A randomised, double‐blind study investigating the relationship between early childhood trauma and the rewarding effects of morphine

Abstract

Experiences of childhood trauma (abuse and neglect) are disproportionately higher in those with opioid use disorder (OUD). Childhood trauma may affect the reinforcing and rewarding properties of opioid drugs and responses to pain, potentially via developmental changes to the endogenous opioid system. This has been supported by preclinical research, yet this has not been investigated in non‐addicted humans. Physically healthy participants with either a history of severe childhood trauma or no previous history of childhood trauma attended two sessions where they received either an intramuscular active dose of morphine (0.15 mg/kg) or a very low dose control (0.01 mg/kg) in a randomised, double‐blind crossover design. Sessions were held 1 week apart. Participants' physical pain threshold and tolerance were measured pre‐ and post‐drug administration using the cold water pressor test, alongside acute subjective and behavioural responses over 2.5 h. The trauma group reported liking the effects of morphine, feeling more euphoric and wanting more of the drug over the session, as well as feeling less nauseous, dizzy, and dislike of the effects of morphine compared to the non‐trauma comparison group. Morphine increased pain threshold and tolerance, yet this did not differ between the groups. Childhood trauma may therefore sensitise individuals to the pleasurable and motivational effects of opioids and reduce sensitivity to the negative effects, providing compelling evidence for individual differences in opioid reward sensitivity. This may explain the link between childhood trauma and vulnerability to OUD, with consequent implications on interventions for OUD, the prescribing of opioids, and reducing stigmas surrounding OUD.

Subtypes in addiction and their neurobehavioral profiles across three functional domains

“…Overall, these results support the existence of substantial individual differences in the three mechanisms that have been linked to addiction. Importantly, while previous work had revealed abundant evidence on heterogeneity in approach/reward behavior, executive function and negative emotionality in addiction by investigating each functional domain separately [ 74 – 82 ], this is the first study to show that there are subgroups with differential functional profiles across these three domains.…”

An Umbrella Review of the Links Between Adverse Childhood Experiences and Substance Misuse: What, Why, and Where Do We Go from Here?

“…68 In humans, those exposed to ACEs show a stronger dopamine response to drugs, report greater pleasurable effects (eg euphoria), greater desire for more, and fewer negative effects of opioids compared to those non-exposed to ACEs, as well as a positive association between the number of adverse events in adulthood and dopamine response. 68,69 These alterations may potentially enhance the rewarding effects of substances, increasing the risk of transitioning from controlled to Substance Abuse and Rehabilitation 2022:13 https://doi.org/10.2147/SAR.S341818 DovePress 93 Dovepress compulsive use of substances, and help to explain severity of those presenting with substance use disorder with a history of ACEs. 63,68 Indeed, differences in function and structure of these brain regions have been shown to mediate the relationship between ACEs and subsequent alcohol dependence.…”

Accelerating Opioid Use Disorders Research by Integrating Multiple Data Modalities

“…The risk factors documented are multiple, ranging from genetic influences [10][11][12][13]; personality risk factors, such as impulsivity or the tendency toward risky behavior [14], including use of other substances; traumatic experiences, including early life adversity and family history of substance use disorders [15,16]; demographic characteristics, including exposure to opioids at young age and being male [17,18]; subjective experiences at first opioid use, such as euphoria [19]; nonmedical opioid use, including the use of opioids to get high, improve sleep, decrease anxiety [20]; medical and psychiatric comorbidities, particularly pain conditions or incidence of other substance use disorders [21]; surgical procedures, either minor or major [22,23]; higher and prolonged doses of opioids used [21]. diagnosis, prevention, and treatments.…”

“…For example, studies have shown that high ratings of opiate liking, as well as other subjective effects to first exposure to opioids (e.g., good mood, happy ratings), increase liability to dependence and misuse, compared to dysphoria and sedation [19, 29]. Laboratory studies also allow us to capture hard-to-measure characteristics associated with OUD, such as impulsivity [30], adverse childhood events [31], and trauma [15, 16]. Notably, laboratory studies allow for the direct control of environmental variables, including the ability to administer certain doses of opioids under controlled settings [32], akin or generalizable to the data collected from “real-world” settings, such as that from hospital cohorts [33, 34].…”