Appearance of hexahydrocannabinols as recreational drugs and implications for cannabis drug testing - focus on HHC, HHC-P, HHC-O and HHC-H.

This study investigated the effects of hexahydrocannabinol (HHC) and other unclassified cannabinoids, which were recently introduced to the recreational drug market, on cannabis drug testing in urine and oral fluid samples. After the appearance of HHC in Sweden in 2022, the number of posts about HHC on an online drug discussion forum increased significantly in the spring of 2023, indicating increased interest and use. In parallel, the frequency of false positive screening tests for tetrahydrocannabinol (THC) in oral fluid, and for its carboxy metabolite (THC-COOH) in urine, rose from <2% to >10%. This suggested that HHC cross-reacted with the antibodies in the immunoassay screening, which was confirmed in spiking experiments with HHC, HHC-COOH, HHC acetate (HHC-O), hexahydrocannabihexol (HHC-H), hexahydrocannabiphorol (HHC-P), and THC-P. When HHC and HHC-P were classified as narcotics in Sweden on 11 July 2023, they disappeared from the online and street shops market and were replaced by other unregulated variants (e.g. HHC-O and THC-P). In urine samples submitted for routine cannabis drug testing, HHC-COOH concentrations up to 205 (mean 60, median 27) µg/L were observed. To conclude, cannabis drug testing cannot rely on results from immunoassay screening, as it cannot distinguish between different tetra- and hexahydrocannabinols, some being classified but others unregulated. The current trend for increased use of unregulated cannabinols will likely increase the proportion of positive cannabis screening results that need to be confirmed with mass spectrometric methods. However, the observed cross-reactivity also means a way to pick up use of new cannabinoids that otherwise risk going undetected.

Alternative routine for reporting chiral amphetamine test results in assessment of attention-deficit/hyperactivity disorder medication: experiences from 2013 to 2023.

This study evaluated an alternative routine for reporting urinary chiral amphetamine results in assessment of attention-deficit/hyperactivity disorder (ADHD) treatment with amphetamine medications and for detecting side-use of illicit racemic amphetamine. Currently in Sweden, only enantiopure d-amphetamine-based ADHD medications (lisdexamphetamine dimesylate and dexamphetamine sulfate) are approved. It is therefore unsuitable to express the chiral result as the l/d-ratio, as before, because l-amphetamine should not be present provided treatment compliance. A new routine for LC-MS/MS chiral amphetamine testing was therefore introduced in 2020, whereby the relative proportion (%) of l-amphetamine and the total amphetamine and creatinine concentrations are reported. Evaluation of the new routine on 24,354 results from 2013 to 2023 revealed that it was useful to distinguish ADHD medication adherence from illicit drug use as the source for a positive test. The l-amphetamine proportion also reflected the enantiomeric content of the medications used. Overall, most results confirmed adherence to ADHD medication, as the l-amphetamine percentage was <1% in 76% of samples (2023) which is the recommended cutoff with enantiopure d-amphetamine medications. However, in all years, illicit drug use was indicated (>40% l-amphetamine) in 8.3%-14.5% of cases. In conclusion, this study demonstrated the clinical value and utility of a new routine for reporting urinary chiral amphetamine results to differentiate adherence to ADHD medication from illicit drug use. Unlike the l/d-amphetamine ratio, it considers differences in total amphetamine concentration and urine dilution, factors that can affect the interpretation.

The alcohol biomarker phosphatidylethanol (PEth) - test performance and experiences from routine analysis and external quality assessment.

