densities were significantly (p < 0.05) influenced by planting geometry, cultivars, and non-chemical weed management at 25 and 60 DAS (Table 1 ). At 25 DAS, grass, sedge, broadleaf, and total weed densities were 18.14%, 21.13%, 29.04% and 22.36%, lower respectively, for P N compared to P S geometry. In contrast, inverse occurred at 60 DAS, where P S observed 23.93%, 26.64%, 18.03%, and 22.67% lower weed densities of grasses, sedges, broadleaf, and total weeds, respectively, than P N . Lower weed densities in P S geometry may be due to weed growth smothering as a result of uniform plant-to-plant and row-to-row spacing 30 , 36 . Square planting further encourages crops to compete with weeds as a result of the better availability of space, light, and nutrients 18 , 37 , 38 . Nichols et al. 39 , and Dass et al. 13 , reported that a uniform row-to-row and plant-to-plant distance in rice had a lower weed-competition. Among cultivars, Arize 6444 (hybrid from Bayer) was more competitive with weeds than PHB 71 (hybrid from Pioneer) at 25 and 60 DAS. Faster emergence and robust seedlings of Arize 6444 were thought to be reasons for increased competitiveness. The cultivars that achieve early vegetative vigor and quick ground cover have a competitive advantage over weeds compared to varieties that have slow initial growth 35 , 40 . With regards to weed management treatments, H H  + S C had the lowest grass, broad-leaf, sedge, and total weed densities at 25 DAS, with reductions of 90.61%, 91.81%, 89.05%, and 90.19%, respectively, compared to the weedy check.

However, H H  + W H treatment had the lowest weed densities at 60 DAS with 92.77%, 46.77%, 58.52% and 53.64% lower densities of grassy, broad-leaf, sedges, and total weeds compared to the weedy check. Further, treatments H H  + M R4 and H H  + M R6 recorded lower weed densities than W C at both the stages. Early prevention and suppression of weed germination and growth could be the reason for the lowest weed density in the H H  + S C treatment. Keeping the weeds free at an early stage (hand hoeing at 12 DAS) and during the peak weed emergence period (manual weeding during the active tillering stage at 30 DAS) might have resulted in reduced weed competition and weed density of all the weeds at later stages 12 , 18 .

Interaction of planting geometry (PG) × cultivar (CV), CV × weed management (WM), and PG × CV × WM did not influence the weed density at 25 and 60 DAS (Table 1 ). However, planting geometry × weed management significantly (p < 0.05) influenced the broadleaf, sedge, and total weed densities at 25 DAS, and broadleaf weed density at 60 DAS (Table 1 ). The interaction of PG × WM revealed that P N and H H  + S C combinations resulted in the lowest broadleaf, sedge, and total weed densities (Fig.  1 a,b). This could be due to the lack of space available for weed growth in close spacing and smothering effect of sesbania co-culture treatments 18 , 41 . The lowest broadleaf density at later stage under P S and H H  + W H combinations may be due to keeping the plots weed free in hand hoeing fb hand weeding treatments and faster crop growth when planted in the square pattern.

Interaction effect of planting geometry × weed management on sedge, broadleaf and total weed densities at 25 DAS ( a ) and broadleaf density at 60 DAS ( b ). PN, sowing with seed drill at 18.5 cm row spacing; PS, square planting at 25 cm × 25 cm row to row and plant to plant spacing; W0, weedy check (no weed management); HH + WH, one hand hoeing at 12 DAS fb one hand weeding at 30 DAS; HH + SC, one hand hoeing at 12 DAS fb Sesbania aculeata co-culture and mulched 45 DAS; HH + MR4, one hand hoeing at 12 DAS fb rice residue mulching @ 4 t ha −1 ; HH + MR6, one hand hoeing at 12 DAS fb rice residue mulching @ 6 t ha −1 . Means with different alphabets are significant (P < 0.05). Values shown in the figure are square-root [√(x + 0.5)]-transformed means.

Weed diversity indices

Weed diversity indices such as dominance, evenness, and diversity were not influenced by PG, CV, or their interaction (Table 2 ). However, weed management (WM) had a significant effect on all the weed indices at 25 and 60 DAS. The H H  + S C weed management treatment had the lowest Shannon–Wiener and evenness indices but the highest dominance index (Table 2 ). The lowest Shannon–Wiener and evenness indices values in H H  + S C treatment indicate greater control of weeds 42 . Data on evenness (close to 1) indicates that weed species distribution in this experiment is more uniform across treatments. Weed evenness was not influenced by the interaction between PG and CV and PG, CV and WM at either evaluation date (25 or 60 DAS). However, at 25 DAS, PG × WM and CV × WM had a significant effect on evenness (Fig.  2 a,b).

Interaction effect of planting geometry × weed management and cultivar × weed management on evenness at 25 ( a , b ) and 60 DAS ( c , d ). P N , sowing with seed drill at 18.5 cm row spacing; P S , square planting at 25 cm × 25 cm row to row and plant to plant spacing; W C , weedy check (no weed management); H H  + W H , one hand hoeing at 12 DAS fb one hand weeding at 30 DAS; H H  + S C , one hand hoeing at 12 DAS fb Sesbania aculeata co-culture and mulched 45 DAS; H H  + M R4 , one hand hoeing at 12 DAS fb rice residue mulching @ 4 t ha −1 ; H H  + M R6 , one hand hoeing at 12 DAS fb rice residue mulching @ 6 t ha −1 . Means with different alphabets are significant (P < 0.05).

Likewise, at 60 DAS, the interaction of PG × WM and CV × WM had a significant effect on evenness (Fig.  2 b,c), dominance (Fig.  3 a,b), and the Shannon–Wiener index (Fig.  3 b,c). Compared to other treatments, Ps and the H H  + S C combination had significantly lower values of evenness and Shannon–Wiener index and the highest dominance value.

Interaction effect of planting geometry × weed management and cultivar × weed management on dominance ( a , b ) and Shannon-Weiner index ( c , d ) at 60 DAS. P N , sowing with seed drill at 18.5 cm row spacing; P S , square planting at 25 cm × 25 cm row to row and plant to plant spacing; W C , weedy check (no weed management); H H  + W H , one hand hoeing at 12 DAS fb one hand weeding at 30 DAS; H H  + S C , one hand hoeing at 12 DAS fb Sesbania aculeata co-culture and mulched 45 DAS; H H  + M R4 , one hand hoeing at 12 DAS fb rice residue mulching @ 4 t ha −1 ; H H  + M R6 , one hand hoeing at 12 DAS fb rice residue mulching @ 6 t ha −1 . Means with different alphabets are significant (P < 0.05).

Weed control efficiency indices

Planting geometry had a significant effect (p < 0.05) on WMI, AMI, and IWMI, but did not influence the CRI and WPI (p > 0.05, Table 3 ). Compared to the zero-till seed drill sown method, the square planting (P S ) method had a lower WMI, AMI, and IWMI, which indicates the effectiveness of this method on weed suppression. The lowest values of WMI, AMI, and IWMI indicate better weed control and a higher yield. The lowest values of WMI and AMI were recorded in earlier studies by Mishra et al. 43 and Kumar et al. 24 with treatments that efficiently reduced weeds and increased grain yield.

Cultivars influenced the CRI significantly (p < 0.05) compared to other indices. The cultivar Arize 6444 resulted in a higher CRI value than the cultivar PHB 71. CRI indicates increased vigor of crop plants due to weed control. Superior crop growth and biomass production of the Arize 6444 cultivar could be the reason for the higher CRI value. Garko et al. 44 also reported a significant effect of different varieties on CRI in maize crop. The weed management treatments greatly influenced all the weed management indices. Among weed management treatments, H H  + W H performed well; therefore, this treatment had a 169% higher CRI than the weedy check.

Furthermore, H H  + W H treatment resulted in the lowest values of WPI, WMI, AMI, and IWMI over other treatments. The lower WPI, WMI, AMI, and IWMI indicate superior weed control.

The interaction effect of planting geometry × weed management revealed that P S  × H H  + W H had a lower value of WPI, WMI, AMI, and IWMI (Fig. S2 a). Square planting and hand hoeing at the early stage fb hand weeding at peak weed emergence period could have resulted in better weed control than other combinations. The interaction of cultivar × weed management only had a significant effect on CRI (Fig. S2 b). Greater suppression and control of weeds under the combination of Arize 6444 × H H  + W H treatment might have led to a higher CRI.

