Psychotropic Research Articles

Analysis of crude wastewater from two treatment plants in South Wales for 35 new psychoactive substances and cocaine, and cannabis

This study investigates the presence of new psychoactive substances (NPS) and their metabolites in two wastewater treatment plants (WWTPs) situated in South Wales, UK (WWTP-1 and WWTP-2). Analysis was conducted for 35 NPS and metabolites, along with the inclusion of benzoylecgonine (main cocaine metabolite) and cannabis, the most detected illicit substances. Benzoylecgonine was identified as the predominant substance in both WWTPs. Epidemiological calculations revealed the average population consumption of cocaine to be 3.88 mg/d/1000 inhabitants around WWTP-1 and 1.97 mg/d/1000 inhabitants for WWTP-2. The removal efficiency of benzoylecgonine across both WWTPs was observed at an average of 73%. Subsequent qualitative analyses on randomly selected wastewater samples detected medicinal compounds including buprenorphine, methadone, and codeine in both WWTPs. An additional experiment employing enzymatic hydrolysis revealed the presence of morphine, an increased presence of codeine, and 11-Nor-9-Carboxy-THC (THC-COOH) post-hydrolysis. These findings underscore the significant presence of illicit substances and medicinal compounds in wastewater systems with the absence of NPS within the South Wales area, highlighting the necessity for enhanced monitoring and treatment strategies to address public health and environmental concerns.

Does the Use of Psychoactive Substances Reveal Underlying Trauma or Common Mental Health Problems?

The paper evaluates the prevalence of psychoactive substance use in a non-clinical sample of university students and examines its relation to childhood traumatic experiences and common mental health problems. An anonymous online survey was conducted between September 2022 and May 2023 in two major universities in Bulgaria using opportunity sampling. The study has a cross-sectional, observational, and retrospective design, using self-rating scales for depression, anxiety, alexithymia, empathy, quality of life, and lifetime history of substance use. One hundred and forty-six university students completed the survey, with a mean age of 23 years (SD=2), 66% females. Ninety-eight percent of the participants have used caffeine, 90% alcohol, 62% tobacco, 50% cannabis, 26% sedatives, 19% amphetamines, 12% inhalants, 8% hallucinogens, 4% opiates, and 9% other/unknown substances. The mean number of psychoactive substances used within a lifetime is 4 (SD=2). Forty-two (29%) participants have a history of use of multiple (≥ 5) types of psychoactive substances. Statistically significant differences from the rest of the sample include lower empathy (p=.016), higher scores on the childhood trauma scale (p=.001), and a higher percentage of dissociative symptoms (47.6%, p=.012). The binary logistic regression model revealed that higher scores on the childhood trauma scale (p=.003) and lower empathy (p=.004) are statistically significant predictors of multiple substance use. In conclusion, the lifetime use of multiple psychoactive substances in non-clinical settings is related to underlying childhood traumatic experiences and lower empathy.

Наркотики в армии: постановка вопроса и попытка переосмысления данной проблемы в мировом масштабе. Часть I

The purpose of the study is to study the determinants (social, moral, behavioral, psychophysiological, purely pathological, etc.) that can motivate military personnel to consume illegal psychoactive substances. An additional goal is the desire to give an objective assessment of the attempts of Western politicians to create a “universal soldier”, and in fact, a kamikaze of the 21st century (“suicide bomber-drug addict”). Research methods: the theoretical and methodological basis of the work is a set of philosophical, criminological, socio-psychological, medical-biological and political science approaches through which the problem of drug addiction in the military environment is studied. The criminological concept of causality and the interdisciplinary approach to the study of drug crime were most widely used in the process of writing this article. Conclusions: despite the fact that military personnel are an organic part of society, drug addiction in the army should be considered as a rather specific social phenomenon. Drug consumption in the military environment (at the micro level) shows an upward trend only in cases where the psychological and pedagogical support of personnel is not carried out professionally enough, and the discipline and microclimate in the team “leave much to be desired.” In general (already at the macro level), the determination of drug use by military personnel is determined by the influence of social, socio-economic, political, cultural (subcultural), psychological (including ethnopsychological) and medical and biological factors. The problems of drug addiction among personnel are more relevant for NATO countries than for Russia (which over many centuries has developed its own, unique approach to educating defenders of the Fatherland). The experiments of Western specialists on “mind control” of military personnel using all kinds of drugs (stimulants) and neurochips deserve close attention. Such activities (directed to harm people) should be recognized as inhumane and illegal. Scientific and practical significance of the study: The scientific novelty and theoretical significance of the research results lies in the fact that it provides a clinical and psychological interpretation of the aggressive and violent behavior of military personnel who abuse psychotropic substances and narcotic drugs (using the example of personnel of the armies of foreign states). The practical significance of this article lies in the fact that the conclusions and recommendations formulated in it can contribute to the development of measures to optimize educational and psychological-pedagogical work with military personnel of the Russian army, for the early identification of persons both distributing prohibited psychoactive substances among colleagues and regularly using them.