Phosphatidylethanol (PEth) are membrane molecules formed from phosphatidylcholine and ethanol through transphosphatidylation catalyzed by phospholipase D. Measurement of the main PEth form 16:0/18:1 is used as a specific and sensitive alcohol biomarker, since its formation requires ethanol, it accumulates in the blood upon repeated ethanol exposure, and it is only slowly eliminated during abstinence. PEth formation correlates with alcohol intake at the population level, albeit with considerable inter-individual variation as for the half-life during withdrawal. Over the past decade, the use of PEth has increased significantly and the applications have broadened. In Sweden, routine decision limits and the interpretation of test results for PEth were harmonized in 2013, using < 0.05 µmol/L (∼35 µg/L) as the recommended lower reporting limit and values > 0.30 µmol/L (∼210 µg/L) to indicate regular high alcohol intake. Routine test results show a large variation with about half being < 0.05 µmol/L and some even exceeding 10 µmol/L. In 2013, an external quality assessment (EQA) scheme for PEth 16:0/18:1 measurement in whole blood was also started (Equalis, Uppsala, Sweden), presently involving 56 laboratories from 13 countries. The agreement of PEth results between the laboratories has gradually improved to a CV < 15%. The current clinical and scientific information suggests that PEth values below the lower reporting limit (typically ∼0.03-0.05 µmol/L, or ∼20-35 µg/L) indicates sobriety or only low or occasional alcohol consumption, while regular high alcohol intake at levels corresponding to harmful drinking is required in most cases to reach PEth values > 0.30 µmol/L.

[The alcohol biomarker phosphatidylethanol (PEth) - recommendations for use and interpretation of test results]. / Alkoholmarkören fosfatidyletanol (PEth) ­ så bedöms testresultatet.

Phosphatidylethanol (PEth) is a group of phospholipids that are formed in blood from the corresponding phosphatidylcholines in the presence of ethanol by action of phospholipase D. Since PEth formation requires ethanol, it is used as a specific alcohol biomarker. Use of PEth measurement in whole blood as an alcohol biomarker has risen sharply in recent years, increasing the demand for knowledge about how it should be utilized and test results evaluated. In Sweden, the use since 2013 of harmonized LC-MS analytical methods targeting the main form PEth 16:0/18:1, and confirmation of comparable test results between laboratories in the Equalis (Uppsala, Sweden) external quality control program (CV <15%), has enabled use of common decision limits. A measurable PEth result confirms ethanol exposure, but due to interindividual variations in test response to a given dose and elimination half-life during abstinence, it is not possible to indicate the exact amount or time of alcohol intake. However, a PEth level above 0.30 µmol/L (~210 µg/L) is a strong indicator of harmful drinking, while a test result below 0.05 µmol/L (~35 µg/L) excludes harmful drinking but does not confirm complete abstinence. According to current test statistics from two Swedish hospital laboratories, each performing > 60 000 routine PEth measurements annually, ~45-50% of the values were < 0.05 µmol/L, ~23-24% between 0.05-0.30 µmol/L, ~16-19% between 0.30-1.0 µmol/L, and ~10-12% > 1.0 µmol/L. Some PEth results even exceeded 10 µmol/L.

Urine Drug Tests Indicate Higher Prevalence of Combined Alcohol and Cocaine Use Compared to Alcohol Together with Cannabis or Amphetamine-A Possible Link to Cocaethylene.

AIM: This retrospective study examined the prevalence of combined ethanol and cocaine use, which produces an enhanced psychoactive effect through formation of the active metabolite cocaethylene, compared to combined use of ethanol and two other common recreational drugs, cannabis and amphetamine, based on urine drug test results. METHODS: The study was based on >30,000 consecutive samples from routine urine drug testing in 2020, and 2627 samples from acute poisonings in the STRIDA project (2010-2016), in Sweden. Drug testing for ethanol (i.e. ethyl glucuronide and ethyl sulfate), cocaine (benzoylecgonine), cannabis (Δ9-THC-COOH) and amphetamine was done by routine immunoassay screening and LC-MS/MS confirmatory methods. Seven samples testing positive for cocaine and ethyl glucuronide were also analyzed for cocaethylene by LC-HRMS/MS. RESULTS: Among routine samples for which testing of ethanol and cocaine had been requested, 43% tested positive for both substances, compared with 24% for ethanol and cannabis and 19% for ethanol and amphetamine (P < 0.0001). Among the drug-related intoxications, 60% of cocaine-positive samples were also positive for ethanol, compared to 40% for cannabis and ethanol and 37% for amphetamine and ethanol. Cocaethylene was detected (range 1.3-150 µg/L) in all randomly selected samples testing positive for ethanol and cocaine use. CONCLUSIONS: These results, which were based on objective laboratory measures, indicated that combined ethanol and cocaine exposure was more prevalent than expected from drug use statistics. This may relate both to the common use of these substances in party and nightlife settings, and the amplified and prolonged pharmacological effect by the active metabolite cocaethylene.

