Amyotrophic lateral sclerosis

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

Chandrasekaran Raman, Sean D McAllister, Gulrukh Rizvi, Sonal G Patel, Dan H Moore, Mary E Abood

Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders, 2004 March; 5(1):33-39

Publisher: Taylor & Francis Health Sciences, part of the Taylor & Francis Group

URL: Taylor & Francis Health Sciences

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

Chandrasekaran Raman ^A1, Sean D McAllister ^A1, Gulrukh Rizvi ^A1, Sonal G Patel ^A1, Dan H Moore ^A2, Mary E Abood ^A1

^A1 Forbes Norris MDA/ALS Research Center 2351 Clay Street, Suite 416

^A2 Geraldine Brush Cancer Research Institute California Pacific Medical Center San Francisco CA 94115 USA

Abstract:

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 delta9-tetrahydrocannabinol (delta9-THC) was effective if administered either before or after onset of signs in the ALS mouse model (hSODG93A transgenic mice).

Administration at the onset of tremors delayed motor impairment and prolonged survival in delta9-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, delta9-THC was extremely effective at reducing oxidative damage in spinal cord cultures. Additionally, delta9-THC is anti-excitotoxic in vitro. These cellular mechanisms may underlie the presumed neuroprotective effect in ALS. As delta9-THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS.