Psychotropic Research Articles

Predictors for chronic opioid use in patients with inflammatory bowel disease - a population based cohort study.

A significant proportion of patients with Crohn's disease (CD) and ulcerative colitis (UC) become opioid users, but data pertaining to predictors of chronic opioid use remain sparse. We examined predictors for chronic opioid use in CD/UC. A nationwide cohort study based on Danish registries, comprising incident patients with CD/UC (≥ 18 years) from January 1, 1996-December 31, 2021. Chronic opioid use was defined as >1 prescriptions in at least two of three consecutive quarters. Cox regression models were used to estimate adjusted Hazard Ratios (aHRs) for predictors for chronic opioid use. Several variables and time-varying covariates (IBD surgery, IBD and psychotropic medications) were included. In 15,092 CD patients, 4,141 (27.4%) became chronic opioid users (median follow up 7.35 years, 25%-75% percentiles (IQR) 3.40-13.66 years). The three most important predictors were surgery (4.20, 95% CI 3.72-4.75), hypnotics/sedatives (2.02, 95% CI 1.81-2.25), and age > 50 years (1.92, 95% CI 1.77-2.09). In 30,416 UC patients, 6,777 (22.3%) became chronic users (median follow up 8.80 years, IQR 4.20-15.22 years). The three most important predictors were surgery (4.81, 95% CI 4.20-5.52), age > 50 years (2.62 (95% CI 2.44-2.82), and hypnotics/sedatives (2.11, 95% CI 1.95-2.29). An alarming proportion of patients became chronic opioid users. These results are helpful to risk-stratify patients to prevent chronic opioid use. Clinicians should be particularly attentive in patients who have had surgery, who use hypnotics/sedatives, and who are elderly. We need evidence regarding pain management strategies, efficacy of non-opioid analgesics, and opioid cessation strategies.

Toxicokinetics and analytical toxicology of the phenmetrazine-derived new psychoactive substance 3,4-methylenedioxyphenmetrazine studied by means of in vitro systems.

Compounds derived from known drugs are usually brought on the new psychoactive substance (NPS) market without any previous toxicological risk assessment. The European Union Drugs Agency issued an EU early notification for 3,4-methylenedioxyphenmetrazine (MDPM) in 2024. It is structurally related to the stimulants amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), and phenmetrazine and expected to have similar effects. So far, no scientific reports are available describing its toxicokinetic and analytical profile. This study aimed to provide such data to allow a thorough risk assessment and to ease its analytical detectability in forensic and clinical toxicology and doping control. Data reported include the in vitro plasma protein binding, the in vitro half-life and in vitro metabolism of MDPM by human liver microsomes and S9 fraction (pHLS9) and by HepaRG cells. A monooxygenase mapping and the in vitro cytochrome P450 inhibition of MDPM was elucidated. Results showed that HepaRG cells and pHLS9 formed the same MDPM metabolites via demethylenation and O-methylation and that MDPM has a low plasma protein binding and is a low-turnover drug. Monooxygenase mapping revealed that the demethylenation was exclusively CYP2D6-mediated. MDPM showed strong inhibition of CYP2D6 and moderate inhibition of CYP1A2 and CYP3A4. Polymorphisms or the simultaneous intake of substances that are also CYP2D6 substrates can have a considerable impact on the toxicity of MDPM. Based on in vitro data, the demethylenyl-methyl metabolite of MDPM and the parent compound are recommended as analytical urine screening targets.

Premature Mortality and Health Inequality among Adult New Yorkers with Serious Mental Illness.

