The cannabinoid delta 9-tetrahydrocannabinol (THC) is the primary psychoactive component of
marijuana. THC is believed to be a significant factor in the addictive potential associated
with marijuana use. In addition, attenuated levels of endogenous endocannabinoids have been
found in alcohol-dependent individuals as compared to social drinkers, suggesting that
changes in the sensitivity of the endogenous endocannabinoid system play a role in the
transition from recreational drug use to substance use disorders. Thus, pharmacotherapies
that target the cannabinoid system may be effective strategies for reducing marijuana use and
dependence. Recent preclinical data demonstrate that the neurosteroid pregnenolone (PREG)
inhibits THC activation of cannabinoid receptors and decreases symptoms of marijuana
intoxication. In addition, other studies show that PREG inhibits drug-seeking behavior. This
pilot study will provide important preliminary data on the effect of an acute dose of PREG on
cue-related craving in individuals with cannabis use disorder.