Inter Individual Variation and Factors Regulating the Formation of Phosphatidylethanol.

BACKGROUND: Alcohol use disorders are a major but often unrecognized health problem. Alcohol markers can therefore be of great value for diagnosis, follow-up, and treatment evaluation. Phosphatidylethanol in blood (B-PEth) is an alcohol biomarker with higher clinical sensitivity and specificity than commonly used alcohol markers but has shown a considerable interindividual variation in relation to reported consumption. METHODS: An in vitro system was used to investigate factors, which may affect the formation rate of PEth or which may give rise to interindividual variation in the rate of formation. In this system, isolated erythrocytes from 31 individuals were incubated in the presence of various concentrations of ethanol (EtOH). The concentration of PEth and phosphatidylcholine (PC), the parent molecule of PEth, was determined by chromatographic methods. RESULTS: Time, EtOH, and PC concentration were major factors determining the amount of PEth formed. The interindividual variation in PEth formation rate, calculated at an EtOH concentration of 50 mmol/l, showed a coefficient of variation (CV) from 23 to 31% for the different PEth forms studied (PEth 16:0/18:2, total PEth and PEth 16:0/18:1). The concentration of PC was found to be an important determinant of this variation. The formation rate for PEth 16:0/18:2 was somewhat higher than for PEth 16:0/18:1. The formation of PEth 16:0/18:1 but not PEth 16:0/18:2 showed a positive correlation to the concentration of PEth at baseline (endogenous PEth). Calculation of enzyme kinetics for the reaction resulting in the formation of PEth 16:0/18:1 or PEth 16:0/18:2 showed an apparent Km (Michaelis constant) of approximately 160 to 170 mmol/l. CONCLUSIONS: Interindividual variation in the formation rate of PEth appears to be a significant but relatively modest source of variation in the relation between B-PEth and reported consumption. Correction for interindividual variation in PC concentrations might substantially reduce the interindividual variability in PEth formation and consequently in B-PEth.

Varenicline for treatment of alcohol dependence: a randomized, placebo-controlled trial.

BACKGROUND: Alcohol dependence is a devastating illness affecting a large population, and new pharmacological treatments with good efficacy are greatly needed. One potential candidate is varenicline, a smoking cessation agent with partial agonist action at α4 ß2 nicotinic acetylcholine receptors. METHODS: A total of 160 subjects, 30 to 70 years of age, fulfilling DSM-IV criteria for alcohol dependence without any serious physical or mental disorders, were recruited through advertisement at 3 university clinics in Sweden during March 2009 to January 2011. After a 2-week placebo run-in period, subjects received 2 mg varenicline daily (titrated from 0.5 mg during first week) or placebo for 12 weeks in a double-blind manner. RESULTS: The primary outcome was the proportion of heavy drinking days, measured by self-reported alcohol consumption. Primary and secondary outcomes were calculated as a mean over the 10-week steady-state active treatment period. In the primary outcome analysis, no effect of varenicline over placebo was found (p = 0.73 for the intention to treat [ITT] and 0.92 for per protocol [PP]). Secondary outcome analysis found a significant reduction of specific alcohol marker phosphatidylethanol (PEth) in the blood in the varenicline group compared to placebo (p = 0.02 ITT). Craving (p = 0.048 PP) and Alcohol Use Disorders Identification Test (AUDIT) scores (p = 0.015 ITT) were also reduced in the active treatment group. PEth more strongly correlated with self-reported alcohol consumption than carbohydrate-deficient ttransferrin and γ-glutamyl transferase, and correlation coefficients were higher in the varenicline group than in the placebo group for all markers. CONCLUSIONS: Although the results of the main outcome of this study did not support an effect of varenicline in alcohol-dependent individuals, the secondary analyses of PEth, craving and AUDIT score support an effect of varenicline on alcohol consumption. The disclosure of a treatment effect and the lack of a clear placebo effect when using PEth as outcome variable, together with a nonsymmetric bias associated with self-reported data, strongly argue for using the specific biomarker PEth in studies of treatments of alcohol dependence.