Drug testing for mitragynine and kratom: Analytical challenges and medico-legal considerations.

Mitragyna speciosa, known as kratom, is a tropical tree native to Southeast Asia that has long been used to increase energy and in traditional medicine. Kratom leaves contain several indole alkaloids including mitragynine, mitraciliatine, speciogynine, and speciociliatine, which have the same molecular formula and connectivity, but different spatial arrangements (i.e., diastereomers). A routine liquid-chromatographic-high-resolution mass-spectrometric (LC-HRMS) multi-analyte method for addictive and herbal drugs in urine did not separate mitragynine from speciogynine and speciociliatine. Separation and individual measurement of the four diastereomers was possible with an improved LC method. All diastereomers were detected in 29 patient urine samples who tested positive for mitragynine with the routine method, albeit at variable absolute amounts and relative proportions. The presence of all diastereomers rather than individual substances indicated that they originated from the intake of kratom (i.e., plant material). Speciociliatine dominated in most samples (66%), whereas mitragynine and mitraciliatine were the highest in 17% each. A kratom product (powdered plant material) marketed in Sweden contained all diastereomers with mitragynine showing the highest level. In Sweden, there are signs of an increasing use of kratom in society, based on the results from drug testing, the number of poisons center consultations on intoxications, and customs seizure statistics. Because there may be health risks associated with kratom use, including dependence, serious adverse reactions, and death, analytical methods should be able to identify and quantify all diastereomers. In Sweden, this is important from a legal perspective, as only mitragynine is classified, whereas the other three diastereomers, and kratom (plant material), are not.

[Improved access to test results for toxic alcohols can save lives]. / Bättre tillgång till provsvar för toxiska alkoholer kan rädda liv.

Acute poisoning involving toxic alcohols other than ethanol is not uncommon. Poisonings from drinking isopropanol are rarely life threatening, whereas methanol and ethylene glycol without prompt treatment cause severe metabolic acidosis, organ damage, and death, mainly due to toxic metabolites. Rapid identification of the type of alcohol responsible for the poisoning requires access to 24/7 toxicological service. The analysis of alcohols is usually done with gas chromatographic (GC) methods, which are not always available at smaller or medium-sized hospitals. As a complement to GC methods, reliable enzymatic oxidation procedures are now available for the analysis of ethanol, methanol, and ethylene glycol. The present study showed good agreement (r2 = 0.996) between the results of methanol analysis with a new enzymatic method (Catachem Inc.) and with GC over the clinically relevant concentration range (1-50 mmol/l). Moreover, high concentrations of ethanol (up to 80 mmol/l), ethylene glycol (to 40 mmol/l), isopropanol (to 100 mmol/l) or acetone (to 20 mmol/l) did not interfere with the analytical results for methanol. Toxicological analysis of the two most dangerous alcohols (methanol and ethylene glycol) can now be done with rapid and specific enzymatic methods, which makes it possible to diagnose and treat poisoned patients at smaller regional hospitals.

Minor effect of patient education for alcohol cessation intervention on outcomes after acute fracture surgery: a randomized trial of 70 patients.

BACKGROUND AND PURPOSE: High alcohol intake is associated with increased risk of postoperative complications. Alcohol cessation intervention is recommended prior to elective surgery. We investigated short- and long-term effects of perioperative intensive alcohol intervention in relation to acute ankle fracture surgery. PATIENTS AND METHODS: 70 patients requiring ankle fracture surgery and consuming ≥ 21 drinks weekly (1 drink = 12 g ethanol) were randomized to a manual-based 6-week intensive standardized alcohol cessation program, the Gold Standard Program (GSP-A), or treatment as usual (TAU), on the day of operation. GSP-A included 5 personal meetings, patient education, and motivational and pharmacological support (alcohol withdrawal prophylaxis, B vitamins, and low-dose disulfiram). Complications requiring treatment were measured after 6 weeks and 1 year. Alcohol intake was validated by biomarkers. Quality of life (QoL) was measured by the SF-36. Hospital costs were obtained from the National Hospital Costs Register. RESULTS: Postoperatively, complete alcohol cessation was higher in the GSP-A than in the TAU group (18/35 vs. 5/35, number needed to treat = 3, p ≤ 0.001), but not lowrisk consumption in the long term (10/35 vs. 7/33, p = 0.5). Number of complications in the short and long term (12/35 vs. 14/33, 16/35 vs. 18/33), the SF-36 score, or hospital costs in the short and long term (€6,294 vs. €8,024, €10,662 vs. €12,198), were similar between the groups. INTERPRETATION: Despite an effect on alcohol cessation and a positive tendency as regards the other outcomes, the postoperative complications, QoL, and costs were similar. Better perioperative strategies for acute surgical patients with high alcohol intake therefore need to be developed.

