Medical Marijuana and Other Cannabinoids _____________________________________________________
SLEEP DISORDERS Sleep disturbances contribute to greater pain, disease activity, mood disturbance, and disability in patients with chronic pain, and restoring normal sleep improves pain and mood disorders associated with uncontrolled pain and sleep impairment [60]. However, drugs used for sleep induction (such as benzodiaz- epines) increase rates of sleep-disordered breathing and elevate the risk of respiratory depression and fatal respiratory arrest when combined with opioids, antihistamines, or alcohol. Unlike sedative-hypnotics, cannabinoids suppress sleep-related apnea and do not enhance opioid-induced respiratory depres- sion [37]. Research in chronic pain patients has consistently shown beneficial cannabinoid effects on sleep quality [60]. CANCER- AND HIV-ASSOCIATED ANOREXIA AND WEIGHT LOSS Anorexia, early satiety, weight loss, and cachexia are prevalent in late-stage cancer and advanced HIV disease. Most standard treatments are ineffective, but many patients show favorable response with marijuana and cannabinoids [88]. A 2005 survey of HIV-positive medical marijuana users found decreased nau- sea and other burdensome symptoms in 93% of participants and substantial improvement of nausea in 56% [4]. A double- blind clinical trial of HIV-positive patients found smoked can- nabis increased daily caloric intake and body weight, with few adverse effects [217]. Benefits from smoked cannabis reported by 252 patients with HIV/AIDS included relief of anxiety and/or depression (57%), improved appetite (53%), increased pleasure (33%), and pain relief (28%). However, recent use of marijuana was strongly associated with severe nausea [218]. Long-term data on the sustained effect of cannabis and can- nabinoids for the treatment of HIV/AIDS-associated anorexia are lacking [219]. A review of cannabinoid use in patients with cancer found a beneficial effect in stimulating appetite in patients who were receiving chemotherapy or experiencing pain [220]. Interest- ingly, the results of several preclinical and preliminary clinical testing studies have suggested that cannabinoids inhibit tumor and/or malignant cell growth in pancreatic, lung, leukemic, melanoma, oral, and lymphoma cancers and other malignant tumors [220; 222]. GLAUCOMA High intraocular pressure is a risk factor for glaucoma, and smoked cannabis has been found to reduce pupil constriction, conjunctival hyperemia, and intraocular pressure by approxi- mately 25% in those with normal range intraocular pressure with visual field changes, healthy adults, and patients with glaucoma [223]. However, the short duration of effect (three to four hours), side effect profile (including potentially lowering blood supply to the optic nerve by lowering systemic blood pressure), and lack of evidence regarding impact on the course of the disease limit the potential positive impact of cannabis for the treatment of treatment-resistant glaucoma [223; 224]. The
American Glaucoma Society recommends against the use of smoked cannabis for the treatment of glaucoma, and the IOM and the American Academy of Ophthalmology concluded that smoked cannabis is neither a safer alternative nor offers increased benefits compared with conventional pharmaceutical agents [224]. More research is necessary to determine if topical administration may confer greater benefits.
NATURALISTIC STUDIES OF MEDICAL CANNABIS USE
Naturalistic studies have been performed in persons illicitly using medicinal cannabis for symptom relief over diverse diseases and conditions. These studies provide important background information on medicinal cannabis users and improved understanding of limitations with standard thera- peutics [15]. Diverse backgrounds have been found in medical user members of Cannabis Buyer’s Cooperatives. A 1998 study of 1,500 cooperative members in Oakland and Los Angeles found illicit cannabis was used for HIV/AIDS in 62% to 70% of members and cancer in 4% to 10%. In the remaining Oakland members, another 10% reported using cannabis for pain or arthritis, 8% for mood disorders, 6% for neurologic symptoms, 4% for glaucoma, and 6% for “other” conditions; in remaining Los Angeles members, 20% used cannabis for “other” diagnoses, including neurologic diseases, glaucoma, hepatitis, cardiovascular disease, and renal failure [225]. These patients differed from those in a UK study of 2,969 adults who used cannabis for symptom relief in chronic pain (25%), multiple sclerosis (22%), depression (22%), arthritis (21%), and neuropathy (19%) [226]. In another study of 209 Canadians using cannabis to control chronic (median: eight years) non-cancer pain, the most frequent pain type was trauma or postsurgical pain (51%), with the most frequent pain sites being neck/upper body pain (68%) and myofascial pain (65%) [227]. Frequency of cannabis analgesic use was evenly distrib- uted over the intervals of more than once daily, once daily, weekly, and rarely. Greatest symptom improvement was in pain, sleep, and mood [227]. In a report involving 220 Canadian patients with multiple sclerosis, 36% had used cannabis prior to legalization and 14% continued its use for symptom relief; the greatest improvements were in pain, stress, sleep difficulties, mood, and muscle spasm/stiffness [228]. Another study found that 80% of patients with limitations in activity or function from chronic illness attained consistent pain reduction, on a 1–10 scale, ranging from 7 to 10 [32]. ALTERNATIVES TO CANNABIS Opponents of medicinal cannabis often state that dronabi- nol provides the alleged benefits of smoked cannabis and fewer risks, essentially arguing that any benefit is the result of Δ 9-THC. However, dronabinol is not a realistic substitute for inhaled cannabis for a number of reasons. Many patients describe dronabinol’s effect as unpleasant, due to excessive sedation and an overwhelming psychoactive effect. This is likely
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