Targeting the CB2 receptor and other endocannabinoid elements to delay disease progression in amyotrophic lateral sclerosis

Br J Pharmacol. 2021 Mar;178(6):1373-1387. doi: 10.1111/bph.15386. Epub 2021 Feb 20.


Cannabinoids form a singular group of plant-derived compounds, endogenous lipids and synthetic derivatives with multiple therapeutic effects exerted by targeting different elements of the endocannabinoid system. One of their therapeutic applications is the preservation of neuronal integrity exerted by attenuating the multiple neurotoxic events that kill neurons in neurodegenerative disorders. In this review, we will address the potential of cannabinoids as neuroprotective agents in amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disorder characterized by muscle denervation, atrophy and paralysis, and progressive deterioration in upper and/or lower motor neurons. The emphasis will be paid on the cannabinoid type 2 (CB2 ) receptor, whose activation limits glial reactivity, but the potential of additional endocannabinoid-related targets will be also addressed. The evidence accumulated so far at the preclinical level supports the need to soon move towards the patients and initiate clinical trials to confirm the potential of cannabinoid-based medicines as disease modifiers in ALS. LINKED ARTICLES: This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit

Keywords: CB2 receptors; amyotrophic lateral sclerosis; cannabinoids; endocannabinoid signalling system; neurodegeneration; neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis* / drug therapy
  • Cannabinoids* / therapeutic use
  • Disease Progression
  • Endocannabinoids
  • Humans
  • Motor Neurons
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2


  • Cannabinoids
  • Endocannabinoids
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2