Monthly Archives: November 2012

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

Posted on by
Reply

“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

Posted on by
Reply

“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.

Posted on by
Reply

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.

Posted on by
Reply

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/

Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception evoked by the chemotherapeutic agent vincristine in rats.

Posted on by
Reply

“BACKGROUND AND PURPOSE:

The ability of cannabinoids to suppress mechanical hypersensitivity (mechanical allodynia) induced by treatment with the chemotherapeutic agent vincristine was evaluated in rats. Sites of action were subsequently identified.

CONCLUSIONS AND IMPLICATIONS:

Cannabinoids suppress the maintenance of vincristine-induced mechanical allodynia through activation of CB1 and CB2 receptors. These anti-allodynic effects are mediated, at least in part, at the level of the spinal cord.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190028/

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

Posted on by
2

“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.

Posted on by
1

“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.

Posted on by
Reply

“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/

Targeting cannabinoid agonists for inflammatory and neuropathic pain.

Posted on by
Reply

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.”

http://www.ncbi.nlm.nih.gov/pubmed/17594182

Cannabinoid receptors and pain.

Posted on by
Reply

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