Endocannabinoids and acute pain after total knee arthroplasty.

Posted on January 22, 2015 by David

“Osteoarthritis (OA) of the knee is a progressive disease that is associated with inflammation of the joints and lower extremity pain. Total knee arthroplasty (TKA) is a surgical procedure that aims to reduce pain and restore motor function in patients suffering from OA. The immediate postoperative period can be intensely painful leading to extended recovery times including persistent pain.

The endocannabinoid system regulates nociception, and the activation of cannabinoid receptors produces antinociceptive effects in preclinical models of OA…

Taken together, our results are the first to reveal associations between central and peripheral endocannabinoid levels and postoperative pain. This suggests that endocannabinoid metabolism may serve as a target for the development of novel analgesics both for systemic or local delivery into the joint.”

http://www.ncbi.nlm.nih.gov/pubmed/25599456

Proapoptotic effect of endocannabinoids in prostate cancer cells.

Posted on January 22, 2015 by David

“Recent evidence shows that derivatives of Cannabis sativa and its analogs may exert a protective effect against different types of oncologic pathologies.

The purpose of the present study was to detect the presence of cannabinoid receptors (CB1 and CB2) on cancer cells with a prostatic origin and to evaluate the effect of the in vitro use of synthetic analogs…

Based on these results, we suggest that endocannabinoids may be a beneficial option for the treatment of prostate cancer that has become nonresponsive to common therapies.”

http://www.ncbi.nlm.nih.gov/pubmed/25606819

http://www.thctotalhealthcare.com/category/prostate-cancer/

Role of endocannabinoid signalling in the dorsolateral periaqueductal grey in the modulation of distinct panic-like responses.

Posted on January 21, 2015 by David

“Since the cannabinoid CB1 receptor modulates various types of aversive responses, this study tested the hypothesis that enhancement of endocannabinoid signalling in the dorsolateral periaqueductal grey inhibits panic-like reactions in rats…

The present results confirm the anti-aversive property of direct CB1 receptor activation in the dorsolateral periaqueductal grey…

Altogether, these results suggest that anandamide signalling is recruited only under certain types of aversive stimuli.”

http://www.ncbi.nlm.nih.gov/pubmed/25601395

http://www.thctotalhealthcare.com/category/panic-attack/

Cannabinoid CB1 receptors in the dorsal hippocampus and prelimbic medial prefrontal cortex modulate anxiety-like behavior in rats: additional evidence.

Posted on January 18, 2015 by David

“Endocannabinoids (ECBs) such as anandamide (AEA) act by activating cannabinoid type 1 (CB1) or 2 (CB2) receptors. The anxiolytic effect of drugs that facilitate ECB effects is associated with increase in AEA levels in several encephalic areas, including the prefrontal cortex (PFC).

Activation of CB1 receptors by CB1 agonists injected directly into these areas is usually anxiolytic.

However, depending on the encephalic region being investigated and on the stressful experiences, opposite effects were observed, as reported in the ventral HIP. In addition, contradictory results have been reported after CB1 activation in the dorsal HIP (dHIP).

Therefore, in the present paper we have attempted to verify if directly interfering with ECB metabolism/reuptake in the prelimbic (PL) portion of the medial PFC (MPFC) and dHIP would produce different effects in two conceptually distinct animal models: the elevated plus maze (EPM) and the Vogel conflict test (VCT).

We observed drugs which interfere with ECB reuptake/metabolism in both the PL and in the dentate gyrus of the dHIP induced anxiolytic-like effect, in both the EPM and in the VCT via CB1 receptors, suggesting CB1 signaling in these brain regions modulate defensive responses to both innate and learned threatening stimuli.

This data further strengthens previous results indicating modulation of hippocampal and MPFC activity via CB1 by ECBs, which could be therapeutically targeted to treat anxiety disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/25595265

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

Endocannabinoid-mediated modulation of Gq/11 protein-coupled receptor signaling-induced vasoconstriction and hypertension.

Posted on January 18, 2015 by David

“Activation of G protein-coupled receptors (GPCRs) can induce vasoconstriction via calcium signal-mediated and Rho-dependent pathways…

Our aim was to provide evidence that GPCR signaling-induced 2-AG production and activation of vascular type1 cannabinoid receptors (CB1R) is capable of reducing agonist-induced vasoconstriction and hypertension…

Pharmacological or genetic loss of CB1R function augmented AngII-induced blood pressure rise in mice.

These data demonstrate that vasoconstrictor effect of GPCR agonists is attenuated via Gq/11-mediated vascular endocannabinoid formation.

Agonist-induced endocannabinoid-mediated CB1R activation is a significant physiological modulator of vascular tone.

Thus, the selective modulation of GPCR signaling-induced endocannabinoid release has a therapeutic potential in case of increased vascular tone and hypertension.”

http://www.ncbi.nlm.nih.gov/pubmed/25595485

http://www.thctotalhealthcare.com/category/hypertension-high-blood-pressure/

Regulation of circulating endocannabinoids associated with cancer and metastases in mice and humans.

Posted on January 17, 2015 by David

“Endocannabinoids may modify cancer development, progression and associated pain.

We determined whether cancer-evoked dysregulations in this system become manifest in altered tissue and plasma endocannabinoids…

The endocannabinoid system was subject to cancer-associated regulations to an extent that led to measurable changes in circulating endocannabinoid levels, emphasizing the importance of the endocannabinoid system in the pathophysiology of cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/25594019

http://www.thctotalhealthcare.com/category/cancer/

Targeting the endocannabinoid system to treat haunting traumatic memories

Posted on November 11, 2014 by David

“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.

Posted on October 28, 2014 by David

“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.

Posted on October 28, 2014 by David

“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

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

Posted on September 11, 2014 by David

“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/