Medical marijuana in neurology

Abstract

Constituents of the Cannabis plant, cannabinoids, may be of therapeutic value in neurologic diseases. The most abundant cannabinoids are Δ⁹-tetrahydrocannabinol, which possesses psychoactive properties, and cannabidiol, which has no intrinsic psychoactive effects, but exhibits neuroprotective properties in preclinical studies. A small number of high-quality clinical trials support the safety and efficacy of cannabinoids for treatment of spasticity of multiple sclerosis, pain refractory to opioids, glaucoma, nausea and vomiting. Lower level clinical evidence indicates that cannabinoids may be useful for dystonia, tics, tremors, epilepsy, migraine and weight loss. Data are also limited in regards to adverse events and safety. Common nonspecific adverse events are similar to those of other CNS ‘depressants’ and include weakness, mood changes and dizziness. Cannabinoids can have cardiovascular adverse events and, when smoked chronically, may affect pulmonary function. Fatalities are rare even with recreational use. There is a concern about psychological dependence, but physical dependence is less well documented. Cannabis preparations may presently offer an option for compassionate use in severe neurologic diseases, but at this point, only when standard-of-care therapy is ineffective. As more high-quality clinical data are gathered, the therapeutic application of cannabinoids will likely expand.

Keywords::

• CBD
• epilepsy
• headaches
• marijuana
• multiple sclerosis
• neurology

Financial & competing interests disclosure

K Kalidas is on the speakers’ bureau for Allergan and Depomed. L Katzin is on the speakers’ bureau for Grifols and Baxter pharmaceuticals. D Robertson has served as a consultant for Biogen Idec, Genzyme/Sanofi Aventis, Teva Neuroscience and Pfizer; is on the speakers’ bureau for Biogen Idec, Pfizer, EMD Serono, Genzyme/Sanofi Aventis, Novartis, Teva Neuroscience, Mallinckrodt and Acorda; and has received grant support from Biogen Idec, Genzyme/Sanofi Aventis, Novartis, Sun Pharma, MedImmune, GlaxoSmithKline and Roche/Genetech. T Vu is on the speakers’ bureau for Allergan. AG Smith has received grant/research support from Merck, Eli Lilly, AVID Radiopharmaceuticals, Eisai, TauRx and Cognate nutritionals. T Zesiewicz receives research support from GSK Pharmaceuticals, UCB Pharmaceuticals, Astellas Pharmaceuticals, Friedreich’s Ataxia Research Alliance, Allon Pharmaceuticals, Edison Pharmaceuticals and ViroPharma Inc. J Sanchez-Ramos is on the speakers bureau for UCB Pharmaceuticals. Dr. Benbadis has served as a consultant for Cyberonics, Eisai, Lundbeck, Sunovion, Supernus, UCB pharma, Upsher-Smith. He is on the speakers bureau for Cyberonics, Eisai, Glaxo Smith Kline, Lundbeck, Sunovion, Supernus, UCB pharma and has received grant support from Cyberonics, Lundbeck, Sepracor, Sunovion, Supernus, UCB pharma, Upsher-Smith. Dr. Benbadis received royalties as an author or Editor for Emedicine-Medscape-WebMD, UpToDate. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The Cannabis plant consists of a large number of cannabinoids, many of which interact with CNS receptors to produce biological effects that may improve neurologic functions and disorders for which there are few effective treatments.

• Most of the evidence for beneficial effects of cannabis is from observation and open-label studies, but there are some high-quality clinical trials of cannabinoids using gold standard designs (double-blind, placebo-controlled studies) that report its therapeutic effects.

• In our view, the adverse effects reported in the literature are most often benign, though there are deleterious effects that depend highly on the route and frequency of administration (e.g., inhalation and pulmonary symptoms).

• Some reports overemphasize the potential for drug dependence, even suggesting that cannabis is a ‘gateway’ drug to ‘hard’ drugs of abuse. In addition, the ‘amotivational syndrome’ that is often mentioned as an adverse effect of chronic use is poorly documented.

• Medical (regulated) use is clearly not the same as recreational use.

• There is a need for more research, both basic and clinical. Pharmaceutical companies would do well to research specific cannabinoid molecules or agents that selectively benefit specific symptoms or conditions. The critical variables are the respective proportions of specific compounds, routes of administration and dosing.

• It is possible that combinations of cannabinoids are necessary to produce clinical benefits, so that quality control measurements of the principal bioactive components of the preparation will be helpful when conducting future clinical studies.

• Sensationalized media anecdotes tend to not provide a denominator and do not report failures because those do not increase ratings. They should not be the basis for our decisions.

• A common theme of all neurology specialties is that referral centers treat the most refractory, difficult and often ‘desperate’ patients. For these, medical marijuana should be considered. However, until we have more and better data, they should only be considered after more standard and proven treatments have been exhausted, and should not be offered ‘out of order’ to patients who are not compliant with, or want to bypass, standard treatments.

Notes