The Association between Cannabis Product Characteristics and Symptom Relief
Federal barriers and logistical challenges have hindered measurement of the real time effects from the types of cannabis products used medically by millions of patients in vivo. Between 06/06/2016 and 03/05/2018, 3,341 people completed 19,910 self- administrated cannabis sessions using the mobile device software, ReleafApp to record: type of cannabis product (dried whole natural Cannabis flower, concentrate, edible, tincture, topical), combustion method (joint, pipe, vaporization), Cannabis subspecies (C. indica and C. sativa), and major cannabinoid contents (tetrahydrocannabinol, THC; and cannabidiol, CBD), along with real-time ratings of health symptom severity levels, prior-to and immediately following administration, and reported side effects. A fixed effects panel regression approach was used to model the within-user effects of different product characteristics. Patients showed an average symptom improvement of 3.5 (SD = 2.6) on an 11-point scale across the 27 measured symptom categories. Dried flower was the most commonly used product and generally associated with greater symptom relief than other types of products. Across product characteristics, only higher THC levels were independently associated with greater symptom relief and prevalence of positive and negative side effects. In contrast, CBD potency levels were generally not associated with significant symptom changes or experienced side effects.
Medical cannabis markets are currently being flooded with thousands of cannabis strains with unique cannabinoid profiles1, novel, uninvestigated cannabis-derived formulates and products with little to no clinical references or formal guidance on how fundamental characteristics of the products themselves may affect pharmacodynamics2,3. Federal laws have all but prohibited the use of prospective, pragmatic, naturalistic studies with random treatment assignment for measuring the effects of cannabis consumed in vivo. What little clinical research does exist is mostly limited to randomized controlled trials (RCTs) using synthetic cannabinoids or low quality and potency cannabis obtained from the federal government that is unrepresentative of the cannabis products used by millions of people every day4,5. Contributing to further confusion are historically contradictory messages coming from the scientific community on the true risks and benefits of cannabis consumption. For example, whereas cannabis was once often and sometimes still is described as component cause of schizophrenia6,7, several studies now suggest the use of medical cannabis as an effective alternative therapy to antipsychotics and for treating schizophrenia more generally8–11. Contradictory effects are often attributed to the distinction between what has been historically interpreted as cannabis’ harmful, psychoactive cannabinoid, tetrahydrocannabinol (THC), often described as providing the ‘high’ effects versus the therapeutic, non-psychoactive potential (sometimes described as a ‘miracle cure’ in the popular media) of cannabidiol (CBD)12. In actuality, few large-scale investigations to date have measured the relative effects of THC and CBD consumption in real-time under naturalistic conditions among people diagnosed with schizophrenia or any other user group.
This is the first study to measure how fundamental characteristics of cannabis products consumed in vivo affect immediate symptom relief and experienced side effects. We operationalize our research question using a mobile device software application (app). Although hundreds of cannabis-themed software apps are available for public use13, the ReleafApp educational software14 is the first app designed specifically to record how the route of administration, combustion method, cannabis subspecies, and major cannabinoid contents are associated with real-time measurements of symptom severity levels, prior to and immediately following administration of cannabis, and the manifestation of myriad possible side effects. Despite recent advocacy for the benefits of CBD over THC, the vast majority of observational studies showing an association between patient-managed cannabis use and improvements in symptoms related to, for example, chronic pain15, multiple sclerosis and Parkinson’s disease16, post-traumatic stress disorder17, and schizophrenia18 relied on public or commercially available cannabis that has been hybridized for high THC and low CBD contents, thus suggesting that THC may be an important determinant of user outcomes. Findings from this study are expected to contribute to guidelines for safe and effective cannabis consumption19,20, which until now have been limited to anecdotal or retrospective reporting and ungeneralizable experiments.41598_2019_Article_39462