Frontline physicians, nurses, and therapists working with COVID-19 patients had fewer emotional exhaustion symptoms when they were treated with cannabidiol (CBD), the BONSAI randomized clinical trial showed.
Scores on the emotional exhaustion subscale of the Maslach Burnout Inventory substantially decreased at days 14, 21, and 28 among 120 healthcare workers randomized to either CBD 300 mg plus standard care or standard care alone, reported José Alexandre Crippa, PhD, of University of São Paulo in Brazil, and co-authors in JAMA Network Open.
Five participants, all in the CBD group, experienced serious adverse events, including four cases of elevated liver enzymes and one case of severe pharmacodermia, with recovery after treatment was discontinued.
“Cannabidiol may act as an effective agent for the reduction of burnout symptoms among a population with important mental health needs worldwide,” Crippa and colleagues wrote. “However, it is necessary to balance the benefits with potential adverse and undesired effects when making decisions regarding the use of this compound.”
The findings were “consistent with a growing number of placebo-controlled studies in both rodents and humans suggesting that CBD lowers stress-provoked negative emotional states including fear, anxiety, depression, and anger,” observed Michael Telch, PhD, of the University of Texas at Austin, who wasn’t involved with the study.
“What accounts for this multi-emotion dampening? One potential explanation is that CBD appears to directly affect multiple brain targets implicated in stress reactivity, which plays a central role in the activation of emotional dysfunction,” Telch told MedPage Today.
Other studies, however, suggest that CBD may not significantly curb emotional distress. “The jury’s still out on how robust the anxiolytic effects of CBD actually are,” noted Mallory Loflin, PhD, of the University of California, San Diego, who also wasn’t involved with the trial. “We have a lot of folks self-reporting benefits, but that data is hard to interpret because it’s conflated by expectation or placebo, and uncontrolled amounts of trace THC [tetrahydrocannabinol].”
The latter is important because THC also might be anxiolytic, at least in small doses, Loflin pointed out. “We do have a couple of studies showing acute improvement in social anxiety, but in highly contrived, experimental settings. Those data look pretty compelling, but the doses are exponentially higher than most folks are taking on a daily basis,” she told MedPage Today.
“The big benefit here, though, is that if CBD actually does end up being effective, its safety profile looks really good, particularly in comparison to benzodiazepines or SSRIs [selective serotonin reuptake inhibitors],” Loflin added.
The open-label BONSAI trial randomized 120 physicians, nurses, and physical therapists working with patients with COVID-19 at the Ribeirão Preto Medical School University Hospital in São Paulo between June and November 2020 to either oral cannabidiol 300 mg (150 mg twice per day) plus standard care, or standard care alone, for 28 days. CBD had 99.6% purity and was dissolved in medium-chain triglyceride oil.
Standard care included motivational and instructional videos about low-impact physical exercise and weekly consultations with psychiatrists who offered psychological support. Hospital executives offered personal protective equipment, work schedule adjustments, and ongoing testing, and also hired new personnel and provided a specific outpatient treatment unit during the pandemic.
The primary outcome was assessed with the emotional exhaustion subscale of the Brazilian version of the Maslach Burnout Inventory, Human Services Survey for Medical Personnel (subscale score range is 0-54 points, with higher scores indicating greater emotional exhaustion). Secondary outcomes including anxiety and depression, were assessed with other measures. Blood samples were collected at baseline and days 7, 14, 21, and 28.
The average age of healthcare workers involved in the study was about 34, and 67% were women. About 55% were nurses, and 42% were physicians; all worked in ICUs, emergency departments, or hospital wards.
Three participants in the CBD arm withdrew from the study: one experienced severe pharmacodermia, one had critical elevation of liver enzymes, and one left to participate in a COVID-19 vaccine clinical trial. During follow-up, both participants who discontinued CBD therapy because of serious adverse events experienced full recovery.
Compared with participants who received standard care alone, participants who received CBD plus standard care had substantial reductions on the Maslach Burnout Inventory emotional exhaustion 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
- Day 28: mean difference 4.01 points, 95% CI 0.43-7.59 points, ηp2=0.04
At day 28, CBD plus standard care significantly reduced the number of participants with scores indicating anxiety on the seven-item Generalized Anxiety Disorder questionnaire and depression on the nine-item Patient Health Questionnaire. CBD also decreased the number of diagnoses of burnout syndrome based on ICD-11 criteria, but the difference was not statistically significant (P=0.08).
The trial had several limitations, Crippa and co-authors acknowledged. It was a single-center study with a short follow-up period and a single-intervention dose. It also did not have a double-blind placebo-controlled design.
There still are many unanswered questions about CBD, including optimal dosing regimens and formulations, Telch noted. Ongoing studies, including one comparing the effects of broad-spectrum, full-spectrum, and CBD-isolate oil on the emotional impact of COVID-19, may address some of these issues.
The study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo, the Instituto Nacional de Ciência e Tecnologia Translational em Medicina; the Global Priorities in Cannabinoid Research Excellence Program, University Global Partnership Network, the Conselho Nacional de Desenvolvimento Científico e Tecnológico, and donations from PurMed Global and Laboratório Chromatox.
Researchers reported relationships with the Fundação de Amparo à Pesquisa do Estado de São Paulo, the Instituto Nacional de Ciência e Tecnologia Translational em Medicina, the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Australian Centre for Cannabinoid Clinical and Research Excellence, National Health and Medical Research Council, Phytecs, Prati-Donaduzzi, Canada Foundation for Innovation, Mitacs, Stanley Medical Research Institute, Aché Laboratorios Farmaceuticos, Daiichi Sankyo, Janssen-Cilag, Salomao Zoppi Serviços, BioSynthesis Pharma Group, and a patent pending for a cannabinoid-containing oral pharmaceutical composition.