Synthetic Cannabinoid Receptor Agonist ‘JWH-018’ does not mimic Serotonin

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 the neurotransmitter serotonin (5-HT). This be responsible for features of toxicity similar syndrome observed in cases SCRA intoxication. To determine whether indole-SCRAs targets we investigated effect JWH-018, an SCRA, with a non-indole-containing (CP55,940) and endocannabinoid (anandamide) on 5-HT neuronal functions rat brain slices; was examined using vitro extracellular single-unit electrophysiology dorsal raphe nucleus presynaptic uptake radiolabeled 5-HT(3[H] 5-HT) hippocampus. (50µM) inhibited firing rate but JWH-018 had no basal or NMDA (30µM) augmented rate. In contrast, anandamide (10uM) increased NMDA-augmented neurons, not The selective reuptake inhibitor fluoxetine (0.001 – 10 µM) uptake. Our data suggest non-indole do directly interact either Further mechanistic studies needed if affect neurotransmission through modulation afferents neurons.