A Critical Review of the Role of the Cannabinoid Compounds Δ9-Tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD) and their Combination in Multiple Sclerosis Treatment

Molecules. 2020 Oct 25;25(21):4930. doi: 10.3390/molecules25214930.


Many people with MS (pwMS) use unregulated cannabis or cannabis products to treat the symptoms associated with the disease. In line with this, Sativex, a synthetic combination of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) has been approved to treat symptoms of spasticity. In animals, CBD is effective in reducing the amounts of T-cell infiltrates in the spinal cord, suggesting CBD has anti-inflammatory properties. By doing this, CBD has shown to delay symptom onset in animal models of multiple sclerosis and slow disease progression. Importantly, combinations of CBD and Δ9-THC appear more effective in treating animal models of multiple sclerosis. While CBD reduces the amounts of cell infiltrates in the spinal cord, Δ9-THC reduces scores of spasticity. In human studies, the results are less encouraging and conflict with the findings in animals. Drugs which deliver a combination of Δ9-THC and CBD in a 1:1 ratio appear to be only moderately effective in reducing spasticity scores, but appear to be almost as effective as current front-line treatments and cause less severe side effects than other treatments, such as baclofen (a GABA-B receptor agonist) and tizanidine (an α2 adrenergic receptor agonist). The findings of the studies reviewed suggest that cannabinoids may help treat neuropathic pain in pwMS as an add-on therapy to already established pain treatments. It is important to note that treatment with cannabinoid compounds may cause significant cognitive dysfunction. Long term double-blind placebo studies are greatly needed to further our understanding of the role of cannabinoids in multiple sclerosis treatment.

Keywords: animal models; cannabidiol; cannabinoid; cognition; experimental autoimmune encephalomyelitis; inflammation; multiple sclerosis; neuropathic pain; neuroprotection; spasticity; Δ9-tetrahydrocannabinol.

Publication types

  • Review

MeSH terms

  • Analgesics / chemistry*
  • Analgesics / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Baclofen / pharmacology
  • Cannabidiol / chemistry*
  • Cannabidiol / pharmacology
  • Clinical Trials as Topic
  • Clonidine / analogs & derivatives
  • Clonidine / pharmacology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Dronabinol / chemistry*
  • Dronabinol / pharmacology
  • Drug Approval
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Multiple Sclerosis / drug therapy*
  • Spinal Cord / drug effects
  • Treatment Outcome
  • United States
  • United States Food and Drug Administration


  • Analgesics
  • Anti-Inflammatory Agents
  • Drug Combinations
  • Cannabidiol
  • tizanidine
  • Dronabinol
  • Baclofen
  • nabiximols
  • Clonidine