Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

21st Annual Meeting of the Consortium of Multiple Sclerosis Centers

Washington, DC / May 30-June 2, 2007

Pain is a common symptom of multiple sclerosis (MS), occurring in 50% to 70% of people with the disease. About 20% of patients rate their pain as severe, and 20% suffer daily pain. However, most drugs fail to provide consistent pain relief and about 70% do not get adequate relief from pain, according to Dr. Virginia Devonshire, Director, University of British Columbia Multiple Sclerosis Pain Clinic, Vancouver.

“Pain can be a clinical challenge to diagnose and treat and is often under-reported,” she noted. “Patients often feel they must simply live with it.” Many have a fear of medications and are concerned about side effects and drug interactions among the numerous therapies often needed to manage their MS symptoms.

As Dr. Devonshire stated, neuropathic pain, or the generation of pain from the nerve itself, can be particularly difficult to address. “Sometimes the patient may not even recognize it as pain or realize its impact.” Clinical features may include dysesthetic burning pain, paroxysmal lancinating pain, painful paresthesias, touch-evoked pain (allodynia) and hyperalgesia. “My own patients most commonly report a deep aching or burning pain,” she informed delegates.

A variety of approaches exist for treating pain in MS, including nonpharmacological strategies (e.g. physical therapy, acupuncture, relaxation, meditation, stretching, aerobic exercise) as well as pharmacological therapies. “Pain management is like life management,” remarked Dr. Mark A. Ware, Assistant Professor of Anesthesia and Family Medicine, McGill University, Montreal, Quebec. “We need to try to help our patients manage their life and their pain, and address their functional recovery, sleep, mood, spasticity and other MS symptoms.”

In the recently published guidelines from the Canadian Pain Society, tricyclic antidepressants and anticonvulsants such as gabapentin and pregabalin are recommended as first-line treatments for chronic neuropathic pain (Moulin et al. Pain Res Manag 2007; 12:13-21). Serotonin noradrenaline reuptake inhibitors and topical lidocaine are recommended as second-line treatments, and tramadol and controlled-release opioid analgesics as third-line treatments for moderate to severe pain. Recommended fourth-line treatments include cannabinoids, methadone and several anticonvulsants (lamotrigine, topiramate and valproic acid).

Reviewing the Evidence

Dr. Ware stated that the cannabinoids (CBs) are the newest of the new treatments for pain, noting that the compounds were actually well known many years ago when an extract of the marijuana plant was in use until the mid-1940s. Although tetrahydrocannabinol (THC) was isolated as the active ingredient in the mid-1960s, little significant clinical research was carried out on its therapeutic properties until about the last 10 years, he noted. There is now a growing body of clinical trial evidence indicating that cannabis-based medicines are effective analgesics for cancer pain, spinal cord injury and visceral pain.

About 2% of Canadians currently use marijuana for medical purposes to decrease pain and improve sleep, mood and function, Dr. Ware told delegates. In Canada, about 1500 patients have obtained authorization to use herbal marijuana through the Medical Marijuana Access Regulations. In general, doses of CBs are modest and can allow for reductions in the use of opioids and other medications, he reported.

Mode of Action

“CBs have multiple targets that allow for pain reduction,” concurred Dr. Pamela Squire, Assistant Clinical Professor, University of British Columbia, Vancouver, who described two CB receptors that have been identified: the CB1 receptors in the brain and peripheral nervous system and the CB2 receptors found peripherally in reproductive and immune cells and tissues.

About 60 different CBs have been extracted from the cannabis plant, explained Dr. Squire, and a number of preparations are under investigations for clinical use. Currently, only one CB preparation—a whole-plant preparation containing delta-9-tetrahydrocannabinol/cannabidiol (THC:CBD)—is approved for use in Canada. This preparation is administered under the tongue or on the inside of the cheek via a spray pump, providing self-administered pain relief. Each spray delivers 2.7 mg of THC and 2.5 of CBD. According to Dr. Squire, patients can gradually self-titrate to a maximum of 48 sprays in 24 hours. The approved indication states patients may increase the dose gradually as needed and tolerated.

Corroborative Study Findings

Dr. Ware reviewed several recent studies on the use of cannabis-based medicine (CBM) for the relief of the common symptoms of MS.

Findings from a randomized, double-blind, placebo-controlled, parallel-group trial showed that the currently approved THC:CBD preparation was effective in reducing pain and sleep disturbance in patients with MS-related central neuropathic pain (Rog et al. Neurology 2005;65:812-9). This five-week trial included 66 patients with MS, two-thirds of whom were suffering from moderate to severe central neuropathic pain uncontrolled by other currently available medications. Patients received either the THC:CBD preparation or placebo in addition to their existing medications. The results showed that the CBM was significantly more efficacious than placebo in reducing the mean intensity of pain (P=0.005) and sleep disturbance (P=0.003). It was generally well tolerated, although more patients on THC:CBD than placebo reported dizziness, dry mouth and somnolence.

Spasticity

Randomized placebo-controlled trials have also demonstrated a beneficial effect of CBs on spasticity. Spasticity, which occurs in up to 84% of patients with MS, can severely affect quality of life and is one of the most difficult symptoms of MS to treat. A 15-week trial of 667 patients with stable MS and muscle spasticity showed evidence of a treatment effect of CBs on patient-reported spasticity and pain (P=0.003) (Zajicek et al. Lancet 2003;362:1517-26). A recent six-week study showed that the currently approved THC:CBD preparation, when added to existing anti-spasticity medication, was significantly better than placebo in reducing spasticity (P<0.05) in patients with MS and significant spasticity (Collin et al. Eur J Neurol 2007;14:290-6).

Patient Experience

In clinical trials, the most frequent side effects of the THC:CBD preparation were nausea, fatigue, dizziness and application-site reactions, usually mild or moderate in severity and often resolved with down-titration or interruption of treatment.

Although a “high” or euphoria may be experienced by some, it is not as pronounced as with inhaled marijuana, stressed Dr. Ware. “The risk of addiction is extremely low. Patients can stop the drug when they like and take it intermittently,” added Dr. Squire. The oromucosal spray formulation allows for flexible dosing and patients can choose how much to take, depending on the severity of their symptoms. “Many patients tend to dose at night, when side effects such as sleepiness are more of a benefit than a problem,” she noted.

“The CBs do not have same toxicity as the opioids,” affirmed Dr. Ware, adding that tolerance has also not been a problem. “In the two years since approval, I have not seen any evidence of tolerance in my patients using the drug.”

Summary

The successful management of pain ultimately requires a coordinated interdisciplinary approach among the patient, physician(s), nurse, physical therapist, occupational therapist, trainer and counsellor, as well as family and friends. “We need to recognize up front that patients may require more than one treatment by more than one person,” Dr. Devonshire stressed. Among the newer therapeutic choices available today in Canada, the CBs have been shown to be a useful and safe option in the management of neuropathic pain in MS patients.