marijuana paper outline

Marijuana and Cannabinoids: Health, Research and Regulatory Considerations (Position Paper)

Executive summary.

Marijuana and related substance misuse are complex issues impacting family medicine, patient health, and public health. The American Academy of Family Physicians (AAFP) believes family physicians are essential in addressing all forms of inappropriate substance use. The AAFP urges its members to be involved in the diagnosis, treatment, and prevention of substance use, as well as secondary diseases impacted or caused by use. The World Health Organization (WHO) reports approximately 2.5% of the global population uses cannabis annually, making it the most commonly used drug worldwide. 1  Simultaneously, the AAFP acknowledges preliminary evidence indicates marijuana and cannabinoids may have potential therapeutic benefits, while also recognizing subsequent negative public health and health outcomes associated with cannabis use. 2

During the 20 th  century, law enforcement and public policy activities have undermined opportunities for scientific exploration. Barriers to facilitating both clinical and public health research regarding marijuana is detrimental to treating patients and the health of the public. The lack of regulation poses a danger to public health and impedes meaningful, patient-centered research to exploring both therapeutic and negative impacts of marijuana and cannabinoids.

Relevant AAFP Policy

Marijuana Possession for Personal Use The American Academy of Family Physicians (AAFP) opposes the recreational use of marijuana. However, the AAFP supports decriminalization of possession of marijuana for personal use. The AAFP recognizes the benefits of intervention and treatment for the recreational use of marijuana, in lieu of incarceration, for all individuals, including youth. 3

The AAFP also recognizes that several states have passed laws approving limited recreational use and/or possession of marijuana. Therefore, the AAFP advocates for further research into the overall safety and health effects of recreational use, as well as the effects of those laws on patient and societal health. 4

It should be noted that cannabis and marijuana are not interchangeable terms. In this position paper, cannabis is an overarching term used to refer to the plant  Cannabis sativa . Substances derived from the cannabis   plant include marijuana, hemp, and cannabinoids.

Call to Action Family physicians have a vested interest in policies that advance and protect the health of their patients and the public. The regulatory environment surrounding cannabis, medical and recreational marijuana, and cannabidiol (CBD) is rapidly changing, along with the retail environment. This shift has not been accompanied by robust scientific research regarding the health effects of cannabis, both therapeutic or detrimental. The AAFP recognizes the need for substantial clinical, public health, and policy evidence and research regarding cannabis, marijuana, cannabinoids, and CBD to inform evidence-based practice and the impact on public health.

• The AAFP promotes a society which is free of substance misuse, including alcohol and drugs. 3
• The AAFP recognizes there is support for the medical use of marijuana and cannabinoids, but advocates that usage be based on high-quality, evidence-based public health, policy, and patient-centered research, including the impact on vulnerable populations. 3
• The AAFP advocates for further studies into the use of medical marijuana and related compounds. This process should also ensure appropriate funding allocated for this research.
• The AAFP calls for decreased regulatory barriers to facilitate clinical and public health cannabis research, including reclassifying cannabis from a Schedule I controlled substance. 3
• The AAFP advocates for further research into the overall safety and health effects of recreational use, as well as the impact of legal recreational marijuana use laws on patient and societal health. 4
• The AAFP advocates for robust regulation regarding labeling and child-proof packaging of all marijuana and cannabinoid products.
• The AAFP opposes the recreational use and legalization of marijuana, but supports decriminalization of marijuana for personal use. The AAFP recognizes the benefits associated with intervention and treatment, in lieu of incarceration. 4
• The AAFP advocates for regulation regarding marketing claims, labeling, and advertising of all marijuana and cannabinoid products.
• The AAFP supports requirements testing current marijuana and cannabinoid products for safety, dosing, and product consistency.

In the Exam Room

• The AAFP urges its members to be involved in the diagnosis, treatment, and prevention of substance use, as well as the secondary diseases impacted by use.
• The AAFP calls for family physicians to discuss the health consequences of marijuana and cannabis use, as well as prevention strategies to prevent use and unintended consequences of marijuana exposure in at-risk populations.

Cannabis use, both medically and recreationally, is prevalent throughout history. Extensive evidence indicates cannabis was used by ancient civilizations, dating back more than 5,000 years ago. 1  In the U.S. in the 19th and early 20th centuries, cannabis was frequently used for medicinal purposes, often prescribed by clinicians. 1,5  Cannabis was first listed in the  United States Pharmacopoeia  in 1851, indicating use as an analgesic, hypnotic, and anticonvulsant agent. 5  After the 1937  Marihuana Tax Act , in 1942, cannabis was removed from the  United States Pharmacopoeia . 5

Attitudes and perceived risk of marijuana use have changed with the varying levels of legalization in the U.S. Surveying marijuana use is essential to gauge public health implications of increased access to marijuana, cannabinoid, and cannabis products. According to the 2018 National Institute on Drug Abuse (NIDA) Monitoring the Future Survey (MTF), daily, past month, past year, and lifetime marijuana use among 8 th  graders has declined, and remained unchanged in 10 th  and 12 th  graders, when compared to the 2013 MTF survey. 6  Despite the changing landscape of marijuana regulations nationwide, past year use of marijuana reached and maintained its lowest levels in more than two decades in 2016 among 8 th  and 10 th  graders. 6  However, marijuana vaping did significantly increase between 2017 and 2018, mirroring trends in youth tobacco use. 6  The NIDA 2017 National Survey on Drug Use and Health indicates nearly 53% of adults between the ages of 18-25 have tried marijuana at some point in their lifetime, 35% have used marijuana within the past year, and 22% within the past month. 7  While the lifetime use remains relatively stable for this cohort, from 2015-2017, past year and past month use increased 2.7% and 2.3%, respectively. 7  Nearly half of adults 26 or older reported using marijuana at some point in their lifetime. 7  Although adults ages 26 and up report the highest percentage of lifetime use, this age group has a significantly lower past year use (12%) and past month use (8%). 7

Forms and Use of Cannabis The cannabis plant,  Cannabis sativa , is comprised of both non-psychoactive and psychoactive chemicals called cannabinoids. 5  The cannabinoid commonly known for its psychoactive properties is delta-9-tetrahydrocannabinol (THC). 5  CBD is the most abundant cannabinoid in cannabis, and is considered to be largely non-psychoactive. 5  The biological system responsible for the synthesis and degradation of cannabinoids in mammals is referred to as the endocannabinoid system, which is largely comprised of two g-coupled protein receptors (GPCRs). 8  The GPCRs—CB1 and CB2—are found throughout many bodily tissues. However, CB1 is most concentrated in the neural tissues. 5,8  CB2 receptors are found in the brain, but are mostly found in immune cells, like macrophages, microglia, osteoclasts, and osteoblasts. 5,8

