Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid

Amyotroph Lateral Scler Other Motor Neuron Disord. 2004 Mar;5(1):33-9. doi: 10.1080/14660820310016813.


Effective treatment for amyotrophic lateral sclerosis (ALS) remains elusive. Two of the primary hypotheses underlying motor neuron vulnerability are susceptibility to excitotoxicity and oxidative damage. There is rapidly emerging evidence that the cannabinoid receptor system has the potential to reduce both excitotoxic and oxidative cell damage. Here we report that treatment with Delta(9)-tetrahydrocannabinol (Delta(9)-THC) was effective if administered either before or after onset of signs in the ALS mouse model (hSOD(G93A) transgenic mice). Administration at the onset of tremors delayed motor impairment and prolonged survival in Delta(9)-THC treated mice when compared to vehicle controls. In addition, we present an improved method for the analysis of disease progression in the ALS mouse model. This logistic model provides an estimate of the age at which muscle endurance has declined by 50% with much greater accuracy than could be attained for any other measure of decline. In vitro, Delta(9)-THC was extremely effective at reducing oxidative damage in spinal cord cultures. Additionally, Delta(9)-THC is anti-excitotoxic in vitro. These cellular mechanisms may underlie the presumed neuroprotective effect in ALS. As Delta(9)-THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Animals
  • Cannabinoids / antagonists & inhibitors
  • Cannabinoids / therapeutic use*
  • Cell Count / methods
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Dronabinol / analogs & derivatives*
  • Dronabinol / therapeutic use*
  • Drug Interactions
  • Embryo, Mammalian
  • Humans
  • L-Lactate Dehydrogenase
  • Mice
  • Mice, Transgenic
  • Motor Neurons / drug effects
  • Piperidines / pharmacology
  • Psychomotor Performance / drug effects
  • Pyrazoles / pharmacology
  • Rimonabant
  • Spinal Cord / cytology
  • Spinal Cord / drug effects
  • Superoxide Dismutase / genetics
  • Time Factors
  • tert-Butylhydroperoxide / toxicity


  • Cannabinoids
  • Piperidines
  • Pyrazoles
  • Dronabinol
  • tert-Butylhydroperoxide
  • L-Lactate Dehydrogenase
  • SOD1 G93A protein
  • Superoxide Dismutase
  • delta(9)-tetrahydrocannabinolic acid
  • Rimonabant