Return to use, or relapse, is a major challenge in the treatment of opioid use disorder (OUD). Relapse can be precipitated by several factors, including exposure to drug-conditioned cues. Identifying successful treatments to mitigate cue-induced relapse has been challenging, perhaps due to extinction memory recall (EMR) deficits. Previously, inhibition of estradiol (E2) signaling in the basolateral amygdala (BLA) impaired heroin-cue EMR. This effect was recapitulated by antagonism of BLA estrogen receptors (ER) in a sex-specific manner such that blocking ERα in males, but ERβ in females, impaired EMR. However, it is unclear whether increased E2 signaling, in the BLA or systemically, enhances heroin-cue EMR. We hypothesized that ERβ agonism would enhance heroin-cue EMR in a sex- and region-specific manner. To determine the capacity of E2 signaling to improve EMR, we pharmacologically manipulated ERβ across several translationally designed experiments. First, male and female rats acquired heroin or sucrose self-administration. Next, during a cued extinction session, we administered diarylpropionitrile (DPN, an ERβ agonist) and tested anxiety-like behavior on an open field. Subsequently, we assessed EMR in a cue-induced reinstatement test and, finally, measured ERβ expression in several brain regions. Across all experiments, females took more heroin and sucrose than males and had greater responses during heroin-cued extinction. Administration of DPN in the BLA enhanced EMR in females only, driven by ERβ\'s impacts on memory consolidation. Interestingly, however, systemic DPN administration improved EMR for heroin cues in both sexes across several different tests, but did not impact sucrose-cue EMR. Immunohistochemical analysis of ERβ expression across several different brain regions showed that females only had greater expression of ERβ in the basal nucleus of the BLA. Here, in several preclinical experiments, we demonstrated that ERβ agonism enhances heroin-cue EMR and has potential utility in combatting cue-induced relapse.

Xylazine has been increasingly detected in illegally manufactured fentanyl (IMF) products and overdose deaths in the United States; most xylazine-involved overdose deaths involve IMF. A convenience sample of U.S. adults aged ≥18 years was identified from those evaluated for substance use treatment during July 2022-September 2023. Data were collected using the Addiction Severity Index-Multimedia Version clinical assessment tool. Among 43,947 adults, 6,415 (14.6%) reported IMF or heroin as their primary lifetime substance-use problem; 5,344 (12.2%) reported recent (i.e., past-30-day) IMF or heroin use. Among adults reporting IMF or heroin as their primary lifetime substance-use problem, 817 (12.7%) reported ever using xylazine. Among adults reporting recent IMF or heroin use, 443 (8.3%) reported recent xylazine use. Among adults reporting IMF or heroin use recently or as their primary lifetime substance-use problem, those reporting xylazine use reported a median of two past nonfatal overdoses from any drug compared with a median of one overdose among those who did not report xylazine use; as well, higher percentages of persons who reported xylazine use reported other recent substance use and polysubstance use. Provision of nonjudgmental care and services, including naloxone, wound care, and linkage to and retention of persons in effective substance use treatment, might reduce harms including overdose among persons reporting xylazine use.

The nucleus accumbens (NAc) and the anterior limb of internal capsule (ALIC) are effective targets for treating addiction using deep brain stimulation (DBS). However, there have been no reports on the electrophysiological characteristics of addiction nuclei at the single-cell level in humans. This study aimed to investigate the electrical activity characteristics of neurons in the NAc and ALIC using microelectrode recording (MER) during DBS surgery in patients with addiction, and six patients with addiction were included (five with heroin addiction and one with alcohol addiction). The microelectrode recording trajectories were reconstructed and recording sites at different depths were determined by merging the pre- and post-operative images in the FrameLink system. The results showed that among the 256 neurons, 204 (80 %) were burst neurons. NAc neurons accounted for the majority (57 %), and the mean firing rate (MFR) was the highest (1.94 Hz). ALIC neurons accounted for the least (14 %), and MFR was the lowest (0.44 Hz). MFR increased after entering the NAc and decreased after entering the ALIC. In the patients with addiction treated using DBS, the single-cell level electrophysiological characteristics of the different nuclei were found to be distinct along the surgical trajectory.

