“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
Category Archives: Chronic Pain
CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms.
Reply
“These results confirm that CB2 is present in the central nervous system and suggest that CB2 agonists may elicit their analgesic effect by acting not only at non-neuronal peripheral sites but also at neural level, making CB2 an attractive target for chronic pain treatment.”
The cannabinoid system and pain: towards new drugs?
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.”
[The pharmacology of cannabinoid derivatives: are there applications to treatment of pain?].
“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.”
Cannabinoid analgesia as a potential new therapeutic option in the treatment of chronic pain.
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.”
Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes
“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…”
Cannabis stops the pain
“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 CB2 receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain.
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.”
Targeting cannabinoid agonists for inflammatory and neuropathic pain.
Abstract
“The cannabinoid receptors CB(1) and CB(2) are class A G-protein-coupled receptors. It is well known that cannabinoid receptor agonists produce relief of pain in a variety of animal models by interacting with cannabinoid receptors. CB(1) receptors are located centrally and peripherally, whereas CB(2) receptors are expressed primarily on immune cells and tissues. A large body of preclinical data supports the hypothesis that either CB(2)-selective agonists or CB(1) agonists acting at peripheral sites, or with limited CNS exposure, will inhibit pain and neuroinflammation without side effects within the CNS. There has been a growing interest in developing cannabinoid agonists. Many new cannabinoid ligands have been synthesized and studied covering a wide variety of novel structural scaffolds. This review focuses on the present development of cannabinoid agonists with an emphasis on selective CB(2) agonists and peripherally restricted CB(1) or CB(1)/CB(2) dual agonists for treatment of inflammatory and neuropathic pain.”
Cannabinoid type 2 receptor as a target for chronic – pain.
Abstract
“Availability of selective pharmacological tools enabled a great advance of our knowledge of cannabinoid receptor 2 (CB2) role in pathophysiology. In particular CB2 emerged as an interesting target for chronic pain treatment as demonstrated by several studies on inflammatory and neuropathic preclinal pain models. The mechanisms at the basis of CB2-mediated analgesia are still controversial but data are pointing out in two main directions: an effect on inflammatory cells and/or an action on nociceptors and spinal cord relay centers. In this review will be described the second messenger pathways activated by CB2 agonists, the data underpinning the analgesic profile of CB2 selective agonists and the mechanisms invoked to explain their analgesic action. Finally the ongoing clinical trials and the potential issues for the development of a CB2 agonist drug will be examined.”