Cannabidiol as a Therapeutic Alternative for Post-traumatic Stress Disorder: From Bench Research to Confirmation in Human Trials

Rafael M. Bitencourt and Reinaldo N. Takahashi  (July 2018)

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Post-traumatic stress disorder (PTSD) is characterized by poor adaptation to a traumatic experience. This disorder affects approximately 10% of people at some point in life. Current pharmacological therapies for PTSD have been shown to be inefficient and produce considerable side effects. Since the discovery of the involvement of the endocannabinoid (eCB) system in emotional memory processing, pharmacological manipulation of eCB signaling has become a therapeutic possibility for the treatment of PTSD. Cannabidiol (CBD), a phytocannabinoid constituent of Cannabis sativa without the psychoactive effects of Δ9-tetrahydrocannabinol, has gained particular attention. This paper reviews the therapeutic potential of CBD in the treatment of PTSD. It starts from the first evidence obtained in animal studies (“bench research”) and proceeds to knowledge gathered in human trials (“confirmation in human trials”).

Endocannabinoid System in Posttraumatic Stress Disorder (PTSD) Early After Traumatic Injury

Terri deRoon-Cassini, Samantha Chesney, Cecilia Hillard  (April 2018)

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In the immediate aftermath of injury it is unclear who demonstrates risk for posttraumatic stress disorder (PTSD). Pre-clinical data suggests the endocannabinoid signaling system responds to stress and acts as a buffer after trauma. The purpose of the present study was: 1) evaluate the role of early circulating endocannabinoid (2-AG, AEA) functioning in 6-month PTSD, and 2) evaluate polymorphisms of the cannabinoid receptor type 1 (CB1) and fatty acid amide hydrolase (FAAH) genes to determine differential PTSD risk.

Investigating Endocannabinoid Mechanisms in Posttraumatic Stress Disorder: Neuroimaging Studies With the Novel Fatty Acid Amide Hydrolase Probe, [11C]CURB

IsabelleBoileauDuncanWestwoodDonaldRichardsonShawnRhindRachel F.TyndaleRuthLaniusRichardBazinetNancy J.LobaughSylvainHoule  (April 2018)

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Fatty Acid Amide Hydrolase (FAAH), the enzyme responsible for terminating endocannabinoid signaling, is believed to be a key modulator of fear-related circuitry and to be increased in post-traumatic stress disorder (PTSD). This enzyme and other components of the endocannabinoid system are drug targets for stress-related conditions.

Enhancing Endocannabinoid Neurotransmission Augments The Efficacy of Extinction Training and Ameliorates Traumatic Stress-Induced Behavioral Alterations in Rats

Maria MorenaAndrea BerardiPaola ColucciMaura PalmeryViviana TrezzaMatthew N Hill and Patrizia Campolongo  (December 2017)

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Exposure to a traumatic event may result in the development of post-traumatic stress disorder (PTSD). Endocannabinoids are crucial modulators of the stress response, interfere with excessive retrieval and facilitate the extinction of traumatic memories. Exposure therapy, combined with pharmacotherapy, represents a promising tool for PTSD treatment. We investigated whether pharmacological manipulations of the endocannabinoid system during extinction learning ameliorates the behavioral changes induced by trauma exposure. Rats were exposed to inescapable footshocks paired with social isolation, a risk factor for PTSD.

Integrating Endocannabinoid Signaling and Cannabinoids into the Biology and Treatment of Posttraumatic Stress Disorder

Matthew N HillPatrizia CampolongoRachel Yehuda and Sachin Patel  (July 2017)

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Here we review the current state of knowledge regarding the effects of cannabis and cannabinoids in PTSD and the preclinical and clinical literature on the effects of cannabinoids and endogenous cannabinoid signaling systems in the regulation of biological processes related to the pathogenesis of PTSD. Potential therapeutic implications of the reviewed literature are also discussed. Finally, we propose that a state of endocannabinoid deficiency could represent a stress susceptibility endophenotype predisposing to the development of trauma-related psychopathology and provide biologically plausible support for the self-medication hypotheses used to explain high rates of cannabis use in patients with trauma-related disorders.

The endocannabinoid system as a possible target to treat both the cognitive and emotional features of post-traumatic stress disorder (PTSD)

Viviana Trezza and Patrizia Campolongo  (August 2013)

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Endocannabinoids regulate affective states and participate in memory consolidation, retrieval, and extinction. Clinical findings showing a relationship between Cannabis use and PTSD, as well as changes in endocannabinoid activity in PTSD patients, further suggest the existence of a link between endocannabinoids and maladaptive brain changes after trauma exposure. Along these lines, we suggest that endocannabinoid degradation inhibitors may be an ideal therapeutic approach to simultaneously treat the emotional and cognitive features of PTSD, avoiding the unwanted psychotropic effects of compounds directly binding cannabinoid receptors.