There are many forms of, and products derived from, the  Cannabis sativa  plant, including hemp, CBD, and marijuana.  Cannabis sativa  with less than 0.3% THC is considered industrial hemp, and can be used for industrial agriculture cultivation. 9,10  Industrial hemp can be harvested and used for many things, including fibers for textiles, food products, and building materials. 11,12  CBD, the non-psychoactive cannabinoid, is extracted from the flower of industrial hemp. 13  Marijuana and hemp, technically speaking, are the same plant. 13  However, the hemp variety of cannabis contains no more than 0.3% THC, while the marijuana variety contains 5-20% THC. 13

Marijuana and CBD are most commonly used via inhalation, ingestion, and topical absorption. 5  Inhalation can be through combustible mechanisms using dried flowers, including the use of a pipe, rolled joints, blunts, and water pipes (also called bongs). 14  Vaping marijuana and CBD concentrates are an increasingly popular inhalation method. 5,6  Concentrates, the concentrated form of marijuana and CBD, come in various forms, including oil, butter, or a dark sticky substance often referred to as shatter. 15  Concentrates can be both smoked or vaporized, and may also be used as additives or cooking agents for ingestion. 5,15  There are many different ways to ingest cannabinoids. Food products—called edibles—like brownies, gummies, cookies, and candies are common forms of cannabis ingestion, as well as liquid forms like juices, soda, and tea. 5,16  Tinctures are liquid, ultra-concentrated alcohol-based cannabis extracts commonly applied in and absorbed through the mouth. 17  Topical cannabis is applied to, and absorbed through, the skin in a cream or salve form. 18

Routes or methods of administration affect cannabis delivery. When cannabis is smoked or vaporized, onset of effect is within 5-10 minutes with a duration of 2-4 hours. 19  When ingested, effect is within 60-180 minutes with a duration of 6-8 hours. 19  The oromucosal route has an onset of 15-45 minutes and a duration of 6-8 hours. 19  Topical administration of cannabis or cannabinoids has variable onset and duration. 19  The smoked or vaporized method offers the more rapid activity for acute symptoms with the topical preparations offering less systemic effects. 19

Health Effects of Cannabis

Although there is preliminary evidence indicating cannabinoids may have some therapeutic benefit, a large portion of the evidence is very limited for many reasons. These include small sample sizes, lack of control groups, poor study design, and the use of unregulated cannabis products. There are also clear negative health and public health consequences that must be considered, as well as the need for a significant increase in evidence. More research is needed to create a robust evidence base to weigh the potential therapeutic benefits against potential negative impacts on health and public health. Currently, there are three medical formulations of cannabis approved for use in the U.S.; dronabinol, nabilone, and epidiolex. 20  Nabiximols is approved for use in the United Kingdom. 21  Dronabinol is delta-9 THC and ingested as either an oral solution or an oral capsule. 22  Nabilone is an oral capsule containing synthetic THC. 23  Epidiolex is a CBD oral solution. 24  Nabiximols is an oral mucosa spray containing the cannabinoids THC and CBD. 25

In 2015, Whiting, et al, performed a meta-analysis and systematic review of research on the medical use of cannabis. 25  This systematic review served as the basis for many recommendations in 2017 by the National Academy of Science, Engineering, and Health Report on medical marijuana. 5  Dronabinol, nabilone, and nabiximols were included in the studies. However, other cannabis formulations were found in research trials, including CBD, marijuana, and other cannabinoids. 26  Evidence is most substantial for nausea and vomiting associated with chemotherapy, chronic pain treatment, multiple sclerosis spasticity, and intractable seizures associated with Dravet syndrome and Lennox-Gastaut syndrome. 27  There is moderate evidence for the use of cannabinoids for sleep and limited evidence for use in psychiatric conditions, such as post-traumatic stress disorder, depression, anxiety, and psychosis; appetite stimulation and weight gain; and no evidence for cancer treatment. 5

Dronabinol and nabilone were both approved in 1985 for use in treating refractory chemotherapy-induced nausea and vomiting. 5,23  Dronabinol is approved by the Food and Drug Administration (FDA) for appetite stimulation and weight gain, despite limited and often inconclusive evidence that it or other cannabinoids are effective. 22  This drug has traditionally been used in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients to mitigate weight loss and to treat anorexia-cachexia syndrome associated with cancer and anorexia nervosa. 5,22

Cannabinoids have been assessed for chronic pain management. Many forms of chronic pain management were studied, including cancer and chemotherapy-induced pain, fibromyalgia, neuropathic pain, rheumatoid arthritis, non-cancer pain, and musculoskeletal pain. Several studies indicate smoked THC and nabiximols were both associated with pain reduction. 5,25,26  There is limited, mixed evidence regarding the viability of cannabinoids for some forms of chronic pain management. 5  However, limitations exist with these studies, including the variable doses of THC and CBD; unregulated, non-FDA approved products; and conflicting evidence. Studies assessing cannabinoids in treating the spasticity due to multiple sclerosis or paraplegia have mixed results. The cannabinoids nabiximols, dronabinol, and TCH/CBD have all been associated with decreased spasticity. Nabilone and nabiximols were the only drugs with statically-significant decreases. 2,25

In 2018, the FDA approved a cannabidiol oral solution called epidiolex for the treatment of refractory seizures associated with Dravet syndrome and Lennox-Gastaut syndrome. 28  Epidiolex was associated with significant seizure reduction when compared to placebo. 29–31  Dravet syndrome and Lennox-Gastaut syndrome are disorders associated with severe seizures, impaired cognitive skills and development, and uncontrollable muscle contractions. 29–31

Moderate evidence exists for the use of cannabis for sleep. Nabilone and nabiximols have been associated with improvement in sleep from a baseline and sleep restfulness. 2,5,25  Improved sleep was also considered a secondary outcome when evaluating other conditions (chronic pain, multiple sclerosis) with various cannabinoids. 2,5,25

There is limited evidence for the use of cannabis or cannabinoids for the treatment of post-traumatic stress disorder (PTSD), anxiety, depression, or psychosis. Of the limited evidence, nabilone was associated with a decrease in PTSD related nightmares. 5,25  One small study indicated CBD improved public speaking anxiety. 5  There are no studies directly evaluating the effectiveness of cannabis in the treatment of depression. However, some studies measured depression as a secondary outcome, but indicated no difference in depression when compared to placebo. 25  Limited evidence (two studies) have shown no difference in treating psychosis with CBD, amisulpride, or placebo. 25  Evidence indicates individuals who use marijuana are more likely to experience temporary psychosis and chronic mental illness, including schizophrenia. 5,32

