Maintained anxiolytic effects of cannabidiol after treatment discontinuation in healthcare workers during the COVID-19 pandemic

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Abstract

Objective: To assess whether the effects of oral administration of 300 mg of Cannabidiol (CBD) for 28 days on mental health are maintained for a period after the medication discontinuation.

Methods: This is a 3-month follow-up observational and clinical trial study. The data were obtained from two studies performed simultaneously by the same team in the same period and region with Brazilian frontline healthcare workers during the COVID-19 pandemic. Scales to assess emotional symptoms were applied weekly, in the first month, and at weeks eight and 12.

Results: The primary outcome was that, compared to the control group, a significant reduction in General Anxiety Disorder-7 Questionnaire (GAD-7) from baseline values was observed in the CBD group on weeks two, four, and eight (Within-Subjects Contrasts, time-group interactions: F _1-125 = 7.67; p = 0.006; η _p ² = 0.06; F _1-125 = 6.58; p = 0.01; η _p ² = 0.05; F _1-125 = 4.28; p = 0.04; η _p ² = 0.03, respectively) after the end of the treatment.

Conclusions: The anxiolytic effects of CBD in frontline health care professionals during the COVID-19 pandemic were maintained up to 1 month after the treatment discontinuation, suggesting a persistent decrease in anxiety in this group in the real world. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings and weigh the benefits of CBD therapy against potential undesired or adverse effects.

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Safety and side effects of cannabidiol, a Cannabis sativa constituent.

Mateus Machado Bergamaschi, Regina Helena Costa Queiroz, Antonio Waldo Zuardi … (2011)

Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were "cannabinoids", "cannabidiol" and "side effects". Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.

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Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report.

Antonio Zuardi, T. Micelli Ferrari, K. Ashlee McGuire … (2010)

Animal and human studies indicate that cannabidiol (CBD), a major constituent of cannabis, has anxiolytic properties. However, no study to date has investigated the effects of this compound on human pathological anxiety and its underlying brain mechanisms. The aim of the present study was to investigate this in patients with generalized social anxiety disorder (SAD) using functional neuroimaging. Regional cerebral blood flow (rCBF) at rest was measured twice using (99m)Tc-ECD SPECT in 10 treatment-naïve patients with SAD. In the first session, subjects were given an oral dose of CBD (400 mg) or placebo, in a double-blind procedure. In the second session, the same procedure was performed using the drug that had not been administered in the previous session. Within-subject between-condition rCBF comparisons were performed using statistical parametric mapping. Relative to placebo, CBD was associated with significantly decreased subjective anxiety (p < 0.001), reduced ECD uptake in the left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (p < 0.001, uncorrected), and increased ECD uptake in the right posterior cingulate gyrus (p < 0.001, uncorrected). These results suggest that CBD reduces anxiety in SAD and that this is related to its effects on activity in limbic and paralimbic brain areas.

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Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients.

Marcos H. N. Chagas, Antonio Zuardi, E Nardi … (2011)

Generalized Social Anxiety Disorder (SAD) is one of the most common anxiety conditions with impairment in social life. Cannabidiol (CBD), one major non-psychotomimetic compound of the cannabis sativa plant, has shown anxiolytic effects both in humans and in animals. This preliminary study aimed to compare the effects of a simulation public speaking test (SPST) on healthy control (HC) patients and treatment-naïve SAD patients who received a single dose of CBD or placebo. A total of 24 never-treated patients with SAD were allocated to receive either CBD (600 mg; n=12) or placebo (placebo; n=12) in a double-blind randomized design 1 h and a half before the test. The same number of HC (n=12) performed the SPST without receiving any medication. Each volunteer participated in only one experimental session in a double-blind procedure. Subjective ratings on the Visual Analogue Mood Scale (VAMS) and Negative Self-Statement scale (SSPS-N) and physiological measures (blood pressure, heart rate, and skin conductance) were measured at six different time points during the SPST. The results were submitted to a repeated-measures analysis of variance. Pretreatment with CBD significantly reduced anxiety, cognitive impairment and discomfort in their speech performance, and significantly decreased alert in their anticipatory speech. The placebo group presented higher anxiety, cognitive impairment, discomfort, and alert levels when compared with the control group as assessed with the VAMS. The SSPS-N scores evidenced significant increases during the testing of placebo group that was almost abolished in the CBD group. No significant differences were observed between CBD and HC in SSPS-N scores or in the cognitive impairment, discomfort, and alert factors of VAMS. The increase in anxiety induced by the SPST on subjects with SAD was reduced with the use of CBD, resulting in a similar response as the HC.