Although numerous studies have documented excess mortality and health inequality among individuals with serious mental illness (SMI), none has been done among individuals in a large, diverse urban setting, such as New York City (NYC). We used referral data for adults aged 18 and older referred to the NYC Department of Health and Mental Hygiene public mental health services between January 2004 and December 2018 and matched it to the NYC death registry. Age at death, leading causes of death, years of potential life lost (YPLL), and standardized mortality ratios (SMRs) were calculated for this population. We found individuals with SMI in NYC died at younger ages and had higher rates of YPLL compared to the total population (147.4 YPLL vs. 66.8 YPLL per 1000 population). Age and gender-adjusted SMRs show these individuals have more than twice the mortality rate of the total NYC adult population (overall SMR 2.2 [95% CI 2.1-2.2]). Cause-specific SMRs show an increased risk of death among SMI from diabetes (SMR 2.8 [95% CI 2.4-3.10]), heart disease (SMR 2.7 [95% CI 2.6-2.9]), psychoactive substance use and accidental overdose (SMR 4.5 [95% CI 4.1-4.9]), and suicide (SMR 6.7 [95% CI 6.0-7.4]). Our results highlight the need to implement effective, preventive, and rehabilitative measures that integrate physical and behavioral healthcare services and address upstream drivers of health to achieve health equity and eliminate health disparities. In order to achieve gains in life expectancy, specific considerations for reducing excess mortality in the SMI population must be accounted for.

A small area analysis of acute exposure to temperatures and mental health in North Carolina.

Increasing evidence suggests that temperatures adversely impact mental and behavioral disorders (MBD). This study explores the effects of temperatures on mental health outcomes using over 5.9million MBD-related emergency department (ED) visits across three geographical regions of North Carolina (i.e., Mountains, Piedmont, and Coast) from 2016 to 2019. A distributed lag non-linear model (DLNM) with a generalized linear model and quasi-Poisson distribution adjusted for humidity, long-term seasonal time trends, and day of the week examined the acute impact (i.e., 7-day) of temperature on daily MBD-related ED visits at zip code tabulation area (ZCTA) locations. Results were pooled at the region and state levels and reported in reference to the median temperature using a case-time series design for the analysis of small-area data. Stratified analyses were conducted for age, sex, and specific mental-health related ED visits (substance use, mood disorders, anxiety disorders). At the state level, we found significant positive associations between high temperatures (97.5th percentile) and an increase in relative risk (RR) for total MBDs (RR:1.04, 95% CI,1.03-1.05) and psychoactive substance use (RR:1.04, 95% CI, 1.02-1.06). Low air temperatures (2.5th percentile) only increased risk for the elderly (i.e., 65 and older) and predominantly white communities (RR: 1.03, CI: 1.03-1.05). During high temperatures (97.5th percentile), majority-white communities (RR:1.06, CI: 1.01-1.10) and low-income communities had the highest risk for MBDs (RR: 1.05, CI: 1.03-1.07). Our findings suggest there is a positive association between exposure to high temperatures and increased MBD-related ED visits, modified by patient age and place-based sociodemographic (ie., race and income) context.

The development of opioid vaccines as a novel strategy for the treatment of opioid use disorder and overdose prevention.

Opioid use disorder (OUD) affects over 40 million people worldwide, creating significant social and economic burdens. Medication for opioid use disorder (MOUD) is often considered the primary treatment approach for OUD. MOUD, including methadone, buprenorphine, and naltrexone, is effective for some, but its benefits may be limited by poor adherence to treatment recommendations. Immunopharmacotherapy offers an innovative approach by using vaccines to generate antibodies that neutralize opioids, blocking them from crossing the blood-brain barrier and reducing their psychoactive effects. To date, only 3 clinical trials for opioid vaccines have been published. While these studies demonstrated the potential of opioid vaccines for relapse prevention, there is currently no standardized protocol for evaluating their effectiveness. We have reviewed recent preclinical studies that demonstrated the efficacy of vaccines targeting opioids, including heroin, morphine, oxycodone, hydrocodone, and fentanyl. These studies showed that vaccines against opioids reduced drug reinforcement, decreased opioid-induced antinociception, and increased survival rates against lethal opioid doses. These studies also demonstrated the importance of vaccine formulation and the use of adjuvants in enhancing antibody production and specificity. Finally, we highlighted the strengths and concerns associated with the opioid vaccine treatment, including ethical considerations.

Robust Detection of Ecstasy-Like and Adulterants Through ASAP-MS and DD-SIMCA.

