[An overview of natural entheogens]. / Un aperçu des enthéogènes naturels.

Entheogens are a group of little-known psychoactive substances which consumption is nevertheless frequently mentioned in outpatient care and which can have harmful effects. This raises the question of appropriate management of their effects, as well as the treatment of any overdose. In this article, we focus on five of these substances, which are rarely described in the medical literature. At present, few studies exist on their long-term effects on health, and this type of niche consumption does not seem problematic from the authorities' point of view. Rapid screening is unavailable because it has not been developed, and the management of overdoses is often limited to non-specific supportive treatment with benzodiazepines.

Les enthéogènes sont un groupe de substances psychoactives méconnues mais dont la consommation apparaît toutefois lors de consultations ambulatoires et qui peuvent engendrer des effets néfastes. Se pose alors la question de la prise en charge adaptée concernant leurs effets mais également le traitement d'un éventuel surdosage. Dans cet article, le focus a été mis sur cinq de ces substances peu décrites dans la littérature médicale. Actuellement, peu d'études existent sur leurs effets à long terme sur la santé et ce type de consommation de niche ne semble pas problématique du point de vue des autorités. Le dépistage rapide n'est pas disponible car pas développé et la prise en charge des surdosages se limite souvent à un traitement de soutien non spécifique par benzodiazépines.

Randomly controlled drivers using minimally invasive sampling: assessment of drug prevalence in Western Switzerland over two time periods.

BACKGROUND: According to the World Health Organization, road traffic injuries lead to 1.3 million deaths each year and represent the leading cause of death for young adults under 30 years old. The use of psychoactive substances, including alcohol, drugs and pharmaceuticals, is a well-known risk factor for road traffic injuries. Our study aims to assess the prevalence of substances consumed by drivers in western Switzerland. Such studies are pivotal to improving prevention and developing public awareness campaigns. METHODS: To assess the prevalence of psychoactive substances among drivers, roadside controls were performed in collaboration with local police, using their classical sampling procedures to detect drivers under the influence of drugs or alcohol over two time periods (P1: 2006-2008, P2: 2017-2020). When impaired driving was not suspected by the police, minimally invasive sampling strategies (i.e., oral fluids during P1 and dried blood spots during P2) were performed on volunteer drivers after a road safety survey. A posteriori analyses and statistical interpretation were then performed. RESULTS: Among the 1605 drivers included in the study, 1048 volunteers provided an oral fluid sample, while 299 provided a dried blood spot sample. The percentage of drivers testing positive for at least one substance that can impact driving abilities was stable over time, with a rate of 10.5% positivity measured over both periods. Considering the different categories of substances, a slight variation was observed between both periods, with 7.6 and 6.3% of pharmaceuticals and 3.6 and 4.9% of illicit drugs for P1 and P2, respectively. Regarding the consumption of illicit drugs, the highest percentage of positivity was measured in biological fluids of drivers under the age of 35, during nights and week-ends, periods which are considered particularly prone to fatal accidents for this age group. Disturbingly, the road safety survey highlighted that drivers' perception of the risk of getting positively controlled while driving after drug consumption is low (3.3 on a 1-to-10 scale, N = 299). CONCLUSION: The number of positive cases measured in voluntary drivers who passed the preliminary police check demonstrates the importance of systematic biofluid sampling strategies regarding driving under the influence of psychoactive substances. Although the number of fatal road accidents globally has decreased over time, the results of this study reveal the need for both better prevention and deterrent processes that could potentially reduce the risk of fatal road accidents associated with drug consumption.

Gonadotropin axis and semen quality in young Swiss men after cannabis consumption: Effect of chronicity and modulation by cannabidiol.