Phosphatidylethanol is superior to carbohydrate-deficient transferrin and γ-glutamyltransferase as an alcohol marker and is a reliable estimate of alcohol consumption level.

BACKGROUND: In clinical practice as well as research situations, it is of great importance to get reliable information about a patient's alcohol consumption. The aim of the study was to investigate the correlation of alcohol biomarkers (phosphatidylethanol [PEth], carbohydrate-deficient transferrin [CDT], γ-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase) to retrospective as well as diary-based alcohol self-reports and to examine whether it is possible to correlate a biomarker result to a more precise level of alcohol consumption. METHODS: One hundred and sixty alcohol-dependent patients were included in a randomized, placebo-controlled clinical trial of pharmacotherapy for alcohol dependence, of which 115 (76 men and 39 women) completed the study. Retrospective alcohol consumption data were collected at baseline, and alcohol diaries were used during the study. Blood samples for determination of alcohol biomarkers were collected on 5 occasions during the study. RESULTS: PEth and CDT showed a better correlation with alcohol consumption documented in the diary (PEth rs = 0.56 and CDT rs = 0.35) than with retrospective consumption data (PEth rs = 0.23 and CDT rs = 0.22). An even higher correlation (rs = 0.63) was seen between the 2 alcohol biomarkers PEth and CDT. At all consumption levels, PEth had the highest sensitivity of all biomarkers studied. CONCLUSIONS: PEth was the biomarker with the best correlation to self-reported alcohol consumption. PEth was superior to CDT owing to its substantially higher sensitivity but also due to its closer correlation to self-report. PEth values can be translated into an approximate level of alcohol consumption and PEth appears to be a more reliable measure of alcohol consumption than self-reports.

Phosphatidylethanol Compared with Other Blood Tests as a Biomarker of Moderate Alcohol Consumption in Healthy Volunteers: A Prospective Randomized Study.

AIM: It is generally agreed that traditional alcohol biomarkers lack in sensitivity to detect hazardous alcohol consumption. The present study was undertaken to evaluate the ability of phosphatidylethanol (PEth) and traditional alcohol markers to detect moderate alcohol consumption and to distinguish between moderate alcohol consumption and abstinence. METHODS: Forty-four subjects, 32 females and 12 males, were included in the study. They were randomized to alcohol abstention or to alcohol consumption. Female participants consumed 150 ml of red wine (equivalent to 16 g of alcohol) per 24 h and the male participants double the amount. The study lasted for 3 months. Blood samples were drawn at the start and at the end of the study period. Blood samples were analysed for PEth, carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), γ-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). RESULTS: ROC curves for the various biochemical markers were plotted in order to assess their ability to discriminate between abstention and moderate daily consumption of alcohol. PEth and CDT were the only markers with AUROCs significantly higher than 0.5, and PEth was detected in all participants randomized to alcohol consumption. CONCLUSION: PEth was the only marker that could detect moderate intake and the present results also indicate that PEth probably can distinguish moderate alcohol consumption from abstinence.

NT-proBNP on Cobas h 232 in point-of-care testing: Performance in the primary health care versus in the hospital laboratory.

BACKGROUND: NT-proBNP may be useful for ruling out heart failure in primary health care. In this study we examined the analytical quality of NT-proBNP in primary health care on the Cobas h 232 point-of-care instrument compared with measurements performed in a hospital laboratory. MATERIALS AND METHODS: Blood samples requested for NT-proBNP were collected in primary health care (n = 95) and in a hospital laboratory (n = 107). NT-proBNP was measured on-site on Cobas h 232 instruments both in primary health care centres and at the hospital laboratory and all samples were also analyzed with a comparison method at the hospital. Precision, trueness, accuracy, and lot-variation were determined at different concentration levels and evaluated according to acceptance criteria. Furthermore user-friendliness was assessed by questionnaires. RESULTS: For Cobas h 232 repeatability CV was 8.5-10.7% in the hospital setting and 5.3-10.0% in the primary health care and within the analytical quality specifications, but higher than with the comparison method (< 4%). NT-proBNP results obtained in primary health care were significantly higher than by the hospital comparison method (bias ranged from 14.3-23.7%), whereas there was no significant bias when Cobas h 232 was used in the hospital setting (bias ranged from - 4.9 to 7.0%). User-friendliness of Cobas h 232 was overall acceptable. CONCLUSION: Cobas h 232 point-of-care instrument for measurement of NT-proBNP performed satisfactorily with regard to precision, user-friendliness, and lot-variation. A decrease in NT-proBNP levels observed in samples transported to a central laboratory needs further attention and investigation.

