Wellness
With Every Breath We Take
Marijuana and Pain Management
By: Bill McCarberg, M.D.
Millions of people in the United States suffer from chronic pain, and much of that suffering cannot be relieved adequately by existing treatments. Patients are in desperate need of new pain management approaches. Cannabinoid medicines appear very promising, although the subject often is obscured by controversy, prejudice, and confusion in part because cannabinoids have some relation to the cannabis plant – also known by the slang term marijuana.
What scientific reasons do doctors have to think that cannabinoids actually work? Do they provide genuine symptom improvement, or do patients become intoxicated and merely think that their symptoms are reduced?
Basic research conducted over the past 20 years provides us with many answers. In the early 1990s, researchers identified the cannabinoid receptor system. This system is found in some of the most primitive animal forms on earth – it is also the most widespread receptor system in the human body.
The cannabinoid receptor system has two types of receptors:
CB1 receptors are found primarily in the brain, spinal cord, and periphery.
CB2 receptors are on the immune tissues.
Specific molecules (called endocannabinoids) are produced by the body that interact with these CB1 and CB2 receptors, much like endorphins interact with the body's opioid receptor system. These findings initiated a new era of scientific interest and research in cannabinoids.
Numerous studies have now established that cannabinoids help lessen pain and affect a wide range of symptoms and bodily functions. Such research has also demonstrated that cannabinoids may work together with opioids to enhance their effectiveness and reduce tolerance.
This body of research has allowed cannabinoids to be informally classified into three types:
endocannabinoids (produced by the body)
phytocannabinoids (produced by the cannabis plant)
synthetic cannabinoids (produced in the laboratory)
Each type is being studied aggressively, but because endocannabinoids are quickly metabolized and probably cannot be patented, they have not yet been researched in humans.
What progress is being made toward developing cannabinoids as prescription pain relievers? Some cannabinoids are unstable and many are insoluble in water, which makes them difficult to research and turn into modern medicines. Patients react very differently to cannabinoids. Data from recent clinical trials are encouraging, but somewhat mixed. Looking closely at the results suggests that composition and delivery route (i.e., how a medicine is administered) are extremely important to the viability of cannabinoid medicines.
The Delivery Route
When taken orally, cannabinoids are not very well absorbed and often have unpredictable effects. Patients often become sedated or have intoxication-like symptoms when tetrahydrocannabinol (THC – the primary psychoactive cannabinoid in cannabis) is metabolized by the liver. A small number of studies with Marinol (synthetic THC in sesame oil in a gelatin capsule) and Cesamet (synthetic THC analogue) have shown some effectiveness in pain relief, but optimal doses that relieve pain often cannot be achieved because of unpleasant psychologic side effects.
Inhaling cannabinoids, especially THC, also may cause problems for many patients. Blood levels rise suddenly and then drop off sharply. This rapid on-off effect may produce significant intoxication, particularly in patients who are new to cannabinoids. This may pose the risk of abuse potential. Smoking cannabis produces this effect, which is the very reason that recreational users prefer the inhaled route. Patients, however, generally wish to avoid psychologic effects, and it is unclear how difficult it might be to find a dosing pattern that enables them to have pain control without side effects.
A new product, called Sativex, was approved by Health Canada in June 2005 for marketing as an adjunctive medicine for central neuropathic pain in multiple sclerosis. Adjunctive therapy means taking two or more medications to help control pain.
Sativex has a different delivery system – an oromucosal/sublingual spray absorbed by the lining of the mouth – that, according to the manufacturer, generally allows patients to gradually work up to a stable dose at which they obtain therapeutic pain relief without unwanted psychologic effects.
In the United States, Sativex is being studied in large randomized trials in cancer pain that has not been adequately relieved by opioids. Three early and six pivotal controlled studies in the United Kingdom demonstrated positive results treating chronic pain of various origins including neurologic pain, various symptoms of multiple sclerosis, rheumatoid arthritis, and cancer pain. Initial results show improvement in pain for more than one year despite lack of effectiveness of the opioids. Common adverse effects of Savitex have included complaints of bad taste, stinging, dry mouth, dizziness, nausea or fatigue.
Additional research also may uncover other ways of avoiding the problems associated with oral or inhaled delivery. Ajulemic acid, a synthetic cannabinoid, binds to both the CB1 and CB2 receptors, and has shown benefit in a small neuropathic pain trial. It may have reduced psychologic effects and is being studied for the treatment of interstitial cystitis.
The Interplay of Cannabinoids
The use of herbal cannabis – usually smoked – has received considerable media attention since California and Arizona passed "medical marijuana" initiatives in 1996. Despite numerous anecdotal reports of effectiveness, very few controlled studies have been published in the pain area. Little is known about the number of patients who actually experience some degree of benefit or side effects.
Furthermore, herbal cannabis is neither standardized nor monitored for quality. The cannabinoid content can vary a great deal, and cannabis sold at dispensaries may be contaminated with pesticides or mold. Dosing is uncertain, depending on the preparation or method of use. So-called "vaporizers" do not eliminate all the contaminants. Without clinical trial data and an assurance of product quality, physicians lack the information necessary to assist patients in making informed therapeutic decisions. Both the FDA and Institute of Medicine have stated that there is no future for herbal cannabis as a prescription medicine.
Nevertheless, there may be some truth to the idea that there is pain relief potential in phytocannabinoids (plant-based cannabinoids) and that such potential may be affected by the interaction of THC with other botanical components, particularly with other cannabinoids. Modern strains of cannabis have been bred to maximize the THC at the expense of all other cannabinoids, most of which do not have psychologic effects. Some of those cannabinoids, such as cannabidiol (CBD), have been demonstrated to have important therapeutic value, particularly on pain and inflammation.
Concluding Thoughts
The possibilities for cannabinoid medicines are very promising, and much exciting research is proceeding at a rapid pace. As new FDA-approved cannabinoid products become available, physicians and patients will have a solid scientific foundation from which to assess their appropriateness. Hopefully, robust scientific data will soon allow cannabinoids to take their place – along with opiates and other pain relievers – in the modern medical supply for treating chronic pain.
Bill H. McCarberg, MD, is founder of the Chronic Pain Management Program for Kaiser Permanente, San Diego, and assistant clinical professor in the Department of Family Practice at the University of California, San Diego, School of Medicine. He has served on the board of directors of the American Pain Society and currently is co-president of the Western Pain Society and a National Pain Foundation Advisor.
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