Nightmares and the Cannabinoids.

“The cannabinoids, δ9 tetrahydrocannabinol and its analogue, nabilone, have been found to reliably attenuate the intensity and frequency of post-traumatic nightmares.

This essay examines how a traumatic event is captured in the mind after just a single exposure and repeatedly replicated during the nights that follow.

The adaptive neurophysiological, endocrine and inflammatory changes that are triggered by the trauma and that alter personality and behavior are surveyed. These adaptive changes, once established, can be difficult to reverse. But cannabinoids, uniquely, have been shown to interfere with all of these post-traumatic somatic adaptations.

While cannabinoids can suppress nightmares and other symptoms of the post-traumatic stress disorder, they are not a cure. There may be no cure.

The cannabinoids may best be employed, alone, but more likely in conjunction with other agents, in the immediate aftermath of a trauma to mitigate or even abort the metabolic changes which are set in motion by the trauma and which may permanently alter the reactivity of the nervous system. Steps in this direction have already been taken.”

https://www.ncbi.nlm.nih.gov/pubmed/31934840

http://www.eurekaselect.com/178302/article

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Cannabidiol-induced panicolytic-like effects and fear-induced antinociception impairment: the role of the CB1 receptor in the ventromedial hypothalamus.

Image result for Springer Link“The behavioural effects elicited by chemical constituents of Cannabis sativa, such as cannabidiol (CBD), on the ventromedial hypothalamus (VMH) are not well understood. There is evidence that VMH neurons play a relevant role in the modulation of unconditioned fear-related defensive behavioural reactions displayed by laboratory animals.

OBJECTIVES:

This study was designed to explore the specific pattern of distribution of the CB1 receptors in the VMH and to investigate the role played by this cannabinoid receptor in the effect of CBD on the control of defensive behaviours and unconditioned fear-induced antinociception.

METHODS:

A panic attack-like state was triggered in Wistar rats by intra-VMH microinjections of N-methyl-D-aspartate (NMDA). One of three different doses of CBD was microinjected into the VMH prior to local administration of NMDA. In addition, the most effective dose of CBD was used after pre-treatment with the CB1 receptor selective antagonist AM251, followed by NMDA microinjections in the VMH.

RESULTS:

The morphological procedures demonstrated distribution of labelled CB1 receptors on neuronal perikarya situated in dorsomedial, central and ventrolateral divisions of the VMH. The neuropharmacological approaches showed that both panic attack-like behaviours and unconditioned fear-induced antinociception decreased after intra-hypothalamic microinjections of CBD at the highest dose (100 nmol). These effects, however, were blocked by the administration of the CB1 receptor antagonist AM251 (100 pmol) in the VMH.

CONCLUSION:

These findings suggest that CBD causes panicolytic-like effects and reduces unconditioned fear-induced antinociception when administered in the VMH, and these effects are mediated by the CB1 receptor-endocannabinoid signalling mechanism in VMH.”

https://www.ncbi.nlm.nih.gov/pubmed/31919563

https://link.springer.com/article/10.1007%2Fs00213-019-05435-5

“panicolytic: That reduces the flight reflex in animals when faced with danger. Any drug that has this effect.” https://en.wiktionary.org/wiki/panicolytic

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Cannabinoids as an Emerging Therapy for Posttraumatic Stress Disorder and Substance Use Disorders.

Related image “Posttraumatic Stress Disorder (PTSD) is a leading psychiatric disorder that mainly affects military and veteran populations but can occur in anyone affected by trauma. PTSD treatment remains difficult for physicians because most patients with PTSD do not respond to current pharmacological treatment. Psychotherapy is effective, but time consuming and expensive. Substance use disorder is often concurrent with PTSD, which leads to a significant challenge for PTSD treatment.

Cannabis has recently received widespread attention for the potential to help many patient populations. Cannabis has been reported as a coping tool for patients with PTSD and preliminary legalization data indicate Cannabis use may reduce the use of more harmful drugs, such as opioids. Rigorous clinical studies of Cannabis could establish whether Cannabis-based medicines can be integrated into treatment regimens for both PTSD and substance use disorder patients.”

https://www.ncbi.nlm.nih.gov/pubmed/31895187

https://insights.ovid.com/crossref?an=00004691-202001000-00005

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Use of cannabidiol in anxiety and anxiety-related disorders.

“Cannabidiol (CBD) has a proposed novel role in the management of anxiety owing to its actions on the endocannabinoid system.

