Cannabidiol Cigarettes as Adjunctive Treatment for Psychotic Disorders - A Randomized, Open-Label Pilot-Study

Abstract

Background: Psychotic disorders are associated with high rates of comorbid substance use disorders. Use of cannabis rich in tetrahydrocannabinol (THC) is linked to an increased risk of psychosis, worsening of psychotic symptoms, and an adverse course of psychotic disorders. Previous studies suggest oral cannabidiol (CBD) as possible novel antipsychotic agent; however, no studies evaluated the effects of smoked CBD. Objective: The main aim of the study was to clarify the antipsychotic potential of CBD used as adjunctive therapy simulating a naturalistic setting. Our trial is the first study evaluating the effects of smoked CBD-cigarettes as adjunctive therapy for psychotic symptoms. Methods: A randomized, placebo-controlled open-label trial of cigarettes containing CBD-rich cannabis (THC < 1%) as adjunctive therapy to standard psychiatric treatment was conducted (ClinicalTrials.gov identifier NCT04700930). Primary outcomes were mean scores of Positive and Negative Syndrome Scale (PANSS), Brøset Violence Checklist, the Beck's Depression Inventory (BDI), the Subjective Well-Being Under Neuroleptics Scale short form (SWN-K), and antipsychotic medication equivalent doses. Outcomes were assessed after 4 weeks of acute treatment and long-term follow-up after discontinuation of CBD-cigarettes after 25 weeks. Participants were 31 acutely psychotic patients with tobacco use disorder and a mean age of 35.1 ± 10.58 years (71% male). Comorbid cannabis use was diagnosed in 51.6%. Results: A discontinuous multilevel model revealed no significant group differences for primary outcomes. After 4 weeks of acute treatment, mean PANSS and BDI decreased in both groups, while an increase of antipsychotic medication equivalent was observed in the placebo group. Conclusions: The presented findings might suggest an antipsychotic medication sparing effect of CBD-cigarettes as adjunctive treatment of acute psychosis. However, the low number of participants did not allow for further statistical analysis. Hence, a larger study sample and a more rigorous study design (blinding of the interventional product, fixed dosing regimen) may reveal different results. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04700930.

Keywords: antipsychotic agents; cannabis; comorbidity; schizophrenia; substance-related disorders.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Köck, Lang, Trulley, Dechent, Mercer-Chalmers-Bender, Frei, Huber and Borgwardt.

Figures

Figure 1

Study flow diagram.

Figure 2

Predicted PANSS scores (in points) for interaction effects for both groups over time (days) with discontinuous multilevel model. Interaction days x group during acute therapy (days 0–28), Interaction days x group follow-up period (days 28–175); PANSS, Positive and Negative Syndrome Scale Scores; days, days 0–28 during acute therapy, days 28–175 follow-up period.

Figure 3

Predicted olanzapine equivalents (in mg) for both groups over time (days) with discontinuous multilevel model. Interaction days x group during acute therapy (days 0–28), Interaction days x group following acute therapy (days 28–175); PANSS, Positive and Negative Syndrome Scale Scores; days, days 0–28 during acute therapy, days 28–175 follow-up period.