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. 2021 Aug 2;4(8):e2120603.
doi: 10.1001/jamanetworkopen.2021.20603.

Efficacy and Safety of Cannabidiol Plus Standard Care vs Standard Care Alone for the Treatment of Emotional Exhaustion and Burnout Among Frontline Health Care Workers During the COVID-19 Pandemic: A Randomized Clinical Trial

José Alexandre S Crippa  1   2 , Antonio W Zuardi  1   2 , Francisco S Guimarães  2   3 , Alline Cristina Campos  3 , Flávia de Lima Osório  1   2 , Sonia Regina Loureiro  1 , Rafael G Dos Santos  1   2 , José Diogo S Souza  1 , Juliana Mayumi Ushirohira  1 , Julia Cozar Pacheco  1 , Rafael Rinaldi Ferreira  3 , Karla Cristinne Mancini Costa  3 , Davi Silveira Scomparin  3 , Franciele Franco Scarante  3 , Isabela Pires-Dos-Santos  3 , Raphael Mechoulam  4 , Flávio Kapczinski  2   5   6 , Benedito A L Fonseca  7 , Danillo L A Esposito  7 , Karina Pereira-Lima  8   9 , Srijan Sen  8 , Maristela Haddad Andraus  10 , Jaime E C Hallak  1   2 ; Burnout and Distress Prevention With Cannabidiol in Front-line Health Care Workers Dealing With COVID-19 (BONSAI) Trial Investigators
Collaborators, Affiliations

Efficacy and Safety of Cannabidiol Plus Standard Care vs Standard Care Alone for the Treatment of Emotional Exhaustion and Burnout Among Frontline Health Care Workers During the COVID-19 Pandemic: A Randomized Clinical Trial

José Alexandre S Crippa et al. JAMA Netw Open. .

Abstract

Importance: Frontline health care professionals who work with patients with COVID-19 have an increased incidence of burnout symptoms. Cannabidiol (CBD) has anxiolytic and antidepressant properties and may be capable of reducing emotional exhaustion and burnout symptoms.

Objective: To investigate the safety and efficacy of CBD therapy for the reduction of emotional exhaustion and burnout symptoms among frontline health care professionals working with patients with COVID-19.

Design, setting, and participants: This prospective open-label single-site randomized clinical trial used a 1:1 block randomization design to examine emotional exhaustion and burnout symptoms among frontline health care professionals (physicians, nurses, and physical therapists) working with patients with COVID-19 at the Ribeirão Preto Medical School University Hospital in São Paulo, Brazil. Participants were enrolled between June 12 and November 12, 2020. A total of 214 health care professionals were recruited and assessed for eligibility, and 120 participants were randomized in a 1:1 ratio by a researcher who was not directly involved with data collection.

Interventions: Cannabidiol, 300 mg (150 mg twice per day), plus standard care or standard care alone for 28 days.

Main outcomes and measures: The primary outcome was emotional exhaustion and burnout symptoms, which were assessed for 28 days using the emotional exhaustion subscale of the Brazilian version of the Maslach Burnout Inventory-Human Services Survey for Medical Personnel.

Results: A total of 120 participants were randomized to receive either CBD, 300 mg, plus standard care (treatment arm; n = 61) or standard care alone (control arm; n = 59) for 28 days. Of those, 118 participants (59 participants in each arm; 79 women [66.9%]; mean age, 33.6 years [95% CI, 32.3-34.9 years]) received the intervention and were included in the efficacy analysis. In the treatment arm, scores on the emotional exhaustion subscale of the Maslach Burnout Inventory significantly decreased at day 14 (mean difference, 4.14 points; 95% CI, 1.47-6.80 points; partial eta squared [ηp2] = 0.08), day 21 (mean difference, 4.34 points; 95% CI, 0.94-7.73 points; ηp2 = 0.05), and day 28 (mean difference, 4.01 points; 95% CI, 0.43-7.59 points; ηp2 = 0.04). However, 5 participants, all of whom were in the treatment group, experienced serious adverse events: 4 cases of elevated liver enzymes (1 critical and 3 mild, with the mild elevations reported at the final 28-day assessment) and 1 case of severe pharmacodermia. In 2 of those cases (1 with critical elevation of liver enzymes and 1 with severe pharmacodermia), CBD therapy was discontinued, and the participants had a full recovery.

