Cannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis

Summary & key facts

This Cochrane review looked at carefully controlled trials of cannabinoids up to December 2021 to see if they help people with multiple sclerosis (MS) who have muscle tightness (spasticity) and long-lasting nerve pain. The review found that a cannabis-based spray called nabiximols probably reduces spasticity in the short term. The reviewers were unsure whether cannabinoids help chronic nerve pain or improve overall quality of life. Cannabinoids may cause more nervous system problems and more psychiatric problems, and slightly more people stopped treatment because of side effects. The overall confidence in these findings is limited because most studies were short and the evidence was low to very low certainty.

Key facts:

• The review combined results from many carefully controlled trials up to December 2021.
• A cannabis-based spray called nabiximols probably reduces muscle tightness (spasticity) in people with MS in the short term.
• The evidence is uncertain about whether cannabinoids help chronic nerve pain or improve quality of life for people with MS.
• Cannabinoids may increase nervous system problems compared with placebo, based on about 1,150 people in seven studies.
• Cannabinoids may increase psychiatric problems compared with placebo, based on about 1,120 people in six studies.
• There was little to no clear difference in serious adverse events between cannabinoids and placebo in about 3,100 people across 20 studies.
• A small increase in stopping treatment because of side effects was seen with cannabinoids, and the evidence on developing drug tolerance is very uncertain.
• The overall certainty of the evidence is limited because most trials were short-term and the quality of evidence was low to very low.

Abstract

BACKGROUND: Spasticity and chronic neuropathic pain are common and serious symptoms in people with multiple sclerosis (MS). These symptoms increase with disease progression and lead to worsening disability, impaired activities of daily living and quality of life. Anti-spasticity medications and analgesics are of limited benefit or poorly tolerated. Cannabinoids may reduce spasticity and pain in people with MS. Demand for symptomatic treatment with cannabinoids is high. A thorough understanding of the current body of evidence regarding benefits and harms of these drugs is required. OBJECTIVES: To assess benefit and harms of cannabinoids, including synthetic, or herbal and plant-derived cannabinoids, for reducing symptoms for adults with MS. SEARCH METHODS: We searched the following databases from inception to December 2021: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), CINAHL (EBSCO host), LILACS, the Physiotherapy Evidence Database (PEDro), the World Health Organisation International Clinical Trials Registry Platform, the US National Institutes of Health clinical trial register, the European Union Clinical Trials Register, the International Association for Cannabinoid Medicines databank. We hand searched citation lists of included studies and relevant reviews. SELECTION CRITERIA: We included randomised parallel or cross-over trials (RCTs) evaluating any cannabinoid (including herbal Cannabis, Cannabis flowers, plant-based cannabinoids, or synthetic cannabinoids) irrespective of dose, route, frequency, or duration of use for adults with MS. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane Risk of bias 2 tool for parallel RCTs and crossover trials. We rated the certainty of evidence using the GRADE approach for the following outcomes: reduction of 30% in the spasticity Numeric Rating Scale, pain relief of 50% or greater in the Numeric Rating Scale-Pain Intensity, much or very much improvement in the Patient Global Impression of Change (PGIC), Health-Related Quality of Life (HRQoL), withdrawals due to adverse events (AEs) (tolerability), serious adverse events (SAEs), nervous system disorders, psychiatric disorders, physical dependence. MAIN RESULTS: = 0%; low-certainty evidence); • SAEs: cannabinoids may result in little to no difference in the number of participants who have SAEs compared with placebo (OR 1.38, 95% CI 0.96 to 1.99; 20 studies, 3124 participants; I² = 0%; low-certainty evidence); • AEs of the nervous system: cannabinoids may increase nervous system disorders compared with placebo (OR 2.61, 95% CI 1.53 to 4.44; 7 studies, 1154 participants; I² = 63%; low-certainty evidence); • Psychiatric disorders: cannabinoids may increase psychiatric disorders compared with placebo (OR 1.94, 95% CI 1.31 to 2.88; 6 studies, 1122 participants; I² = 0%; low-certainty evidence); • Drug tolerance: the evidence is very uncertain about the effect of cannabinoids on drug tolerance (OR 3.07, 95% CI 0.12 to 75.95; 2 studies, 458 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: Compared with placebo, nabiximols probably reduces the severity of spasticity in the short-term in people with MS. We are uncertain about the effect on chronic neurological pain and health-related quality of life. Cannabinoids may increase slightly treatment discontinuation due to AEs, nervous system and psychiatric disorders compared with placebo. We are uncertain about the effect on drug tolerance. The overall certainty of evidence is limited by short-term duration of the included studies.

Topics

Cannabis and Cannabinoid Research Psychedelics and Drug Studies Vaccine Coverage and Hesitancy

Categories

Health Sciences Medicine Pharmacology

Tags

Cannabis CINAHL Clinical trial Cochrane Library Internal medicine Law Medicine MEDLINE Physical therapy Political science Psychiatry Psychological intervention Randomized controlled trial Spasticity Systematic review

Substances

Cannabis medical cannabis

Conditions & symptoms

Chronic Pain Chronic pain