Некоторые правовые и организационные основы проведения оперативно-разыскного мероприятия «оперативное внедрение» при противодействии незаконному обороту наркотиков

Purpose: based on the analysis of the legal and organizational foundations of the operational investigative event "operational implementation", to reveal the essential feature of operational implementation; to show the importance of compliance with the conditions established by law for its implementation and to reveal some legal mechanisms for recognizing drug trafficking as legitimate during operational implementation in order to combat drug trafficking. Research methods: comparative legal, dogmatic, analysis of judicial practice, description. Conclusions: it is substantiated that the main essential feature of operational implementation is the permission to commit, in cases provided for by law, by the person being introduced as part of a drug community or in a personal capacity, acts in order to complete a task that objectively (formally) fall under the signs of acts provided for by a Special part of the Criminal Code of the Russian Federation. An obligatory sign of the legality of operational implementation, the conduct of which is objectively associated with a violation of a criminal law prohibition, is a resolution approved by the head of the body carrying out operational investigative activities. Scientific and practical significance: the possibility of using as a legal basis the recognition of acts committed by an embedded person as part of a drug community or in a personal capacity in order to complete a task, the provisions of legislation on necessary defense, on narcotic drugs and psychotropic substances, on the status of military personnel, on service in internal affairs bodies and on service in the penitentiary the system, as well as active repentance.

New psychoactive substances - 96 cases of deaths related to their use based on the material originating from forensic toxicological practice

Among the emerging investigative fields, forensic medicine and toxicology lead to analyzing fatalities in medico-legal expert opinion formulating. While discussing the problem, the authors have selected 96 fatal cases from their expert practice including the period from 2010 to 2023, in which deaths were connected with taking new psychoactive substances (NPS’s) belonging to various chemical categories, mainly synthetic cathinones (SC), synthetic cannabinoids (SCan) and non-medical synthetic opioids (NSO). In the investigated cases, toxicological analysis revealed 37 NPS’s and their 9 metabolites. The cases involved the use of SC’s (64 cases - 67 %), Scan’s, including their metabolites (10 cases - 10 %) and NSO’s, including their metabolites (6 cases - 6 %). The remaining cases involved the simultaneous use of NSO with SC and/or SCan, including their metabolites (8 cases - 8 %), or SC with SCan (5 cases - 5 %). In three cases (3 %), compounds belonging to other groups were taken. In twenty-five cases, more than one NPS was found. Moreover, in twenty-seven cases, ethyl alcohol was also detected at the concentration range of 0.6–3.6 ‰. The concentration of xenobiotics determined in blood represented extensive ranges of concentration. The victims were at the age of 16–58 years of life. The group included eleven women (11 %). Generally, the deaths related to NPS’s were predominantly of an accidental character (81 %), while the manner of death in sixteen cases (17 %) was suicide, including hanging (5 cases), jumping from a great height (3 cases), self-injury and exsanguination (1 case), as well as acute drug intoxication (6 cases) and intoxication with central nervous system hypoxia after an hanging (1 case). Among the analyzed cases there were two victims of homicide (2 %), in one of which the perpetrator being under the influence of the mixture of the synthetic opioid U-47700 and synthetic cannabinoid AB-FUBINACA. In twenty-eight cases, medications used in psychiatry were found, which suggested that the victims were struggling with mental problems before death. As it was implied by the available information, more than 36 % of the victims had mental problems.