Is your stress my stress? A standardized, randomized-controlled paradigm to study physiological stress contagion based on direct stress observation.

BACKGROUND & OBJECTIVES: Existing research indicates that not only own stress leads to physiological stress reactions, but also observing stress in others. So far, a standardized paradigm to reliably induce physiological stress contagion based on direct face-to-face stress observation compared to an active placebo-stress observing control condition is lacking. Here, we tested a standardized randomized placebo-controlled experimental paradigm to investigate physiological reactivity to direct stress observation and characterized the stress contagion response of the major endocrine stress systems, including full reactivity kinetics. METHODS: Healthy young male participants were randomly assigned to (1) undergo an adapted version of the Trier Social Stress Test ("TSST participants", n = 20), (2) observe it ("stress observers", n = 36), or (3) observe a corresponding placebo-stress control condition ("placebo-stress observers", n = 30). We repeatedly assessed heart rate, salivary alpha-amylase, salivary cortisol, and salivary aldosterone. RESULTS: Stress observers exhibited greater physiological reactivity to stress observation as compared to placebo-stress observers to placebo-stress observation in heart rate, salivary alpha-amylase, and cortisol (p's ≤ .027), but not in aldosterone. We observed similar reactivity kinetics in TSST participants and stress observers but less pronounced in stress observers. DISCUSSION: Extending previous literature, our findings indicate that independent of secondary effects of the observation setting, direct observation of stress in other individuals induces activation of the hypothalamus-pituitary-adrenal axis and the sympathetic-adrenal-medullary axis. Moreover, the physiological stress contagion response resembles the physiological reactivity to first-hand stress but is less pronounced. Potential implications of physiological stress contagion regarding health, cognition, or behavior, as well as modulating factors need to be further elucidated.

Stress in the collective: Psychophysiological reactivity to an orchestra concert as a collective naturalistic, real-life stressor of psychosocial nature.

BACKGROUND & OBJECTIVES: The investigation of collective stress experiences, including collective stressors and the psychophysiological reactivity of a collective to these stressors, has been widely neglected so far. Here, we examined public non-professional orchestra concerts as collective naturalistic, real-life stressors of psychosocial nature and the resulting psychophysiological reactivity in a collective of non-professional orchestra musicians. METHODS: The members of two non-professional music orchestras (N = 54) were accompanied during a public concert (stress condition) and a rehearsal (control condition). We repeatedly assessed heart rate, salivary cortisol, and excitement levels before, during, and after the concert/rehearsal in addition to the anticipatory cognitive stress appraisal. RESULTS: We observed greater physiological reactivity to the concert compared to the rehearsal (p's ≤.017), with higher increases in heart rate levels in anticipation of and in reaction to the concert and in cortisol levels in reaction to the concert compared to the rehearsal. Moreover, orchestra members reported greater psychological reactivity to the concert than to the rehearsal (p's ≤.024) in terms of higher cognitive stress appraisal in anticipation and increased excitement levels before and during the concert compared to the rehearsal. DISCUSSION: Our findings indicate that orchestra concerts by non-professional musicians constitute collective naturalistic, real-life stressors of psychosocial nature, resulting in significant psychophysiological stress responses with reactivity kinetics differing between the sympathetic-adrenal-medullary axis, the hypothalamic-pituitary-adrenal axis, and the psychological response. Potential implications and modulating factors need to be elucidated in future studies.

Physiological reactivity to acute mental stress in essential hypertension-a systematic review.