Analytical and medico-legal problems linked to the presence of delta-8-tetrahydrocannabinol (delta-8-THC): Results from urine drug testing in Sweden.

During routine urine drug testing for cannabis use targeting delta-9-tetrahydrocannabinol carboxylic acid (delta-9-THC-COOH) at the Karolinska University Laboratory in Sweden, an unknown interfering peak was observed in the liquid-chromatographic-tandem mass-spectrometric (LC-MS/MS) confirmative analysis. The peak showed the same exact mass and most abundant fragments as delta-9-THC-COOH but a slightly shorter retention time, thereby not fulfilling all requirements for a positive identification. The analytical results suggested that it was a similar compound, and with access to reference material, it could be identified as the double bond isomer delta-8-THC-COOH. Delta-8-THC has recently become popular as a recreational drug, although its legality varies and is sometimes unclear. In Sweden, all THC isomers are classified substances. The slight difference in retention times was sufficient to distinguish the THC-COOH isomers in the routine LC-MS/MS method, but another LC method allowed better peak separation and individual quantification. At the Karolinska University Laboratory, delta-8-THC-COOH was first observed in April 2020, and the highest incidence was noted in June 2020 when it was present in 5.3% of all THC-COOH-positive samples. The incidence later decreased to today only occasional findings. Large differences in the relative presence of the isomers in the urine samples indicated different origin, for example, synthetically produced pure delta-8-THC, or mixtures of both THC isomers formed during combustion of cannabidiol (CBD). In conclusion, the appearance of delta-8-THC and other isomers on the recreational drug market risks causing analytical and medico-legal problems, due to confusion with delta-9-THC.

[Drug use and drug trends in Sweden 2010-2020 - results from urine drug testing in the workplace]. / Ökad droganvändning i arbetslivet ­ vart tjugonde urinprov positivt.

Workplace alcohol and drug testing is increasingly used at employment, for regular checks, and in case of accident, incident, or suspicion of drug exposure. The test results provide valuable objective information about drug use in the society. At the Karolinska University Laboratory (Stockholm, Sweden), the number of samples from drug testing in the workplace has quadrupled in the last decade. Almost all urine samples are tested for amphetamines (amphetamine, methamphetamine and MDMA), benzodiazepines (prescribed substances), cannabis, cocaine and opiates, and some also for alcohol (i.e. the metabolites ethyl glucuronide and ethyl sulfate) and drugs such as tramadol and oxycodone. The proportion of samples that test positive for one or more drugs has increased steadily in recent years to over 5%. Substances commonly detected are, in order of appearance, cannabis, amphetamines (amphetamine and MDMA), benzodiazepines, opiates (mainly codeine and only few due to heroin use), and cocaine. Other common substances are alcohol, tramadol, and oxycodone, but these are only tested for in a limited, and possibly selected, proportion of samples. After an MRO has reviewed the positive laboratory results, about 30% of cases are excluded mainly due to legal prescription as medicine. In 2020, the proportion of positive test results decreased, possibly due to reduced access to illicit drugs during the corona pandemic. In summary, results from drug testing in the workplace indicate that illicit use of drugs shows an increasing trend in Sweden.

Measurement of the alcohol biomarker phosphatidylethanol (PEth) in dried blood spots and venous blood-importance of inhibition of post-sampling formation from ethanol.