BACKGROUND: The World Health Organization has identified methadone maintenance therapy (MMT) as the most effective treatment for reducing patient dependence on heroin. In Taiwan, MMT has been used as a heroin harm reduction strategy since 2006. Although the effectiveness of MMT in reducing heroin addiction has been examined quantitatively in prison samples, little attention has been paid to the experiences and perspectives of patients with heroin addiction receiving MMT. This study was designed to address this gap in scientific knowledge.
OBJECTIVE: The aim of this study was to investigate the experiences of individuals struggling with heroin addiction who are receiving MMT in the community.
METHODS: A qualitative descriptive research approach and semistructured interviews were used in this study. We interviewed 14 participants who had received MMT in a medical center in central Taiwan. All of the interview data were recorded, transcribed, and analyzed using qualitative content analysis.
RESULTS: Four themes emerged: (a) a chance to change one\'s life, (b) the helpfulness of MMT, (c) a sense of being restricted and controlled, and (d) need for support.
CONCLUSIONS: This article fills a gap in current scholarly understanding of patient experiences and their perspectives on the helpfulness of MMT. Understanding patient experiences and perspectives is critical to informing and developing concrete strategies for clinical practice and MMT policy. Clinical professionals should assess patient needs and concerns to determine whether they are met by current treatment programs. Policymakers should design more flexible policies to facilitate easier access by patients to methadone to reduce the risk of relapse.

Drug dependence is a chronic brain disease characterized by craving and recurrent episodes of relapse. Tramadol HCl is a promising agent for withdrawal symptoms management, considering its relatively low abuse potential and safety. Oral administration, however, is not preferred in abstinence maintenance programs. Introducing an implantable, long-lasting formula is suggested to help outpatient abstinence programs achieve higher rates of treatment continuation. Tramadol implants (T350 and T650) were prepared on polycaprolactone polymer ribbons by the wet method. Male Wistar rats were adapted to heroin-conditioned place preference (CPP) at escalating doses (3-30 mg/kg, intraperitoneally, for 14 days). Implants were surgically implanted in the back skin of rats. After 14 days, the CPP score was recorded. Naloxone (1 mg/kg, intraperitoneally) was used to induce withdrawal on day 15, and symptoms were scored. Elevated plus maze and open field tests were performed for anxiety-related symptoms. Striata were analyzed for neurochemical changes reflected in dopamine, 3,4-dihydroxyphenyl acetic acid, gamma-aminobutyric acid, and serotonin levels. Brain oxidative changes including glutathione and lipid peroxides were assessed. The tramadol implants (T350 and T650) reduced heroin CPP and limited naloxone-induced withdrawal symptoms. The striata showed increased levels of 3,4-dihydroxyphenyl acetic acid, and serotonin and decreased levels of gamma-aminobutyric acid and dopamine after heroin withdrawal induction, which were reversed after implanting T350 and T650. Implants restore the brain oxidative state. Nonsignificant low naloxone-induced withdrawal score after the implant was used in naive subjects indicating low abuse potential of the implants. The presented tramadol implants were effective at diminishing heroin CPP and withdrawal in rats, suggesting further investigations for application in the management of opioid withdrawal.

This study aims to investigate the effect of detoxification on acoustic features of Mandarin speech. Speech recordings were collected from 66 male abstinent heroin users with different durations of drug detoxification, specifically early abstinent users with a detoxification duration of less than 2 years, sustained abstinent users with 2 years of detoxification, and long-term abstinent users with a detoxification duration of more than 2 years. The results of the acoustic analyses showed that early abstinent users exhibited lower loudness, relative energies of F1, F2, and F3, higher H1-A3, and fewer loudness peaks per second, as well as a longer average duration of unvoiced segments, compared to the sustained and long-term abstinent users. The findings suggest that detoxification may lead to a rehabilitation process in the speech production of abstinent heroin users (e.g., less vocal hoarseness). This study not only provides valuable insights into the effect of detoxification on speech production but also provides a theoretical basis for the speech rehabilitation and detoxification treatment of heroin users.