Objective: Exaggerated physiological reactions to acute mental stress (AMS) are associated with hypertension (development) and have been proposed to play an important role in mediating the cardiovascular disease risk with hypertension. A variety of studies compared physiological reactivity to AMS between essential hypertensive (HT) and normotensive (NT) individuals. However, a systematic review of studies across stress-reactive physiological systems including intermediate biological risk factors for cardiovascular diseases is lacking. Methods: We conducted a systematic literature search (PubMed) for original articles and short reports, published in English language in peer-reviewed journals in November and December 2022. We targeted studies comparing the reactivity between essential HT and NT to AMS in terms of cognitive tasks, public speaking tasks, or the combination of both, in at least one of the predefined stress-reactive physiological systems. Results: We included a total of 58 publications. The majority of studies investigated physiological reactivity to mental stressors of mild or moderate intensity. Whereas HT seem to exhibit increased reactivity in response to mild or moderate AMS only under certain conditions (i.e., in response to mild mental stressors with specific characteristics, in an early hyperkinetic stage of HT, or with respect to certain stress systems), increased physiological reactivity in HT as compared to NT to AMS of strong intensity was observed across all investigated stress-reactive physiological systems. Conclusion: Overall, this systematic review supports the proposed and expected generalized physiological hyperreactivity to AMS with essential hypertension, in particular to strong mental stress. Moreover, we discuss potential underlying mechanisms and highlight open questions for future research of importance for the comprehensive understanding of the observed hyperreactivity to AMS in essential hypertension.

Alpha-Adrenergic Mechanisms in the Cardiovascular Hyperreactivity to Norepinephrine-Infusion in Essential Hypertension.

Aims: Essential hypertension (EHT) is characterized by cardiovascular hyperreactivity to stress but underlying mechanism are not fully understood. Here, we investigated the role of α-adrenergic receptors (α-AR) in the cardiovascular reactivity to a norepinephrine (NE)-stress reactivity-mimicking NE-infusion in essential hypertensive individuals (HT) as compared to normotensive individuals (NT). Methods: 24 male HT and 24 male NT participated in three experimental trials on three separate days with a 1-min infusion followed by a 15-min infusion. Trials varied in infusion-substances: placebo saline (Sal)-infusions (trial-1:Sal+Sal), NE-infusion without (trial-2:Sal+NE) or with non-selective α-AR blockade by phentolamine (PHE) (trial-3:PHE+NE). NE-infusion dosage (5µg/ml/min) and duration were chosen to mimic duration and physiological effects of NE-release in reaction to established stress induction protocols. We repeatedly measured systolic (SBP) and diastolic blood pressure (DBP) as well as heart rate before, during, and after infusions. Results: SBP and DBP reactivity to the three infusion-trials differed between HT and NT (p's≤.014). HT exhibited greater BP reactivity to NE-infusion alone compared to NT (trial-2-vs-trial-1: p's≤.033). Group differences in DBP reactivity to NE disappeared with prior PHE blockade (trial-3: p=.26), while SBP reactivity differences remained (trial-3: p=.016). Heart rate reactivity to infusion-trials did not differ between HT and NT (p=.73). Conclusion: Our findings suggest a mediating role of α-AR in DBP hyperreactivity to NE-infusion in EHT. However, in SBP hyperreactivity to NE-infusion in EHT, the functioning of α-AR seems impaired suggesting that the SBP hyperreactivity in hypertension is not mediated by α-AR.

Hyperreactivity of Salivary Alpha-Amylase to Acute Psychosocial Stress and Norepinephrine Infusion in Essential Hypertension.

