Abstract
Natural cannabinoids and their synthetic substitutes are the most widely used recreational drugs. Numerous clinical cases describe acute toxic symptoms and neurological consequences following inhalation of the mixture of synthetic cannabinoids known as “Spice.” Here we report that an intraperitoneal administration of the natural cannabinoid Δ9-tetrahydrocannabinol (10 mg/kg), one of the main constituent of marijuana, or the synthetic cannabinoid JWH-018 (2.5 mg/kg) triggered electrographic seizures in mice, recorded by electroencephalography and videography. Administration of JWH-018 (1.5, 2.5 and 5 mg/kg) increased seizure spikes dose-dependently. Pretreatment of mice with AM-251 (5 mg/kg), a cannabinoid receptor 1-selective antagonist, completely prevented cannabinoid-induced seizures. These data imply that abuse of cannabinoids can be dangerous and represents an emerging public health threat. Additionally, our data strongly suggest that AM-251 could be used as a crucial prophylactic therapy for cannabinoid-induced seizures or similar life-threatening conditions.
Highlights
Marijuana (Cannabis sativa L.) is the most commonly abused drug in the United States[1], with a similar tendency worldwide[2]
We observed a significant decrease in locomotor activity (LMA) and EMG activity that coincided with low-intensity behavioral seizures
Electrographic seizures were apparent for 256 ± 15.3 minutes after ∆9-THC; after JWH-018 administration they persisted
Summary
Marijuana (Cannabis sativa L.) is the most commonly abused drug in the United States[1], with a similar tendency worldwide[2]. In recent years, strains of herbal cannabis with an increased CB1R potency have appeared: one example is sinsemilla, a female non-pollinated cannabis plant in which the content of ∆9-THC has been raised from 3.96% in 1995 to 12.3% in 20141. This recent shift in the generation of high-potency cannabis plant material has led to an increasing demand for cannabis-related treatments and emergency department admissions stemming from acute anxiety, psychosis or cognitive impairment[7,8,9]. Rapid analogue development and the growing popularity of SCs impose a strong demand for evaluation of their pharmacology and toxicology to reveal the mechanism of action and to facilitate future development of a drug-specific therapy for intoxication
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