In the past year not a week has gone by when a patient didn’t ask me if marijuana would be useful to treat their neurological condition, with many patients asking me directly for a prescription. This is partly a response to Connecticut, where I work, legalizing medical marijuana. But also there is a lot of hype surrounding marijuana, driving belief that it is safe and effective for many conditions. The truth, however, is that there is little clinical science showing this to be true.
A recent survey, published in the Annals of Internal Medicine, finds that the majority of Americans have a very distorted view of the science behind medical marijuana:
About 81% of U.S. adults believe marijuana has at least 1 benefit, whereas 17% believe it has no benefit. The most common benefit cited was pain management (66%), followed by treatment of diseases, such as epilepsy and multiple sclerosis (48%), and relief from anxiety, stress, and depression (47%). About 91% of U.S. adults believe marijuana has at least 1 risk, whereas 9% believe it has no risks. The most common risk identified by the public was legal problems (51.8%), followed by addiction (50%) and impaired memory (42%). Among U.S. adults, 29.2% agree that smoking marijuana prevents health problems. About 18% believe exposure to secondhand marijuana smoke is somewhat or completely safe for adults, whereas 7.6% indicated that it is somewhat or completely safe for children. Of the respondents, 7.3% agree that marijuana use is somewhat or completely safe during pregnancy. About 22.4% of U.S. adults believe that marijuana is not at all addictive.
The reality is quite different. Cannabinoids are an interesting class of drugs with the potential to be developed into useful pharmaceuticals. But this process takes time, and ultimately we will need to do rigorous clinical trials looking at specific doses of specific preparations to determine safety and efficacy for specific clinical indications.
There is no reason to think that cannabis is a magical plant with special properties. The chemical constituents of marijuana are drugs, and all drugs have side effects, and need to be evaluated for their bioavailability, pharmacokinetics, drug-drug interactions, and toxicity. David Gorski has written about medical marijuana as the new herbalism – he wrote in 2014:
Medical marijuana. It’s promoted as a seeming panacea that can cure whatever ails you. While there are potentially useful medicinal compounds in marijuana, in general the medical marijuana movement vastly oversells the promise. The truth is far more prosaic and nuanced.
Let’s take an updated look at the science, starting with headaches. A 2017 review concluded:
Currently, there is not enough evidence from well-designed clinical trials to support the use of cannabis for headache, but there are sufficient anecdotal and preliminary results, as well as plausible neurobiological mechanisms, to warrant properly designed clinical trials. Such trials are needed to determine short- and long-term efficacy for specific headache types, compatibility with existing treatments, optimal administration practices, as well as potential risks.
This is also what I find. There are no double-blind placebo controlled trials. Most published studies are retrospective, or uncontrolled observational studies. This is, at best, considered preliminary evidence, which has a very poor track record of predicting ultimate definitive clinical evidence. As the authors above conclude, the plausibility is there, but the current state of evidence only supports doing clinical trials, not recommending its use.
Also, the “encouraging” preliminary evidence is actually not that impressive. One retrospective study found that about 40% of patients who used medical marijuana to treat their migraines found any positive effect. Only 20% reported decreased frequency, which is at about placebo response level.
Further, we need research to tease apart any specific anti-migraine effect from other effects of cannabis that could affect the perception and reporting of pain. It is common for people to gloss over this distinction, with the argument that as long as people feel better, who cares how it works. There is a small point here, in that overall quality of life is an important outcome to measure. But we want to know if any cannabis derivative is actually reducing migraines or other headache types, or if patients just don’t care as much because they are sedated or their mood is mellowed.
This is an important distinction (which applies to all pain indications for cannabis) because it impacts whether or not we will be able to disentangle a specific anti-pain effect from the psychoactive effects of these drugs. Further, this factor likely predicts long term effects and addictive potential. The history of using addictive psychoactive drugs to treat chronic pain is not a good one. They tend not to be effective long term, and just make the chronic pain worse and more difficult to treat.
These concerns are reflected in a 2018 review of cannabis for neuropathic pain:
The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes.
The preliminary evidence for neuropathic pain is actually better than other pain indications, but even here the data is weak, and there are some early indications of potential risk that need to be further explored.
A 2015 systematic review of medical marijuana for all chronic pain found:
There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9-tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical marijuana remain unknown. Generalizing the use of medical marijuana to all CNCP [chronic noncancer pain] conditions does not appear to be supported by existing evidence. Clinicians should exercise caution when prescribing medical marijuana for patients, especially in those with nonneuropathic CNCP.
Many experts consider the use of cannabis for the treatment of nausea (specifically chemotherapy-induced nausea) to be the most well-established. A 2015 systematic review found:
Cannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions.
So even here the results are preliminary and all we can really say is that further research is needed.
Another condition for which there is positive (although still preliminary) evidence is in muscle spasticity from multiple sclerosis (MS). A 2018 review found that:
Based on this review, they concluded that nabiximols (Sativex oral spray), oral cannabis extract (OCE), and synthetic tetrahydrocannabinol (THC) are probably effective at reducing patient-reported symptoms of spasticity in people with MS, but OCE and synthetic THC were not found to be effective for reducing physician-administered measures of spasticity.
I note that they specify “patient-reported” symptoms showed a response, implying a subjective effect, but no real evidence for an objective effect. Again – more research is needed. The same review also cautioned:
However, cannabis use has been associated with an increased risk of psychosis and schizophrenia in at-risk individuals, there is growing evidence that cannabis can increase the risk for cardiovascular diseases, including myocardial infarction (MI), hypertension, heart failure, and stroke, and a recently recognized adverse effect of cannabis is cannabinoid hyperemesis syndrome.
You cannot simultaneously accept the preliminary evidence on efficacy and reject the preliminary evidence on risks. Supporters of medical marijuana might argue that we can separate out the beneficial effects from the unwanted side effects and risks. Possibly. But that is actually the point – we need to do much more research to isolate specific compounds, and study their risks and benefits.
The premature hype surrounding medical marijuana is unfortunate, and actually likely to hamper much needed further research. States are rushing to legalize medical marijuana, and this may also happen at the federal level. If patients can get medical marijuana they are less likely to enroll in a clinical trial where they may be allocated to a placebo group.
The research is likely to continue, however, and we will know in 10-20 years if all the hype was worth it.