Psychedelic and dissociative agents in psychiatry: challenges in the treatment

With the discovery of the antidepressive effects of ketamine and the increasing withdrawal of the pharmaceutical industry from the development of new psychotropic drugs, the psychiatric research into the clinical application of hallucinogens in psychiatry has literally blossomed in the last two decades. Promising results for various treatment approaches with psychedelic agents, such lysergic acid diethylamide (LSD) and psilocybin, and dissociative agents, such as ketamine and esketamine, have raised great hopes among researchers, clinicians and patients in recent years, so that there was already talk of a new era in psychiatry. As one of the first of these substances, in December 2019 intranasal esketamine was approved in the USA and the EU for the treatment of treatment-resistant depression and Switzerland followed in 2020. Recently, psilocybin was approved in Australia, Canada and Switzerland for compassionate use in exceptional cases for the treatment of depression, while large approval studies with various psychedelic agents are currently ongoing worldwide. The medical application of psychedelic agents and ketamine/esketamine is considered to be safe; however, as with all new forms of treatment it is of crucial importance that, in addition to the hopes, the specific challenges of these new treatment approaches must also be carefully considered and assessed. Excessive expectations and an insufficient risk-benefit estimation are detrimental to the patients and the reputation of the treating physician. Although a possible paradigm shift in the care of mental health is already being discussed, this review article consciously concentrates on the possible risks of treatment and the methodological weaknesses of the studies carried out so far.

The role of mental illness and neurodevelopmental conditions in human papillomavirus vaccination uptake within the Swedish school-based vaccination programme: a population-based cohort study

Despite documented mental illness-related disparities in cervical cancer screening and incidence, insufficient data exist on differences in cervical cancer prevention strategies, such as human papillomavirus (HPV) vaccination. We aimed to investigate the association of mental illness and neurodevelopmental conditions among girls and their parents with uptake of HPV vaccination in Sweden. This population-based cohort study was based on the Swedish school-based HPV vaccination programme, which offers the first vaccine dose to girls aged 10-13 years, with a second dose offered within 12 months. We identified all girls born between Jan 1, 2002, and March 1, 2004, using the Swedish Total Population Register-ie, those eligible for two vaccine doses in the vaccination programme from its initiation in autumn 2012, to March, 2019. Nationwide Swedish register data (National Patient Register, Prescribed Drug Register, HPV Vaccination Register, National Vaccination Register, Total Population Register, Multi-Generation Register, Longitudinal Integrated Database for Health Insurance and Labour Market Studies, Education Register, National Cervical Screening Registry, and Cancer Register) were used to define individual and parental mental health conditions, including mental illness and neurodevelopmental conditions (defined by a clinical diagnosis and prescribed psychotropic medication use), HPV vaccine uptake (first and second dose), and sociodemographic and clinical characteristics. The two outcomes were uptake of the first HPV vaccine dose by the girl's 14th birthday and uptake of the second dose by the 15th birthday in relation to individual and parental mental health conditions, calculated using multivariable Poisson regression models. 115 104 girls were included in the study population. 2211 girls (1·9%) had a specialist diagnosis of any mental health condition. Uptake of the first HPV vaccine dose was 80·7% (92 912 of 115 104) and was lower among girls with versus without any mental health condition (adjusted relative risk 0·89 [95% CI 0·87-0·91]). The diagnosis of autism (0·79 [0·75-0·85]) or intellectual disability (0·78 [0·73-0·83]) were most strongly associated with lower HPV vaccine uptake. Vaccine uptake was also lower among girls with versus those without prescribed use of psychotropic medication (0·93 [0·92-0·95]), with the strongest association observed for antipsychotics (0·68 [0·56-0·82]). Uptake of the second dose was 95·0% (88 308 of 92 912), with no strong associations between uptake and mental health conditions in girls or their parents. Our findings suggest disparities in cervical cancer prevention among girls with mental health conditions, and call for further research to ensure equitable protection. Swedish Cancer Society.