There was no evidence or insufficient evidence for the use of cannabis or cannabinoids in the treatment of cancer; neurodegenerative disorders like Huntington’s chorea, Parkinson’s disease, or amyotrophic lateral sclerosis; irritable bowel syndrome; or addiction. 5

Cannabis overdose is rare in adults and adolescents. 33  Children who experience acute intoxication from cannabis generally ingest marijuana or other cannabinoids through experimentation. 33  When compared to adults and adolescents, children are more likely to experience life-threatening symptoms of acute cannabis intoxication, which may include depressed respiration rates, hyperkinesis, or coma. 33  Management consists of supportive care dependent on the manifestation of symptoms. 33  Adults and adolescents may experience increased blood pressure and respiratory rates, red eyes, dry mouth, increased appetite, and slurred speech. 33

Negative health effects are also associated with marijuana and cannabinoid use. Frequent marijuana use has been associated with disorientation. In teens, it has been linked with depression, anxiety, and suicide. 5,32  However, this is not a proven causal relationship. Lung health can also be negatively impacted depending on the delivery mechanism. 34  Smoking marijuana can cause lung tissue scarring and damage blood vessels, further leading to an increased risk of bronchitis, cough, and phlegm production. 34  This generally decreases when users quit. 34

Secondhand smoke is a serious issue associated with marijuana use. However, there is limited evidence on how it impacts heart and lung health. 34  Detectable THC has been found in children who live in the home or have a caretaker who use marijuana, subjecting children to developmental risks of THC exposure. 35  Fetal, youth, and adolescent exposure to THC is associated with negative health effects, including impacting brain development. 34  There is inconsistent, insufficient evidence to determine the long-term effects of marijuana and cannabinoid use while breastfeeding. 36  However, THC has been detected in breast milk for up to six days post-cannabinoid use, and exposure to cannabinoids is known to impact development in children. 37  Evidence also suggests cannabis use during pregnancy may be linked with preterm birth. 38  Cardiovascular health may be impacted by smoked marijuana use. However, the negative health effects are associated with the harmful chemicals in smoke similar to tobacco smoke. 34

Approximately 9% of all individuals who use marijuana develop an addiction, which is variable by age of first use and frequency of use. 34  That number for addiction jumps to 17% for individuals who begin using marijuana as teenagers and 25-50% of those who smoke marijuana daily. 34  Marijuana use does not typically lead to harder drug use, like cocaine and heroin, in most individuals. 39  Further research is needed to evaluate any potential gateway effect. 39

Mental health outcomes associated with marijuana use include an increased risk of anxiety and depression. Marijuana has been linked to schizophrenia, psychoses, and advancing the trajectory of the disease, particularly in individuals with pre-existing genetic indicators. 5,34  Global research also suggests daily use of high-potency marijuana increases risk for psychotic episodes among individuals with no underlying mental health condition. 40  While it is widely accepted that marijuana acutely impairs cognitive function, studies suggest differential outcomes regarding short- versus long-term cognitive impairment. 34

Research Considerations

The regulatory environment surrounding cannabis, marijuana, and cannabinoid research creates barriers detrimental to facilitating meaningful medical, public health, policy, and public safety research. Approval for research expands beyond institutional review boards. Due to the Schedule I classification by the Drug Enforcement Agency (DEA), researchers seeking to investigate health effects associated with cannabis must follow a regimented application process. 41  Applicants must submit an Investigational New Drug (IND) application to the FDA, which will then be reviewed to determine scientific validity and research subjects’ rights and safety. 42  Researchers must also follow the NIDA regulatory procedures for obtaining cannabis for research purposes. 41  Researchers may only use cannabis supplied by the University of Mississippi, the single NIDA-approved source for cannabis research. 41  Requiring research to rely on one source of cannabis limits availability and the variety of products. While the University of Mississippi cultivates different strains of cannabis, it is unable to supply the vast array of strains of cannabis found in the evolving retail environment with varying levels of THC, CBD, and cannabinoid content. 5  Substantial funding and capacity is required for researchers to obtain all regulatory approval and remain in compliance while conducting cannabis-related research. The required processes and procedures present a serious burden, dissuading researchers from pursuing cannabis-related projects. This has led to a lack of empirical evidence regarding a myriad of health-related issues, including potential therapeutic benefits of cannabis, public health impact, health economics, and the short- and long-term health effects from cannabis use.

In order to address the research gaps associated with both beneficial and harmful effects of cannabinoids used in both medical and recreational capacities, the AAFP calls for a comprehensive review of processes and procedures required to obtain approval for cannabis research.  

The AAFP encourages the appropriate regulatory bodies, such as the DEA, NIDA, FDA, Department of Health and Human Services (DHHS), National Institutes of Health (NIH), and the Centers for Disease Control and Prevention (CDC), to collaborate with non-governmental stakeholders to determine procedures to decrease the burden of cannabis-related research while maintaining appropriate regulatory safety guards. This should include a reclassification of marijuana from Schedule I to facilitate clinical research. The AAFP calls for increased funding from both public and private sectors to support rigorous scientific research to address gaps in evidence regarding cannabis to protect the health of the public and inform evidence-based practices. 3  Future research should address the impact of cannabis use on vulnerable and at-risk populations.

Regulatory Considerations

While cannabis was federally regulated in 1906 for consumer and safety standards and labeling requirements, the  Marihuana Tax Act  of 1937 was the first federal regulation to impose a fine or imprisonment for non-medical use and distribution of cannabis. 5  The tax act also regulated production, distribution, and use of cannabis, further requiring anyone dealing with cannabis to register with the federal government. 5  In 1970, the DEA classified marijuana as a Schedule I drug, which is defined as a drug with no current acceptable medical use and a high potential for abuse. 43  Other Schedule 1 drugs include heroin, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (ecstasy), methaqualone, and peyote. 43  Since this class of substances is determined as having no medical usage, they cannot be legally prescribed and thus, there is no medical coverage for them.

Marijuana is illegal under federal law. Penalties cover possession, sale, cultivation, and paraphernalia. However, the Agriculture Improvement Act of 2018 included a U.S. Department of Agriculture (USDA) Hemp Production Program, removing hemp from the Controlled Substances Act. 10,44  As a result, CBD  sourced from hemp plants containing no more than 0.3% THC is legal to produce. 10,44  The FDA has approved three medications containing cannabinoids: epidiolex (CBD), dronabinol, and nabilone (synthetic cannabinoids). 5  No other forms of cannabis are currently regulated by the FDA. The AAFP calls upon the FDA to take swift action to regulate CBD and cannabinoid products now legal in order to protect the health of the public.

