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HISTORY AND CONTROVERSY OF MEDICAL MARIJUANA
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Cannabis has been utilized as a medicine and in various cultural practices for millennia with accounts of its use dating back over 5000 years.1 There is reference to the use of cannabis for the treatment of headache from the sixth and seventh centuries.2 In the mid-1800s, reports of the therapeutic potential of cannabis entered the medical literature and its use became more widespread.3 However, in the early twentieth century, cannabis was increasingly scrutinized for its psychoactive effects and recreational use, and it was removed from the US Pharmacopoeia in 1942.4 Nonetheless, preclinical studies continued and many neurobehavioral tests confirmed its analgesic effects.5-8 In addition to its use for analgesia, cannabis is under investigation for use in a number of neurological disorders, glaucoma, and as an antiemetic and appetite stimulant.
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In the United States, the use of medical marijuana continues to be a politically charged issue. In November 1996, voters in the states of California and Arizona passed referenda designed to permit the use of marijuana as a medicine, though Arizona's referendum was invalidated 5 months later. Since then, several states have passed ballot initiatives in support of medical marijuana. In January 1997, the White House Office of National Drug Control asked the Institute of Medicine to conduct a review of scientific evidence to assess the health risks and benefits of marijuana. The 1999 Institute of Medicine report contained several recommendations regarding medical marijuana which stated: 1) research should continue into the physiologic effects of synthetic and plant-derived cannabinoids; 2) development of new delivery systems should be pursued;3) the psychological effects of cannabis should be evaluated; 4) studies to define health risks of smoked marijuana should be conducted, and; 5) clinical trials should involve short-term use, reasonable expectations of efficacy, and approval by an Institutional Review Board. The report stated that short-term use of smoked cannabis for patients with debilitating symptoms must meet the following conditions: (1) failure of approved medications, (2) reasonable expectation of efficacy, (3) administration under medical supervision, and (4) inclusion of an oversight strategy.9
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1999 Institute of Medicine Recommendations for Research Focus of Medical Marijuana
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Physiologic effects of synthetic and plant-derived cannabinoids
Development of new delivery systems
Psychological effects of cannabis
Health risks of smoked marijuana
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CANNABINOID BACKGROUND
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The two cannabinoid receptors are CB1 and CB2.10,11 The term cannabinoid refers to a variety of compounds which are (1) derived from cannabis plants (phytocannabinoids), (2) endogenous cannabinoids (referred to as endocannabinoids), and (3) synthetic cannabinoids.12
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Cannabis is a genus of flowering plants that contain three species: Cannabis sativa (the largest variety), C indica, and C ruderalis. The popular name, marijuana, refers to the dried leaves and flowers of C sativa, which are most commonly smoked.4 Marijuana contains nearly ...