Objective With the rising misuse of benzodiazepine (BZD) and associated overdose deaths, cannabis has been touted as a potential substitute with proposed benefit of better health outcomes. This two-year retrospective analysis examined whether cannabis use among BZD users was associated with changes in outcomes of (1) all-cause mortality, (2) hospitalizations, (3) emergency department (ED) visits, and (4) whether it demonstrated BZD-sparing effects on prescription quantity over time.

Methods Using data from Yale New Haven Health System, we conducted a retrospective, longitudinal cohort study among BZD users. Cannabis use was the primary exposure, with BZD users without cannabis exposure as controls. Using inverse probability of treatment weighting and propensity score matching techniques, cohorts were balanced at baseline adjusting for medical comorbidities, socioeconomic status and other clinical factors. Kaplan-Meier curves and Cox proportional hazard models were examined with four outcomes of interest.

Results The sample included 1,026 patients with 60.3% females and mean age was 54.2. There was no significant effect of cannabis use on BZD quantity. Cannabis use was not significantly associated with all-cause mortality, hospitalization, or ED visits. In exploratory analysis, medical cannabis users had a lower risk of all-cause mortality but greater risk for hospitalizations among those aged < 50 years.

Conclusion In this longitudinal cohort study, cannabis use was not significantly associated with all-cause mortality, hospitalization and ED visits, or benzodiazepine dose reduction. Our results do not support a benzodiazepine-sparing effect for cannabis use.

The authors have declared no competing interest.

The study was funded by National Institute of Drug Abuse (R21DA057540).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by Yale University institutional review board (IRB)

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

↵* Dr. Singh and Ms. Dai are shared co-first authors.

↵** Drs. Rhee and Radhakrishnan are shared co-last authors.

Declaration of competing interest: None

Primary funding: The study was funded by National Institute of Drug Abuse (R21DA057540).

All data produced in the present study are available upon reasonable request to the authors