JWH-018 impairs sensorimotor functions in mice

1‐cyclohexyl‐x‐methoxybenzene derivatives, novel psychoactive substances seized on the internet market. Synthesis and in vivo pharmacological studies in mice

“…Interestingly, these NPS (1‐cyclohexyl‐x‐methoxybenzene derivatives) induced a deep dose‐dependent impairment of visual sensorimotor responses in mice during a wide range of doses (0.1–100/kg) that did not cause catalepsy (data not shown), or reduced stimulated motor activity (accelerod test Figure ). Therefore, these findings point out that effects induced by 1‐cyclohexyl‐x‐methoxybenzene derivatives on visual responses do not result from a disruption of motor function as previously demonstrated also for synthetic cannabinoids (Ossato et al, , ). These effects were observed at lower doses that did not affect others behavioral and physiological parameters, suggesting that these compounds primarily induce visual sensorimotor alterations, as caused by the hallucinogenic drug PCP (Morris & Wallach, ).…”

“…The wide range of doses of 1‐cyclohexyl‐x‐methoxybenzene derivatives tested (0.1–100 mg/kg i.p.) were chosen based on previous safety pharmacology studies on NPS (Vigolo et al, ; Ossato et al, , ).…”

“…For the lateral visual response, a small dentist's mirror was moved into the mice's field of view in a horizontal arc, until the stimulus was between the mice's eyes. The procedure was conducted bilaterally (Ossato et al, , ) and was repeated three times. The score assigned was a value of 1 if there was a reflection in the mouse movement, or 0 if not.…”

Synthetic Pot: Not Your Grandfather’s Marijuana

“…The selective CB 1 cannabinoid antagonist rimonabant reverses the effects of these SCBs in a functional observational battery in mice ( e.g., muscle tone, equilibrium, sensorimotor activity, alertness, ease of handling and autonomic effects). Furthermore, sensorimotor dysfunction in mice produced by JWH-018, JWH-250 and JWH-073 [60, 167], and impaired motor activity and seizures resulting from JWH-018 and JWH-018-Br [168] are all normalized by co-administration with CB 1 cannabinoid receptor antagonists rimonabant and AM-251. Finally, antinociception and hypothermic effects produced by the SCBs CP-55,950, WIN-55,212-2, JWH-073, A-834,735D and CP-47,497 are absent in CB 1 cannabinoid receptor knockout mice [169].…”

“…Since SCBs lack appreciable affinity for non-CB 1 cannainoid receptor targets [61] and almost all acute SCB responses in animals are blocked by co-administration with CB 1 cannabinoid receptor antagonists ( e.g., rimonabant or AM-251) [60, 61, 167–169], it is unfortunate that clinical studies to examine the potential use of CB 1 cannabinoid receptor antagonists for treatment of acute SCB overdose in emergency departments have not been conducted. The CB 1 cannabinoid receptor antagonist/inverse agonist rimonabant was withdrawn from clinical trials for use in obesity by the European Medicines Agency in October of 2008 due to adverse psychiatric consequences [184].…”