Studies with cannabidiol (CBD) suggest that this compound has anxiolytic properties and may mediate the reconsolidation and extinction of aversive memories. The objective of this study was to test whether the administration of CBD 300 mg before the recall of traumatic events attenuated symptoms usually induced by recall in subjects diagnosed with posttraumatic stress disorder (PTSD) and if its potential effects interfere with the reconsolidation of aversive memories. The double-blind trial included 33 participants of both sexes, aged between 18 and 60 years, diagnosed with PTSD according to the SCID-5 and randomly allocated to two groups treated with CBD (n = 17) and placebo (n = 16). In the first experimental section, participants were matched by sex, age, body mass index (BMI), and PTSD symptoms as assessed with the Posttraumatic Stress Disorder Checklist (PCL-5). On the same day, participants prepared the behavior test, recording accounts of their traumas in digital audio for a minute and a half and then imagining the trauma for 30 s. After 7 days, participants received CBD (300 mg) or placebo and performed the behavioral test, listening to the trauma account and imagining themselves in that situation. Before and after the behavioral test, subjective changes in mood and anxiety were recorded (Visual and Analogical Mood Scale — VAMS and STAI-state), along with physiological correlates of anxiety blood pressure (BP), heart rate (HR), and salivary cortisol (SC). Seven days later, participants underwent the same procedures as the previous session, but without the pharmacological intervention, to assess the effect on reconsolidation of traumatic memories. We found that CBD significantly attenuated the increase in the VAMS scale cognitive impairment factor scores, under the CBD’s effect, with this effect remaining 1 week after drug administration. No significant differences between the effects of CBD and placebo on anxiety, alertness, and discomfort induced by the recall of the traumatic event during the pharmacological intervention and in the subsequent week, in the absence of it. There were no significant differences between the CBD and placebo groups regarding physiological data (BP, HR, and SC). The attenuation of cognitive impairments during trauma recall under the effect of CBD may have interfered with the reconsolidation of traumatic memories concerning its association with cognitive impairments.
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This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), and by the Instituto Nacional de Ciência e Tecnologia Translational em Medicina (INCT-TM; CNPq/FAPESP; 2008/09009–2; 2020/ 05416–4). JAC received a grant from the University Global Partnership Network (UGPN) – Global Priorities in Cannabinoid Research Excellence Program. JAC, JEH, and AWZ are recipients of CNPq research fellowships. The funders 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.
Conflict of interest
JAC, JEH, and AWZ are coinventors of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023,” Def. US number Reg. 62193296; July 29, 2015; INPI on August 19, 2015 (BR1120150164927; Mechoulam R, Zuardi AW, Kapczinski F, Hallak JEC, Guimarães FS, Crippa JAS, Breuer A). Universidade de São Paulo (USP) has licensed this patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1) and has an agreement with Prati-Donaduzzi to “develop a pharmaceutical product containing synthetic CBD and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson’s disease, and anxiety disorders.” JAC, JEH, and AWZ are coinventors of the patent “Cannabinoid-containing oral pharmaceutical composition, method for preparing and using same,” INPI on September 16th, 2016 (BR 112018005423–2). JASC is a consultant and/or has received speaker fees and/or sits on the advisory board and/or receives research funding from Janssen-Cilag, Torrent Pharm, Prati-Donaduzzi, PurMed Global, BSPG Pharm, and the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE) – National Health and Medical Research Council (NHMRC) over the past 3 years. JEH was a consultant from BSPG-Pharm and PurMed Global over the past 3 years. The other authors declare that they have no conflicts of interest.
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Bolsoni, L.M., Crippa, J.A.S., Hallak, J.E.C. et al. Effects of cannabidiol on symptoms induced by the recall of traumatic events in patients with posttraumatic stress disorder. Psychopharmacology 239, 1499–1507 (2022). https://doi.org/10.1007/s00213-021-06043-y