The Health Effects of Cannabis and Cannabinoids The Current State of Evidence and Recommendations for Research (2017) / Chapter Skim
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4 Therapeutic Effects of Cannabis and Cannabinoids
4 Therapeutic Effects of Cannabis and Cannabinoids
Pages 85-140
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• In adults with multiple sclerosis (MS) -related spasticity, short term use of oral cannabinoids improves patient-reported spas ticity symptoms.
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Given the steady liberalization of cannabis laws, the numbers of these states are likely to increase and therefore support the efforts to clarify the potential therapeutic benefits of medical cannabis on various health outcomes. For example, the most common conditions for which medical cannabis is used in Colorado and Oregon are pain, spasticity associated with multiple sclerosis, nausea, posttraumatic stress disorder, cancer, epilepsy, cachexia, glaucoma, HIV/AIDS, and degenerative neurological 1 ClinicalTrials.gov: NCT02447198, NCT02926859.
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The resulting therapeutic uses covered by this chapter are chronic pain, cancer, chemotherapy-induced nausea and vomiting, anorexia and weight loss associated with HIV, irritable bowel syndrome, epilepsy, spasticity, Tourette syndrome, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, dystonia, dementia, glaucoma, traumatic brain injury, addiction, anxiety, depression, sleep disorders, posttraumatic stress disorder, and schizophrenia and other psychoses. The committee is aware that there may be other conditions for which there is evidence of efficacy for cannabis or cannabinoids.
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for chronic pain. Are Cannabis or Cannabinoids an Effective Treatment for the Reduction of Chronic Pain?
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. One of those studies found a dose-dependent effect of vaporized cannabis flower on spontaneous pain, with the high dose (7 percent THC)
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Given the ubiquitous availability of cannabis products in much of the nation, more research is needed on the various forms, routes of administration, and combination of cannabinoids. CONCLUSION 4-1 There is substantial evidence that cannabis is an effective treatment for chronic pain in adults.
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Primary Literature The committee did not identify any good-quality primary literature that reported on cannabis or cannabinoids for the treatment of cancer that were published subsequent to the data collection period of the most recently published good- or fair-quality systematic review addressing the research question. Discussion of Findings Clearly, there is insufficient evidence to make any statement about the efficacy of cannabinoids as a treatment for glioma.
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, with 9 placebocontrolled trials (819 participants) and 15 with active comparators (prochlorperazine, 11; metoclopramide, 2; chlorpromazine, 1; domperidone, 1)
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Despite an abundance of anecdotal reports of the benefits of plant cannabis, either inhaled or ingested orally, as an effective treatment for chemotherapy-induced nausea and vomiting, there are no good-quality randomized trials investigating this option.
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AIDS Wasting Syndrome Systematic Reviews Two good-quality systematic reviews included trials investigating cannabinoid therapies in patients with HIV/AIDS. Four randomized controlled trials involving 255 patients were assessed by Whiting et al.
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These investigators concluded that the evidence for the efficacy and safety of cannabis and cannabinoids is lacking to support utility in treating AIDS-associated anorexia. Primary Literature The committee did not identify any good-quality primary literature that reported on cannabis or cannabinoids as effective treatments for AIDS wasting syndrome that were published subsequently to the data collection period of the most recently published good- or fair-quality systematic review addressing the research question.
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. Anorexia Nervosa Systematic Reviews The committee did not identify a good- or fairquality systematic review that reported on medical cannabis as an effective treatment for anorexia nervosa.
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This is, in part, due to existing obstacles to investigating the potential therapeutic benefit of the cannabis plant. CONCLUSION 4-4 There is limited evidence that cannabis and oral cannabi 4-4(a)
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Systematic Reviews The committee did not identify a good- or fair-quality systematic review that reported on medical cannabis as an effective treatment for symptoms of irritable bowel syndrome. Primary Literature We identified a single relevant trial (Wong et al., 2012)
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CONCLUSION 4-5 There is insufficient evidence to support or refute the conclusion that dronabinol is an effective treatment for the symptoms of irritable bowel syndrome. EPILEPSY Epilepsy refers to a spectrum of chronic neurological disorders in which clusters of neurons in the brain sometimes signal abnormally and cause seizures (NINDS, 2016a)
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Randomized trials of the efficacy of cannabidiol for different forms of epilepsy have been completed,7 but their results have not been published at the time of this report. Discussion of Findings Recent systematic reviews were unable to identify any randomized controlled trials evaluating the efficacy of cannabinoids for the treatment of epilepsy.
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. Are Cannabis or Cannabinoids an Effective Treatment for Spasticity Associated with Multiple Sclerosis or Spinal Cord Injury?
