Effects Of Naltrexone Research Articles

Is Naltrexone Effective and Safe for Treating Amphetamine-Type Stimulant Use Disorder? A Systematic Review and Meta-analysis.

We conducted a systematic review and meta-analysis (PROSPERO ID: CRD42023401796) of randomized placebo-controlled trials evaluating the effectiveness and safety of naltrexone as a standalone pharmacotherapy for amphetamine-type stimulant use disorder (ATSUD). We searched EMBASE, MEDLINE, EBM Reviews, PsycINFO, CINAHL, Google Scholar, and trial registries on April 11, 2023, and updated on September 24, 2024, to identify randomized placebo-controlled trials evaluating the effectiveness of naltrexone for the treatment of ATSUD. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were followed for reporting the study. Risk of bias and quality of evidence were assessed with the Cochrane Risk-of-bias Assessment tool and the Grading of Recommendations, Assessment, Development, and Evaluation. Risk ratios (RRs) or Peto odds ratio were estimated for binary outcomes as appropriate. Standardized mean differences were calculated for continuous outcomes. Five studies (n = 419 participants) were eligible. We found no significant difference between naltrexone and placebo for amphetamine-type stimulant use (RR = 0.903, 95% confidence interval [CI] = 0.698 to 1.167, P = 0.44, I2 = 96.1%; 4 studies), study retention (RR = 1.055, 95% CI = 0.942 to 1.182, P = 0.35, I2 = 45.0%; 4 studies), end-of-treatment craving (standardized mean difference = 0.069, 95% CI = -0.272 to 0.410, P = 0.69, I2 = 0.0%; 2 studies), and serious adverse events (odds ratio = 1.086, 95% CI = 0.414 to 2.849, P = 0.87, I2 = 0.0%; 3 studies). The quality of evidence was low to very low. The available evidence does not support the use of standalone naltrexone to treat ATSUD. Significant research efforts must be put toward to identify effective pharmacotherapies to complement psychosocial interventions for ATSUD.

Comparative effects of topiramate and naltrexone on neural activity during anticipatory anxiety in individuals with alcohol use disorder.

Topiramate has been found to be effective in reducing alcohol use and may also attenuate anxiety severity in patients with alcohol use disorder (AUD). This study compared the neural response of treatment-seeking patients with AUD on either topiramate or naltrexone during an anticipatory anxiety task. Participants were 42 patients with AUD who were randomized to receive either topiramate (n =23; titrated dose up to 200mg/day) or naltrexone (n = 19; 50mg/day) for 12-weeks as part of a larger randomized controlled trial. Following 6weeks of treatment, participants completed an anticipatory anxiety task during a functional magnetic resonance imaging (fMRI) session. The task presented a series of high-threat and low-threat stimuli followed by an unpleasant or pleasant image, respectively. Primary whole-brain analyses revealed no significant differences in neural activation between the topiramate and naltrexone groups. Deactivation for safe cues relative to threat cues was observed within the precuneus, inferior parietal lobule and the cingulate gyrus. In the precentral and middle frontal gyri, threat cues elicited greater activation. Exploratory analyses revealed an effect of change in anxiety from baseline to week 6, with a greater reduction associated with a reduced response to threat cues relative to safe cues in the cuneus and lingual gyrus. The current study is the first to examine and compare neural activation during anticipatory anxiety in treatment-seeking individuals on topiramate and naltrexone. This preliminary research contributes to our understanding of the therapeutic mechanisms of these alcohol pharmacotherapies.

Safety and Effectiveness of Naltrexone in the Management of Alcohol Use Disorder in Patients With Alcohol-associated Cirrhosis: First Clinical Observation From Indian Cohort

