Clinical Implications of the Relationship Between Naltrexone Plasma Levels and the Subjective Effects of Heroin in Humans.

BACKGROUND: Extended-release naltrexone (NTX) is an opioid antagonist approved for relapse prevention after medical withdrawal. Its therapeutic effect is dependent on the NTX plasma level, and as it decreases, patients may lack protection against relapse and overdose. Therefore, identifying the minimally effective NTX level needed to block opioid-induced subjective effects has important clinical implications. METHODS: This secondary, individual-level analysis of data collected in a human laboratory study was conducted to evaluate the relationship between NTX levels and subjective effects of an intravenously administered 25-mg challenge dose of heroin in non-treatment-seeking participants with opioid use disorder (N = 12). Subjective ratings of drug liking using a 100-mm visual analog scale (VAS) and NTX levels were measured across 6 weeks after participants received a single injection of either extended-release NTX 192 mg (N = 6) or 384 mg (N = 6). Cubic spline mixed-effects models were used to provide 95% prediction intervals for individual changes in liking scores as a function of NTX levels. RESULTS: Naltrexone levels above 2 ng/mL blocked nearly all VAS ratings of drug liking after intravenous heroin administration. Participants with NTX levels ≥ 2 ng/mL had minimal (≤20 mm) changes from placebo in VAS ratings of drug liking based on 95% prediction intervals. In contrast, NTX levels < 2 ng/mL were associated with greater variability in individual-level subjective responses. CONCLUSIONS: In clinical practice, a plasma level range of 1 to 2 ng/mL is considered to be therapeutic in providing heroin blockade. The current findings suggest that a higher level (>2 ng/mL) may be needed to produce a consistent blockade.

Neuropsychological, Medical, and Psychiatric Findings After Recovery From Acute COVID-19: A Cross-sectional Study.

BACKGROUND: Persistent cognitive, medical and psychiatric complaints have been extensively described after recovery from acute SARS-CoV-2 infection. OBJECTIVE: To describe neuropsychological, medical, psychiatric, and functional correlates of cognitive complaints experienced after recovery from acute COVID-19 infection. METHODS: Sixty participants underwent neuropsychological, psychiatric, medical, functional, and quality-of-life assessments 6-8 months after acute COVID-19. Those seeking care for cognitive complaints in a post-COVID-19 clinical program for post-acute symptoms of COVID-19 (clinical group, N = 32) were compared with those recruited from the community who were not seeking care (nonclinical, N = 28). A subset of participants underwent serological testing for proinflammatory cytokines C-reactive protein, interleukin-6, and tumor necrosis factor-α to explore correlations with neuropsychological, psychiatric, and medical variables. RESULTS: For the entire sample, 16 (27%) had extremely low test scores (less than second percentile on at least 1 neuropsychological test). The clinical group with cognitive complaints scored lower than age-adjusted population norms in tests of attention, processing speed, memory, and executive function and scored significantly more in the extremely low range than the nonclinical group (38% vs. 14%, P < 0.04). The clinical group also reported higher levels of depression, anxiety, fatigue, posttraumatic stress disorder, and functional difficulties and lower quality of life. In logistic regression analysis, scoring in the extremely low range was predicted by acute COVID-19 symptoms, current depression score, number of medical comorbidities, and subjective cognitive complaints in the areas of memory, language, and executive functions. Interleukin-6 correlated with acute COVID symptoms, number of medical comorbidities, fatigue, and inversely with measures of executive function. C-reactive protein correlated with current COVID symptoms and depression score but inversely with quality of life. CONCLUSION: Results suggest the existence of extremely low neuropsychological test performance experienced by some individuals months after acute COVID-19 infection, affecting multiple neurocognitive domains. This extremely low neuropsychological test performance is associated with worse acute COVID-19 symptoms, depression, medical comorbidities, functional complaints, and subjective cognitive complaints. Exploratory correlations with proinflammatory cytokines support further research into inflammatory mechanisms and viable treatments.