Accepted for Publication: June 1, 2021.
Published: August 13, 2021. doi:10.1001/jamanetworkopen.2021.20603
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Crippa JAS et al. JAMA Network Open.
Corresponding Author: José Alexandre S. Crippa, PhD, Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, Terceiro Andar, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, Brazil, CEP 14049-900 (jcrippa@fmrp.usp.br).
Author Contributions: Drs Zuardi and Guimarães had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Crippa, Zuardi, Guimarães, Osório, Loureiro, Souza, Ushirohira, Pacheco, Mechoulam, Hallak.
Acquisition, analysis, or interpretation of data: Crippa, Zuardi, Campos, dos Santos, Souza, Ushirohira, Pacheco, Rinaldi Ferreira, Mancini Costa, Scomparin, Scarante, Pires-Dos-Santos, Kapczinski, Fonseca, Esposito, Pereira-Lima, Sen, Andraus, Hallak.
Drafting of the manuscript: Crippa, Zuardi, Campos, Osório, dos Santos, Ushirohira, Pacheco, Rinaldi Ferreira, Mancini Costa, Scomparin, Scarante, Pires-Dos-Santos, Hallak.
Critical revision of the manuscript for important intellectual content: Crippa, Zuardi, Guimarães, Campos, Osório, Loureiro, dos Santos, Souza, Ushirohira, Pacheco, Mechoulam, Kapczinski, Fonseca, Esposito, Pereira-Lima, Sen, Andraus, Hallak.
Statistical analysis: Crippa, Zuardi, Guimarães, Campos, Rinaldi Ferreira, Mancini Costa, Scomparin, Scarante, Pires-Dos-Santos, Esposito.
Obtained funding: Crippa, Hallak.
Administrative, technical, or material support: Crippa, Campos, Osório, Loureiro, Souza, Ushirohira, Pacheco, Rinaldi Ferreira, Mancini Costa, Scomparin, Scarante, Pires-Dos-Santos, Andraus, Hallak.
Supervision: Crippa, Campos, Osório, Pacheco, Kapczinski, Hallak.
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.
Funding/Support: This work was supported by grant 2020/12110-9 from the Fundação de Amparo à Pesquisa do Estado de São Paulo; grant 2008/09009-2 from the Instituto Nacional de Ciência e Tecnologia Translational em Medicina; a grant from the Global Priorities in Cannabinoid Research Excellence Program, University Global Partnership Network (Dr Crippa); funding via research fellowships from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (Drs Crippa, Hallak, de Lima Osório, Loureiro, Campos, and Zuardi); in-kind donations of cannabidiol from PurMed Global; and donated services (dosing plasma levels of cannabidiol) from Laboratório Chromatox.
Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Group Members: Information on the Burnout and Distress Prevention With Cannabidiol in Front-line Health Care Workers Dealing With COVID-19 (BONSAI) trial investigators appears in Supplement 3.
Data Sharing Statement: See Supplement 4.
Additional Contributions: We thank PurMed Global (Delray Beach, Florida) for donating cannabidiol and Salomão e Zoppi Serviços Médicos e Participações (São Paulo, Brazil) and Laboratório Chromatox (São Paulo, Brazil) for dosing plasma levels of cannabidiol at no cost. We also thank the following members of the data and safety monitoring board for their commitment and responsiveness: Antonio Carlos dos Santos, MD, PhD, of the Department of Medical Imaging, Haematology, and Clinical Oncology, University of São Paulo (São Paulo, Brazil); Fábio Carmona, MD, PhD, of the Department of Pediatrics, University of São Paulo (São Paulo, Brazil); and Osvaldo Takayanagui, MD, PhD, of the Department of Health Sciences, University of São Paulo (São Paulo, Brazil). None of the contributors received compensation for their assistance.
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