Policy Analysis | April 2018

Efficacy and Adverse Effects of Medical Marijuana: An Overview

Anne Roberts Brody

State legislatures continue to grapple with the myriad issues surrounding the legalization of marijuana – both medical and recreational.  This brief summarizes the findings of several peer-reviewed studies focusing on the efficacy and outcomes of medical marijuana and CBD in the treatment of disease, the association between marijuana use and motor vehicle crashes, and the 2017 National Institute on Drug Abuse update on marijuana.  Hyperlinks have been provided to all studies referenced herein.

Cannabis and cannabidiol (CBD) are now widely used to treat or alleviate a variety of diseases and symptoms.  While often conflated, the ratio in botanical and pharmaceutical preparations determines therapeutic or psychoactive effects.  Tetrahydrocannabinoil (THC) is the cannabinoid in marijuana that produces psychoactive effects, whereas CBD is nonpsychoactive. 

Marijuana has been approved for recreational and medicinal use in a growing number of states. According to Governing, 30 states and the District of Columbia have laws broadly legalizing marijuana in some form as of January 2018.  Of those, eight states and the District of Columbia have legalized recreational marijuana.  Twenty-two states allow for limited use of medical marijuana under certain circumstances.  Some medical marijuana laws are broader than others, with types of medical conditions that qualify for treatment varying from state to state. 

Although marijuana use – both medical and recreational – is increasingly accepted in states, it remains a Schedule I narcotic.  Because of this classification, efficacy studies have been limited and largely are focused on negative impacts of marijuana and “medical marijuana.” Cannabis for research purposes is available only through the National Institute on Drug Abuse (NIDA) Drug Supply Program.  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 other drugs.  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.  Because NIDA funded the majority of all the National Institutes of Health-sponsored cannabinoid research in fiscal year 2015, its focus on the consequences of drug use and addiction constitutes an impediment to research on the potential beneficial uses of cannabis and cannabinoids.  All of the cannabis that NIDA provides to investigators is sourced from the University of Mississippi, which currently is the sole cultivator of the plant material and has been since 1968.

While the U.S. Food and Drug Administration (FDA) has not approved medical marijuana, there is mounting anecdotal evidence for the efficacy of marijuana-derived compounds. Whether marijuana consumption has therapeutic benefits that outweigh its health risks still is an open question that science has not yet resolved due to the dearth of longitudinal studies.  Nonetheless, safe medicines based on cannabinoid chemicals derived from the marijuana plant have been available for decades.

Although the FDA has not approved medical marijuana, it has approved THC-based medications, including dronabinol and nabilone.  Both medications received FDA approval in 1985.  These medications are prescribed in pill form for the treatment of nausea in patients undergoing chemotherapy and to stimulate appetite in patients with AIDS.  Additionally, CBD-based liquid medication, called Epidiolex, currently is being tested in the United States for the treatment of two forms of severe childhood epilepsy.  Several other marijuana-based medications have been approved or are undergoing clinical trials in the United Kingdom, Canada and several European countries. 

National Institute on Drug Abuse: Marijuana

The National Institute on Drug Abuse is a federal scientific research institute under the National Institutes of Health, U.S. Department of Health and Human Services.  This report reviews current scientific research on marijuana and its effects.

There is emerging evidence that medical marijuana, when paired with access to marijuana dispensaries, may result in decreased opioid dependence as well as Medicare savings.  A detailed analysis by the RAND Corporation, funded by NIDA and cited in the report, found that legal access to medical marijuana dispensaries is associated with lower levels of opioid prescribing, lower self-reporting of nonmedical prescription opioid use, lower treatment admissions for prescription opioid use disorders, and reduction in prescription opioid overdose deaths.  Notably, the reduction in deaths was present only in states with dispensaries (and not just medical marijuana laws).  Another recent study conducted by RAND, and cited in the report, analyzed Medicare prescription drug coverage data and found that availability of medical marijuana significantly reduced prescribing of medications used for conditions that medical marijuana can treat, including opioids for pain.  In 2013, overall savings for all prescription drugs were estimated to exceed $165 million.

Whether smoking marijuana causes lung cancer, as cigarette smoking does, has not been determined.  While a few small, uncontrolled studies have suggested that habitual marijuana smoking could increase the risk of respiratory cancers, NIDA asserts that well-designed population studies have not identified an association between marijuana use and an increased risk of lung cancer.

While marijuana often is considered a gateway drug, NIDA found that the majority of people who use marijuana do not go on to use other, “harder” substances.  Thus, an alternative to the gateway-drug hypothesis is that individuals who are more vulnerable to drug use are more likely to start with readily available substances such as marijuana, tobacco, or alcohol.

Several studies referenced in the report have linked marijuana use to increased risk for psychiatric disorders, including some discussed in this brief.  However, research using longitudinal data from the National Epidemiological Survey on Alcohol and Related Conditions examined associations between marijuana use, mood and anxiety disorders, and substance use disorders.  After adjusting for various confounding factors, no association between marijuana use and mood and anxiety disorders was found; however, recent research has found that individuals who carry a specific gene variant may be at increased risk of developing psychosis if they use marijuana.  One study reviewed by NIDA found that the risk among individuals with this variant was seven times higher for those who used marijuana daily compared with those who used it infrequently or not at all.

Cannabinoids for Medical Use: A Systematic Review and Meta-Analysis

In 2015, a systematic review of the benefits and adverse events of cannabinoids published in the Journal of the American Medical Association found moderate-quality evidence to support the use of cannabinoids for the treatment of chronic neuropathic or cancer pain and spasticity due to multiple sclerosis, and low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in patients with HIV, sleep disorders, and Tourette syndrome. According to the authors, although most studies suggested that cannabinoids were associated with improvements in symptoms, the associations were not statistically significant.   The study also found an increased risk of short-term adverse effects with cannabinoid use.  Common adverse effects included extreme weakness, balance problems, confusion, dizziness, disorientation, diarrhea, euphoria, drowsiness, dry mouth, fatigue, hallucination, somnolence, and vomiting.