Ecstasy is a complex and hazardous substance, and its identification is increasingly challenging. Conventional analytical methods have limitations in terms of sensitivity and selectivity, and more precise techniques are time-consuming and necessitate sample preparation. ASAP-MS and DD-SIMCA are two methods that have the potential to address these issues. This research delves into the efficacy of ASAP-MS and DD-SIMCA as a rapid and dependable approach for detecting ecstasy and its adulterants. PCA was conducted as an initial exploration, with the first three principal components (PCs) capturing 69% of the overall data variability. The score plot of PC1 × PC3 revealed the distribution of samples containing MDA and MDMA. The DD-SIMCA model exhibited high sensitivity in identifying the target samples (MDA) and relatively high specificity in training and test sets. These results underscore the effectiveness of ASAP-MS, PCA, and DD-SIMCA for precise identification of ecstasy and its adulterants, indicating their potential in drug identification and analysis. We observed that the chemometric model associated with ASAP-MS was able to accurately identify, when compared to the results obtained by the standard technique, the constituents of ecstasy tablets, even in the presence of adulterants. Furthermore, the method could detect emerging psychoactive substances that are typically not targeted by traditional analytical approaches. These findings suggest that ASAP-MS and DD-SIMCA could be valuable tools in forensic drug analysis laboratories. The method is rapid, reliable, and versatile for identifying a wide range of ecstasy and its adulterants.

Efficacy of e-cigarettes for smoking cessation in populations with psychiatric and/or substance use problems: A secondary analysis of a randomized controlled trial.

People with psychiatric and substance use disorders are more likely to smoke and less likely to quit than smokers in the general population. We evaluated the efficacy of e-cigarettes for abstinence from tobacco smoking in people with psychiatric and substance use problems. We analyzed data collected in the larger 'Efficacy, Safety, and Toxicology of ENDS as an Aid for Smoking Cessation' (ESTxENDS) trial (n=1246): the intervention group received e-cigarettes and e-liquids, plus standard-of-care smoking cessation counseling (SOC) for 6 months; the control group received SOC and a voucher. The primary outcome was biochemically validated continuous self-reported abstinence at 6 months; secondary outcomes included 6-month and 7-day self-reported abstinence. We calculated adjusted relative risks (ARR) for two subsamples meeting these conditions at the baseline visit: 1) psychotropic medication use; and 2) problematic substance or polysubstance use. Among the participants using psychotropic medications (n=239), the ARR for validated abstinence was 2.62 (95% CI: 1.40-4.90) in the intervention group versus the control group, 2.95 (95% CI: 1.72-5.07) for 6-month and 2.96 (95% CI: 1.92-4.55) for 7-day self-reported abstinence, while among participants with problematic substance or polysubstance use (n=818), the ARR was 1.57 (95% CI: 1.20-2.04), 1.42 (95% CI: 1.15-1.74), and 1.53 (95% CI: 1.31-1.79), respectively. Adding e-cigarettes to standard-of-care counseling increased the likelihood that participants with psychiatric and substance use problems would abstain from smoking, but larger studies should test the efficacy and safety of smoking cessation interventions in this often-marginalized population.

A New Trick of Old Dogs: Can Kappa Opioid Receptor Antagonist Properties of Antidepressants Assist in Treating Treatment-Resistant Depression (TRD)?

