Medical Marijuana and Other Cannabinoids _____________________________________________________
but is not yet approved for clinical use in the United States [192]. Several clinical trials of cannabis in multiple sclerosis have been performed, and these studies have demonstrated cannabis efficacy in reducing spasticity and pain [193; 194]. Cannabis-based medicine was effective in reducing pain and sleep disturbance in patients with multiple sclerosis and central neuropathic pain in one trial, while other RCTs demonstrated significant improvements in spasticity, disability, cognition, mood, sleep, and fatigue [195; 196; 197]. A 2004 study also found that cannabis helped alleviate bladder dysfunction, a problematic multiple sclerosis symptom [198]. A double-blind, placebo-controlled crossover study randomized patients with multiple sclerosis to smoke 4% THC or placebo cannabis cigarettes once daily for three days [194]. The findings of sig- nificant objective improvement in pain and spasticity differed from earlier trials showing significant improvement in patient perceptions but not objective measurements of spasticity [194]. Side effects have been acceptable to patients, and no serious safety concerns have emerged. Preclinical studies suggest a positive effect on the underlying disease processes in multiple sclerosis, evidence of an anti-inflammatory effect, and facilita- tion of remyelination and neuroprotection [199].
Other beneficial effects included increased alertness, elevated mood, and improved sleep, and side effects included drowsi- ness and fatigue. In 2018, the FDA approved purified can- nabidiol for use in patients with Lennox-Gastaut and Dravet syndromes, but until recently, most published studies were relatively short-term (12 to 16 weeks) [83; 203; 204]. The objec- tive of a 2019 study was to evaluate the long-term safety, toler- ability, and efficacy of cannabidiol in children with epilepsy [204]. This open-label prospective study enrolled 26 children 1 to 17 years of age with refractory epilepsy, most with genetic epilepsies with daily or weekly seizures and multiple seizure types. All of the children were refractory to prior antiepileptic drugs and were, on average, taking two antiepileptic drugs. The duration of therapy ranged from 4 to 53 months (mean: 21 months). Adverse events were reported in 21 patients (80.8%) and included reduced appetite, diarrhea, and weight loss. Seri- ous adverse events were reported in six patients (23.1%) and included status epilepticus, catatonia, and hypoalbuminemia. Fifteen patients (57.7%) discontinued cannabidiol for lack of efficacy. At 24 months, 9 of the original 26 patients (34.6%) remained on cannabidiol as adjunctive therapy. Of these, seven reported a more than 50% reduction in motor seizures and three remained seizure free [204]. Fibromyalgia A matched case control study of medicinal cannabis use for symptom control in fibromyalgia found patient accounts of cannabis efficacy in alleviating pain, sleep disturbance, stiffness, problematic mood and anxiety, and headache, and objectively measured significant improvements in pain, stiffness, relax- ation, and well-being [205]. An estimated 68% of participants experienced a reduction in standard therapies following can- nabis initiation. Frequent side effects were somnolence, dry mouth, sedation, and dizziness. Significantly higher mental health-related quality of life scores were found in medicinal cannabis users compared with non-users [205].
The American Academy of Neurology asserts that clinicians might offer oral cannabis extract to patients with multiple
sclerosis to reduce patient-reported symptoms of spasticity and pain (excluding central neuropathic pain). (https://www.aan.com/Guidelines/home/Guideline Detail/641. Last accessed November 21, 2023.) Level of Evidence : A (Established as effective for the given condition in the specified population.) Post-Traumatic Stress Disorder Numerous case reports describe substantial reduction in PTSD symptoms with cannabis use [200]. An open-label study of nabilone in 47 patients with treatment-refractory PTSD- associated nightmares found cessation or significantly reduced nightmare intensity in 72% of participants and diminished daytime flashbacks and night sweats and/or improved sleep duration and quality for some [201]. More robust research supporting the safety and efficacy of this use is lacking [202]. Seizure Disorders As noted, cannabis can be bred to overexpress CBD in order to avoid psychoactive effects. In one study, CBD-enriched canna- bis was administered to 19 children with treatment-refractory epilepsy (after an average of 12 pre-study antiepileptic drugs) and their parents were interviewed to assess efficacy. Of the 19 patients, 84% showed reduced seizure frequency, 11% became completely seizure-free, 42% showed greater than 80% seizure reduction, and 32% showed a 25% to 60% seizure reduction.
GASTROINTESTINAL DISORDERS/DYSFUNCTION Irritable Bowel Syndrome and Crohn Disease
In one study of patients with chronic irritable bowel syndrome, inhaled cannabis for three months led to improvements in quality of life, disease activity, and weight gain [206]. Obser- vational study data in patients with Crohn disease suggest that cannabis helps alleviate disease symptom severity and reduces the requirements for other medications and/or the need for surgery [207]. Nausea and Vomiting Chemotherapy-induced nausea and vomiting was very difficult to manage before the introduction of 5-HT3 receptor antago- nists. However, 5-HT3 antagonists are not very effective in blocking acute nausea and are ineffective in reducing delayed (24 hours or more) and anticipatory (conditioned) nausea and
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