The purpose of this systematic review was to evaluate the current evidence on the safety and efficacy of CBD in anxiety and anxiety-related disorders.

RESULTS:

Eight articles were included in the review: 6 small, randomized controlled trials; 1 case series; and 1 case report. These studies examined the role of CBD in the anxiety response of healthy volunteers; in generalized anxiety disorder; in social anxiety disorder; and in the anxiety component of posttraumatic stress syndrome. No articles that evaluated CBD in panic disorder, specific phobia, separation anxiety, and obsessive-compulsive disorder were identified. In the studies, CBD was administered orally as a capsule or as a sublingual spray and as either monotherapy or adjunctive therapy. Doses varied widely, with studies employing fixed CBD doses ranging from 6 mg to 400 mg per dose. Various anxiety assessment scales were used in the studies to assess efficacy, with CBD demonstrating improved clinical outcomes among the instruments. In general, CBD was well-tolerated and associated with minimal adverse effects, with the most commonly noted adverse effects being fatigue and sedation.

CONCLUSION:

CBD has a promising role as alternative therapy in the management of anxiety disorders. However, more studies with standardized approaches to dosing and clinical outcome measurements are needed to determine the appropriate dosing strategy for CBD and its place in therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/31866386

https://www.japha.org/article/S1544-3191(19)30514-X/fulltext

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Cannabinoids and the endocannabinoid system in anxiety, depression, and dysregulation of emotion in humans.

Image result for ovid journal“This review is to summarize most recent evidence published in the last 18 months on medical and recreational use of cannabis and cannabinoids in relation to anxiety, depression (unipolar and bipolar), and dysregulation of emotions as part of posttraumatic stress disorders (PTSD) and emotionally instable personality disorders.

It also covers the investigation of endocannabinoids as potential biomarkers in these conditions. This is important with increasing medicinal use of cannabinoids and growing social tolerance towards recreational cannabis use.

RECENT FINDINGS:

There is some recent evidence suggesting cannabinoids, cannabidiol or cannabidiol-enriched cannabis preparations have anxiolytic properties. In addition, depression may be worsened by cannabis use, however, randomized controlled trials (RCT) are lacking.

New evidence also suggests that cannabidiol or cannabidiol-enriched cannabis use for PTSD and emotion regulation can induce hyporesponse to fear and stress. Further, several lines of evidence point to the endocannabinoid system as a key player in some of the reviewed disorders, in particular anxiety and PTSD.

SUMMARY:

The most recent evidence for a therapeutic use of cannabinoids in the reviewed conditions is weak and lacking well designed RCTs. However, there is some indication of the role of the endocannabinoid system in these conditions that warrant further studies.”

https://www.ncbi.nlm.nih.gov/pubmed/31714262

https://insights.ovid.com/crossref?an=00001504-900000000-99165

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Does cannabis use modify the effect of post-traumatic stress disorder on severe depression and suicidal ideation? Evidence from a population-based cross-sectional study of Canadians

Image result for journal of psychopharmacology“Post-traumatic stress disorder sharply increases the risk of depression and suicide. Individuals living with post-traumatic stress disorder frequently use cannabis to treat associated symptoms.

We sought to investigate whether cannabis use modifies the association between post-traumatic stress disorder and experiencing a major depressive episode or suicidal ideation.

This study provides preliminary epidemiological evidence that cannabis use may contribute to reducing the association between post-traumatic stress disorder and severe depressive and suicidal states. There is an emerging need for high-quality experimental investigation of the efficacy of cannabis/cannabinoids for the treatment of post-traumatic stress disorder.”

https://www.ncbi.nlm.nih.gov/pubmed/31684805

https://journals.sagepub.com/doi/10.1177/0269881119882806

“Cannabis could help alleviate depression and suicidality among people with PTSD” https://medicalxpress.com/news/2019-11-cannabis-alleviate-depression-suicidality-people.html

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Endocannabinoid System Alterations in Posttraumatic Stress Disorder: A Review of Developmental and Accumulative Effects of Trauma.

 Image result for sage journals chronic stress“The role of the endocannabinoid system in stress-related psychiatric symptoms has been investigated in many animal and human studies.

Although most of these studies consistently report long-lasting effects of prolonged stress and trauma on the endocannabinoid system, the nature and direction of these changes are controversial.

We reviewed the available preclinical and clinical studies investigating the endocannabinoid system alterations long after chronic stress and trauma.

