Abuse of psychoactive substances is an actual medical and pharmaceutical, social and economic, pedagogical and educational, criminal and legal problem. Prevention should be the priority strategy for dealing with abuse. The most common psychoactive substances in abuse are: alcohol, nicotine, hemp, cocaine, heroin, medicinal drugs. Information about psychoactive substances prohibited for circulation in the state is aggressively disseminated through mass media, the Internet, films, and computer games. Abuse of psychoactive substances affects the quality of life and health, has negative physical, physiological, and psychological consequences. Forensic and pharmaceutical, criminal and legal studies indicate that the law enforcement agencies of Ukraine, under the procedural guidance of prosecutors of all levels, take operative and investigative measures and investigative actions. In the structure of polydrug addiction, the syndrome of dependence due to the use of alcohol, which develops after multiple simultaneous use of psychoactive alcohol-containing liquids, alcoholic beverages (beer, vodka, wine), psychoactive alcohol drugs, prevails. Comorbid disorders associated with polydrug addiction were systematized. Estimated that 51.6% are mental illnesses. The results of an interdisciplinary forensic and pharmaceutical, organizational and legal, clinical and pharmacological study indicate the need for further multi-stage pharmacotherapy of polydrug addiction and related comorbid disorders during drug circulation.