Sex and Gender Differences in the Effects of Novel Psychoactive Substances.

Sex and gender shape how people respond to drugs, with men more likely to use illicit drugs and seek emergency care for serious overdoses, while women are equally prone to substance use disorders and may be more vulnerable to craving and relapse. Research on classic drugs like THC, morphine, and cocaine shows clear male-female differences. With over 900 new psychoactive substances (NPS) now identified—including synthetic cannabinoids, cathinones, opioids, and dissociatives—knowledge of their sex- and gender-specific effects remains minimal. This review gathers the limited evidence from animal and human studies, emphasizing how much remains unknown about NPS effects across sexes and genders.

Study at a glance

Abstract

Sex and gender deeply affect the subjective effects and pharmaco-toxicological responses to drugs. Men are more likely than women to use almost all types of illicit drugs and to present to emergency departments for serious or fatal intoxications. However, women are just as likely as men to develop substance use disorders, and may be more susceptible to craving and relapse. Clinical and preclinical studies have shown important differences between males and females after administration of "classic" drugs of abuse (e.g., Δ9-tetrahydrocannabinol (THC), morphine, cocaine). This scenario has become enormously complicated in the last decade with the overbearing appearance of the new psychoactive substances (NPS) that have emerged as alternatives to regulated drugs. To date, more than 900 NPS have been identified, and can be catalogued in different pharmacological categories including synthetic cannabinoids, synthetic stimulants (cathinones and amphetamine-like), hallucinogenic phenethylamines, synthetic opioids (fentanyls and non-fentanyls), new benzodiazepines and dissociative anesthetics (i.e., methoxetamine and phencyclidine-derivatives). This work collects the little knowledge reached so far on the effects of NPS in male and female animal and human subjects, highlighting how much sex and gender differences in the effects of NPS has yet to be studied and understood.