Tag Archives: endocannabinoid system

Variations in the human cannabinoid receptor (CNR1) gene modulate striatal responses to happy faces.

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Abstract

“Happy facial expressions are innate social rewards and evoke a response in the striatum, a region known for its role in reward processing in rats, primates and humans. The cannabinoid receptor 1 (CNR1) is the best-characterized molecule of the endocannabinoid system, involved in processing rewards. We hypothesized that genetic variation in human CNR1 gene would predict differences in the striatal response to happy faces. In a 3T functional magnetic resonance imaging (fMRI) scanning study on 19 Caucasian volunteers, we report that four single nucleotide polymorphisms (SNPs) in the CNR1 locus modulate differential striatal response to happy but not to disgust faces. This suggests a role for the variations of the CNR1 gene in underlying social reward responsivity. Future studies should aim to replicate this finding with a balanced design in a larger sample, but these preliminary results suggest neural responsivity to emotional and socially rewarding stimuli varies as a function of CNR1 genotype. This has implications for medical conditions involving hypo-responsivity to emotional and social stimuli, such as autism.”

http://www.ncbi.nlm.nih.gov/pubmed/16623851

An analgesic role for cannabinoids.

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Abstract

“Cannabinoids have significant analgesic properties in animal models, particularly for chronic pain states, but there are few human studies. An endogenous cannabinoid system, with specific receptors and transmitters, has recently been discovered. This discovery has led pharmacologists to explore the potential of synthetic cannabinoids to selectively target chronic pain disorders without producing the side effects associated with cannabis. Well-controlled clinical trials on cannabinoids, and cannabinoid delivery systems, are now required.”

http://www.ncbi.nlm.nih.gov/pubmed/11130354

Recent data on cannabinoids and their pharmacological implications in neuropathic pain.

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Abstract

“Natural cannabinoids have been used for centuries for their psychotropic properties, but their possible therapeutic implications in analgesia have been recently documented. The present review intended to make an analysis of the neuroanatomy and physiology of the cannabinoid system (receptors, functions, agents acting on these receptors) and of its implications in neuropathic pain. There were also described the complex phenomena implicated in the generation and maintenance of neuropathic pain, by high lightening the implications of endogenous cannabinoids in this complex of painful conditions. The pharmacological analgesia test proves of cannabinoid implication in neuropathic pain was sustained by many studies presented in this paper. Therapeutic approaches using natural and synthetic cannabinoid receptor agonists were reviewed. Therapeutic perspectives in neuropathic pain might involve the development of new agents that influence the cannabinoid system. Thus, peripheral acting cannabinoid 1 receptors agonists, selective cannabinoid 2 receptor agonists and also modulators of endocannabinoids metabolism might be a way to success in the treatment of this complex entity called neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/20108515

The Endocannabinoid System and Pain

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“Cannabis has been used for more than twelve thousand years and for many different purposes (i.e. fiber, medicinal, recreational). However, the endocannabinoid signaling system has only recently been the focus of medical research and considered a potential therapeutic target. Endocannabinoids … Continue reading → Continue reading →

The cannabinoid system and pain: towards new drugs?

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Abstract

“The various components of the endocannabinoid system were discovered in the last twenty years. The cannabinoid system has attracted pharmacologists interest for its potential as therapeutic targets for several diseases ranging from obesity to Parkinson’s disease and from multiple sclerosis to pain. Research initially focused on cannabinoid receptor 1 (CB1), but, due to psychotropic side effects related to its activation, the attempts to develop an agonist drug for this receptor has been so far unsuccessful. Recently the possibility to target CB2 has emerged as an alternative for the treatment of pain. The main advantage of targeting CB2 resides in the possibility to elicit the analgesic effect without the psychotropic side effects. Evidence of the analgesic effect of CB2 selective agonists has been obtained in various models of both inflammatory and neuropathic chronic pain. To explain the mechanism at the basis of this analgesic effect different hypotheses have been proposed: effect on inflammatory cells, reduction of basal NGF tone, induction of beta-endorphin release from keratinocytes, direct action on nociceptors. Evidence in support of this last hypothesis comes from down regulation of capsaicin-induced CGRP release in spinal cord slices and Dorsal Root Ganglia (DRG) neurons in culture after treatment with CB2 selective agonists. CB2 agonists are probably acting through several mechanisms and thus CB2 represents an interesting and promising target in the chronic pain field. Further clarification of the mechanisms at the basis of CB2 analgesic effect would surely be an intriguing and stimulating area of research for the years to come.”

http://www.ncbi.nlm.nih.gov/pubmed/19358815

Cannabinoids and pain.

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Abstract

“Recent advances have dramatically increased our understanding of cannabinoid pharmacology: the psychoactive constituents of Cannabis sativa have been isolated, synthetic cannabinoids described and an endocannabinoid system identified, together with its component receptors, ligands and their biochemistry. Strong laboratory evidence now underwrites anecdotal claims of cannabinoid analgesia in inflammatory and neuropathic pain. Sites of analgesic action have been identified in brain, spinal cord and the periphery, with the latter two presenting attractive targets for divorcing the analgesic and psychotrophic effects of cannabinoids. Clinical trials are now required, but are hindered by a paucity of cannabinoids of suitable bioavailability and therapeutic ratio.”

http://www.ncbi.nlm.nih.gov/pubmed/11575713

[The pharmacology of cannabinoid derivatives: are there applications to treatment of pain?].