Crop growth parameters

Planting geometry, cultivar, and weed management influenced the crop growth parameters (Table 4 ). However, the interaction effect of planting geometry, cultivar, and weed management did not influence except the number of tillers by planting geometry-by-cultivar and dry matter production by cultivar-by-weed management. The number of tillers (number m −2 ) and dry matter production (g running m −1 ) were (p < 0.05) 7.6% and 13.11% higher, respectively, for the square planting (P S ) compared to the zero-till seed drill sown crop (P N ). This could be due to optimum crop spacing that allowed the radiant energy, nutrients, and water to utilize; as a result, more tillers and robust crop growth were achieved under the square planting method 6 . On the other hand, De Datta 45 , reported that a higher seed rate in a seed drill-sown crop with normal spacing increases inter-and intra-plant competition, which leads to poor utilization of applied inputs, poor crop growth, and a lesser number of tillers. Furthermore, the square planting treatment decreased weed competition compared to zero-till seed drill-sown crop; this could also be the reason for the better growth and development. Cultivars only influenced the dry matter accumulation but not the number of tillers (Table 4 ). The Arize 6444 resulted in 8.41% higher dry matter production than the PHB 71; the higher dry matter for Arize 6444 could be the result of greater plants height and tiller production 46 .

The weed management treatments, H H  + W H and H H  + S C resulted in the highest number of tillers and dry matter compared to other weed management treatments (Table 4 ). Hoeing and hand weeding at the early phases of crop growth might have nullified the early weed competition and ultimately led to a greater number of tillers and dry matter. Our findings are in agreement with Johnson et al. 47 who reported that early-stage weed control in direct-seeded rice reduced weed pressure and increased grain yield. Growing S. aculeata and retaining its mulch in rice can suppress the weeds effectively 48 . Additionally, mineralization of residues provides available nutrients to crops at critical stages, which has a positive effect on crop growth at an early stage 49 , 50 .

Planting geometry × weed management had a significant effect on the number of tillers. The interaction effect of P S and H H  + W H resulted in a maximum number of tillers, followed by P N and H H  + S C and P N and H H  + M R treatment combinations (Fig.  4 a). Cultivar × weed management was found significant for dry matter accumulation. Arize 6444 and H H  + W H , Arize 6444 and H H  + S C combinations had a higher dry matter accumulation (Fig.  4 b). The authors believed that this could be due to the synergistic effect of wider spacing in square planting and control of weeds by hand hoeing fb hand weeding, and hand hoeing fb Sesbania co-culture treatments.

Interaction effect of planting geometry × weed management, and cultivar × non-chemical weed management on number of tillers ( a ), dry matter production ( b ) and production efficiency of rice ( c , d ). P N , sowing with seed drill at 18.5 cm row spacing; P S , square planting at 25 cm × 25 cm row to row and plant to plant spacing; W C , weedy check (no weed management); H H  + W H , one hand hoeing at 12 DAS fb one hand weeding at 30 DAS; H H  + S C , one hand hoeing at 12 DAS fb Sesbania aculeata co-culture and mulched 45 DAS; H H  + M R4 , one hand hoeing at 12 DAS fb rice residue mulching @ 4 t ha −1 ; H H  + M R6 , one hand hoeing at 12 DAS fb rice residue mulching @ 6 t ha −1 . Means with different alphabets are significant (P < 0.05).

Crop productivity

Compared to zero-till seed drill-sown crop (P N ), square planting (P S ) achieved a ~ 7.6% higher grain yield (Table 4 ). Vigorous crop growth, minimum inter-specific competition, a higher number of tillers, and greater weed suppression might be responsible for higher yields in the square planting method 12 , 18 , 51 . Previous studies reported that direct-seeded rice in the square planting method had a higher grain yield compared to normal planting 52 . Among cultivars, Arize 6444 produced a 10.7% higher grain yield than PHB 71. The higher grain yield for Arize 6444 could be attributed to increased dry matter accumulation, more tillers, faster crop growth, and better weed suppression 15 . With respect to weed management tactics, the H H  + W H recorded the highest grain yields (4.85 t ha −1 ), followed by the H H  + S C (4.68 t ha −1 ). Hoeing fb hand weeding during the critical crop-weed competition period might have reduced the weed competition and led to better crop performance 14 , 53 . Early weed control is crucial in DSR for improved crop growth and yield 5 , 6 . The hand hoeing fb either hand weeding or Sesbania spp. co-culture resulted in a weed-free condition and improved yield. Similarly, Maity and Mukherjee 49 , also reported that co-culture of Sesbania with rice smothered weeds and enhanced the grain yield of rice. Likewise, Baumann et al. 27 , and Gopal et al. 54 , observed a higher grain yield and available N content in soil under S. aculeata co-culture in direct seeding.

The interaction between planting geometry or cultivar and weed management tactics significantly influenced the grain yield. The treatment P S and H H  + W H combination achieved the highest grain yield, followed by P S and H H  + S c , P N and H H  + S c , and P N and H H  + W H (Table S1 ). Among weed management and cultivar interactions, the highest grain yield was observed for Arize 6444 × H H  + W H and Arize 6444 × H H  + Sc combinations (Table S2 ). Better crop growth, higher dry matter accumulation, and greater weed suppression ability of the Arize 6444 cultivar with square planting and hand hoeing fb hand weeding or hand hoeing fb Sesbania spp. co-culture could be the reasons for the higher grain yield.

Planting geometry, cultivar, and weed management had a significant impact on production efficiency. The results showed that square planting (P S ) had the maximum production efficiency compared to zero-till seed drill-sown crops (P N ). The higher yield with square planting could be attributed to improved production efficiency. Among cultivars, Arize 6444 resulted in higher production efficiency than PHB 71. The H H  + W H achieved the highest production efficiency across weed management treatments and was comparable to H H  + Sc. The increased crop yield per day was believed to be a reason for the higher production efficiency in H H  + W H and H H  + Sc. The P S and H H  + W H interactions increased production efficiency (Fig.  4 c). The cultivar × weed management interaction revealed that maximum production efficiency was recorded for Arize 6444 and H H  + W H (Fig.  4 d). This could also be because of the higher grain yield ha −1  day −1 and effective weed control 12 .

Economic analysis

A slightly higher cost of cultivation (COC) was registered for P N (600.55 US$) compared to P S (591.47 US$), which was due to the higher cost of hybrid seeds used under seed-drill sown crops (Table 5 ). Square planting had higher gross returns (GR) by 7.24%, net returns (NR) by 15.59%, and B: C ratio of 8.78% than zero-till drill sown crops. This was because of the lower COC coupled with a higher GR in P S than P N . Cultivars did not influence the COC due to similar seed rates, seed costs, and other inputs. However, higher GR, NR, and BCR were obtained for Arize 6444 compared to PHB 71 because of the higher yield under Arize 6444 12 , 18 . The COC for weed control treatments ranged from 459.46 to 763.22 US$ ha −1 ; W C had the lowest COC and H H  + M R6 had the highest. Rice straw was applied at a rate of 6 t ha −1 and the higher cost of rice straw was the reason for the higher COC in the H H  + M R6 treatment. Higher GR (1398.26 US$ ha –1 ) and NR (851.03 US$ ha –1 ) were observed under H H  + W H and H H  + S C, and the least was with W C in both years. However, BCR was higher for H H  + S C fb H H  + W H treatment. These results could be the result of lower weed density under H H  + W H and H H  + S C 14 . The interaction effect between planting geometry × weed management was found to be significant for GR, NR and BCR (Fig.  5 a–c). Highest GR, NR, and BCR were recorded under interaction of P s and H H  + W H as compared to other treatment combinations.

Interaction effect of planting geometry × weed management on gross return, net return and B:C ratio of rice. P N , sowing with seed drill at 18.5 cm row spacing; P S , square planting at 25 cm × 25 cm row to row and plant to plant spacing; W C , weedy check (no weed management); H H  + W H , one hand hoeing at 12 DAS fb one hand weeding at 30 DAS; H H  + S C , one hand hoeing at 12 DAS fb Sesbania aculeata co-culture and mulched 45 DAS; H H  + M R4 , one hand hoeing at 12 DAS fb rice residue mulching @ 4 t ha −1 ; H H  + M R6 , one hand hoeing at 12 DAS fb rice residue mulching @ 6 t ha −1 . Means with different alphabets are significant (P < 0.05).

Conclusions

The results emphasize the importance of selecting appropriate weed management strategies for sustainable DSR, taking into account both environmental considerations and economic feasibility. The findings from this study revealed that Arize 6444, the square planting system, and the hoeing fb hand weeding performed better in terms of yield than PHB 71, normal planting and other weed management practices. However, the higher cost of manual weeding and the unavailability of labors are the main drawbacks of the hoeing fb hand weeding system. Alternatively, Arize 6444, square planting geometry, and hoeing at 12 DAS fb Sesbania co-culture mulch at 45 DAS enhanced the productivity and profitability of DSR and significantly reduced weed density in the Eastern region of India. These findings contribute valuable insights to the ongoing efforts to promote sustainable and environmental friendly weed management practices, mitigating the risks associated with herbicide use and potential evolution of resistant weeds in direct-seeded rice systems. Development and research on precise seeding machines is a future research area for wider adoption of hybrids in DSR systems, higher weed control efficiency, and higher yield. Additionally, an assessment of the long-term impacts of the proposed weed management strategies on soil health, biodiversity, and overall ecosystem resilience is needed.

