An analgesic role for cannabinoids.

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

Reassessment of the role of cannabinoids in the management of pain.

“The aim of this article is to assess the role of cannabinoids in the treatment of acute and chronic pain in humans.

 …to date there is increasing evidence that cannabinoids are safe and effective for refractory chronic pain conditions including neuropathic pain associated with multiple sclerosis, rheumatoid arthritis, and peripheral neuropathy associated with HIV/AIDS.

SUMMARY:

The precise role of cannabinoids in pain treatment still needs further evaluation. Cannabinoid compounds may be more effective in the context of chronic neuropathic pain than for the management of acute pain.”

http://www.ncbi.nlm.nih.gov/pubmed/17873600

Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials.

“Effective therapeutic options for patients living with chronic pain are limited. The pain relieving effect of cannabinoids remains unclear. A systematic review of randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to the PRISMA statement update on the QUORUM guidelines for reporting systematic reviews that evaluate health care interventions. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabis based medicine, nabilone, dronabinol and a novel THC analogue. Chronic non-cancer pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Overall the quality of trials was excellent. Fifteen of the eighteen trials that met the inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared with placebo and several reported significant improvements in sleep. There were no serious adverse effects. Adverse effects most commonly reported were generally well tolerated, mild to moderate in severity and led to withdrawal from the studies in only a few cases. Overall there is evidence that cannabinoids are safe and modestly effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. The context of the need for additional treatments for chronic pain is reviewed. Further large studies of longer duration examining specific cannabinoids in homogeneous populations are required.

In conclusion this systematic review of 18 recent good quality randomized trials demonstrates that cannabinoids are a modestly effective and safe treatment option for chronic non-cancer (predominantly neuropathic) pain. Given the prevalence of chronic pain, its impact on function and the paucity of effective therapeutic interventions, additional treatment options are urgently needed. More large scale trials of longer duration reporting on pain and level of function are required.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243008/

Cannabinoids for pain management.

Abstract

“Cannabinoids have been used for thousands of years to provide relief from suffering, but only recently have they been critically evaluated in clinical trials. This review provides an in-depth examination of the evidence supporting cannabinoids in various pain states, along with an overview of potential adverse effects. In summary, there is strong evidence for a moderate analgesic effect in peripheral neuropathic and central pain conditions, and conflicting evidence for their use in nociceptive pain. For spasticity, most controlled studies demonstrate significant improvement. Adverse effects are not uncommon with cannabinoids, though most are not serious and self-limiting. In view of the limited effect size and low but not inconsequential risk of serious adverse events, cannabinoids should be employed as analgesics only when safer and more effective medication trials have failed, or as part of a multimodal treatment regimen.”

http://www.ncbi.nlm.nih.gov/pubmed/21508629

Cannabinoids for the treatment of neuropathic pain: clinical evidence.

Abstract

“Neuropathic pain is a worldwide epidemic that occurs in 3 to 8% of individuals in industrialized countries and is often refractory to existing treatments. Drugs currently available to target neuropathic pain are, at best, moderately effective and include antidepressants, gabapentin, NMDA receptor antagonists, as well as other anticonvulsants, all of which are limited by their adverse-effect profiles. Cannabinoid drugs are emerging as a promising class of drugs to treat neuropathic pain and have been tested for analgesic effects in a range of chronic pain conditions. Data show that cannabinoids are often effective in individuals with refractory pain receiving concomitant analgesic drugs. Clinical studies on cannabinoids for the treatment of neuropathic pain are reviewed, focusing on clinical trials published within the last five years. Data from large, well-controlled studies show that cannabinoids are moderately effective in reducing chronic pain and that side effects are comparable to existing treatments, suggesting that cannabinoids can play a useful role in the management of chronic pain. Like other drugs for neuropathic pain, cannabinoids have a dose titration that is limited by psychoactive side effects. The development of cannabinoid drugs to target neuropathic pain with improved therapeutic ratios will depend upon the development of cannabinoid treatments with reduced psychoactivity.”

http://www.ncbi.nlm.nih.gov/pubmed/18183533

Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain.

“OBJECTIVE:

Debilitating pain, occurring in 50-70% of multiple sclerosis (MS) patients, is poorly understood and infrequently studied. We summarized efficacy and safety data of cannabinoid-based drugs for neuropathic pain.

CONCLUSION:

Cannabinoids including the cannabidiol/THC buccal spray are effective in treating neuropathic pain in MS.”

http://www.ncbi.nlm.nih.gov/pubmed/17257464

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

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

Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside.

“Neuropathic pain is a debilitating form of chronic pain resulting from nerve injury, disease states, or toxic insults. Neuropathic pain is often refractory to conventional pharmacotherapies, necessitating validation of novel analgesics. Cannabinoids, drugs that share the same target as Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the psychoactive ingredient in cannabis, have the potential to address this unmet need…

In humans, effects of smoked marijuana, synthetic Delta(9)-THC analogs (e.g., Marinol, Cesamet) and medicinal cannabis preparations containing both Delta(9)-THC and cannabidiol (e.g., Sativex, Cannador) in neuropathic pain states are reviewed. Clinical studies largely affirm that neuropathic pain patients derive benefits from cannabinoid treatment…

Evidence for the use of Cannabis sativa as a treatment for pain can be traced back to the beginnings of recorded history…

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755639/

Marijuana Eases Neuropathic Pain

“Smoking marijuana modestly reduced pain and other symptoms of chronic neuropathic pain, results of a small randomized, placebo-controlled trial showed.

These results are important in light of the fact that patients who hear about pain relief from ongoing publicity about medical marijuana have had only a “trickle” of evidence to prove it, explained Henry J. McQuay, DM, of Oxford University, in an accompanying editorial.

This study does offer hope since few drugs have proven effective in these patients, commented Steven P. Cohen, MD, who as director of pain research at Walter Reed Army Medical Center in Washington, D.C., sees chronic pain in most of his patients with major war injuries.”

Marijuana smoking appeared well tolerated…

Patients rarely got high on the single hit they took through a pipe three times a day as part of the study, Ware’s group noted.”

Read more: http://www.medpagetoday.com/Neurology/PainManagement/21939

Smoking Marijuana Eases Chronic Neuropathic Pain.

“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