Cannabidiol Compared to Pharmacological Treatment as Usual for Crack Use Disorder: A Feasibility, Preliminary Efficacy, Parallel, Double-Blind, Randomized Clinical Trial
Authors: Gallassi Andrea Donatti , de Oliveira André Wagner Carvalho , Rodrigues Larissa Alencar , Nakano Eduardo Yoshio , Ruas Pedro A. S. , de La Mata José Antonio Iturri , Júnior Ettore Ferrari , de Andrade Gomes Juliano , Caroba Mariana Emanuele Silva , dos Santos Silva Marianna Gabriella , Vieira Mariana G. Q. , Reis Julia G. G. R. , Leite Jade Luiza Moreira , de Lima Guilherme Henrique Alves , Lima Jonathan Morais , Lima Yasmim P. V. , Ribas Jorge A. A. , das Chagas Nathalia A. L. , Magalhães Mateus A. , da Silva Mateus F. , Filev Renato , Malcher-Lopes Renato 
Published: April 2024

Cannabidiol (CBD) has been studied for substance use disorders treatment due to its anxiolytic effects, for sleep, appetite, reduction of craving, and maintenance of abstinence. The study aims to assess CBD’s feasibility, safety/tolerability, and preliminary efficacy compared to pharmacological treatment as usual for reducing crack use in people with crack use disorder (CUD) and investigate other parameters: adverse events, physical health symptoms, and craving. A double-blind, randomized clinical trial (RCT) with two treatment arms (CBD and control group) was conducted. Ninety participants were randomized and 73 were allocated: 37 control group and 36 CBD group for a 10-week treatment, comparing CBD (600 mg) with three drugs (fluoxetine, valproic acid, and clonazepam). The per-protocol analysis of participants who did not deviate from the study protocol compared the control and CBD treatment groups. Thirty-four completed at least half of the study and 25 finished. Participants attended weekly meetings for the study procedures (e.g., to receive the medication and provide urine for toxicological tests). Inter-group differences were performed with the Mann–Whitney test, the Wilcoxon test for differences intra-group, and Pearson’s Chi-square test or Fisher’s exact test to compare inter-group demographic data. The significance level was 5%. A “veracity index” (VI) was created as counterevidence (questionnaire data vs. the toxicological test result). Medications were considered safe/tolerable. The CBD group presented significantly fewer adverse events compared to the control group [e.g., dizziness (p = 0.001), memory impairment (p = 0.043)], which performed better in the reduction of clinical and psychiatric complaints (p = 0.008). In the intra-group analyses, the CBD group performed better in more parameters than the control group [e.g., reducing crack use (p = 0.016; T0 to T1)]. Data questionnaires were reliable regarding the use/non-use of crack (VI = 0.787). CBD is a safe/tolerable product. The CBD group manifested fewer adverse events than the control group, which had better clinical and psychiatric complaints results. There are some advantages for the CBD group in the intra-group analysis. Drug use self-report methodologies can be reliable. Trial registration details: This study is registered with Universal Trial Number (UTN) code: U1111-1234-0806. Available at https://ensaiosclinicos.gov.br/rg/RBR-4stgs8 (Effect of cannabidiol in the treatment of crack dependents)