COMMENTARY

Medical Marijuana: The State of the Science

Michael E. Schatman, PhD

Disclosures

February 06, 2015

In This Article

Is THC "Medical"?

As previously discussed, the tolerability of synthetic THC is limited, making its use in clinical practice dubious. Perhaps the greatest difficulty in assessing the efficacy of medical marijuana relates to an inability to define what elements make marijuana "medical."

For many years, taxonomists considered marijuana to be a single-species genus, until Small and Cronquist[75] identified subspecies based on "intoxicant ability." Subsequently, we have learned considerably more, and we should speak of "medical marijuanas" rather than erroneously assuming that what is considered "medical" (or, for that matter, "recreational") cannabis represents one specific entity. Regardless, it is important to review some of the research that evaluates the efficacy of whole-plant marijuana for medical purposes.

Complicating the assessment of efficacy is the wide variety of disease states for which patients choose to use marijuana as an element of treatment. The nation's first medical cannabis law that was enacted (California's Compassionate Use Act of 1996) stipulated that marijuana could be recommended to a patient by a physician for "treatment of cancer, anorexia, AIDS, chronic pain, spasticity, glaucoma, arthritis, migraine, or any other illness for which marijuana provides relief."[76] Although the law mentioned specific diseases, its clause referencing "any other illness for which marijuana provides relief" added a considerable degree of subjectivity to the Act.

States' medical cannabis laws all tend to be nonspecific, and all but three consider "pain" as an appropriate condition to authorize medical cannabis. In a recent survey,[3] 94% of all medical cannabis registrants listed "severe pain" as their condition necessitating cannabis. Given the subjective nature of pain, providers would be challenged by the prospect of disproving a patient's report of pain. Accordingly, medical cannabis authorization has been extremely easy to obtain in states allowing it; data from Arizona indicate that between April and October of 2011, only seven of 14,925 applicants for medical marijuana registration were denied.[77]

There is a paucity of high-quality data supporting the efficacy of medical cannabis—again, primarily owing to the lack of a definition of "medical" cannabis. Furthermore, the available literature is very inconsistent with regard to study endpoints and outcomes. For example, is "pain relief" sufficient as the sole dependent variable in assessing efficacy, or should functionality also be taken into consideration? Although some patients will report high levels of pain relief after using the high-THC/low-CBD concentration marijuana that is typically sold at dispensaries, few, if any, studies show evidence to the contrary that these agents will reduce function in the vast majority of patients owing to intoxication.

A lack of dosing uniformity is also of concern. The recent review released by the American College of Neurology[21] considered six different disease states and symptoms and a variety of THC/CBD ratios and methods of administration (eg, oral, oromucosal, inhaled), with no assessment of patient function; the conclusions that could be drawn regarding efficacy were therefore limited.

For pain, the most common indication for medical cannabis, a review by Aggarwal[78] noted that "little data are available on the risks associated with long-term medical use in published clinical trials," but for "notoriously difficult to treat conditions," cannabinergic pain medicines may have appropriate evidence of safety and efficacy. Although recommending smoked cannabis, Aggarwal did not address issues of dosing, functionality, and tolerability, but appropriately called for additional research.

Finally, nabiximols, which has approximately a 1:1 THC/CBD ratio and oromucosal administration, was not considered, owing to the paucity of supportive data comparing efficacy and safety with other cannabis preparations. This is not to suggest that nabiximols is not beneficial in the treatment of several conditions, given findings of efficacy, safety, and tolerability in selected placebo-controlled trials.[79,80,81] Proper dosing of nabiximols, however, has not been determined.[82] Most relevant to this review, the lack of comparison with other cannabinoid-based products makes the role of nabiximols in solving the medical cannabinoid dilemma unclear.

In their review of herbal cannabis for rheumatologic conditions, Fitzcharles and colleagues[23] noted the dilemma experienced by physicians: "Simply acceding to patient demands for a treatment on the basis of popular advocacy, without comprehensive knowledge of an agent, does not adhere to the ethical standards of medical practice...any recommended therapy requires proof of concept by sound scientific study that attests to both efficacy and safety." All but the most biased reviews articles on this topic conclude with generic statements, such as, "Medical cannabis appears to have some benefit in patients with certain conditions."[83]

Multiple other systematic reviews of medical cannabis in which formulation, dosage, and route of administration were specified or were consistent across randomized controlled trials have failed to yield definitive conclusions regarding the safety and efficacy of medical cannabis for a variety of conditions.[8,84,85,86,87,88,89,90,91,92] Considering this ambiguity, how are providers supposed to know which cannabinoids, formulations, dosages, and routes of administration are safe, tolerable, and effective, and in which conditions and which patients? Unfortunately, current arguments for the use of medical cannabis are considerably more politically, and often emotionally, based, rather than scientifically based, resulting in the proliferation of "medical marijuana pseudoscience."[93]

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