States have separate marijuana, cannabinoid, and cannabis laws, some of which mirror federal laws, while others may be more harsh, or have decriminalized and even legalized marijuana and cannabis. 45  In 1996, California was the first state to legalize the medical use of marijuana. 46  States have subsequently decriminalized and/or legalized cannabinoids, medical marijuana, and recreational marijuana. 46  As of August 2019, 30 states, along with the District of Columbia, Guam, and Puerto Rico have legalized marijuana in varying forms. 46  Decriminalization laws may include reduction of fines for possession of small amounts of marijuana, reclassification of criminal to civil infractions, excluding the infraction from criminal records and expunging prior offenses and convictions related to marijuana. 47  Thirty-three states, along with the District of Columbia, Guam, Puerto Rico, and the U.S. Virgin Islands have a comprehensive, publicly-available medical marijuana/cannabis program, and 13 of these states have also removed jail time for possessing small amounts of non-medical marijuana. 47  Adult recreational marijuana use is legal in 13 states and the District of Columbia. 47  Vermont and the District of Columbia, however, do not allow the sale of marijuana for recreational purposes. This means it is not a crime to use and possess marijuana recreationally, but commercial sales are not allowed. 47  States have also authorized the sale of products that have low levels of THC, but high levels of CBD. These products are widely available in retail locations, but are highly unregulated. 47  The benefits of CBD touted by the public and retailers are largely anecdotal. The vast majority of these claims are not substantiated by valid research.

Decriminalizing and legalizing marijuana can decrease the number of individuals arrested and subsequently prosecuted for possession and/or use. 48  However, evidence suggests that these practices are not applied equitably. People of color are more likely to be arrested and prosecuted for marijuana possession despite overall decreased arrest rates. 48  Incarceration impacts health. People who are incarcerated have significantly higher rates of disease than those who are not, and are less likely to have access to adequate medical care. 49

The AAFP “opposes the recreational use of marijuana. However, the AAFP supports decriminalization of possession of marijuana for personal use. The AAFP recognizes the benefits of intervention and treatment for the recreational use of marijuana, in lieu of incarceration, for all individuals, including youth.” 4  The AAFP calls for family physicians to advocate to prevent unnecessary incarceration by diverting eligible people from the justice system to substance abuse and/or mental health treatment. 49

There are many public health considerations when regulating cannabis products. Serious public health concerns include impaired driving, youth exposure to advertisements, and accidental poisoning in children. Second to alcohol, marijuana is the most common illicit drug associated with impaired driving and accidents. 34  Marijuana slows reaction time and decision making, substantially increasing risk for traffic accidents. 50  Some states have a zero-tolerance policy, where there is no allowable detectable level of THC while driving, while other states have set five nanograms per milliliter or higher limits of THC, or minimally-detectable amounts of THC. 51

Evidence indicates adolescents who are exposed to medical marijuana advertising are more likely to have positive views of and subsequently use marijuana. 52  Those exposed to medical marijuana advertising were more likely to report past use and expectant future use. 52  These adolescents also reported agreeing with statements like, marijuana helps people relax and get away from their problems. 52  Adolescent exposure to medical marijuana advertising was also associated with self-reporting negative consequences associated with marijuana use, including missing school and concentration issues. 52  The AAFP calls for immediate regulation of advertising of all marijuana and cannabinoid products to decrease youth exposure to aid in preventing initiation and subsequent use of marijuana.

Children are most susceptible to severe effects associated with marijuana poisoning, including decreased coordination, lethargy, sedation, difficulty concentrating, and slurred speech. 53  Exposure may also include serious, potentially life-threatening symptoms like respiratory distress and coma. 33  Unintentional exposures to marijuana in children have increased each year since 2012, likely due to legalization policies across the U.S. and popularity of edibles. 53  Edibles often look exactly like their non-THC counterparts, and come in brightly colored packaging appealing to children, often mimicking candy products. 53  Effective legislation requiring childproof packaging for edible products can help mitigate and prevent unintentional exposure in children. 54  Family physicians should discuss safe storage of all cannabis products with their patients who live with children. 54  Under the Child Abuse Prevention and Treatment Act (CAPTA), physicians are mandated reporters of suspected child abuse and neglect. 55  The 2010 law requires states to enact laws for reporting substance use-exposed infants to child protective services. 55

Family physicians play a key role in addressing marijuana, cannabinoid, and cannabis product use; reducing barriers to research; and advocating for appropriate policy to protect the health of patients and the public.

Family physicians can address the inappropriate use of marijuana, cannabinoid, and cannabis products. Family physicians should discuss safe storage of all cannabis products with patients who live with or serve as primary caregivers for children to prevent unintended exposure. 56  It is important to discuss the developmental and negative impacts of marijuana and cannabis products with individuals who are or can become pregnant, children, and adolescents. Family physicians should also emphasize the serious consequences of impaired driving and marijuana intoxication.

It is essential to decrease barriers to research all forms of marijuana, cannabis, and cannabinoids, including a reclassification of cannabis as a Schedule I drug. High-quality research regarding the impact on patients, public health, society, and health policy are essential to providing patient-centered care and promoting evidence-based public health practices. Immediate regulations for marijuana and cannabinoid products, including CBD, like product safety and consistency safeguards, child-proof packaging, labeling, marketing claims and advertising, and impairment standards are vital for consumer safety and injury prevention. Regulatory measures focused on preventing youth initiation of marijuana and cannabinoid product use must be prioritized to prevent a public health epidemic.

The health benefits associated with intervention and treatment of recreational marijuana and cannabinoid use, in lieu of incarceration, is an important policy consideration.

Utilizing an interdisciplinary, evidence-based approach to addressing both medical and recreational marijuana and cannabis use is essential to promote public health, inform policy, and provide patient-centered care. Family physicians, in partnership with public health and policy professionals, can play an imperative role in addressing the changing landscape of marijuana and cannabis products.

