Community Series - Purple Haze: Issues on Cannabis Legalization, volume II

Background: Ineffective cannabis regulatory frameworks such as prohibition have sparked interest in alternative solutions to reduce individual and societal harms. While it has been suggested that the recreational legalization process has yielded early successes, the relatively recent implementation of the novel policies has provided a modest time frame for a truly thorough establishment and assessment of key population-level indicators. The following systematic review focuses on identifying the downstream public health sequelae of cannabis legalization policies, including parameters such as cannabis consumption rates, hospitalization rates, vehicular accidents and fatalities, criminal activity, and suicidal behaviors, as well as other substance use trends.

Methods: An exhaustive search of the MEDLINE and Google Scholar databases were performed to identify high-quality (1) longitudinal studies, which (2) compared key public health outcomes between regions which had and had not implemented recreational cannabis legalization (RML) policies, (3) using distinct databases and/or time frames. Thirty-two original research articles were retained for review.

Results: Adult past-month cannabis consumption (26+ years) seems to have significantly increased following RML, whereas young adult (18–26 years) and adolescent (12–17 years) populations do not show a significant rise in past-month cannabis use. RML shows preliminary trends in increasing service use (such as hospitalizations, emergency department visits, or poisonings) or vehicular traffic fatalities. Preliminary evidence suggests that RML is related to potential increases in serious/violent crimes, and heterogeneous effects on suicidal behaviors. While the research does not illustrate that RML is linked to changing consumptions patterns of cigarette, stimulant, or opioid use, alcohol use may be on the rise, and opioid prescribing patterns are shown to be significantly correlated with RML.

Conclusion: The current data supports the notion that RML is correlated with altered cannabis consumption in adults, potentially increased criminal activity, and a decline in opioid quantities and prescriptions provided to patients. Future work should address additional knowledge gaps for vulnerable populations, such as individuals with mental health problems or persons consuming cannabis frequently/at higher THC doses. The effects of varying legalization models should also be evaluated for their potentially differing impacts on population-level outcomes.

The majority of states have fully legalized the use of medical cannabis (MC), and nearly all other states allow limited access to cannabidiol (CBD), a non-intoxicating constituent of cannabis often touted for a range of therapeutic indications. Further, the Agricultural Improvement Act of 2018 legalized hemp-derived products in all 50 states; typically high in CBD, these products are derived from cannabis varieties containing ≤0.3% delta-9-tetrahydrocannabinol (THC) by weight. The recent “green rush” has resulted in a striking increase in cannabis use among patients and consumers who often use a wide variety of novel product types, each with a unique blend of cannabinoid constituents. Importantly, however, several cannabinoids have the potential to cause drug-drug interactions (DDI) with other medications, primarily due to their involvement with the hepatic cytochrome P450 (CYP450) system. This article examines the potential for individual cannabinoids, particularly CBD, to interact with the hepatic metabolic system, which is concerning given its involvement in the metabolism of commonly-prescribed medications. CBD and other cannabinoids are metabolized extensively by the CYP450 system, and also inhibit many of these enzymes, potentially leading to variable serum levels of other medications, as well as variable levels of cannabinoids when other medications modify the system. As access and interest in cannabinoid-based products continues to increase, critical questions remain unanswered regarding their safety. The complex relationship between cannabinoids and the hepatic metabolic system, including common potential DDI resulting from cannabinoid exposure, are explored along with the clinical significance of these potential interactions and monitoring or mitigation strategies.