Materials and methods

Experimental site and weather conditions.

Field experiments were carried out at the Agricultural Research Farm of the Institute of Agricultural Sciences, Banaras Hindu University, Varanasi (25,018′ N and 88,003′E), Uttar Pradesh, India, during the rainy seasons (June to October) in 2015 and 2016. The cropping system at the site has been rice followed by wheat for the last six years. The climate of the site is sub-tropical; May and June were the hottest months (maximum temperature 31–36 °C) and January was the coldest month (minimum temperature 7–14 °C). Annual rainfall averages 1036.8 mm and 87.3% of them are received between June and September (South-West Monsoon), and the remaining 13.7% is received between October and May (western disturbances and other climatological factors). The weather parameters are presented in Fig. S3 . The soil type was a sandy clay loam (Typic Haplusteptiso-hyperthermic family, Inceptisol) 55 with 0.4% organic carbon, 7.5 pH, 0.21 dsm –1 EC, 182.67 kg ha –1 available N, 22.12 kg ha –1 available P, and 216.5 kg ha –1 exchangeable K.

Treatment details and crop management

The experiments were arranged in a split-split plot design with three trial factors (planting geometries, cultivars, and non-chemical weed management) in three replications. Two planting geometries [normal (PN) and square planting (PS)] were arranged in the main-plots, two cultivars (Arize 6444 and PHB 71) in the sub-plots, and five non-chemical weed management treatments [weedy check (WC), single hoeing (1 HH) at 12 DAS fb one hand weeding (1 HW) at 30 DAS (HH + WH), 1 HH at 12 DAS fb Sesbania co-culture and its mulching (HH + Sc), 1 HH at 12 DAS fb rice straw mulching @ 4t ha −1 (HH + MR4), and 1 HH at 12 DAS rice straw mulching @ 6 t ha −1 (HH + MR6)] in the sub-subplots (Table 1 ). The main plot size was 40 m × 5 m, the sub-plot size was 20 m × 5 m, and the sub-sub plot was 4 m × 5 m. The field was prepared with one pass of moldboard plough fb disk to uproot established perennial weeds. Finally, two passes of cultivator and planking were done to provide a good tilth suitable for a DSR crop. The sowing dates were June 22, in 2015 and June 28, in 2016. Nitrogen (150 kg ha −1 ), P 2 O 5 (60 kg ha −1 ), and K 2 O (60 kg ha −1 ) were applied at the recommended rates through urea (NH 2 ) 2 CO), di-ammonium phosphate ((NH4) 2 HPO 4 ) and muriate of potash (KCl), respectively. Half of the recommended nitrogen and full doses of phosphorus and potassium were applied at the time of sowing. The remaining nitrogen was given in two equal portions at the tillering and panicle initiation stages. The crop was harvested manually on 28th October in 2015 and 5th November in 2016 (Table 6 ).

Weed observations

Weed density and composition.

In each plot, two quadrates (1 m 2 ) were placed randomly for weed observations (25 and 60 DAS). Weeds were classified as grass, broadleaf, and sedge after identification. At 60 DAS, the relative density of various weed flora was calculated by dividing the weed density of each weed species by the overall weed density in the weedy check plot and multiplying the result by 100.

Weed dominance, diversity and evenness were assessed at 25 and 60 DAS by estimating the Simpson’s index 56 , Shannon–Wiener index 57 and Pielou’s measure 58 , respectively using the Past software (v.4.03) (Eqs.  1 – 3 ).

where ni is the number of species i , pi is the proportion of the species i in total number of species, N is the total number of individuals in a sample.

where H is the species diversity index (i.e., Shannon–Wiener index), and S is the species richness (number of weed species present in a plot).

Weed control indices

The weed control efficiency indices were calculated using weed dry matter and density data as well as crop dry matter and yield data at 25 and 60 DAS 59 , 60 (Eqs.  4 – 8 ).

where, CRI = Crop Resistance Index, DMC T  = Dry matter of crop in treated plot, DMC C  = Dry matter of crop in control plot (weedy), DMW C  = Dry matter of weed in control plot, DMW T  = Dry matter of weed in treated plot.

where, WPI = Weed Persistence Index, DMW T  = Dry matter of weed in treated plot, DMW C  = Dry matter of weed in control plot, WC C  = Weed count in control plot, WC T  = Weed count in treated plot.

where, WMI = Weed Management Index, Y T  = Crop yield in treated plot, Y C  = Crop yield in control plot, DMW C  = Dry matter of weed in control plot, DMW T  = Dry matter of weed in treated plot.

where, AMI = Agronomic Management Index, Y T  = Crop yield in treated plot, Y C  = Crop yield in control plot, DMW C  = Dry matter of weed in control plot, DMW T  = Dry matter of weed in treated plot.

where, IWMI = Integrated Weed Management Index, WMI = Weed Management Index, AMI = Agronomic Management Index.

Crop studies

At 90 DAS, the number of tillers in each plot was counted from a 1 m 2 area. To calculate the dry matter accumulation, destructive plant sampling was performed from a meter row. These samples were sun-dried and then oven-dried at 65 °C for 72 h to achieve a constant dry weight. The plant dry weight is expressed in g m −1 row length. At harvest, plot-wise produce was threshed independently, and grain yield was measured in kg ha –1 . The production efficiency was calculated (kg ha −1  day −1 ) by dividing the grain yield by the number of days needed for each treatment to reach maturity.

The economics were computed using current market input prices and the return on the final output (grain and straw yield). The production cost includes human labour, tilling, seeding, seed, straw, fertilizer, irrigation, harvesting and threshing, and the cost of transportation to market (Table S3 ). The following formulae were used to calculate the gross and net returns and the benefit-cost (B: C) ratio (Eqs.  9 – 11 ) 24 .

All economic analyses were expressed in US$ by converting 1 USD = 67 Indian rupees (INR).

Statistical analysis

The data were subjected to analysis of variance (ANOVA) as described by Gomez and Gomez 61 . The normality of weed data was confirmed using the Shapiro–Wilk test (p < 0.05) and it was found non-normal. Therefore, the square-root transformation √(x + 0.5) was performed. Weed diversity indices such as dominance, diversity and evenness were calculated using the PAST software (version 4.03). In ANOVA, planting geometry, cultivars, weed management, and year were considered as the fixed effects, and replication was considered as the random effect. We did the combine analysis of data and found that there was no significant effect (p > 0.05) of years on weed density, diversity indices, weed control efficiency indices, available NPK in soil, number of tillers, dry matter production, grain yield, production efficiency and economics. Therefore, we did the pooled analysis of years. The treatment means were compared using Fisher’s LSD test at a 5% level of significance. All the analysis was performed using R software (version 4.0) 62 .

Authors have confirmed that all the plant studies were carried out in accordance with relevant national, international or institutional guidelines.

Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to private and ethical restrictions.

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These authors are equally contributed: Mona Nagargade, Manoj Kumar Singh, Vishal Tyagi and Prabhu Govindasamy.

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Agronomy, ICAR-Indian Agricultural Research Institute, New Delhi, 110012, India

Mona Nagargade, Vishal Tyagi, Prabhu Govindasamy & Anil K. Choudhary

Department of Agronomy, Institute of Agricultural Sciences, Banaras Hindu University, Uttar Pradesh, Varanasi, 221005, India

Mona Nagargade, Manoj Kumar Singh & Kuldeep Rajpoot

ICAR-National Research Centre for Banana, Tiruchirappalli, 620 102, India

Prabhu Govindasamy

ICAR-Central Potato Research Institute, Himachal Pradesh, Shimla, 171001, India

Anil K. Choudhary

ICAR-National Bureau of Agriculturally Important Microorganisms, Mau, Uttar Pradesh, 275101, India

Adarsh Kumar

ICAR- Indian Agricultural Research Institute, Jharkhand, 825405, India

Preeti Singh

University of Minnesota, Minneapolis, MN, 55108-6026, USA

Debalin Sarangi

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M.N., M.K.S., V.T., led the research work, planned, supervised, and conducted field experiments, and read and edited the manuscript. P.G., A.K.C., K.R., A.K., statistical analysis, data curation, review and editing. P.S., review and editing, data curation. D.S., final editing.

