Considering gender in cannabinoid research: a step towards personalized treatment of marijuana addicts

Addiction is a complex disorder with interacting factors, including environmental factors, drug-induced neurobiological changes, comorbidity, personality traits and stress responsivity. Numerous genetic variants that affect these factors may work in concert to affect vulnerability and severity of addiction. Traditionally, abuse of illicit drugs, including cannabis, was considered to be primarily a problem specific to men but the recent focus on drug addiction in women has brought attention to numerous sex differences in the central effects of these drugs, epidemiology of abuse-related disorders, etiologic considerations and psychiatric comorbidity. Gender is now recognised as a major factor in the modulation of the pharmacological effects of drugs of abuse, and sex differences have been reported in various phases of the addiction cycle in both humans and animals. Recently, important gender-dependent differences have been detected in the rates of initiation of marijuana smoking and in the frequency of use. Several animal studies, and in particular self-administration studies, confirmed the crucial role played by sex and gonadal hormones in determining higher sensitivity to marijuana's rewarding properties and vulnerability to cannabis addiction in females than in males. In general, women also show higher rate of relapse to drug use than men, likely due to divergent withdrawal experiences and increased reactivity to internal (emotional) and external (drug-associated) cues. According with this, craving for marijuana smoking and propensity to re-use cannabis after abstinence may also develop differently between the sexes and require distinct treatment approaches, thus highlighting the urgent need for gender-tailored prevention strategies and detoxification treatments.