A research team at The University of Texas at Dallas Center for BrainHealth has found that drug paraphernalia triggers the reward areas of the brain differently in dependent and non-dependent marijuana users. The study, published July 1 in the journal Drug and Alcohol Dependence, demonstrates that different areas of the brain are activated when dependent and non-dependent users respectively were exposed to drug-related cues.
The journal paper, entitled “Differential reward network functional connectivity in cannabis dependent and non-dependent users” (Drug and Alcohol Dependence – 1 July 2014 (Vol. 140Complete, Pages 101-111, DOI: 10.1016/j.drugalcdep.2014.04.002), coauthored by UT Dallas professor Dr. Francesca M. Filbey, and Research Assistant III Dr. Joseph Dunlop, notes that emergent studies show that as with other substances of abuse, cue-reactivity to cannabis is also associated with neural response in the brain’s reward pathway (viz. Filbey et al., 2009). However, the inter-relatedness of brain regions during cue-reactivity in cannabis users remains unknown.
For the study, Drs. Filbey, Dunlop, and the Filbey Lab team conducted a series of investigations, including brain-imaging scans called functional magnetic resonance imaging (fMRI), to determine functional connectivity during cue-reactivity in 71 cannabis users. Just over half of the subjects were classified as dependent users. While being scanned, the participants were given either a used marijuana pipe or a pencil of approximately the same size that they could see and feel.
The researchers then used psychophysiological interaction (PPI) analysis to examine coherent neural response to cannabis cues, followed by scientific evaluation of whether these patterns of network functional connectivity differentiated in dependent and non-dependent users respectively. Finally, as an exploratory analysis, the researchers determined the directionality of these connections via Granger connectivity analyses.
A comparison of the images revealed that the nucleus accumbens, the reward region in the brain, was activated in all users in response to the pipe. However, the strengths of the connections with other areas differed between dependent and non-dependent users.
The researchers found that both the PPI and Granger analyses demonstrated strong functional coherence in reward regions during exposure to cannabis cues in current cannabis users. Functional connectivity (but not regional activation) in the reward network also differentiated dependent from non-dependent cannabis users.
Non-dependent users showed greater activations in the orbital frontal cortex and hippocampus, suggesting that memory and attention were connected to the activation of the reward network. Dependent users had greater activations in the amygdala and anterior cingulate gyrus, suggesting a more emotional connection.
Additionally, the areas of the brain activated resemble areas activated for other addictions, such as nicotine or cocaine, lending greater support to the addictiveness of marijuana.
Drs. Filbey and Dunlop conclude that their findings suggest repeated exposure to cannabis causes observable changes in functional connectivity in the reward network and should be considered in intervention strategies.
The UT Dallas release cites a 2012 National Survey on Drug Use and Health showing that marijuana is the most widely used illegal drug in the United States, with metrics from a 2013 Pew Research Center survey finding that 48 percent of Americans aged 18 and older have experimented with marijuana, and a National Institute on Drug Abuse projection that 9 percent of daily users will become dependent on marijuana.
“We know that people have a hard time staying abstinent because seeing cues for the drug use triggers this intense desire to seek out the drugs,” says Dr. Filbey, lead author of the study paper and a professor at the Center for BrainHealth in the School of Behavioral and Brain Sciences. “That’s a clinically validated phenomenon and behavioral studies have also shown this to be the case. What we didn’t know was what was driving those effects in the brain.”
The investigators contend that their findings suggest marijuana abuse intervention needs to cater more specifically to a user’s level of addiction. “Clinicians treating people with problems with marijuana dependence should consider the different processes that trigger the reward response when determining possible pharmacological or behavioral interventions,” Dr. Filbey observes.
The Filbey lab at UT Dallas focuses on combining neuroimaging and genetic techniques to characterize neural mechanisms associated with reward system dysfunction (e.g., addictive disorders). Specifically, the researchers are interested in how environmental factors (e.g., adolescent onset of use, early life stress) mediate the neural mechanisms that are associated with changes in the reward system and how genetic risk moderates these effects. Their current projects involve the determination of these effects using neuroimaging tools (sMRI, DTI, fMRI during cue-exposure tasks, reward and punishment tasks, response inhibition tasks and stress tasks, resting state fMRI) and genetic studies in substance abusers, compulsive eaters and risk-taking individuals.
Dr. Joseph Dunlop, Ph.D works closely with Dr. Francesca Filbey on studying how genetic and environmental factors interact in the brain of addicts. His role as a cognitive researcher allows him to evaluate both imaging (e.g., fMRI) and behavioral statistics to determine changes that happen in the brain.
Research was conducted in part at the Mind Research Network and was funded by a grant from the National Institute on Drug Abuse.
University of Texas at Dallas
Drug and Alcohol Dependence
University of Texas at Dallas