Impulsivity, Compulsivity & The Brain During Opioid Addiction, Methadone Treatment & Abstinence

Opioid use disorder is associated with a wide range of cognitive deficits and impairments. Studies suggest that opioid-related deficits may improve in some cognitive domains but not in others.

WHAT PROBLEM DOES THIS STUDY ADDRESS?

Impulsivity and compulsivity are important factors in the addiction cycle, but it is not entirely understood how these cognitive functions and their associated brain structures look over the course of opioid addiction.

TWO IMPORTANT COGNITIVE DOMAINS IN ADDICTION & RECOVERY:

IMPULSIVITY (“leap before you look” instead of “looking before you leap”), poor self-regulation, impaired decision making
COMPULSIVITY (finding yourself compelled to leap whether you look or not), characterized by inflexible repetitive behaviors

This study examined cognitive impulsivity, compulsivity, and brain structure, as well as relationships between them in individuals with opioid use disorder during periods of active addiction, methadone treatment, and abstinence-based recovery.

HOW WAS THIS STUDY CONDUCTED?

Four groups of men were recruited, including 3 patient groups diagnosed with opioid use disorder (determined with the Mini International Neuropsychiatric Interview) and 1 healthy control group.

MORE ON STUDY METHODS

Among those with opioid use disorder, 24 individuals were actively engaged in daily heroin use at the time of the study (heroin group; ~26 years old), 48 were in recovery and receiving methadone maintenance treatment (methadone treated group; ~30 years old; ~67 mg methadone per day for at least 6 months), and 24 were in recovery, no longer receiving methadone treatment, and free of all psychoactive substances for approximately 6 months (abstinent group; ~37 years old). The healthy control group consisted of 50 men (~28 years old) without a history of substance use disorder.

All participants provided information regarding their substance use histories and completed neuropsychological tests that examine various aspects of compulsivity and impulsivity. Compulsivity was investigated with the Intra-Extra Dimensional set-shifting task, which requires participants to learn task rules as they go and adapt their behavior as the rules of the task change (i.e. cognitive flexibility). Impulsivity was measured with the Cambridge Gambling Task for which participants make bets on their decisions in a game of probability/chance (i.e. decision making and risk-taking). A subset of the participants also completed brain scans, including 33 individuals in the methadone treated group, 15 in the abstinent group, and 23 in the healthy control group. Brain scans were performed with Magnetic Resonance Imaging (MRI) and structural brain images were assessed for probability of regional gray and white matter atrophy (reductions) by comparing opioid use disorder groups to the healthy control group.

None of the participants had a history of benzodiazepine, stimulant, or alcohol dependence, other significant psychiatric disorders (e.g., psychosis), or serious medical conditions (e.g., neurodevelopmental disorder). All patient groups had similar opioid use histories and demographic characteristics. Relative to the control group, the abstinent group was older and all three groups with opioid use disorder had lower premorbid IQ (baseline intellectual functioning). Only age-related differences persisted among the subgroups that completed brain scans.

WHAT DID THIS STUDY FIND?

In general, the abstinent group and heroin group performed similarly to one another on set-shifting task, with both showing higher levels of compulsivity than healthy controls. Worse performance on this specific task was related to reduced gray and white matter in a variety of cortical (at the brain’s surface) and subcortical (below the brain’s surface) regions. In the abstinent group poorer task performance was associated with reduced white matter in brain regions important for cognitive flexibility and adaptive responding (orbitofrontal and prefrontal cortex).

Impulsivity was impaired across all opioid use disorder groups relative to healthy controls. The heroin group showed the highest level of impulsivity and the methadone treated group showed the lowest degree of impulsivity, with the abstinent group fall in between. In the opioid use disorder group, lower levels of impulsivity were associated with higher levels of compulsivity. This compulsive/impulsive trade-off was related to structural brain abnormalities in the brain (prefrontal cortex & striatum) that control compulsivity and impulsivity.

Longer duration or histories of opioid misuse was associated with worse performance on both neuropsychological tasks (compulsivity & impulsivity) and with reduced gray matter in the globus pallidus, a region associated with heroin intoxication and impulsive behaviors.

WHY IS THIS STUDY IMPORTANT?

Studies like these, that provide information about both brain and behavior, advance our understanding of recovery related processes and provide a more complete picture of the cognitive difficulties associated with substance use disorders, the brain abnormalities that underlie these behavioral deficits, and their potential to improve during treatment and recovery.

The results of this study revealed heightened compulsivity in individuals actively using heroin and in abstinent individuals recovering from opioid use disorder, suggesting that impaired cognitive flexibility (i.e. compulsive behaviors) may persist with short-term abstinence. Persistence of heightened compulsivity has the potential to increase risk of relapse.

Importantly, this study suggests that methadone may reduce compulsivity by normalizing dopamine and serotonin chemical imbalances in the brain, thereby alleviating compulsive tendencies. Furthermore, heightened compulsivity observed in abstinent individuals may suggest a recurrence of this chemical imbalance when ending methadone treatment.

The relationship between compulsivity and impulsivity suggests a dominant/subordinate relationship, in that impairments in impulsivity may become less pronounced as compulsive behaviors dominate, and vise-versa. This relationship speaks to theories of addiction that propose a dynamic shift from impulsivity dominating during the early stages of addiction to compulsivity dominating during the later stages. Nonetheless, impulsivity appears to be present to some degree at multiple stages of opioid addiction/recovery.

