Marijuana research: Overcoming the barriers

APA works for legislation to advance research on marijuana.

Election Day 2016 wasn’t all about selecting the next president.   Whether to legalize marijuana for recreational use was on the ballot in five states.  The outcome was that California, Maine, Massachusetts and Nevada were added to the earlier list of four states, plus the District of Columbia, in which recreational use of marijuana is legal.  The measure was defeated in Arizona. An additional four states voted on medicinal use, with Arkansas, Florida, Montana and North Dakota voting in the affirmative and increasing the total number of states allowing medicinal or recreational use of marijuana to 28 (plus DC).

Legal or not, people across the country are using marijuana for medicinal purposes.  But the evidence base for its therapeutic effects remains insufficient and people are using a range of product formulations of unknown potencies and compositions.  In general, both recreational and therapeutic users are encountering higher potency forms of marijuana than those available in the 1960s and ‘70s.  Marijuana and its constituent compounds are now available in a wide variety of products, including oils for use in vaporizers, edibles, beverages and even transdermal creams and gels. The public health implications of use of these varied products are currently unknown.  Most research has been conducted on lower potency varieties of plant material or specific cannabinoids (tetrahydrocannabinol -- THC, or cannabidiol -- CBD); little work has been done on the effects of any of the other pharmacologically active compounds in marijuana.

While there is significant polarization among advocacy groups -- those calling for legalization versus those supporting continued prohibition -- there is broad agreement on the need for more research.  Indeed, research is being conducted on such topics as the basic biology of the endogenous cannabinoid system in the nervous system, therapeutic effects of cannabinoids, risks associated with acute and chronic marijuana use, and changing state policies on the use of marijuana and related health and safety outcomes.  However, major barriers to research are preventing scientists from pursuing the full range of research that is needed to understand the impacts of recreational and therapeutic use of cannabinoids.

Legal barriers to research

Despite preclinical evidence suggesting the efficacy of cannabinoids for treating a number of health conditions (including multiple sclerosis, epilepsy, anxiety, and pain), progress in clinical research has been very slow.  Marijuana is regulated by the Drug Enforcement Agency (DEA), within the Department of Justice (DoJ), under the Controlled Substances Act. Within that framework, marijuana and its constituent compounds are categorized as Schedule I (having no Food and Drug Administration-approved therapeutic use), and all research conducted with marijuana requires that investigators register with the DEA.  The registration process can take more than a year to complete and creates administrative burdens that serve as significant disincentives to pursuing research.

In addition to a complicated application process, DEA oversight involves redundant scientific protocol review (for human studies, protocols are also reviewed by the FDA).  Additional review of minor protocol modifications can delay research further.  Investigators often report that the guidance they receive is unclear and that DEA inspections, security requirements and variable experiences with state DEA field offices add to the obstacles they face.

Adding to the complexity are differences between state and federal laws.  In an attempt to strike a balance between these, the DoJ under the Obama administration issued guidance that focused federal law enforcement resources on the most serious criminal activities (e.g., trafficking, drug violence) rather than on individual adults using marijuana for recreational or therapeutic purposes.  The guidance instructed DoJ attorneys and other federal law enforcement bodies to focus on eight priorities in enforcing the Controlled Substances Act against marijuana-related activities.  Authored by then Deputy Attorney General, James Cole, the guidance has become known as the “Cole memo.”  Whether the Trump administration’s DoJ will continue to honor that guidance remains to be seen but early signals suggest that this administration will take a harder line on therapeutic uses of marijuana.

Changing the law

Recognizing the need to reduce obstacles for clinical research on marijuana, legislation has been introduced in the U.S. Congress.  In the House of Representatives, the Medical Marijuana Research Act of 2017 was introduced by Rep. Andy Harris (R-MD) on July 25, 2017.  Harris, a member of the conservative Freedom Caucus, was an anesthesiologist on the faculty at Johns Hopkins University School of Medicine prior to running for Congress.  This bill has bipartisan support: it is cosponsored by Reps. Earl Blumenauer (D-OR), Morgan Griffith (R-VA) and Zoe Lofgren (D-CA).  A companion Senate bill, the Marijuana Effective Drug Studies Act of 2017, was introduced on September 13th by Sen. Orrin Hatch (R-UT) and co-sponsored by Sens. Brian Schatz (D-HI) and Chris Coons (D-DE). Sen. Hatch's office put out this press release which includes the floor statement the Senator gave upon the bill's introduction. 

Both bills allow for increases in the supply of marijuana for research. Until recently there was only one entity authorized to produce marijuana to supply researchers in the United States: the University of Mississippi, operating under a contract with the National Institute on Drug Abuse (NIDA).  Known colloquially among researchers as “the farm,” the university grows a single variety of marijuana (cannabis sativa) in strains that have been bred to contain specific concentrations of THC and CBD.

Unfortunately, anecdotal reports suggest that marijuana from “the farm” is inferior in its appeal to users in both real world contexts and research studies, which may affect the validity and generalizability of self-administration studies.  In 2016, the DEA announced that it would allow other manufacturers to register and grow marijuana for research purposes. However, the DoJ has not yet taken action on the 25 grower applications DEA has submitted for approval, so there is still no new marijuana product in the pipeline for research.

In addition, the bills amend the process for DoJ approval of applications from entities seeking to manufacture or dispense marijuana exclusively for legitimate medical research.  They require DoJ to approve an application unless it is demonstrated that it would not be in the public interest.  

Further, the House bill calls for the Department of Health and Human Services to review existing medical and other research on marijuana and to report to Congress on the results of the review. Understanding the characteristics of a broader range of marijuana strains and varieties, including their potencies (i.e., amount of THC) and concentrations of other components (e.g., CBD), will be critical for studying the health effects of marijuana use.  Such information can provide the basis for further research on the physiological and behavioral effects of specific constituents of marijuana and eventually to development of cannabinoid medications for specific conditions.

Working with the Friends of NIDA coalition, the American Psychological Association has led the effort to gain endorsements from scientific and professional organizations for the bills and will continue to urge support for them in hopes they will move through the committee process, pass each chamber of Congress, and get signed into law.

See also:

Marijuana and Cannabinoids: A Neuroscience Research Summit (National Institutes of Health, 2016)

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research (National Academies, 2017)

Geoff Mumford, PhD, is associate executive director for government relations in the Science Directorate of the American Psychological Association.

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