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.
Cannabinoids including the cannabidiol/THC buccal spray are effective in treating neuropathic pain in MS.”
“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…
“A chemical component of the marijuana plant could prevent the onset of pain associated with drugs used in chemo therapy, particularly in breast cancer patients, according to researchers at Temple University’s School of Pharmacy.
“We found that cannabidiol completely prevented the onset of the neuropathic, or nerve pain caused by the chemo drug Paclitaxel, which is used to treat breast cancer,” said Ward, who is also a research associate professor in Temple’s Center for Substance Abuse Research.
Ward said that one of cannabidiol’s major benefits is that, unlike other chemicals found in marijuana such as THC, it does not produce psycho-active effects such as euphoria, increased appetite or cognitive deficits. “Cannabidiol has the therapeutic qualities of marijuana but not the side effects,” she said.”
Read more: http://medicalxpress.com/news/2011-10-marijuana-component-ease-pain-chemotherapy.html
“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/
Erica Klarreich
“Early trials suggest cannabis spritz may give relief to chronic pain sufferers.”
Cannabis: 5,000 years of medicinal use.© Photodisc
“A spray that delivers the active ingredient of cannabis under the tongue may ease chronic pain, preliminary clinical trials suggest.
Of the 23 patients who participated in the controlled study, only a few failed to respond to the spray, William Nortcutt of James Paget Hospital in Gorleston, UK told the British Association for the Advancement of Science’s Annual Festival of Science on Monday. Seventeen have gone on to use the drug to treat their pain in the long term, he said.
“Some of the patients said it made a huge difference; others just said it lets them sleep,” Nortcutt said. “But when you’re in chronic pain, being able to sleep is one of the most important things.”
Earlier clinical trials have also shown the pain-relieving benefits of cannabis. But researchers have struggled to find a good way to deliver the drug, says Roger Pertwee, a neuropharmacologist and cannabis expert at the University of Aberdeen, UK.
“The study with a spray is very interesting,” he says. “The past clinical trials have been with pills, but absorption by swallowing is very unreliable.”
About half of the trial’s participants had multiple sclerosis; the rest suffered chronic pain from severe nerve damage and spinal-cord injuries. Although a few of the multiple sclerosis patients had been using cannabis to treat pain before the trials, most participants had seldom or never used it.
The most common side-effect appeared to be dry mouth, Nortcutt reports. Several patients experienced panic or a high during tests to find appropriate dosages. Most preferred a drug in which the active substance, tetrahydrocannabinol (THC), was mixed with another, less psychoactive ingredient of cannabis. Previous clinical studies have involved only pure THC, Pertwee says.
The research comes as many groups are pushing for cannabis to be legalized for therapeutic use in the United Kingdom. If cannabis were to be made legal, Nortcutt says, the path to approval might be much faster than for typical drugs, which take an average of six years.
“There is a huge amount of anecdotal evidence that would help scientists,” Nortcutt told the Glasgow meeting. “We have to recognize that cannabis has been used for 5,000 years.” But much more work is needed to understand how cannabis might be exploited as a pain treatment, Nortcutt warned. “I wouldn’t call for it to be prescribed now.””
http://www.nature.com/news/1998/010906/full/news010906-7.html
“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
“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 Continue reading
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.
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.
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.
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.
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.”
“The medicinal properties of cannabis (Cannabis sativa, marijuana) have been known for millennia, as shown by reports from China and India underscoring its analgesic, antiemetic, and appetite-stimulating properties. During the 19th century, the prescription of cannabis gained popularity for a variety of conditions ranging from epilepsy to rheumatism and abdominal symptoms. Concerns about abuse led to discontinuation of therapeutic use in the 1940s. The characterization of marijuana-derived bioactive molecules began during the early 20th century with the identification of several hydrophobic compounds and culminated in 1964 with the isolation of Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of the plant. Subsequent studies identified over 60 other phytocannabinoids and allowed the synthesis of active analogs with varying potencies. This step was critical in the identification of the endocannabinoid system, comprising specific cannabinoid binding sites (CB1 and CB2), their endogenous ligands (endocannabinoids), and synthetic and degradative pathways.”
“Cannabinoid receptors (CB1 and CB2) and their endogenous ligands (endocannabinoids) have recently emerged as novel mediators of liver diseases. Endogenous activation of CB1 receptors promotes nonalcoholic fatty liver disease (NAFLD) and progression of liver fibrosis associated with chronic liver injury; in addition, CB1 receptors contribute to the pathogenesis of portal hypertension and cirrhotic cardiomyopathy. CB2 receptor-dependent effects are also increasingly characterized, including antifibrogenic effects and regulation of liver inflammation during ischemia-reperfusion and NAFLD. It is likely that the next few years will allow us to delineate whether molecules targeting CB1 and CB2 receptors are useful therapeutic agents for the treatment of chronic liver diseases.”
“The endocannabinoid system plays a protective role in various inflammatory diseases, and it is considered an attractive therapeutic target.”
“The aim of the present study was to determine the immunomodulatory effect of THC in the murine model of ConA-induced hepatitis. We demonstrate that a single injection of THC significantly ameliorates ConA-induced T-cell-mediated liver injury by up-regulating Forkhead helix transcription factor p3 (Foxp3)+ regulatory T cells and down-regulating inflammatory cytokines. Using select cannabinoid receptor agonists and antagonists, we demonstrate that THC mediates immune modulation in this model by signaling through both CB1 and CB2 receptors. We also demonstrate that anandamide, an endocannabinoid can effectively attenuate the disease.”
“There is growing interest in recent years to target cannabinoid receptors for treating liver diseases. In the current study, CB1 or CB2 activation alone had no anti-inflammatory effect on hepatitis. However, cannabinoids that bind to both CB1 and CB2 receptors (THC, CP55,940, WIN55212, and anandamide) effectively attenuated hepatitis. That CB1/CB2 mixed agonists could suppress the disease but not the coadministered CB1 and CB2 agonists indicates that both the cannabinoid receptors need to be activated simultaneously to produce the observed effect and that the different pharmacokinetics of the two coadministered agonists may not allow this to happen. Signaling through both the receptors is important because blocking either CB1 or CB2 could reverse the effect of THC.”
“Taken together, our data suggest that exogenous cannabinoids such as THC upon binding to CB1 and CB2 receptors on immune cells, induce apoptosis in effector T cells, up-regulate Treg function, and suppress inflammatory cytokines there by preventing ConA-induced activated T-cell-mediated liver injury. The observation that the anandamide treatment ameliorates ConA-induced hepatitis, together with FAAH deficiency or inhibition leading to increased resistance to the disease, strongly suggests that the endocannabinoid system serves to attenuate the inflammatory response in ConA-induced acute hepatitis. These findings raise the promising potential of developing novel pharmacological treatments for T-cell-mediated liver diseases.”