Background/Objectives: Approximately one in five individuals will experience major depressive disorder (MDD), and 30% exhibit resistance to standard antidepressant treatments, resulting in a diagnosis of treatment-resistant depression (TRD). Historically, opium was used effectively to treat depression; however, when other medications were introduced, its use was discontinued due to addiction and other hazards. Recently, kappa opioid receptor (KOR) antagonism has been proposed as a potential mechanism for treating TRD. The main research question is whether commonly used psychotropic medications possess KOR antagonist properties and whether this characteristic could contribute to their efficacy in TRD. Methods: We investigated the antinociceptive effects of many psychotropic medications and their interactions with the opioid system. Mice were tested with a hotplate or tail-flick after being injected with different doses of these agents. Results: The antidepressants mianserin and mirtazapine (separately) induced dose-dependent antinociception, each yielding a biphasic dose–response curve. Similarly, the antidepressant venlafaxine produced a potent effect and reboxetine produced a weak effect. The antipsychotics risperidone and amisulpride exhibited a dose-dependent antinociceptive effect. The sedative–hypnotic zolpidem induced a weak bi-phasic dose-dependent antinociceptive effect. All seven psychotropic medications elicited antinociception, which was reversed by the non-selective opiate antagonist naloxone and, separately, by the kappa-selective antagonist Nor-BNI. Conclusions: Clinical studies are mandatory to establish the potential efficacy of augmentation of the treatment with antidepressants with these drugs in persons with treatment-resistant depression and the optimal dosage of medications prescribed. We suggest a possible beneficial effect of antidepressants with kappa antagonistic properties.

Improved LC-MS Detection of Opioids, Amphetamines, and Psychedelics Using TrEnDi.

Substances of misuse are becoming increasingly difficult to analyze as unique methods of smuggling are adopted and due to the rapid emergence of new psychoactive substances, increasing the pool of compounds to characterize and identify. Technologies such as gas chromatography and liquid chromatography coupled to mass spectrometry (MS) represent the gold standard for accurate and robust analysis, with on-site ambient- and portable-MS systems providing rapid methods of drug screening and testing. For many samples containing residual analyte quantities, methods to improve sensitivity through chemical derivatization are critical for accurate determination. Herein, we demonstrate for the first time the use of trimethylation enhancement using diazomethane (TrEnDi) to improve the MS-based sensitivity of 13 different drugs of misuse. All analytes were successfully permethylated, with 11 demonstrating improved analytical characteristics from TrEnDi with MS sensitivity enhancements ranging from 1.2-fold to as high as 24.2-fold in the case of psilocybin, as well as increases in reversed-phase chromatographic retention for most species. Derivatization using 13C-isotopically labeled TrEnDi reagents were used to successfully resolve isobaric interference issues between three pairs of controlled substances. By using an unconventional aprotic solvent system for electrospray ionization, the benefit of a fixed-permanent positive charge was highlighted as TrEnDi-modified amphetamine was easily measured while unmodified was not detected. Finally, TrEnDi was employed to boost the sensitivity of morphine in a real urine matrix. Our results demonstrate a percent recovery of 103.1% and a sensitivity enhancement of 2.4-fold, demonstrating the versatility and applicability of TrEnDi to pre-existing analytical workflows for trace analysis.

Law Enforcement of Middlemen in the Crime of Narcotics Group I Not Plants

The use of narcotics, psychotropic substances and other addictive substances has a huge impact if misused. However, on the other hand, these substances can provide benefits for the development of science and the treatment of disease if used according to the instructions of the authorities. Therefore, this scientific legal work discusses two main things: first, how the legal regulations relate to intermediaries in the sale and purchase of class I non-plant narcotics according to positive law, and second, how to apply criminal law to these perpetrators. This research uses a normative method with a statutory approach. Eradicating narcotics faces very complex obstacles, ranging from internal and external factors of perpetrators to the involvement of law enforcement officers in abuse. As a solution, the government needs to optimize the role of society to increase supervision and legal awareness, revise narcotics laws, and tighten supervision of the morality of law enforcement officers.

Neuroimaging as a Tool for Advancing Pediatric Psychopharmacology.