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“OBJECTIVE:

To present the cannabinoid system together with recent findings on the pharmacology of these compounds in the treatment of pain.

DATA SOURCES:

Search through Medline database of articles published in French and English since 1966. Also use of other publications such as books on cannabis.

DATA SYNTHESIS:

Recent advances have dramatically increased our understanding of cannabinoid pharmacology. The psychoactive constituents of Cannabis sativa have been isolated, synthetic cannabinoids described and an endocannabinoid system identified, together with its component receptors and ligands. Strong laboratory evidence now underwrites anecdotal claims of cannabinoid analgesia in inflammatory and neuropathic pain. Sites of analgesic action have been identified in brain, spinal cord and the periphery, with the latter two presenting attractive targets for divorcing the analgesic and psychotrophic effects of cannabinoids. Clinical trials are now required, but are hindered by a paucity of cannabinoids of suitable bioavailability and therapeutic ratio.

CONCLUSION:

The cannabinoid system is a major target in the treatment of pain and its therapeutic potential should be assessed in the near future by the performance of new clinical trials.”

http://www.ncbi.nlm.nih.gov/pubmed/12134594

Cannabinoid analgesia as a potential new therapeutic option in the treatment of chronic pain.

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Abstract

“OBJECTIVE:

To review the literature concerning the physiology of the endocannabinoid system, current drug development of cannabinoid agonists, and current clinical research on the use of cannabinoid agonists for analgesia.

DATA SOURCES:

Articles were identified through a search of MEDLINE (1966-August 2005) using the key words cannabis, cannabinoid, cannabi*, cannabidiol, nabilone, THC, pain, and analgesia. No search limits were included. Additional references were located through review of the bibliographies of the articles identified.

STUDY SELECTION AND DATA EXTRACTION:

Studies of cannabinoid agonists for treatment of pain were selected and were not limited by pain type or etiology. Studies or reviews using animal models of pain were also included. Articles that related to the physiology and pharmacology of the endocannabinoid system were evaluated.

DATA SYNTHESIS:

The discovery of cannabinoid receptors and endogenous ligands for these receptors has led to increased drug development of cannabinoid agonists. New cannabimimetic agents have been associated with fewer systemic adverse effects than delta-9-tetrahydrocannabinol, including recent development of cannabis medicinal extracts for sublingual use (approved in Canada), and have had promising results for analgesia in initial human trials. Several synthetic cannabinoids have also been studied in humans, including 2 cannabinoid agonists available on the international market.

CONCLUSIONS:

Cannabinoids provide a potential approach to pain management with a novel therapeutic target and mechanism. Chronic pain often requires a polypharmaceutical approach to management, and cannabinoids are a potential addition to the arsenal of treatment options.”

http://www.ncbi.nlm.nih.gov/pubmed/16449552

Cannabinoid receptors and pain.

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Abstract

“Mammalian tissues contain at least two types of cannabinoid receptor, CB(1) and CB(2), both coupled to G proteins. CB(1) receptors are expressed mainly by neurones of the central and peripheral nervous system whereas CB(2) receptors occur centrally and peripherally in certain non-neuronal tissues, particularly in immune cells. The existence of endogenous ligands for cannabinoid receptors has also been demonstrated. The discovery of this ‘endocannabinoid system’ has prompted the development of a range of novel cannabinoid receptor agonists and antagonists, including several that show marked selectivity for CB(1) or CB(2) receptors. It has also been paralleled by a renewed interest in cannabinoid-induced antinociception. This review summarizes current knowledge about the ability of cannabinoids to produce antinociception in animal models of acute pain as well as about the ability of these drugs to suppress signs of tonic pain induced in animals by nerve damage or by the injection of an inflammatory agent. Particular attention is paid to the types of pain against which cannabinoids may be effective, the distribution pattern of cannabinoid receptors in central and peripheral pain pathways and the part that these receptors play in cannabinoid-induced antinociception. The possibility that antinociception can be mediated by cannabinoid receptors other than CB(1) and CB(2) receptors, for example CB(2)-like receptors, is also discussed as is the evidence firstly that one endogenous cannabinoid, anandamide, produces antinociception through mechanisms that differ from those of other types of cannabinoid, for example by acting on vanilloid receptors, and secondly that the endocannabinoid system has physiological and/or pathophysiological roles in the modulation of pain.”

http://www.ncbi.nlm.nih.gov/pubmed/11164622

Cannabinoid CB2 receptor-mediated anti-nociception in models of acute and chronic pain.

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Abstract

“The endocannabinoid system consists of cannabinoid CB(1) and CB(2) receptors, endogenous ligands and their synthesising/metabolising enzymes. Cannabinoid receptors are present at key sites involved in the relay and modulation of nociceptive information. The analgesic effects of cannabinoids have been well documented. The usefulness of nonselective cannabinoid agonists can, however, be limited by psychoactive side effects associated with activation of CB(1) receptors. Following the recent evidence for CB(2) receptors existing in the nervous system and reports of their up-regulation in chronic pain states and neurodegenerative diseases, much research is now aimed at shedding light on the role of the CB(2) receptor in human disease. Recent studies have demonstrated anti-nociceptive effects of selective CB(2) receptor agonists in animal models of pain in the absence of CNS side effects. This review focuses on the analgesic potential of CB(2) receptor agonists for inflammatory, post-operative and neuropathic pain states and discusses their possible sites and mechanisms of action”

http://www.ncbi.nlm.nih.gov/pubmed/17952647