RGD Reference Report - Symptom-relieving and neuroprotective effects of the phytocannabinoid D(9) -THCV in animal models of Parkinson's disease. - Rat Genome Database

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Symptom-relieving and neuroprotective effects of the phytocannabinoid D(9) -THCV in animal models of Parkinson's disease.

Authors: Garcia, C  Palomo, C  Garcia-Arencibia, M  Ramos, JA  Pertwee, RG  Fernandez-Ruiz, J 
Citation: Garcia C, etal., Br J Pharmacol. 2011 Feb 16. doi: 10.1111/j.1476-5381.2011.01278.x.
RGD ID: 5128616
Pubmed: PMID:21323909   (View Abstract at PubMed)
PMCID: PMC3165958   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1476-5381.2011.01278.x   (Journal Full-text)

Background and purpose. Previous findings have indicated that a cannabinoid, such as Delta(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 Delta(9) -THCV to reduce motor inhibition and provide neuroprotection was investigated in rats lesioned with 6-hydroxydopamine and in mice lesioned with LPS. Key results. Acute administration of Delta(9) -THCV attenuated the motor inhibition caused by 6-hydroxydopamine, presumably through changes in glutamatergic transmission. Moreover, chronic administration of Delta(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 CBD-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, Delta(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, Delta(9) -THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Parkinson's disease  ISOTh (Mus musculus)5128616; 5128616protein:decreased expression:substantia nigra (mouse)RGD 
Parkinson's disease  IEP 5128616protein:decreased expression:substantia nigra (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Th  (tyrosine hydroxylase)

Genes (Mus musculus)
Th  (tyrosine hydroxylase)

Genes (Homo sapiens)
TH  (tyrosine hydroxylase)


Additional Information