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Nagargade, M., Singh, M.K., Tyagi, V. et al. Ecological weed management and square planting influenced the weed management, and crop productivity in direct-seeded rice. Sci Rep 14 , 10356 (2024). https://doi.org/10.1038/s41598-024-56945-y

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eFigure. Flowchart for Sample Construction

eTable 1. Association Between Baseline e-Cigarette Use and Subsequent Cannabis Use (Past 12-Month and Past 30-Day) Among Baseline Never Cannabis Users, Comparing aRRs and aORs

eTable 2. Association Between Baseline Ever e-Cigarette Use and Subsequent Cannabis Use (Past 12-Month and Past 30-Day) Among Baseline Never Cannabis Users

eTable 3. Association Between Baseline Past 12-Month e-Cigarette Use and Subsequent Cannabis Use (Past 12-Month and Past 30-Day) Among Baseline Never Cannabis Users

eTable 4. Association Between Baseline Past 30-Day e-Cigarette Use and Subsequent Cannabis Use (Past 12-Month and Past 30-Day) Among Baseline Never Cannabis Users

eTable 5. Global Appraisal of Individual Needs – Short Screener (GAIN-SS) Items

eTable 6. Association Between Baseline e-Cigarette Use and Subsequent Cannabis Use Among Baseline Never Cannabis Users, With Additional Measures of Internalizing and Externalizing Problems

eTable 7. Association Between Baseline e-Cigarette Use and Subsequent Cannabis Use Among Baseline Never Cannabis Users, Without Sensation Seeking

eTable 8. Association Between Baseline e-Cigarette Use and Subsequent Cannabis Use Among Baseline Never Cannabis Users, With Participants Answering “Don’t Know” or “Refused” Considered Users or Nonusers of the Product

eTable 9. Association Between Baseline e-Cigarette Use and Subsequent Past 12-Month Cannabis Vaping Among Baseline Never Cannabis Users

eTable 10. Predicted Changes in Youth Cannabis Use (2018-2019) Due to Changes in e-Cigarette Use (2017-2018), Assuming Estimated Association to be 100% Causal

• Association Between e-Cigarette Use Among Cannabis-Naive Adolescents and Future Cannabis Use JAMA Network Open Invited Commentary July 22, 2022 Wilson M. Compton, MD, MPE; Emily B. Einstein, PhD

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Sun R , Mendez D , Warner KE. Use of Electronic Cigarettes Among Cannabis-Naive Adolescents and Its Association With Future Cannabis Use. JAMA Netw Open. 2022;5(7):e2223277. doi:10.1001/jamanetworkopen.2022.23277

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Use of Electronic Cigarettes Among Cannabis-Naive Adolescents and Its Association With Future Cannabis Use

• 1 Department of Health Policy and Organization, School of Public Health, University of Alabama at Birmingham
• 2 Department of Health Management and Policy, School of Public Health, University of Michigan, Ann Arbor
• Invited Commentary Association Between e-Cigarette Use Among Cannabis-Naive Adolescents and Future Cannabis Use Wilson M. Compton, MD, MPE; Emily B. Einstein, PhD JAMA Network Open

Question   Is electronic cigarette use among cannabis-naive adolescents in the US associated with increased likelihood of future cannabis use?

Findings   With the use of longitudinal data on a nationally representative cohort of 9828 youths from 2017 to 2019, this cohort study found that cannabis-naive adolescents who have used electronic cigarettes are significantly more likely to report cannabis use 1 year later compared with those who have not used electronic cigarettes.

Meaning   The findings of this cohort study suggest that adolescent electronic cigarette use was associated with an increased likelihood of future cannabis use, but the overall association of electronic cigarette use with youth cannabis use at the population level is likely quite small.

Importance   Electronic cigarette (e-cigarette) use has been reported to increase the likelihood of future cigarette smoking among adolescents. The prospective association between e-cigarette use and cannabis use has been less clear, especially in recent years.

Objective   To examine the association between e-cigarette use among cannabis-naive adolescents and cannabis use 1 year later.

Design, Setting, and Participants   The Population Assessment of Tobacco and Health (PATH) Study, a nationally representative cohort study, uses a 4-stage, stratified probability sample design to select participants aged 12 years or older from the US civilian, noninstitutionalized population. This study sample included 9828 cannabis-naive adolescents at the baseline survey who participated in both wave 4.5 (2017-2018) and wave 5 (2018-2019) of PATH.

Exposures   e-Cigarette use, assessed by ever use, past 12-month use, and past 30-day use.

Main Outcomes and Measures   Cannabis use in wave 5, assessed by past 12-month and past 30-day use. Multivariable logistic regressions assessed the association between e-cigarette use and cannabis use 1 year later. Results were weighted to produce nationally representative findings.

Results   Of the 9828 adolescents included in the analysis, 5361 (57.3%) were aged 12 to 14 years, 5056 (50.7%) were male, and 4481 (53.0%) were non-Hispanic White. After adjustment for sociodemographic characteristics, environmental factors, other substance use, and sensation seeking, e-cigarette use among cannabis-naive adolescents was associated with increased likelihoods of both self-reported past 12-month and past 30-day cannabis use 1 year later. The adjusted relative risks (aRRs) of subsequent past 12-month cannabis use with ever use of e-cigarettes was 2.57 (95% CI, 2.04-3.09), with past 12-month use of e-cigarettes was 2.62 (95% CI, 2.10-3.15), and with past 30-day use of e-cigarettes was 2.18 (95% CI, 1.50-2.85). The aRRs of subsequent past 30-day cannabis use with ever use of e-cigarettes was 3.20 (95% CI, 2.10-4.31), with past 12-month use of e-cigarettes was 3.40 (95% CI, 2.17-4.63), and with past 30-day use of e-cigarettes was 2.96 (95% CI, 1.52-4.40).

Conclusions and Relevance   This cohort study’s findings suggest a strong association between adolescent e-cigarette use and subsequent cannabis use. However, despite the strong association at the individual level, e-cigarette use seems to have had a minimal association with the prevalence of youth cannabis use at the population level.

Since 2014, electronic cigarettes (e-cigarettes) have become the most commonly used nicotine-containing product among US middle school and high school students. 1 , 2 According to the National Youth Tobacco Survey, the prevalence of past 30-day e-cigarette use increased from 11.7% to 27.5% among high school students from 2017 to 2019. 3 , 4 For middle school students, the prevalence of past 30-day e-cigarette use increased from 3.3% to 10.5% from 2017 to 2019. e-Cigarette use decreased significantly among middle school and high school students in 2020 and 2021; 11.3% of high school students and 2.8% of middle school students reported past 30-day e-cigarette use in 2021. 5 , 6

The popularity of e-cigarettes has raised concern owing to their potential to serve as a gateway to smoking cigarettes. 7 , 8 Many studies have found that youths who use e-cigarettes have higher odds of future cigarette smoking compared with those who do not use e-cigarettes. A systematic review of 17 studies comprising youths and young adults found strong evidence for a significant association between e-cigarette use and later smoking, with an odds ratio (OR) of 4.59 (95% CI, 3.60-5.85). 9 However, the positive association may disappear with a comprehensive selection of control variables. 10

Although most studies have focused on the association between e-cigarette use and smoking cigarettes, similar concerns have been raised for the use of e-cigarettes as a gateway to cannabis use. 11 , 12 Vaping (use of e-cigarettes and similar devices) involves heating liquid, oil, or plant material to a temperature that releases an aerosolized mixture of water vapor and active ingredients, such as nicotine in e-cigarettes and tetrahydrocannabinol (THC) in cannabis. The availability of these vaping devices makes it easier for adolescents to try cannabis. The National Academies of Sciences, Engineering, and Medicine reported evidence that cannabis use among youths is correlated with impaired cognitive abilities and life achievement, along with increased rates of mental health disorders, such as depression and anxiety. 13

A growing body of literature has found that youths who use e-cigarettes are more likely to initiate cannabis use than their peers who do not use e-cigarettes. 14 - 21 A meta-analysis from Chadi et al 21 reported that the odds of cannabis use increased significantly among youths who used e-cigarettes, both in longitudinal studies (adjusted OR [aOR], 2.43 [95% CI, 1.51-3.90]) and in cross-sectional studies (aOR, 3.70 [95% CI, 2.76-4.96]).

All of the longitudinal studies assessing the association between e-cigarette use and cannabis use among US adolescents examined data from 2013 to 2017. 13 , 16 - 19 Little is known about whether this positive association has persisted more recently, especially from 2017 to 2019 when the prevalence of youth e-cigarette use rapidly increased. To address this gap, we analyzed longitudinal data from the 2 most recent waves of the Population Assessment of Tobacco and Health (PATH) Study (wave 4.5 [2017-2018] and wave 5 [2018-2019]). We also examined multiple measures of e-cigarette use and cannabis use. We assessed e-cigarette use using ever, past 12-month, and past 30-day use, with cannabis use examined via past 12-month and past 30-day use. Thus, we investigated the association between baseline e-cigarette use and cannabis use 1 year later among never cannabis users at baseline, controlling for multiple independent risk factors, including sociodemographic characteristics, environmental factors, other substance use, and sensation seeking.

