Implementation Challenges for Medical Cannabis Studies
Updated: Aug 28, 2019
The double blind placebo control study (DBPCS) is designed to be free of unintentional bias. We’ve all been friends with someone who is a bit needier than another, or had a relationship with a needy person. As much as humans tend to interact in the same way, the needs of one particular person can cause you, the reader, to alter your responses to accommodate the needs of your friend. This is bias, it’s intentional bias if you are responding to prevent a problem; but, over time it becomes unintentional because you become ‘trained’ to respond that way.
Now, let’s transfer this concept to a scientific medical study. If you were a researcher, who also happened to be a medical professional, and you were in charge of a medical study and happened to know which patients are getting a placebo (no real medication) vs. actual cancer treatment, how would you behave? Wouldn’t you tend toward unintentional bias by paying closer attention to your patients receiving the placebo treatment? Wouldn’t you make certain that those patients received proper medical care, monitoring them more closely, etc? Because this is is what medical professionals are specifically trained to do, it’s a natural response for them to pay attention to patients and deliver care. This is where bias comes into play - if the study is not a double blind study.
Aside from bias, another challenge to the DBPCS with medical cannabis is the differing legal status across the United States, our continent, and the world. Here in the mid-western USA, medical cannabis is not legal everywhere. Lack of legality drastically limits the research capabilities across our country. Technically, if a medical professional were conducting a study on medical cannabis in Colorado but had a patient in Indiana, the Indiana resident would be breaking the laws of our state if they left Colorado and continued their treatment at home.
Another limitation is design of a placebo for Medical Cannabis and testing only ONE treatment option at a time. Did you know medical researchers have “554 identified compounds in C. sativa L., among them 113 phytocannabinoids and 120 terpenes.” (Calvi, 2018) Much research has been done on the chemical makeup of medical cannabis and one thing is certain, the natural product contains variations in cannabinoids and terpenes no matter the preparation of the treatment (Casano, 2011). It has been demonstrated that these phytocannabinoids work together synergistically with the receptors and naturally occurring terpenes, of which there are over 200. (Russo, 2011) Not only is there variation among plants cultivated at the same time by the same grower, there is much variation in the active compounds in different strains of the same plant. Further, the variations in growing, harvesting, storage and preparation of the cannabis plant also influence the therapeutic benefits.
Imagine trying to isolate just ONE of these numerous terpenes or cannabinoids to test their therapeutic efficacy in a DBPCS. Anyone who understands how medical cannabis works should know this method of study will eliminate many of the health benefits of medical cannabis. The beauty of the plant is how all the naturally occurring terpenes and cannabinoids work together with the patient’s endocannabinoid system to produce beneficial effects. When you look at cannabinoids as single components used therapeutically, there are challenging side effects. Through genetic crosses, many growers have focused on the recreational and therapeutic effects of THC resulting in lower concentrations of other balancing cannabinoids and terpenes. As the concentrations of THC increase the modulating effects of the other phytocannabinoids and terpenes must also increase to moderate the intoxicating side effects of THC. If this doesn't happen, the user experiences a feeling of being “high". Not only do these modifications alter the user’s physical experience, they alter the smell, taste, and therapeutic benefits of the subject consuming the cannabis product. This makes it difficult to find or design an appropriate placebo.
My next article will focus on the experimental design of DBPCS using medical cannabis
Calvi, Lorenzo, et al. “Comprehensive Quality Evaluation of Medical Cannabis Sativa L. Inflorescence and Macerated Oils Based on HS-SPME Coupled to GC-MS and LC- HRMS (q-Exactive Orbitrap®) Approach.” Journal of Pharmaceutical and Biomedical Analysis, U.S. National Library of Medicine, 20 Feb. 2018, www.ncbi.nlm.nih.gov/pubmed/29247961.
Casano, Salvatore & Grassi, Gianpaolo & Martini, V & Michelozzi, Marco. (2011). Variations in Terpene Profiles of Different Strains of Cannabis sativa L. Acta horticulturae. 925. 115-121. 10.17660/ ActaHortic.2011.925.15.
Rains, JC, and DB Penzien. “Behavioral Research and the Double-Blind Placebo-Controlled Methodology: Challenges in Applying the Biomedical Standard to Behavioral Headache Research.” PubMed, US National Library of Medicine, National Institutes of Health, May 2005, www.ncbi.nlm.nih.gov/pubmed/15953264.
Russo, Ethan B. “Taming THC: Potential Cannabis Synergy and Phytocannabinoid- Terpenoid Entourage Effects.” British Journal of Pharmacology, Blackwell Publishing Ltd, Aug. 2011, www.ncbi.nlm.nih.gov/pmc/articles/PMC3165946/.