Effects of Cannabidiol on anxiety induced by recall of traumatic event in patients diagnosed with posttraumatic stress disorder

Author(s)

Lívia Maria Bolsoni

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2020-09-18

Examining board members

Antonio Waldo Zuardi; Francisco Silveira Guimarães; Silvana Maria Quintana; Reinaldo Naoto Takahashi

• Advisor: Antonio Waldo Zuardi

Abstract

Cannabidiol (CBD), a major component of the Cannabis sativa plant, has been investigated in animal and human studies. These studies corroborate hypotheses of the anxiolytic effect of CBD, as well as its association with the reconsolidation and extinction of aversive memories. The objective of the present study was to evaluate whether the administration of 300 mg of CBD before the recall of a traumatic event would attenuate anxiety symptoms induced by this recall, as well as associate with the reconsolidation of this aversive memory in people diagnosed with Post-Traumatic Stress Disorder (PTSD). A total of 33 participants of both sexes, aged between 18 and 60 years old, who met a PTSD diagnosis according to The Structured Clinical Interview for DSM-5 (SCID-5) were selected for the present study and signed the informed consent form. An experimental protocol administered once weekly for three weeks, was adopted. On day 1, participants completed the State-Trait Anxiety Inventory (STAI-T), Posttraumatic Stress Disorder Checklist (PCL-5), and had their body mass index (BMI) calculated. In addition, changes in subjective mood and anxiety indicators (Analog and Visual Mood Scale-VAMS and STAI-state), as well as in physiological correlates of anxiety (blood pressure [BP], heart rate [HR], and salivary cortisol [SC]) were assessed before and after the conduction of the following two-step behavioral test. First, participants\' reports of the trauma were recorded in digital audio for 90 seconds. After the audio was recorded, participants were asked to imagine the traumatic event for 30 seconds. On day 2, 7 days after day 1, participants were randomized into two groups (300 mg of CBD vs. placebo) using a double-blind procedure. Randomization was stratified by sex, age, BMI, and PCL-5 score. Two hours and 30 minutes after the pharmacological intervention, participants completed the same 2-step behavioral test that was administered on day one, and their changes in subjective mood and anxiety indicators, as well as in their physiological correlates were assessed before and after the behavioral test. On day 3, 7 days after day 2, participants underwent the same procedure as the one performed on day 2 but without pharmacological intervention in order to assess possible effects of CBD on the reconsolidation of the traumatic memory. Most participants were female, with a mean age of 32 years, and a PCL-5 score ranging from 52 to 54 points. In both groups, the predominant type of trauma was sexual, which comprised nearly half of the participants. Repeated measures ANOVA did not show significant differences between the CBD and placebo groups in relation to changes in anxiety induced by the recall of the traumatic event during the pharmacological intervention or in the subsequent week. However, in subgroup analyses for participants whose trauma was non-sexual, participants assigned to the CBD group demonstrated significant attenuation in the increase in VAMS anxiety factor scores when compared to participants assigned to placebo therapy. CBD was associated with reduced cognitive impairment (per VAMS scale) compared to placebo, with this effect remaining one week after the drug was administered. With regard to physiological measures (i.e., BP, HR, and SC), no significant differences were identified between the CBD and placebo groups on any of the three test days. Our study identifies a novel role for CBD in attenuating the cognitive impairment induced by the recall of trauma through a proposed mechanism whereby CBD mediates the traumatic memory reconsolidation. (AU)

• FAPESP's process: 16/01801-5 - Use of Canabidiol in the consolidation of aversive memories in victims of PTSD.
• Grantee: Lívia Maria Bolsoni
• Support Opportunities: Scholarships in Brazil - Doctorate