The PATH Study is a nationally representative, longitudinal cohort study of youths and adults in the US. The study uses a 4-stage, stratified probability sample design to select youths and adults from the US civilian, noninstitutionalized population. Surveys were conducted via audio computer-assisted self-interviews and computer-assisted personal interviews to collect self-reported data on tobacco use and related health behaviors. A full description of the PATH Study design and methods is available elsewhere. 22 Our sample consisted of youths aged 12 to 17 years who participated in both wave 4.5 (2017-2018) and wave 5 (2018-2019) of the PATH Study, including those who turned 18 years of age in wave 5 and were therefore included in the adult survey. The weighted response rate was 83.5% for wave 5 youths and 88.0% for wave 5 adults. 23 Our cohort study comprises 9828 youths who had never used cannabis (cannabis-naive) by wave 4.5. See the eFigure in the Supplement for a flowchart of sample construction. Adolescents were recruited for the PATH Study after written consent was given by the parents. The University of Alabama at Birmingham institutional review board exempted this study from review because it used deidentified data. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline.

The independent variable of interest was self-reported e-cigarette use by wave 4.5, assessed by 3 different measures: ever use of e-cigarettes, past 12-month use of e-cigarettes, and past 30-day use of e-cigarettes. The main outcome measures were past 12-month use and past 30-day cannabis use in wave 5. Past 12-month use of cannabis was defined by an affirmative answer to any of the following 4 questions in the PATH Study: “In the past 12 months, have you used marijuana, hash, THC, grass, pot, or weed?” “In the past 12 months, have you smoked part or all of a traditional cigar, cigarillo, or filtered cigar with marijuana in it?” “Have you ever smoked marijuana in a hookah?” “Have you ever used marijuana, marijuana concentrates, marijuana waxes, THC, or hash oils in an electronic product such as an e-cigarette, vape, mod, personal vaporizer, e-hookah, or hookah pen?” Past 30-day cannabis use was defined by responses to the following 2 questions: “Have you used marijuana, hash, THC, grass, pot, or weed in the past 30 days?” “When was the last time you smoked a traditional cigar/cigarillo/filtered cigar as a blunt, even 1 or 2 puffs?” We converted the latter question into a binary measure of 1 to 30 days or no use. Participants reporting “yes” to the first 30-day question or 1 to 30 days in response to the second question were categorized as past 30-day cannabis users. Those who answered “don’t know” or “refused” were considered missing for that question.

Consistent with previous studies, we included basic sociodemographic variables as covariates. Sociodemographic variables included age (12-14 years vs 15-17 years), sex (male vs female), race and ethnicity (Hispanic, non-Hispanic Black, non-Hispanic White, and non-Hispanic other [includes American Indian or Alaska Native, Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, other Asian, Native Hawaiian, Guamanian or Chamorro, Samoan, and Other Pacific Islander]), highest parental educational level (≤high school or GED [General Educational Development certification], some college, and ≥college), household income (<$50 000, $50 000-$100 000, and >$100 000), and school grades (<mostly B’s vs ≥mostly B’s). Questions on highest parental educational level, household income, and school grades were answered by the parent, whereas the other questions were answered by the adolescent participant.

Family tobacco use (0 vs 1) was evaluated by asking if anyone living with the respondent used cigarettes, smokeless tobacco, cigars, cigarillos, filtered cigars, or any other form of tobacco. Peer tobacco use (0 vs 1) was scored 1 if participants reported any positive number to questions asking, “How many of your best friends use [tobacco product]?” Tobacco products included were cigarettes, e-cigarettes, cigarillos, snus, and smokeless tobacco.

Ever use of tobacco products other than e-cigarettes (0 vs 1) was defined by any positive response to questions asking about ever use of cigarette, cigar, pipe, hookah, snus, smokeless tobacco, bidi, kretek, or dissolvable tobacco. Past 12-month use of alcohol (0 vs 1) was assessed by the question, “In the past 12 months, have you used any alcohol?” Participants who answered “yes” to the question, “Have you ever used any of the following prescription drugs (Ritalin or Adderall, painkillers, sedatives, or tranquilizers) that were not prescribed for you or that you took only for the experience or feeling they caused?” were considered as ever nonmedical users of prescription drugs.

We assessed sensation seeking using 3 questions measured on a 5-point scale (where 1 indicates strongly disagree and 5 indicates strongly agree), modified from the Brief Sensation Seeking Scale. 24 The sensation seeking score was calculated as the mean response to these 3 questions, which asked about respondents’ affinity for frightening things, new and exciting experiences, and exciting and unpredictable friends. The score was treated as a continuous variable. 24 , 25 Questions on sensation seeking were asked only once when the participants first joined the PATH Study.

We conducted the statistical analysis using Stata, version 17 (StataCorp LLC), with the Fay method of balanced repeated replication to estimate variance. Stata’s svy command was used to incorporate survey weights. Multivariable logistic regressions were performed to examine the association between e-cigarette use at baseline (wave 4.5) and cannabis use 1 year later (wave 5), controlling for the variables identified. All P values were from 2-sided tests, and results were deemed statistically significant at P  < .05.

We report our main results as adjusted relative risks (aRRs) and adjusted risk differences (aRDs), calculated using Stata’s margins command. Other studies have reported the association in aORs. 14 , 16 - 19 However, ORs are commonly misinterpreted as relative risks 26 , 27 and would produce biased estimates of relative risks given the high prevalence of our outcome in wave 5. 28 , 29 This bias is demonstrated by comparing our main results in aRRs with aORs in eTable 1 in the Supplement .

The variable with the most missing data was sensation seeking (14.7%), while other variables had few missing values (<5%). Our complete-case analysis excluded participants with missing data.

To examine the robustness of the association between e-cigarette use and subsequent cannabis use, we conducted several sensitivity analyses: (1) adding psychological measures of internalizing and externalizing problems, 30 , 31 (2) removing sensation seeking owing to a large number of cases with missing values, and (3) considering participants answering “don’t know” or “refused” as users or nonusers of that product (instead of missing).

Results were weighted to produce nationally representative findings. Of the 9828 adolescents included in the analysis, 5361 (57.3% [95% CI, 56.8%-57.9%]) were aged 12 to 14 years, 5056 (50.7% [95% CI, 50.3%-51.2%]) were male, and 4481 (53.0% [95% CI, 52.4%-53.5%]) were non-Hispanic White ( Table 1 ). Highest parental educational level was high school or GED or less for 2824 individuals (25.6% [95% CI, 24.5%-26.8%]), some college for 2822 individuals (28.2% [95% CI, 26.7%-29.6%]), and college or higher for 4088 individuals (46.2% [95% CI, 44.6%-47.9%]). Annual household income was less than $50 000 for 4087 participants (39.2% [95% CI, 38.0%-40.5%]), between $50 000 and $100 000 for 2393 participants (26.4% [95% CI, 25.2%-27.5%]), and more than $100 000 for 2894 participants (34.3% [95% CI, 32.8%-36.0%]). A total of 2472 participants (24.2% [95% CI, 23.3%-25.2%]) reported grades less than mostly B’s, and a total of 7175 participants (75.8% [95% CI, 74.8%-76.7%]) reported mostly B’s or higher. A total of 2649 participants (27.4% [95% CI, 26.2%-28.7%]) had family members who used tobacco, and a total of 2859 participants (29.2% [95% CI, 28.0%-30.4%]) had best friends who used tobacco. A small fraction (465 [4.8%; 95% CI, 4.3%-5.4%]) had ever used any tobacco product other than e-cigarettes, but 1824 participants (19.2% [95% CI, 18.0%-20.4%]) reported past 12-month alcohol use. A total of 1272 participants (12.6% [95% CI, 11.9%-13.4%]) reported ever nonmedical use of prescription drugs. The mean (SE) sensation seeking score was 2.43 (0.01).

We found significant differences between ever users and never users of e-cigarettes. Those reporting ever e-cigarette use were more likely than those reporting never e-cigarette use to be older (15-17 y, 71.2% [95% CI, 67.3%-74.8%] vs 40.2% [95% CI, 39.6%-40.8%]) and non-Hispanic White (67.7% [95% CI, 63.0%-72.1%] vs 51.8% [95% CI, 51.2%-52.3%]) and to have lower school grades (less than mostly B’s, 33.2% [95% CI, 29.2%-37.6%] vs 23.4% [95% CI, 22.5%-24.4%]), family members who used any tobacco product (42.4% [95% CI, 38.1%-46.8%] vs 26.2% [95% CI, 24.9%-27.5%]), and best friends who used any tobacco product (71.8% [95% CI, 68.1%-75.2%] vs 25.7% [95% CI, 24.5%-26.9%]) ( Table 1 ). They were also more likely to report ever use of tobacco products other than e-cigarettes (25.8% [95% CI, 21.7%-30.5%] vs 3.1% [95% CI, 2.7%-3.5%]), past 12-month alcohol use (44.6% [95% CI, 40.0%-49.2%] vs 17.1% [95% CI, 15.9%-18.3%]), ever nonmedical use of prescription drugs (20.7% [95% CI, 17.7%-24.0%] vs 11.9% [95% CI, 11.1%-12.7%]), and higher mean (SE) sensation seeking scores (2.78 [0.05] vs 2.40 [0.01]).

