Opioid use

We’re looking at three very different studies of opioid use. First, Snyder, Hartinger-Saunders, Yoon, Scott, Jr. & DiGirolamo (2025) published “Childhood Maltreatment and Adult Opioid Use: A systematic review of the literature” in Traumatology. Here’s the edited abstract:

This review fills an important gap in the literature by identifying studies linking childhood maltreatment to adult opioid misuse, assessing methodological rigor including study measures and analyses, and reviewing substantive findings to identify common relationships across studies. We included empirical articles published, in-press, or published online without setting start dates, but setting an end date through November 30, 2023, from key databases including CINAHL Plus, PsycINFO, and PubMed. Qualitative studies, reviews, animal studies, non-English studies, univariate studies, bivariate studies, and studies with individuals under 18 years old were excluded. After removing 278 duplicates, the initial screening yielded 392 articles with 11 meeting the criteria for the final qualitative synthesis. Across studies, the sample size ranged from 60 to 14,800 participants, with studies employing multivariate analyses (n = 11). Measures for child maltreatment varied widely, with studies setting different cutoffs for when child maltreatment ended and few studies establishing the frequency, intensity, duration, or perpetrators of child maltreatment. Despite the methodological issues with the studies included, child maltreatment was directly associated with opioid use disorder, prescription opioid use, or younger age of onset for opioid use in nine studies. Interventions and policies should address the enduring effects of child maltreatment on opioid use. 

I thought this study was important in examining a huge number of studies and finding child maltreatment an important precursor of opioid use. The next study looks at rats but is also helpful. King'uyu, Edgar, Figueroa, Kirkland & Kopec (2023) published “Morphine Exposure During Adolescence Induces Enduring Social Changes Dependent on Adolescent Stage of Exposure, Sex, and Social Test” in Behavioral Neuroscience. Here are some excerpts:

Drug exposure during adolescence, when the “reward” circuitry of the brain is developing, can permanently impact reward-related behavior into adulthood. Epidemiological studies show that opioid treatment during adolescence, such as pain management for a dental procedure or surgery, increases the incidence of psychiatric illness including substance use disorders. Moreover, the opioid epidemic currently in the United States is affecting younger individuals raising the impetus to understand the pathogenesis of the negative effects of opioids. One reward-related behavior that develops during adolescence is social behavior. We previously demonstrated that developmental changes in the nucleus accumbens reward region regulate social development in rats during sex-specific adolescent periods: early to mid-adolescence in males (postnatal day, P30–40) and preearly adolescence in females (P20–30). We thus hypothesized that the developmental stage of morphine exposure will differentially impact social behavior development such that drug administered during the female critical period would result in adult sociability deficits in females, but not males, and morphine administered during the male critical period would result in adult sociability deficits in males, but not females. We found that morphine exposure during the female critical period primarily resulted in deficits in sociability in females, while morphine exposure during the male critical period primarily resulted in deficits in sociability primarily in males. However, depending on the test performed and the social parameter measured, social alterations could be found in both sexes that received morphine exposure at either adolescent stage. These data indicate that when drug exposure occurs during adolescence, and how the endpoint data are measured, will play a large role in determining the effects of drug exposures on social development.

 The epidemiological evidence indicating that juvenile opioid exposure can increase the incidence of psychiatric disorders are limited in distinguishing the outcome trajectories based on juvenile age and sex. Our data suggest that consideration of these factors is necessary to understand the link between opioid exposure and negative outcomes. Nearly all psychiatric disorders, including substance use disorder, contain abnormal social components or consequences. Social contexts and cues are similarly important in reward-related substance use behaviors (Strickland & Smith, 2014). Understanding how to manage reward-related substance use behaviors in the clinical setting would be a pathway to the treatment of substance use disorders and combatting the current opioid crisis.

In summary, we characterized long-lasting opioid-induced social deficits that depend on period of exposure and sex. The context of social behavior revealed different types of deficits and the period of opioid exposure and the resulting effects by sex hint at the underlying mechanisms causing the deficits. The direction of deficits depending on sex is not as clear as our original hypothesis, thus our reformed hypothesis is that morphine-induced deficits are period specific depending on behavioral task and can be sex specific or sex neutral. These results suggest a complex interplay of different sociability features disrupted in different ways by opioids leading to different social deficits.

This study is a logical extension of the first one in illustrating that morphine exposure during critical periods of adolescence impacts social deficits in adulthood. I found it especially fascinating that morphine exposure for males during the female critical period or females during the male critical period doesn’t impact the rats as much as exposure in their respective critical periods. The final study looks at heroin use vs. prescription opioid use.  Dash, Gizer, Martin & Slutske (2024) published “Differential Etiologic Associations of Heroin Use and Prescription Opioid Misuse with Psychopathology” in Journal of Psychopathology and Clinical Science. Here are the edited abstract and impact statement:

Patterns of association with externalizing and internalizing features differ across heroin use and prescription opioid misuse (POM). The present study examined whether heroin use and POM display differential etiologic overlap with symptoms of conduct disorder (CD), adult antisocial behavior (AAB), and major depressive episodes (MDEs), how aggregating heroin use and POM into a single phenotype may bias results, and explored potential sex differences. Seven thousand one hundred and sixty-four individual twins from the Australian Twin Registry (ATR; 59.81% female; Mage = 30.58 years) reported lifetime heroin use, POM, CD symptoms, AABs, and MDE symptoms within a semi-structured interview. Biometric models decomposed phenotypic variance and covariance into additive genetic, common environmental, and unique environmental effects. The proportion of variance in heroin use attributable to factors shared with CD, AAB, and MDE, respectively, was 41%, 41%, and 0% for men and 26%, 19%, and 42% for women; for POM, the proportions were 33%, 35%, and 20% for men and 15%, 9%, and 13% for women. CD and AAB were more strongly genetically correlated with heroin use among women and with POM among men. MDE was more strongly genetically correlated with POM than with heroin use among men, but more strongly genetically correlated with heroin use than with POM among women. Analyses using an aggregate opioid (mis)use variable were biased toward POM, which was the more prevalent phenotype. Magnitude and source of etiologic influence may differ across forms of opioid (mis)use and sex. Disaggregating heroin use and POM in future opioid research may be warranted. 

This study provides preliminary evidence of differences in the magnitude and source of etiologic associations of heroin use and prescription opioid misuse (POM) with psychopathology. Whereas conduct disorder showed differences in the source of shared etiology (genes vs. environment) across heroin use and POM, overlap with depression was solely attributable to genetic influences across both opioid types. However, depression showed differences in the magnitude of shared genetic etiology with heroin use versus POM that also differed across men and women. 

This is a huge sample. Once again, we find gender differences in that, for women, using heroin is more closely associated with conduct disorder and antisocial behavior while, for men, prescription opioid use is associated with conduct disorder and antisocial behavior. In contrast, depression is more associated with heroin use in men, but prescription opioid use in women. Although these three studies make clear the adverse consequences of early opioid exposure for children, the data are complex. They do merit asking good questions about personal and drug history.