The article reviews sex differences in drug abuse, both in humans and animal models. It highlights that females initiate and escalate drug use at lower doses than males and are more susceptible to relapse after abstinence. The review discusses the neuroendocrine mechanisms underlying these differences, particularly the role of estradiol and progesterone. In humans, women tend to escalate drug use more rapidly and find it harder to quit compared to men. In animal models, females exhibit faster acquisition of drug self-administration and show greater behavioral sensitization to psychomotor stimulants like cocaine and amphetamine. The effects of estradiol and progesterone on striatal dopamine release and receptor activity are also explored, suggesting that these hormones play a crucial role in mediating sex differences in drug abuse. The article concludes by emphasizing the need for further research to understand the neural bases of sex differences in drug abuse and to improve treatment strategies for both genders.The article reviews sex differences in drug abuse, both in humans and animal models. It highlights that females initiate and escalate drug use at lower doses than males and are more susceptible to relapse after abstinence. The review discusses the neuroendocrine mechanisms underlying these differences, particularly the role of estradiol and progesterone. In humans, women tend to escalate drug use more rapidly and find it harder to quit compared to men. In animal models, females exhibit faster acquisition of drug self-administration and show greater behavioral sensitization to psychomotor stimulants like cocaine and amphetamine. The effects of estradiol and progesterone on striatal dopamine release and receptor activity are also explored, suggesting that these hormones play a crucial role in mediating sex differences in drug abuse. The article concludes by emphasizing the need for further research to understand the neural bases of sex differences in drug abuse and to improve treatment strategies for both genders.