In Table 2 , we present the proportion of baseline never cannabis users who reported subsequent past 12-month and past 30-day cannabis use by selected characteristics. Among baseline cannabis-naive adolescents consisting of both users and nonusers of e-cigarettes, 1 year later, 10.7% (95% CI, 9.9%-11.6%) reported past 12-month cannabis use, and 4.7% (95% CI, 4.2%-5.2%) reported past 30-day cannabis use. In the past 12 months, 38.8% (95% CI, 34.6%-43.3%) of ever e-cigarette users initiated cannabis use compared with 8.3% (95% CI, 7.6%-9.1%) of never e-cigarette users. In the past 30 days, 19.3% (95% CI, 16.0%-23.0%) of ever e-cigarette users used cannabis compared with 3.4% (95% CI, 3.0%-3.9%) of never e-cigarette users. Baseline past 12-month and past 30-day e-cigarette use were also factors significantly associated with subsequent past 12-month and past 30-day cannabis use. In addition, age, school grades, family tobacco use, peer tobacco use, ever use of tobacco products other than e-cigarettes, past 12-month use of alcohol, and ever nonmedical use of prescription drugs were significantly associated with future cannabis use.

Table 3 shows the association of baseline e-cigarette use and future 12-month cannabis use after adjusting for all study covariates. Ever e-cigarette use at baseline was associated with a 13.93–percentage point increase (95% CI, 9.83-18.04 percentage points) in reported past 12-month cannabis use 1 year later, from 8.90% (95% CI, 8.05%-9.75%) for never e-cigarette users to 22.84% (95% CI, 18.92%-26.75%) for ever e-cigarette users. Past 12-month e-cigarette use was associated with a 14.89–percentage point increase (95% CI, 10.52-19.26 percentage points) in past 12-month cannabis use. Past 30-day e-cigarette use was associated with an increase of 11.86 percentage points (95% CI, 5.34-18.38 percentage points) in past 12-month cannabis use. The resulting aRR for 12-month cannabis use within the next year was 2.57 (95% CI, 2.04-3.09) for ever e-cigarette use at baseline, 2.62 (95% CI, 2.10-3.15) for past 12-month e-cigarette use at baseline, and 2.18 (95% CI, 1.50-2.85) for past 30-day e-cigarette use at baseline.

Table 4 presents the association of e-cigarette use (wave 4.5) and future 30-day cannabis use (wave 5), adjusted for all study covariates. Ever e-cigarette use was associated with an increase in cannabis use from 3.61% (95% CI, 3.06%-4.16%) to 11.57% (95% CI, 8.24%-14.89%), an increase of 7.96 percentage points (95% CI, 4.49-11.42 percentage points). Past 12-month use of e-cigarettes was associated with an increase of 8.94 percentage points (95% CI, 4.77-13.11 percentage points), and past 30-day use of e-cigarettes was associated with an increase of 8.29 percentage points (95% CI, 2.30-14.29 percentage points). The aRR for future past 30-day cannabis use was 3.20 (95% CI, 2.10-4.31) for ever e-cigarette use at baseline, 3.40 (95% CI, 2.17-4.63) for past 12-month e-cigarette use at baseline, and 2.96 (95% CI, 1.52-4.40) for past 30-day e-cigarette use at baseline. Complete regression results can be found in eTables 2 to 4 in the Supplement .

The results of all of the sensitivity analyses are similar to those in Table 3 and Table 4 . See eTable 5 in the Supplement for definitions of internalizing and externalizing problems and eTables 6 to 8 in the Supplement for sensitivity analysis results. Given the popularity of cannabis vaping, we also examined the prospective association between e-cigarette use and past 12-month cannabis vaping. The aRRs were close to our main results (eTable 9 in the Supplement ).

Consistent with previous literature using data from 2013 to 2017, 14 - 20 we found a significant and robust association between baseline e-cigarette use among cannabis-naive youth and subsequent cannabis use. We add to this literature by using more recent nationally representative data from 2017 to 2019, a period with substantial increases in vaping prevalence. For example, among high school students, past 30-day use of e-cigarettes increased from 4.5% in 2013 to 11.7% in 2017 and then increased to 27.5% in 2019. 3 , 4 , 32 We present our results as aRRs and aRDs rather than the aORs used in most previous studies. (However, 2 of these studies did present results in aRRs. 15 , 20 ) As observed, aRRs and aRDs provide a more readily comprehensible assessment of the association between e-cigarette use and subsequent cannabis use. 26 , 27 Unlike most previous studies, we examined the association via multiple measures of e-cigarette use (ever, past 12 months, and past 30 days) and cannabis use (past 12 months and past 30 days). All comparisons yielded similar results.

There are a few possible explanations for the prospective association between e-cigarette use and cannabis use. Even though we controlled for sensation seeking and some risky behaviors, e-cigarette use may be a marker for other risk-taking behaviors that are also associated with cannabis use. e-Cigarette users may be more likely to befriend peers who engage in other risky behaviors, such as cannabis use. Peer pressure has been identified by many studies as a risk factor for cannabis use. 33 , 34 Another possible reason for this association is the increased prevalence of vaping as a means of using cannabis. The prevalence of past 12-month cannabis vaping among 12th-grade students increased from 9.5% in 2017 to 22.1% in 2020. 35 More than half of current e-cigarette users aged 15 to 24 years reported cannabis vaping. 36 e-Cigarette use could increase adolescents’ likelihood to vape cannabis because the same vaping devices can be used for both products. eTable 9 in the Supplement shows the prospective association between e-cigarette use and past 12-month cannabis vaping. The aRRs were close to our main findings, suggesting a limited difference across modes of cannabis use. Similar findings were also reported by another study. 37 The lack of difference is likely because most cannabis users consume cannabis via multiple modes, including vaping.

The association between e-cigarette use and cannabis use at the individual level appears inconsistent with their use at the population level. Although there is clearly a strong association between e-cigarette use and subsequent cannabis use at the individual level, 14 - 20 the prevalence of adolescent cannabis use at the population level has remained relatively stable from 1995 to 2020 among adolescents in 8th, 10th, and 12th grade. 35 There are some possible explanations for this discrepancy. First, despite the association between individuals’ e-cigarette use and subsequent cannabis use, the size of this population (ie, cannabis-naive adolescents who have tried e-cigarettes) is relatively small, resulting in minimal changes in cannabis use at the population level. For example, 7.8% (95% CI, 7.3%-8.3%) of cannabis-naive adolescents at wave 4.5 had ever used e-cigarettes. That is 6.3% (95% CI, 5.9%-6.8%) of the entire youth population. Even if the estimated association were completely causal, our calculations in eTable 10 in the Supplement demonstrate that the estimated change in cannabis use at the population level due to e-cigarette use is less than 1 percentage point. Another explanation is that subsequent cannabis use associated with e-cigarette use may not persist over time. Some adolescent e-cigarette users likely simply experiment with cannabis use without becoming established users.

This study has some limitations. One potentially important factor associated with cannabis use is the legalization of the recreational use of cannabis for adults in several states. Although it is still illegal for adolescents to purchase cannabis, cannabis legalization for adults may make it easier for adolescents to access cannabis. Owing to a lack of geographic information, our study was unable to control for state-level cannabis legalization. In 2019, 20.4% of all 12- to 17-year-old adolescents lived in states with licensed sales for recreational cannabis. 38 However, with four-fifths of adolescents not living in states with recreational cannabis sales, we suspect that legalization of recreational cannabis is not associated with our results. Nevertheless, the effect of legalizing recreational cannabis use is a topic worthy of study.

Another limitation is the possibility of response bias in the PATH Study’s self-reported data, including e-cigarette use and cannabis use. However, Bachman et al 39 found evidence supporting the validity of self-reported data. In addition, although all of the results in this study were weighted to produce nationally representative findings, the participants excluded from our analysis owing to missing data might have affected the generalizability of our findings. Finally, there is 1 limitation associated with the PATH Study survey questions regarding cannabis. Questions on past 30-day cannabis use did not explicitly ask about cannabis use through hookah or electronic products, unlike questions on past 12-month use. Because some respondents provided inconsistent answers to questions about past 12-month cannabis use and cannabis use via hookah or electronic products (“no” to past 12-month cannabis use but “yes” to cannabis use via hookah or electronic products), the measure of past 30-day cannabis use likely missed some participants who used cannabis through hookah or electronic products.