Opioid use disorder groups showed heightened impulsivity relative to control group participants. Cognitive impulsivity may be a risk factor that precedes opioid addiction and persists despite recovery from opioid use disorder or taking methadone. Adjunct therapies to enhance functioning (i.e. cognitive enhancement therapies) within this cognitive domain might help to prevent relapse.

LIMITATIONS

Brain imaging was not performed in the heroin group. Although these data facilitate our understanding of the relationship between brain structure, compulsivity, and opioid use in treatment and recovery, they do not speak to these associations during active opioid addiction. Further investigation is needed to characterize these relationships in individuals with active use and to identify how these relationships change during addiction recovery transitions.
The study sample only consisted of men. Therefore, it is not clear if these findings extend to women with opioid use disorder. Furthermore, groups differed with respect to age and premorbid intelligence, and the influence of these factors on study outcomes was not clear. While the authors noted controlling for these factors in follow-up analyses, their effect on results was not explicitly reported.
Though these data facilitate our understanding of impulsive and compulsive impairments and their neural correlates across the addiction and recovery trajectory, the cross-sectional nature of this study limits interpretation. Given that this was not a longitudinal assessment, findings are subject to the potential influence of other factors that may have differed between groups but were unaccounted for (e.g., patterns of non-opioid substance use).
Impulsivity was not emphasized in this study. Different patterns of impulsivity between the heroin group, methadone group, and abstinent group were not reported in detail. Although a previous publication by the same authors offers some insight, it does not provide a full picture of impulsivity and related brain abnormalities over the course of opioid addiction, treatment, and recovery.

BOTTOM LINE

For individuals & families seeking recovery: Individuals with opioid use disorder may have heightened impulsivity (poor self-regulation and impaired decision making), compulsivity (inflexible repetitive behaviors), and injury to related brain regions that persist even when opioid use has stopped, effects which may worsen with prolonged opioid misuse. A better understanding of these cognitive functions can ultimately lead to strategies for enhancing treatment and recovery. Importantly, engaging in methadone treatment (a medication frequently used to treat opioid use disorder) might help to alleviate cognitive impairment, particularly compulsivity. Given buprenorphine/naloxone (Suboxone) has similar properties and therapeutic effects as methadone, future research will help to determine if some of these same benefits might be seen if your loved-one were to engage in Suboxone treatment.
For scientists: Opioid use disorder is accompanied by heighted compulsivity, impulsivity, and associated neurostructural compromise to frontal and striatal regions, which appear more pronounced with protracted duration of opioid misuse and persist during abstinence. Importantly, methadone might help to alleviate compulsive behaviors. Prospective research is needed to identify whether methadone is directly responsible for these cognitive benefits, the neural and pharmacological mechanisms that underlie this effect, and processes by which these benefits might be maintained after cessation of opioid agonist treatment. Furthermore, impulsivity and compulsivity may be inversely related in individuals with opioid use disorder. Characterizing the dynamic and shifting aspects of their disproportional presentation throughout the course of opioid addiction, treatment, and recovery will ultimately advance theoretical models of addiction among the scientific community and guide our understanding of this multifaceted disorder.
For policy makers: Research studies like this one provide important information about cognitive function at different stages of addiction, treatment, and recovery and the factors associated with dysfunction. In the context of this study, cognitive abilities (specifically impulsivity and compulsivity) that play an important role in the addiction cycle and recovery from substance use disorders appear to be dysfunctional in individuals with opioid use disorder and persist during abstinence. Importantly, methadone might have the potential to alleviate some of this cognitive difficulty. Methadone is a federally regulated medication for the treatment of opioid use disorder that reduces withdrawal and craving but does not produce the euphoric feelings caused by the original opioid of misuse. Given that impulsivity and compulsivity play an important role in maintaining the addiction cycle, therapeutic enhancement of these functions has significant potential to support successful recovery outcomes. Although the beneficial effects of methadone on these cognitive abilities needs to be confirmed with longitudinal studies, methadone’s positive influence on treatment and recovery outcomes merits its continued distribution to those in need of its therapeutic effects. Allocating additional funds to better understand the effects and correlates of pharmacotherapies for opioid addiction (methadone, buprenorphine/naloxone (i.e. Suboxone)), particularly in longitudinal studies, will undoubtedly improve our nation’s ability to more effectively help the growing population of individuals with opioid use disorder.
For treatment professionals and treatment systems: Individuals with opioid use disorder exhibit abnormally high levels of impulsivity, compulsivity, and compromise to related brain structures that persist during early abstinence and appear to be more pronounced among individuals with longer opioid misuse histories. Interestingly, methadone might help to alleviate compulsive behaviors. Given that methadone’s benefits do not seem to extend to impulsivity and heightened compulsivity may return upon cessation of opioid agonist treatment, adjunct therapies that address these cognitive difficulties might promote further cognitive improvement in domains that play a key role in addiction and recovery. Longitudinal investigation is needed to assess whether these effects are directly attributable to methadone’s pharmacological properties or secondary factors and to determine if these same benefits extend to buprenorphine.

CITATIONS

Tolomeo, S., Matthews, K., Steele, D., & Baldacchino, A. (2018). Compulsivity in opioid dependence. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 81, 333-339.