Interventions to reduce harms related to drug use among people who experience incarceration: systematic review and meta-analysis

Mortality, suicide, self-harm, and substance use are elevated among people who are incarcerated. There is a wide range of heterogeneous interventions aimed at reducing these harms in this population. Previous reviews have focused on specific interventions or limited their findings to drug use and recidivism and have not explored interventions delivered after release from prison. Our aim is to examine the effect of interventions delivered to people who use drugs during incarceration or after release from incarceration, on a wide range of outcomes. In this systematic review and meta-analysis, we searched Embase, MEDLINE, and PsycINFO databases up until Sept 12, 2023 for studies published from Jan 1, 1980 onwards. All studies evaluating the effectiveness of any intervention on drug use, recidivism outcomes, sexual or injecting risk behaviours, or mortality among people who use psychoactive drugs and who were currently or recently incarcerated were included. Studies without a comparator or measuring only alcohol use were excluded. Data extracted from each study included demographic characteristics, interventions, and comparisons. Pooled odds ratios and risk ratios were calculated using random-effects meta-analyses. We identified 126 eligible studies (47 randomised controlled trials and 79 observational studies) encompassing 18 interventions; receiving opioid-agonist treatment (OAT) in prison reduced the risk of death in prison (one study; hazard ratio 0·25; 95% CI 0·13-0·48), whereas receiving OAT in the first 4 weeks following release reduced risk of death in the community (two studies; relative risk 0·24; 95% CI 0·15-0·37). Therapeutic community interventions reduced re-arrest at 6-12 months (six studies; odds ratio [OR] 0·72; 95% CI 0·55-0·95) and reincarceration at 24 months (two studies; OR 0·66; 95% CI 0·48-0·96). There was scarce evidence that OAT and syringe service provision are effective in reducing injecting risk behaviours and needle and syringe sharing. There are effective interventions to reduce mortality and recidivism for people who use drugs who have been incarcerated. Nonetheless, there are also substantial gaps in the research examining the effect of interventions on risk behaviours and mortality during incarceration and a need for randomised designs examining outcomes for people who use drugs after release. Australian National Health and Medical Research Council.

Ensiling conditions and changes of cannabinoid concentration in industrial hemp.

Hemp (Cannabis sativa L.) is an important source of fibre and seed oil and protein. By-products of industrial hemp fibre production, like hemp seeds and cakes, can be used as feed for all animal species as fat and protein source and the whole hemp plant (including stalk and leaves) might be a suitable fibre source for ruminants. However, a previous feeding experiment with leaf-flower-seed hemp silage, made from an industrial hemp variety, demonstrated detrimental effects on cow health parameters and a significant transfer of several cannabinoids, including the psychoactive tetrahydrocannabinol (∆9-THC), into cow's milk, posing a potential risk to the safety of consumers. Based on those observations, the present study tested the hypothesis that anaerobic fermentation, as during ensiling, increases the content of ∆9-THC in hemp. Therefore, silages of whole plants from the industrial hemp Cannabis sativa L. var. Ivory were prepared in a multifactorial design, with the four treatments 1) untreated control (CON), 2) addition of 10 mL per kg fresh weight homofermentative lactobacilli at 105 cfu/mL (LBAC), 3) addition of 10 mL per kg fresh weight homofermentative lactobacilli at 105 cfu/mL plus 30 g molasses (LBACmol) and 4) addition of propionic acid (10 mL/kg fresh weight) (PRO). Ultra high performance liquid chromatography coupled with tandem mass spectrometry with electrospray ionisation (UHPLC-MS/MS) was performed for analysis of cannabinoids in fresh hemp material and after 10 and 90 days of ensiling. The study revealed that ensiling decreased all acid forms of analysed cannabinoids in hemp at about 40-65% of the initial values after 90 days of storage, with the exception of cannabinolic acid (CBNA), and CBGA, the acidic form of cannabigerol (CBG). This decrease in most acidic forms was accompanied by an increase of the corresponding non-acidic forms of all cannabinoids, including the psychoactive ∆9-THC. Thus, although ensiling decreases the total cannabinoid content, psychoactive compounds like ∆9-THC can increase, enhancing the risk for animal health and a transfer of these substances into animal derived products.

Rapid mitragynine quantification and fingerprinting of products from Mitragyna speciosa Korth. leaf (Kratom) using high-performance thin-layer chromatography.

