Estrogen receptor beta signaling enhances extinction memory recall for heroin-conditioned cues in a sex- and region-specific manner.

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 ERß in females, impaired EMR. However, it is unclear whether increased E2 signaling, in the BLA or systemically, enhances heroin-cue EMR. We hypothesized that ERß 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 ERß 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 ERß agonist) and tested anxiety-like behavior on an open field. Subsequently, we assessed EMR in a cue-induced reinstatement test and, finally, measured ERß 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 ERß'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 ERß expression across several different brain regions showed that females only had greater expression of ERß in the basal nucleus of the BLA. Here, in several preclinical experiments, we demonstrated that ERß agonism enhances heroin-cue EMR and has potential utility in combatting cue-induced relapse.

"Tranq-dope": The first fatal intoxication due to xylazine-adulterated heroin in Italy.

BACKGROUND AND AIMS: The number of xylazine-involved overdose deaths tremendously increased from 2019 onwards in the US. This is due to the "tranq-dope" trend consisting in mixing opioids with the sedative to reduce drug manufacturing costs and enhance their effects. In this study, we report the first fatality involving xylazine-adulterated heroin in the EU. MATERIALS AND METHODS: The subject was a 33-year-old Caucasian male with a documented history of drug abuse who was found dead in a public area with puncture marks at the elbow. Peripheral blood and urine were collected at the autopsy and analyzed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) after protein precipitation. RESULTS: 6-Monoacetylmorphine, total/free morphine, and codeine blood concentrations of 20.3, 236/105, and 38.3 ng/mL, respectively, indicated recent heroin consumption. Methadone blood concentration was below 10 ng/mL. Alprazolam, nordiazepam, and flurazepam blood concentrations were 23.9, 61.4, and 55.0 ng/mL, respectively. Benzoylecgonine blood concentration was below 5 ng/mL. Xylazine blood and urine concentrations were 105 and 72.6 ng/mL, respectively. CONCLUSION: The combination of central nervous system depressants, i.e., opioids, benzodiazepines, and xylazine, was the principal cause of death by cardiorespiratory failure. The case was promptly reported to the UE Early Warning System on drugs.

A novel tramadol-polycaprolactone implant could palliate heroin conditioned place preference and withdrawal in rats: behavioral and neurochemical study.

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.

Cebranopadol, a novel long-acting opioid agonist with low abuse liability, to treat opioid use disorder: Preclinical evidence of efficacy.

Maintenance therapy with buprenorphine and methadone is the gold standard pharmacological treatment for opioid use disorder (OUD). Despite these compounds demonstrating substantial efficacy, a significant number of patients do not show optimal therapeutic responses. The abuse liability of these medications is also a concern. Here we used rats to explore the therapeutic potential of the new long-acting pan-opioid agonist Cebranopadol in OUD. We tested the effect of cebranopadol on heroin self-administration and yohimbine-induced reinstatement of heroin seeking. In addition, we evaluated the abuse liability potential of cebranopadol in comparison to that of heroin under fixed ratio 1 (FR1) and progressive ratio (PR) operant self-administration contingencies. Oral administration of cebranopadol (0, 25, 50 µg/kg) significantly attenuated drug self-administration independent of heroin dose (1, 7, 20, 60µg/inf). Cebranopadol also reduced the break point for heroin (20 µg/inf). Finally, pretreatment with cebranopadol significantly attenuated yohimbine-induced reinstatement of drug seeking. In abuse liability experiments under FR1 contingency, rats maintained responding for heroin (1, 7, 20, 60µg/inf) to a larger extent than cebranopadol (0.03, 0.1, 0.3, 1.0, 6.0µg/inf). Under PR contingency, heroin maintained responding at high levels at all except the lowest dose, while the break point (BP) for cebranopadol did not differ from that of saline. Together, these data indicate that cebranopadol is highly efficacious in attenuating opioid self-administration and stress-induced reinstatement, while having limited abuse liability properties. Overall, the data suggest clinical potential of this compound for OUD treatment.

[Sexual health in female under treatment for opiate dependence using diacetylmorphine]. / La sexualité au féminin chez les patientes traitées par diacétylmorphine.

