Marijuana craving in the brain

Abstract

Craving is one of the primary behavioral components of drug addiction, and cue-elicited craving is an especially powerful form of this construct. While cue-elicited craving and its underlying neurobiological mechanisms have been extensively studied with respect to alcohol and other drugs of abuse, the same cannot be said for marijuana. Cue-elicited craving for other drugs of abuse is associated with increased activity in a number of brain areas, particularly the reward pathway. This study used functional magnetic resonance imaging (fMRI) to examine cue-elicited craving for marijuana. Thirty-eight regular marijuana users abstained from use for 72 h and were presented with tactile marijuana-related and neutral cues while undergoing a fMRI scan. Several structures in the reward pathway, including the ventral tegmental area, thalamus, anterior cingulate, insula, and amygdala, demonstrated greater blood oxygen level dependent (BOLD) activation in response to the marijuana cue as compared with the neutral cue. These regions underlie motivated behavior and the attribution of incentive salience. Activation of the orbitofrontal cortex and nucleus accumbens was also positively correlated with problems related to marijuana use, such that greater BOLD activation was associated with greater number of items on a marijuana problem scale. Thus, cue-elicited craving for marijuana activates the reward neurocircuitry associated with the neuropathology of addiction, and the magnitude of activation of these structures is associated with severity of cannabis-related problems. These findings may inform the development of treatment strategies for cannabis dependence.

Fig. 1.

Greater activation in several areas of interest during marijuana cues compared with neutral cues. There were significantly greater BOLD response to the marijuana pipe in reward areas such as the dorsal ACC, insula, thalamus, ventral tegmental area, and amygdala (cluster-corrected z > 2.3, P < 0.05). Right hemispheric activations are illustrated on the right side of the image.

Fig. 2.

Significantly positive areas of correlation between BOLD response to marijuana cues (vs. neutral cues) and total MPS score in the orbitofrontal cortex and nucleus accumbens (cluster-corrected z > 2.3, P < 0.05). Right hemispheric activations are illustrated on the right side of the image.

Fig. 3.

Schematic of a single trial. During the exposure period, an experimenter handed the item (pipe or pencil) to the participant's left hand. The participants were explicitly instructed to hold the item as they would normally, but also so they were able to view both the item and their hand in the mirror system throughout the entire period. After the exposure period, a 5-second urge rating period followed during which participants were asked to respond on a scale of 0–10 via right-handed button press to the statement, “Please rate your level of urge to use marijuana right now.” The trial ended with a washout period during which the experimenter took the item away from the participant. The visual presentations and timing of each event (in seconds) are illustrated.