BACKGROUND: While cannabis is the most widely used recreational drug in the world, the effects of phytocannabinoids on semen parameters and reproductive hormones remain controversial. Cannabinoid receptors are activated by these compounds at each level of the hypothalamus-pituitary-gonadotropic axis. OBJECTIVES: To assess the impact of the consumption of Δ-9-tetrahydrocannabinol and cannabidiol on semen parameters, as well as on male reproductive hormone and endocannabinoid levels, in a cohort of young Swiss men. MATERIALS AND METHODS: The individuals in a Swiss cohort were divided according to their cannabis consumption. In the cannabis user group, we determined the delay between the last intake of cannabis and sample collection, the chronicity of use and the presence of cannabidiol in the consumed product. Urinary Δ-9-tetrahydrocannabinol metabolites were quantified via gas chromatography-mass spectrometry. Blood phytocannabinoids, endocannabinoids and male steroids were determined via liquid chromatography-mass spectrometry/mass spectrometry, and other hypothalamus-pituitary-gonadotropic axis hormones were determined via immunoassays. Semen parameters such as sperm concentration and motility were recorded using computer-assisted sperm analysis. RESULTS: Anandamide, N-palmitoyl ethanolamide, androgens, estradiol and sex hormone binding globulin levels were all higher in cannabis users, particularly in chronic, recent and cannabidiol-positive consumers. Gonadotropin levels were not significantly different in these user subpopulations, whereas prolactin and albumin concentrations were lower. In addition, cannabis users had a more basic semen pH and a higher percentage of spermatozoa with progressive motility. However, the two latter observations seem to be related to a shorter period of sexual abstinence in this group rather than to the use of cannabis. CONCLUSIONS: Because both cannabidiol and Δ-9-tetrahydrocannabinol are frequently used by men of reproductive age, it is highly relevant to elucidate the potential effects they may have on human reproductive health. This study demonstrates that the mode of cannabis consumption must be considered when evaluating the effect of cannabis on semen quality.

Sensitivity and specificity of NT-proBNP to detect heart failure at post mortem examination.

NT-proBNP, a marker of cardiac failure, has been shown to be stable in post mortem samples. The aim of this study was to assess the accuracy of NT-proBNP to detect heart failure in the forensic setting. One hundred sixty-eight consecutive autopsies were included in the study. NT-proBNP blood concentrations were measured using a chemiluminescent immunoassay kit. Cardiac failure was assessed by three independent forensic experts using macro- and microscopic findings complemented by information about the circumstances of body discovery and the known medical story. Area under the receiving operator curve was of 65.4% (CI 95%, from 57.1 to 73.7). Using a standard cut-off value of >220 pg/mL for NT-proBNP blood concentration, heart failure was detected with a sensitivity of 50.7% and a specificity of 72.6%. NT-proBNP vitreous humor values were well correlated to the ones measured in blood (r (2) = 0.658). Our results showed that NT-proBNP can corroborate the pathological findings in cases of natural death related to heart failure, thus, keeping its diagnostic properties passing from the ante mortem to the post mortem setting. Therefore, biologically inactive polypeptides like NT-proBNP seem to be stable enough to be used in forensic medicine as markers of cardiac failure, taking into account the sensitivity and specificity of the test.

Suspicion of driving under the influence of alcohol or drugs: Cross sectional analysis of drug prevalence in the context of the Swiss legislation.

Driving under the influence of alcohol and drugs (DUID) is a major field of study to improve road safety. In Switzerland, during controls whether or not they follow an accident, the police can request toxicological analysis targeted either on alcohol only (ALC cases), or on drugs and alcohol (DUID cases). To evaluate both the drugs consumption on the road and whether or not these requests are well correlated with toxicological results, we built a database recording 4003 offenders (3443 males, 550 females) over a two-year period (2018-2019) in Western Switzerland. ALC case samples were then analyzed to target other substances than ethanol. We found one or more psychoactive drugs in 89% of DUID cases and alcohol alone was found in 56% of ALC cases. In ALC cases, alcohol alone was found in 72% of non-accident cases and in 52% of accident cases. This highlights an influence of accident context, inducing a too high suspicion of alcohol after accidents, and therefore an underestimation of the prevalence of other drugs. The most frequently detected drugs in DUID cases were cannabinoids (58%), ethanol (30%), cocaine (21%), benzodiazepines (11%), amphetamines (7%), opiates (6%), and antidepressants (5%). For the ALC cases, the drugs found were ethanol (84%), cannabinoids (13%), benzodiazepines (9%), antidepressants (6%), opiates (5%), cocaine (4%), methadone (3%), and amphetamines (1%). Prescription drugs, such as benzodiazepines, were common in accidents (22%) but rare in non-accidents DUID cases (5%). Thus, these drugs highly impact driving skills while being hard to suspect. This is of first concern as prescription drugs are largely found in poly-drug consumption, especially in combination with alcohol in accident cases. This emphasizes the emerging issue of prescription drugs and should motivate a strategy of prevention focused on the noxious effect of combining alcohol and prescription drugs on driving skills.