It is unknown whether the observed general physiological hyperreactivity to acute psychosocial stress in essential hypertension also extends to salivary alpha-amylase (sAA), a surrogate sympathetic nervous system marker. Here, we investigated sAA reactivity to acute psychosocial stress in essential hypertensive males (HT) as compared to normotensive controls (NT). To shed light on underlying mechanisms, we moreover tested for sAA reactivity following a standardized norepinephrine (NE) infusion. We hypothesized that both acute psychosocial stress and an NE infusion of similar duration would lead to greater sAA reactivity in HT than in NT. In the stress study, we examined sAA reactivity to 15 min of acute psychosocial stress induced by the Trier Social Stress Test (TSST) in 19 HT and 23 NT up to 40 min after stress. In the infusion study, 20 HT and 22 NT received a standardized NE infusion (5 µg/mL/min) over 15 min mimicking NE release in reaction to acute psychosocial stress. HT exhibited greater sAA reactivity to the TSST as compared to NT (p = 0.049, ηp2 = 0.08, f = 0.29). In reaction to the standardized NE infusion, HT showed higher sAA reactivity as compared to NT (p = 0.033, ηp2 = 1.00, f = 0.33). Our findings suggest stress-induced sAA hyperreactivity in essential hypertension that seems to be at least in part mediated by a higher reactivity to a standardized amount of NE in HT. With respect to clinical implications, sAA stress reactivity may serve as a noninvasive marker indicative of early cardiovascular risk.

Effect of a Smoking and Alcohol Cessation Intervention Initiated Shortly Before Radical Cystectomy-the STOP-OP Study: A Randomised Clinical Trial.

BACKGROUND: Evidence concerning the reduction of postoperative complications due to smoking and alcohol drinking in patients undergoing radical cystectomy is incomplete. OBJECTIVE: To evaluate the efficacy of a 6-wk smoking and/or alcohol cessation intervention, initiated shortly before surgery and continued until 4 wk after, in reducing complications. DESIGN, SETTING, AND PARTICIPANTS: Between 2014 and 2018, we enrolled 104 patients with high-risk bladder cancer who were daily smokers or consuming at least 3 units of alcohol daily in a multicentre randomised clinical trial. INTERVENTION: Patients were randomised to a 6-wk intensive smoking and/or alcohol cessation intervention or treatment as usual. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the number of patients developing any postoperative complication, or death, within 30 d after surgery. The secondary endpoints were successful quitters, health-related quality of life, length of stay, time back to habitual activity, and mortality. An intention-to-treat analysis was applied to evaluate treatment effect. RESULTS AND LIMITATIONS: There were some differences in baseline demographic and lifestyle characteristics. Postoperatively, 64% in the intervention group versus 70% in the control group (risk ratio [RR] 0.91, confidence interval [CI] 0.68-1.21, p = 0.51) developed complications. Significantly fewer patients developed three or more complications after 30 d (RR 0.39; CI 0.18-0.84, p = 0.01). The rates of successful quitting were 51% in the intervention group and 27% in the control group (RR 2, CI 1.14-3.51, p = 0.01). The external validity of this trial may be limited because 53% of eligible patients refused participation. CONCLUSIONS: Despite a significant effect on the quit rate at completion of the intervention, this multimodal prehabilitation did not show a significant difference regarding our primary outcome postoperative complications. PATIENT SUMMARY: A 6-wk smoking and alcohol cessation intervention in relation to bladder cancer surgery did not reduce postoperative complications, but it was effective in supporting people to quit in the short term.

Altered Cardiovascular Reactivity to and Recovery from Cold Face Test-Induced Parasympathetic Stimulation in Essential Hypertension.

Essential hypertension is associated with increased sympathetic and diminished parasympathetic activity as well as impaired reactivity to sympathetic stimulation. However, reactivity and recovery from parasympathetic stimulation in hypertension are unknown. We investigated reactivity and recovery to primarily parasympathetic stimulation by Cold Face Test (CFT) in essential hypertension. Moreover, we tested whether chronic stress modulates CFT-reactivity dependent on hypertension status. The CFT was conducted by applying a cold face-mask for 2 min in 24 unmedicated, otherwise healthy hypertensive men and in 24 normotensive controls. Systolic and diastolic blood pressure (BP) and heart rate (HR) were measured repeatedly. Chronic stress was assessed with the Trier-Inventory-for-Chronic-Stress-Screening-Scale. Hypertensives did not exhibit diastolic BP decreases after CFT-cessation (p = 0.59) as did normotensives (p = 0.002) and failed to show HR decreases in immediate response to CFT (p = 0.62) when compared to normotensives (p < 0.001). Systolic BP reactivity and recovery patterns did not differ between hypertensives and normotensives (p = 0.44). Chronic stress moderated HR (p = 0.045) but not BP CFT-reactivity (p's > 0.64) with chronically stressed normotensives showing similar HR reactivity as hypertensives. Our findings indicate impaired diastolic BP and HR reactivity to and recovery from CFT in hypertensives and a moderating effect of chronic stress on HR reactivity potentially reflecting reduced relaxation ability of the cardiovascular system.