Using PATH Study data from 2017 to 2019, this cohort study found that, among cannabis-naive adolescents, those who have used e-cigarettes were significantly more likely to use cannabis 1 year later compared with those who had not used e-cigarettes. However, despite this association, e-cigarette use seems to have had a minimal association with the overall prevalence of youth cannabis use. At the population level, adolescent use of cannabis has remained relatively stable for the past quarter century.

Accepted for Publication: May 23, 2022.

Published: July 22, 2022. doi:10.1001/jamanetworkopen.2022.23277

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2022 Sun R et al. JAMA Network Open .

Corresponding Author: Ruoyan Sun, PhD, Department of Health Policy and Organization, School of Public Health, University of Alabama at Birmingham, 1665 University Blvd, 310C Ryals Public Health Bldg, Birmingham, AL 35294 ( [email protected] ).

Author Contributions: Dr Sun had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Sun, Warner.

Acquisition, analysis, or interpretation of data: Sun, Mendez.

Drafting of the manuscript: Sun.

Critical revision of the manuscript for important intellectual content: Mendez, Warner.

Statistical analysis: Sun.

Supervision: Mendez, Warner.

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank Edward C. Norton, PhD, University of Michigan, for his suggestions on Stata commands. He was not compensated for his contributions.

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Cannabis Facts and Stats

At a glance.

A variety of information sources are available to monitor the prevalence and trends of cannabis use in the United States. The resources below cover cannabis-related issues, including data around use, emergency department visits, substance use and misuse, policy measures, and other related tools.

• Cannabis is the most commonly used federally illegal drug in the United States; 52.5 million people, or about 19% of Americans, used it at least once in 2021. 1
• Recent research estimated that approximately 3 in 10 people who use cannabis have cannabis use disorder. 2
• The risk of developing cannabis use disorder is even greater for people who begin to use it before age 18. 3
• Cannabis use directly affects the parts of the brain responsible for memory, learning, attention, decision-making, coordination, emotion, and reaction time. 4 5
• Infants, children, and teens (who still have developing brains) are especially susceptible to the adverse effects of cannabis. 4 5
• Long-term or frequent cannabis use has been linked to increased risk of psychosis or schizophrenia in some users. 6
• Using cannabis during pregnancy may increase the person's risk for pregnancy complications. Pregnant and breastfeeding persons should avoid cannabis. 7

National Surveys That Collect Information About Cannabis Use

Cdc sponsored surveys.

Behavioral Risk Factor Surveillance System (BRFSS)

World's largest, continuously conducted telephone survey that tracks health behaviors, chronic diseases, and preventive health practices among noninstitutionalized adults in the United States.

Youth Risk Behavior Surveillance System (YRBSS)

Monitors six categories of priority health risk behaviors, including cannabis use, among high school youth at national, state, and local levels.

Pregnancy Risk Assessment Monitoring System (PRAMS)

Collects state-specific, population-based data on cannabis use before, during, and shortly after pregnancy.

National Health and Nutrition Examination Survey (NHANES)

Assesses the health and nutritional status of adults and children, aged 12 years and older, in the United States. The survey is unique in that it combines interviews and physical examinations. Voluntary drug use questions ask lifetime cannabis use, age of first use, age when starting to use cannabis regularly, amount used, frequency of use, and time since last use. These data are available from 2005-2007 survey period onward.

Other National Surveys

National Survey on Drug Use and Health (NSDUH)

Ongoing and long-term system, sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA) NSDUH is the primary source of information on the prevalence, patterns, and consequences of alcohol, tobacco, and illegal drug use and abuse in the general U.S. civilian noninstitutionalized population, ages 12 and older.

Monitoring the Future Survey

Ongoing and long-term system, sponsored by the National Institute on Drug Abuse (NIDA) that collects data on the behaviors, attitudes, and values regarding substance use of American teens, college students, and adults. Each year a total of approximately 50,000 students in 8th, 10th, and 12th grades are surveyed about substance use, including cannabis, and a subset are sent follow-up questionnaires through age 45 years.

National Drug Early Warning System (NDEWS)

NDEWS monitors drug use trends in 12 sentinel communities across the United States. Sentinel Site profiles describing drug abuse trends and emerging issues are available on NDEWS website.

National Programs That Collect Information About Cannabis Policies

Alcohol Policy Information System (APIS)

A policy monitoring system sponsored by the National Institute on Alcohol Abuse and Alcoholism (NIAA) that provides detailed information on a wide variety of alcohol-related policies in the United States at both state and federal levels. The system was expanded in 2016 to include policies related to legalizing the cultivation, sale, or use of cannabis for prohibitions and restrictions on such practices.

State Cannabis Policy Enactment Database

A policy monitoring system sponsored by the National Conference of State Legislatures that provides up-to-date information on cannabis legislation that has been enacted in the 50 states, District of Columbia, and its territories. The database is sortable by state, topic, keyword, and primary sponsor.

• Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators in the United States: Results from the 2021 National Survey on Drug Use and Health (HHS Publication No. PEP22-07-01-005, NSDUH Series H-57). Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. 2022. https://www.samhsa.gov/data/report/2021-nsduh-annual-national-report . Accessed on February 9, 2024.
• Hasin DS, Saha TD, Kerridge BT, et al. Prevalence of marijuana use disorders in the United States between 2001-2002 and 2012-2013. JAMA Psychiatry. 2015 Dec;72(12):1235-1242. doi: 10.1001/jamapsychiatry.2015.1858.
• Winters KC, Lee C-YS. Likelihood of developing an alcohol and cannabis use disorder during youth: Association with recent use and age. Drug Alcohol Depend. 2008;92(1-3):239-247. doi: 10.1016/j.drugalcdep.2007.08.005.
• National Academies of Sciences, Engineering, and Medicine. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. Washington, DC: The National Academies Press; 2017. https://nap.nationalacademies.org/catalog/24625/the-health-effects-of-cannabis-and-cannabinoids-the-current-state. Accessed February 8, 2024.
• Giedd JN. The teen brain: Insights from neuroimaging. J Adolesc Health. 2008;42(4):335–343. doi: 10.1016/j.jadohealth.2008.01.007.
• Volkow ND, Swanson JM, Evins AE, et al. Effects of cannabis use on human behavior, including cognition, motivation, and psychosis: A review. JAMA Psychiatry. 2016 Mar;73(3):292-297. doi: 10.1001/jamapsychiatry.2015.3278.
• Ryan SA, Ammerman SD, O’Connor ME, et al. Marijuana use during pregnancy and breastfeeding: Implications for neonatal and childhood outcomes. Pediatrics. 2018;142(3):e20181889. doi: 10.1542/peds.2018-1889.

Cannabis and Public Health

Cannabis—which can also be called marijuana —is the most commonly used federally illegal drug in the United States.

Bill could end holdup for California research on psychedelics and addiction treatment

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California lawmakers could soon clear a governmental logjam that has held up dozens of studies related to addiction treatment, psychedelics or other federally restricted drugs.

The holdup revolves around the Research Advisory Panel of California , established decades ago to vet studies involving cannabis, hallucinogens and treatments for “abuse of controlled substances.”

It has been a critical hurdle for California researchers exploring possible uses of psychedelics or seeking new ways to combat addiction. Scientists cannot move forward with such research projects without the panel’s blessing.

The panel had long met behind closed doors to make its decisions, but concerns arose last year that it was supposed to fall under the Bagley-Keene Act, a state law requiring open meetings. Holding those meetings in public, however, raised alarm about exposing trade secrets and other sensitive information.

So the panel stopped meeting at all. It has not convened since August. Meetings ordinarily scheduled for every other month have been canceled since October.

The result has been a ballooning backlog: As of early May, there were 42 new studies and 28 amendments to existing projects awaiting approval, according to state officials.

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Ziva Cooper, director of the UCLA Center for Cannabis and Cannabinoids, said she had submitted one study to the California panel over a year ago — one already approved by the National Institutes of Health, the Food and Drug Administration, and an institutional review board. That research will assess the health risks of cannabis for seniors and young adults ages 18 to 25, two groups whose cannabis use has been on the rise, she said. Cooper said the panel sought a small change: adjusting two words in a consent form for study participants. But because the panel has not been meeting, she has been unable to proceed.

The holdup has also snarled two other studies her UCLA center had submitted to the panel — one examining whether cannabis could be used as an alternative to opioids for pain relief, another on whether a psychedelic compound found in mushrooms, psilocybin, could help treat people struggling with cocaine addiction.

And Cooper said she hasn’t even bothered to submit three more studies, including research on the effects of high-potency cannabis. The holdup has left Cooper and other researchers fearing they could lose funding for planned studies or be forced to lay off staff.

The idea of having to study something different because “in California I can’t do the research that I’m trained to do ... is demoralizing,” Cooper said. It aggravates her “to not be able to answer the questions that are desperately needed right now” as the range of cannabis products on the market has grown.

