Effects of cannabis use on antidepressant treatment response to repetitive transcranial magnetic stimulation and ketamine.

Background The antidepressant effects of ketamine and repetitive transcranial magnetic stimulation (rTMS) are hypothesized to rely on mechanisms of long-term-potentiation and synaptic plasticity. Cannabis, via activation of CB1 receptors has been shown to impair synaptic plasticity, suggesting that cannabis use might moderate the antidepressant effects of ketamine and/or rTMS. Methods We performed a retrospective chart review of 222 Veterans, including 58 females, treated for depression with either rTMS or ketamine/esketamine at the VA San Diego Medical Center (VASDMC). We estimated the effects of treatment using changes in the Patient-Health-Questionnaire 9 (PHQ-9) split by cannabis use. Cannabis use was determined using self-report for rTMS (102 total, 23 screening positive for cannabis use) or urinary drug screens for ketamine (120 total, 40 screening positive for cannabis use). Mixed-level repeated measures ANOVA was utilized to determine whether cannabis use affected PHQ-9 scores (group effect) or the change in PHQ-9 over time (group x time interaction). Results Cannabis use did not affect overall symptom severity (group effect F (1, 100) = 0.58, p = 0.45) for rTMS, group effect (F (1, 118) = 0.58, p = 0.45) for ketamine, nor did it impact changes in symptoms for either treatment (group x time effect for ketamine: (F (7, 759) = 0.36, p = 0.93); group x time effect for rTMS (F (5, 412) = 0.4160, p = 0.83). Conclusions Cannabis use was unrelated to antidepressant treatment outcomes for either rTMS or ketamine, suggesting that cannabis use should not be a contraindication for these treatments. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding was received via ORD funding for the Center of Excellence for Stress and Mental Health, and Burroughs-Wellcome Fund Career Award for Medical Scientists on behalf of DR. ### Author Declarations 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: This study was approved as an institutional review board (IRB) exemption by the VA San Diego Healthcare system institutional review board (IRB 1223219). Ethical approval was waived for this study. 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 All data produced in the present work are contained in the manuscript