Neuroimaging, specifically magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET), plays an important role in improving the therapeutic landscape of pediatric neuropsychopharmacology by detecting target engagement, pathway modulation, and disease-related changes in the brain. This review provides a comprehensive update on the application of neuroimaging to detect neural effects of psychotropic medication in pediatrics. Additionally, we discuss opportunities and challenges for expanding the use of neuroimaging to advance pediatric neuropsychopharmacology. PubMed and Embase were searched for studies published between 2012 and 2024 reporting neural effects of attention deficit hyperactivity disorder (ADHD) medications (e.g., methylphenidate, amphetamine, atomoxetine, guanfacine), selective serotonin reuptake inhibitors (e.g., fluoxetine, escitalopram, sertraline), serotonin/norepinephrine reuptake inhibitors (e.g., duloxetine, venlafaxine), second-generation antipsychotics (e.g., aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone), and others (e.g., lithium, carbamazepine, lamotrigine, ketamine, naltrexone) used to treat pediatric psychiatric conditions. Of the studies identified (N = 57 in 3314 pediatric participants), most (86%, total participants n = 3045) used MRI to detect functional pathway modulation or anatomical changes. Fewer studies (14%, total participants n = 269) used MRS to understand neurochemical modulation. No studies used PET. Studies that included healthy controls detected normalization of disease-altered pathways following treatment. Studies that focused on affected youth detected neuromodulation following single-dose and ongoing treatment. Neuroimaging is positioned to serve as a biomarker capable of demonstrating acute brain modulation, predicting clinical response, and monitoring disease, yet biomarker validation requires further work. Neuroimaging is also well suited to fill the notable knowledge gap of long-term neuromodulatory effects of psychotropic medications in the context of ongoing brain development in children and adolescents. Future studies can leverage advancements in neuroimaging technology, acquisition, and analysis to fill these gaps and accelerate the discovery of novel therapeutics, leading to more effective prescribing and ensuring faster recovery.

Health, social, and violence profiles of women in treatment for psychoactive substance use in Madrid.

This study aimed to describe the profile of women seeking treatment for the use of psychoactive substances in the city of Madrid. The study used a sample of 1968 women who sought treatment at the Addiction Care Centers (CAD) of the Madrid City Council in the year 2022, which accounted for 22.9% of the total population attended. This quantitative study used secondary data provided by the Institute of Addictions (General Subdirectorate of Addictions, Madrid Salud). The analyses included bivariate analysis, correspondence analysis, K-means clustering, and ANOVA. Bivariate analysis was conducted to determine the association between the principal psychoactive substance and sociodemographic characteristics. Statistically significant results were employed to develop a correspondence analysis and used to conduct a K-means clustering analysis. The objective was to determine the profile of the women who sought treatment at the CAD of the Institute of Addictions (General Subdirectorate of Addictions of Madrid Salud). The results revealed three profiles of women: 1) women who use cocaine and heroin, were unemployed with children, and had lower education; 2) women who used cannabis were not working, had no children, and had intermediate education; 3) women who used alcohol had children, higher education, and were working. All three profiles were associated with situations of domestic violence, where the percentages were very high in each of the profiles, regardless of the principal substance of use and the sociodemographic and health characteristics. The results highlight the need for tailored addiction treatment approaches that address the distinct social and health profiles of women in Madrid, including challenges such as motherhood, drug-related infections, and violence. These findings emphasize the importance of providing specialized services to approach the complex needs of women undergoing addiction treatment.

Comprehensive evaluation of the toxicological effects of commonly encountered synthetic cathinones using in silico methods.

Synthetic cathinones (SCs), a group of new psychoactive substances (NPS), are designer molecules with hallucinogenic and psychostimulatory effects. Although the structural similarities of SCs to amphetamines suggest that they may have similar toxicity profiles to those of amphetamine congeners, little is known about SCs from a toxicological point of view. In the present study, the toxicity profiles of commonly encountered SCs (n = 65), listed in the 2020 Report of the United Nations Office on Drugs and Crime (UNODC), were evaluated using in silico methods. We aimed to gain a deeper understanding of key toxicological endpoints: acute oral toxicity (LD50), mutagenicity, genotoxicity, and carcinogenicity prediction using EPA TEST (v.5.1.2 and 4.2.1), VEGA (v.1.2.3), and ProTox (v.3.0). Physicochemical and pharmacokinetic (ADME) properties were estimated using SwissADME and pkCSM. 2,3-MDMC (41) was predicted to be the most lethal SC by the VEGA KNN and the EPA TEST v.5.1.2 with an oral rat LD50 value of 105.17 and 117.77mg/kg, respectively. 4-BEC (2) was the only molecule with a consensus score of positive prediction greater than 0.90 in both TEST mutagenicity models. 2,3-MDMC (41) and methylone (52) were predicted as carcinogenic by VEGA carcinogenicity CAESAR, ISS, IRFMN-ISSCAN-CGX, oral classification, and ProTox models. These two SCs were predicted to be active by VEGA chromosomal aberration (CORAL) and in vitro micronuclei-inducing activity (IRFMN-VERMEER) models. Our results concluded that given the prolonged exposure duration and age range, the genotoxic and carcinogenic potential of SCs should be considered, among other known toxic effects.