• Bridgeman MB, Abazia DT. Medicinal cannabis: history, pharmacology, and implications for the acute care setting.  P T . 2017;42(3):180-188. Accessed August 20, 2019.
• Abrams DI. The therapeutic effects of cannabis and cannabinoids: An update from the National Academies of Sciences, Engineering and Medicine report.  Eur J Intern Med . 2018;49:7-11.
• American Academy of Family Physicians. Substance abuse and addiction . Accessed August 20, 2019.
• American Academy of Family Physicians. Marijuana possession for personal use . Accessed August 20, 2019.
• The National Academies of Science, Engineering, and Medicine.  The Health Effects of Cannabis and Cannabinoids . Washington, D.C.: National Academies Press; 2017.
• National Institute on Drug Abuse. DrugFacts: Monitoring the Future Survey: high school and youth trends. www.drugabuse.gov/publications/drugfacts/monitoring-future-survey-high-school-youth-trends. Accessed August 20, 2019.
• National Institute on Drug Abuse. National Survey of Drug Use and Health . Accessed August 20, 2019.
• Mackie K. Cannabinoid receptors: where they are and what they do.  J Neuroendocrinol . 2008;20(s1):10-14.
• Hilderbrand RL. Hemp & cannabidiol: what is a medicine?  Mo Med . 2018;115(4):306-309. Accessed August 20, 2019.
• U.S. Department of Agriculture. Hemp production program . Accessed August 20, 2019.
• Heidi H. Oregon State University launches largest, most comprehensive hemp research center in the nation. Oregon State University. www.today.oregonstate.edu/news/oregon-state-university-launches-largest-most-comprehensive-hemp-research-center-nation. Accessed August 20, 2019.
• Lee MJ. The legalization of hemp. Accessed August 20, 2019.
• Shipman M. Is hemp the same thing as marijuana? NC State University. Accessed August 20, 2019.
• National Institute on Drug Abuse. What is marijuana?  Accessed August 20, 2019.
• Drug Policy Alliance. Marijuana concentrates.  Accessed August 20, 2019.
• MacCoun RJ, Mello MM. Half-baked — the retail promotion of marijuana edibles.  N Engl J Med . 2015;372(11):989-991.
• Peschel W, Peschel, Wieland. Quality control of traditional cannabis tinctures: pattern, markers, and stability.  Sci Pharm . 2016;84(3):567-584.
• Rosenblatt S, Tucker J, DeAngelo S. Methods and compositions of cannabis extracts. Accessed August 20, 2019.
• MacCallum CA, Russo EB. Practical considerations in medical cannabis administration and dosing.  Eur J Intern Med . 2018;49:12-19.
• U.S. Food and Drug Administration. FDA regulation of cannabis and cannabis-derived products: questions and answers . Accessed August 20, 2019.
• National Cancer Institute. NCI Drug Dictionary. Nabiximols.  Accessed August 20, 2019.
• U.S. Food and Drug Administration. Syndros (dronabinol) oral solution . Accessed August 20, 2019.
• U.S. Food and Drug Administration. CESAMETTM (nabilone) capsules.  Accessed August 20, 2019.
• Greenwich Biosciences. Epidiolex® (cannabidiol). www.epidiolex.com/. Accessed August 20, 2019.
• Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use. A systematic review and meta-analysis.  JAMA . 2015;313(24):2456-2473.
• Abuhasira R, Shbiro L, Landschaft Y. Medical use of cannabis and cannabinoids containing products – Regulations in Europe and North America.  Eur J Intern Med . 2018;49:2-6.
• Devinsky O, Cilio MR, Cross H, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.  Epilepsia . 2014;55(6):791-802.
• U.S. Food and Drug Administration. FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy.  Accessed August 20, 2019.
• Devinsky O, Patel AD, Cross JH, et al. Effect of cannabidiol on drop seizures in the Lennox–Gastaut syndrome.  N Engl J Med . 2018;378(20):1888-1897.
• Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome.  N Engl J Med . 2017;376(21):2011-2020.
• Perucca E. Cannabinoids in the treatment of epilepsy: hard evidence at last?  J Epilepsy Res . 2017;7(2):61-76.
• 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;73(3):292-297.
• Wang GS. Cannabis (marijuana): acute intoxication. UpToDate. Accessed August 20, 2019.
• Volkow ND, Baler RD, Compton WM, Weiss SRB. Adverse health effects of marijuana use.  N Engl J Med . 2014;370(23):2219-2227.
• Wilson KM, Torok MR, Wei B, et al. Detecting biomarkers of secondhand marijuana smoke in young children.  Pediatr Res . 2017;81(4):589-592.
• Reece-Stremtan S, Marinelli KA. ABM Clinical Protocol #21: Guidelines for Breastfeeding and Substance Use or Substance Use Disorder, Revised 2015.  Breastfeed Med . 2015;10(3):135-141.
• Bertrand KA, Hanan NJ, Honerkamp-Smith G, Best BM, Chambers CD. Marijuana use by breastfeeding mothers and cannabinoid concentrations in breast milk.  Pediatrics . 2018;142(3):e20181076.
• Corsi DJ, Walsh L, Weiss D, et al. Association between self-reported prenatal cannabis use and maternal, perinatal, and neonatal outcomes.  JAMA . 2019;322(2):145-152.
• Centers for Disease Control and Prevention. Does marijuana use lead to other drug use?  Accessed August 20, 2019.
• Di Forti M, Quattrone D, Freeman TP, et al. The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study.  The Lancet Psychiatry . 2019;6(5):427-436.
• U.S. Food and Drug Administration. Marijuana research with human subjects . Accessed August 20, 2019.
• National Institute on Drug Abuse (NIDA). NIDA’s role in providing marijuana for research. www.drugabuse.gov/drugs-abuse/marijuana/nidas-role-in-providing-marijuana-research. Accessed August 20, 2019.
• U.S. Drug Enforcement Administration. Drug scheduling . Accessed August 20, 2019.
• U.S. Food and Drug Administration. Statement from FDA Commissioner Scott Gottlieb, M.D., on signing of the Agriculture Improvement Act and the agency's regulation of products containing cannabis and cannabis-derived compounds. Accessed August 20, 2019.
• American Bar Assocation. Conflicting state and federal marijuana laws create ethical complications for lawyers. Accessed August 20, 2019.
• National Conference of State Legislatures. Marijuana laws. www.ncsl.org/bookstore/state-legislatures-magazine/marijuana-deep-dive.aspx. Accessed August 20, 2019.
• National Conference of State Legislatures. Marijuana laws. Accessed August 20, 2019.
• Drug Policy Alliance. From prohibition to progress: a status report on marijuana legalization. Accessed August 20, 2019.
• American Academy of Family Physicians. Incarceration and health: a family medicine perspective (position paper) . Accessed August 20, 2019.
• Centers for Disease Control and Prevention. What you need to know about marijuana use and driving . Accessed August 20, 2019.
•  National Conference of State Legislatures. Drugged driving | Marijuana-impaired driving . Accessed August 20, 2019.
• RAND Corporation. Adolescents who view more medical marijuana advertising are more likely to use marijuana, have positive views about the drug . Accessed August 20, 2019.
• Center on Addiction. Childhood poisoning: safeguarding young children from addictive substances. Accessed August 20, 2019.
• Center on Addiction. Toddlers and THC: the number of young children exposed to marijuana is on the rise. Accessed August 20, 2019.
• Child Welfare Information Gateway. Mandatory reporters of child abuse and neglect.  Accessed August 20, 2019.
• Children’s Hospital Colorado. Marijuana safety in the home . Accessed August 20, 2019.