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Contributors

José Diogo S. Souza: URI : https://loop.frontiersin.org/people/505930/overview

Antonio W. Zuardi: URI : https://loop.frontiersin.org/people/76826/overview

Francisco S. Guimarães: URI : https://loop.frontiersin.org/people/40439/overview

Flávia de Lima Osório: URI : https://loop.frontiersin.org/people/1219322/overview

Sonia Regina Loureiro: URI : https://loop.frontiersin.org/people/1408898/overview

Alline Cristina Campos: URI : https://loop.frontiersin.org/people/115275/overview

Jaime E. C. Hallak: URI : https://loop.frontiersin.org/people/115869/overview

Rafael G. Dos Santos: URI : https://loop.frontiersin.org/people/128867/overview

Isabella Lara Machado Silveira: URI : https://loop.frontiersin.org/people/1408887/overview

Karina Pereira-Lima: URI : https://loop.frontiersin.org/people/1382948/overview

Juliana Mayumi Ushirohira: URI : https://loop.frontiersin.org/people/692440/overview

Karla Cristinne Mancini Costa: URI : https://loop.frontiersin.org/people/1563637/overview

Franciele Franco Scarante: URI : https://loop.frontiersin.org/people/1945521/overview

Flávio Kapczinski: URI : https://loop.frontiersin.org/people/341684/overview

Maristela Haddad Andraus: URI : https://loop.frontiersin.org/people/1773546/overview

José Alexandre S. Crippa: URI : https://loop.frontiersin.org/people/75853/overview

Journal

Journal ID (nlm-ta): Front Pharmacol

Journal ID (iso-abbrev): Front Pharmacol

Journal ID (publisher-id): Front. Pharmacol.

Title: Frontiers in Pharmacology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1663-9812

Publication date (Electronic): 03 October 2022

Publication date Collection: 2022

Publication date PMC-release: 03 October 2022

Volume: 13

Electronic Location Identifier: 856846

Affiliations

[1] ¹ Department of Neuroscience and Behavior , Ribeirão Preto Medical School , University of São Paulo , Ribeirão Preto, Brazil

[2] ² National Institute for Science and Technology—Translational Medicine , Ribeirão Preto, Brazil

[3] ³ Department of Pharmacology , Ribeirão Preto Medical School , University of São Paulo , Ribeirão Preto, Brazil

[4] ⁴ University of Michigan Medical School , Ann Arbor, IN, United States

[5] ⁵ Department of Psychiatry , Federal University of São Paulo , São Paulo, São Paulo, Brazil

[6] ⁶ The Institute for Drug Research , School of Pharmacy , The Hebrew University of Jerusalem , Jerusalem, Israel

[7] ⁷ Department of Psychiatry and Behavioural Neurosciences , McMaster University and St. Joseph’s Healthcare Hamilton , Hamilton, ON, Canada

[8] ⁸ Department of Psychiatry , Faculty of Medicine , Graduate Program in Psychiatry and Behavioral Sciences , Universidade Federal do Rio Grande do Sul , Porto Alegre, Brazil

[9] ⁹ Department of Internal Medicine , Ribeirão Preto Medical School , University of São Paulo , Ribeirão Preto, Brazil

[10] ¹⁰ Chromatox Laboratory Ltd São Paulo , Brazil

Author notes

Edited by: Francisco Navarrete, Miguel Hernández University of Elche, Spain

Reviewed by: Marta Marin, University Hospital October 12, Spain

Elena Martín-García, Pompeu Fabra University, Spain

*Correspondence: José Diogo S. Souza, jose.diogo.souza@ 123456usp.br

This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology

Article

Publisher ID: 856846

DOI: 10.3389/fphar.2022.856846

PMC ID: 9574068

PubMed ID: 36263136

SO-VID: c09245ce-990b-41f1-bb50-da1fc38c9439

Copyright © Copyright © 2022 Souza, Zuardi, Guimarães, Osório, Loureiro, Campos, Hallak, Dos Santos, Machado Silveira, Pereira-Lima, Pacheco, Ushirohira, Ferreira, Costa, Scomparin, Scarante, Pires-Dos-Santos, Mechoulam, Kapczinski, Fonseca, Esposito, Andraus and Crippa.

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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 17 January 2022

Date accepted : 10 August 2022

Funding

Funded by: Fundação de Amparo à Pesquisa do Estado de São Paulo , doi 10.13039/501100001807;

Award ID: 2014/50891-1 2020/12110-9

Funded by: Instituto Nacional de Ciência e Tecnologia Translacional em Medicina , doi 10.13039/501100007762;

Award ID: 2008/09009-2

Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico , doi 10.13039/501100003593;

Award ID: 401058/2020-4 465458/2014-9

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Maintained anxiolytic effects of cannabidiol after treatment discontinuation in healthcare workers during the COVID-19 pandemic

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Most cited references 37

Safety and side effects of cannabidiol, a Cannabis sativa constituent.

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report.

Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients.

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