Alcohol Consumption in Obese Patients Before and After Gastric Bypass as Assessed with the Alcohol Marker Phosphatidylethanol (PEth).

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) causes more rapid and enhanced absorption of alcohol. RYGB patients have also been reported to use more inpatient care for alcohol-related disease than do patients after other bariatric procedures. The present study was designed to evaluate alcohol consumption level before and after gastric bypass using a sensitive and specific alcohol biomarker. MATERIALS AND METHODS: Two separate consecutive groups of patients and a group of healthy blood donors, as reference group, were included in the study. Alcohol intake was assessed using the alcohol marker phosphatidylethanol (PEth) at preoperative baseline and at 1 and 2 years postoperatively. In the first patient group (n = 133), neither surgeon nor patient was informed about the results of PEth testing. In the second group (n = 214), PEth results above 0.30 µmol/L were considered to indicate excessive alcohol consumption and led to preoperative alcohol counseling. The groups were followed for 2 and 1 year, respectively. RESULTS: PEth results were significantly lower in both patient groups at baseline as well as postoperatively compared with the reference group. In both patient groups, there was a significant increase in PEth values at postoperative follow-up compared to baseline. CONCLUSIONS: Several physiological changes postoperatively have to be considered when interpreting PEth results in obese patients with dramatic weight reductions. According to results for PEth, obese patients treated with bariatric surgery would seem to have lower alcohol consumption compared with the reference group. Although slightly increasing their PEth values postoperatively, the RYGB patients did not reach the PEth values of the reference group.

High-Throughput LC-MS/MS Method for Determination of the Alcohol Use Biomarker Phosphatidylethanol in Clinical Samples by Use of a Simple Automated Extraction Procedure-Preanalytical and Analytical Conditions.

BACKGROUND: Phosphatidylethanol (PEth) is an alcohol use biomarker with higher clinical sensitivity and specificity than commonly used alcohol markers. Since its introduction as a clinical alcohol-marker in 2006, the number of samples sent to our laboratory for the determination of PEth has shown a strong annual increase. This has prompted the need to develop a cost-effective and reliable analytical procedure with high capacity. METHODS: An LC-MS/MS method for the determination of PEth 16:0/18:1 with a short turnaround time (3 min) has been evaluated with respect to accuracy, sensitivity, and precision. We compared this method with a previously used HPLC method, as well as a manual and a simplified automated method for sample workup, and investigated potential causes of analytic and preanalytic errors. RESULTS: The method shows limits of detection and quantification of 0.0075 µmol/L (5.2 ng/mL) and <0.05 µmol/L (<35 ng/mL), respectively. During a 2.1-year period, the method has shown a total CV < 8% for control samples (n = 2808) in the range of 0.10 (70) to 3.5 µmol/L (2461 ng/mL). The simplified automated method for sample preparation works equally well as the manual one. No specific and clinically significant causes of preanalytic errors were found. CONCLUSIONS: This LC-MS/MS method with automated sample workup is well suited for a clinical laboratory with LC-MS/MS experience and has the capability, proven from several years of use, to produce reliable PEth results in a high-volume laboratory (>50000 clinical samples/year).

Evidence-based Treatment Options in Cannabis Dependency.

