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Keywords:

  • Amyotrophic lateral sclerosis;
  • Cannabinoids;
  • CB1 and CB2 receptors;
  • Endocannabinoid enzymes;
  • Sativex-like combination of phytocannabinoids;
  • SOD1 mutant mice

Summary

Aims

Cannabinoids afford neuroprotection in SOD1G93A mutant mice, an experimental model of amyotrophic lateral sclerosis (ALS). However, these mice have been poorly studied to identify alterations in those elements of the endocannabinoid system targeted by these treatments. Moreover, we studied the neuroprotective effect of the phytocannabinoid-based medicine Sativex® in these mice.

Methods

First, we analyzed the endocannabinoid receptors and enzymes in the spinal cord of SOD1G93A transgenic mice at a late stage of the disease. Second, 10-week-old transgenic mice were daily treated with an equimolecular combination of Δ9-tetrahydrocannabinol- and cannabidiol-enriched botanical extracts (20 mg/kg for each phytocannabinoid).

Results

We found a significant increase of CB2 receptors and NAPE-PLD enzyme in SOD1G93A transgenic males and only CB2 receptors in females. Pharmacological experiments demonstrated that the treatment of these mice with the Sativex®-like combination of phytocannabinoids only produced weak improvements in the progression of neurological deficits and in the animal survival, particularly in females.

Conclusions

Our results demonstrated changes in endocannabinoid signaling, in particular a marked up-regulation of CB2 receptors, in SOD1G93A transgenic mice, and provide support that Sativex® may serve as a novel disease-modifying therapy in ALS.