Naltrexone is a promising drug to treat alcohol use disorder with limited evidence of safety in liver diseases. An observational study was performed to study the safety, effectiveness, and tolerability of Naltrexone in the management of alcohol use disorder in patients with alcohol-associated cirrhosis. Naltrexone was started in patients with alcohol-related liver disease for the management of alcohol use disorder in 86 patients who were followed up for 4 weeks. Baseline liver parameters were compared with those at 4 weeks to establish safety of the drug. Effectiveness was determined by observing reduction in AUDIT scores, craving, number and days of drinking. Self-report of side effects was noted. After 4 weeks of starting Naltrexone there was a decrease in AST-89.86 vs 57.61, ALT-50.19 vs 27.08, SAP-121.81 vs 98.19, GGT-166.93 vs 109 and MELD 16.32 vs 12.13 (none statistically significant). There was a statistically significant reduction in Serum Bilirubin- (4.31 vs 1.98), INR (1.49 vs 1.32), self-reported craving (3.71 Vs 1.97; P= 0.01), AUDIT scores (24.13 Vs 16.91; P <0.01) and number of drinking days in last one month (10.22 Vs 4.19; P= 0.03). The reduction in all liver parameters and AUDIT scores and craving after treatment with Naltrexone supports its safety and utility in the management of alcohol use disorder in alcohol-related liver cirrhosis.

Comparative effectiveness of extended-release naltrexone and sublingual buprenorphine for treatment of opioid use disorder among Medicaid patients.

Extended-release naltrexone (XR-NTX) and sublingual buprenorphine (SL-BUP) are both approved for opioid use disorder (OUD) treatment in any medical setting. We aimed to compare the real-world effectiveness of XR-NTX and SL-BUP. This was an observational active comparator, new user cohort study of Medicaid claims records for patients in New Jersey and California, USA, 2016-19. The participants were adult Medicaid patients aged 18-64 years who initiated XR-NTX or SL-BUP for maintenance treatment of OUD and did not use medications for OUD in the 90 days before initiation. Our cohort included 1755 XR-NTX and 9886 SL-BUP patients. We examined two outcomes up to 180 days after medication initiation: (1) composite of medication discontinuation and death and (2) composite of overdose and death. In adjusted analyses, treatment with XR-NTX was more likely to result in discontinuation or death by the end of follow-up than treatment with SL-BUP: cumulative risk 75.9% [95% confidence interval (CI) = 73.9%, 77.9%] versus 62.2% (95% CI = 61.2%, 63.2%), respectively (risk difference = 13.7 percentage points, 95% CI = 11.4, 16.0). There was minimal difference in the cumulative risk of overdose or death by the end of follow-up: XR-NTX 3.9% (95% CI = 3.0%, 4.8%) versus SL-BUP 3.3% (95% CI = 2.9%, 3.7%); risk difference = 0.5 percentage points, 95% CI = -0.4, 1.5. Results were consistent across sensitivity analyses. Medicaid patients in California and New Jersey, USA, receiving treatment for opioid use disorder stayed in treatment longer on sublingual buprenorphine than on extended-release naltrexone, but the risk of overdose was similar. Most patients in this study discontinued medication within 6months, regardless of which medication was initiated.

Topical naltrexone potentiates cutaneous wound healing in blackbelt cichlids (Vieja maculicauda).

To evaluate the effects of topical naltrexone on wound healing in freshwater fish. 25 blackbelt cichlids (Vieja maculicauda). A randomized, controlled, experimental trial was performed, with each individual serving as its own control. Bilateral 6-mm periepaxial cutaneous wounds were created in the body-wall skin of each fish under anesthesia. Three treatment groups were as follows: topical 0.04% naltrexone in administration vehicle (iLEX ointment; iLEX Health Products) at day 0 only (n = 10), topical 0.04% naltrexone in iLEX every 72 to 96 hours (n = 10), or iLEX only every 72 to 96 hours (n = 5) for 10 total treatments. The contralateral wound was left untreated as a control. Fish were maintained in a common enclosure at 24.7 to 25.4 °C for 35 days. Macroscopic wound assessment and image collection were performed every 72 to 96 hours. On day 35, fish were humanely euthanized, and skin samples were collected for histopathology. Time to complete visual resolution of wound healing was faster (P = .002) in wounds treated every 72 to 96 hours with topical 0.04% naltrexone in iLEX (day 19.4) compared to untreated wounds (day 23.3). An interaction between treatment and day was observed (P = .002), with fish treated with 0.04% naltrexone in iLEX every 72 to 96 hours having reduced (P < .05) wound area compared to both controls and fish treated with topical 0.04% naltrexone in iLEX once. No significant differences were noted in histologic sections of wound sites examined at day 35. Fish improved earlier postsurgery and time to complete wound resolution was faster in wounds treated with topical 0.04% naltrexone in iLEX every 72 to 96 hours.