Kratom (leaves from Mitragyna speciosa Korth.; Rubiaceae) is a herbal medicine known for its analgesic properties and psychoactive effects. Kratom in Thailand is currently legal; however, it is prohibited in some countries and considered a narcotic plant. Our aim was to establish a reliable, simple, and rapid method for quantifying mitragynine in Kratom leaves and related products through a combination of high-performance thin-layer chromatography (HPTLC) and densitometry. A densitometric HPTLC method was developed and validated in terms of specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, and robustness. The fingerprints of kratom leaves, Mitragyna spp., and related products were constructed. For HPTLC, samples were applied to silica gel 60 F254 plates, and the mobile phase comprised n-hexane, ethyl acetate, and triethylamine (1:1:0.15, v/v/v). Densitometric detection was carried out under ultraviolet light at a wavelength of 226 nm. The validated method exhibited a range of 14.31-143.10 μg/mL, yielding a correlation coefficient of 0.9993. Spiked recovery rates were within a range of 98.3%-100.9%, and the LOD and LOQ were 3.80 and 11.53 μg/mL, respectively. Kratom samples were analyzed with the developed method, and the correlation coefficient was 0.9641, compared to the high-performance liquid chromatography-diode-array detection (HPLC-DAD) method. The HPTLC fingerprints displayed a distinctive pattern, facilitating discrimination among different plant parts and Mitragyna spp. The established method offers the advantages of simplicity, ease of use, and speed of analysis, serving as a practical alternative for mitragynine quantification in kratom leaf and its related products.

Identifying and Exploring Jean Watson's Theory of Human Caring in Nursing Approaches for Patients with Psychoactive Substance Dependence in Medical and Surgical Acute Wards.

Patients with substance use disorders may view healthcare professionals as capable of supporting them through their suffering and experience. Although numerous studies have focused on the roles, approaches, and attitudes of healthcare professionals, there is a lack of information on the nursing perspective. This study aims to explore the experiences and nursing approaches towards patients with psychoactive substance dependence admitted to an Italian acute hospital ward. A qualitative phenomenological study was conducted. Data were collected using semi-structured face-to-face interviews. The interviews were transcribed, read thoroughly, and analysed. Fifteen nurses were interviewed. Six main themes were extracted: (1) origin context, (2) participants' personal thoughts, (3) type of approach provided, (4) school education received on the topic, (5) effectiveness of rehabilitative therapy, and (6) methods that can improve nursing care. The findings suggest that most respondents experience stigma and discrimination when providing care to these patients. In response to the results obtained, models have been suggested, such as Jean Watson's Human Caring Theory, which shows how practising a holistic approach based on empathy and active listening can improve the relationship between nurses and patients. Furthermore, to eliminate stereotypes, it would be appropriate to act on the university education of nurses. This study was not registered.

Accelerated solvent extraction of apomorphine from Nymphaea caerulea (Blue Water Lily) products: A proof‐of‐concept Green extraction for plant materials

AbstractNymphaea caerulea (Blue water lily) is an esthetically pleasing aquatic plant which is widely located across India and Africa. The blue water lily contains an alkaloid called apomorphine which is said to be a sedative, and a nonselective dopamine agonist and is now available in the local and online market in the form of powders and oils for various applications such as sleeping aid, anxiety reliever and sexual performance enhancer. These properties are abused by the consumption of Nymphaea caerulea to achieve a state of “high” which has led the categorization of the same as a novel psychoactive substance. In this paper, a rapid mass spectral analysis was performed for the preliminary screening of commercially available blue water lily products using the Waters Radian as soon as possible instrument, followed by the high performance liquid chromatography‐photo diode array method development and validation of the samples for the qualitative and quantitative analysis of apomorphine. Accelerated solvent extraction as a green alternative to the conventional soxhlet extraction was used in the extraction of the plant material. The method was finally screened for its greenness using the Complex green analytical procedure index method. The method was validated with a linearity of 0.9973; limit of detection and limit of quantitation of 0.02 and 0.18 µg/mL, respectively. The method was able to detect and quantitate apomorphine in two samples from the commercially available natural products of Nymphaea caerulea.

Resting-state electroencephalogram in drug-free subjects with at-risk mental states who later developed psychosis: a low-resolution electromagnetic tomography analysis.

