We Know Virtually Nothing About the Clinical Effects of Cannabinoids and Medical Marijuana on Alzheimer’s Disease

Remember the popular medical school training aphorism: “See one, do one, teach one”? Well, with medical research it goes something like this: Think of an unstudied topic, write an article, become a key opinion leader! Such has been my experience with the use of cannabinoids (CB) for Alzheimer’s disease (AD) since my colleagues and I published our recent article. The frenzy of interest has been fueled by legalization of recreational marijuana use in some locales, and the increasingly popular use of medical marijuana (MM) for therapeutic purposes. In truth, however, our lab has been interested in CBs for several years, as the focus of our research for the past 2 decades has been to optimize the pharmacological management of neuropsychiatric symptoms in dementia including agitation, aggression, apathy, and depression. In terms of agitation and aggression, clinicians are acutely aware that the treatment with the best efficacy, the atypical antipsychotics, are only modestly effective at best, and are associated with numerous treatment-limiting side effects including extrapyramidal symptoms, falls, cognitive impairment, cerebrovascular adverse events, and mortality. Is it any wonder why we have turned to other potential treatments in search of safer and more effective therapies?

So why cannabinoids? There are intriguing pre-clinical data on potential neuroprotective, anti-neuro-inflammatory, and pro-cognitive effects of some of the components of MM. Similarly, from recreational use, the effects of marijuana on anxiety, depression, and agitation are also well known, leading to the research question about whether CB compounds would be useful for AD, especially in patients with agitation and aggression. We therefore searched the existing medical literature for studies that examined the effects of various CB compounds on agitation and aggression in patients with AD. We found only 7 studies with fewer than 150 patients which had been published to date, including a study our lab had just completed, which is currently in press. These studies provided very little proof that CBs effectively reduce agitation and aggression and raise the concern that sedation might be a treatment-limiting side effect that requires careful monitoring. There was some suggestion that synthetic CBs might potentially be more useful than MM, but the methodological limitations and small sample sizes of all the studies make definitive conclusions impossible.

There is still far too much we don’t know about CBs and MM for the treatment of AD. Are there truly beneficial effects on behavior? Could MM, especially with higher tetrahydrocannabinol (THC) content, worsen behaviors like psychosis and impair cognition? Is the sedation that is already evident in the small number of studies published to date going to lead to serious adverse events like falls? We need to know more about the basic pharmacokinetics of THC, cannabidiol (CBD), and their varying preparations. This information is essential to help clinicians decide on dosing schedules and the potential for drug-drug interactions.

Finally, regulations, standardization, and quality control of MM products are sorely lacking. We do not know exactly what dose our patients are taking, what the ratios of THC:CBD are, what other active phytochemicals may be included in the preparations used, and how different compounds that may be labeled similarly, differ from one grower to another. The use of synthetic CBs addresses these particular issues, but more research on their efficacy and safety is still required.

We completely agree with the recent American Academy of Neurology position statement that concludes that while more research is needed into the safety and efficacy of MM, at the present time, the use of CBs for the treatment of patients with neurological conditions like AD cannot be recommended.

Financial disclosure:Dr Herrmann has no relevant personal financial relationships to report​