Search Results (59)

Background: Heroin addiction is associated with profound dysregulation of the endogenous opioid and stress response systems, yet current diagnostic frameworks may inadequately capture the traumatising aspects of this condition. This perspective proposes the concept of post-heroin post-traumatic stress spectrum (pH-PTSD/S) as a clinical syndrome emerging from chronic opioid-induced neurobiological and psychosocial dysregulation, even in the absence of Criterion A trauma. Methods: The authors review evidence from neuroendocrinology, behavioural neuroscience, and clinical psychopathology to support a sensitisation-based model of trauma vulnerability in heroin use disorder (HUD). Results: Findings suggest that HUD patients frequently exhibit PTSD-spectrum symptoms, including hyperarousal, avoidance, emotional dysregulation, and altered stress reactivity. Opioid agonist treatment (OAT) may mitigate these symptoms by stabilising HPA axis function and reducing exposure to trauma-related contexts. The pH-PTSD/S construct, measured through a dedicated instrument, identifies patients with subthreshold trauma-related symptoms and greater psychopathological burden. Conclusions: Heroin dependence may constitute a traumatising condition, requiring dimensional diagnostic tools and trauma-informed treatment strategies. Further research is needed to validate the nosological status of pH-PTSD/S, clarify its distinction from protracted withdrawal or complex PTSD, and determine its implications for OAT duration and integrated care pathways. Full article

Opioid-use disorder (OUD) poses a growing global health crisis, with chronic opioid exposure linked not only to addiction but also to enduring neurological impairments. While traditional research has focused primarily on neuronal alterations, emerging evidence underscores the pivotal role of astrocytes, abundant glial cells in the central nervous system, and their secreted extracellular vesicles (EVs) in opioid-mediated neuropathology. This review delineates the mechanistic roles of astrocytes and astrocyte-derived EVs (ADEVs) across a spectrum of opioids, including morphine, heroin, fentanyl, codeine, tramadol, buprenorphine, and methadone. Opioids disrupt astrocytic homeostasis by impairing glutamate regulation, altering the redox balance, and activating pro-inflammatory signaling pathways. In response, astrocytes release EVs enriched with neurotoxic cargo, including amyloidogenic proteins, cytokines, microRNAs, and long non-coding RNAs, that propagate neuroinflammation, compromise blood–brain barrier (BBB) integrity, and exacerbate synaptic dysfunction. Preclinical models and in vitro studies reveal drug-specific astrocytic responses and ADEV profiles, implicating these vesicles in modulating microglial function, neuroimmune signaling, and neuronal viability. Notably, morphine-induced ADEVs promote amyloidosis and inflammatory signaling, while heroin and fentanyl affect glutamatergic and inflammasome pathways. Even opioids used in therapy, such as buprenorphine and methadone, alter astrocyte morphology and EV cargo, particularly during neurodevelopment. Collectively, these findings advance a neuro-glial paradigm for understanding opioid-induced brain injury and highlight ADEVs as both biomarkers and mediators of neuropathology. Targeting astrocyte-EV signaling pathways represents a promising therapeutic avenue to mitigate long-term neurological consequences of opioid exposure and improve outcomes in OUD. Full article

