Effects of Extended Cannabis Abstinence on Cognitive Outcomes in Cannabis Dependent Patients with Schizophrenia vs Non-Psychiatric Controls

Cross-sectional studies of the effects of cannabis on cognition in schizophrenia have produced mixed results. Heavy and persistent cannabis use in schizophrenia is a common clinical problem, and effects of controlled abstinence from cannabis in these patients have not been carefully evaluated. The present study sought to determine the effects of cannabis abstinence on cognition in patients with schizophrenia and co-occurring cannabis dependence. We utilized a 28-day cannabis abstinence paradigm to investigate the state-dependent effects of cannabis on select cognitive outcomes in cannabis-dependent patients with schizophrenia and non-psychiatric controls. Nineteen patients and 20 non-psychiatric male cannabis-dependent participants underwent 28 days of cannabis abstinence. Cognition was assessed on day 0, 14, and 28 using a comprehensive neuropsychological battery. Clinical symptoms were assessed weekly. Abstinence was facilitated by contingency reinforcement confirmed by twice weekly urinalysis. Forty-two percent of patients and 55% of controls achieved end-point abstinence (p=0.53), which was biochemically-verified (day 28 urinary THC-COOH <20 ng/ml). In this preliminary study, schizophrenia-abstainers demonstrated improvements in Hopkins Verbal Learning Test-Revised (HVLT-R) performance over time [F(2,14)=4.73, p<0.03] (d=1.07). Lesser improvements on HVLT-R were observed in non-psychiatric control abstainers (d=0.66), and with abstinence on other cognitive test measures, in both patients and controls. Verbal memory and learning may improve in schizophrenia and control subjects with cannabis abstinence, but larger more definitive studies are needed. Our findings underscore the importance of developing effective interventions for cannabis use disorders in schizophrenia.