Δ⁹-Tetrahydrocannabinol-like discriminative stimulus effects of compounds commonly found in K2/Spice

Abstract

A number of cannabinoid compounds are being sold in the form of incense as ‘legal’ alternatives to marijuana. The purpose of these experiments was to determine whether the most common of these compounds have discriminative stimulus effects similar to Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the main active component in marijuana. Locomotor depressant effects of JWH-018, JWH-073, JWH-200, JWH-203, JWH-250, AM-2201, and CP 47,497-C8-homolog were tested in mice. The compounds were then tested for substitution in rats trained to discriminate Δ⁹-THC (3 mg/kg, intraperitoneally). The time course of the peak dose of each compound was also tested. Each of the synthetic cannabinoids dose-dependently decreased locomotor activity for 1–2 h. Each of the compounds fully substituted for the discriminative stimulus effects of Δ⁹-THC, mostly at doses that produced only marginal amounts of rate suppression. JWH-250 and CP 47,497-C8-homolog suppressed response rates at doses that fully substituted for Δ⁹-THC. The time courses varied markedly between compounds. Most of the compounds had a shorter onset than Δ⁹-THC, and the effects of three of the compounds lasted substantially longer (JWH-073, JWH-250, and CP 47,497-C8-homolog). Several of the most commonly used synthetic cannabinoids produce behavioral effects comparable with those of Δ⁹-THC, which suggests that these compounds may share the psychoactive effects of marijuana responsible for abuse liability. The extremely long time course of the discriminative stimulus effects and adverse effects of CP 47,497-C8-homolog suggest that CP 47,497-C8-homolog may be associated with increased hazards among humans.