Systematic combinations of major cannabinoid and terpene contents in Cannabis flower and patient outcomes: a proof-of-concept assessment of the Vigil Index of Cannabis Chemovars.

Background: Little is known about the frequency with which different combinations of phytochemicals (chemovars) arise in Cannabis flower or whether common chemovars are associated with distinct pharmacodynamics and patient health outcomes. This study created a clinically relevant, user-friendly, scalable chemovar indexing system summarizing primary cannabinoid and terpene contents and tested whether the most frequently consumed chemovars differ in their treatment effectiveness and experienced side effects.

Methods: Between 09/10/2016 and 03/11/2021, 204 people used the freely available, educational mobile software application, Releaf App, to record 6309 real-time consumption sessions using 633 distinct Cannabis flower products, unique at the user level, with terpene and cannabinoid potency information. The indexing system is based on retrospective data analysis of the products' primary and secondary terpene contents and tetrahydrocannabinol (THC) and cannabidiol (CBD) potencies and yielded a total of 478 distinct chemovars. Analyses of covariances (ANCOVAs) were used to compare symptom levels and side effects experienced across the five most common chemovars before and after cannabis consumption for app users overall and for those treating chronic pain and depression or anxiety.

Results: Examination of the five most frequently consumed chemovars showed significant differences in symptom treatment effectiveness for chronic pain and for depression and anxiety (ps < .001). While the effects varied in magnitude, the five chemovars were effective across conditions except for MC61 (mercene .01-0.49%/beta-caryophyllene .01 to 0.49%/THC 20-25%/CBD 0.01-1.0%), which exacerbated feelings of anxiety or depression. The chemovars also differed in their association with experiencing positive, negative, and context-specific side effects, with two chemovars, MC61 and MC62 (mercene .01-0.49%/beta-caryophyllene .01-0.49%/THC 20-25%/CBD 1-5%), generating two to three fewer positive side effects and as much as one more negative and two more context-specific side effects than the other three chemovars.

Conclusions: The findings provide "proof-of-concept" that a simple, yet comprehensive chemovar indexing system can be used to identify systematic differences in clinically relevant patient health outcomes and other common experiences across Cannabis flower products, irrespective of the product's commercial or strain name. This study was limited by self-selection into cannabis and app use and a lack of user-specific information. Further research using this chemovar indexing system should assess how distinct combinations of phytochemicals interact with user-level characteristics to produce general and individualized Cannabis consumption experiences and health outcomes, ideally using randomized methods to assess differences in effects across chemovars.