Background/Objectives: Opioid use disorder (OUD) remains a severe health problem globally, resulting in substantial social and economic challenges. While existing medications for managing OUD are proven to be effective, they also present certain challenges. A vaccine offers a promising therapeutic strategy to combat OUD and potentially reduce the risk of overdose death. The TT-6-AmHap heroin conjugate vaccine has effectively reduced heroin-induced pharmacological effects in behavioral assays as well as demonstrated the induction of high titer and high affinity antibody responses in mice and rats. In this GLP study conducted in rabbits, the potential local and systemic toxicity of the TT-6-AmHap heroin vaccine in combination with or without adjuvants ALF43 and Alhydrogel^® (ALFA) was investigated. Methods: Male and female New Zealand White rabbits were administered with vaccines or a saline control intramuscularly at two-week intervals over a 57-day study period. The presence, persistence or reversibility of any toxic effects of the vaccine was determined over a four-week recovery period. Results: Administration of TT-6-AmHap with or without the adjuvants induced high antibody-specific IgG in treatment groups compared to the controls. The study found no TT-6-AmHap-related effects on mortality, physical examinations, dermal Draize observations, body weights, body weight changes, food consumption, ophthalmology, clinical pathology (hematology, coagulation, clinical chemistry, and urinalysis), macroscopic pathology, or organ weights. Conclusions: Under the conditions of this study, these results demonstrate that the TT-6-AmHap vaccine with or without adjuvants was well tolerated, immunogenic, and the effects were not considered adverse in both male and female rabbits. Full article

Background/Objectives: In 2022, 2.2 million adolescents were diagnosed with substance use disorders, including 265,000 with opioid use disorder. The National Survey on Drug Use and Health revealed that 130,000 adolescents misused prescription pain medications, often obtaining them from friends or relatives. This age group perceives weekly heroin use as less risky than those younger or older. Methods: A questionnaire was developed for 7th to 12th graders in a rural Texas school district as part of a fentanyl awareness curriculum. The questionnaire included Likert scale, multiple choice, and yes/no questions. The participants were categorized into younger (grades 7th and 8th) and older students (grades 9th through 12th), and associations were explored between demographic characteristics, responses, and grade groups using chi-square tests. To assess confidence, behavior, and the impact of education, we used chi-square and Fisher’s exact tests. Results: The participants (n = 94; 85.11%) identified as Hispanic or Latino, with a smaller percentage identifying as White or more than one race. An association was found between feeling more in control of actions related to substances and fentanyl (p-value = 0.04) after receiving education. No association was found between education and confidence in identifying fentanyl. Conclusions: This study aligns with a surge in fentanyl-related overdose deaths in a high-intensity drug trafficking region. Recent fentanyl overdoses among school-age children prompted legislative changes in 2023, making this study valuable for understanding the epidemic within the geographical context. These results suggest that school-based education may play a role in strengthening adolescents’ behavioral intentions to fentanyl exposure, though additional efforts are needed to improve risk identification. Full article

Background: Alcohol use disorder in the context of heroin addiction presents a significant challenge for clinicians, particularly in selecting the most appropriate pharmacological treatment. Methods: The present study aimed to retrospectively evaluate the efficacy of a six-month methadone maintenance (MM)/sodium oxybate (SMO) combination treatment in reducing ethanol intake among chronic alcohol-dependent patients with heroin use disorder (HUD). Specifically, we compared outcomes between those who continued SMO treatment after alcohol detoxification (MM/SMO-Maintained) and those who discontinued it (MM/SMO-Detoxified). Data were recruited using the ‘Pisa Addiction Database’ through a retrospective, naturalistic, cross-sectional comparative design involving a single patient assessment. Results: Our results indicate that treatment retention was higher in the MM/SMO-Maintained group. Conversely, discontinuing SMO treatment after alcohol detoxification was associated with a higher likelihood of dropout. At the endpoint, the MM/SMO-Maintained group showed significant improvement and was considered less severely ill. Conclusions: Long-term SMO treatment has proven to be well tolerated and effective in preventing relapse in individuals with both alcohol and HUD undergoing agonist opioid treatment. SMO may be considered the closest pharmacological option to substitution therapy for alcohol use disorder, and ongoing agonist opioid treatment should not preclude its co-administration. Full article

