Category Archives: Post-Traumatic Stress Disorder (PTSD)

Cannabinoid interventions for PTSD: Where to next?

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Progress in Neuro-Psychopharmacology and Biological Psychiatry

“Cannabinoids are a promising method for pharmacological treatment of post-traumatic stress disorder (PTSD). Despite considerable research devoted to the effect of cannabinoid modulation on PTSD symptomology, there is not a currently agreed way by which the cannabinoid system should be targeted in humans. In this review, we present an overview of recent research identifying neurological pathways by which different cannabinoid-based treatments may exert their effects on PTSD symptomology. We evaluate the strengths and weaknesses of each of these different approaches, including recent challenges presented to favourable options such as fatty acid amide hydrolase (FAAH) inhibitors. This article makes the strengths and challenges of different potential cannabinoid treatments accessible to psychological researchers interested in cannabinoid therapeutics and aims to aid selection of appropriate tools for future clinical trials.”

https://www.ncbi.nlm.nih.gov/pubmed/30946942

https://www.sciencedirect.com/science/article/pii/S027858461930034X?via%3Dihub

Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies.

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“Aversive learning and memory are essential to cope with dangerous and stressful stimuli present in an ever-changing environment. When this process is dysfunctional, however, it is associated with posttraumatic stress disorder (PTSD). The endocannabinoid (eCB) system has been implicated in synaptic plasticity associated with physiological and pathological aversive learning and memory.

OBJECTIVE AND METHODS:

The objective of this study was to review and discuss evidence on how and where in the brain genetic or pharmacological interventions targeting the eCB system would attenuate aversive/traumatic memories through extinction facilitation in laboratory animals and humans. The effect size of the experimental intervention under investigation was also calculated.

RESULTS:

Currently available data indicate that direct or indirect activation of cannabinoid type-1 (CB1) receptor facilitates the extinction of aversive/traumatic memories. Activating CB1 receptors around the formation of aversive/traumatic memories or their reminders can potentiate their subsequent extinction. In most cases, the effect size has been large (Cohen’s d ≥ 1.0). The brain areas responsible for the above mentioned effects include the medial prefrontal cortex, amygdala, and/or hippocampus. The potential role of cannabinoid type-2 (CB2) receptors in extinction learning is now under investigation.

CONCLUSION:

Drugs augmenting the brain eCB activity can temper the impact of aversive/traumatic experiences by diverse mechanisms depending on the moment of their administration. Considering the pivotal role the extinction process plays in PTSD, the therapeutic potential of these drugs is evident. The sparse number of clinical trials testing these compounds in stress-related disorders is a gap in the literature that needs to be addressed.”

https://www.ncbi.nlm.nih.gov/pubmed/30604182

https://link.springer.com/article/10.1007%2Fs00213-018-5127-x

Social isolation as a promising animal model of PTSD comorbid suicide: neurosteroids and cannabinoids as possible treatment options.

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Progress in Neuro-Psychopharmacology and Biological Psychiatry

“Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by drastic alterations in mood, emotions, social abilities and cognition. Notably, one aspect of PTSD, particularly in veterans, is its comorbidity with suicide.

Elevated aggressiveness predicts high-risk to suicide in humans and despite the difficulty in reproducing a complex human suicidal behavior in rodents, aggressive behavior is a well reproducible behavioral trait of suicide. PTSD animal models are based on a peculiar phenotype, including exaggerated fear memory, anxiety- and depressive-like behaviors associated with neurochemical dysregulations in emotional brain circuitry.

The endocannabinoid and the neurosteroid systems regulate emotions and stress responses, and recent evidence shows these two systems are interrelated and critically compromised in neuropsychiatric disorders. For instance, levels of the neurosteroid, allopregnanolone, as well as those of the endocannabinoids, anandamide and its congener, palmitoylethanolamide are decreased in PTSD.

Similarly, the endocannabinoid system and neurosteroid biosynthesis are altered in suicidal individuals.

Selective serotonin reuptake inhibitors (SSRIs), the only FDA-approved treatments for PTSD and depression, fail to help half of the treatment-seeking patients. This highlights the need for developing biomarker-based efficient therapies. One promising hypothesis points to stimulation of allopregnanolone biosynthesis as a valid end-point to predict treatment response in PTSD patients.

