Tag Archives: pain

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

Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes

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“Hemp, Cannabis sativa, is a coarse bushy annual plant with palmate leaves and clusters of small green flowers that grows wild in regions of mild or tropical weather and can attain a height of 3 metres. The genus name Cannabis is complemented by sativa (which means useful). Cannabis has indeed been used throughout history for a variety of purposes…

 Cannabis has been utilised for centuries throughout the world to alleviate disease. Its derivatives were named “panacea”, or “cure-all”, and were sold as a legal medicine, mainly for pain…

The discovery of cannabinoid receptors, their endogenous ligands, and the machinery for the synthesis, transport, and degradation of these retrograde messengers, has equipped us with neurochemical tools for novel drug design. Agonist-activated cannabinoid receptors, modulate nociceptive thresholds, inhibit release of pro-inflammatory molecules, and display synergistic effects with other systems that influence analgesia, especially the endogenous opioid system. Cannabinoid receptor agonists have shown therapeutic value against inflammatory and neuropathic pains, conditions that are often refractory to therapy…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430692/

Cannabis stops the pain

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“Ann Vernon would like to understand one thing about the lawmakers who oppose the medical use of cannabis.

“I think you would have to be pretty heartless if you’re faced with these absolutely desperate people . . . and they say this [cannabis] helps and you turn them down? I don’t know.”

It is a question Ms Vernon, who sufferers from chronic pain and post-traumatic stress disorder, asks herself often. The most recent occasion was last week when she was standing before a judge on charges of cultivating cannabis.

Ms Vernon, 40, had plants in her home because she uses cannabis to ease her chronic pain. When the judge heard her medical evidence, backed by her doctor, he discharged her without conviction.

“He listened to me talk about what it was like to live with constant pain.”

The mother of three has now vowed to devote her time to fighting for changes in the law to allow the use of cannabis for medical purposes.

It was a doctor who first suggested cannabis to Ms Vernon.

Years and years of chronic pain – she was thrown from a horse as a teen and later suffered complications from surgery – left the once-active woman bedridden and in constant agony.

Sitting and standing were so agonising she would cart a mattress from room to room just so she could lie down.

Conventional painkillers failed and eventually cannabis was recommended.

“At first I was like ‘Oh what!’ I’d smoked cannabis as a teenager . . . now and then,” she says. “But then you get that desperate you will try anything.”

The drug – ingested with a vapouriser she imported from Australia – worked.

“With cannabis I have quality of life. I’ve come so far now that clearly I am not bedridden.”

Ms Vernon says that, while cannabis comes with a high, medical users get used to that very quickly. “I don’t find the high from the cannabis anywhere near as debilitating as the high I was getting from normal painkillers.”

Cannabis also helps with sleep and with appetite. “I also had a huge amount of nausea and that just wipes it.”

But she says it is hard not to feel like a criminal: “I have never even had a traffic infringement notice, not a parking ticket, nothing. So, yes, breaking the law is awful. To be made to feel like a criminal for something a doctor recommended to me and has helped me is awful.”

Being allowed to grow cannabis for medicinal use would mean less harm to the community, she says.

“It is also very hard, and very expensive, to get decent-quality cannabis. The supply is inconsistent, you don’t know what you are getting.”

Medical-cannabis patients are rendered vulnerable, she says.

“Many of them are much worse off physically than me and can’t come forward to speak.

“Some of the things I have seen, some of the effects I’ve seen of people when they consume cannabis. I’ve seen people get some movement back in limb they’ve had no movement in for eight years.

“I can’t imagine how cold people have to be to stop them from using the one thing that helps them.””

http://www.stuff.co.nz/dominion-post/news/national/7992118/Cannabis-stops-the-pain

Cannabinoid 1 (CB1) receptor–pharmacology, role in pain and recent developments in emerging CB1 agonists.

