Targeting the endocannabinoid system to treat haunting traumatic memories

“One of the core symptoms in post-traumatic stress disorder (PTSD) is the traumatic memory that constantly haunts the patient.

An increasing body of evidence points to the endocannabinoid (eCB) system as a key system in the regulation of emotionality and memory.

Hence, eCB enhancers may be the ideal pharmacological treatment for PTSD…

…eCBs have an essential role in maintaining emotional homeostasis and in modulating memory consolidation, retrieval and extinction.

Hence, the authors concluded that eCBs could be an ideal drug to treat PTSD by addressing both the emotional and cognitive aspects of the disorder.

Indeed, accumulating data from both clinical and pre-clinical studies suggest that targeting the eCB system may benefit PTSD.

Several studies support the self-medication hypothesis explanation for cannabis use to cope with PTSD symptoms.

To conclude, the eCB system may be a useful target for treating both the cognitive and emotional features of PTSD…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776936/

http://www.thctotalhealthcare.com/category/post-traumatic-stress-disorder-ptsd/

Seizing an opportunity for the endocannabinoid system.

“Exogenous cannabinoids can limit seizures and neurodegeneration, and their actions are largely mimicked by endogenous cannabinoids (endocannabinoids).

Endocannabinoids are mobilized by epileptiform activity and in turn influence this activity by inhibiting synaptic transmission; both excitatory and some inhibitory synapses can be suppressed, leading to potentially complex outcomes.

Moreover, the endocannabinoid system is not a fixed entity, and its strength can be enhanced or reduced.

Endocannabinoids and their receptors are altered by epileptic seizures in ways that can reduce the efficacy of both exogenous and endogenous cannabinoids in sometimes unexpected ways.”

http://www.ncbi.nlm.nih.gov/pubmed/25346637

http://www.thctotalhealthcare.com/category/epilepsy-2/

Endocannabinoids, Related Compounds and Their Metabolic Routes.

“Endocannabinoids are lipid mediators able to bind to and activate cannabinoid receptors, the primary molecular targets responsible for the pharmacological effects of the Δ9-tetrahydrocannabinol.

These bioactive lipids belong mainly to two classes of compounds: N-acylethanolamines and acylesters, being N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, their main representatives.

During the last twenty years, an ever growing number of fatty acid derivatives (endocannabinoids and endocannabinoid-like compounds) have been discovered and their activities biological is the subject of intense investigations.

Here, the most recent advances, from a therapeutic point of view, on endocannabinoids, related compounds, and their metabolic routes will be reviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/25347455

Evaluation of the tolerability and efficacy of Sativex in multiple sclerosis.

“Refractory spasticity, central neuropathic pain and bladder dysfunction are common clinical problems in patients with multiple sclerosis (MS). None of the currently available oral medications has proven to be reliably effective and can be limited by toxicity.

Cannabinoids have shown therapeutic effects on those MS-associated symptoms.

Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) Sativex (nabiximols) is an oromucosal spray formulation that contains THC and CBD in an approximate 1:1 ratio and is described as an endocannabinoid system modulator.

The efficacy of THC/CBD on MS-associated spasticity, pain and bladder dysfunction has been studied in clinical trials as well as in clinical practice studies. Adverse effects are usually mild or moderate and the low rate of drug discontinuation provides good evidence of long-term tolerability. This article focuses on the pharmacological properties, clinical efficacy and tolerability of THC/CBD in MS patients.”

http://www.ncbi.nlm.nih.gov/pubmed/25331416

Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity nervous pathways.

“Involvement of the endocannabinoid system in pathophysiological mechanisms responsible for spasticity has been demonstrated in animal models of MS…

Evidence indicates that the antispasticity effects of THC:CBD oromucosal spray (Sativex®) are associated with enhanced cortical long-term potentiation.

CB1 receptors, which are associated with movement, postural control, and pain and sensory perception, influence glutamatergic pathways.

THC:CBD oromucosal spray was shown to reverse motor cortex plasticity from long-term depression through long-term potentiation of synaptic transmission, thereby restoring, at least in part, effective corticospinal inputs to spinal circuits.”

http://www.ncbi.nlm.nih.gov/pubmed/25278116

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Cannabinoids Alleviate Experimentally Induced Intestinal Inflammation by Acting at Central and Peripheral Receptors.

“… an attempt to further investigate the role of cannabinoid (CB) system in the pathogenesis of inflammatory bowel diseases…

CONCLUSIONS:

This is the first evidence that central and peripheral CB receptors are responsible for the protective and therapeutic action of cannabinoids in mouse models of colitis.

Our observations provide new insight to CB pharmacology and validate the use of novel ligands AM841 and CB13 as potent tools in CB-related research.”

http://www.ncbi.nlm.nih.gov/pubmed/25275313

Tapping into the endocannabinoid system to ameliorate acute inflammatory flares and associated pain in mouse knee joints.

URB597.svg

“During the progression of rheumatoid arthritis (RA), there are frequent but intermittent flares in which the joint becomes acutely inflamed and painful.

Although a number of drug therapies are currently used to treat RA, their effectiveness is variable and side effects are common.

Endocannabinoids have the potential to ameliorate joint pain and inflammation, but these beneficial effects are limited by their rapid degradation.

One enzyme responsible for endocannabinoid break down is fatty acid amide hydrolase (FAAH). The present study examined whether URB597, a potent and selective FAAH inhibitor, could alter inflammation and pain in a mouse model of acute synovitis.

Conclusions: These results suggest that the endocannabinoid system of the joint can be harnessed to decrease acute inflammatory reactions and the concomitant pain associated with these episodes.”

http://www.ncbi.nlm.nih.gov/pubmed/25260980

http://www.thctotalhealthcare.com/category/rheumatoid-arthritis-2/

Effects of cannabidiol in the treatment of patients with Parkinson’s disease: An exploratory double-blind trial.

“Parkinson’s disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons.

… the endocannabinoid system has emerged as a promising target.

…Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities…”

http://www.ncbi.nlm.nih.gov/pubmed/25237116

http://www.thctotalhealthcare.com/category/parkinsons-disease/

Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxic-ischemic brain injury.

“One of the most important causes of brain injury in the neonatal period is a perinatal hypoxic-ischemic event. This devastating condition can lead to long-term neurological deficits or even death. After hypoxic-ischemic brain injury, a variety of specific cellular mechanisms are set in motion, triggering cell damage and finally producing cell death.

Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury. After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury, various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes.

Among them, the endocannabinoid system emerges as a natural system of neuroprotection.

The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant.

The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury, and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.”

http://www.ncbi.nlm.nih.gov/pubmed/25206720

The endocannabinoid system as a potential therapeutic target for pain modulation.

“Although cannabis has been used for pain management for millennia, very few approved cannabinoids are indicated for the treatment of pain and other medical symptoms.

Cannabinoid therapy re-gained attention only after the discovery of endocannabinoids and fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), the enzymes playing a role in endocannabinoid metabolism.

Nowadays, research has focused on the inhibition of these degradative enzymes and the elevation of endocannabinoid tonus locally; special emphasis is given on multi-target analgesia compounds, where one of the targets is the endocannabinoid degrading enzyme.

In this review, I provide an overview of the current understanding about the processes accounting for the biosynthesis, transport and metabolism of endocannabinoids, and pharmacological approaches and potential therapeutic applications in this area, regarding the use of drugs elevating endocannabinoid levels in pain conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/25207181

http://www.thctotalhealthcare.com/category/pain-2/