(July 2019 BOD)

Copyright © 2024 American Academy of Family Physicians. All Rights Reserved.

Understanding the evidence for medical cannabis and cannabis-based medicines for the treatment of chronic non-cancer pain

Affiliations.

• 1 National Drug and Alcohol Research Centre (NDARC), Faculty of Medicine, UNSW Sydney, 22-32 King Street, Randwick, NSW, 2031, Australia. [email protected].
• 2 National Drug and Alcohol Research Centre (NDARC), Faculty of Medicine, UNSW Sydney, 22-32 King Street, Randwick, NSW, 2031, Australia.
• 3 Monash Addiction Research Centre, Eastern Health Clinical School, Faculty of Medicine Nursing and Health Sciences, Monash University, Level 2, 5 Arnold Street, Box Hill, VIC, 3128, Australia.
• PMID: 30635715
• DOI: 10.1007/s00406-018-0960-9

The use of medical cannabis and cannabis-based medicines has received increasing interest in recent years; with a corresponding surge in the number of studies and reviews conducted in the field. Despite this growth in evidence, the findings and conclusions of these studies have been inconsistent. In this paper, we outline the current evidence for medical cannabis and cannabis-based medicines in the treatment and management of chronic non-cancer pain. We discuss limitations of the current evidence, including limitations of randomised control trials in the field, limits on generalisability of previous findings and common issues such as problems with measurements of dose and type of cannabinoids. We discuss future directions for medicinal cannabinoid research, including addressing limitations in trial design; developing frameworks to monitor for use disorder and other unintended outcomes; and considering endpoints other than 30% or 50% reductions in pain severity.

Keywords: Cannabis; Cannabis-based medicines; Chronic pain; Medical cannabis.

Publication types

• Cannabinoid Receptor Modulators / pharmacology*
• Cannabinoids / pharmacology*
• Chronic Pain / drug therapy*
• Medical Marijuana / pharmacology*
• Cannabinoid Receptor Modulators
• Cannabinoids
• Medical Marijuana

Marijuana as Medicine? The Science Beyond the Controversy.

• Hardcopy Version at National Academies Press

1 INTRODUCTION

There are many reasons for wanting to understand what science has so far revealed—and what remains unknown—about marijuana's medical potential. Can marijuana really help people with AIDS (acquired immune deficiency syndrome), cancer, glaucoma, multiple sclerosis, or any of several other conditions it is purported to relieve? How does marijuana affect the human body? Could the potential benefits of legalizing marijuana for medicinal use possibly outweigh the risk of encouraging drug abuse? All of these questions remain to be answered completely, but over the past two decades scientists have made significant progress in revealing how chemicals in marijuana act on the body. Researchers have also studied how marijuana use affects individuals and society as a whole.

Unfortunately, much of what scientists have learned about the medical use of marijuana has been obscured by highly polarized debate over the drug's legal status. At times advocates for medical marijuana have appeared to be discussing a different drug than their opponents. Consider the following statements:

There are over ten thousand documented studies available that confirm the harmful physical and psychological effects of . . . marijuana.

—from the California Narcotic Officers' Association

Marijuana is NOT a Medicine, Santa Clarita, CA (1996), p. 2.

The cannabis plant (marijuana) . . . [has] therapeutic benefits and could ease the suffering of millions of persons with various illnesses such as AIDS, cancer, glaucoma, multiple sclerosis, spinal cord injuries, seizure disorders, chronic pain, and other maladies.

—from the editor's introduction to Cannabis in Medical Practice, by Mary Lynn Mathre, R.N.

Conflicts regarding the legitimacy of medical marijuana use extend even to the level of state versus federal law. Between 1996 and 1999, voters in eight states (Alaska, Arizona, California, Colorado, Maine, Nevada, Oregon, and Washington) and the District of Columbia * registered their support for the prescription of marijuana by physicians, defying the policies of the federal government and the convictions of many of its leaders.

Prior to the 1998 election, former Presidents Ford, Carter, and Bush released a statement urging voters to reject state medical marijuana initiatives because they circumvented the standard process by which the Food and Drug Administration (FDA) tests medicines for safety and effectiveness. “Compassionate medicine,” these leaders insisted, “must be based on science, not political appeals.” Nevertheless, medical marijuana initiatives proceeded to pass in every state in which they appeared on the ballot.

Both those who advocate and those who oppose the medical use of marijuana claim to have science on their side. Each camp selectively cites research that supports its position, and each occasionally misrepresents study findings. Unfortunately, these skewed interpretations have frequently served as the main source of scientific information on the subject. Until now it has been difficult for people other than scientists to find unbiased answers to questions about the medical use of marijuana—questions that have often drawn conflicting responses from either side of the debate.

But the public controversy over the medical use of marijuana does not reflect scientific controversy. Scientists who study marijuana and its effects on the human body largely agree about the risks posed by its use as well as the potential benefits it may provide. That is what researchers at the Institute of Medicine (IOM) learned when they undertook the study on which this book is based.

The goal of the study, performed at the request of the White House Office of National Drug Control Policy, was to conduct a critical review of all scientific evidence pertaining to the medical use of marijuana and its chemical components. For more than a year, researchers from the IOM—an arm of the National Academy of Sciences, which acts as an independent adviser to the federal government—compiled and assessed a broad range of information on the subject. One of us (Janet E. Joy) coordinated the IOM study. John A. Benson, Jr., dean and professor of medicine emeritus from the Oregon Health Sciences University School of Medicine and Stanley J. Watson, Jr., codirector and research scientist at the University of Michigan's Health Research Institute in Ann Arbor, served as its chief investigators. Nine other medical scientists with expertise concerning the medical use of marijuana served as technical advisers throughout the project.

In the course of its work, the study team examined research on how marijuana exerts its effects in the body and its ability to treat a wide variety of medical conditions. Team members compared the effectiveness of using marijuana versus approved medicines to treat numerous specific disorders. They also evaluated the effects of chronic marijuana use on physical and mental health as well as its possible role as a “gateway” drug to cocaine, heroin, and other illicit drugs.