Opioid use disorder is a major public health crisis that is manifested by persistent drug-seeking behavior and high relapse frequency. Most of the available treatments rely on targeting opioid receptors using small molecules that do not provide sustained symptom alleviation. Psychoplastogens are a novel class of non-opioid drugs that produce rapid and sustained effects on neuronal plasticity, intended to produce therapeutic benefits. Ibogalogs are synthetic derivatives of iboga alkaloids that lack hallucinogenic or adverse side effects. In the current study, we examine the therapeutic potential of DM506, a novel ibogalog lacking any cardiotoxic or hallucinogenic effects, in cue-induced seeking behavior following heroin self-administration. At a single systemic dose of 40 mg/kg, DM506 significantly decreased cue-induced seeking in both male and female rats at abstinence day 1 (AD1) following heroin self-administration. Upon re-testing for cue-induced seeking at AD14, we found that males receiving DM506 continued to show decreased cue-induced seeking, an effect not observed in females. Since there is evidence of psychedelics influencing tonic GABA currents, and opioid and psychoplastogen-mediated neuroadaptations in the medial prefrontal cortex (PrL) underlying its functional effects, we performed patch-clamp recordings on PrL slices of drug-naïve rats with an acute application or chronic incubation with DM506. Tonic GABA current was decreased in slices incubated with DM506 for 2 h. qPCR analysis did not reveal any differences in the mRNA levels of GABAA receptor α and δ subunits at AD14 in heroin and saline self-administered animals that received vehicle or DM506 at AD1. Overall, our data indicate that DM506 attenuates cue-induced heroin seeking and inhibits tonic GABA current in the prelimbic cortex.

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. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

OBJECTIVE: To determine if patients presenting to our toxicology unit following self-reported heroin use had positive urine immunoassay testing for fentanyl or its analogues.
METHODS: Urine samples from consenting patients were tested at the bedside for the presence of opiates or fentanyl and its analogues.
RESULTS: Over a 30-month period, 58 patients were recruited. All samples tested positive for opiates, but none tested positive for fentanyl or its analogues.
CONCLUSIONS: In patients presenting to our toxicology unit in Brisbane, we did not find any cases where the urine of patients self-reporting heroin exposure tested positive for fentanyl or its analogues.

Prior studies have shown that individuals and their peers often have similar substance use behaviors, but the mechanisms driving these similarities - particularly in rural settings, are not well understood. The primary objectives of this analysis are to (1) identify factors that contribute to relationship turnover and maintenance within a rural network of persons who use drugs (PWUD), (2) determine whether assimilation and/or homophily shape participants use of injection drugs, heroin, and stimulants (methamphetamine and cocaine), and (3) assess the extent that these mechanisms influence networks ties and/or behaviors and whether these effects vary across time.
Sociometric network data were collected from a cohort of PWUD in rural Eastern Kentucky at baseline (2008-2010) and at four follow-up visits conducted approximately semiannually. Stochastic actor-oriented models (SAOMS) were used to model network structure and participant behaviors as jointly dependent variables and to identify characteristics associated with the maintenance, dissolution, and formation of network ties and changes in drug use behaviors.
Findings suggest (1) greater network stability over time for reciprocal and transitive relationships, (2) both homophily and assimilation played a greater role in shaping injection drug use (IDU) initiation and cessation than they did in shaping heroin and stimulant use, and (3) the importance of these mechanisms appeared consistent over time.
Given the stability of particular network structures and evidence of both homophily and assimilation with respect to drug-use behaviors, interventions that leverage social networks could be used to motivate health-promoting behaviors.