We propose that the effects of prolonged stress or trauma on the endocannabinoid system are different based on the developmental age of subjects at the time of experiencing the trauma and its repetitiveness and accumulative effects.

The current literature consistently demonstrates decreased levels of endocannabinoid ligands and receptors if the trauma occurs in childhood, whereas decreased levels of endocannabinoid ligands and increased levels of cannabinoid receptors are reported when trauma has happened in adulthood.

It is important to note that these changes are region-specific in the brain and also there are important sex differences, which are beyond the scope of this review.”

https://www.ncbi.nlm.nih.gov/pubmed/31660473

“More studies are needed to compare the effects of childhood and adulthood trauma, with or without PTSD presentations, on the eCB system. These studies would have important clinical implications, not only for individuals with trauma and PTSD who commonly have comorbid recreational cannabis use, and medical marijuana users with PTSD being one of its main indicators but also for studies investigating the potential therapeutic use of cannabinoids and eCB enhancers in PTSD treatment.”

https://journals.sagepub.com/doi/10.1177/2470547019864096

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A time-dependent contribution of hippocampal CB1, CB2, and PPARγ receptors to cannabidiol-induced disruption of fear memory consolidation.

Publication cover image“Preclinical studies have shown that cannabidiol (CBD) mitigates fear memories by facilitating their extinction or interfering with their generalization and reconsolidation. The brain regions and mechanisms underlying these effects, and their temporal window, are still poorly understood. The present paper aimed at investigating related questions in the dorsal hippocampus (DH) during contextual fear consolidation.

KEY RESULTS:

CBD impaired memory consolidation when given immediately or 1 h after fear conditioning, but not after 3 h. The DH Arc expression was reduced by systemic CBD treatment in both cases. Immediately after fear conditioning, the CBD effect was abolished by CB1 or CB2 receptor blockade, partly reduced by 5-HT1A or A2A antagonism, and remained unchanged after antagonism of PPARγ receptors. 1 h after fear conditioning, the CBD effect was only prevented by PPARγ receptor antagonism. Besides, the FAAH inhibition impaired memory consolidation when URB597 was infused immediately, but not 1 hour after fear conditioning.

CONCLUSIONS AND IMPLICATIONS:

CBD disrupts memory consolidation up to 1 h after fear conditioning, allowing an extended window of opportunity to mitigate aversive memories after their acquisition. The results suggest time-dependent participation of DH anandamide, CB1, CB2, and PPARγ receptors in this process.”

https://www.ncbi.nlm.nih.gov/pubmed/31648363

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14895

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Cannabinoid receptor type 1 modulates the effects of polyunsaturated fatty acids on memory of stressed rats.

 Publication Cover“Memory and GABAergic activity in the hippocampus of stressed rats improve after n-3 polyunsaturated fatty acid (PUFA) supplementation.

On the other hand, cannabinoid receptor type 1 (CB1) strongly regulates inhibitory neurotransmission in the hippocampus. Speculation about a possible relation between stress, endocannabinoids, and PUFAs.

Here, we examined whether the effects of PUFAs on memory of chronically stressed rats depends on pharmacological manipulation of CB1 receptors.

Memory improved in the stressed rats that were treated with AM251 and/or n-3 PUFAs. Supplementation with n-6 PUFAs did not affect memory of stressed rats, but co-treatment with AM251 improved it, while co-treatment with WIN55,212-2 did not affect memory.

Our results demonstrate that activity of the CB1 receptors may modulate the effects of PUFAs on memory of stressed rats. This study suggests that endocannabinoids and PUFAs can both become a singular system by being self-regulated in limbic areas, so they control the effects of stress on the brain.”

https://www.ncbi.nlm.nih.gov/pubmed/31637966

https://www.tandfonline.com/doi/abs/10.1080/1028415X.2019.1659561?journalCode=ynns20

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Neuropeptide Y and cannabinoids interaction in the amygdala after exposure to shock and reminders model of PTSD.

Neuropharmacology“Modulation of cannabinoid and neuropeptide Y (NPY) receptors may offer therapeutic benefits for post-traumatic stress disorder (PTSD).

In this study, we aimed to investigate the functional interaction between these systems in the basolateral amygdala (BLA) in a rat model of PTSD.

The findings suggest that the functional interaction between the eCB and NPY1 systems is complex and provide a rationale for exploring novel therapeutic strategies that target the cannabinoid and NPY systems for stress-related diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/31622603

https://www.sciencedirect.com/science/article/pii/S0028390819303661?via%3Dihub

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