JWH-018 and Selective Serotonin Reuptake Inhibitors: Drug-Drug Interactions and Implications on Toxicity

Abstract

Drug abuse has expanded from more well-known substances, such as cocaine and marijuana, to relatively new novel psychoactive substances. A group of these substances called synthetic cannabinoids have been increasing in usage throughout the 2000\u27s, and these compounds carry significant and varying risks depending on the dose and composition of the synthetic cannabinoid. Patients have been observed having symptoms associated with high doses of synthetic cannabinoids when they take lower doses of the synthetic cannabinoid in addition to their antidepressant medication. In order to test the effects of co-administration of selective serotonin reuptake inhibitors (SSRis) and synthetic cannabinoids, mice were observed in a marble burying assay under the influence of the different drugs. Mice were given either fluoxetine (10-mg/kg), citalopram (20-mg/kg), or JWH-018 (0.1-mg/kg or 0.3-mg/kg) or a combination of the drugs. Mice without being injected with any of the drugs buried 6.375 marbles on average in the twenty-minute test. Mice injected with fluoxetine or citalopram alone buried 4.25 marbles and 4.0 marbles respectively. The JWH-018 doses were chosen to be ineffective so that the marbles buried at 0.1-mg/kg was 6.125 and the 0.3-mg/kg dose resulted in 6.375 marbles buried. Fluoxetine in combination with JWH-018 resulted in 3.0 marbles being buried for the lower dose and 1.875 marbles were buried with the high dose. Citalopram in combination with JWH-018 resulted in 3.625 marbles buried for the lower dose and 2.875 marbles buried for the high dose. When the SSRis were taken with an ineffective dose of JWH-018 a greater than anticipated drug effect occurred, since it occurred in both combinations it points to a pharmacodynamic effect instead of a pharmacokinetic effect

    Similar works