Cannabis effects on physical and mental health in medical cannabis patients

ABSTRACT With increasing legalization of medicinal cannabis, there is an urgent need to identify patients at-risk for cannabis use disorder (CUD), which can occur as an unintended adverse effect of using medicinal cannabis. A national survey indicated that 11% who used medicinal cannabis met criteria for a past year DSM-IV CUD. However, DSM-based CUD diagnosis has limitations when applied to medicinal cannabis (MC). Specifically, many MC patients might report tolerance and withdrawal due to frequent MC use, but not show a pathological pattern of cannabis use (e.g., impaired control over use). To improve identification of MC patients who show a pathological pattern of use, we extend DSM-5’s model for diagnosing substance use disorder for prescription medication to MC (CUD-MC). CUD-MC addresses limitations by putting the focus on symptoms indicating a pathological pattern of cannabis use, and recognizing that tolerance and withdrawal might occur as expected neuroadaptations from cannabis used in a medicinal dosing regimen. However, tolerance can be a significant clinical problem because it decreases a medication's effects, resulting in dose escalation and, for some people, impaired control over use, whereas withdrawal can drive continuing, heavy cannabis use (e.g., use to avoid or relieve withdrawal) that may be associated with cannabis-related problems. This project investigates the roles of tolerance and withdrawal in the likelihood of a pathological pattern of cannabis use (CUD-MC), and identifies risk factors for cannabis misuse in MC patients to help prevent the iatrogenic effect of CUD-MC resulting from MC use. To generate new insights into the roles of tolerance to specific cannabis effects (e.g., relief of pain, anxiety) and withdrawal in likelihood of CUD-MC over 2-year follow-up, this project uses the innovative combination of Ecological Momentary Assessment (EMA) with longer-term follow-up to examine the likelihood of CUD-MC, focusing on two key criteria, tolerance and withdrawal, in MC patients. This project will recruit patients (N=400, age >18; 50% female; 25% new patients), e.g., from MC dispensaries. In this repeated measures study, participants complete a baseline visit, followed by 14-day EMA. Follow-ups at 6-month intervals through 18-months trigger 14-day EMA data collection. Follow-ups occur on-line at 6- and 18-months; and in-person at 12- and 24-months to collect biomarkers such as quantitative THC and CBD metabolite level and lung function measures (spirometry). Project aims are to (1) examine how DSM-5 tolerance is associated with THC dose, specific cannabis effects (e.g., relief of pain, anxiety) and CUD-MC; (2) determine how pattern of MC use (in EMA and at longer intervals) is associated with DSM-5 withdrawal and CUD-MC over 2-years; and (3) identify risk factors for CUD-MC; and examine cannabis-related health outcomes (e.g., lung functioning), including change in use of other medications, over 2-years. Identifying risk factors for CUD-MC aligns with NIDA's Cannabis Policy Research Agenda and Strategic Plan. Project results will help inform MC practice guidelines and the development of personalized interventions to minimize cannabis-related harms.