Sexual health is a key element to the well-being and quality of life of individuals. However, it is rarely incorporated into care delivery for women with an addictive condition. Female with severe dependence to opiate have their medical and social conditions improved by diacetylmorphine treatment. Which allows them to escape situations of high-risk of sexual violence. However, this pharmacotherapy can also induce adverse effects on the sexual sphere. This paper describes the relevance of integrating psycho-socio-sexological counselling into the care provision for the opiate dependence. The counselling should be oriented to respond to the specific relational and sexual issues faced by these female patients and empowering them on their lives and in recovering a better quality of life.

La santé sexuelle constitue un élément important au bien-être et à la qualité de vie, or c'est un élément peu abordé au cours des soins des patientes souffrant de trouble addictologique. Le traitement de diacétylmorphine améliore la situation médicale et sociale des patientes souffrant d'une dépendance sévère aux opiacés et leur permet de sortir de situations à haut risque de violences sexuelles ; mais il peut également induire des effets indésirables sexuels. Cet article décrit l'importance d'intégrer à la prise en charge addictologique un accompagnement psychosocio-sexologique axé sur les difficultés sexuelles et relationnelles spécifiquement rencontrées par les patientes afin de leur offrir la possibilité de retrouver du pouvoir sur leur vie et une meilleure qualité de vie.

Bedside urine testing for fentanyl in self-reported heroin users in a tertiary Brisbane emergency department.

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. CONCLUSION: 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.

Changes in injecting versus smoking heroin, fentanyl, and methamphetamine among people who inject drugs in San Diego, California, 2020-2023.

BACKGROUND: Amidst an increasingly toxic drug supply in North America, people who inject drugs may be transitioning to smoking them. We aimed to assess changes in injecting and smoking opioids and methamphetamine among a cohort of people who inject drugs from San Diego, California. METHODS: Over five six-month periods spanning October 2020-April 2023, we assessed prevalence of injecting and smoking opioids or methamphetamine and whether participants used these drugs more frequently by smoking than injecting. Multivariable Poisson regression via generalized estimating equations was used to examine time trends. RESULTS: Of 362 participants, median age was 40 years; a minority were female (29%), Hispanic/Latinx/Mexican (45%), and housed (33%). Among this cohort, of whom 100% injected (and 84% injected and smoked) in period one (October 2020-April 2021), by period five (November 2022-April 2023), 34% only smoked, 59% injected and smoked, and 7% only injected. By period five, the adjusted relative risk (aRR) of injecting opioids was 0.41 (95% Confidence Interval [CI]: 0.33, 0.51) and the aRR for injecting methamphetamine was 0.50 (95% CI: 0.39, 0.63) compared to period one. Risks for smoking fentanyl rose significantly during period three (aRR=1.44, 95% CI: 1.06, 1.94), four (aRR=1.65, 95% CI: 1.24, 2.20) and five (aRR=1.90, 95% CI: 1.43, 2.53) compared to period one. Risks for smoking heroin and methamphetamine more frequently than injecting these drugs increased across all periods. CONCLUSIONS: Opioid and methamphetamine injection declined precipitously, with notable increases in smoking these drugs. Research is needed to understand the health consequences of these trends.

Exploring racial and secondary substance use differences in route of administration of opioid drugs: Analysis of the 2015-2019 treatment admission data.

INTRODUCTION: The opioid crisis continues to evolve with increasing opioid-related overdose deaths among under-represented minorities. A better understanding of substance use differences in the route of administration for people using heroin and other opioids can lead to targeted strategies and interventions. METHODS: Using the 2015-2019 Treatment Episode Data Set - Admissions (TEDS-A), a multinomial logistic regression model examined the relationship between race/ethnicity and secondary substance use with route of administration in a subset of 591,078 admissions. RESULTS: For individuals reporting heroin as their primary substance, minoritized clients were both more likely to smoke (NH Blacks RR: 2.28, 95 % CI 2.16-2.41; Hispanic RR: 1.80, 95 % CI: 1.74, 1.87; Other RR: 2.09, 95 % CI: 2.00, 2.20) or inhale heroin (Hispanic RR: 1.82, 95 % CI 1.78-1.85; Other RR: 1.30, 95 % CI 1.25, 1.34) compared to non-Hispanic (NH) Whites. NH Black clients were nearly seven and a half times more likely to report inhaling (RR: 7.45, 95 % CI 7.28, 7.62) heroin over injecting it. Clients were more likely to smoke heroin compared to injection if they reported secondary drug use of methamphetamines (RR: 2.28, 95 % CI 2.21, 2.35) and other opioids (RR: 1.21, 95 % CI 1.15, 1.28). For clients reporting other opioids as their primary substance, Hispanic (RR: 1.33, 95 % CI 1.19, 1.47) and other racial/ethnic minority clients (RR: 2.50, 95 % CI 2.23, 2.79) were more likely to smoke opioids vs take it orally compared to their NH White counterparts. Individuals who reported methamphetamine use as a secondary substance were significantly more than three times as likely to smoke (RR: 3.07, 95 % CI 2.74, 3.45) or inject (RR: 3.36, 95 % CI 3.17, 3.57) compared to orally ingesting opioids, while those who reported cocaine or crack cocaine use were more than twice as likely to inject (RR: 2.22, 95 % CI 2.09-2.36) opioids than taking them orally. CONCLUSION: Findings demonstrate significant racial and ethnic differences in the route of administration. This work expands on the understanding of the complex nature of polysubstance use in the evolving opioid crisis and the secondary substance use of clients on routes of administration of opioids and heroin, highlighting the need for tailored interventions to address the treatment needs of under-represented minorities.

Broad evidence of xylazine in the UK illicit drug market beyond heroin supplies: Triangulating from toxicology, drug-testing and law enforcement.

BACKGROUND AND AIMS: Xylazine is a non-opioid sedative which has spread rapidly throughout the US illicit drug supply. This study aimed to describe the spread of xylazine throughout the UK illicit drug supply. METHODS: Xylazine detections in human biological samples were collated from toxicology laboratories operating in the United Kingdom with the date, location, case type, xylazine concentration and co-detected drugs (with quantifications where performed) detailed, where permitted, by the corresponding coroner. Drug-testing cases positive for xylazine were collated from the Welsh Emerging Drugs and Identification of Novel Substances (WEDINOS) drug-testing postal service with the date, location, purchase intent and co-detected drugs detailed. Drug seizures made by UK law enforcement were communicated by the Office for Health Improvement and Disparities with the date and location detailed. RESULTS: By the end of August 2023, xylazine was detected in 35 cases from throughout toxicology, drug-testing and drug seizure sources covering England, Scotland and Wales. There were no cases reported from Northern Ireland. Xylazine was detected in biological samples from 16 people. In most cases where full toxicology results were provided, xylazine was detected with heroin and/or a strong opioid (n = nine of 11), but this polydrug use pattern was not evident in all cases (n = two of 11), suggesting a wider circulation of xylazine in the UK illicit drug market beyond heroin supplies. Evidence from WEDINOS supports this claim, as all 14 drug samples (100%) submitted from across the UK contained xylazine; however, in none of these cases was heroin the purchase intent but rather counterfeit prescription medication tablets (n = 11 of 14), tetrahydrocannabinol (THC) vapes (n = two of 14) or white powder (n = one of 14). Additional evidence for the spread of illicit xylazine comes from five drug seizures made by law enforcement. CONCLUSIONS: Xylazine has penetrated the UK illicit drug market and is not limited to heroin supplies.

Prolonged diacetylmorphine take-home during the COVID-19 pandemic-Results of a retrospective cohort study.

BACKGROUND AND AIMS: Legal regulations for dispensing in Swiss heroin-assisted treatment were relaxed during the COVID-19 pandemic, allowing prolonged take-home of up to 7 days instead of two to reduce patient contact and the risk of infection. Our study aimed to measure the consequences of this new practice. DESIGN, SETTING AND PARTICIPANTS: This was a retrospective cohort study set in Switzerland's largest outpatient centre for opioid agonist therapy. One hundred and thirty-four (72.4%) of the 185 patients receiving oral diacetylmorphine (DAM) participated in the study. MEASUREMENTS: Through the utilization of electronic medication prescription and dispensing software, as well as the electronic medical record, the following data were extracted to explore the potential consequences: dose of DAM, the number of antibiotic therapies, emergency hospitalizations and incarcerations. Age, gender, prescriptions for psychotrophic drugs and additional prescription for injectable DAM were tested to assess an increased risk of losing prolonged take-home privileges. Data in the year since prolonged take-home (period 2) were compared with data from the equivalent prior year (period 1). FINDINGS: DAM take-home was not associated with a change in DAM dose (P = 0.548), the number of emergency hospitalizations (P = 0.186) or the number of incarcerations (P = 0.215); 79.1% of all patients were able to maintain their extended take-home privileges. However, patients who had injectable DAM experienced significant reductions in their prolonged take-home privileges. CONCLUSION: Allowing patients to take home oral diacetylmorphine for up to 7 days as treatment for opioid use disorder does not appear to pose any demonstrable health risk. It is generally manageable for the large majority of patients. However, careful consideration of prolonged take-home for patients with additional injectable diacetylmorphine is recommended, as these patients are more likely to lose take-home privileges.