Neural correlates of impulsivity in amphetamine use disorder

Impulsivity is a trait associated with several psychiatric conditions, not least addictive disorders. While the neural mechanisms behind certain aspects of impulsivity have been studied extensively, there are few imaging studies examining this neurocircuitry in populations with substance use disorders. Therefore, we aimed to examine the functional connectivity of relevant neural networks, and their possible association with trait impulsivity, in a sample with severe amphetamine use disorder and a control group of healthy subjects. We used data collected in a randomized clinical trial studying the acute effects of oral naltrexone in amphetamine use disorder. Our final sample included 32 amphetamine users and 27 healthy controls. Trait impulsivity was rated with the Barratt Impulsiveness Scale-11, and functional connectivity was measured during resting-state fMRI, looking specifically at networks involving prefrontal regions previously implicated in studies of impulsivity. Amphetamine users had higher subjective ratings of impulsivity as compared to healthy controls, and these scores correlated positively with a wide-spread prefrontal hyperconnectivity that was found among the amphetamine users. These findings highlight the importance of aberrant prefrontal function in severe addiction.

Naltrexone accelerated oral traumatic ulcer healing and downregulated TLR-4/NF-kB pathway in Wistar rats

ObjectiveTo assess the effect of naltrexone on oral mucosal healing using a traumatic ulcer model DesignWistar rats (n = 112) received distilled water (control) or naltrexone (0.5, 10, or 50 mg/kg/day). Ulcers were induced on the buccal mucosa using a round skin biopsy punch (diameter 6 mm). Euthanasia was performed on days 1, 3, 7, and 14. Healing was assessed by ulcer area, histological scores, histomorphometric analysis (number of polymorphonuclears, mononuclears, and fibroblasts), and collagen percentage. Immunohistochemistry for TLR-2, TLR-4, NF-kB, and CD31 was evaluated. Nociceptive threshold was measured daily. ResultsThe 50 mg/kg group showed reduced ulcer area on days 1 (p < 0.001), 3 (p < 0.05), and 14 (p < 0.01). In this group, there was, on day 14, an increase in the percentage of reepithelization (p = 0.043) and collagen (p < 0.05), an increase in connective tissue maturation (p = 0.016), and on day 7 an increase in fibroblasts (p < 0.001). The 10 mg/kg dose reduced the ulcer area on day 1 (p < 0.001). The 50 mg/kg group showed lower expression of TLR-4 (p < 0.001) on day 1, NF-kB on days 1 (p < 0.05) and 14 (p < 0.05), and CD31 on day 14 (p < 0.05). The 0.5 and 10 mg/kg doses reduced TLR-4 expression on day 1 (p < 0.05; p < 0.01, respectively). Nociceptive threshold increased in the 50 mg/kg group (p < 0.01). ConclusionNaltrexone enhanced traumatic oral ulcer healing by reducing TLR-4/NF-kB signaling and promoting fibroblast proliferation and collagen deposition. Additionally, naltrexone reduced pain in rats.

Effects of Naltrexone on Sleep Quality and Periodic Breathing at High Altitude.

Foster, Katharine, James D. Anholm, Gary Foster, Suman Thapamagar, and Prajan Subedi. Effects of naltrexone on sleep quality and periodic breathing at high altitude. High Alt Med Biol. 00:000-000, 2024. Objective: This study examined the effects of naltrexone on breathing and sleep at high altitude. Mu-opioid receptor (MOR) agonists have a depressive effect on respiration. Naltrexone is known to block the MOR. We hypothesized that MOR blockade with naltrexone would result in higher nocturnal oxygen saturations, fewer apneas, and improved sleep at high altitude. Methods: This double-blind, placebo-controlled, crossover study included nine healthy volunteers (four females, five males) aged 27.9 (4.6) (mean [standard deviation]) years. Two overnight trips spaced at least 2 weeks apart took participants from Loma Linda, CA (355 m) to the Barcroft Laboratory, CA (3,810 m) for each arm. Participants ingested either 50 mg naltrexone or matching placebo at bedtime. Sleep metrics were recorded using an ambulatory physiological sleep monitor (APSM). Subjective data were measured with the Groningen Sleep Quality Scale, Stanford Sleepiness Scale, and the 2018 Lake Louise Score (LLS) for acute mountain sickness (AMS). Results: Mean overnight SpO2 was lower after taking naltrexone, 81% (6) versus 83% (4) (mean difference 1.9% [2.1, 95% confidence interval or CI = 0.1-3.6, p = 0.040]). The lowest overnight SpO2 (nadir) was lower on naltrexone 70% (6) versus 74% (4) (dif. 4.6% [4.3], CI = 1.0-8.2, p = 0.020). Total sleep time and total apnea-hypopnea index were unchanged. Subjective sleep quality was significantly worse on naltrexone measured via the Groningen Sleep Quality Scale (p = 0.033) and Stanford Sleepiness Scale (p = 0.038). AMS measured via LLS was significantly worse while taking naltrexone (p = 0.025). Conclusion: Contrary to our hypothesis, this study demonstrated a significant decrease in nocturnal oxygen saturation, worse sleep quality, and AMS scores. Further characterization of the MOR's effects on sleep and AMS is needed to evaluate potential exacerbating mechanisms for AMS and poor sleep quality at altitude.

