Medical Marijuana for Pain: What the Evidence Shows

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If one listens to advocates of medical marijuana, it seems like a miracle drug that not only is far more effective than the currently available analgesics but also has a more benign adverse-effect profile. Two new reviews of studies provide a clearer picture as to just how close these claims fit with what actual research has shown.

The first is a review and meta-analysis of cannabinoids for multiple medical conditions, including pain.¹ Of the 79 trials for all conditions the review identifies, only 4 studies were found to have a low risk of bias based on the methodology employed; 55 studies were found to have high risk; and the risk was unclear in 20 studies. Although most of the studies indicated they were double-blind, only 57% were found to actually have employed methods to ensure this with study participants and only 24% were found to have appropriately blinded the outcome assessors.

Twenty-eight studies were undertaken to evaluate the effectiveness of cannabinoids for chronic pain. Of these, only 2 were found to be at low risk of bias. The most commonly used cannabinoids were nabiximols-used in 13 studies; the rest of the studies evaluated the effect of smoked tetrahydrocannabinol (THC), nabilone, THC oromucosal spray, and dronabinol. One study compared cannabinoids with an active ingredient, the analgesic amitriptyline; in the others, cannabinoids were compared with placebo.

In 17 of the studies, the most common form of pain was neuropathic pain, including central pain, diabetic peripheral neuropathic pain, and HIV-associated neuropathy; 3 or fewer studies included cancer pain, fibromyalgia, arthritic pain, and a variety of other pain conditions.

Across the studies, more patients reported a 30% or greater reduction in pain with the cannabinoids than with placebo. On the basis of these studies, the authors of the review rated the support for cannabinoid use as moderate. Smoked THC appeared to provide the most benefit.

The second review examined 5 randomized controlled studies on cannabinoids for neuropathic pain and 6 for other forms of pain.² All but one of the studies found a significant decrease in pain with cannabinoids compared with placebo. However, in the crossover study that compared nabilone with the opioid dihydrocodeine, the latter provided better analgesia.

Overall, these studies seem to indicate that cannabinoids have a significant role to play in the management of chronic pain. However, there are important issues that limit the validity of this conclusion. First and most important is how the improvement in pain was evaluated. In many of the studies, only instruments to measure the level of pain, most notably the Visual Analogue Scale, were used. This is fine when one is measuring acute pain. But when it comes to chronic pain-which is what the studies were looking at-the most important measures of the impact of any treatment are improvement in functioning and other objective measures, such as reduction in use of analgesic medications.

In fact, an editorial accompanying the reviews specifically notes that there is no evidence that initiating cannabinoid therapy in patients with chronic pain who are taking opioids helps reduce opioid use as would be expected if the cannabinoid was having a marked effect on the pain.³

The failure to ensure blinding in many of the studies adds to the importance of seeking objective measures of pain reductions. Users of cannabinoids might easily note responses that did not occur with placebo, which may make them more willing to report cannabinoid’s benefits.

The studies also have the same drawback that virtually all the studies of analgesic medications have: the lack of data on their effectiveness for more than 3 to 4 months. Because chronic pain may require extended treatment, the absence of this information is of special concern. If future studies of cannabinoids for chronic pain are to have an impact on treatment, researchers will need to follow the same outcome measures that are used for other pain treatment and go beyond just measuring the level of pain.

The review by Whiting and colleagues¹ also notes that cannabinoids were associated with an increased number and severity of adverse effects compared with controls-most notably, dry mouth, dizziness, somnolence, anxiety, psychosis, and euphoria. What is especially problematic is that the review was unable to identify any studies that evaluated long-term adverse effects associated with cannabinoid use.

The review found minimal evidence that cannabinoids are beneficial for the nausea and vomiting associated with chemotherapy or for stimulation of appetite in patients with HIV/AIDS. It also found no evidence of effectiveness for the treatment of glaucoma or mental disorders; instead, it found that cannabinoids were more likely to worsen the latter. There was some evidence that cannabinoids might be beneficial for the spasticity associated with multiple sclerosis, but even here the results did not reach statistical significance.

I am a bit surprised by the lack of support for the nausea and vomiting associated with chemotherapy and for appetite stimulation in wasting illnesses-two conditions for which a number of my patients have benefitted from cannabinoid use. In contrast, I cannot recall any patients who informed me of benefits associated with medical marijuana use for pain.

Certainly more studies on cannabinoids are needed, but clearly they must be better designed than currently available studies. Current research has fallen far short of criteria required by the FDA to approve any drug, much less for conditions not considered acutely life-threatening and for which there are already many other effective and safe treatments. The variation from state to state as to which medical conditions are approved for cannabinoid use is not because lawmakers have ignored scientific evidence. Rather, it reflects the absence of such evidence and an approval process based on politics, not science.

One other important point raised by the D’Souza and Ranganathan³ editorial is whether the goal of the medical marijuana movement is a backdoor approach to attaining legalization of marijuana or whether the real goal is to provide a treatment that benefits patients. I suspect that for many advocates, the former is the goal. This feeling has only been reinforced when I have seen that in many states that have legalized medical marijuana, people can acquire prescriptions for marijuana from physicians who do not perform what anyone would consider anything close to even a basic medical evaluation of the requesters’ complaints. Giving a prescription to someone simply because he or she complains of pain or depression or nausea or glaucoma or any of the other conditions for which states have approved medical marijuana without doing any kind of a examination makes a mockery of medicine.

Whether marijuana use should be legalized is a subject worthy for debate. It is unfair, however, for patients who have real health problems to be misled into believing that there is a magical cure that federal or state governments or pharmaceutical companies are keeping from them or for anecdotal evidence to replace true scientific research.

References:

1. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313:2456-2473.

2. Hill KP. Medical marijuana for treatment of chronic pain and other medical and psychiatric problems: a clinical review. JAMA. 2015;313:2474-2483.

3. D’Souza DC, Ranganathan M. Medical marijuana: is the cart before the horse? JAMA. 2015;313:2431-2432.