Journal of Opioid Management 5.3, May/June 2009
Sunil Kumar Aggarwal, MD, PhD
Gregory T. Carter, MD, MS
Mark D. Sullivan, MD, PhD
Craig ZumBrunnen, PhD
Richard Morrill, PhD
Jonathan D. Mayer, PhD
Cannabis (marijuana) has been used for medicinal purposes for millennia, said to be first noted by the Chinese in c. 2737 BCE. Medicinal cannabis arrived in the United States much later, burdened with a remarkably checkered, yet colorful, history. Despite early robust use, after the advent of opioids and aspirin, medicinal cannabis use faded.
Cannabis was criminalized in the United States in 1937, against the advice of the American Medical Association submitted on record to Congress. The past few decades have seen renewed interest in medicinal cannabis, with the National Institutes of Health, the Institute of Medicine, and the American College of Physicians, all issuing statements of support for further research and development.
The recently discovered endocannabinoid system has greatly increased our understanding of the actions of exogenous cannabis. Endocannabinoids appear to control pain, muscle tone, mood state, appetite, and inflammation, among other effects. Cannabis contains more than 100 different cannabinoids and has the capacity for analgesia through neuromodulation in ascending and descending pain pathways, neuroprotection, and anti-inflammatory mechanisms.
This article reviews the current and emerging research on the physiological mechanisms of cannabinoids and their applications in managing chronic pain, muscle spasticity, cachexia, and other debilitating problems.
Keywords: cannabinoids, cannabis, marijuana, chronic pain, opioids, opiates, botanical medicine
INTRODUCTION: AN OVERVIEW OF CANNABINOID MEDICINE IN THE UNITED STATES
Though disrupted by a post-1937 Cannabis sativa L. prohibition, the emerging field of cannabinoid medicine is growing in the United States (seeFigure 1) as ever greater numbers of healthcare providers become educated about the physiologic importance of the endogenous cannabinoid system1-3 and about the wide safety margins4 and broad clinical efficacies5-8 of cannabinoid drugs. Cannabinoid medicines are available in both purely botanical and purely chemical varieties and are useful for managing pain and other conditions in the growing chronically and critically ill patient population.9
This article provides a current and historical perspective of the use of cannabinoid therapies in the United States. The following is a brief overview of the various cannabinoid medicines currently utilized in the American healthcare sector.
They fall into three categories: single molecule pharmaceuticals, cannabis-based liquid extracts, and phytocannabinoid-dense botanicals–the main focus of this article (Figure 2).
The first category includes US Food and Drug Administration (FDA)-approved synthetic or semi-synthetic single molecule cannabinoid pharmaceuticals available by prescription. Currently, these are dronabinol, a Schedule III drug and nabilone, a Schedule II drug. Though both are also used off-label, dronabinol, a (-)trans- 9-tetrahydrocannabinol (THC) isomer found in natural cannabis, has been approved for two uses since 1985 and 1992, respectively: the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments and the treatment of anorexia associated with weight loss in patients with AIDS.10,11 Nabilone, a synthetic molecule shaped similarly to THC, has also been approved since 1985 for use in the treatment of nausea and vomiting associated with cancer chemotherapy.12,13
The second category of cannabinoid medicines being used in the United States includes a line of cannabis-based medicinal extracts developed by several companies.
The industry leader is GW Pharmaceuticals, a UK-based biopharmaceutical company whose lead product is currently undergoing FDA-approved, multisite Phase IIb clinical trials for the treatment of opioid-refractory cancer pain in the United States14 and has received prior approval for Phase III clinical trials in the United States. This botanical drug extract which goes by the nonproprietary name nabiximols has already secured approval in Canada for use in the treatment of central neuropathic pain in multiple sclerosis (in 2005) and in the treatment of intractable cancer pain (in 2007).15 It is also available on a named patient basis in theUnited Kingdom and Catalonia,16,17 a scheme which allows a doctor to prescribe an unlicensed drug to a particular “named patient,” and has been exported to 22 countries to date.
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