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, although oral cannabis extract and orally administered THC are "possibly effective" for objective measures at 1 year. Primary Literature An additional placebo-controlled crossover trial of nabiximols for the treatment of spasticity in patients with MS was published after the period covered by the Whiting and Koppel systematic reviews (Leocani et al., 2015)
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CONCLUSION 4-7 4-7(a) There is substantial evidence that oral cannabinoids are an effective treatment for improving patient-reported multiple sclerosis spasticity symptoms, but limited evi dence for an effect on clinician-measured spasticity.
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Primary Literature The committee did not identify any good-quality primary literature that reported on medical cannabis as an effective treatment for Tourette syndrome, and that were published subsequent to the data collection period of the most recently published good- or fair-quality systematic review addressing the research question. Discussion of Findings No clear link has been established between symptoms of Tourette syndrome and cannabinoid sites or mechanism of action.
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Systematic Reviews The committee did not identify a good- or fair-quality systematic review that reported on medical cannabis as an effective treatment for symptoms associated with amyotrophic lateral sclerosis. Primary Literature On the basis of proposed pathogenesis and anecdotal reports of symptomatic benefit from the use of cannabis in patients with ALS, two small trials of dronabinol have been conducted.
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The effect of cannabis was not investigated. CONCLUSION 4-9 There is insufficient evidence that cannabi noids are an effective treatment for symptoms associated with amyotrophic lateral sclerosis.
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There were no statistically significant differences between cannabidiol and placebo in any outcomes, although the American Academy of Neurology considered the study to be underpowered. Primary Literature The committee did not identify any good-quality primary literature that reported on medical cannabis as an effective treatment for the declines in motor function and cognitive performance associated with Huntington's disease that were published subsequent to the data collection period of the most recently published good- or fair-quality systematic review addressing the research question.
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; thus, it may be useful to determine the efficacy of cannabinoids in treating the symptoms of neurodegenerative diseases. Are Cannabis or Cannabinoids an Effective Treatment for the Motor System Symptoms Associated with Parkinson's Disease or the Levodopa-Induced Dyskinesia?
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. Primary Literature Cannabidiol capsules were evaluated in a randomized, double-blind, placebo-controlled trial conducted in 21 patients with Parkinson's disease (Chagas et al., 2014)
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An observational study of inhaled cannabis demonstrated improved outcomes, but the lack of a control group and the small sample size are limitations. CONCLUSION 4-11 There is insufficient evidence that can nabinoids are an effective treatment for the motor system symptoms associated with Parkinson's disease or the levodopa induced dyskinesia.
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Cannabis has not been studied in the treatment of dystonia. CONCLUSION 4-12 There is insufficient evidence to support or refute the conclusion that nabilone and dronabinol are an effective treatment for dystonia.
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Are Cannabis or Cannabinoids an Effective Treatment for the Symptoms Associated with Dementia? Systematic Reviews We identified two good-quality systematic reviews (Krishnan et al., 2009; van den Elsen et al., 2014)
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CONCLUSION 4-13 There is limited evidence that cannabi noids are ineffective treatments for improving the symptoms associated with dementia. GLAUCOMA Glaucoma is one of the leading causes of blindness within the United States (Mayo Clinic, 2015)
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No differences in intraocular pressure were found between placebo and cannabinoids. Primary Literature The committee did not identify any good-quality primary literature that reported on medical cannabis as an effective treatment for the symptoms of glaucoma and that were published subsequent to the data collection period of the most recently published good- or fair-quality systematic review addressing the research question.
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Systematic Reviews The committee did not identify a good- or fair-quality systematic review that evaluated the efficacy of cannabinoids as a treatment or prevention for traumatic brain injury or intracranial hemorrhage. Primary Literature There were two fair- to high-quality observational studies found in the literature.
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However, more conclusive observational studies or randomized controlled trials will be necessary before any conclusions can be drawn about the neuroprotective effect of cannabinoids in clinical populations. CONCLUSION 4-15 There is limited evidence of a statistical association between cannabinoids and better outcomes (i.e., mortality, disability)
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Over the 6-day treatment period, subjects in the nabiximols group reported a mean 66 percent reduction from baseline in the cannabis withdrawal scale, while patients in the placebo group reported a mean increase in the cannabis withdrawal scale of 52 percent (p-value for between-group difference = 0.01)
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Primary Literature The committee did not identify any good-quality primary literature that reported on medical cannabis as an effective treatment for the reduction in use of addictive substances and that were published subsequent to the data collection period of the most recently published good- or fairquality systematic review addressing the research question. Discussion of Findings Based on the systematic reviews, neither of the two trials evaluating the efficacy of a cannabinoid in achieving or sustaining abstinence from cannabis showed a statistically significant effect.