Background: Understanding immune response is essential for preparing for public health crises. COVID-19 vaccination provides robust immunity against SARS-CoV-2, but immunocompromised populations may have weaker immune responses. We assessed SARS-CoV-2 spike (trimer) total IgG/IgM/IgA (total Ig) to investigate immune response to COVID-19 vaccination in people living with HIV (PLWH), considering CD4⁺ T cell count, viral load, substance use, and comorbidities. Methods: This cross-sectional study was conducted in Miami, Florida, between May 2021 and December 2021 as part of the NIH Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) initiative (3U01DA040381-05S1) and the Miami Adult Studies on HIV (MASH) cohort (U01DA040381). Blood samples were collected and SARS-CoV-2 spike (trimer) total Ig was quantified. HIV serostatus, viral load, CD4⁺ T cell count, and COVID-19 vaccinations were abstracted from medical records. Substance use (tobacco, alcohol, and drug use [marijuana, cocaine, heroin, fentanyl, methamphetamine, amphetamine, hallucinogens, ecstasy, or misuse of prescription drugs]), and comorbidities (hypertension, diabetes, autoimmune disease, obesity, chronic kidney disease, and substance use disorders) were assessed via validated questionnaires. Drug use was confirmed via urine toxicology. Multivariable linear regression was conducted. Results: Median age (n = 1317) was 57.8 years, 49.8% were male, 50% were Black non-Hispanic, 66.2% had received ≥1 dose of a COVID-19 vaccine, and 29.6% were PLWH (71.3% virally suppressed and median CD4⁺ T cell count > 500 cells/µL). PLWH, compared to people without HIV, were more likely to have received ≥1 dose of a COVID-19 vaccine (76.2% vs. 62.0%, p < 0.001) and present with substance use (77.2% vs. 42.9%, p < 0.001) and comorbidities (72.8% vs. 48.2%, p < 0.001). Vaccinated PLWH, compared to unvaccinated PLWH, had higher CD4⁺ T cell counts (577.5 vs. 517.5, p = 0.011) and were more likely to be virally suppressed (76.4% vs. 54.8%, p < 0.001). A lower CD4⁺ T cell count (<200 vs. ≥500, β = −0.400, p = 0.033) and higher HIV viral load (≥200–<5000 vs. <200, β = −0.275, p < 0.001) were associated with lower spike (trimer) total Ig titers, indicating a diminished response to COVID-19 vaccination. Conclusions: A lower CD4⁺ T cell count and higher HIV viremia were linked to reduced SARS-CoV-2 immunogenicity in racial/ethnic minority PLWH, a population underrepresented in vaccine clinical trials. HIV care providers should target efforts to maintain viral suppression to avoid diminished responses to COVID-19 vaccination. Full article

Background: An effective treatment for Opioid Use Disorder is Medication-Assisted Treatment (MAT). However, in the United States (US), this is still being underutilized by youth. Research indicates the need to develop strategies to reduce treatment barriers among these youth. Thus, we explored the rates of treatment completion and dropout among youth receiving MAT in US substance use treatment facilities and examined factors associated with treatment completion and dropout. Methods: This study used the 2019 Treatment Episode Data Set—Discharges. Our analysis was restricted to youth (12–24 years) who primarily used heroin at admission. Log-binomial regression was used to examine various determinants of treatment completion and dropout, guided by Andersen’s Behavioral Model. Results: The final sample size was 4917. Among youth reporting heroin use with receipt of MAT, those showing a higher likelihood of treatment completion than dropout were males [ARR: 1.23; 95% CI: 1.088–1.381; p = 0.0008], had 1–7 times [ARR: 1.33; 95% CI: 1.115–1.584; p = 0.0015] and 8–30 times self-help group participation [ARR: 1.50; 95% CI: 1.246–1.803; p < 0.0001], had co-occurring mental and substance use disorders [ARR: 1.28; 95% CI: 1.133–1.448, p < 0.0001], were admitted to detoxification [ARR: 2.80; 95% CI: 2.408–3.255; p < 0.0001] and residential/rehabilitation settings [ARR: 2.05; 95% CI: 1.749–2.400; p < 0.0001], and were located in the Midwest/West [ARR: 1.18; 95% CI: 1.030–1.358; p = 0.0173]. Conversely, other races (excluding Whites and Blacks/African Americans) [ARR: 0.75; 95% CI: 0.609–0.916; p = 0.0051], those who used MAT [ARR: 0.81; 95% CI: 0.694–0.946; p = 0.0077], and youth in the South [ARR: 0.45; 95% CI: 0.369–0.549; p < 0.0001] were less likely to report treatment completion than dropout. Conclusions: The majority of youth receiving MAT dropped out of treatment. We identified various factors that should be prioritized to address youth underutilization of MAT in the US. Full article

Buprenorphine and methadone are widely used as medication for addiction treatment (MAT) in patients with opioid use disorders. However, there is no compelling evidence of their impact on the immune–endocrine response. Therefore, the aim of this study was to examine the effects of the aforementioned medications on craving and on biomarkers of inflammation and cortisol, approaching the dose issue concurrently. Sixty-six patients (thirty-four under methadone and thirty-two under buprenorphine) who had just entered a MAT program and were stabilized with the suitable administered doses after a two-week process were divided into four groups based on medication dose (i.e., methadone high dose, buprenorphine high dose, methadone medium dose, and buprenorphine medium dose). The heroin craving questionnaire for craving assessment was completed, and the blood biomarkers were measured on Days 1 and 180. According to the results, high doses of both medications were accompanied by low levels of craving, cortisol, and inflammation on Day 1, and no alterations were observed on Day 180. On the contrary, medium doses reduced the tested psychosocial and biochemical parameters in terms of time, indicating a positive action for the patients. Concludingly, modifications in MAT doses are needed soon after the stabilization process to prevent inflammation and avoid relapse, thus helping opioid-addicted patients toward rehabilitation. Full article

Background: Treatment dropout in substance use disorder (SUD) programs poses a significant challenge to achieving successful outcomes and leads to legal and financial issues. Socioeconomic factors have been identified as key contributors to treatment attrition; yet, the specific impact of patients’ socioeconomic conditions remains underexplored. The purpose of this study is to examine the relationship between socioeconomic factors and SUD treatment dropout. Methods: We conducted a retrospective analysis of socioeconomic factors associated with treatment dropout among individuals with alcohol, marijuana, and heroin substance abuse. Logistic regression was used to examine the association between patients’ socioeconomic factors and treatment dropout. Adjusted odds ratios were calculated to quantify the strength of these associations. Results: Our findings demonstrate that demographic factors and financial status, including age (12–19 years), Black or African American race, and reliance on public assistance, correlate with an increased likelihood of treatment dropout. Black or African American patients receiving public assistance exhibit elevated dropout rates in ambulatory services, while patients of other single races without private insurance show higher dropout rates in detox services. Individuals aged 18–49 who are not part of the labor force have increased dropout rates in rehab services. Interestingly, patients in dependent living situations, who pay for services through private insurance or receive them at no charge, experience lower dropout rates as the number of arrests increases. Conversely, independently living patients with prior SUD treatments have higher dropout rates compared to those undergoing treatment for the first time. Conclusions: This study underscores the critical importance of addressing financial barriers to treatment access and retention in order to improve outcomes for individuals with substance use disorders (SUDs). Targeted interventions that support economically disadvantaged populations are essential for reducing treatment dropout rates and enhancing the effectiveness of SUD treatment programs. Full article

