Cannabinoids in the management of difficult to treat pain
Cannabinoids in the management of difficult to treat pain
Ethan B Russo
Ethan B Russo, GW Pharmaceuticals, Vashon, WA, USA;
Correspondence: Ethan Russo, MD 20402 81st Avenue SW, Vashon, WA 98070, USA Tel +1 206 408 7082 Fax +1 866 234 7757 Email erusso@gwpharm.com
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Abstract
This article reviews recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms, as well as randomized clinical trials employing cannabinoids in pain treatment. Tetrahydrocannabinol (THC, Marinol®) and nabilone (Cesamet®) are currently approved in the United States and other countries, but not for pain indications. Other synthetic cannabinoids, such as ajulemic acid, are in development. Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation. Sativex®, a cannabis derived oromucosal spray containing equal proportions of THC (partial CB1 receptor agonist ) and cannabidiol (CBD, a non-euphoriant, anti-inflammatory analgesic with CB1 receptor antagonist and endocannabinoid modulating effects) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain. Numerous randomized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain, rheumatoid arthritis and cancer pain. An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006. Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles. Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise.
Keywords: cannabinoids, tetrahydrocannabinol, cannabidiol, analgesia, pain management, multiple sclerosis
Introduction
Chronic pain represents an emerging public health issue of massive proportions, particularly in view of aging populations in industrialized nations. Associated facts and figures are daunting: In Europe, chronic musculoskeletal pain of a disabling nature affects over one in four elderly people (Frondini et al 2007), while figures from Australia note that older half of older people suffer persistent pain, and up to 80% in nursing home populations (Gibson 2007). Responses to an ABC News poll in the USA indicated that 19% of adults (38 million) have chronic pain, and 6% (or 12 million) have utilized cannabis in attempts to treat it (ABC News et al 2005).
Particular difficulties face the clinician managing intractable patients afflicted with cancer-associated pain, neuropathic pain, and central pain states (eg, pain associated with multiple sclerosis) that are often inadequately treated with available opiates, antidepressants and anticonvulsant drugs. Physicians are seeking new approaches to treatment of these conditions but many remain concerned about increasing governmental scrutiny of their prescribing practices (Fishman 2006), prescription drug abuse or diversion. The entry of cannabinoid medicines to the pharmacopoeia offers a novel approach to the issue of chronic pain management, offering new hope to many, but also stoking the flames of controversy among politicians and the public alike.
This article will attempt to present information concerning cannabinoid mechanisms of analgesia, review randomized clinical trials (RCTs) of available and emerging cannabinoid agents, and address the many thorny issues that have arisen with clinical usage of herbal cannabis itself (“medical marijuana”). An effort will be made to place the issues in context and suggest rational approaches that may mitigate concerns and indicate how standardized pharmaceutical cannabinoids may offer a welcome addition to the pharmacotherapeutic armamentarium in chronic pain treatment.
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