New Psychoactive Substance and Polysubstance Use Patterns Among Adults in 19 US Cities: A Latent Class Analysis

New Psychoactive Substance and Polysubstance Use Patterns Among Adults in 19 US Cities: A Latent Class Analysis

Simultaneous determination of 51 indazole-type synthetic cannabinoids in urine and blood by online solid-phase extraction-liquid chromatography-linear ion trap mass spectrometry

To evade legal controls, new psychoactive substances (NPS), which have been designed as substitutes for traditional and synthetic drugs, are gradually dominating the drug market. Synthetic cannabinoids (SCs), which account for the majority of NPS, are rapidly being derivatized; consequently, controlling increasing abuse by merely listing individual compounds is difficult. Therefore, China has included the entire SC category of SCs listed as legal controlled substances since July 1, 2021. However, new SCs obtained through structural modification are still appearing and pose significant analytical challenges for forensic laboratories. Therefore, an efficient, green, and automated detection method is urgently required to provide technical support for the accurate screening actual samples. Meanwhile, the number of indazole-type SCs has increased sharply since 2013, which is ascribable to their stronger psychoactive effects. Indeed, forensic laboratories mainly analyze this key SC subclass. Therefore, in this study, we developed a new method for analyzing 51 indazole-type SCs in human urine and blood, which involves online solid-phase extraction (online SPE) as the preprocessing technology, with analysis performed using liquid chromatography-linear ion trap mass spectrometry. Deproteinization was achieved by adding acetonitrile, with dilution performed using 10 mmol/L ammonium acetate solution (pH 4.8) containing 0.1% formic acid. Samples were then analyzed directly using acetonitrile-10 mmol/L ammonium acetate aqueous solution (containing 0.1% formic acid) as the mobile phase. The mass-to-charge ratios of protonated molecular ions ([M+H]+) in the mass spectra acquired in full-scan mode, and the retention times in the chromatograms of the analytes were selected with the aim of monitoring the MS2 ions of the various compounds. Characteristic fragment ions of the various SC structures were summarized, with five groups of isomers, each containing ten compounds, successfully distinguished using multistage mass spectrometry and their retention times. Multistage MS was used to qualitatively screen 51 indazole-type SCs, which were then quantitatively analyzed using MS2 ion pairs (as quantitative ion pairs). The analytes exhibited limits of detection (LODs) of 0.02-1 ng/mL, with limits of quantification (LOQs) of 0.04-4 and 0.1-4 ng/mL in urine and blood, respectively. Linear fitting (weighting factor 1/x) revealed good linearity for each analyte within its respective linear range, with correlation coefficients (R2) greater than 0.99 in both urine and blood. The validity of the analytical method was tested by determining precision and spiked recovery values (n=6). Recoveries of 83.47%-116.95% were obtained at LOQ levels, with precisions of 2.29%-13.40%. In addition, recoveries of 86.63%-113.38% and precisions of 0.58%-13.79% were obtained at low, medium, and high levels. The method described herein is not only easy to operate but also can be automated. Indeed, high-throughput sample analysis was achieved when sample extraction, enrichment, and analysis were performed in dynamic mode through valve switching. Meanwhile, the method exhibited good sensitivity and is applicable to a wider range of compounds than those previously reported; it also provides a scientific basis and technical support for the rapid screening and quantitative analysis of SCs in actual relevant cases.

