Cannabidiol for COVID-19 Patients with Mild to Moderate Symptoms (CANDIDATE Study): A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Author(s):Show less -

Crippa, Jose Alexandre S. ^{[1, 2]} ; Pacheco, Julia Cozar ^[1] ; Zuardi, Antonio W. ^{[1, 2]} ; Guimaraes, Francisco S. ^{[3, 2]} ; Campos, Alline Cristina ^[3] ; Lima Osorio, Flavia de ^{[1, 2]} ; Loureiro, Sonia Regina ^[1] ; dos Santos, Rafael G. ^{[1, 2]} ; Souza, Jose Diogo S. ^[1] ; Ushirohira, Juliana Mayumi ^[1] ; Ferreira, Rafael Rinaldi ^[3] ; Mancini Costa, Karla Cristinne ^[3] ; Scomparin, Davi Silveira ^[3] ; Scarante, Franciele Franco ^[3] ; Pires-Dos-Santos, Isabela ^[3] ; Mechoulam, Raphael ^[4] ; Kapczinski, Flavio ^{[5, 2, 6, 7]} ; Fonseca, Benedito A. L. ^[8] ; Esposito, Danillo L. A. ^[8] ; Costa Passos, Afonso Dinis ^[9] ; Dal Fabbro, Amaury Lelis ^[9] ; Bellissimo-Rodrigues, Fernando ^[9] ; Arruda, Eurico ^[10] ; Scarpelini, Sandro ^[11] ; Andraus, Maristela Haddad ^[12] ; Nather Junior, Julio Cesar ^[13] ; Wada, Danilo Tadao ^[13] ; Koenigkam-Santos, Marcel ^[13] ; Santos, Antonio Carlos ^[13] ; Busatto Filho, Geraldo ^[14] ; Hallak, Jaime E. C. ^{[1, 2]} ; CAND, Cannabidiol COVID-19 Patients

Affiliation:Show less -

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Natl Inst Sci & Technol Translat Med, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil

^[4] Hebrew Univ Jerusalem, Sch Pharm, Inst Drug Res, Dept Med Chem & Nat Prod, Jerusalem - Israel

^[5] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON - Canada

^[6] Univ Fed Rio Grande do Sul, Fac Med, Dept Psychiat, Grad Program Psychiat & Behav Sci, Porto Alegre, RS - Brazil

^[7] St Josephs Healthcare Hamilton, Hamilton, ON - Canada

^[8] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Ribeirao Preto - Brazil

^[9] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Social Med, Ribeirao Preto - Brazil

^[10] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol, Ribeirao Preto - Brazil

^[11] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Ribeirao Preto - Brazil

^[12] Chromatox Lab Ltda, Sao Paulo - Brazil

^[13] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med Imaging Hematol & Clin Oncol, Ribeirao Preto - Brazil

^[14] Univ Sao Paulo, Fac Med, Dept Psychiat, Lab Psychiat Neuroimaging LIM 21, Sao Paulo - Brazil

• Document type: Journal article
• Source: CANNABIS AND CANNABINOID RESEARCH; OCT 2021.
• Web of Science Citations: 0

Abstract

Importance: Owing to its anti-inflammatory properties and antiviral ``in vitro{''} effect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cannabidiol (CBD) has been proposed as a potential treatment for coronavirus disease 2019 (COVID-19).</p> Objective: To investigate the safety and efficacy of CBD for treating patients with mild to moderate COVID-19.</p> Design: Randomized, parallel-group, double-blind, placebo-controlled clinical trial conducted between July 7 and October 16, 2020, in two sites in Brazil.</p> Setting: Patients were recruited in an emergency room.</p> Participants: Block randomized patients (1:1 allocation ratio-by a researcher not directly involved in data collection) with mild and moderate COVID-19 living in Ribeirao Preto, Brazil, seeking medical consultation, and those who voluntarily agreed to participate in the study.</p> Interventions: Patients received 300 mg of CBD or placebo added to standard symptomatic care during 14 days.</p> Main Outcome and Measure: The primary outcome was reduction or prevention of the deterioration in clinical status from mild/moderate to severe/critical measured with the COVID-19 Scale or the natural course of the resolution of typical clinical symptoms. Primary study outcome was assessed on days 14, 21, and 28 after enrollment.</p> Results: A total of 321 patients were recruited and assessed for eligibility, and 105 were randomly allocated either in CBD (n=49) or in placebo (n=42) group. Ninety-one participants were included in the analysis of efficacy. There were no baseline between-group differences regarding disease severity (chi(2)=0.025, p=0.988) and median time to symptom resolution (12 days {[}95% confidence interval, CI, 6.5-17.5] in the CBD group, 9 days {[}95% CI, 4.8-13.2] in the placebo group {[}chi(2)=1.6, p=0.205 by log-rank test]). By day 28, 83.3% in the CBD group and 90.2% in the placebo group had resolved symptoms. There were no between-group differences on secondary measures. CBD was well tolerated, producing mostly mild and transient side effects (e.g., somnolence, fatigue, changes in appetite, lethargy, nausea, diarrhea, and fever), with no significant differences between CBD and placebo treatment groups.</p> Conclusions and Relevance: Daily administration of 300 mg CBD for 14 days failed to alter the clinical evolution of COVID-19. Further trials should explore the therapeutic effect of CBD in patients with severe COVID-19, possibly trying higher doses than the used in our study. Trial Registration: ClinicalTrials.gov identifier NCT04467918 (date of registration: July 13, 2020).</p> (AU)

• FAPESP's process: 14/50891-1 - INCT 2014: Translational Medicine
• Grantee: Jaime Eduardo Cecilio Hallak
• Support Opportunities: Research Projects - Thematic Grants