Phosphatidylethanol (PEth) is a group of phospholipids formed in cell membranes following alcohol consumption by action of the enzyme phospholipase D (PLD). PEth measurement in whole blood samples is established as a specific alcohol biomarker with clinical and forensic applications. However, in blood specimens containing ethanol, formation of PEth may continue after sampling leading to falsely elevated concentrations. This study evaluated the use of dried blood spot (DBS) and microsampling specimens to avoid post-sampling formation of PEth. Filter paper cards and three commercial devices for volumetric microsampling of finger-pricked blood were assessed, using PEth-negative and PEth-positive whole blood fortified with 2 g/L ethanol. PEth (16:0/18:1) was measured by LC-MS/MS. Post-sampling formation of PEth occurred in wet blood and in the volumetric devices, but not filter paper cards, when stored at room temperature for 48 h. Addition of an inhibitor of PLD, sodium metavanadate (NaVO3), eliminated post-sampling formation during storage and drying. In conclusion, the present study confirmed previous observations that PEth can be formed in blood samples after collection, if the specimen contains ethanol. The results further demonstrated that post-sampling formation of PEth from ethanol also occurred with commercial devices for volumetric dried blood microsampling. In order for a PEth result not to be questioned, it is recommended to use a PLD inhibitor, whether venous blood is collected in a vacutainer tube or finger-pricked blood is obtained using devices for dried blood microsampling.

[Harmonized measurement and reporting of chiral amphetamine in the follow-up of ADHD treatment]. / Ny testrutin för kiralt amfetamin minskar risken att missa sidobruk.

Amphetamine is an illicit central nervous system stimulant that is also used for the treatment of attention-decific/hyperacticity disorder (ADHD). Amphetamine exits as two enantiomers, dex(tro)amphetamine (D-amphetamine; also called S-amphetamine) and levoamphetamine (L-amphetamine; or R-amphetamine), of which mainly the former is used as medication for ADHD, whereas illicit street amphetamine is a racemic mixture. To monitor patient compliance with treatment and detect (side) intake of racemic amphetamine, chiral analysis in samples of urine, oral fluid, or blood is used and has traditionally involved reporting of the L/D ratio. Today in Sweden, however, only ADHD medications based on D-amphetamine (lisdexamphetamine lysate and dexamphetamine sulfate) are approved, so no L-amphetamine should be found in the samples provided treatment compliance. It is therefore advisable to instead report the total amphetamine concentration and the relative amount of L-amphetamine. A proposed L-amphetamine cutoff for compliance with ADHD medication is less than 1%, or as low as possible in samples with low amphetamine concentration, as there may be traces of L-amphetamine in the approved pharmaceutical products. Since (supervised) urine sampling is sometimes considered sensitive to ADHD patients without any underlying drug problem, using oral fluid testing is a less invasive alternative and would facilitate sampling for both patients and healthcare professionals. However, an analytical disadvantage is that the amphetamine concentration is generally lower in oral fluid than in urine.

Performance of PEth Compared With Other Alcohol Biomarkers in Subjects Presenting For Occupational and Pre-Employment Medical Examination.

AIMS: To compare the performance of short- and long-term alcohol biomarkers for the evaluation of alcohol drinking in employment-related health controls. METHODS: The 519 blood samples originated from 509 patients (80% men) presenting at occupational health units and medical centers at employment agencies for the evaluation of risky drinking. The laboratory investigation comprised the measurement of phosphatidylethanol (PEth 16:0/18:1), carbohydrate-deficient transferrin (CDT; % disialotransferrin), gamma-glutamyl transferase (GGT), mean corpuscular volume (MCV), ethanol and ethyl glucuronide (EtG). RESULTS: Many samples tested positive for acute (57%) and chronic (69%) alcohol biomarkers. PEth was the single most positive biomarker (64%; cut-off 0.05 µmol/l or 35 µg/l) and the only positive chronic biomarker in 100 cases. The highest PEth concentrations were seen in samples positive for all chronic biomarkers, followed by those also being CDT positive (cut-off 2.0%). All 126 CDT-positive samples were positive for PEth using the lower reporting limit (≥0.05 µmol/l) and for 114 cases (90%) also using the higher limit (≥0.30 µmol/l or 210 µg/l). In the CDT-positive cases, the PEth median concentration was 1.71 µmol/l, compared with 0.45 µmol/l for the CDT-negative cases (P < 0.0001). PEth and CDT values were correlated significantly (r = 0.63, P < 0.0001). Among the EtG-positive cases (≥1.0 ng/ml), 95% were also PEth positive, and all ethanol-positive cases (≥0.10 g/l) were also PEth positive. CONCLUSIONS: For optimal detection of drinking habits, using a combination of short- and long-term alcohol biomarkers provided best information. PEth was the single most positive alcohol biomarker, whereas GGT and MCV offered little additional value over PEth and CDT.

