In a new review article, my colleague Aimee Techau looks at the effect that chronic inflammation might have on people’s ability to follow through with treatment for substance use disorders. Many people who start treatment for substance use disorders drop out in the first few months — in our recent research as many as 70%! Dropping out doesn’t necessarily mean that people relapsed, but it certainly suggests they aren’t getting the full benefit of treatment. In a number of studies, predicting treatment failures of this kind has proven difficult. Aimee’s new paper suggests a biological marker — inflammation — that might help to explain why some patients drop out, and that might therefore be useful in predicting or even preventing this problem.
Inflammation is a problem that’s common to many chronic diseases. It’s part of the body’s basic response to infection and helps the immune system do its work. But inflammation also can result from long-term illness or psychological stress, and when it becomes chronic it can have a variety of negative effects. I wrote about some of these in a previous post on sleep, because poor sleep is one of the common results of chronic inflammation. Some other symptoms associated with chronic inflammation are depressed mood, increased pain, and feelings of fatigue. This same inflammation-related “symptom cluster” has been observed in studies of patients with cancer, with lung disease, and with HIV. Aimee’s review shows that inflammation is also common among people with substance use disorders of various types, and that particular drugs like cocaine, opioids, and methamphetamine can also increase inflammation directly via their chemical effects on the brain and the immune system.
When inflammation is present, people can have a harder time managing their behavior. I wrote in previous posts about how drugs such as opioids or traumatic experience can take the logic and planning functions of the Narrative mind offline, and why counseling is an important part of medication-assisted treatment to address substance use problems. Aimee’s review shows how inflammation can similarly weaken the brain’s Narrative functions. For people who already have weakened impulse control due to drug-induced changes in the brain, inflammation might make impulsive behavior even more likely. Aimee found several studies showing that people with higher inflammation levels have weaker executive functioning (i.e., less activity in the Narrative mind), leading to more immediate reward-seeking and less attention being paid to long-term consequences. Three studies found this pattern of inhibited reflection and greater reward-seeking specifically among substance-using patients with elevated inflammation based on the amount of a protein called interleukin 6 (IL-6) that promotes inflammation, measured either in saliva or in the bloodstream.
Besides its direct effect on the brain, inflammation may have indirect effects on behavior by way of its associated symptoms. In a second section of her review, Aimee looked at studies showing that people with higher levels of inflammation also tend to withdraw from social situations. This might be due to the symptom cluster associated with inflammation, because people who are feeling depressed or fatigued often don’t want to be around others. Alternately, inflammation may simply represent a drain on people's limited attentional resources or finite supply of willpower, and in this context they naturally may attempt to minimize any other potential stressors. Or social withdrawal might be a direct consequence of inflammation: Aimee identified four experimental studies that directly caused inflammation in volunteer participants (e.g., by giving them a flu vaccine), and found that people randomly assigned to the inflammation group did in fact report more feelings of loneliness and isolation, as well as having higher levels of IL-6.
In three studies using fMRI technology, researchers even found brain activity changes related to inflammation in Intuitive-system areas like the striatum, insular cortex, and amygdala. One of these studies specifically showed that when people with inflammation were exposed to an ambiguous social situation, the ventral striatum lit up in their brains — an area linked to threat perception. If people with inflammation find social situations more threatening, that provides another good explanation for why they might avoid them. And social withdrawal could contribute to treatment failure if people with inflammation are more likely to avoid social interaction with the health care professionals who are trying to help them. Social judgment is also, of course, a key function of the Narrative mind even though it is supported by basic Intuitive-level processes like threat perception. So inflammation may indirectly affect the narratives we create about our social world as well.
Overall, Aimee’s review summarizes evidence for the link between inflammation and behavior, and suggests two different ways — impulsivity and social withdrawal — in which inflammation might interfere with patients remaining in substance use treatment. Further research is needed to confirm this theory, such as directly comparing IL-6 levels between people who do versus do not drop out of substance use treatment. But if Aimee is right, there are several practical implications: First, we could screen people with substance use for inflammation (e.g., using IL-6) to predict who is more likely to drop out of treatment. Second, we could try to reduce inflammation (e.g., with a non-steroidal anti-inflammatory drug like ibuprofen) and see if that makes people more likely to remain in substance use treatment. And finally, we might devise other approaches to address the needs of people with high levels of inflammation: Aimee suggests, for instance, that people with inflammation-related social withdrawal nevertheless seek increased support from specific trusted individuals, so we might help patients develop that type of trusting relationship with a counselor or other support person. This is yet another reason for preferring “medication-assisted treatment” (MAT) that also includes counseling, instead of simply providing treatment with medications for opioid use disorder (MOUD).
Inflammation is unlikely to be the only explanation for treatment failure among patients with substance use disorders. But substance use treatment is very challenging and there is currently a lot of room for improvement. Every little bit helps, and addressing inflammation seems like a promising avenue for future research and practice efforts to help people with substance use disorders.
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