COMMENTARY

Medical Marijuana: The State of the Science

Michael E. Schatman, PhD

Disclosures

February 06, 2015

In This Article

Background

"Medical" cannabis, in some shape or form, is here to stay. Currently legal in 23 states and the District of Columbia,[1] the paradoxical federal illegality of cannabis remains relevant, particularly in the eyes of many healthcare providers.[2] The discrepancy between federal and state laws has created uncertainty about whether medical cannabis is legal and should be legal, and whether its use is in the best interest of physicians and their patients.

Physicians' ambivalence regarding medical cannabis was clearly illustrated in a 2013 survey of 520 members of the Colorado Academy of Family Physicians.[3] The survey found that whereas only 19% of respondents believed that physicians should recommend medical cannabis, 80% agreed that it should be incorporated into medical school education, 82% agreed that it should incorporated into residency training, and 92% agreed that it should be a topic of continuing medical education for practicing physicians. In addition, the majority of respondents agreed that there are significant mental and physical health risks associated with marijuana.

Undoubtedly, healthcare providers are left with more questions than answers about the use of medical cannabis. Some key questions include:

  • Is it safe?

  • Is there adequate evidence for its efficacy? If so, for what conditions is it effective?

  • If it is sold in dispensaries rather than on street corners, should it be considered "medical"?

  • If it is "medical," can it still be abused?

  • Is marijuana medical, or do certain components of marijuana have medical benefit and are safe?

These key questions will be addressed in this review, with the goal of reducing provider confusion and offering guidance on how certain cannabinoids—if not whole-plant marijuana—canbe integrated into evidence-based care.

THC vs Cannabidiol

Few users, and perhaps fewer healthcare providers, understand the composition of marijuana. The marijuana plant contains over 100 cannabinoids, which are the active chemical components of cannabis.[4] Delta-9-tetrahydrocannabinol (THC) is considered the most psychoactive component of marijuana,[5] and accordingly gets most of the press, both good and bad.

THC was first isolated and synthesized in 1964,[6] and is responsible for the euphoria associated with marijuana use. Since 1985, synthetic THC has been available in the United States for medical use as dronabinol, a Schedule III substance, and nabilone, a Schedule II substance. Initially approved for appetite stimulation in patients with AIDS and for chemotherapy-induced nausea and vomiting,[7] dronabinol has been widely used off-label, often without adequate evidence.[8]

Common side effects of dronabinol include drowsiness, unsteady gait, dizziness, inability to focus, confusion, mood changes, delusions, and hallucinations,[9] all of which may be associated with poor tolerability. A recent randomized, placebo-controlled, crossover trial of dronabinol for the treatment of chronic pain found that dronabinol produced similar psychoactive effects as smoked marijuana,[10] which may limit its use in persons with chronic pain. Similar side effects have been identified for nabilone,[11] also bringing into question its clinical value. In a review, Russo[12] suggested that these side effects preclude use of synthetic THC as the solution to incorporating medical cannabis into clinical practice.

Contrary to popular belief, THC is not necessarily the most relevant cannabinoid with medical applications.[13] First isolated in 1934,[14] cannabidiol (CBD) was partially synthesized from hashish in 1964,[6] and fully synthesized several years later.[15] Whereas the number of publications regarding cannabis has increased, little on CBD was published until the early 2000s, "with the confirmation of a plethora of pharmacological effects, many of them with therapeutic potential."[16]

CBD was viewed as unimportant for many years. Research indicated that it mitigated the euphoria associated with THC,[17] resulting in efforts to remove CBD from marijuana.[18] The use of genetic engineering to remove CBD from marijuana is supported by findings of Burgdorf and colleagues[19] in their examination of changes in the composition of marijuana seized by law enforcement in California between 1996 and 2008. They found that the concentration of THC increased from 2.17% to 9.93%, while the concentration of CBD decreased from 0.24% to 0.08%. These dramatic changes were less pronounced in marijuana seized close to the Mexican border compared with non-border areas, suggesting that genetic engineering of marijuana primarily occurred in the United States.

Although reducing the euphoria associated with marijuana by increasing the CBD content may not necessarily be of interest to the recreational marijuana industry, its medical application has been compelling.

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