Neuroprotective effects of naltrexone in a mouse model of post-traumatic seizures

Traumatic Brain Injury (TBI) induces neuroinflammatory response that can initiate epileptogenesis, which develops into epilepsy. Recently, we identified anti-convulsive effects of naltrexone, a mu-opioid receptor (MOR) antagonist, used to treat drug addiction. While blocking opioid receptors can reduce inflammation, it is unclear if post-TBI seizures can be prevented by blocking MORs. Here, we tested if naltrexone prevents neuroinflammation and/or seizures post-TBI. TBI was induced by a modified Marmarou Weight-Drop (WD) method on 4-week-old C57BL/6J male mice. Mice were placed in two groups: non-telemetry assessing the acute effects or in telemetry monitoring for interictal events and spontaneous seizures both following TBI and naltrexone. Molecular, histological and neuroimaging techniques were used to evaluate neuroinflammation, neurodegeneration and fiber track integrity at 8 days and 3 months post-TBI. Peripheral immune responses were assessed through serum chemokine/cytokine measurements. Our results show an increase in MOR expression, nitro-oxidative stress, mRNA expression of inflammatory cytokines, microgliosis, neurodegeneration, and white matter damage in the neocortex of TBI mice. Video-EEG revealed increased interictal events in TBI mice, with 71% mice developing post-traumatic seizures (PTS). Naltrexone treatment ameliorated neuroinflammation, neurodegeneration, reduced interictal events and prevented seizures in all TBI mice, which makes naltrexone a promising candidate against PTS, TBI-associated neuroinflammation and epileptogenesis in a WD model of TBI.

Extended observation of reduced methamphetamine use with combined naltrexone plus bupropion in the ADAPT-2 trial.

A 12-week placebo-controlled, sequential parallel Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT-2) trial evaluated the effects of extended-release injectable naltrexone plus extended-release oral bupropion (NTX + BUPN) on methamphetamine (MA) use over two stages. This study reports on the previously unpublished stage 2 MA use in participants randomized at stage 1 to receive NTX + BUPN through both stages compared with those assigned to placebo. This is a secondary analysis of the US National Institute on Drug Abuse (NIDA) ADAPT-2 network trial. The parent ADAPT-2 trial was carried out across multiple NIDA Clinical Trials Network (CTN) sites in the United States. This analysis includes 403 people with MA use disorder who participated in the ADAPT-2 CTN trial. NTX + BUPN was compared with placebo over the course of the trial. MA use was measured by urine drug screens conducted twice weekly for 12 weeks, then once in week 13 and once in week 16 post-treatment follow-up. Participants on NTX + BUPN in stage 1 showed an additional 9.2% increase [95% confidence interval (CI),0.09%-17.9%, P = 0.038]during stage 2 in their probability of testing negative for MA, with a total increase of 27.1% (95% CI, 13.2%-41.1%, P < 0.001) over the full 12 weeks of treatment. In contrast, participants on placebo in both stages increased in probability of testing MA-negative by a total of 11.4% (95% CI, 4.1%-18.6%, P = 0.002) over all 12 weeks. The 12-week increase among participants on NTX + BUPN was significantly greater-by 15.8% (95% CI, 4.5%-27.0%, P = 0.006)-than the increase among those on placebo. For people with methamphetamine (MA) use disorder receiving treatment with extended-release injectable naltrexone plus extended-release oral bupropion (NTX + BUPN), continued treatment with NTX + BUPN after 6weeks is associated with additional reductions in MA use up to 12 weeks.

