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

José Alexandre S. Crippa, PhD; AntonioW. Zuardi, PhD; Francisco S. Guimarães, PhD; Alline Cristina Campos, PhD; Flávia de Lima Osório, PhD; Sonia Regina Loureiro, PhD;
Rafael G. dos Santos, PhD; José Diogo S. Souza, MD; Juliana Mayumi Ushirohira, MD, MSc; Julia Cozar Pacheco, RPh; Rafael Rinaldi Ferreira, PhD, RPh;
Karla Cristinne Mancini Costa, MSc; Davi Silveira Scomparin, MSc; Franciele Franco Scarante, MSc; Isabela Pires-Dos-Santos, VMD; Raphael Mechoulam, PhD;
Flávio Kapczinski, PhD; Benedito A. L. Fonseca, PhD; Danillo L. A. Esposito, PhD; Karina Pereira-Lima, PhD; Srijan Sen, PhD; Maristela Haddad Andraus, MSc, RPh;
Jaime E. C. Hallak, PhD; for the Burnout and Distress Prevention With Cannabidiol in Front-line Health CareWorkers Dealing With COVID-19 (BONSAI) Trial Investigators

JAMA Network Open, 2021, 4, (8), e2120603.

doi : 10.1001/jamanetworkopen.2021.20603

 

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, 300mg (150mg 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, whichwere 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, 300mg, 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 [ηp 2] = 0.08), day 21 (mean difference, 4.34 points; 95%CI, 0.94-7.73 points; ηp 2 = 0.05), and day 28 (mean difference, 4.01 points; 95%CI, 0.43-7.59 points; ηp 2 = 0.04). However, 5 participants, all of whomwere 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 (continued) 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

Key Points

Question : Is cannabidiol (CBD) therapy capable of reducing emotional exhaustion and burnout symptoms among frontline health care professionals working with patients with
COVID-19?

Findings : In this randomized clinical trial of 120 frontline health care professionals, emotional exhaustion scoreswere reduced among participants receiving CBD plus standard care compared with those receiving standard care alone. Five participants who received CBD plus standard care experienced serious adverse events, with full recovery after discontinuation.

Meaning : The study’s findings suggest that CBD may act as an effective agent for the reduction of emotional exhaustion and burnout symptoms among frontline health care professionals, although it is necessary to balance the benefits with potential undesired effects when making decisions regarding the use of CBD.

 

Introduction

During the COVID-19 pandemic, most countries adopted lockdown and physical distancing measures as containment strategies. This situation led to severe social and economic consequences and affected mental health.1-4 Several surveys have reported pandemic-related increases in emotional distress, depression,3,5 anxiety,3,5 posttraumatic stress disorder (PTSD),3-6 and insomnia,6 particularly among frontline health care workers.2 The usual pharmacological treatments for these conditions (antidepressant, anxiolytic, and hypnotic medications) often require several weeks to be effective and can produce substantial adverse effects (AEs). Safer and more effective drugs to treat the symptoms of emotional exhaustion and burnout are needed, especially during the current COVID-19 pandemic.

Cannabidiol (CBD) is a nonpsychotomimetic phytocannabinoid with a favorable safety and tolerability profile. The drug has been reported to have anxiolytic effects in healthy volunteers7-10 and patients with social anxiety disorder11 at doses ranging from a single administration of 300 to 600mg12-16 to daily administration of 300mg for 4 weeks.17 Cannabidiol also been found to have antidepressant12-14 and antiinflammatory15-21 effects in preclinical studies.

Considering the potential beneficial properties of CBD and its favorable safety profile, we assessed the efficacy and safety of daily administration of CBD therapy to decrease the symptoms of emotional exhaustion and burnout among frontline health care workers treating patients with COVID-19 in a Brazilian hospital. Our secondary outcomes were to evaluate anxiety, depression, and PTSD symptoms and to examine proinflammatory cytokine levels and general laboratory measurements.

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