Fentanyl is a synthetic opioid widely used for its potent analgesic effects in chronic pain management and intraoperative anesthesia. However, its high potency, low cost, and accessibility have also made it a significant drug of abuse, contributing to the global opioid epidemic. This review aims to provide an in-depth analysis of fentanyl’s medical applications, pharmacokinetics, metabolism, and pharmacogenetics while examining its adverse effects and forensic implications. Special attention is given to its misuse, polydrug interactions, and the challenges in determining the cause of death in fentanyl-related fatalities. Fentanyl misuse has escalated dramatically, driven by its substitution for heroin and its availability through online platforms, including the dark web. Polydrug use, where fentanyl is combined with substances like xylazine, alcohol, benzodiazepines, or cocaine, exacerbates its toxicity and increases the risk of fatal outcomes. Fentanyl undergoes rapid distribution, metabolism by CYP3A4 into inactive metabolites, and renal excretion. Genetic polymorphisms in CYP3A4, OPRM1, and ABCB1 significantly influence individual responses to fentanyl, affecting its efficacy and potential for toxicity. Fentanyl’s side effects include respiratory depression, cardiac arrhythmias, gastrointestinal dysfunction, and neurocognitive impairments. Chronic misuse disrupts brain function, contributes to mental health disorders, and poses risks for younger and older populations alike. Fentanyl-related deaths require comprehensive forensic investigations, including judicial inspections, autopsies, and toxicological analyses. Additionally, the co-administration of xylazine presents distinct challenges for the scientific community. Histological and immunohistochemical studies are essential for understanding organ-specific damage, while pharmacogenetic testing can identify individual susceptibilities. The growing prevalence of fentanyl abuse highlights the need for robust forensic protocols, advanced research into its pharmacogenetic variability, and strategies to mitigate its misuse. International collaboration, public education, and harm reduction measures are critical for addressing the fentanyl crisis effectively. Full article

Background/Objectives: As long-term prescription opioid use is associated with increased morbidity and mortality, timely dose reduction of prescription opioids should be considered. However, most research has been conducted on patients using heroin. Given the differences between prescription and illicit opioid use, the aim of this review was to provide an overview of pharmacological strategies to reduce prescription opioid use or improve clinical outcomes for people who experience long-term prescription opioid use, including those with opioid use disorder. Methods: We conducted a systematic database search of PubMed, Embase, CINAHL, and the Cochrane Library. Outcomes included dose reduction, treatment dropout, pain, addiction, and outcomes relating to quality of life (depression, functioning, quality of life). Results: We identified thirteen studies (eight randomized controlled trials and five observational studies). Pharmacological strategies were categorized into two categories: (1) deprescribing (tapering) opioids or (2) opioid agonist treatment (OAT) with long-acting opioids. Tapering strategies decreased opioid dosage and had mixed effects on pain and addiction. OAT with buprenorphine or methadone led to improvements in pain relief and quality of life, with a slight (non-significant) preference for methadone in terms of treatment retention (RR = 1.10 [CI: 0.89–1.37]) but not for other outcomes. Most studies had high dropout rates and a serious risk of bias. Conclusions: Tapering reduced prescription opioid doses had mixed effects on pain. OAT improved clinical outcomes without dose reduction. Based on our review findings, there is no clear preference for either tapering or OAT. Tapering may be considered first as it reduces dependency, tolerance, and side effects, but is associated with adverse events and not always feasible. OAT can be a suitable alternative. Non-pharmacological interventions may facilitate tapering. Further research is needed to identify novel pharmacological strategies to facilitate opioid tapering. Registration: PROSPERO 2022 CRD42022323468. Full article

The United Nations World Drug Report published in 2022 alarmed that the global market of illicit drugs is steadily expanding in space and scale. Substances of abuse are usually perceived in the light of threats to human health and public security, while the environmental aspects of their use and subsequent emissions usually remain less explored. However, as with other human activities, drug production, trade, and consumption of drugs may leave their environmental mark. Therefore, this paper aims to review the occurrence of illicit drugs in surface waters and their bioaccumulation and toxicity in fish. Illicit drugs of different groups, i.e., psychostimulants (methamphetamines/amphetamines, cocaine, and its metabolite benzoylecgonine) and depressants (opioids: morphine, heroin, methadone, fentanyl), can reach the aquatic environment through wastewater discharge as they are often not entirely removed during wastewater treatment processes, resulting in their subsequent circulation in nanomolar concentrations, potentially affecting aquatic biota, including fish. Exposure to such xenobiotics can induce oxidative stress and dysfunction to mitochondrial and lysosomal function, distort locomotion activity by regulating the dopaminergic and glutamatergic systems, increase the predation risk, instigate neurological disorders, disbalance neurotransmission, and produce histopathological alterations in the brain and liver tissues, similar to those described in mammals. Hence, this drugs-related multidimensional harm to fish should be thoroughly investigated in line with environmental protection policies before it is too late. At the same time, selected fish species (e.g., Danio rerio, zebrafish) can be employed as models to study toxic and binge-like effects of psychoactive, illicit compounds. Full article