Machine Learning-Driven Analysis of Individualized Treatment Effects Comparing Buprenorphine and Naltrexone in Opioid Use Disorder Relapse Prevention.

A trial comparing extended-release naltrexone and sublingual buprenorphine-naloxone demonstrated higher relapse rates in individuals randomized to extended-release naltrexone. The effectiveness of treatment might vary based on patient characteristics. We hypothesized that causal machine learning would identify individualized treatment effects for each medication. This is a secondary analysis of a multicenter randomized trial that compared the effectiveness of extended-release naltrexone versus buprenorphine-naloxone for preventing relapse of opioid misuse. Three machine learning models were derived using all trial participants with 50% randomly selected for training (n = 285) and the remaining 50% for validation. Individualized treatment effect was measured by the Qini value and c-for-benefit, with the absence of relapse denoting treatment success. Patients were grouped into quartiles by predicted individualized treatment effect to examine differences in characteristics and the observed treatment effects. The best-performing model had a Qini value of 4.45 (95% confidence interval, 1.02-7.83) and a c-for-benefit of 0.63 (95% confidence interval, 0.53-0.68). The quartile most likely to benefit from buprenorphine-naloxone had a 35% absolute benefit from this treatment, and at study entry, they had a high median opioid withdrawal score ( P < 0.001), used cocaine on more days over the prior 30 days than other quartiles ( P < 0.001), and had highest proportions with alcohol and cocaine use disorder ( P ≤ 0.02). Quartile 4 individuals were predicted to be most likely to benefit from extended-release naltrexone, with the greatest proportion having heroin drug preference ( P = 0.02) and all experiencing homelessness ( P < 0.001). Causal machine learning identified differing individualized treatment effects between medications based on characteristics associated with preventing relapse.

Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial.

There have been no well-controlled and well-powered comparative trials of topiramate with other pharmacotherapies for alcohol use disorder (AUD), such as naltrexone. Moreover, the literature is mixed on the effects of two polymorphisms-rs2832407 (in GRIK1) and rs1799971 (in OPRM1)-on response to topiramate and naltrexone, respectively. The authors sought to examine the comparative effectiveness of topiramate and naltrexone in improving outcomes in AUD and to examine the role of the rs2832407 and rs1799971 polymorphisms, respectively, on response to these medications. In a 12-week, double-blind, placebo-controlled, randomized, multisite, genotype-stratified (rs2832407 and rs1799971) clinical trial comparing topiramate and naltrexone in treating AUD, 147 patients with AUD were randomly assigned to treatment with topiramate or naltrexone, stratified by genotype (rs2832407*CC and *AC/AA genotypes and rs1799971*AA and *AG/GG genotypes). The predefined primary outcome was number of heavy drinking days per week. Predefined secondary outcomes included standard drinks per drinking day per week, body mass index (BMI), craving, markers of liver injury, mood, and adverse events. For the number of heavy drinking days per week, there was a near-significant time-by-treatment interaction. For the number of standard drinks per drinking day per week, there was a significant time-by-treatment interaction, which favored topiramate. There were significant time-by-treatment effects, with greater reductions observed with topiramate than naltrexone for BMI, craving, and gamma-glutamyltransferase level. Withdrawal due to side effects occurred in 8% and 5% of the topiramate and naltrexone groups, respectively. Neither polymorphism showed an effect on treatment response. Topiramate is at least as effective and safe as the first-line medication, naltrexone, in reducing heavy alcohol consumption, and superior in reducing some clinical outcomes. Neither rs2832407 nor rs1799971 had effects on topiramate and naltrexone treatments, respectively.

Activation of epidermal growth factor receptors in triple-negative breast cancer cells by morphine; analysis through Raman spectroscopy and machine learning

