Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ⁹-THCV in animal models of Parkinson's disease

Br J Pharmacol. 2011 Aug;163(7):1495-506. doi: 10.1111/j.1476-5381.2011.01278.x.


Background and purpose: Previous findings have indicated that a cannabinoid, such as Δ(9)-THCV, which has antioxidant properties and the ability to activate CB(2) receptors but to block CB(1) , might be a promising therapy for alleviating symptoms and delaying neurodegeneration in Parkinson's disease (PD).

Experimental approach: The ability of Δ(9)-THCV to reduce motor inhibition and provide neuroprotection was investigated in rats lesioned with 6-hydroxydopamine and in mice lesioned with lipopolysaccharide (LPS).

Key results: Acute administration of Δ(9)-THCV attenuated the motor inhibition caused by 6-hydroxydopamine, presumably through changes in glutamatergic transmission. Moreover, chronic administration of Δ(9)-THCV attenuated the loss of tyrosine hydroxylase-positive neurones caused by 6-hydroxydopamine in the substantia nigra, through an effect related to its antioxidant properties (it was reproduced by cannabidiol -enriched botanical extract). In addition, CB(2) receptor-deficient mice responded to 6-hydroxydopamine in a similar manner to wild-type animals, and CB(2) receptors were poorly up-regulated in the rat substantia nigra in response to 6-hydroxydopamine. By contrast, the substantia nigra of mice that had been injected with LPS exhibited a greater up-regulation of CB(2) receptors. In these animals, Δ(9)-THCV also caused preservation of tyrosine hydroxylase-positive neurones. This effect probably involved CB(2) receptors as it was also elicited by the selective CB(2) receptor agonist, HU-308, and CB(2) receptor-deficient mice were more vulnerable to LPS lesions. CONCLUSIONS AND IMPLICATIONS Given its antioxidant properties and its ability to activate CB(2) but to block CB(1) receptors, Δ(9)-THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Cannabinoids / pharmacology
  • Cyclohexanols / pharmacology
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dronabinol / pharmacology*
  • Glutamic Acid / metabolism
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Motor Activity / drug effects
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology*
  • Oxidopamine / pharmacology
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Receptor, Cannabinoid, CB2 / agonists
  • Receptor, Cannabinoid, CB2 / deficiency
  • Receptor, Cannabinoid, CB2 / metabolism*
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Tyrosine 3-Monooxygenase / metabolism


  • Antioxidants
  • Cannabinoids
  • Cyclohexanols
  • Lipopolysaccharides
  • Neuroprotective Agents
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • lipopolysaccharide A
  • Glutamic Acid
  • Dronabinol
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
  • Oxidopamine
  • HU 308
  • Tyrosine 3-Monooxygenase
  • Dopamine