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Synthetic Cannabinoid Receptor Agonist ‘JWH-018’ does not mimic Serotonin | ||
| Iraqi Journal of Pharmacy | ||
| Article 1, Volume 19, Issue 1, 2022, Pages 1-7 PDF (885.51 K) | ||
| Document Type: Research Paper | ||
| DOI: 10.33899/iphr.2022.174794 | ||
| Authors | ||
| Adam J. Pottsa1; Israa M. Albanaa* 2; Sarah E. Gartsidec3; Peter S. Hansonb4; Simon L. Hilld5; Simon H. Thomasb4; Sarah J. Judgec3 | ||
| 1Northumbria Healthcare NHS Foundation Trust, UK | ||
| 2College of Pharmacy, University of Mosul, Iraq | ||
| 3Institute of Neuroscience, Newcastle University, NE2 4HH, UK | ||
| 4Translational and Clinical Research Institute, Newcastle University, UK | ||
| 5Regional Drugs and Therapeutics Centre16/17, NE2 4AB; Framlington Place School of Biomedical, Nutritional and Sport Sciences Newcastle University | ||
| Abstract | ||
| Synthetic cannabinoid receptor agonists (SCRAs) are popular recreational drugs. It has been suggested that indole-containing SCRAs may have activity at several serotonergic targets, owing to their structural similarity to the neurotransmitter serotonin (5-HT). This similarity may be responsible for features of toxicity similar to serotonin syndrome observed in cases of SCRA intoxication. To determine whether indole-SCRAs have activity at serotonergic targets we investigated the effect of JWH-018, an indole-containing SCRA, with a non-indole-containing SCRA (CP55,940) and an endocannabinoid (anandamide) on 5-HT neuronal functions in rat brain slices; 5-HT neuronal activity was examined using in vitro extracellular single-unit electrophysiology in the dorsal raphe nucleus and 5-HT presynaptic uptake was examined using radiolabeled 5-HT(3[H] 5-HT) in the hippocampus. 5-HT (50µM) inhibited the 5-HT neuronal firing rate but JWH-018 (50µM) had no effect on the basal or NMDA (30µM) augmented firing rate. In contrast, anandamide (10uM) increased the NMDA-augmented firing rate of 5-HT neurons, but not the basal rate. The selective serotonin reuptake inhibitor fluoxetine (0.001 – 10 µM) inhibited 5-HT reuptake but JWH-018 (0.001 – 10 µM) had no effect on serotonin uptake. Our data suggest that indole-SCRAs and non-indole SCRAs do not directly interact with serotonergic targets in either the dorsal raphe nucleus or hippocampus. Further mechanistic studies are needed to determine if SCRAs affect serotonergic neurotransmission through modulation of afferents to 5-HT neurons. | ||
| Keywords | ||
| Synthetic Cannabinoids; Serotonin; JWH-018; Dorsal raphe nucleus; Hippocampus | ||
| References | ||
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23-05-2022 30-06-2022 | ||
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