Triple negative breast cancer (TNBC) is a very aggressive form of breast cancer, and the analgesic drug morphine has been shown to promote the proliferation of TNBC cells. This article investigates whether morphine causes activation of epidermal growth factor receptors (EGFR), the roles of μ-opioid and EGFR receptors on TNBC cell proliferation and migration. While examining the changes with molecular techniques, we also aimed to investigate the analysis ability of Raman spectroscopy and machine learning-based approach. Effects of morphine on the proliferation and migration of MDA.MB.231 cells were evaluated by MTT and scratch wound-healing tests, respectively. Morphine-induced phosphorylation of the EGFR was analyzed by western blotting in the presence and absence of μ-receptor antagonist naltrexone and the EGFR-tyrosine kinase inhibitor gefitinib. Morphine-induced EGFR phosphorylation and cell migration were significantly inhibited by pretreatments with both naltrexone and gefitinib; however, morphine-increased cell proliferation was inhibited only by naltrexone. While morphine-induced changes were observed in the Raman scatterings of the cells, the inhibitory effect of naltrexone was analyzed with similarity to the control group. Principal component analysis (PCA) of the Raman confirmed the epidermal growth factor (EGF)-like effect of morphine and was inhibited by naltrexone and partly by gefitinib pretreatments. Our in vitro results suggest that combining morphine with an EGFR inhibitor or a peripherally acting opioidergic receptor antagonist may be a good strategy for pain relief without triggering cancer proliferation and migration in TNBC patients. In addition, our results demonstrated the feasibility of the Raman spectroscopy and machine learning-based approach as an effective method to investigate the effects of agents in cancer cells without the need for complex and time-consuming sample preparation. The support vector machine (SVM) with linear kernel automatically classified the effects of drugs on cancer cells with ∼95% accuracy.

Unraveling the neuroprotective mechanisms of naltrexone against aluminum-induced neurotoxicity

Aluminum (Al) is a known neurotoxic trace element linked to Alzheimer’s disease (AD). Naltrexone, an opioid antagonist, has shown promising effects in reducing neuroinflammation at lower doses than those prescribed for addiction. This study aimed to determine the neuroprotective effects of naltrexone on Al-induced neurotoxicity in an in vitro AD model. The SH-SY5Y cells were first cultivated in a standard growth medium. Subsequently, the cells were induced to differentiate by decreasing the concentration of fetal bovine serum and introducing retinoic acid (RA) into the culture media. Subsequently, the inclusion of brain-derived neurotrophic factor (BDNF) was implemented in conjunction with RA. The process of differentiation was concluded on the seventh day. Study groups (n = 3) were designed as the control group, naltrexone group, Al group, Al-Nal group, Alzheimer’ model (AD) group, Alzheimer model + Al-exposed group (AD-Al), Alzheimer model + Nal applied group (AD-Nal) and Alzheimer model + Al-exposed + Nal applied group (AD-Al-Nal). Hyperphosphorylated Tau protein as the specific marker of AD was measured in all groups. Glycogen synthase kinase-3 (GSK-3)β, Protein phosphatase 2A (PP2A), Akt and Wnt signaling pathways were analyzed comparatively. In addition, oxidative stress parameters (total antioxidant capacity, lipid peroxidase, protein carbonyl and reactive oxygen species) were measured comparatively in the study groups. The results showed that naltrexone reduced hyperphosphorylated tau protein levels by regulating GSK-3β, PP2A, Akt and Wnt signaling. Also, exposure to naltrexone decreased oxidative stress parameters. Based on these results, naltrexone shows promise as a potential therapy for AD, subject to additional clinical assessments.

The association between attitudes and the provision of medications for opioid use disorder (MOUD) in United States jails

BackgroundOpioid use disorder is prevalent among individuals who are incarcerated, yet medications for opioid use disorder (MOUD) are not widely available in United States jails and prisons. Negative staff attitudes across the criminal legal system may prevent MOUD from being provided. We sought to determine if staff attitudes are associated with the provision of MOUD in prisons or jails. Methods227 staff members of 43 jails and partnering community-based treatment providers answered questions on the effectiveness and acceptability of methadone, buprenorphine, and naltrexone. Response patterns were summarized with principal component analysis. Mixed-effects regression was performed to determine if attitudes toward MOUD were associated with the number of individuals screened and diagnosed with an OUD, referred to treatment, provided MOUD and referred to treatment after release. ResultsSites whose staff had negative attitudes towards methadone and positive attitudes towards naltrexone were associated with fewer people being screened (Mean ratio [MR] = 0.84, 95 % CI: [0.72, 0.97]), diagnosed (MR = 0.85, 95 % CI: [0.73, 0.99]), referred (MR = 0.76, 95 % CI: [0.65, 0.89]), provided MOUD (MR = 0.70, 95 % CI: [0.58, 0.84]), and referred after release (MR = 0.82, 95 % CI: [0.72, 0.94]). Sites with overall positive attitudes towards all MOUD were associated with more people being screened (MR = 1.16, 95 % CI: [1.01, 1.34]), diagnosed (MR = 1.37, 95 % CI: [1.18, 1.60]), and referred to treatment (MR = 1.41, 95 % CI: [1.20, 1.65]). ConclusionsAttitudinal barriers exist in the criminal legal system and are associated with the provision of MOUD.