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Primary Literature The committee did not identify any good-quality primary literature that reported on medical cannabis as an effective treatment for the improvement of anxiety symptoms and that were published subsequent to the data collection period of the most recently published good- or fairquality systematic review addressing the research question. Discussion of Findings There is limited evidence that cannabidiol improves anxiety symptoms, as assessed by a public speaking test, in patients with social anxiety disorder.
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. CONCLUSION 4-17 There is limited evidence that cannabidiol is an effective treatment for the improvement of anxiety symp toms, as assessed by a public speaking test, in individuals with social anxiety disorders.
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CONCLUSION 4-18 There is limited evidence that nabiximols, dronabinol, and nabilone are ineffective treatments for the reduction of depressive symptoms in individuals with chronic pain or multiple sclerosis. SLEEP DISORDERS Sleep disorders can be classified into major groups that include insomnia, sleep-related breathing disorders, parasomnias, sleep-related movement disorders, and circadian rhythm sleep–wake disorders (Sateia, 2014)
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The summary estimate showing benefit was based primarily on studies of nabiximols. Primary Literature The committee did not identify any good-quality primary literature that reported on medical cannabis as an effective treatment to improve sleep outcomes and that were published subsequent to the data collection period of the most recently published good- or fair-quality systematic review addressing the research question.
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The committee did not identify any clinical trials that evaluated the effects of cannabinoids in patients with primary chronic insomnia. CONCLUSION 4-19 There is moderate evidence that canna binoids, primarily nabiximols, are an effective treatment to improve short-term sleep outcomes in individuals with sleep disturbance associated with obstructive sleep apnea syndrome, fibromyalgia, chronic pain, and multiple sclerosis.
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This limited evidence is most applicable to male veterans and contrasts with non-randomized studies showing limited evidence of a statistical association between cannabis use (plant derived forms) and increased severity of posttraumatic stress disorder symptoms among individuals with posttraumatic stress disorder (see Chapter 12)
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. Primary Literature The committee did not identify any good-quality primary literature that reported on medical cannabis as an effective treatment for the mental health outcomes of patients with schizophrenia or other psychoses and that were published subsequent to the data collection period of the most recently published good- or fair-quality systematic review addressing the research question.
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CONCLUSION 4-21 There is insufficient evidence to sup port or refute the conclusion that cannabidiol is an effective treatment for the mental health outcomes in individuals with schizophrenia or schizophreniform psychosis. RESEARCH GAPS In reviewing the research evidence described above, the committee has identified that research gaps exist concerning the effectiveness of cannabidiol or cannabidiol-enriched cannabis in treating the following: • cancer in general • treating chemotherapy-induced nausea and vomiting • symptoms of irritable bowel syndrome • epilepsy • spasticity due to paraplegia from spinal cord injury • symptoms associated with amyotrophic lateral sclerosis • motor function and cognitive performance associated with Huntington's Disease • motor system symptoms associated with Parkinson's disease or levodopa-induced dyskinesia • achieving abstinence or reduction in the use of addictive sub stances, including cannabis itself • sleep outcomes in individuals with primary chronic insomnia • posttraumatic stress disorder symptoms
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For chemotherapy-induced nausea and vomiting and spasticity associated with multiple sclerosis, the primary route of administration examined was the oral route. For chronic pain, most studies examined oral cannabis extract, although some examined smoked or vaporized cannabis.
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(4-7a) There is moderate evidence that cannabis or cannabinoids are effective for: • I mproving short-term sleep outcomes in individuals with sleep disturbance associated with obstructive sleep apnea syndrome, fibromyalgia, chronic pain, and multiple sclerosis (cannabinoids, primarily nabiximols)
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(4-14) • R educing depressive symptoms in individuals with chronic pain or multiple sclerosis (nabiximols, dronabinol, and nabilone)
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2016. Medical cannabis use is associated with decreased opiate medication use in a retrospective cross-sectional survey of patients with chronic pain.
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2011. Posttraumatic stress disorder and cannabis use in a nationally representative sample.
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2015. Sativex® and clinical neurophysiological measures of spasticity in progressive multiple sclerosis.
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2016. State medical marijuana laws.
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2016c. Traumatic brain injury: Hope through research.
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2010. The endocannabinoid system in the inflamma tory and neurodegenerative processes of multiple sclerosis and of amyotrophic lateral sclerosis.
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for cramps in amyotrophic lateral sclerosis: A randomised, double-blind crossover trial. Journal of Neurology, Neurosurgery & Psychiatry 81(10)
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2012. Multiple sclerosis and extract of cannabis: Results of the MUSEC trial.
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Part III Other Health Effects
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