JWH-018 impairs sensorimotor functions in mice

Area of Science:

• Neuroscience
• Pharmacology
• Toxicology

Background:

• Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) is a potent synthetic cannabinoid agonist.
• Illegally marketed as "Spice" or "herbal blends," JWH-018 produces psychoactive effects exceeding those of cannabis.
• While JWH-018 mimics some cannabis effects in rodents, its impact on sensorimotor functions remains largely uncharacterized.

Purpose of the Study:

• To investigate the acute effects of JWH-018 on sensorimotor functions in male CD-1 mice.
• To compare the sensorimotor effects of JWH-018 with those of Δ(9)-THC (Dronabinol®).
• To assess neurological changes and spontaneous locomotion following JWH-018 administration.

Main Methods:

• Acute administration of JWH-018 and Δ(9)-THC at doses ranging from 0.01 to 6 mg/kg (i.p.) to male CD-1 mice.
• Utilized a battery of behavioral tests to evaluate visual, auditory, and tactile sensorimotor responses.
• Employed video-tracking analysis for spontaneous locomotion and observed for neurological alterations like convulsions and myoclonia.
• Administered the CB1 receptor antagonist AM 251 to assess the mechanism of action.

Main Results:

• JWH-018 inhibited sensorimotor responses at low doses (0.01-0.1 mg/kg).
• Intermediate to high doses of JWH-018 (1-6 mg/kg) reduced spontaneous locomotion.
• High-dose JWH-018 (6 mg/kg) induced convulsions, myoclonia, and hyperreflexia.
• Δ(9)-THC reduced sensorimotor responses but did not affect locomotion or induce neurological alterations.
• All observed effects of JWH-018 and Δ(9)-THC were reversed by the CB1 antagonist AM 251.

Conclusions:

• JWH-018 significantly impairs sensorimotor functions in mice, a novel finding.
• JWH-018 induces neurological alterations and affects locomotion, differentiating it from Δ(9)-THC.
• The findings underscore the potential public health risks of JWH-018, particularly concerning impaired driving and performance in hazardous activities.