[Simplified laboratory analysis of ethylene glycol allows improved management of poisoning cases]. / Förenklad analys av etylenglykol kan ge snabbare diagnos vid förgiftningsfall.

Toxicological analysis constitutes an important part of the acute treatment of poisonings. Timely laboratory results are essential for the patient to be diagnosed and treated appropriately, but also to exclude poisoning and avoid unnecessary overtreatment. Ingestion of ethylene glycol may cause acute kidney injury and, in severe cases, death, unless treated early with an antidote (ethanol infusion or fomepizole) to inhibit the formation of toxic metabolites. Diagnosis of poisoning is based on detection of ethylene glycol in plasma or serum, but a challenge remains that acute toxicology service is only available at major hospital laboratories using gas chromatography. A simple enzymatic method for the quantification of ethylene glycol (Catachem) was evaluated as a complement to currently used methods and demonstrated to provide fast and accurate measurement in a clinically relevant concentration range (1-80 mmol/l) with a minimal risk of analytical interference. The method is suitable for use on several automated clinical chemistry analyzers. Use of the enzymatic method can improve availability of acute toxicology service for ethylene glycol and contribute to better healthcare from both a patient and health resource perspective.

Drug trends and harm related to new psychoactive substances (NPS) in Sweden from 2010 to 2016: Experiences from the STRIDA project.

BACKGROUND: In the past decade, hundreds of new psychoactive substances (NPS) have been introduced as unclassified alternatives to the illicit drugs. The NPS represent a growing health concern by causing adverse effects and deaths but are usually undetectable by conventional drug tests. This report summarizes results and experiences from analytically confirmed drug-related acute intoxications in emergency departments (ED) and intensive care units (ICU) enrolled in the Swedish STRIDA project on NPS in 2010-2016. METHODS AND FINDINGS: ED/ICU intoxications suspected to involve NPS were enrolled in the project, after initial contact with the Poisons Information Centre (PIC). Serum/plasma and urine samples, and sometimes drug products, were subjected to a comprehensive toxicological investigation, and the PIC retrieved information on associated clinical symptoms and treatment. Between January 2010-February 2016, 2626 cases were enrolled. The patients were aged 8-71 (mean 27, median 24) years and 74% were men. Most biological samples (81%) tested positive for one, or more (70%), psychoactive drugs, including 159 NPS, other novel or uncommon substances, classical recreational and illicit drugs, and prescription medications. When first detected, most NPS or other novel substances (75%) were not banned in Sweden, but they usually disappeared upon classification, which however often took a year or longer. Some NPS were found to be especially harmful and even fatal. CONCLUSIONS: The STRIDA project provided a good overview of the current drug situation in Sweden and demonstrated a widespread use and rapid turnover of many different psychoactive substances. The accomplishment of the project can be attributed to several key factors (close collaboration between the PIC and laboratory to identify suspected poisonings, free analysis, continuous updating of analytical methods, evaluation of adverse effects, and sharing information) that are useful for future activities addressing the NPS problem. The results also illustrated how drug regulations can drive the NPS market.

γ-Hydroxybutyrate does not mediate glucose inhibition of glucagon secretion.

