Category Archives: Neuropathic Pain

Smoking Marijuana Eases Chronic Neuropathic Pain.

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“Smoking cannabis reduces chronic neuropathic pain and also improves sleep, according to new research published today in the Canadian Medical Association Journal.

A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis 3 times a day for 5 days was sufficient to achieve these outcomes, lead study author Mark A. Ware, MBBS, from McGill University Health Center, Montreal, Canada, told Medscape Medical News in an interview.

“Patients have been reporting that cannabis helps control their pain, and they have been saying so for a long time,” Dr. Ware said. “At the time that we had secured the funding and began the trial, there had been no clinical trials that had established this or investigated it.”

In addition, a large body of scientific knowledge is emerging abound the role of cannabinoid receptors and cannabinoid ligands in the human body, providing a potential scientific explanation as to why cannabinoids would be analgesic, he added. “So the 2 main supports came together, and in Canada at the time, there was an environment where we were able to secure funding sufficient for studies of this.”

Posttraumatic and Postsurgical Neuropathy

The study included 21 individuals older than 18 years (mean age, 45.4 years) with posttraumatic or postsurgical neuropathic pain lasting for at least 3 months. They were randomly assigned to receive cannabis at 4 potencies — 0%, 2.5%, 6%, and 9.4% tetrahydrocannabinol — during 4 periods in a crossover design. Each period lasted 14 days and began with 5 days of cannabis use followed by a 9-day washout period.

The cannabis doses were delivered in a single smoked inhalation using a titanium pipe. Patients self-administered the first dose of each period under supervision and were instructed to inhale for 5 seconds while the cannabis was lit, hold the smoke in their lungs for 10 seconds, and then exhale. They self-administered the remaining doses for each period at home.

The participants were allowed to continue their routine medications, and the use of acetaminophen as breakthrough analgesia was also permitted.

Pain intensity was measured using an 11-item numeric rating scale that used “no pain” and “worst pain possible” as anchors.

The study found that the higher dose of cannabis was the most efficient in reducing pain. The average daily pain intensity was 5.4 with the 9.4% tetrahydrocannabinol cannabis dose compared with 6.1 with the 0% or placebo dose (95% confidence interval, 0.02 – 1.4; P = .023).

In addition, participants reported significantly more drowsiness and reported getting to sleep more easily, faster, and with fewer periods of wakefulness when taking the 9.4% dose than when taking the 0% dose ( P < .05). The higher dose also improved anxiety and depression compared with the placebo dose.

Blind Held; Studies Feasible

“It was feared that participants would know right away if they were smoking cannabis because of the acute psychoactive effects of the drug, but our results do not support this,” Dr. Ware noted. “They do show that short-term placebo-controlled trials of smoked cannabis are feasible.”

He would like his study to act as a stimulus for other studies on cannabis and pain relief.

“Studies of this kind can be done. Ours was difficult to do because it was the first time we had done anything like this. We were breaking new ground with regard to regulations and so on, but it is possible. Having done it once, it’s not as difficult to do it again. So our results raise the possibility of extending the study for a longer duration, or being able to look at safety issues, and so on. It is possible to do a scientific trial with this compound. Your political views shouldn’t matter. This is just good science,” Dr. Ware said.

In a related commentary, Henry J. McQuay, DM, from Balliol College, Oxford, United Kingdom, writes that the study authors should be congratulated for tackling the question of whether cannabis helps in neuropathic pain, “particularly given that the regulatory hurdles for their trial must have been a nightmare.”

He concludes that the study “adds to the trickle of evidence that cannabis may help some of the patients who are struggling at present.””

http://www.medscape.com/viewarticle/727702

Study: Smoking Pot May Ease Chronic Pain

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By Amanda Gardner
smoking pot chronic pain 200x150 Study: Smoking Pot May Ease Chronic Pain

 “People with chronic pain who aren’t getting enough relief from medications may be able to ease their pain by smoking small amounts of marijuana, a new study suggests.

Marijuana also helps pain patients fall asleep more easily and sleep more soundly, according to the report, one of the first real-world studies to look at the medicinal use of smoked marijuana. Most previous research has used extracts of tetrahydrocannabinol (THC), the active ingredient in the cannabis plant.

“This is the first time anyone has done a trial of smoked cannabis on an outpatient basis,” says the lead researcher, Mark Ware, MBBS, the director of clinical research at McGill University’s Alan Edwards Centre for Research on Pain, in Montreal.

The study included 21 adults with nervous-system (neuropathic) pain stemming from surgery, accidents, or other trauma. Fourteen of the participants were on short-term disability or permanently disabled. All of them had tried marijuana before, but none were current or habitual smokers.

“They were not experienced marijuana users,” Ware says. “They came because they had severe pain that was not responding to any conventional treatment.”

Each patient in the study smoked four different strengths of marijuana over a period of 56 days. The THC potency ranged from 9.4%—the strongest dose the researchers could obtain legally—to 0%, a “placebo” pot that looked and tasted like the real thing but was stripped of THC. (By comparison, the
strongest marijuana available on the street has a THC potency of about 15%, Ware estimates.)

