medical use of marijuana

JAMA just published a systematic review and meta-analysis of the medical use of cannabinoids (see cannabis medical use jama 2015, or JAMA. 2015;313(24):2456-2473.). This is rather timely as several states are moving forward implementing new procedures for use of medical marijuana (as of may 2015, 23 states and Washington DC). The researchers evaluated 79 studies with 6462 participants. Details:

--Nausea/vomiting from chemotherapy: 28 studies, most with high risk of bias.

-all studies showed cannabinoid benefit (some not reaching statistical significance), whether vs placebo or active comparator (procholorperizine, chlorpromazine, domperidone, and with single studies on alizapride, hydroxyzine, metoclopramide and ondansetron)

        -cannabinoids vs placebo: also higher average number of patients showing complete response with cannabinoids [OR 3.82 (1.55-9.42); 3 trials]

--Appetite stimulation in HIV infection. 4 studies, all at high risk of bias

-some evidence that cannabinoids led to increased weight vs placebo, though the one trial comparing it to megastrol found the latter led to more weight gain [by the way, I have had pretty good success withcyproheptadine, with many fewer adverse effects vs megastrol]

        -there is also limited evidence that cannabinoids are associated with increased appetite, greater percentage of body fat, reduced nausea and improved functional status.

--Chronic Pain, 28 studies, 2 of which were at low risk of bias

        -cannabinoids better than placebo, assessing reduction of pain of at least 30%  [OR 1.41 (0.99-2.00); 8 trials]. Greatest benefit in the 1 trial using smoked THC, with OR 3.4 (1.03-11.48). This was true using a variety of pain scales and measurements.

        -no difference in benefit if neuropathic pain [OR 1.38 (0.93-2.03); 6 trials] vs cancer pain [OR 1.41 (0.99-2.00); 2 trials].

--Spasticity from multiple sclerosis or paraplegia, 14 studies, 2 of which had low risk of bias

        -cannabinoids demonstrated greater improvement of spasticity by Ashworth scale, vs placebo, though not reach statistical significance.

        -Greater average improvement in spasticity

--Depression, no good studies.

        -Secondary analysis of studies for other indications did not find improvement in depression

--Anxiety disorder, 1 trial at high risk of bias

        -Cannabinoids associated with statistically significant decrease in anxiety on a visual analog scale (p=0.01)

--Sleep disorder, 2 studies

        -Improvement in sleep apnea/hypopnea index (mean difference -19.64, p=0.02)

        -Compared to amitriptyline in patients with fibromyalgia, cannabinoids were associated with improvements in insomnia but amitriptyline had greater sleep restfulness.

        -In cannabinoid trials for other indications (MS, pain), secondary analysis noted improvement in sleep quality and sleep disturbance

--Psychosis, 2 studies both at high risk of bias

        -No benefit

--Glaucoma, 1 remarkably small trial (n=6)

        -No difference in intraocular pressures in patients with glaucoma [rather surprising to me, but a really small and therefore suspect study]

--Movement disorder from Tourette syndrome, 2 studies, 36 participants

        -Significant improvement in tic severity

--Adverse events (AEs)

        -In 29 studies, risk of any AE had OR 3.03 (2.42-3.80)

        -In 34 studies, risk of serious AE had OR 1.41 (1.04-1.92)

        -In 29 studies, risk withdrawal due to AE had OR 2.94 (2.18-3.96)

        -Major AEs were dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, disorientation, drowsiness, confusion, balance, hallucination, paranoia [newer studies which I have blogged on over the past couple of years have raised significant questions about longer-term cognitive problems, some finding structural brain changes, and psychosis – though it is hard to know for sure which came first: the marijuana leading to anatomic and physiologic brain changes or vice-versa]

So, overall not great data (pretty poor-quality data, per the Cochrane risk of bias tool). The best quality data supporting cannabinoid use were for chronic neuropathic or cancer pain, and spasticity from MS. Less good data supported use for nausea/vomiting from chemotherapy, weight gain in HIV, sleep disorders and tics from Tourette syndrome. Very low quality data for anxiety disorders. Other outstanding issues include: whether there are significant differences either between different cannabinoids or their mode of administration (orally, sublingually, topically; or if smoked, inhaled, mixed with food or made into tea). It should be emphasized that any medication with so many AEs make it very difficult to have a real placebo control (ie, the patients are pretty likely to know if they are on the active med vs placebo….)