Double-Blind Blindness

Very few double-blinded placebo-controlled trials (called CTs from here on out) exist for medical cannabis and this is a significant shortcoming that needs to be remedied into the future. However, as it stands, the regulatory environment makes it impossible to conduct these CTs, thus making “proving” cannabis’ medical value and its safety impossible for the providers interested in evidence-based medicine.

However, CTs are not the gold-standard for determining a drug’s safety and efficacy in the long-term, in a broad population. It only provides a brief, tiny, and deeply biased snapshot into the nature of a drug. Most CTs are funded by the industry trying to get them to market, they don’t have to publish negative results, most avoid the use of women due to pregnancy fears, and they don’t use a diverse population. Women and racially diverse populations are commonly excluded and there might be good reason: pregnancy risk and the increased risk of side-effects in a diverse population can prevent a drug from coming to market.

What is more valuable than any CT is post-market surveillance data (PMSD); that is the true gold-standard. PMSD will tell you what really happens when you give a drug to millions of genetically diverse people over years and decades and, as any practitioner knows, a lot of PMSD is not kind to many approved medications.

A good example are the hypnotics like zolpidem that are used for helping patients sleep. However, hypnotics were never intended for use beyond 14 days. What medical professionals unfortunately extrapolated from these CTs is that it was OK to give to huge populations for decades on end. Now, the PMSD is coming out and it turns out that wasn’t so great an idea. Hypnotics, like zolpidem, increase mortality and cancer risk dramatically, even less than 18 doses/year increasing mortality by 250%.

Similarly, proton-pump inhibitors (PPIs), again never intended for use beyond 14 days, have been used for huge populations for decades on end. Post-market surveillance data show increased risk of kidney damage, small-intestinal bacterial growth, low iron/magnesium/calcium/vitamin B12, pneumonia, intestinal infection, colonization with C. difficile (which can result in life-threatening diarrhea, especially with antibiotic therapy). None of these risks were predicted by the CTs approving PPIs and they only came out after we gave them to patients for decades on end.

The above are only a small sample of examples where PMSD have illustrated the long-term risks of medications. COX-2 inhibitors, NSAIDs in general, hormone replacement therapy, antipsychotics, and many other drugs show a similar pattern of unanticipated risk despite having CTs.

CTs could never have predicted the long-term safety and efficacy data for giving these and many other drugs to a broad population for decades on end beyond their intended use. Now, although we don’t have many CTs for cannabis, what we do have is decades and decades worth of PMSD. It may be post-BLACK-MARKET-surveillance data, but that is still PMSD. It is arguable that we have more long-term broad use data on medical cannabis than we do on any other drug on the market and we should take that seriously. Cannabis does not increase mortality, kidney damage, heart attacks or strokes, dementia, cancer, psychosis, suicide, or any other major health-risk indicator. Can one say that about even half of the drugs on the market?

I think that many medical professionals have turned on their blinders with regards to medical cannabis’ lack of CTs and do not realize the wealth of long-term PMSD they have. I think there is a need for CTs but, until we change cannabis’ regulatory status, there is no way to conduct them and thus encounter the classic problem of the chicken and the egg. There is sufficient pharmacologic data for cannabis indicating medicinal use and low abuse potential. Change cannabis’ regulatory status, and the CTs will follow. Until then, avail yourself of the PMSD showing quite clearly cannabis benefits and low risk.

Ethan Carruthers