Several studies have reported on the resting-state electroencephalogram (EEG) power in patients with schizophrenia, with a decrease in α (especially α2) and an increase in δ and β1 power compared with healthy control; however, reports on at-risk mental states (ARMS) are few. In this study, we measured the resting-state EEG power in ARMS, and investigated its features and the relationship between the power of the frequency bands and their diagnostic outcomes. Patients with ARMS who were not on any psychotropic medication and met the Comprehensive Assessment of At-Risk Mental State criteria were included. Patients who developed psychotic disorders were labeled as the ARMS-P group, while patients with ARMS who were followed up prospectively for more than 2 years and did not develop psychotic disorders were classified as the ARMS-NP group. EEGs were measured in the resting state, and frequencies were analyzed using standardized low-resolution brain electromagnetic tomography (sLORETA). Seven bands (δ, θ, α1, α2, β1-3) underwent analysis. The sLORETA values (current source density [CSD]) were compared between the ARMS-P and ARMS-NP groups. Clinical symptoms were assessed at the time of EEG measurements using the Positive and Negative Syndrome Scale (PANSS). Of the 39 patients included (25 males, 14 females, 18.8 ± 4.5 years old), eight developed psychotic disorders (ARMS-P). The ARMS-P group exhibited significantly higher CSD in the β1 power within areas of the left middle frontal gyrus (MFG) compared with the ARMS-NP group (best match: X = -35, Y = 25, Z = 50 [MNI coordinates], Area 8, CSD = 2.33, p < 0.05). There was a significant positive correlation between the β1/α ratio of the CSD at left MFG and the Somatic concern score measured by the PANSS. Increased β1 power was observed in the resting EEG before the onset of psychosis and correlated with a symptom. This suggests that resting EEG power may be a useful marker for predicting future conversion to psychosis and clinical symptoms in patients with ARMS.

High-Dose Propranolol for Severe and Chronic Aggression in Autism Spectrum Disorder: A Pilot, Double-Blind, Placebo-Controlled, Randomized Crossover Study.

Despite the use of behavioral interventions and psychotropic medications, many individuals with autism spectrum disorder (ASD) who engage in severe aggression remain refractory to conventional treatment. Propranolol, a beta-blocker, has accumulated much anecdotal evidence as a promising option. However, well-designed studies are rare, and the apprehension about cardiovascular side effects from large doses continues to exist. The aims of this study were (1) to demonstrate the feasibility of treating aggression with high-dose propranolol using telehealth study visits and (2) to document cardiac safety. This study utilized a randomized, double-blind, placebo-controlled, crossover design. Dosing was titrated up in a flexible but stepwise fashion until therapeutic response was obtained or up to 200 mg tid. Following washout, those who were assigned propranolol were crossed over to placebo and vice versa. Six participants between the ages 12-19 participated. The primary outcome measures were the final Clinical Global Impression Improvement Scale (CGI-I) and the Aberrant Behavior Checklist-Community Irritability (ABC-C/I) scores at 200 mg tid. The CGI-I indicated a 50% reduction in symptoms in the propranolol phase, while the ABC-I indicated a 37% reduction in comparison to placebo. The effect sizes ( r ) for the CGI-I and the ABC-C/I were large, -0.74 and -0.64, respectively. The average blood pressure was 122/68 during the placebo phase and 109/72 during the propranolol phase. All Holter monitor exams were unremarkable. These results suggest that propranolol is an effective option in decreasing aggression in individuals with ASD. As this was a small study, a larger clinical trial is needed.

Substance use and driver fatality in Norway: An expanded case-control study.

Using alcohol or psychoactive drugs before driving a motor vehicle may increase the risk of crash involvement, injury, and death. This is better documented for alcohol than for drugs. The aim of this study was to expand a previous case-control study on substance use and driver fatality by doubling the number of cases and controls, and hence improve the statistical power and enable the analysis of combined substance use. We collected data on alcohol and drug use from all 1197 drivers of cars and vans who were fatally injured in road traffic crashes in Norway between 2005 and 2020 ('cases') by analyzing blood samples or reviewing other information on substance use. We also collected data on alcohol and drug use among 17,219 drivers in random road traffic ('controls') by analyzing oral fluid samples. Substance use was converted to dichotomous variables (no use/use). We used unconditional logistic regression to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of driver fatality for mutually exclusive substance groups, adjusted for sex, age, geographic region, urban centrality class, and time interval of the week. Compared to no substance use, the aOR (95% CI) for driver fatality was for alcohol 91 (61-137), stimulants (primarily amphetamines) aOR 22 (9-56), benzodiazepines and z-hypnotics (BZDs) aOR 4.0 (2.7-5.9), tetrahydrocannabinol (THC) aOR 3.4 (1.7-6.7), and opioids aOR 1.4 (0.4-4.9). The aOR for any polysubstance use was 168 (96-297). The combinations of BZDs with stimulants or THC were associated with markedly higher aORs for driver fatality than the use of single substance groups. Alcohol and polysubstance use are the most important predictors of fatal injury, followed by stimulants.

