Anders Helander

Tarmjäsningssyndrom (auto-brewery syndrome) kan teoretiskt producera etanol i mängder som överstiger leverns förstapassagemetabolism. Detta kan i sällsynta fall orsaka symtom på alkoholpåverkan och få rättsliga konsekvenser. Diagnosen baseras på ett glukosbelastningstest, etanolanalys och undersökning av tarmfloran. Behandlingen innefattar kolhydratreducerad kost och antimykotika eller antibiotika.

Phosphatidylethanol (PEth) in whole blood and carbohydrate-deficient transferrin (CDT) in serum are routinely used alcohol biomarkers of repeated high intake and harmful drinking over the preceding weeks to month. The study compared 27,293 paired measurements of PEth (PEth 16:0/18:1) and CDT (%disialotransferrin) from occupational health care testing in Sweden. PEth concentrations ranged R = 0.64, p < 0.0001) but with substantial individual variability. Clinical classification was concordant in most cases, 66% being negative for both and 16% being positive for both at routine cutoffs (PEth >0.30 µmol/L; CDT ≥2.0%). However, PEth alone was positive in 15% and CDT alone in ∼3%. PEth identified 90% of all positive cases (i.e. by PEth and/or CDT) compared with 57% for CDT, while 47% were positive for both. Increasing the PEth cutoff to >0.50 µmol/L reduced positivity to 66%, whereas lowering the CDT cutoff to ≥1.7% increased positivity to 90%. The prevalence of positive test results increased with age. For CDT, men showed higher positivity across all age groups, while PEth scored higher for men only in those aged 64,000 test per biomarker), the monthly average and proportion of positive PEth values correlated with population-level alcohol consumption showing peaks during summer holidays and after Christmas-New Year, whereas no correlation was observed for CDT. In conclusion, differences between PEth and CDT are largely driven by cutoff-dependent classification rather than discordant biomarker behavior.

Methamphetamine is relatively uncommon on the European drug market, but Swedish drug test laboratories repeatedly detect low methamphetamine concentrations in urine samples containing high amphetamine levels, warranting clinical evaluation for suspected polydrug use. Of 12,062 routine samples screened positive for amphetamines, 86% were confirmed positive (≥ 200 μg/L) for amphetamine, 2.1% for methamphetamine, and 4.0% for 3,4‐methylenedioxymethamphetamine (ecstasy) by liquid chromatography–tandem mass spectrometry. Of the 259 methamphetamine‐positive samples, 98% contained amphetamine concentrations above the reporting limit, consistent with the metabolic conversion of methamphetamine to amphetamine in the body. However, in most (69%) of these samples, the methamphetamine concentration was only < 2% of the amphetamine level, suggesting methamphetamine was not the primary drug taken. Chiral analysis of selected samples showed that after use of illicit street amphetamine with a racemic content of the l ‐ and d ‐enantiomers, a similar l/d proportion was observed for methamphetamine. Similarly, in samples from patients receiving d ‐amphetamine‐based ADHD medication, low d ‐methamphetamine levels were detected, even though the pharmaceutical products contained no methamphetamine. This observation, together with the parallel l/d ‐enantiomer distributions, supports amphetamine N ‐methylation as a trace, albeit quantitatively insignificant, metabolic pathway in humans. From both a clinical and forensic perspective, a low urinary methamphetamine concentration of less than a few percent of the amphetamine level therefore does not warrant further clinical evaluation for suspected polydrug use. The present findings further demonstrate that chiral analysis of both amphetamine and methamphetamine is an effective approach for distinguishing between illicit and therapeutic sources in positive screening drug tests for the amphetamines.

Suspicion of proactive drug-facilitated sexual assault (DFSA) where the perpetrator covertly administers psychoactive drugs to the victim has been reported in considerable proportions from sexual assault centers and forensic units all over the world. Substances implicated in DFSA are often referred to as 'date-rape drugs'. This study investigated toxicological findings in cases of suspected proactive DFSA presenting to the Emergency Clinic for Rape Victims in Stockholm, Sweden within 48 h of the assault. Urine samples for toxicological analysis were collected on the first visit to the clinic. During follow-up 10-14 days later, participants provided a control urine sample and reported voluntary intake of alcohol, recreational and prescription drugs in connection with the assault according to a standardized protocol. Urine samples were subjected to extensive toxicological LC-MS/MS analysis that covered common recreational drugs and >100 DFSA-associated substances. 31 out of the 55 women who presented to the clinic after a suspected proactive DFSA during the study period returned for follow-up and completed the study. Almost all women (97%) reported voluntary alcohol intake in connection with the assault, which exceeded 70 g ethanol in half of the cases. Unexpected toxicological findings were made only in five cases (16%), with the most common substance being cocaine. No typical date-rape drug was identified in cases where involuntary intake was considered likely. In conclusion, the greatest risk factor exploited by perpetrators of DFSA appears to be voluntary alcohol intoxication, while toxicological evidence of illicit drugging is rare.

Recent data indicate that the use of controlled substances is increasing in working life, which can negatively affect work environment, performance, and safety. Many employers have an alcohol and drug policy that describes routines for preventive measures and early detection of illicit drug use. This often includes drug tests that provide objective information about recent use, and can be done routinely, randomly, and on suspicion. For some substances, however, a positive drug test may also result from prescription as medicine. Controlled substances that are abused and prescribed include amphetamines (ADHD medication), benzodiazepines and opiates. In a 2023 study of 23,900 urine and oral fluid drug test results from Swedish workplaces, 4.6% tested positive for one or more controlled substances. Most samples were collected in connection with random testing (40%) and new employment (36%), whereas the highest proportions of drug‐positive samples were observed in cases related to accidents or incidents, or on suspicion of drug use. The highest percentage of positive random drug tests was recorded in the construction sector. The most common substances were cannabis (> 40% of cases), amphetamine (> 20%), and cocaine and benzodiazepines (> 10% each). However, many samples containing opiates (71% of cases), amphetamine (63%) and benzodiazepines (44%) were verified by a specialist trained Medical Review Officer (MRO) to be due to medical prescription, while those containing cannabis or cocaine were almost entirely due to illicit drug use. Considering the potentially negative consequences of a positive drug test in working life, an MRO should verify the results before they become final.

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 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.

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 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.

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.

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. 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. 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. 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.