Addiction, particularly in relation to psychostimulants and opioids, persists as a global health crisis with profound social and economic ramifications. Traditional interventions, including medications and behavioral therapies, often encounter limited success due to the chronic and relapsing nature of addictive disorders. Consequently, there is significant interest in the development of innovative therapeutics to counteract the effects of abused substances. In recent years, vaccines have emerged as a novel and promising strategy to tackle addiction. Anti-drug vaccines are designed to stimulate the immune system to produce antibodies that bind to addictive compounds, such as nicotine, cocaine, morphine, methamphetamine, and heroin. These antibodies effectively neutralize the target molecules, preventing them from reaching the brain and eliciting their rewarding effects. By obstructing the rewarding sensations associated with substance use, vaccines aim to reduce cravings and the motivation to engage in drug use. Although anti-drug vaccines hold significant potential, challenges remain in their development and implementation. The reversibility of vaccination and the potential for combining vaccines with other addiction treatments offer promise for improving addiction outcomes. This review provides an overview of anti-drug vaccines, their mechanisms of action, and their potential impact on treatment for substance use disorders. Furthermore, this review summarizes recent advancements in vaccine development for each specific drug, offering insights for the development of more effective and personalized treatments capable of addressing the distinct challenges posed by various abused substances. Full article

Ketamine as an old–new drug has a variety of clinical implications. In the last 30 years, ketamine has become popular for acute use in humans. Ketamine in standard doses is principally utilized for the induction and maintenance of surgical procedures. Besides its use in anesthesia and analgesia, recent studies have shown that ketamine has found a place in the treatment of asthma, epilepsy, depression, bipolar affective disorders, alcohol and heroin addiction. Ketamine primarily functions as a noncompetitive antagonist targeting the N-methyl-D-aspartate (NMDA) receptor, but its mechanism of action is complex. It is generally regarded as safe, with low doses and short-term use typically not leading to significant adverse effects. Also, ketamine is known as a powerful psychostimulant. During the past decade, ketamine has been one of the commonly abused drugs. Full article

Patients with heroin use disorder (HUD) often exhibit trait impulsivity, which may be an important factor in and a good predictor of addiction. However, the factor structure of HUD trait impulsivity (motor, attentional, and nonplanning) and its neural correlates are not yet known. A total of 24 male volunteers with HUD and 16 healthy control volunteers were recruited for this cross-sectional study. The Barratt Impulsiveness Scale (BIS-11) and resting-state functional magnetic resonance imaging (rs-fMRI) were employed using the insula as a seed point in an effort to understand the association between trait impulsivity and its intrinsic factors and functional connectivity (FC) between the insula and the whole brain. The HUD group in this study exhibited higher total trait impulsivity scores, motor impulsivity, and nonplanning impulsivity than the control group. Changes in FC between the right insula and the lateral occipital cortex and the right angular gyrus were significantly positively correlated with total trait impulsivity scores, motor impulsivity, and nonplanning impulsivity, whereas changes in the FC between the left insula and the left superior frontal gyrus and left frontopolar brain region were significantly negatively correlated with trait impulsivity. Thus, the insula may serve as an important biomarker for identifying trait impulsivity and its intrinsic factor structure in patients with HUDs. Full article