Effects of naltrexone on amphetamine choice in rhesus monkeys and rats.

Clinical amphetamine use is constrained by high abuse potential, and amphetamine use disorder is a persistent clinical problem with no approved medications for its treatment. The opioid antagonist naltrexone has been reported to reduce some abuse-related effects of amphetamine. This study used an amphetamine-versus-food choice procedure in rhesus monkeys and rats to test the hypothesis that naltrexone might serve as either (a) a maintenance medication for amphetamine use disorder treatment or (b) an "abuse-deterrent" adjunct to clinical amphetamine formulations. Male rhesus monkeys and male and female rats were trained to choose between increasing unit doses of intravenous amphetamine and an alternative food reinforcer during daily behavioral sessions. Experiment 1 evaluated effectiveness of continuous naltrexone maintenance to reduce amphetamine-versus-food choice in both monkeys and rats. Experiment 2 combined naltrexone with amphetamine in fixed-proportion amphetamine + naltrexone mixtures to evaluate the effectiveness of naltrexone in both species to reduce mixture choice relative to amphetamine-alone choice. Amphetamine maintained a dose-dependent increase in amphetamine choice in both monkeys and rats. Naltrexone maintenance did not significantly decrease amphetamine choice in either species. Addition of naltrexone to amphetamine reduced amphetamine choices per session in monkeys, but behavior was not reallocated to food choice, and in rats, the addition of naltrexone only decreased food choice without significantly affecting amphetamine choice. These results argue against the use of naltrexone as either (a) a maintenance medication for treatment of amphetamine use disorder or (b) an "abuse-deterrent" adjunct to amphetamine for clinical applications. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Extinction and reinstatement of methamphetamine-induced conditioned place preference in zebrafish.

Conditioned place preference (CPP) paradigm in zebrafish has been used to measure drug reward, but there is limited research on CPP reinstatement to determine relapse vulnerability. The present study aimed to investigate extinction and reinstatement of methamphetamine (MA)-induced CPP in zebrafish and evaluate the model's predictive validity. Zebrafish received different doses of MA (0-60 mg/kg) during CPP training. The preferred dose of MA at 40 mg/kg was used for extinction via either confined or nonconfined procedures. The extinguished CPP was reinstated by administering a priming dose of MA (20 mg/kg) or various stressors. To assess persistent susceptibility to reinstatement, MA CPP and reinstatement were retested following 14 days of abstinence. In addition, the effects of SCH23390, naltrexone, and clonidine on MA CPP during acquisition, expression, or reinstatement phases were monitored. MA induced CPP in a dose-dependent manner. Both nonconfined and confined extinction procedures time-dependently reduced the time spent on the MA-paired side. A priming dose of MA, chasing stress, or yohimbine reinstated the extinguished CPP. After 14 days of abstinence, the MA CPP remained extinguished and was significantly reinstated by MA priming or chasing stress. Similar to the observations in rodents, SCH23390 suppressed the acquisition of MA CPP, naltrexone reduced the expression and MA priming-induced reinstatement, while clonidine prevented stress-induced reinstatement of MA CPP. This work expanded the zebrafish CPP paradigm to include extinction and reinstatement phases, demonstrating predictive validity and highlighting its potential as a valuable tool for exploring drug relapse.

In Case You Haven't Heard…

These days, people are trying weight‐loss drugs — some originally indicated for diabetes only — even if they don't need to lose weight, but want to lose weight. They are aware of all the possible side effects (nausea, loss of appetite, diarrhea, constipation etc.) but they still want to lose weight. Now, Ozempic is being looked at for the possible effect of reducing drinking; alcohol is high in calories, after all, and there's not much in it that's actually good for you (unlike food, which you need to survive). Now, people have found that when they take the drug to eat less and lose weight, they also lose their taste for alcohol, or at least for drinking a lot of it. Ozempic is a diabetes drug; Wegovy is a weight‐loss drug, but both contain the same active ingredient — semaglutide — which makes people feel satisfied after eating. Questions such as whetherthese drugs reduce the capacity for pleasure, a side effect of naltrexone for some patients, do not appear to be an issue. They do, however, reduce the capacity to enjoy eating, as they are intended to do.

