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Background: In the last 5 years, synthetic cannabinoids (SCBs) rapidly developed as common drugs of abuse in Europe and the US. Rapidly different preparations became available online and in business institutions. Most of these preparations consist of inert plant materials laced with SCBs and are mixed with unknown pharmaceutical materials to possess pharmacological properties like Δ9-tetrahydrocannabinol (Δ9-THC). Most of synthetic cannabinoids (SCBs) are smoked, but preclinical studies usually rely on injection for drug delivery. MDMB-4en-PINACA is extensively metabolized as many other synthetic cannabinoids. Methods: A total of twenty-one male mice were divided into three groups at random (7 per each). Control group; not exposed to any treatment; MDMB-PINACA with clozapine low dose, MDMB-PINACA with clozapine high dose intraperitoneal injection. In our study we assessed this mixture for its abuse liability by an assessment of oxidative stress markers, histopathological and behavioral changes. Result: intraperitoneal injection of MDMB-PINACA mixed with clozapine induced classic cannabinoid effect (tetrad effect) in mice(hypothermia, hypolocomotion, and increased latency in both catalepsy and tail immersion tests in mice); in addition to the biochemical alterations in brain neurotransmitters, cardiac enzymes and histopathological changes in brain and heart (acute inflammatory changes on both brain and heart) at high doses, besides hypothermia and antinoception with low doses Conclusion: Exposure to MDMB-PINACA mixed with clozapine in high doses through intraperitoneal injection induced behavioural, biochemical, and histopathological alterations in nervous and cardiac systems of mice.

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