The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study

Jetly, Rakesh; Heber, Alexandra; Fraser, George A.; Boisvert, Denis

doi:10.1016/j.psyneuen.2014.11.002

Cited by 253 publications

(187 citation statements)

References 13 publications

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“…Since exposure-based psychotherapies for PTSD rely on mechanisms of extinction learning (Anderson and Insel, 2006), it was argued whether stimulation of the ECS might augment therapeutic effects in PTSD (Neumeister et al, 2015). A preliminary randomized controlled trial indicated that treatment with a synthetic cannabinoid (mimicking the effects of THC) significantly reduces the reliving of the traumatic experiences in the form of nightmares in PTSD patients (Jetly et al, 2015). Similarly, a significant reduction in nightmares was observed, if THC was administered in addition to the ongoing medication in a preliminary, openlabel study (Roitman et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Endocannabinoid concentrations in hair are associated with PTSD symptom severity

Wilker

Pfeiffer

Elbert

et al. 2016

Psychoneuroendocrinology

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a b s t r a c tThe endocannabinoid system has been implicated in the regulation of the stress response, fear memory formation, and inflammatory processes. Posttraumatic stress disorder (PTSD) can result from exposure to extreme stress and is characterized by strong, associative memories for the traumatic events experienced. Furthermore, an elevated physical disease risk has been observed in PTSD, likely to be mediated by inflammatory processes. Therefore, altered endocannabinoid regulation can be expected in individuals with PTSD. However, attempts to assess PTSD-associated differences in the endocannabinoid system from human blood samples have provided inconsistent results, possibly due to fluctuating levels of endocannabinoids. In hair, these neuromodulators are accumulated over time and thus give access to a more stable and reliable assessment.We therefore investigated PTSD-associated differences in hair concentrations of endocannabinoids (Nacyl-ethanolamides palmitoylethanolamide [PEA], oleoylethanolamide [OEA] and stearoylethanolamide [SEA]) in 38 rebel war survivors from Northern Uganda suffering from PTSD and N = 38 healthy rebel war survivors without current and lifetime PTSD. PTSD diagnosis and symptom severity were assessed in structured clinical interviews employing the Posttraumatic Diagnostic Scale (PDS). A significant group difference was observed for OEA, with PTSD patients showing reduced hair concentrations. Regression analyses further revealed strong negative relationships between all investigated N-acyl-ethanolamides and symptom severity of PTSD. The observed reductions in endocannabinoids might account for the increased inflammatory state as well as for the failure to extinguish fear memories observed in PTSD. Our findings add to the accumulating evidence suggesting the endocannabinoid system as a target for pharmacological enhancement of exposure-based psychotherapy for PTSD.

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Section: Discussionmentioning

confidence: 99%

Endocannabinoid concentrations in hair are associated with PTSD symptom severity

Wilker

Pfeiffer

Elbert

et al. 2016

Psychoneuroendocrinology

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“…Despite the abundant evidence suggesting the role of inflammation in PTSD, however, thus far this has rarely been translated into treatment strategies. Still, several types of extant (off‐label) pharmacological agents that have anti‐inflammatory properties may represent a promising therapeutic option (Table ).…”

Section: Potential Anti‐inflammatory Treatment Strategiesmentioning

confidence: 99%

Inflammation and post‐traumatic stress disorder

Hori

Kim

2019

Psychiatry Clin Neurosci

258

176

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While post‐traumatic stress disorder (PTSD) is currently diagnosed based solely on classic psychological and behavioral symptoms, a growing body of evidence has highlighted a link between this disorder and alterations in the immune and inflammatory systems. Epidemiological studies have demonstrated that PTSD is associated with significantly increased rates of physical comorbidities in which immune dysregulation is involved, such as metabolic syndrome, atherosclerotic cardiovascular disease, and autoimmune diseases. In line with this, a number of blood biomarker studies have reported that compared to healthy controls, individuals with PTSD exhibit significantly elevated levels of proinflammatory markers, such as interleukin‐1β, interleukin‐6, tumor necrosis factor‐α, and C‐reactive protein. Moreover, various lines of animal and human research have suggested that inflammation is not only associated with PTSD but also can play an important role in its pathogenesis and pathophysiology. In this review, we first summarize evidence suggestive of increased inflammation in PTSD. We then examine findings that suggest possible mechanisms of inflammation in this disorder in terms of two different but interrelated perspectives: putative causes of increased proinflammatory activities and potential consequences that inflammation generates. Given that there is currently a dearth of treatment options for PTSD, possibilities of new therapeutic approaches using pharmacological and non‐pharmacological treatments/interventions that have anti‐inflammatory effects are also discussed. Despite the increasing attention given to the inflammatory pathology of PTSD, there remains much to be elucidated, including more detailed mechanisms of inflammation, potential usefulness of inflammatory biomarkers as diagnostic and prognostic markers, and efficacy of novel treatment strategies targeting inflammation.

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“…There was no evidence of the drug being abused, despite 91% of the participants meeting criteria for marijuana dependence prior to incarceration. Last, in a small randomized placebo-controlled cross-over study, male Canadian military personnel (N = 10) received 0.5 mg nabilone or placebo (maximum dose 3.0 mg) for 7 weeks, followed by a 2-week washout period and 7 weeks of the cross-over treatment (Jetly, Heber, Fraser, & Boisvert, 2015). It should be noted that, while not outcome studies, longitudinal naturalistic investigations examining the association of marijuana use with PTSD symptom severity have also been reported.…”

Section: Available Outcome Data On Marijuana and Other Cannabinoids Fmentioning

confidence: 99%

Marijuana and other cannabinoids as a treatment for posttraumatic stress disorder: A literature review

et al. 2017

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Posttraumatic stress disorder (PTSD) is common in the general population, yet there are limitations to the effectiveness, tolerability, and acceptability of available first-line interventions. We review the extant knowledge on the effects of marijuana and other cannabinoids on PTSD. Potential therapeutic effects of these agents may largely derive from actions on the endocannabinoid system and we review major animal and human findings in this area. Preclinical and clinical studies generally support the biological plausibility for cannabinoids' potential therapeutic effects, but underscore heterogeneity in outcomes depending on dose, chemotype, and individual variation. Treatment outcome studies of whole plant marijuana and related cannabinoids on PTSD are limited and not methodologically rigorous, precluding conclusions about their potential therapeutic effects. Reported benefits for nightmares and sleep (particularly with synthetic cannabinoid nabilone) substantiate larger controlled trials to determine effectiveness and tolerability. Of concern, marijuana use has been linked to adverse psychiatric outcomes, including conditions commonly comorbid with PTSD such as depression, anxiety, psychosis, and substance misuse. Available evidence is stronger for marijuana's harmful effects on the development of psychosis and substance misuse than for the development of depression and anxiety. Marijuana use is also associated with worse treatment outcomes in naturalistic studies, and with maladaptive coping styles that may maintain PTSD symptoms. Known risks of marijuana thus currently outweigh unknown benefits for PTSD. Although controlled research on marijuana and other cannabinoids' effects on PTSD remains limited, rapid shifts in the legal landscape may now enable such studies, potentially opening new avenues in PTSD treatment research.

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The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study

Cited by 253 publications

References 13 publications

Endocannabinoid concentrations in hair are associated with PTSD symptom severity

Endocannabinoid concentrations in hair are associated with PTSD symptom severity

Inflammation and post‐traumatic stress disorder

Marijuana and other cannabinoids as a treatment for posttraumatic stress disorder: A literature review

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