To gather this information, the researchers analyzed scientific publications, consulted extensively with biomedical and social scientists, and conducted public scientific workshops. They also visited four so-called cannabis buyers' clubs and two HIV-AIDS clinics. Organizations and individuals were encouraged to express their views on the medical use of marijuana at the public workshops as well as via the Internet, by mail, and by telephone. The team's draft report was reviewed and critiqued anonymously by more than a dozen experts, whose comments were addressed in preparing the final version of the document. Entitled Marijuana and Medicine: Assessing the Science Base, the final report was released in March 1999. The report was subsequently published as a clothbound book by the National Academy Press; it can also be viewed on the Press's web site.

At the time of its release, the study received considerable attention from the news media. For example, the next week more than 50 U.S. newspapers carried stories on the study. While many of the articles reflected the balanced nature of the report's findings, most of the headlines—which tend to stick in readers' minds—gave the impression that the IOM had fully endorsed the medical use of marijuana. Scores of editorials followed suit, including several expressing uncritical acceptance of marijuana as a medicine.

In fact, the IOM researchers found little reason to recommend crude marijuana as a medicine, particularly when smoked, but they did conclude that active ingredients in marijuana could be developed into a variety of promising pharmaceuticals. Responding to the report's call for clinical trials on such marijuana-based medications, the National Institutes of Health and the Canadian equivalent of that agency, Health Canada, subsequently announced new policies intended to encourage medical research on marijuana (see Chapter 11 ).

While the IOM report was directed at policymakers, the purpose of this book is to present the main findings of that study for use by anyone who wants unbiased, scientifically sound medical information on marijuana. To adapt the IOM's publication for a general audience, considerable technical detail has been removed and in-depth explanations added of several key studies reviewed in the original report. For studies discussed in detail, references are provided in the form of footnotes. When the results of a group of studies are summarized, readers are referred to the relevant pages of the IOM report for more information and complete references. In a few instances, where more recent survey data became available after the IOM report was published, the most current information is used.

This book is divided into three parts, each of which offers a different perspective on marijuana as medicine. Along with this introduction, Chapter 2 and Chapter 3 lay out the scientific and historical foundation of current knowledge on the potential benefits and dangers of marijuana-based medicines. The second section— Chapter 4 , Chapter 5 , Chapter 6 , Chapter 7 , Chapter 8 through Chapter 9 —focuses on specific diseases, including cancer, AIDS, glaucoma, and a variety of movement and neurological disorders. In each case, the current state of knowledge regarding marijuana's effectiveness in treating symptoms of specific disorders is described and compared with conventional therapies. We explain why some marijuana-related studies that may seem convincing are actually inconclusive and what evidence is needed to support various claims about marijuana's harms or benefits. Finally, although this is primarily a book about science, two chapters in Part III are devoted to related issues: the economic prospects for developing pharmaceuticals from marijuana ( Chapter 10 ) and the complex legal environment surrounding the medical use of marijuana ( Chapter 11 ). Much of the information that is included about the legal status of marijuana did not appear in the IOM report but was added here to place the science of medical marijuana in a broader social context.

In addition to providing a critical and up-to-date summary of scientific knowledge that pertains to the medical use of whole marijuana, chemicals derived from the marijuana plant are also discussed, as well as synthetic compounds that represent “improved” versions of marijuana derivatives. This information can help readers evaluate future research news and participate in the ongoing public discussion of medical marijuana.

At the same time, it is important to recognize that science is but one aspect of the medical marijuana controversy. Ultimately, drug laws must address moral, social, and political concerns as well as science and medicine. Although we present scientific evidence related to the social impact of medical marijuana, the intent is not to prescribe policy but to encourage continued debate based on a firm understanding of scientific knowledge. As you read, please bear this in mind, along with the following caveats:

• Neither this book, nor the IOM study on which it is based, is intended to promote specific social policies. Both were designed to provide an objective scientific analysis of marijuana's current and potential usefulness in treating a variety of symptoms.
• In no way do we wish to suggest that patients should, un der any circumstance, medicate themselves with marijuana, an illegal drug.
• The medical information in this book is not intended to substitute for the advice of a physician or other health care professional.

Now that you know where this book came from and where it's going, we offer a few guideposts to aid your journey through it. Because the following key concepts underlie our discussion of medical marijuana, familiarizing yourself with them will help you make the most of your reading.

Marijuana contains a complex mixture of chemicals. Marijuana leaves or flower tops can be smoked, eaten, or drunk as a tea (see Figure 1.1 ). People who use marijuana in these ways expose themselves to the complex mixture of chemical compounds present in the plant. One of these chemicals, tetrahydrocannabinol (THC), is the main cause of the marijuana “high.” Thus, the effects of marijuana on the body include those of THC, but not all of marijuana's effects are necessarily due to THC alone.

Leaves and flower tops of female marijuana plants. (Photo by André Grossman.)

According to federal law, marijuana belongs to a category of substances that have a high potential for abuse and no accepted medical use. Other drugs in this category include LSD (lysergic acid diethylamide) and heroin. By contrast, doctors can legally prescribe THC, in the form of the medicine Marinol (a brand name for a specific formulation of the generic drug dronabinol), under highly regulated conditions. Dronabinol, the “synthetic” THC in Marinol, is identical in every way to the “natural” THC in marijuana.

The FDA has approved Marinol for the treatment of nausea and vomiting associated with cancer chemotherapy and also to counteract weight loss in AIDS patients. Currently classified with controlled substances such as anabolic steroids, Marinol was moved from a more restrictive category, which included cocaine and morphine, in July 1999.

Some of the medical studies discussed in later chapters deal with the effects of marijuana, while others focus on specific chemicals present in the marijuana plant. This distinction should be kept in mind when considering the results of these studies. The psychoactive chemicals in marijuana are members of a family of molecules known as cannabinoids, derived from the plant's scientific name, Cannabis sativa. Most cannabinoids are closely related to THC. Scientists also refer to chemicals that are not found in marijuana but that resemble THC either in their chemical structure or the way they affect the body as cannabinoids.

Occasionally, we also refer to “marijuana-based medicines. ” These encompass the entire spectrum of potential medications derived from marijuana, from whole-plant remedies to extracts to individual cannabinoids, both natural and synthetic.

Marijuana is not a modern medicine. Although people have used marijuana for centuries to soothe a variety of ills, it cannot be considered a medicine in the same sense as, for example, aspirin. Aspirin's chemical cousin, found in willow bark, was long used as a folk remedy for pain. But unlike marijuana, aspirin has been proven safe and effective through rigorous testing. Aspirin tablets contain a pure measured dose of medicine, so they can be relied on to give consistent and predictable results.

