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Medical marijuana for various neurologic conditions: mixed outcomes

Clinical Question:
Is medical marijuana effective in controlling symptoms in various neurologic conditions?

Bottom Line:
Overall, there is a paucity of high-quality data that evaluate the effects of medical marijuana on symptom control for many neurologic conditions. The existing studies include a fair number of secondary outcomes, are often underpowered, and the results are mixed. And the role of publication bias is a significant threat to the validity of this review. The aforementioned concerns are similar to those raised for traditional pharmacologic interventions used for nonapproved purposes. (LOE = 2a)

Reference:
Koppel BS, Brust JC, Fife T, et al. Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2014;82(17):1556-1563.  [PMID:24778283]

Study Design:
Systematic review

Funding:
Foundation

Setting:
Outpatient (any)

Synopsis:
These authors, commissioned by the American Academy of Neurology, systematically searched several databases to identify studies evaluating the effects of marijuana (various extracts or inhaled) in managing nonpain aspects of various neurologic conditions. They excluded surveys, case reports, case series, and non–placebo controlled trials. The authors don't describe the process of study inclusion or quality assessment and don't describe looking for unpublished studies or assessing the potential effect of publication bias. Overall, they identified 34 studies, only 8 of which were high-quality randomized trials. The authors don't report on the grand total number of patients, but the individual trials each included between 12 and 630 patients. In its natural form, marijuana contains several substances: tetrahydrocannabinol (THC), cannabidiol, and so forth. It is no different than other interventions in that researchers who find no effect are unlikely to publish their findings. And the lack of randomized trials lends to a range of methodologic and interpretation biases, the latter especially framed by whether the researcher is for or against the legalization of marijuana. Here is a summary of some of the findings from this review: 1. Spasticity in patients with multiple sclerosis (MS) Of 17 studies, only 4 were high-quality randomized trials and the studies used a wide variety of cannabinoids. The sole high-quality study of nabiximols (a commercial product marketed as Sativex) found it no more effective than placebo, except in the subgroup of 37 patients reporting spasticity as their most bothersome symptom. In lower-quality studies of nabiximols, the results were mixed, with a few studies demonstrating improved symptoms and others finding no meaningful improvement. Eight studies assessed oral cannabis extract (OCE) or THC, only 3 of which were high-quality clinical trials. Two of the high-quality trials found improved spasticity, one did not. The outcomes of the lower-quality studies were equally mixed. One high-quality trial found that smoked marijuana was better than placebo, while a lower-quality study found smoked marijuana was associated with worse outcomes. 2. Central pain or painful spasticity in patients with MS The authors included 13 studies, 5 of which were high-quality randomized trials. The single high-quality trial of nabiximols found it superior to placebo, but 2 lower-quality studies found no improvements. The authors found 4 high-quality trials and 4 lower-quality studies of OCE or THC. Two of the high-quality studies found OCE or THC to be effective, one was uninterpretable because of a dramatic placebo response, and the last syudy found no improvement. Similarly, the lower-quality studies had mixed results. Two low-quality studies found that smoked marijuana improved pain but worsened posture and balance. 3. Bladder function in patients with MS In 2 high-quality trials, nabiximols had no effect on bladder symptoms or incontinence, but decreased the number of daily voids. Two high-quality trials of OCE or THC found no improvement in bladder complaints. The authors present information for a number of other conditions (eg, Huntington disease, levodopa-induced dyskinesia, Tourette syndrome, cervical dystonia, tremor in patients with MS, and seizures), but the quality of data, limited power, and so forth severely limit drawing any conclusions.

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