This review highlights running findings on the role of the endocannabinoid and neurosteroid systems in PTSD and suicidal behavior both in a preclinical and clinical perspective. A specific focus is given to predictive PTSD/suicide animal models. Ultimately, we discuss the idea that disruption of neurosteroid and endocannabinoid biosynthesis may offer novel promising biomarker candidates to develop new treatments for PTSD and, perhaps, suicidal behavior.”

https://www.ncbi.nlm.nih.gov/pubmed/30586627

https://www.sciencedirect.com/science/article/pii/S0278584618305839?via%3Dihub

Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series.

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“Cannabidiol (CBD) is a non-psychotomimetic cannabinoid compound that is found in plants of the genus Cannabis. Preclinical research has suggested that CBD may have a beneficial effect in rodent models of post-traumatic stress disorder (PTSD). This effect is believed to be due to the action of CBD on the endocannabinoid system. CBD has seen a recent surge in research regarding its potential value in a number of neuro-psychiatric conditions. This is the first study to date examining the clinical benefit of CBD for patients with PTSD.

RESULTS:

From the total sample of 11 patients, 91% (n = 10) experienced a decrease in PTSD symptom severity, as evidenced by a lower PCL-5 score at 8 weeks than at their initial baseline. The mean total PCL-5 score decreased 28%, from a mean baseline score of 51.82 down to 37.14, after eight consecutive weeks of treatment with CBD. CBD was generally well tolerated, and no patients discontinued treatment due to side effects.

CONCLUSIONS:

Administration of oral CBD in addition to routine psychiatric care was associated with PTSD symptom reduction in adults with PTSD. CBD also appeared to offer relief in a subset of patients who reported frequent nightmares as a symptom of their PTSD. Additional clinical investigation, including double-blind, placebo-controlled trials, would be necessary to further substantiate the response to CBD that was observed in this study.”

https://www.ncbi.nlm.nih.gov/pubmed/30543451

https://www.liebertpub.com/doi/10.1089/acm.2018.0437

Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age.

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“Among the many cannabinoids in the cannabis plant, cannabidiol (CBD) is a compound that does not produce the typical subjective effects of marijuana.

The aim of the present review is to describe the main advances in the development of the experimental and clinical use of cannabidiol CBD in neuropsychiatry.

CBD was shown to have anxiolytic, antipsychotic and neuroprotective properties. In addition, basic and clinical investigations on the effects of CBD have been carried out in the context of many other health conditions, including its potential use in epilepsy, substance abuse and dependence, schizophrenia, social phobia, post-traumatic stress, depression, bipolar disorder, sleep disorders, and Parkinson.

CBD is an useful and promising molecule that may help patients with a number of clinical conditions. Controlled clinical trials with different neuropsychiatric populations that are currently under investigation should bring important answers in the near future and support the translation of research findings to clinical settings.”

https://www.ncbi.nlm.nih.gov/pubmed/30298064

https://www.frontiersin.org/articles/10.3389/fimmu.2018.02009/full

Acute foot-shock stress decreased seizure susceptibility against pentylenetetrazole-induced seizures in mice: Interaction between endogenous opioids and cannabinoids.

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“Stressful conditions affect the brain’s neurotransmission and neural pathways that are involved in seizure susceptibility. Stress alters the intensity and/or frequency of seizures.

Although evidence indicates that chronic stress exerts proconvulsant effects and acute stress has anticonvulsant properties, the underlying mechanisms which mediate these effects are not well understood.

In the present study, we assessed the role of endogenous opioids, endocannabinoids, as well as functional interaction between opioid and cannabinoid systems in the anticonvulsant effects of acute foot-shock stress (FSS) against pentylenetetrazole (PTZ)-induced seizures in mice.

CONCLUSIONS:

Opioid and cannabinoid systems are involved in the anticonvulsant effects of acute FSS, and these neurotransmission systems interact functionally in response to acute FSS.”

https://www.ncbi.nlm.nih.gov/pubmed/30170259

https://www.epilepsybehavior.com/article/S1525-5050(17)30777-1/fulltext

A Brief Background on Cannabis: From Plant to Medical Indications.

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 Ingenta Connect

“Cannabis has been used as a medicinal plant for thousands of years.

As a result of centuries of breeding and selection, there are now over 700 varieties of cannabis that contain hundreds of compounds, including cannabinoids and terpenes.