By contrast, two identical-looking marijuana cigarettes could produce quite different effects, even if smoked by the same per son. If one of the cigarettes were made mostly from leaves and the other from flower tops, for instance, they would probably contain different amounts of active chemicals. Growing conditions also affect marijuana's potency, which can vary greatly from region to region and even from season to season in the same place. This variability makes marijuana at best a crude remedy, more akin to herbal supplements such as St. John's wort or ginkgo than to conventional medications.

To date, few herbal supplements have been tested for safety and efficacy in the United States, nor are such products subject to mandatory quality controls. Yet despite these drawbacks, increasing numbers of consumers are using herbal treatments, prompted by their desire for “natural” alternatives to man-made medicines. However, another way to view herbal remedies is to recognize that if they are effective, they contain specific active ingredients. Willow bark contains a pain-relieving compound; marijuana contains cannabinoids such as THC, which lessens nausea. Once identified, chemists can duplicate active compounds in the laboratory. Scientists can also use natural compounds as a basis for creating new medicines. By introducing subtle structural changes in natural molecules, chemists have produced drugs that are more effective and easier to administer and that have fewer side effects than their natural counterparts. So far, a few such analogs or derivatives of cannabinoids are known to exist; others are currently under investigation.

Marijuana used as medicine is not a recreational drug. People who use marijuana solely as a medication do so in order to relieve specific symptoms of AIDS, cancer, multiple sclerosis, and other debilitating conditions. Some do so under the advice or consent of doctors after conventional treatments have failed to help them. In mentioning medical marijuana users, we are referring to people who smoke or eat marijuana exclusively as a treatment for medical symptoms. The fact that many such patients may have prior recreational experience with the drug does not mean that they are using illness as an excuse to get high, although it is possible that some patients might do so. Surveys of marijuana buyers' clubs indicate that most of their members do, in fact, have serious medical conditions.

Medical marijuana users tend to come from different seg ments of the population than recreational users. In the United States recreational marijuana use is most prevalent among 18 to 25 year olds and declines sharply after age 34. By contrast, reports on medical marijuana users indicate that most are over 35, as are typical consumers of herbal medicine and other alternative therapies. Most tend to suffer from chronic illnesses or pain that defy conventional treatments.

Medical marijuana advocates assert that patients usually obtain relief with smaller doses of the drug than would be used recreationally and that they rarely feel high when treating their symptoms with marijuana; however, no objective study has tested this claim. As discussed in detail in Chapter 3 , marijuana and its constituent chemicals can produce both physical and psychological dependence. These risks must be taken into account if marijuana or cannabinoids are to be used as medicines.

Many effective medicines have side effects. The fact that marijuana affects the human body adversely does not preclude its use as a source of useful medicines. Many legitimate drugs—including opiates, chemotherapy agents, and steroids—have side effects ranging from the dangerous to the merely unpleasant. When used carefully, though, the benefits of these medications far outweigh their drawbacks. Patients may also develop tolerance, dependence, and withdrawal—conditions associated with marijuana use—when taking proper doses of several commonly prescribed medications. For example, the correct use of some prescription medicines for pain, anxiety, and even hypertension normally produces tolerance and some physiological dependence.

As researchers learn more about the chemicals present in marijuana and their effects on the body, it may be possible to identify beneficial compounds and separate them from harmful substances in the plant. Finding a rapid way to deliver cannabinoids to the body, other than smoking, could lessen some of marijuana's worst side effects. It may also be possible to reduce the adverse effects of specific cannabinoids through chemical modification, as previously noted.

Marijuana's effects vary with different delivery methods. Traditionally, medicinal marijuana has not been smoked but rather swallowed in the form of an extract or applied to the underside of the tongue in the form of an alcohol-based tincture. Although the lat ter method allows the THC to pass directly into the bloodstream, it is far less efficient than smoking. When swallowed, drugs pass through the stomach, intestine, and liver before entering the bloodstream, so they act slowly. This is especially true of the main active ingredient in marijuana. Because THC is barely soluble in water, the body absorbs only a small fraction of the available drug when it is swallowed.

The same is true of Marinol, which is simply THC in capsule form. Marijuana smoke, on the other hand, efficiently delivers THC into the bloodstream via the lungs. Inhaled THC takes effect quickly, allowing patients to use just enough to relieve their symptoms; it is not so easy to fine-tune the dose of oral medications. For this reason, pharmaceutical firms are investigating the use of smokeless inhalers and nasal sprays to deliver THC and possibly other cannabinoids.

The Colorado vote was later disallowed after a court determined that the petition to place the initiative on the ballot did not have enough valid signatures. Congress has prohibited the counting of actual ballots in the District of Columbia referendum, but exit polls indicated that a majority of voters approved the measure. Nevada voters must reapprove their proposal in the year 2000 before it becomes law.

• Cite this Page Mack A, Joy J. Marijuana as Medicine? The Science Beyond the Controversy. Washington (DC): National Academies Press (US); 2000. 1, INTRODUCTION.
• PDF version of this title (3.6M)

Recent Activity

• INTRODUCTION - Marijuana as Medicine? INTRODUCTION - Marijuana as Medicine?

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Connect with NLM

National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894

Web Policies FOIA HHS Vulnerability Disclosure

Help Accessibility Careers

Cannabis (Marijuana) Research Report What are marijuana's effects?

When marijuana is smoked, THC and other chemicals in the plant pass from the lungs into the bloodstream, which rapidly carries them throughout the body to the brain. The person begins to experience effects almost immediately (see " How does marijuana produce its effects? "). Many people experience a pleasant euphoria and sense of relaxation. Other common effects, which may vary dramatically among different people, include heightened sensory perception (e.g., brighter colors), laughter, altered perception of time, and increased appetite.

If marijuana is consumed in foods or beverages, these effects are somewhat delayed—usually appearing after 30 minutes to 1 hour—because the drug must first pass through the digestive system. Eating or drinking marijuana delivers significantly less THC into the bloodstream than smoking an equivalent amount of the plant. Because of the delayed effects, people may inadvertently consume more THC than they intend to.

Pleasant experiences with marijuana are by no means universal. Instead of relaxation and euphoria, some people experience anxiety, fear, distrust, or panic. These effects are more common when a person takes too much, the marijuana has an unexpectedly high potency, or the person is inexperienced. People who have taken large doses of marijuana may experience an acute psychosis, which includes hallucinations, delusions, and a loss of the sense of personal identity. These unpleasant but temporary reactions are distinct from longer-lasting psychotic disorders, such as schizophrenia, that may be associated with the use of marijuana in vulnerable individuals. (See " Is there a link between marijuana use and psychiatric disorders? ")

Although detectable amounts of THC may remain in the body for days or even weeks after use, the noticeable effects of smoked marijuana generally last from 1 to 3 hours, and those of marijuana consumed in food or drink may last for many hours.