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

Abstract

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.

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  • Authors+Show Affiliations

    ,

    Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain.

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    Source

    British journal of pharmacology 163:7 2011 Aug pg 1495-506

    MeSH

    Animals
    Antioxidants
    Cannabinoids
    Cyclohexanols
    Disease Models, Animal
    Dopamine
    Dronabinol
    Glutamic Acid
    Lipopolysaccharides
    Male
    Mice
    Motor Activity
    Neurons
    Neuroprotective Agents
    Oxidopamine
    Parkinson Disease
    Rats
    Rats, Sprague-Dawley
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    Substantia Nigra
    Tyrosine 3-Monooxygenase

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21323909