NMR-based structure elucidation and chiral separation of N-cyclohexylmethylone, a novel designer drug.

Synthetic cathinones belong to one of the biggest and most popular classes of New Psychoactive Substances. Each year, new derivatives appear on the drug market, traded under various labels like "bath salts" or "legal highs". In recent years, the emergence of new cathinone derivatives, containing a cyclohexyl residue, has been observed. Since 2021, threads about N-cyclohexylmethylone have been posted in various user forums.A powder sample of N-cyclohexylmethylone purchased by a client was collected in Austria in a local drug checking program and analyzed by GC-MS, LC-HRMS NMR spectroscopy and chiral HPLC. The aim of this study was to provide experimental NMR data of the compound and to determine the chiral status of the sample. Usually, cathinone derivatives are sold as racemic mixtures on the market. Investigation showed that in the sample both enantiomers were present.

Identification and characterisation of the recently detected cathinone N-cyclohexyl pentylone.

Synthetic cathinones are one of the most consumed new psychoactive substances (NPS) in New Zealand and around the world. The combination of the ease of manufacture and simple modification of the chemical structure of cathinone lends this class of stimulants as one that is difficult to predict and legislate. A major challenge in the rapid identification of NPS is access to valid spectra and reference material and with the constantly changing landscape of these "designer drugs", these are difficult to obtain. This paper reports a new synthetic cathinone, N-cyclohexyl pentylone, which was detected within in a sample received from Drug Checking Service Provider, New Zealand Drug Foundation (NZDF). Structural elucidation and characterisation were carried out using gas chromatography - mass spectrometry (GC-MS), Fourier-transform infrared (FTIR) spectroscopy, high-resolution mass spectrometry (HRMS), and nuclear magnetic resonance (NMR).

Novel Psychoactive Substance Use: Exploring Experiences of Pregnant and Postpartum Individuals With Substance Use Disorders

Novel Psychoactive Substance Use: Exploring Experiences of Pregnant and Postpartum Individuals With Substance Use Disorders

Investigating 3-CMC metabolism: Insights from liver microsomes and postmortem biological matrix.

3-Chloromethcathinone (3-CMC) is a synthetic cathinone that has been identified as a new psychoactive substance (NPS) by the European Monitoring Centre for Drugs and Drug Addiction. Despite its increasing prevalence in the recreational drug market since 2014, scientific literature on 3-CMC remains limited. This study employed a multi-step approach to investigate 3-CMC metabolism. First, an in-silico prediction was conducted to compile a list of potential metabolites. Then, in vitro assays were performed using human liver microsomes at two concentrations of 3-CMC. Samples were analyzed using an ultra-performance liquid chromatography system coupled with a high-resolution mass spectrometer. Chromatographic separation was obtained with an Acquity UPLC HSS C18 1.8 µm, 2.1 × 150 mm column on an Ultimate 3000 system chromatography coupled with a QExactivePlus mass spectrometer). Finally, data mining for metabolite identification was conducted using Compound Discoverer software. The combined in silico and in vitro approaches identified four primary metabolites of 3-CMC in HLM assays:1) hydroxylation of the aliphatic group to give M1 2) followed by reduction of the β-keto group, yielding M4; 3) N-demethylation, affording M2; and 4) Reduction of the β-keto group, yielding M3. Subsequent analysis of biological samples from two postmortem cases revealed that urine was the most informative matrix for detecting 3-CMC and its metabolites. The M3 metabolite, was identified as the third abundant metabolite in human liver microsome but was identified as the predominant metabolite in human postmortem samples. Identifying these key metabolites is crucial for improving the accuracy of forensic investigations and extending the detection window beyond the parent compound.

Identification and Characterization of Unrecognized Compounds including Novel Psychoactive Substances and Fentanyl Analogs in Individuals Undergoing Substance Use Disorder Treatment: A Comprehensive Analysis

Identification and Characterization of Unrecognized Compounds including Novel Psychoactive Substances and Fentanyl Analogs in Individuals Undergoing Substance Use Disorder Treatment: A Comprehensive Analysis