BACKGROUND: Now that the consumption of natural and synthetic cannabinoids is becoming more widespread, the specific treatment of cannabis-related disturbances is an increasingly important matter. There are many therapeutic options, and it is not always clear which ones are evidence-based and appropriate for use in a given clinical situation. METHODS: This review is based on reports of pertinent randomized and controlled trials (RCTs) that were retrieved by a selective search in the PubMed and Cochrane databases. RESULTS: Cognitive behavior therapy (CBT) combined with other techniques has been found to have a moderate to large effect (Cohen's d = 0.53-0.9) on the amount of cannabis consumed as well as on the level of psychosocial functioning or the dependence syndrome. Systemic multidimensional family therapy (MDFT) has been found beneficial for younger adolescents who consume large amounts of cannabis and have psychiatric comorbidities. Short-term interventions with motivational talk therapy have been found effective for patients with or without an initial desire to achieve cannabis abstinence. All of these psychotherapeutic interventions are effective at evidence level Ia. The administration of gabapentin had a weak effect (d = 0.26) on the quantity consumed and on abstinence (evidence level Ib). Withdrawal symptoms can be alleviated with cannabinoid-receptor antagonists (d = 0.223 and 0.481) (evidence level Ib). On the other hand, there is evidence that serotonergic antidepressants can worsen withdrawal manifestations and increase the likelihood of relapse. CONCLUSION: Psychotherapeutic techniques remain the foundation of treatment for cannabis dependence. No drug has yet been approved for the treatment of cannabis dependence because of the lack of scientific evidence. The rates of abstinence that are currently achieved, even with psychotherapy, are still only moderate. Further clinical studies are needed for the evaluation of combinations of various treatments that can meet the needs of individual patients.

Phosphatidylethanol in blood (B-PEth): a marker for alcohol use and abuse.

Phosphatidylethanol (PEth) represents a group of glycerophospholipid homologues where ethanol by phospholipase D has been bound at the position that normally contains an amino-alcohol. Since the formation of PEth is specifically dependent on ethanol, the diagnostic specificity of PEth as an alcohol biomarker is theoretically 100%. The half-life of PEth in blood is approximately 4 days. The amount of alcohol consumed correlates to blood concentration of PEth and PEth has been shown to be a more sensitive indicator of alcohol consumption than traditional alcohol markers, such as CDT (carbohydrate-deficient transferrin), GGT (γ-glutamyl transferase), and MCV (mean corpuscular volume) or a combination of these. Almost all clinical data so far available are based on a high performance liquid chromatography (HPLC) method with limited analytical sensitivity. With the advent of methods with considerably higher analytical sensitivity (e.g. mass spectrometric methods), clinical sensitivity will increase correspondingly. The possibility of determining very low concentrations of PEth by new sensitive analytical techniques may, however, have both ethical and legal consequences that have to be considered.

Detection of phosphatidylethanol (PEth) in the blood of drivers in an alcohol ignition interlock program.

OBJECTIVE: The rate of failed interlock blood alcohol content (BAC) tests is a strong predictor of recidivism post-interlock and a partial proxy for alcohol use. Alcohol biomarkers measured at the start of an interlock program are known to correlate well with rates of failed BAC tests over months of interlock use. This study evaluates 2 methods of measuring low blood levels of the biomarker phosphatidylethanol (PEth). PEth is a 100 percent alcohol-specific biomarker and strongly intercorrelated with several independent indicators of drinking driving risk, including 8 other biomarkers, 3 psychometric assessments, and the rate of failed interlock BAC tests during many months of interlock use. Does a more sensitive method of measuring PEth at program entry detect drinking even among those who subsequently log no failed interlock tests? METHODS: In a sample of 281 driver blood samples, PEth was measured by both high-performance liquid chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LCMSMS) in order to compare sensitivity and accuracy. The average rate of failed interlock BAC tests was the criterion measure for marker sensitivity. LCMSMS, calibrated to detect low levels of drinking as a possible measure of abstinence violation, was judged relative to the standard HPLC assay for PEth measured up to 4 µmol/L. RESULTS: The 2 methods showed a good quantitative relationship (r(2)> .86). LCMSMS detected positive PEth levels in samples that were below the limit of detection of the HPLC method. PEth measured by LCMSMS was positive for a higher proportion of driving under the influence (DUI) offenders who logged zero failed interlock BAC tests than were detected by HPLC. CONCLUSION: Although HPLC is the widely used standard for measuring PEth in clinical alcoholism samples, the LCMSMS method, when calibrated to detect trace amounts of the major component of PEth, can detect abstinence levels of alcohol near zero intake and still correlate strongly with other indicators related to alcohol use and road safety.