Cannabinoids are fatty compounds that are the main biological active constituents of cannabis. Terpenes are volatile compounds that occur in many plants and have distinct odors.

Cannabinoids exert their effect on the body by binding to receptors, specifically cannabinoid receptors types 1 and 2. These receptors, together with endogenous cannabinoids and the systems for synthesis, transport, and degradation, are called the Endocannabinoid System.

The two most prevalent and commonly known cannabinoids in the cannabis plant are delta-9-tetrahydrocannabinol (THC) and cannabidiol.

The speed, strength, and type of effects of cannabis vary based on the route of administration. THC is rapidly distributed through the body to fatty tissues like the brain and is metabolized by the cytochrome P450 system to 11-hydroxy-THC, which is also psychoactive.

Cannabis and cannabinoids have been indicated for several medical conditions.

There is evidence of efficacy in the symptomatic treatment of nausea and vomiting, pain, insomnia, post-traumatic stress disorder, anxiety, loss of appetite, Tourette’s syndrome, and epilepsy. Cannabis has also been associated with treatment for glaucoma, Huntington’s Disease, Parkinson’s Disease, and dystonia, but there is not good evidence to support its efficacy. Side effects of cannabis include psychosis and anxiety, which can be severe.

Here, we provided a summary of the history of cannabis, its pharmacology, and its medical uses.”

https://www.ncbi.nlm.nih.gov/pubmed/30139415

http://www.ingentaconnect.com/content/aoac/jaoac/pre-prints/content-jaoac_180208;jsessionid=jbg0paav7wra.x-ic-live-03

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

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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. Preclinical studies in different rodent behavioral models have shown that CBD can both facilitate the extinction of aversive memories and block their reconsolidation, possibly through potentialization of the eCB system.

These results, combined with the currently available pharmacological treatments for PTSD being limited, necessitated testing CBD use with the same therapeutic purpose in humans as well.

Indeed, as observed in rodents, recent studies have confirmed the ability of CBD to alter important aspects of aversive memories in humans and promote significant improvements in the symptomatology of PTSD.

The goal of this review was to highlight the potential of CBD as a treatment for disorders related to inappropriate retention of aversive memories, by assessing evidence from preclinical to human experimental studies.”

https://www.ncbi.nlm.nih.gov/pubmed/30087591

https://www.frontiersin.org/articles/10.3389/fnins.2018.00502/full

Modulation of the endocannabinoid system by sex hormones: Implications for Posttraumatic Stress Disorder.

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Neuroscience & Biobehavioral Reviews

“The endocannabinoid system is an increasingly recognised pharmacological target for treating stress and anxiety disorders, including post-traumatic stress disorder (PTSD). Recent preclinical developments have implicated the endocannabinoid system in stress responses, emotional memories and fear extinction, all critical to PTSD aetiology. However, preclinical research in endocannabinoid biology has neglected the influential role of sex hormone differences on PTSD symptomology, which is particularly important given that PTSD is twice as common in women as in men. In this review, we compile and consider the evidence that the endocannabinoid system is influenced by ovarian hormones, with application to stress disorders such as PTSD. It is clear that therapeutic modulation of the endocannabinoid system needs to be approached with awareness of ovarian hormonal influences, and knowledge of these influences may enhance treatment outcomes for female PTSD populations.”

https://www.ncbi.nlm.nih.gov/pubmed/30017748
https://www.sciencedirect.com/science/article/pii/S0149763418301052?via%3Dihub

Role of endocannabinoids in the hippocampus and amygdala in emotional memory and plasticity.

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“Posttraumatic stress disorder (PTSD) is characterized by the reexperiencing of a traumatic event and is associated with slower extinction of fear responses.

Impaired extinction of fearful associations to trauma-related cues may interfere with treatment response, and extinction deficits may be premorbid risk factors for the development of PTSD.

We examined the effects of exposure to a severe footshock followed by situational reminders (SRs) on extinction, plasticity, and endocannabinoid (eCB) content and activity in the hippocampal CA1 area and basolateral amygdala (BLA).

The findings suggest that targeting the eCB system before extinction may be beneficial in fear memory attenuation and these effects may involve metaplasticity in the CA1 and BLA.”

https://www.ncbi.nlm.nih.gov/pubmed/29977073

https://www.nature.com/articles/s41386-018-0135-4