FDA Issues Warning About 'Gas Station Heroin'.

The highly addictive dietary supplement mimics opioid effects.

ß-caryophyllene inhibits heroin self-administration, but does not alter opioid-induced antinociception in rodents.

A growing body of research indicates that ß-caryophyllene (BCP), a constituent present in a large number of plants, possesses significant therapeutic properties against CNS disorders, including alcohol and psychostimulant use disorders. However, it is unknown whether BCP has similar therapeutic potential for opioid use disorders. In this study, we found that systemic administration of BCP dose-dependently reduced heroin self-administration in rats under an FR2 schedule of reinforcement and partially blocked heroin-enhanced brain stimulation reward in DAT-cre mice, maintained by optical stimulation of midbrain dopamine neurons at high frequencies. Acute administration of BCP failed to block heroin conditioned place preference (CPP) in male mice, but attenuated heroin-induced CPP in females. Furthermore, repeated dosing with BCP for 5 days facilitated the extinction of CPP in female but not male mice. In the hot plate assay, pretreatment with the same doses of BCP failed to enhance or prolong opioid antinociception. Lastly, in a substitution test, BCP replacement for heroin failed to maintain intravenous BCP self-administration, suggesting that BCP itself has no reinforcing properties. These findings suggest that BCP may have certain therapeutic effects against opioid use disorders with fewer unwanted side-effects by itself.

Pan-striatal reduction in the expression of the astrocytic dopamine transporter precedes the development of dorsolateral striatum dopamine-dependent incentive heroin seeking habits.

The emergence of compulsive drug-seeking habits, a hallmark feature of substance use disorder, has been shown to be predicated on the engagement of dorsolateral striatal control over behaviour. This process involves the dopamine-dependent functional coupling of the anterior dorsolateral striatum (aDLS) with the nucleus accumbens core, but the mechanisms by which this coupling occurs have not been fully elucidated. The striatum is tiled by a syncytium of astrocytes that express the dopamine transporter (DAT), the level of which is altered in individuals with heroin use disorder. Astrocytes are therefore uniquely placed functionally to bridge dopamine-dependent mechanisms across the striatum. Here we tested the hypothesis that exposure to heroin influences the expression of DAT in striatal astrocytes across the striatum before the development of DLS-dependent incentive heroin seeking habits. Using Western-blot, qPCR, and RNAscope™, we measured DAT protein and mRNA levels in whole tissue, culture and in situ astrocytes from striatal territories of rats with a well-established cue-controlled heroin seeking habit and rats trained to respond for heroin or food under continuous reinforcement. Incentive heroin seeking habits were associated with a reduction in DAT protein levels in the anterior aDLS that was preceded by a heroin-induced reduction in DAT mRNA and protein in astrocytes across the striatum. Striatal astrocytes were also shown to be susceptible to direct dopamine- and opioid-induced downregulation of DAT expression. These results suggest that astrocytes may critically regulate the striatal dopaminergic adaptations that lead to the development of incentive heroin seeking habits.

Inhibition of SIRT1 in the nucleus accumbens attenuates heroin addiction-related behavior by decreasing D1 neuronal autophagy.

