The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice

Area of Science:

• Pharmacology
• Neuroscience
• Immunology

Background:

• Delta(9)-tetrahydrocannabivarin (THCV) is a phytocannabinoid known to block cannabinoid CB(1) receptors.
• Emerging evidence suggests combined CB(2) receptor activation and CB(1) receptor blockade may ameliorate certain disorders.

Purpose of the Study:

• To investigate the potential of THCV to activate cannabinoid CB(2) receptors.
• To explore the therapeutic implications of THCV's dual action on CB(1) and CB(2) receptors for inflammatory conditions.

Main Methods:

• Assessed THCV's ability to inhibit forskolin-stimulated cyclic AMP production in cells expressing human CB(2) (hCB(2)) receptors.
• Measured THCV's stimulation of [(35)S]GTPgammaS binding to hCB(2) receptors in cell membranes and mouse spleen.
• Evaluated THCV's efficacy in attenuating inflammation and hyperalgesia in mouse models induced by carrageenan and formalin.
• Determined if THCV's effects were blocked by CB(1) or CB(2) receptor antagonists.

Main Results:

• THCV demonstrated in vitro activation of hCB(2) receptors, evidenced by reduced cyclic AMP production and increased [(35)S]GTPgammaS binding.
• THCV administration in mice significantly decreased carrageenan-induced edema and hyperalgesia, suggesting CB(2) receptor mediation.
• THCV suppressed pain behaviors in formalin tests, with effects appearing to involve both CB(1) and CB(2) receptor pathways.

Conclusions:

• THCV possesses the ability to activate CB(2) receptors in vitro.
• THCV effectively reduces inflammation and inflammatory pain in preclinical models.
• The therapeutic effects of THCV in these models are partly mediated through the activation of CB(1) and/or CB(2) receptors.