A new review article in the journal, Translational Psychiatry, explores the role of negative emotional states in relapse for people being treated for substance use disorders. The three authors from the Imperial College of London say that a great deal of research has gone into studying willpower and impulse control, but very little has gone into examining the brain during the withdrawal cycle.

The authors focused on examining studies that used functional magnetic resonance imaging (fMRI) to reveal “brain reactivity patterns during negative emotional processing in addiction during treatment and/or abstinence.” Figure 1 illustrates the brain regions most involved in emotional processing, according to the authors:

Fig. 1: Emotional processing is governed by brain regions including the extended amygdala, insula, ACC, and mPFC. Image courtesy Translational Psychiatry used under Fair Use: Commentary.

There are four regions of the brain involved in the imaging studies; however, targeting treatments is not so simple. Some regions are blunted in withdrawal and others are hyperactive. Cocaine and alcohol impact the regions differently than opioids or THC. The authors come to an uncomfortable conclusion:

The uniqueness by which each drug class seems to dysregulate brain function suggests there is no ‘shared’ mechanism of addiction.

Well, that certainly makes “treatment development challenging,” the authors note, in a bit of British understatement. If there is no shared neural mechanism for substance use disorders, much of the research done on the brain’s reward system may have to be reconsidered. Studies will have to limit themselves to one substance. Comorbidities — an addiction to two or more substances — further complicate research and might need to be examined separately.

The authors do observe an arc of recovery, from an initial period of days to a few weeks where the brain “adapts to the lack of the substance and is more hyperreactive to negative affective stimuli, manifesting as increases in anxiety, emotional distress, craving and irritability.” The authors continue to describe the brain in recovery:

As abstinence continues into weeks and months, neural circuitry associated with emotion processing may begin to stabilise, which may be accompanied by reduced craving and reactivity to stressful triggers. Longer-term abstinence, from months to years, may facilitate further recovery of brain reactivity to negative stimuli. However, long-term neuroadaptations can persist into protracted withdrawal.

Even with prolonged abstinence, the damage does not go away. Which is why Dr. Nora D. Volkow at the National Institute on Drug Abuse (NIDA) considers addiction to be a chronic brain disease. But it’s a chronic brain disease that can be treated and tamed, and which most people recover from enough to enjoy their lives. Kind of hard to see all of that with fMRI.

Written by Steve O’Keefe. First published November 19, 2024.

Sources:

“Re-evaluating our focus in addiction: emotional dysregulation is a critical driver of relapse to drug use,” Translational Psychiatry, November 9, 2024.

Image courtesy Translational Psychiatry, used under Fair Use: Commentary.