Quantitative analysis of selected alkaloids of Mitragyna speciosa using 1H quantitative nuclear magnetic resonance spectroscopy.

Mitragyna speciosa is a perennial plant native to Asia, well known for its psychoactive properties. Its major alkaloid mitragynine is known to have sedative and euphoric effects. Hence, the plant has been a subject of abuse, leading to addiction, necessitating efficient analytical methods to detect its psychoactive constituents. However, current chromatography-based methods for detecting the alkaloids are time consuming and costly. Quantitative nuclear magnetic resonance (qNMR) spectroscopy emerges as a promising alternative due to its nondestructive nature, structural insights, and short analysis time. Hence, a rapid and precise qNMR method was developed to quantify selected major psychoactive alkaloids in various parts of M.speciosa. Mitragynine, specioliatine, and speciogynine were quantified in relation to the integral value of the -OCH3 groups of the alkaloids and the internal standard 1,4-dinitrobenzene. The precision and reproducibility of the method gave a relative standard deviation (RSD) of 2%, demonstrating the reliability of the method. In addition, the method showed excellent specificity, sensitivity, high linearity range (R2 = 0.999), and limits of detection (LOD) and quantification (LOQ) values. The analysis revealed that the red-veined M.speciosa leaves contained higher levels of mitragynine (32.34 mg/g), specioliatine (16.84 mg/g) and speciogynine (7.69 mg/g) compared to the green-veined leaves, stem bark, or fruits.

Development of a diagnostic variable number tandem repeat marker and dual TaqMan genotyping assay to distinguish Lophophora species.

The Lophophora genus of the Cactaceae family includes Lophophora diffusa and Lophophora williamsii, which has traditionally been used as a natural analgesic; however, its use is now under strict regulation worldwide as it contains mescaline, a unique psychotropic agent. Recently, non-medical and illegal distribution and abuse of L. williamsii have increased worldwide; thus, effective species identification methods are urgently needed. Here, we identified a new variable number tandem repeat (VNTR) marker in the trnL intron region to identify and characterize species in forensic analyses. The VNTR marker has a unique structure of tandem repeats, each with 13 nucleotides; one repeat unit was found in L. williamsii and two in L. diffusa. Phylogenetic and length polymorphism analyses confirmed that this novel VNTR marker could distinguish between Lophophora species. Furthermore, our newly developed TaqMan genotyping assay utilizes two probes; the color and position of dots on the discrimination plot differ according to the tandem repeat count within the VNTR marker. The limits of detection of the assay were 0.000063ng (LW-VNTR probe-1) and 0.000066ng (LW-VNTR probe-2), indicating high sensitivity. Moreover, when crime scene samples of 16 presumed L. williamsii species were analyzed, the results coincided with those of gas chromatography-mass spectrometry, confirming the applicability of our marker for Lophophora species identification. Thus, the tandem repeats within the trnL intron region can be exploited as a VNTR marker to identify L. williamsii and L. diffusa. Our dual TaqMan genotyping assay based on a novel marker demonstrates potential for forensic applications.

Feature-Based Molecular Network for New Psychoactive Substance Identification: The Case of Synthetic Cannabinoids in a Seized e-Liquid and Biological Samples.