Semen endocannabinoids are correlated to sperm quality in a cohort of 200 young Swiss men.

BACKGROUND: A role for endocannabinoids in the male and female reproductive systems has been highlighted during the recent decades. Some of these compounds bind the cannabinoid CB1 receptor, which is abundantly expressed in the central nervous system but also present in the reproductive system, while others act as 'entourage compounds' modulators. OBJECTIVES: The present study aimed at evaluating the relationship between sperm quality and endocannabinoid profiles in a cohort of 200 young Swiss men and whether the presence of specific xenobiotics could influence these profiles. MATERIALS AND METHODS: Semen analysis was performed according to WHO guidelines. Endocannabinoid profiles in blood and semen, as well as bisphenol A and S in urine, were determined by LC-MSMS methods. The presence of selected drugs was tested in urine by immunological screening, and urinary tetrahydrocannabinol (THC) metabolites were quantified by GC-MS. RESULTS: Anandamide concentrations in seminal fluid and oleoylethanolamide (OEA) concentrations in blood serum appeared inversely correlated with sperm motility, while semen palmytoylethanolamide (PEA) was positively linked to sperm concentration. Moreover, OEA and PEA in seminal fluid were associated with better sperm morphology. Interestingly, the concentrations of the same endocannabinoids measured in both blood and semen were not correlated, and the presence of THC metabolites in some individuals was linked to lower concentrations of endocannabinoids. CONCLUSIONS: In the context of the general decline of the sperm count observed within the male population, endocannabinoids in semen constitute a class of promising biochemical markers that open new perspectives as a complement for the usual evaluation of semen quality or for the toxicological screening of individuals' exposure to putative endocrine disruptors.

Concentration of drugs in blood of suspected impaired drivers.

Analytical records concerning 440 living drivers suspected of driving under the influence of drug (DUID) were collected and examined during a 2 years period ranging from 2002 to 2003 in canton de Vaud, Valais, Jura and Fribourg (Switzerland). This study included 400 men (91%) and 40 women (9%). The average age of the drivers was 28+/-10 years (minimum 16 and maximum 81). One or more psychoactive drugs were found in 89% of blood samples. Half of cases (223 of 440, 50.7%) involved consumption of mixtures (from 2 to 6) of psychoactive drugs. The most commonly detected drugs in whole blood were cannabinoids (59%), ethanol (46%), benzodiazepines (13%), cocaine (13%), amphetamines (9%), opiates (9%) and methadone (7%). Among these 440 cases, 11-carboxy-THC (THCCOOH) was found in 59% (median 25 ng/ml (1-215 ng/ml)), Delta(9)-tetrahydrocannabinol (THC) in 53% (median 3 ng/ml (1-35 ng/ml)), ethanol in 46% (median 1.19 g/kg (0.14-2.95 g/kg)), benzoylecgonine in 13% (median 250 ng/ml (29-2430 ng/ml)), free morphine in 7% (median 10 ng/ml (1-111 ng/ml)), methadone in 7% (median 110 ng/ml (27-850 ng/ml)), 3,4-methylenedioxymethamphetamine (MDMA) in 6% (median 218 ng/ml (10-2480 ng/ml)), nordiazepam in 5% (median 305 ng/ml (30-1560 ng/ml)), free codeine in 5% (median 5 ng/ml (1-13 ng/ml)), midazolam in 5% (median 44 ng/ml (20-250 ng/ml)), cocaine in 5% (median 50 ng/ml (15-560 ng/ml)), amphetamine in 4% (median 54 ng/ml (10-183 ng/ml)), diazepam in 2% (median 200 ng/ml (80-630 ng/ml)) and oxazepam in 2% (median 230 ng/ml (165-3830 ng/ml)). Other drugs, such as lorazepam, zolpidem, mirtazapine, methaqualone, were found in less than 1% of the cases.