This study aimed to investigate the effects of SIRT1 modulation on heroin addiction-like behavior and its possible biological mechanisms. Wild-type C57BL/6J and Sirt1loxp/loxp D1-Cre mice were used in this experiment, and Sirt1 loxp/loxp D1-Cre(-) mice were used as a control for conditional knockout mice. Mice were divided into saline control and heroin-dependent groups. Behavioral methods were used to record the withdrawal response, conditioned place preference (CPP) changes, and open field test results. Transmission electron microscopy (TEM) was used to observe the structure of autophagosomes in nucleus accumbens (NAc) neurons. The expression of SIRT1 and autophagy-related proteins and genes, such as LC3Ⅱ, ATG5 , and ATG7 , was detected in the NAc of each mouse group via western blot, real-time quantitative PCR (qPCR) analyzes, and immunofluorescence. The results of this experiment showed that compared with the saline group, mice in the wild-type heroin-dependent group showed marked withdrawal symptoms, with more autophagosomes observed in NAc via TEM. Compared with wild-type and Sirt1loxp/loxp D1-Cre(-) heroin-dependent groups, CPP formation was found to be reduced in the conditional knockout mouse group, with a significant decrease in spontaneous activity. Western blot, qPCR, and immunofluorescence results indicated that the expression of LC3Ⅱ, ATG-5, and ATG-7 was significantly reduced in the NAc of the Sirt1loxp/loxp D1-Cre(+) group. It was still, however, higher than that in the saline control group. These results suggest that inhibition of Sirt1 expression may prevent heroin-induced addiction-related behaviors via reducing D1 neuronal autophagy.

Full Characterisation of Heroin Samples Using Infrared Spectroscopy and Multivariate Calibration.

The analysis of heroin samples, before use in the protected environment of user centra, could be a supplementary service in the context of harm reduction. Infrared spectroscopy hyphenated with multivariate calibration could be a valuable asset in this context, and therefore 125 heroin samples were collected directly from users and analysed with classical chromatographic techniques. Further, Mid-Infrared spectra were collected for all samples, to be used in Partial Least Squares (PLS) modelling, in order to obtain qualitative and quantitative models based on real live samples. The approach showed that it was possible to identify and quantify heroin in the samples based on the collected spectral data and PLS modelling. These models were able to identify heroin correctly for 96% of the samples of the external test set with precision, specificity and sensitivity values of 100.0, 75.0 and 95.5%, respectively. For regression, a root mean squared error of prediction (RMSEP) of 0.04 was obtained, pointing at good predictive properties. Furthermore, during mass spectrometric screening, 10 different adulterants and impurities were encountered. Using the spectral data to model the presence of each of these resulted in performant models for seven of them. All models showed promising correct-classification rates (between 92 and 96%) and good values for sensitivity, specificity and precision. For codeine and morphine, the models were not satisfactory, probably due to the low concentration of these impurities as a consequence of acetylation. For methacetin, the approach failed.

State-level variation in distribution of oxycodone and opioid-related deaths from 2000 to 2021: an ecological study of ARCOS and CDC WONDER data in the USA.

OBJECTIVES: This study aims to characterise oxycodone's distribution and opioid-related overdoses in the USA by state from 2000 to 2021. DESIGN: This is an observational study. SETTING: More than 80 000 Americans died of an opioid overdose in 2021 as the USA continues to struggle with an opioid crisis. Prescription opioids play a substantial role, introducing patients to opioids and providing a supply of drugs that can be redirected to those seeking to misuse them. METHODS: The Drug Enforcement Administration annual summary reports from the Automation of Reports and Consolidated Orders System provided weights of oxycodone distributed per state by business type (pharmacies, hospitals and practitioners). Weights were converted to morphine milligram equivalents (MME) per capita and normalised for population. The Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research provided mortality data for heroin, other opioids, methadone, other synthetic narcotics and other/unspecified narcotics. RESULTS: There was a sharp 280.13% increase in total MME/person of oxycodone from 2000 to 2010, followed by a slower 54.34% decrease from 2010 to 2021. Florida (2007-2011), Delaware (2003-2020) and Tennessee (2012-2021) displayed consistent and substantial elevations in combined MME/person compared with other states. In the peak year (2010), there was a 15-fold difference between the highest and lowest states. MME/person from only pharmacies, which constituted >94% of the total, showed similar results. Hospitals in Alaska (2000-2001, 2008, 2010-2021), Colorado (2008-2021) and DC (2000-2011) distributed substantially more MME/person over many years compared with other states. Florida stood out in practitioner-distributed oxycodone, with an elevation of almost 15-fold the average state from 2006 to 2010. Opioid-related deaths increased +806% from 2000 to 2021, largely driven by heroin, other opioids and other synthetic narcotics. CONCLUSIONS: Oxycodone distribution across the USA showed marked differences between states and business types over time. Investigation of opioid policies in states of interest may provide insight for future actions to mitigate opioid misuse.

Detection of contraband drugs in forensic-correctional mental health services using TeknoScan-a gas chromatography tool.