The participants—who weren’t told which strength they were getting—were instructed to smoke a thimbleful (25 milligrams) from a small pipe three times a day for five days. After a nine-day break, they switched to a different potency.

The highest dose of THC yielded the best results. It lessened pain and improved sleep more effectively than the placebo and the two medium-strength doses (which produced no measurable relief), and it also reduced anxiety and depression. The effects lasted for about 90 minutes to two hours, according to the study.”

Read more: http://news.health.com/2010/08/30/marijuana-chronic-pain/

Marijuana Relieves Chronic Pain, Research Shows – WebMD

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“Three puffs a day of cannabis, better known as marijuana, helps people with chronic nerve pain due to injury or surgery feel less pain and sleep better, a Canadian team has found.

”It’s been known anecdotally,” says researcher Mark Ware, MD, assistant professor of anesthesia and family medicine at McGill University in Montreal. “About 10% to 15% of patients attending a chronic pain clinic use cannabis as part of their pain [control] strategy,” he tells WebMD.

But Ware’s study is more scientific — a clinical trial in which his team compared placebo with three different doses of cannabis. The research is published in CMAJ, the Canadian Medical Association Journal.

The new study ”adds to the trickle of evidence that cannabis may help some of the patients who are struggling [with pain] at present,” Henry McQuay, DM, an emeritus fellow at Balliol College, Oxford University, England, writes in a commentary accompanying the study…” More: http://www.webmd.com/pain-management/news/20100830/marijuana-relieves-chronic-pain-research-show

“Smoked cannabis for chronic neuropathic pain: a randomized controlled trial… A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity ofpain, improved sleep and was well tolerated.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950205/

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 →

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

[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 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/

Targeting cannabinoid agonists for inflammatory and neuropathic pain.

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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

Targeting CB2 receptors and the endocannabinoid system for the treatment of pain.

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Abstract

“The endocannabinoid system consists of the cannabinoid (CB) receptors, CB(1) and CB(2), the endogenous ligands anandamide (AEA, arachidonoylethanolamide) and 2-arachidonoylglycerol (2-AG), and their synthetic and metabolic machinery. The use of cannabis has been described in classical and recent literature for the treatment of pain, but the potential for psychotropic effects as a result of the activation of central CB(1) receptors places a limitation upon its use. There are, however, a number of modern approaches being undertaken to circumvent this problem, and this review represents a concise summary of these approaches, with a particular emphasis upon CB(2) receptor agonists. Selective CB(2) agonists and peripherally restricted CB(1) or CB(1)/CB(2) dual agonists are being developed for the treatment of inflammatory and neuropathic pain, as they demonstrate efficacy in a range of pain models. CB(2) receptors were originally described as being restricted to cells of immune origin, but there is evidence for their expression in human primary sensory neurons, and increased levels of CB(2) receptors reported in human peripheral nerves have been seen after injury, particularly in painful neuromas. CB(2) receptor agonists produce antinociceptive effects in models of inflammatory and nociceptive pain, and in some cases these effects involve activation of the opioid system. In addition, CB receptor agonists enhance the effect of mu-opioid receptor agonists in a variety of models of analgesia, and combinations of cannabinoids and opioids may produce synergistic effects. Antinociceptive effects of compounds blocking the metabolism of anandamide have been reported, particularly in models of inflammatory pain. There is also evidence that such compounds increase the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs), raising the possibility that a combination of suitable agents could, by reducing the NSAID dose needed, provide an efficacious treatment strategy, while minimizing the potential for NSAID-induced gastrointestinal and cardiovascular disturbances. Other potential “partners” for endocannabinoid modulatory agents include alpha(2)-adrenoceptor modulators, peroxisome proliferator-activated receptor alpha agonists and TRPV1 antagonists. An extension of the polypharmacological approach is to combine the desired pharmacological properties of the treatment within a single molecule. Hopefully, these approaches will yield novel analgesics that do not produce the psychotropic effects that limit the medicinal use of cannabis.”

http://www.ncbi.nlm.nih.gov/pubmed/19150370

From cannabis to the endocannabinoid system: refocussing attention on potential clinical benefits.

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“Cannabis sativa is one of the oldest herbal remedies known to man. Over the past four thousand years, it has been used for the treatment of numerous diseases but due to its psychoactive properties, its current medicinal usage is highly restricted. In this review, we seek to highlight advances made over the last forty years in the understanding of the mechanisms responsible for the effects of cannabis on the human body and how these can potentially be utilized in clinical practice. During this time, the primary active ingredients in cannabis have been isolated, specific cannabinoid receptors have been discovered and at least five endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified. Together, these form the framework of a complex endocannabinoid signalling system that has widespread distribution in the body and plays a role in regulating numerous physiological processes within the body. Cannabinoid ligands are therefore thought to display considerable therapeutic potential and the drive to develop compounds that can be targeted to specific neuronal systems at low enough doses so as to eliminate cognitive side effects remains the ‘holy grail’ of endocannabinoid research.”

http://www.ncbi.nlm.nih.gov/pubmed/23155985