Hypersecretion of glucagon from pancreatic α-cells strongly contributes to diabetic hyperglycemia. Moreover, failure of α-cells to increase glucagon secretion in response to falling blood glucose concentrations compromises the defense against hypoglycemia, a common complication in diabetes therapy. However, the mechanisms underlying glucose regulation of glucagon secretion are poorly understood and likely involve both α-cell-intrinsic and intraislet paracrine signaling. Among paracrine factors, glucose-stimulated release of the GABA metabolite γ-hydroxybutyric acid (GHB) from pancreatic ß-cells might mediate glucose suppression of glucagon release via GHB receptors on α-cells. However, the direct effects of GHB on α-cell signaling and glucagon release have not been investigated. Here, we found that GHB (4-10 µm) lacked effects on the cytoplasmic concentrations of the secretion-regulating messengers Ca2+ and cAMP in mouse α-cells. Glucagon secretion from perifused mouse islets was also unaffected by GHB at both 1 and 7 mm glucose. The GHB receptor agonist 3-chloropropanoic acid and the antagonist NCS-382 had no effects on glucagon secretion and did not affect stimulation of secretion induced by a drop in glucose from 7 to 1 mm Inhibition of endogenous GHB formation with the GABA transaminase inhibitor vigabatrin also failed to influence glucagon secretion at 1 mm glucose and did not prevent the suppressive effect of 7 mm glucose. In human islets, GHB tended to stimulate glucagon secretion at 1 mm glucose, an effect mimicked by 3-chloropropanoic acid. We conclude that GHB does not mediate the inhibitory effect of glucose on glucagon secretion.

[Analytical investigation of a suspected case of drug-facilitated crime]. / Säker och känslig analysmetodik viktig vid misstänkta fall av ofrivillig drogning.

Sometimes it is suspected that people have been involuntary exposed to drugs, usually by spiked drinks. A young woman was transported to an emergency department by ambulance. Her clinical symptoms (decreased consciousness, mydriasis, confusion, hallucinations and urine retention) indicated anticholinergic syndrome that was effectively treated with the antidote physostigmine. A urine sample tested negative for common narcotic drugs and alcohol, but an extended toxicological analysis of the urine revealed the presence of the alkaloid scopolamine. Scopolamine occurs naturally in Solanaceae plants and is used in some medications. The woman reported that the symptoms had appeared soon after she was offered tea by a male acquaintance. The analytical results along with the woman's story indicated that she had been subjected to a drug-facilitated crime. The results further demonstrate that in suspected cases of involuntary drug exposure, testing should cover a wide panel of relevant drugs, otherwise poisoning may be missed.

Dose-Response Characteristics of the Alcohol Biomarker Phosphatidylethanol (PEth)-A Study of Outpatients in Treatment for Reduced Drinking.

AIM: Measurement of whole-blood phosphatidylethanol (PEth) offers high sensitivity and specificity as alcohol biomarker. A remaining issue of importance for the routine application is to better establish the relationship between PEth concentration and amount and duration of drinking. METHODS: The study included 36 subjects (32-83 years) voluntarily attending outpatient treatment for reduced drinking. At ~ 3- to 4-week intervals, they provided a diary on their daily alcohol intake and gave blood samples for measurement of PEth and carbohydrate-deficient transferrin (CDT). Whole-blood PEth 16:0/18:1 was measured by liquid chromatography-tandem mass spectrometry and serum CDT (%disialotransferrin) by high-performance liquid chromatography. RESULTS: At start, the self-reported past 2-week alcohol intake ranged 0-1260 (median 330) g ethanol, the PEth 16:0/18:1 concentration ranged 0.05-1.20 (median 0.23) µmol/L, and the CDT value ranged 0.7-13.0% (median 1.5%). At the final sampling after 5-20 (median 12) weeks, neither reported alcohol intake nor PEth and CDT levels differed significantly from the starting values. The PEth concentration showed best association with past 2-week drinking, followed by for intake in the next last week. The changes in PEth concentration vs past 2-week alcohol intake between two successive tests revealed that an increased ethanol intake by ~ 20 g/day elevated the PEth concentration by on average ~ 0.10 µmol/L, and vice versa for decreased drinking. CONCLUSIONS: The PEth concentration correlated well with past weeks alcohol intake, albeit with a large inter-individual scatter. This indicates that it is possible to make only approximate estimates of drinking based on a single PEth value, implying risk for misclassification between moderate and heavy drinking.