Cannabis for Therapeutic Purposes: Patient Characteristics, Access, and Reasons for Use

Published in the International Journal of Drug Policy, this 2013 article reports findings from a large cross-sectional study on cannabis for therapeutic purposes in Canada and compares use across medical conditions, as well as across authorized and unauthorized users.  Participants were queried regarding a single primary condition and asked to check all applicable symptoms treated with cannabis.    The authors found that across medical conditions, respondents reported using cannabis to effectively address diverse symptoms.  Pain, anxiety and sleep problems were the most frequently treated symptoms. This suggests a disconnect between the use of cannabis for therapeutic purposes and research on the risks and benefits of such use.  Extrapolation of the sample to the Canadian population using cannabis for therapeutic purposes indicates levels of use for anxiety and for sedative purposes that may be comparable to the number of Canadians who currently use benzodiazepine and other sedatives, suggesting a need for further research into the effectiveness and adverse effects of cannabis for the treatment of these conditions compared to widely-used pharmaceutical products.

Cognitive and Clinical Outcomes Associated with Cannabis Use in Patients with Bipolar I Disorder

Published in Psychiatry Research, this 2012 article compares clinical and neurocognitive measures in individuals with bipolar disorder and a history of cannabis use disorder (CUD) with those who do not.  Analyzing data from 200 patients collected over a nine-year period, the authors found that patients with a history of CUD had better neurocognitive performance as compared to patients with no history of CUD.  Specifically, patients with a history of CUD demonstrated better neurocognitive performance on measures of attention, processing speed, and working memory.  Consistent with previous studies that demonstrated that patients with CUD had comparatively superior verbal fluency performance (cited in the report), the authors posit that cannabis use may have a beneficial effect on cognitive functioning in patients with severe psychiatric disorders.  However, the authors also found that a history of CUD was associated with an increased rate of psychosis during acute bipolar episodes, indicating a more severe clinical presentation for patients with bipolar disorder who use cannabis when compared to those who do not use cannabis.  The authors suggest treatment implications may include the development of medications with similar properties as cannabis, without its psychotomimetic effects, to be tested in cognitive enhancement trials in patients with bipolar disorder and/or schizophrenia.

Marijuana Use and Motor Vehicle Crashes

Published by Oxford University Press in 2011, this article utilizes a meta-analysis of nine epidemiologic studies to assesses the association between marijuana use and crash risk.  Although the authors note that previous epidemiologic studies have shown contradictory results, the results of this study suggest that marijuana use is associated with a significantly increased risk of motor vehicle crashes.  Specifically, the authors found that drivers who test positive for marijuana, or self-report using marijuana, are more than twice as likely as other drivers to be involved in motor vehicle crashes and that crash risk appears to increase progressively with the dose and frequency of marijuana use.  Importantly, they note that it is impossible to infer causality from these epidemiologic data alone – assessing interaction effects on driving safety of different drug combinations based on epidemiologic data would require very large study samples, comprehensive drug testing data, and a large financial commitment and resources.

Systematic Review: Efficacy and Safety of Medical Marijuana in Selected Neurologic Disorders

This 2014 report from the Guideline Development Subcommittee of the American Academy of Neurology is aimed at determining the efficacy and safety of medical marijuana in several neurologic conditions, including the treatment of symptoms of multiple sclerosis (MS), epilepsy, and movement disorders.  A variety of formulations of medical marijuana was used in this study, with differing amounts of THC and CBD.  The subcommittee concludes that oral cannabis extract is effective in reducing patient-centered and objective measures of spasticity after one year of treatment and in treating central pain/painful spasms; probably effective in treating patient-centered measures of spasticity; and not effective in treating bladder complaints, tremor, or levodopa-induced dyskinesias in Parkinson disease.  They found that nabiximols* probably are effective in reducing patient-centered measures of spasticity, central pain/painful spasms and reducing bladder voids but possibly ineffective in reducing tremor.  Meanwhile, THC was found to be effective in reducing patient-centered and objective measures of spasticity after one year of treatment; probably effective in reducing patient-centered measures of spasticity and central pain/painful spasms; and probably ineffective in reducing bladder complains and tremors.  The authors note that comparative effectiveness of medical marijuana versus other treatment therapies is unknown.  The subcommittee found that the risk of adverse psychopathologic effects was nearly 1 percent. 

* Nabiximols is a specific extract of cannabis that was approved as a botanical drug in the United Kingdom in 2010 as a mouth spray.

The Association Between Cannabis Use and Depression: A Systematic Review and Meta-Analysis of Longitudinal Studies

Utilizing a meta-analysis of longitudinal studies, this 2013 report published in Psychological Medicine analyzes the extent to which different patterns of cannabis use are associated with the development of depression.  The authors found that cannabis use may be associated with an increased risk for developing depressive disorders and recommend further longitudinal exploration of the issue, particularly as it relates to potentially significant confounding factors.  Two broad explanations for the association between cannabis use and the development of depression are discussed.  The first is a possible neurobiological link between cannabinoid effects and symptoms of depression.  However, the authors note that there is little research evidence to support this.  Instead, they suggest that most relevant research implies that cannabinoids may have an antidepressant effect. A second possibility posited by the authors is that cannabis use causes life events or circumstances that increases the likelihood of depression.  In other words, the association between cannabis use and increased risk for depression may be socially mediated.