Dopamine challenge reveals neuroadaptive changes in marijuana abusers.

Abstract

The current watershed in legal status and rising use of marijuana can be traced to a California ballot initiative (Prop. 215, its legal successor SB420), that enabled widespread access to smokeable or edible forms of marijuana for self-reported medical conditions. Circumventing the Food and Drug Administration (FDA) drug approval process, the movement in California was replicated by ballot or legislative initiatives in 23 states and the District of Columbia, and culminated in the legalization of marijuana in 2012 by Washington state and Colorado. The shifting status of marijuana reflects a change in public perception and belief that marijuana is harmless. Marijuana use in the population over age 12 is escalating; 60% of 12th graders do not perceive marijuana as harmful, and daily or nearly daily use has risen dramatically in this cohort (1, 2). Paradoxically, public perception of marijuana as a safe drug is rising simultaneously with accumulating evidence that frequent marijuana use is associated with adverse consequences, especially among youth (3). In PNAS, Volkow et al. register compelling new observations that marijuana abusers manifest adaptive behavioral, physiological, and biological responses, which conceivably contribute to marijuana addiction and compromised function (4). In response to a dopamine challenge (methylphenidate) and compared with non-using controls, marijuana abusers self-reported blunted reward (less “high”) and heightened negative responses (anxiety and restlessness), which were associated with attenuated dopamine responses in brain and cardiovascular responses.