The Use of a Synthetic Cannabinoid in the Management of Treatment‐Resistant Nightmares in Posttraumatic Stress Disorder (PTSD)

Fraser, George A.

doi:10.1111/j.1755-5949.2008.00071.x

Cited by 252 publications

(168 citation statements)

References 22 publications

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“…Although more work is needed to clarify the functional relationship between CCK and Cnr1, the results of this study suggest that dysfunction in a putative Cnr1-CCKBR interaction might be critical to understand the etiology, and ultimately treatment, of fearrelated disorders. Indeed, a synthetic cannabinoid has recently been shown to reduce treatment-resistant nightmares in a majority of PTSD patients (Fraser, 2009). These studies show promise that the use of CCKBR antagonists alone, or in combination with cannabinoid-targeted treatments, may prove to be ameliorative with exposure-based psychotherapy.…”

Section: Discussionmentioning

confidence: 90%

Interaction between the Cholecystokinin and Endogenous Cannabinoid Systems in Cued Fear Expression and Extinction Retention

Bowers

Ressler

2014

Neuropsychopharmacol

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Post-traumatic stress disorder (PTSD) is thought to develop, in part, from improper inhibition of fear. Accordingly, one of the most effective treatment strategies for PTSD is exposure-based psychotherapy. Ideally, neuroscience would inform adjunct therapies that target the neurotransmitter systems involved in extinction processes. Separate studies have implicated the cholecystokinin (CCK) and endocannabinoid systems in fear; however, there is a high degree of anatomical colocalization between the cannabinoid 1 receptor (Cnr1) and CCK in the basolateral amygdala (BLA), a brain region critical for emotion regulation. Although most research has focused on GABA and GABAergic plasticity as the mechanism by which Cnr1 mediates fear inhibition, we hypothesize that a functional interaction between Cnr1 and CCKB receptor (CCKBR) is critical for fear extinction processes. In this study, systemic pharmacological manipulation of the cannabinoid system modulated cued fear expression in C57BL/6J mice after consolidation of auditory fear conditioning. Knockout of the CCKBR, however, had no effect on fear-or anxiety-like behaviors. Nonetheless, administration of a Cnr1 antagonist increased freezing behavior during a cued fear expression test in wild-type subjects, but had no effect on freezing behavior in CCKBR knockout littermates. In addition, we found that Cnr1-positive fibers form perisomatic clusters around CCKBR-positive cell bodies in the BLA. These CCKBR-positive cells comprise a molecularly heterogenous population of excitatory and inhibitory neurons. These findings provide novel evidence that Cnr1 contributes to cued fear expression via an interaction with the CCK system. Dysfunctional Cnr1-CCKBR interactions might contribute to the etiology of, or result from, fear-related psychiatric disease.

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Section: Discussionmentioning

confidence: 90%

Interaction between the Cholecystokinin and Endogenous Cannabinoid Systems in Cued Fear Expression and Extinction Retention

Bowers

Ressler

2014

Neuropsychopharmacol

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“…The present finding that the hippocampal endocannabinoid system is involved in mediating GC effects on memory retrieval impairment could aid in the development of non-GC-based therapies for PTSD. Although clinical studies have not yet investigated interactions between these two stress systems, recent findings indicate that administration of the synthetic cannabinoid nabilone to PTSD patients resulted in a highly comparable reduction of treatment-resistant daytime flashbacks and nightmares (56). Moreover, PTSD is often associated with high levels of cannabis consumption (57), which might be related, in part, to an inadequate activation of the endogenous GC and endocannabinoid systems in these patients (58).…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory

Atsak

Hauer

Campolongo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

123

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There is extensive evidence that glucocorticoid hormones impair the retrieval of memory of emotionally arousing experiences. Although it is known that glucocorticoid effects on memory retrieval impairment depend on rapid interactions with arousalinduced noradrenergic activity, the exact mechanism underlying this presumably nongenomically mediated glucocorticoid action remains to be elucidated. Here, we show that the hippocampal endocannabinoid system, a rapidly activated retrograde messenger system, is involved in mediating glucocorticoid effects on retrieval of contextual fear memory. Systemic administration of corticosterone (0.3-3 mg/kg) to male Sprague-Dawley rats 1 h before retention testing impaired the retrieval of contextual fear memory without impairing the retrieval of auditory fear memory or directly affecting the expression of freezing behavior. Importantly, a blockade of hippocampal CB1 receptors with AM251 prevented the impairing effect of corticosterone on retrieval of contextual fear memory, whereas the same impairing dose of corticosterone increased hippocampal levels of the endocannabinoid 2-arachidonoylglycerol. We also found that antagonism of hippocampal β-adrenoceptor activity with local infusions of propranolol blocked the memory retrieval impairment induced by the CB receptor agonist WIN55,212-2. Thus, these findings strongly suggest that the endocannabinoid system plays an intermediary role in regulating rapid glucocorticoid effects on noradrenergic activity in impairing memory retrieval of emotionally arousing experiences.cannabinoid receptor | norepinephrine | emotional arousal | fear conditioning | posttraumatic stress disorder I t is well-established that glucocorticoid (GC) hormones, released from the adrenal cortex during stressful episodes, can modulate different memory processes (1-4). Although most studies focused on GC effects on the acquisition and consolidation of memory, extensive evidence also indicates that acutely elevated GC levels at the time of retention testing impair the retrieval of memory of spatial and contextual training (5-9). Because a glucocorticoid receptor (GR) agonist infused into the hippocampus before retention induces comparable memory retrieval impairment (10, 11), such findings suggest that GC effects on memory retrieval depend, at least in part, on activation of GRs in the hippocampus. Findings of studies of human subjects are consistent with the findings of animal studies and indicate that exogenous GC administration or exposure to a psychosocial stressor shortly before retention testing impairs retrieval of declarative (mostly episodic) information (7, 12, 13) and reduces hippocampal activity (14). Moreover, previous findings indicate that emotionally arousing information is especially sensitive to the retrieval-impairing effects of GCs (8) and that emotional arousal during the test situation enables GC effects on memory retrieval (15). Findings of recent clinical studies suggest that the administration of stress doses of GCs may have therapeutic v...

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“…The cannabinoid receptors type 1 play a role in the extinction of aversive memories, reducing fear and anxiety. The endocannabinoid system is also involved in the mechanisms of sleep regulation [25][26][27]. For Editorial Neurobiology of suicidal behavior in post-traumatic stress disorder example, it has been reported that the endocannabinoid anandamide increased adenosine in the basal forebrain and increased sleep [27].…”

Section: Leo Shermentioning

confidence: 99%

“…The endocannabinoid system is formed by the cannabinoid receptors and endogenous ligands [25,26]. The cannabinoid receptors type 1 play a role in the extinction of aversive memories, reducing fear and anxiety.…”

Section: Leo Shermentioning

confidence: 99%

Neurobiology of suicidal behavior in post-traumatic stress disorder

Sher

2010

Expert Review of Neurotherapeutics

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The Use of a Synthetic Cannabinoid in the Management of Treatment‐Resistant Nightmares in Posttraumatic Stress Disorder (PTSD)

Cited by 252 publications

References 22 publications

Interaction between the Cholecystokinin and Endogenous Cannabinoid Systems in Cued Fear Expression and Extinction Retention

Interaction between the Cholecystokinin and Endogenous Cannabinoid Systems in Cued Fear Expression and Extinction Retention

Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory

Neurobiology of suicidal behavior in post-traumatic stress disorder

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