JWH018, a common constituent of ‘Spice’ herbal blends, is a potent and efficacious cannabinoid CB1 receptor agonist

摘要: Background and purpose:  ‘Spice’ is an herbal blend primarily marketed in Europe as a mild hallucinogen with prominent cannabis-like effects legal alternative to cannabis. However, recent report identified number of synthetic additives samples ‘Spice’. One these, the indole derivative JWH018, ligand for cannabinoid receptor 1 (CB1) inhibits cAMP production CB1 receptor-expressing CHO cells. Other JWH018 on receptor-mediated signalling are not known, particularly neurons. Here we have evaluated pathways activated by at receptors. Experimental approach:  We investigated neurotransmission cultured autaptic hippocampal further analysed its activation ERK1/2 mitogen protein kinase (MAPK) internalization receptors HEK293 cells stably expressing this receptor. Key results:  In neurons, potently inhibited excitatory postsynaptic currents (IC50= 14.9 nM) concentration- receptor-dependent manner. Furthermore, it increased MAPK phosphorylation (EC50= 4.4 nM). also found that induced rapid robust 2.8 nM; t1/2= 17.3 min). Conclusions implications:  component several preparations their psychoactivity, potent effective agonist activates multiple pathways. Thus, likely subjective due added preparation.