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.

Background: The Releaf App^TM mobile software application (app) data was used to measure self-reported effectiveness and side effects of medical cannabis used under naturalistic conditions. Methods: Between 5/03/2016 and 12/16/2017, 2,830 Releaf App^TM users completed 13,638 individual sessions self-administering medical cannabis and indicated their primary health symptom severity rating on an 11-point (0–10) visual analog scale in real-time prior to and following cannabis consumption, along with experienced side effects. Results: Releaf App^TM responders used cannabis to treat myriad health symptoms, the most frequent relating to pain, anxiety, and depressive conditions. Significant symptom severity reductions were reported for all the symptom categories, with mean reductions between 2.8 and 4.6 points (ds ranged from 1.29–2.39, ps < 0.001). On average, higher pre-dosing symptom levels were associated with greater reported symptom relief, and users treating anxiety or depression-related symptoms reported significantly more relief (ps < 0.001) than users with pain symptoms. Of the 42 possible side effects, users were more likely to indicate and showed a stronger correlation between symptom relief and experiences of positive (94% of sessions) or a context-specific side effects (76%), whereas negative side effects (60%) were associated with lessened, yet still significant symptom relief and were more common among patients treating a depressive symptom relative to patients treating anxiety and pain-related conditions. Conclusion: Patient-managed cannabis use is associated with clinically significant improvements in self-reported symptom relief for treating a wide range of health conditions, along with frequent positive and negative side effects.

Background: We use a mobile software application (app) to measure for the first time, which fundamental characteristics of raw, natural medical Cannabis flower are associated with changes in perceived insomnia under naturalistic conditions. Methods: Four hundred and nine people with a specified condition of insomnia completed 1056 medical cannabis administration sessions using the Releaf App^TM educational software during which they recorded real-time ratings of self-perceived insomnia severity levels prior to and following consumption, experienced side effects, and product characteristics, including combustion method, cannabis subtypes, and/or major cannabinoid contents of cannabis consumed. Within-user effects of different flower characteristics were modeled using a fixed effects panel regression approach with standard errors clustered at the user level. Results: Releaf App^TM users showed an average symptom severity reduction of −4.5 points on a 0–10 point visual analogue scale (SD = 2.7, d = 2.10, p < 0.001). Use of pipes and vaporizers was associated with greater symptom relief and more positive and context-specific side effects as compared to the use of joints, while vaporization was also associated with lower negative effects. Cannabidiol (CBD) was associated with greater statistically significant symptom relief than tetrahydrocannabinol (THC), but the cannabinoid levels generally were not associated with differential side effects. Flower from C. sativa plants was associated with more negative side effects than flower from C. indica or hybrid plant subtypes. Conclusions: Consumption of medical Cannabis flower is associated with significant improvements in perceived insomnia with differential effectiveness and side effect profiles, depending on the product characteristics.

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.