The Effects of Chronic Naltrexone on Reinstatement of Opioid-Induced Drug-Seeking Behavior and Antinociception.

Opioid addiction is a chronic relapsing disorder in which drug-seeking behavior during abstinence can be provoked by exposure to a µ-opioid receptor (MOR) agonist or opioid-associated cues. Opioid self-administration behavior in laboratory subjects can be reinstated by priming with MOR agonists or agonist-related stimuli, providing a procedure suitable for relapse-related studies. The opioid antagonist naltrexone has been forwarded as a medication that can forestall relapse and, in an extended-release formulation, has demonstrated some treatment success. However, chronic naltrexone treatment has not been extensively investigated in nonhuman subjects and aspects of its pharmacology remain uncertain. For example, the relative effectiveness of naltrexone in reducing the priming strength of opioid agonists differing in efficacy is not well understood. Here, using intravenous self-administration and warm-water tail withdrawal procedures, we investigated changes in the direct reinforcing effects of oxycodone and in the priming strength and antinociceptive effects of opioid agonists in squirrel monkeys (n = 4) during chronic treatment with naltrexone (0.2 mg/kg/d). Results show that naltrexone produced: 1) a 10-fold rightward shift in the dose-response function for the reinforcing effects of oxycodone, and 2) in reinstatement and antinociception experiments, comparable rightward shifts in the dose-response functions for higher-efficacy MOR agonists (methadone, heroin, and oxycodone) but rightward and downward shifts in the dose-response functions for lower-efficacy MOR agonists (buprenorphine, nalbuphine, and butorphanol). These results suggest that, although chronic naltrexone should be effective in forestalling relapse following exposure to lower- and higher-efficacy agonists, the inability of lower-efficacy agonists to surmount naltrexone antagonism may complicate the prescription of opioids for pain. SIGNIFICANCE STATEMENT: Although naltrexone is commonly used in the treatment of opioid use disorder, its ability to reduce the priming strength of opioid agonists has not been extensively investigated. This study shows that chronic naltrexone treatment induces rightward shifts in the reinstatement and antinociceptive properties of higher efficacy opioid agonists, but rightward and downward shifts for lower efficacy opioid agonists, suggesting lower efficacy agonists may not be able to surmount naltrexone-induced antagonism of these two effects, and perhaps naltrexone offers greater protection against lower efficacy agonists.

Daily Naltrexone Use Does Not Adversely Affect Physical, Cognitive or Marksmanship Performance inU.S. Army Soldiers.

Considering the potential of weaponized opioids, evaluating how prophylactic countermeasures affect military-relevant performance is necessary. Naltrexone is a commercially available Food and Drug Administration-approved medication that blocks the effects of opioids with minimal side effects. However, the effects of naltrexone on the health and performance of non-substance abusing military personnel are not well described in the existing literature. Active duty U.S. Army Soldiers (n = 16, mean ± SD, age: 23.1 ± 5.3 y) completed a series of physical, cognitive, and marksmanship tasks during a 4-day pretrial, a 7-day active trial, and a 4-day post-trial phase. During the active trial, participants were administered 50 mg of oral naltrexone daily. Physiological and biological processes were monitored with a daily review of systems, sleep monitoring, biochemistry, and hematology blood panels. Naltrexone did not negatively affect physical performance, cognitive functioning, marksmanship, or sleep duration (P > 0.05). Improvements were observed during the active trial compared to the pretrial phase in cognitive tasks measuring logical relations (P = 0.05), matching to sample (P = 0.04), math speed (P < 0.01), math percent correct (P = 0.04), and spatial processing (P < 0.01). Results from biochemistry and hematology blood panels remained within clinically normative ranges throughout all phases of the study. No participants were medically withdrawn; however, one participant voluntarily withdrew due to nausea and reduced appetite. Temporary (7-day) daily use of naltrexone was safe and did not negatively affect physical performance, cognitive functioning, marksmanship ability, or sleep in a healthy cohort of U.S. Army Soldiers.