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Nature

This study identifies a novel µ-opioid receptor (MOR) agonist with supramaximal intrinsic efficacy and a unique pharmacological profile that produced effective analgesia in rodents with minimal adverse effects. N-desethyl-fluornitrazene (DFNZ) was derived from a class of synthetic benzimidazole opioids called nitazenes. DFNZ has impaired brain penetrance, a unique spatiotemporal MOR cellular signaling profile, and diminished efficacy at the MOR–galanin 1 receptor (GAL1) heteromer. DFNZ does not induce respiratory depression, tolerance, or MOR downregulation after repeated exposure. Compared with other MOR agonists, DFNZ has limited effects on dopamine neurotransmission in the nucleus accumbens and weaker reinforcing effects in the drug self-administration procedure. These results provide novel insights about MOR and nitazene pharmacology, have important implications for pain and addiction treatment, and challenge the prevailing dogma that high-efficacy MOR agonists cannot constitute safe and effective therapeutic agents.

Journal of Studies on Alcohol and Drugs

Researchers conducted a cross-sequential study to examine any association between e-cigarette use patterns over one year (never, non-escalating, increasing, and sustained use) and self-reported respiratory symptoms (any respiratory symptoms, days in past 30 days with symptoms, and American Thoracic Society Questionnaire (ATSQ) scores) among adolescents and young adults (aged 15–24). In adjusted logistic regression analysis, there were no statistically significant associations between e-cigarette use patterns and dichotomous respiratory outcomes. In adjusted linear regression analysis, sustained and non-escalating use were associated with higher average days of symptoms. Sustained use was also associated with higher ATSQ scores. Authors noted the data demonstrate dynamic e-cigarette use patterns and frequent use of multiple products (including cannabis), suggesting intervention approaches may need to be individualized.

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Journal of Psychiatry and Neuroscience

Diagnostic frameworks often focus on symptomatic presentations and not underlying psychological and neurobiological mechanisms of substance use disorders (SUD). The Addictions Neuroclinical Assessment (ANA) framework uses three domains (executive function, negative emotionality, and incentive salience) as an approach to describing the underpinnings of SUDs. Researchers conducted machine learning-based computation validation to assess any association between ANA domains and hazardous drinking measured by the Alcohol Use Disorder Identification Test (AUDIT). In two separate samples, researchers found a strong correlation between incentive salience and hazardous drinking. The authors note that while machine learning is unlikely to be used for clinical screening, these approaches could be used to help inform and refine other assessment tools.

Drug and Alcohol Dependence

Neuroimaging studies show that persons with SUD have reduced response to pleasurable experiences (nondrug rewards), and OUD is associated with anhedonia. This study recruited 153 patients receiving MOUD (methadone in 85%) from an outpatient treatment center. Each completed an anhedonia rating scale and then received a daily smartphone prompt to complete an inventory of the day’s nondrug rewards. Of 1,752 person-days recorded, the most common day (47% of days) had 1–2 nondrug rewards, with the most common reward being relaxing at home, followed by hobbies. The number of nondrug rewards was greater in people with higher motivation to pursue rewards (OR=2.64) and greater accessibility to rewards (OR=2.67). Time in recovery and anhedonia were not significant predictors. The mean time in recovery was 3.8 years, and the authors speculate that improvements may have occurred earlier in recovery.

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JAMA Health Forum

This study compared residential SUD treatment facilities owned by private equity (PE, n=127) with other for-profit facilities (n=214). Researchers conducted a secret shopper survey in which callers asked about costs and other facility details. PE facility daily rates were 16% higher ($911 vs $780, p=.04). PE facilities were less likely to offer detox services (75% vs 89%, p=.02) and private rooms (12% vs 26%, p=.02). There was no statistically significant difference in bed availability or acceptance of Medicaid. The authors conclude that PE ownership is associated with higher costs and call for studies of patient outcomes and quality of care.

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Addiction Science and Clinical Practice

This qualitative study explored stakeholders’ perspectives of a mobile health unit (MHU) providing medications for opioid use disorder in Rhode Island. Semi-structured interviews were conducted with 15 participants, including MHU staff, leadership, policymakers, and community partners. Participants found the MHU decreased barriers to care, particularly for people experiencing homelessness; facilitated strong patient-provider relationships; and allowed for linkages to primary care and other social services. Funding sustainability, staffing shortages, and environmental barriers were key challenges faced by the MHU.