Conclusions and relevance: In this study, CBD therapy reduced symptoms of burnout and emotional exhaustion among health care professionals working with patients during the COVID-19 pandemic. However, it is necessary to balance the benefits of CBD therapy with potential undesired or adverse effects. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings.

Trial registration: ClinicalTrials.gov Identifier: NCT04504877.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Crippa reported receiving grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo and the Instituto Nacional de Ciência e Tecnologia Translational em Medicina and personal fees from the Conselho Nacional de Desenvolvimento Científico e Tecnológico and Salomão e Zoppi Serviços Médicos e Participações during the conduct of the study and receiving travel support and personal fees from BioSynthesis Pharma Group; serving as a member of the international advisory board of the Australian Centre for Cannabinoid Clinical and Research Excellence, National Health and Medical Research Council; being a co-owner of a patent for fluorinated cannabidiol compounds (licensed to Phytecs); and having a patent pending for a cannabinoid-containing oral pharmaceutical composition outside the submitted work. Dr Zuardi reported receiving grants from the Instituto Nacional de Ciência e Tecnologia Translational em Medicina and personal fees from the Conselho Nacional de Desenvolvimento Científico e Tecnológico during the conduct of the study, being a co-owner of a patent for fluorinated cannabidiol compounds (licensed to Phytecs), and having a patent pending for a cannabinoid-containing oral pharmaceutical composition outside the submitted work. Dr Guimarães reported receiving grants from Prati-Donaduzzi, being a co-owner of a patent for fluorinated cannabidiol compounds (licensed to Phytecs), and having a patent pending for a cannabinoid-containing oral pharmaceutical composition outside the submitted work. Dr Campos reported having a patent pending for a cannabinoid-containing oral pharmaceutical composition outside the submitted work. Dr dos Santos reported receiving grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico during the conduct of the study. Dr Ushirohira reported receiving personal fees from Ribeirão Preto Medical School, University of São Paulo, during the conduct of the study. Dr Mechoulam reported being a co-owner of a patent for fluorinated cannabidiol compounds (licensed to Phytecs) outside the submitted work. Dr Kapczinski reported receiving grants from the Canada Foundation for Innovation, the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Mitacs, and the Stanley Medical Research Institute; personal fees from Aché Laboratorios Farmaceuticos, Daiichi Sankyo, and Janssen-Cilag; and being a co-owner of a patent for fluorinated cannabidiol compounds (licensed to Phytecs) outside the submitted work. Ms Andraus reported receiving technical support from Salomao Zoppi Serviços Medicos e Participações during the conduct of the study and personal fees from Laboratório Chromatox outside the submitted work. Dr Hallak reported receiving grants from Prati-Donaduzzi, travel support and personal fees from BioSynthesis Pharma Group, being a co-owner of a patent for fluorinated cannabidiol compounds (licensed to Phytecs), and having a patent pending for a cannabinoid-containing oral pharmaceutical composition outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Period and First Wave of COVID-19 Cases
Period with the start, peak, plateau, and initial reduction curve of the first wave of COVID-19 cases in Ribeirão Preto, São Paulo, Brazil.
Figure 2.
Figure 2.. Study Flow Diagram
CBD indicates cannabidiol.
Figure 3.
Figure 3.. Results for Emotional Exhaustion, Depression, and Anxiety
GAD-7 indicates 7-item Generalized Anxiety Disorder questionnaire; ICD-11, International Classification of Diseases, Eleventh Revision; MBI-HSS, Maslach Burnout Inventory–Human Services Survey for Medical Personnel; and PHQ-9, 9-item Patient Health Questionnaire. aDifference between the treatment and control arms was statistically significant.
See this image and copyright information in PMC

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