The standstill “has broad implications, costing researchers money in expired grants and contingent grants, shortened patents on new drugs, lost wages for research personnel, lost talent, and lost costs of research drugs for human use that will expire before use,” according to an analysis prepared for a state committee.

That long hiatus could soon end: Under Assembly Bill 2841, the state panel would be able to hold closed sessions to discuss studies that involve trade secrets or other proprietary information. The bill, proposed by Assemblymember Marie Waldron (R-Valley Center), would go into effect immediately if signed by the governor.

“We are focused on reactivating the large amount of research studies that have been on hold for over a year now,” Waldron said in a statement. “This is the quick and urgent solution needed to address that problem.”

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The bill is supported by the nonprofit Veterans Exploring Treatment Solutions, which supports research into the possible benefits of psychedelics for treating depression and other conditions among military veterans and helps them obtain such treatment abroad.

“Psychedelic research has ground to halt in California — including numerous VA studies, “ said its director of public policy, Khurshid Khoja. If the Legislature does not act swiftly, the state will see “a rapid exodus of skilled researchers from California universities and research institutions to pursue their critically important work elsewhere — not to mention capital flight by funders who’ll deploy research dollars outside the state.”

“AB 2841 is an urgently needed response to address this crisis,” Khoja said.

To many researchers, however, AB 2841 does not go far enough. Dozens of scientists have called for the panel to be eliminated, arguing that even when it was meeting regularly, it was an unnecessary obstruction to research already being scrutinized by other government and institutional reviewers.

In a letter to Gov. Gavin Newsom, a coalition of researchers argued that undergoing the state review could delay a study by at least five months, resulting in more than $100,000 in “unnecessary staff expenditures” in that time. Because other states don’t have that hurdle, they argued, California researchers are losing out on competitive funding — and Californians miss chances to participate in local trials for emerging treatments.

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UCLA psychologist and addiction researcher Steven Shoptaw called it “an unequal burden on addiction research” compared with other scientific studies.

The California panel has been vetting not only studies that involve federally restricted drugs, but also those assessing any kind of medication to treat addiction, said Dr. Phillip Coffin, a UC San Francisco professor of medicine who has called to eliminate the panel.

“If I’m testing Prozac for depression, or Prozac for any other disease, I can do my research without waiting” for the committee, he said, but “If I’m testing Prozac for addiction, I have to wait.” By maintaining such barriers, Coffin argued, “we are seriously harming any chance California has of responding to the addiction crisis.”

Short of eliminating the panel, some have also argued for amending the law to exempt any researchers who have gotten federal approval to do such research.

Others have argued that the panel has a valuable role, even for studies that have undergone review by the FDA or other entities. An analysis of AB 2841 prepared for the Assembly Committee on Health said state data from the Department of Justice show that the Research Advisory Panel regularly catches issues with drug safety, consent forms missing important information about safety and privacy, and other potential problems.

The panel “has a record of providing an extra level of protection, which is important given the volume of controlled substance research that occurs in California,” the analysis said. In addition, the committee analysis said the panel is “the only one which ensures that studies conducted in California comply with state law.”

Coffin disputed such arguments, saying that in his experience and that of many other researchers, its feedback had not “improved patient safety or remotely justified the extreme delays.”

If it is truly finding problems that have escaped other reviewers, he argued, “then all research — not just addiction treatment and controlled substances — should be forced to go through this panel.”

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Michael Smolens: Unshackling research on guns, marijuana

A court ruling in a San Diego case on gun data and a recommendation to reclassify marijuana’s federal drug status should boost much-needed study of both

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Separate recent developments underscore the need for research into two matters of vast public health, economic and social impact: guns and marijuana.

Firearms and cannabis are ubiquitous across much of the country and their effects on American society, while greatly different, are deep.

Yet for decades, federal hurdles have made it difficult to conduct scientific study of either. Such research may become a bit easier because of what happened last week.

The 9th U.S. Circuit Court of Appeals upheld a San Diego federal judge’s dismissal of a lawsuit challenging a California law that allows gun owners’ information to be shared with researchers studying gun violence. That’s significant, though not necessarily a game-changer — but it would have been if the ruling went in the other direction.

Meanwhile, the U.S. Drug Enforcement Agency proposed to reclassify marijuana as a less-dangerous drug, which could have broader impact. Currently, cannabis is a Schedule I controlled substance along with such powerful drugs as heroin and LSD.

The recommendation would make marijuana a less-tightly regulated Schedule III drug, a category that includes ketamine, Tylenol with codeine and some anabolic steroids, among others. The proposal now faces a lengthy approval process.

Should the change happen, experts expect there will be more research into various aspects of cannabis.

Increasingly, state and federal views of marijuana have seemed incompatible. The federal government continues to regulate it among the most potent drugs even though cannabis has been legalized for recreational use in 24 states and for medical use in several others.

Federal and state agencies have established rules for research involving storage, security and reporting, among other things. To study the drug, researchers must obtain a Schedule I license from the federal government. Until recently, the license could take a year or more to obtain.

A Schedule III designation would change much of that.

Even before last week’s proposal, efforts were under way to speed up the timeline for cannabis studies. The Medical Marijuana and Cannabidiol Research Expansion Act signed by President Joe Biden in 2022 gave the attorney general 60 days to approve applications, provide reasons for denying them, or request more information, according to Smithsonian magazine.

Access to cannabis for study has also increased. For decades, researchers could only get marijuana from a facility at the University of Mississippi. A handful of other sources were approved by the federal government in 2021.

Despite those changes and the potential Schedule III classification, some researchers say the study of cannabis may still face limits.

“What we haven’t seen is any ability for researchers — cannabis researchers, clinical researchers — to ... study products that our patients and our recreational consumers or adult consumers are actually using,” neuroscientist Staci Gruber at McLean Hospital and Harvard Medical School told National Public Radio.

Some studies have shown that marijuana being sold today is significantly more potent than what was sold years ago. And higher levels of THC, the main psychoactive component in marijuana, are believed to pose more health risks.

Hospitals in San Diego and across the country have been seeing elevated numbers of young patients, including toddlers, arriving in emergency rooms with cannabis poisoning, according to Paul Sisson of The San Diego Union-Tribune.

Yet many people use marijuana to ease medical conditions and for recreation with no apparent significant side effects. The drug has been recommended for people with a wide range of health issues, including Alzheimer’s disease, HIV/AIDS, severe and chronic pain, and nausea caused by cancer treatment, according to the Mayo Clinic.

Marijuana has remained a Schedule I drug for years in part because of the politically-volatile climate over drug enforcement.

National politics has had much to do with limiting gun-violence research.

California’s moves to expand such research has been challenged in court. A lawsuit by a group of gun owners — including three in San Diego — sought to block Assembly Bill 173, which allows disclosure of gun owners’ personal information to researchers.

The lower court judge ruled that the state already collects information on gun buyers and concealed-carry weapon permit applicants, and that the sharing of information outlined in AB 173 was “merely a limited extension” of those measures, according to City News Service.

The federal appellate court wrote that the information did not “implicate the right to privacy” as the plaintiffs maintained. Further, the court added, there had been no allegations that the researchers violated restrictions against publicly disseminating the information.

A San Diego Superior Court judge earlier had issued a preliminary injunction to block AB 173, but that was overturned last fall by a state appeals court.

State researchers had access to that data for years, but things changed in 1996. That’s when Congress prohibited the use of federal funding to advocate or promote gun control, a measure that was passed after the National Rifle Association argued that Center for Disease Control-funded research was biased. That stymied funding for research on gun violence.

In 2016, the California Legislature established the Firearm Violence Research Center at UC Davis. But the state Department of Justice stopped sharing the database information with the center shortly after, according to Kristina Davis of the Union-Tribune.

That led to AB 173.

The federal spigot to fund gun research and data reopened somewhat following the Parkland school mass shooting in 2018 that left 17 people dead. An omnibus bill was signed by President Donald Trump clarifying that restricting the use of federal funds to advocate or promote gun control doesn’t ban research.

In 2019, Congress again began to allocate funds for research and data collection on gun violence.

Yet the research is still playing catch-up because of the more than two-decade restriction on federal funding, while some researchers say more money is needed.

The Congressional Joint Economic Committee some years back examined the shortage of funding for gun violence research.

The panel arrived at a universal conclusion: The first step in solving any problem requires understanding it.

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Maker of weight loss drug Ozempic plans to study drug’s effects on alcohol consumption

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The feeling has been described by thousands of people taking medicines, which are in a class known as GLP-1 receptor agonists.

Ozempic’s maker, Novo Nordisk, said it intends to study the phenomenon, although cutting the drinking isn’t the study’s main goal.

The company plans to start assessing the effects of semaglutide, the active ingredient in Ozempic and other medicines, on alcohol consumption in a newly announced clinical trial on alcohol-related liver disease.

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