First nationwide study on driving under the influence of drugs in Switzerland.

In Switzerland, a two-tier system based on impairment by any psychoactive substances which affect the capacity to drive safely and zero tolerance for certain illicit drugs came into force on 1 January 2005. According to the new legislation, the offender is sanctioned if Delta(9)-tetrahydrocannabinol THC is >or=1.5ng/ml or amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), cocaine, free morphine are >or=15ng/ml in whole blood (confidence interval+/-30%). For all other psychoactive substances, impairment must be proven in applying the so-called "three pillars expertise". At the same time the legal blood alcohol concentration (BAC) limit for driving was lowered from 0.80 to 0.50g/kg. The purpose of this study was to analyze the prevalence of drugs in the first year after the introduction of the revision of the Swiss Traffic Law in the population of drivers suspected of driving under the influence of drugs (DUID). A database was developed to collect the data from all DUID cases submitted by the police or the Justice to the eight Swiss authorized laboratories between January and December 2005. Data collected were anonymous and included the age, gender, date and time of the event, the type of vehicle, the circumstances, the sampling time and the results of all the performed toxicological analyses. The focus was explicitly on DUID; cases of drivers who were suspected to be under the influence of ethanol only were not considered. The final study population included 4794 DUID offenders (4243 males, 543 females). The mean age of all drivers was 31+/-12 years (range 14-92 years). One or more psychoactive drugs were detected in 89% of all analyzed blood samples. In 11% (N=530) of the samples, neither alcohol nor drugs were present. The most frequently encountered drugs in whole blood were cannabinoids (48% of total number of cases), ethanol (35%), cocaine (25%), opiates (10%), amphetamines (7%), benzodiazepines (6%) and methadone (5%). Other medicinal drugs such as antidepressants and benzodiazepine-like were detected less frequently. Poly-drug use was prevalent but it may be underestimated because the laboratories do not always analyze all drugs in a blood sample. This first Swiss study points out that DUID is a serious problem on the roads in Switzerland. Further investigations will show if this situation has changed in the following years.

Evaluation of postmortem measurement of NT-proBNP as a marker for cardiac function.

Clinical biomarkers of cardiac function could also be monitored postmortem. Among the natriuretic peptides, the aminoterminal portion of pro-brain natriuretic peptide (NT-proBNP) appears to be a more reliable postmortem tool than the BNP, owing to its longer half-life and greater stability. In living persons, NT-proBNP is considered to be a marker of heart failure, and its level rises after cardiac ischemia. The goal of this study was first to evaluate the postmortem stability of NT-proBNP, then to measure the NT-proBNP levels in postmortem cases of heart failure related to coronary ischemia. The goal of this study was also to evaluate the correlations between different specimens collected at autopsy (e.g. blood, serum, vitreous humor and pericardial fluid). The study included 96 cases, which were classified into 4 groups according to the autopsy and histological findings. The NT-proBNP levels were significantly higher in individuals who had suffered from chronic cardiac ischemia, with or without acute coronary events, than in either control cases or those who had suffered from acute thromboembolism or acute rupture of a plaque without chronic cardiac ischemia. The highest levels were registered in individuals who had suffered from acute coronary thromboembolism in association with chronic coronary ischemia. Good correlations in the NT-proBNP levels for the different specimens were observed between samples of femoral blood, serum, and pericardial fluid. Our data indicated that postmortem measurements of NT-proBNP are reliable and compatible with clinical findings.