The comprehensive detection of new psychoactive substances, including synthetic cannabinoids along with their associated metabolites in biological samples, remains an analytical challenge. To detect these chemicals, untargeted approaches using appropriate bioinformatic tools such as molecular networks are useful, albeit it necessitates as a prerequisite the identification of a node of interest within the cluster. To illustrate it, we reported in this study the identification of synthetic cannabinoids and some of their metabolites in seized e-liquid, urine, and hair collected from an 18-year-old poisoned patient hospitalized for neuropsychiatric disorders. A comprehensive analysis of the seized e-liquid was performed using gas chromatography coupled with electron ionization mass spectrometry, 1H NMR, and liquid chromatography coupled with high resolution tandem mass spectrometry combined with data processing based on molecular network strategy. It allowed researchers to detect in the e-liquid known synthetic cannabinoids including MDMB-4en-PINACA, EDMB-4en-PINACA, MMB-4en-PINACA, and MDMB-5F-PICA. Compounds corresponding to transesterification of MDMB-4en-PINACA with pentenol, glycerol, and propylene glycol were also identified. Regarding the urine sample of the patient, metabolites of MDMB-4en-PINACA were detected, including MDMB-4en-PINACA butanoic acid, dihydroxylated MDMB-4en-PINACA butanoic acid, and glucurono-conjugated MDMB-4en-PINACA butanoic acid. Hair analysis of the patient allowed the detection of MDMB-4en-PINACA and MDMB-5F-PICA in the two investigated hair segments. This untargeted analysis of seized materials and biological samples demonstrates the utility of the molecular network strategy in identifying closely related compounds and metabolites of synthetic cannabinoids. It also emphasizes the need for developing strategies to anchor molecular networks, especially for new psychoactive substances.

High-performance liquid chromatography coupled to Orbitrap mass spectrometry for screening of common new psychoactive substances and other drugs in biological samples.

The complexity of the drug market and the constant updating of drugs have been challenging issues for drug regulatory authorities. With the emergence of new psychoactive substances (NPS) and the nonmedical use of prescription drugs, forensic and toxicology laboratories have had to adopt new drug screening methods and advanced instrumentation. Using high-performance liquid chromatography coupled with Orbitrap mass spectrometry, we developed a screening method for common NPS and other drugs. Two milliliters of mixed solvent of n-hexane and ethyl acetate (1:1, v:v) were added to 500 μL of blood or urine sample for liquid-liquid extraction, and methanol extraction was used for hair samples. The developed method was applied to 3897 samples (including 332 blood samples, 885 urine samples, and 2680 hair samples) taken from drug addicts in a province of China during 2019-2021. For urine and blood samples, the limits of detection (LODs) ranged from 1.68 pg/mL to 10.7 ng/mL. For hair samples, the LODs ranged from 3.30 × 10-5 to 4.21 × 10-3 ng/mg. The matrix effects of urine, blood, and hair samples were in the range of 47.6%-121%, 39.8%-139%, and 6.35%-118%, respectively. And the intra-day precision was 3.5%-6.0% and the inter-day precision was 4.18%-9.90%. Analysis of the actual samples showed an overall positive detection rate of 58.9%, with 5.32% of the samples indicating the use of multiple drugs.

Associations Between Mental Disorders in Donors and Matched Recipients of Hematopoietic Stem Cell Transplants: A Population-Based Cohort Study

BackgroundImmunological mechanisms have been implicated in the development of mental disorders, and interestingly, case reports have suggested that hematopoietic stem cell transplantation (HSCT) can both transmit and cure psychotic disorders by replacing immune progenitor cells. MethodsUsing Danish registers, we followed patients who received HSCT from donors with a psychiatric diagnosis or psychotropic medication use. We assessed risk of incident mental disorders or psychotropic medication use compared with recipients with unaffected donors. We identified 464 donor-recipient pairs (51.3% male recipients). All donor-recipient pairs were related. ResultsReceiving HSCT from a donor with a psychiatric history was not significantly associated with incident psychiatric diagnoses (hazard rate ratio [HRR] 2.79, 95% CI, 0.83–9.39; p = .098) or incident use of psychotropics (HRR 1.43, 95% CI, 0.91–2.24; p = .118). Subgroup analysis showed an increased risk of antipsychotic use, which remained significant after adjusting for confounders (HRR 4.73, 95% CI, 1.26–17.78; p = .021); however, this was based on a small number of cases. For depression and antidepressant use, data were available to perform a meta-analysis of our and one additional study, which showed no significant difference (HRR 1.24, 95%, CI 0.66–2.35). ConclusionsReceiving HSCT from a donor with a psychiatric history did not affect risk of mental disorders. An increased risk of antipsychotic use was observed only in subgroup analyses; however, the exploratory nature of the study, the limited sample size, and family relationship between donors and recipients do not allow for causal conclusions, and external replication studies are warranted.