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Abstract

“Cannabinoids are antinociceptive in animal models of acute pain, tissue injury and nerve injury induced nociception and act via their cognate receptors, cannabinoid receptor 1 and 2. This review examines the underlying biology of the endocannabinoids and behavioural, neurophysiological, neuroanatomical evidence supporting the notion of pain modulation by these ligands with a focus on the current evidence encompassing the pharmacological characterization of CB1 agonists in this therapy. Separating the psychotropic effects of CB1 agonists from their therapeutic benefits is the major challenge facing researchers in the field today and with the discovery of peripherally acting agonists there seems to be a ray of hope emerging for the diverse potential therapeutic applications of this class of ligands.”

http://www.ncbi.nlm.nih.gov/pubmed/21631407

Cannabinoid CB2 receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain.

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Abstract

“Cannabinoids suppress behavioural responses to noxious stimulation and suppress nociceptive transmission through activation of CB1 and CB2 receptor subtypes. CB1 receptors are expressed at high levels in the central nervous system (CNS), whereas CB2 receptors are found predominantly, but not exclusively, outside the CNS. CB2 receptors are also upregulated in the CNS and dorsal root ganglia by pathological pain states. Here, we review behavioural, neurochemical and electrophysiological data, which identify cannabinoid CB2 receptors as a therapeutic target for treating pathological pain states with limited centrally, mediated side effects. The development of CB2-selective agonists (with minimal affinity for CB1) as well as mutant mice lacking CB2 receptors has provided pharmacological and genetic tools required to evaluate the effectiveness of CB2 agonists in suppressing persistent pain states. This review will examine the efficacy of cannabinoid CB2-selective agonists in suppressing acute, inflammatory and neuropathic nociception following systemic and local routes of administration. Data derived from behavioural, neurochemical and neurophysiological approaches are discussed to better understand the relationship between antinociceptive effects induced by CB2-selective agonists in behavioural studies and neural mechanisms of pain suppression. Finally, the therapeutic potential and possible limitations of CB2-based pharmacotherapies for pathological pain states induced by tissue and nerve injury are discussed.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219541/

Selective activation of cannabinoid CB2 receptors suppresses neuropathic nociception induced by treatment with the chemotherapeutic agent paclitaxel in rats.

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“Activation of cannabinoid CB(2) receptors suppresses neuropathic pain induced by traumatic nerve injury. The present studies were conducted to evaluate the efficacy of cannabinoid CB(2) receptor activation in suppressing painful peripheral neuropathy evoked by chemotherapeutic treatment with the antitumor agent paclitaxel…

 Our data suggest that cannabinoid CB(2) receptors may be important therapeutic targets for the treatment of chemotherapy-evoked neuropathy.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682949/

Selective activation of cannabinoid CB2 receptors suppresses hyperalgesia evoked by intradermal capsaicin.

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“The present studies were conducted to test the hypothesis that activation of peripheral cannabinoid CB(2) receptors would suppress hyperalgesia evoked by intradermal administration of capsaicin, the pungent ingredient in hot chili peppers.

These data provide evidence that actions at cannabinoid CB(2) receptors are sufficient to normalize nociceptive thresholds and produce antinociception in persistent pain states.”

http://jpet.aspetjournals.org/content/308/2/446.lo

Activation of peripheral cannabinoid CB1 and CB2 receptors suppresses the maintenance of inflammatory nociception: a comparative analysis.

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“Background and Purpose:

Effects of locally administered agonists and antagonists for cannabinoid CB1 and CB2 receptors on mechanical and thermal hypersensitivity were compared after the establishment of chronic inflammation.

Conclusions and Implications:

Cannabinoids act locally through distinct CB1 and CB2 mechanisms to suppress mechanical hypersensitivity after the establishment of chronic inflammation, at doses that produced modest changes in thermal hyperalgesia. Additive antihyperalgesic effects were observed following prophylactic co-administration of the CB1– and CB2-selective agonists. Our results suggest that peripheral cannabinoid antihyperalgesic actions may be exploited for treatment of inflammatory pain states.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042894/