Medical Marijuana and Other Cannabinoids _____________________________________________________
HIV-Associated Distal Sensory Polyneuropathy In a five-day trial of 55 patients with HIV-associated distal sensory polyneuropathy, overall daily pain levels were reduced by 34% with active cannabis vs. 17% with placebo, and pain reduction of more than 30% was attained by 52% with active cannabis vs. 24% with placebo; both differences in pain reduc- tion were statistically significant. Cannabis was well tolerated and no safety concerns were raised. Cannabis produced more side effects than placebo, the most common being sedation, anxiety, and dizziness, all rated as “mild” in severity [179]. Another study titrated 34 patients with HIV-associated distal sensory polyneuropathy to individualized effective and toler- ated inhaled cannabis doses. Titration started with 4% THC or placebo, with downward or upward adjustment for problematic side effects or incomplete pain relief, respectively. In five study phases over seven weeks, >30% pain reduction was attained by 46% with cannabis vs. 18% with placebo (statistically signifi- cant). Side effects were more frequent with cannabis, the most common being sleepiness or sedation, fatigue, and difficulty concentrating. Aside from acute psychotic symptoms develop- ing early in the only cannabis-naïve subject, all side effects were “mild” and no safety concerns emerged [180]. Both of these studies restricted enrollment to patients with refractory pain despite optimal pharmacologic management, and all patients remained on their pre-study analgesic thera- pies. Of note, the significant magnitude of pain reduction in HIV neuropathy with cannabis therapy represents an important medical finding, because this type of pain has been notoriously resistant to standard treatment approaches [60]. Neuropathic Pain of Heterogeneous Origin A trial of 38 patients with complex regional pain syndrome (Type I), physical trauma to nerve bundles, spinal cord injury, multiple sclerosis, or diabetes smoked a single high-(7%), low- (3.5%), or 0% THC (placebo) cannabis cigarette in three six- hour sessions [181]. Previous cannabis exposure was required. Low-and high-THC cannabis produced effective analgesia with comparability, suggesting a dose ceiling. Unpleasant side effects were more frequent with high-dose THC. Side effects were comparable between low-dose and placebo, and no subject terminated their involvement from side effects. Negative mood changes (e.g., sadness, anxiety, fearfulness) were not found. The authors stated the effects produced by cannabis were comparable to those observed with opioid analgesics, with pain relief resulting from equal alleviation of the affective and sensory component of pain but not resulting from a relaxing
with a wide range of other drug agents (as discussed) and acts synergistically with opioids to enhance analgesia and allow opioid dose reduction. Chronic pain treatment often requires multiple drug agents that target different pain mechanisms, and the novel mechanism and superior safety profile of cannabis versus opioids suggests that it can be a valuable addition to therapeutic options for chronic pain [174; 175]. Chronic pain is a highly prevalent, heterogeneous group of disorders that in many patients is refractory or only partially responsive to treatment [174]. Many cannabis analgesia stud- ies use a benchmark of more than 30% reduction in pain intensity, because a 30% decrease in pain has been validated as the threshold necessary for meaningful improvements in quality of life [26]. The following studies on chronic pain are presented in greater detail because their results and the scien- tifically rigorous conditions under which they were conducted are now regarded as providing the most definitive evidence of efficacy [88]. Neuropathic Pain More than 2 million Americans currently suffer chronic and debilitating neuropathic pain from trauma or disease affecting the peripheral or central nervous system. These conditions include diabetic neuropathy, nerve compression syndromes, postherpetic or trigeminal neuralgia, stroke, multiple sclerosis, and spinal cord injury. Neuropathic pain is comprised of a sen- sory component of allodynia (pain response to benign stimuli) and hyperalgesia (exaggerated pain to mild provocation), and an affective component of prominent anxiety or depression, diminished motivation, and changes in motor control. Neu- ropathic pain is difficult to treat, and while the sensory and affective components may respond to opioid therapy, this drug class often produces intolerable side effects or fails to provide meaningful pain reduction. Earlier trials suggested effective analgesia with cannabis, and priorities in finding therapeutic alternatives to high-potency opioids prompted investigation of cannabis efficacy in neuropathic pain [176; 177]. Finding even modest clinical benefit is important given the limited treatment options for these patients, and the RCTs uniformly found the number needed to treat to achieve 30% pain reduction was 3.5 for cannabis [178]. In one study, use of nabiximols was found to be the most effective cannabinoid for multiple sclerosis- associated central pain [177]. Unless otherwise noted, the RCT methods in the following sections were double-blinded and placebo-controlled with inert, non-active cannabis and/or pills.
The National Institute for Health and Care Excellence recommends against starting Cannabis sativa extract to treat neuropathic pain in non-specialist settings, unless advised by a specialist to do so. (https://www.nice.org.uk/guidance/cg173.
or tranquilizing effect [181]. Chronic Post-Traumatic or Postsurgical Neuropathic Pain
In an RCT with crossover, 23 subjects with chronic post- traumatic neuropathic pain smoked a single 25-mg dose of 0%, 2.5%, 6%, or 9.4% THC cannabis, three times daily over four 14-day periods alternating with 9-day washout [134]. The average daily pain intensity score was significantly lower with
Last accessed November 21, 2023.) Level of Evidence : Expert Opinion/Consensus Statement
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