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Atwood BK, Huffman J, Straiker A, Mackie K.
“JWH018, a common constituent of 'Spice' herbal blends, is a potent and efficacious cannabinoid CB1 receptor agonist”.
Br J Pharmacol. 2010 Jan 26.
PURPOSE: 'Spice' is an herbal blend primarily marketed in Europe as a mild hallucinogen with prominent cannabis-like effects and as a legal alternative to cannabis. However, a recent report identified a number of synthetic additives in samples of 'Spice'. One of these, the indole derivative JWH018, is a ligand for the cannabinoid receptor 1 CB1 cannabinoid receptor and inhibits cAMP production in CB1 receptor-expressing CHO cells. Other effects of JWH018 on CB1 receptor-mediated signalling are not known, particularly in neurons. Here we have evaluated the signalling pathways activated by JWH018 at CB1 receptors. Experimental approach: We investigated the effects of JWH018 on neurotransmission in cultured autaptic hippocampal neurons. We further analysed its activation of ERK1/2 mitogen activated protein kinase MAPK and internalization of CB1 receptors in HEK293 cells stably expressing this receptor. Key
RESULTS: In cultured autaptic hippocampal neurons, JWH018 potently inhibited excitatory postsynaptic currents IC50= 14.9 nM in a concentration- and CB1 receptor-dependent manner. Furthermore, it increased ERK1/2 MAPK phosphorylation EC50= 4.4 nM. We also found that JWH018 potently induced rapid and robust CB1 receptor internalization EC50= 2.8 nM t1/2= 17.3 min. Conclusions and implications: JWH018, a prominent component of several herbal preparations marketed for their psychoactivity, is a potent and effective CB1 receptor agonist that activates multiple CB1 receptor signalling pathways. Thus, it is likely that the subjective effects of 'Spice' are due to activation of cannabinoid CB1 receptors by JWH018, added to this herbal preparation.
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