Premium
JWH018, a common constituent of ‘Spice’ herbal blends, is a potent and efficacious cannabinoid CB 1 receptor agonist
Author(s) -
Atwood Brady K,
Huffman John,
Straiker Alex,
Mackie Ken
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00582.x
Subject(s) - cannabinoid receptor , cannabinoid , cannabinoid receptor type 2 , agonist , receptor , pharmacology , cannabinoid receptor agonists , mapk/erk pathway , am251 , chemistry , endocannabinoid system , biology , signal transduction , biochemistry
Background and 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 (CB 1 ) cannabinoid receptor and inhibits cAMP production in CB 1 receptor‐expressing CHO cells. Other effects of JWH018 on CB 1 receptor‐mediated signalling are not known, particularly in neurons. Here we have evaluated the signalling pathways activated by JWH018 at CB 1 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 CB 1 receptors in HEK293 cells stably expressing this receptor. Key results: In cultured autaptic hippocampal neurons, JWH018 potently inhibited excitatory postsynaptic currents ( IC 50 = 14.9 nM) in a concentration‐ and CB 1 receptor‐dependent manner. Furthermore, it increased ERK1/2 MAPK phosphorylation ( EC 50 = 4.4 nM). We also found that JWH018 potently induced rapid and robust CB 1 receptor internalization ( EC 50 = 2.8 nM; t 1/2 = 17.3 min). Conclusions and implications: JWH018, a prominent component of several herbal preparations marketed for their psychoactivity, is a potent and effective CB 1 receptor agonist that activates multiple CB 1 receptor signalling pathways. Thus, it is likely that the subjective effects of ‘Spice’ are due to activation of cannabinoid CB 1 receptors by JWH018, added to this herbal preparation.