Substance misuse is a major problem among individuals involved in forensic-correctional mental health services. Urine drug screening detects substance use and deters the entry of contraband into forensic-correctional units, albeit with limitations. For example, a point-of-care urine sample may not be possible and patients can alter or substitute samples to avoid detection, highlighting the role of ancillary tools to detect contraband substances. This study describes the pattern and types of substances detected from environmental samples using a gas chromatographic analyzer (TeknoScan TSI3000) in forensic-correctional populations to model the benefits of similar tools in similar settings. Samples collected over 18 months (January 2020 to June 2021) by trained staff members using the machine were reviewed. During this period, 217 environmental samples were recorded, and 66 (30%) samples were positive for contraband substances, including tetrahydrocannabinol (25%), methamphetamines (19%), and cocaine (16%). Other substances detected include methylene-dioxymethamphetamine, heroin, morphine, lysergic acid diethylamide, tramadol, and methyl-benzoate. Fewer positive samples were detected, especially during the time corresponding with the COVID-19 restriction on the forensic units. TeknoScan was beneficial as an ancillary tool to detect and deter contraband substances. It also provided evidence for risk management. Adequate training is needed for the successful implementation of the tool.

Adulterants present in the San Diego county fentanyl supply: a laboratory analysis of seized law enforcement samples.

BACKGROUND: The opioid overdose crisis is one of the worst public health crises ever to face the US and emerging evidence suggests its effects are compounded by the presence of drug adulterants. Here we report our efforts to characterize the adulterants present within the local fentanyl supply of San Diego County, obtained from undifferentiated drug samples seized by local law enforcement over the calendar year 2021. METHODS: Thirty-two participating local law enforcement agencies across San Diego submitted 4838 unknown individual illicit drug samples (total of 312 kg) to the San Diego County Sheriff's Department Regional Crime Laboratory for identification. RESULTS: Qualitative analysis of these samples via FTIR and GC-MS identified methamphetamine (38.7%), fentanyl (20.8%), diacetylmorphine (heroin) (10.2%), codeine (5.8%) and alprazolam (4.3%) as the most common illicit substances and the presence of 52 unique adulterants. The most common adulterants included 4-methylaminoantipyrine (4-MAAP) (10.9%), mannitol (9%), acetaminophen (8.5%), methamphetamine (4.2%), diacetylmorphine (heroin) (3.6%), tramadol (1.9%), and xylazine (1.7%). Several additional pharmacologically active adulterants and contaminants of interest were also identified. CONCLUSION: This analysis is vital for public health use and harm reduction efforts at the level of the individual consumer. Continued direct surveillance of the drug supply is necessary for the detection of potentially harmful adulterants that may pose serious threats to the public.

Long-access heroin self-administration induces region specific reduction of grey matter volume and microglia reactivity in the rat.

In opioid use disorder (OUD) patients, a decrease in brain grey matter volume (GMV) has been reported. It is unclear whether this is the consequence of prolonged exposure to opioids or is a predisposing causal factor in OUD development. To investigate this, we conducted a structural MRI longitudinal study in NIH Heterogeneous Stock rats exposed to heroin self-administration and age-matched naïve controls housed in the same controlled environment. Structural MRI scans were acquired before (MRI1) and after (MRI2) a prolonged period of long access heroin self-administration resulting in escalation of drug intake. Heroin intake resulted in reduced GMV in various cortical and sub-cortical brain regions. In drug-naïve controls no difference was found between MRI1 and MRI2. Notably, the degree of GMV reduction in the medial prefrontal cortex (mPFC) and the insula positively correlated with the amount of heroin consumed and the escalation of heroin use. In a preliminary gene expression analysis, we identified a number of transcripts linked to immune response and neuroinflammation. This prompted us to hypothesize a link between changes in microglia homeostasis and loss of GMV. For this reason, we analyzed the number and morphology of microglial cells in the mPFC and insula. The number of neurons and their morphology was also evaluated. The primary motor cortex, where no GMV change was observed, was used as negative control. We found no differences in the number of neurons and microglia cells following heroin. However, in the same regions where reduced GMV was detected, we observed a shift towards a rounder shape and size reduction in microglia, suggestive of their homeostatic change towards a reactive state. Altogether these findings suggest that escalation of heroin intake correlates with loss of GMV in specific brain regions and that this phenomenon is linked to changes in microglial morphology.