Simultaneous use of alcohol, tobacco and cannabis in relation to severity of substance dependence: a study among young Swiss men

Objective: This study investigated patterns of the simultaneous use of alcohol, tobacco and cannabis among young polydrug users, and whether use of one substance might be a cue for use of another and associations with the severity of substance dependence. Methods: The study focused on 3 subsamples from the ongoing Swiss Cohort Study on Substance Use Risk Factors (C-SURF, N=5,990). It used 12 months of data on alcohol/tobacco co-users, alcohol/cannabis co-users and tobacco/cannabis co-users (N=2,660, 1,755 and 1,460 respectively. Simultaneous use, numbers of symptoms of substance dependence, and hazardous use of alcohol, tobacco and cannabis were assessed. The effect of simultaneous polydrug use (SPU) on the numbers of symptoms of substance dependence was tested using analysis of variance. Results: Polydrug use was most common as SPU, and less common as non/occasional SPU. Moreover, when participants started to use one substance while using another, the severity of substance dependence was more strongly associated with the triggered substance than with cue. Conclusions: This study highlights the necessity to take SPU into account. First, SPU rather than separate drug use was the most common pattern for polydrug users. Second, frequent SPU was associated with increased numbers of symptoms of substance dependence compared to non/occasional SPU. Furthermore, SPU may reveal the severity of substance use dependence, when substance use is triggered by a cue substance. For these reasons, SPU should be a serious cause for concern for prevention and intervention purposes.

Rapid high-performance liquid chromatographic determination with fluorescence detection of furosemide in human body fluids and its confirmation by gas chromatography-mass spectrometry.

Furosemide (FD: Lasix) is a loop diuretic which strongly increases both urine flow and electrolyte urinary excretion. Healthy volunteers were administered 40 mg orally (dissolved in water) and concentrations of FD were determined in serum and urine for up to 6 h for eight subjects, who absorbed water at a rate of 400 ml/h. Quantification was performed by HPLC with fluorescence detection (excitation at 233 nm, emission at 389 nm) with a limit of detection of 5 ng/ml for a 300-microliters sample. The elution of FD was completed within 4 min using a gradient of acetonitrile concentration rising from 30 to 50% in 0.08 M phosphoric acid. The delay to the peak serum concentration ranged from 60 to 120 min. FD was still easily measurable in the sera from all subjects 6 h after administration. In urine, the excretion rates reached their maximum between 1 and 3 h. The total amount of FD excreted in the urine averaged 11.2 mg (range 7.6-14.0 mg), with a mean urine volume of 3024 ml (range 2620-3596 ml). Moreover, the urine density was lower than 1.010 (recommended as an upper limit in doping analysis to screen diuretics) only for 2 h. An additional volunteer was administered 40 mg of FD and his urine was collected over a longer period. FD was still detectable 48 h after intake. Gas chromatography-mass spectrometry with different types of ionization was used to confirm the occurrence of FD after permethylation of the extract. Negative-ion chemical ionization, with ammonia as reactant gas, was found to be the most sensitive method of detection.

Externalizing disorders and substance use: empirically derived subtypes in a population-based sample of adults.

PURPOSE: Attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and oppositional defiant disorder (ODD) are common externalizing disorders of childhood. The common effects of these disorders on substance abuse need further investigation. The current study investigated the joint clusters of childhood/adolescence ADHD, CD, and ODD, and their influence on substance abuse/dependence in a population-based sample of adults. METHODS: The data were drawn from the PsyCoLaus study (n = 3,720) conducted in Lausanne, Switzerland. The population-based sample included 238 subjects meeting criteria for ADHD/ODD/CD diagnoses before the age of 15. Latent class analyses (LCA) were performed to derive comorbidity subtypes, which were subsequently characterized with respect to psychosocial correlates and substance use. RESULTS: The best fit in LCAs was achieved with three latent classes: an ADHD subtype (35.7 %); an externalizing multimorbid subtype (33.6 %) involving ODD, ADHD, and CD; and a third subtype with CD (30.7 %). The CD subtype showed the highest association with substance use. Apart from this, the externalizing multimorbid subtype was also significantly linked to substance use. The ADHD subtype had only elevated frequencies for alcohol dependence in comparison with subjects that had no history of ADHD, ODD, and CD during childhood or adolescence. Finally, important interactions between subtypes and sex were observed with regard to substance use. CONCLUSIONS: This study provides evidence showing that subtyping the externalizing disorders, ADHD, ODD and CD, along their comorbidity patterns leads to important differences regarding substance use. This could have implications for the etiology, prevention, and treatment of substance use disorders.

Adolescent substance-use assessment: methodological issues in the use of the Adolescent Drug Abuse Diagnosis (ADAD).

During the past twenty years, various instruments have been developed for the assessment of substance use in adolescents, mainly in the United States. However, few of them have been adapted to, and validated in, French-speaking populations. Consequently, although increasing alcohol and drug use among teenagers has become a major concern, the various health and social programs developed in response to this specific problem have received little attention with regard to follow-up and outcome assessment. A standardized multidimensional assessment instrument adapted for adolescents is needed to assess the individual needs of adolescents and assign them to the most appropriate treatment setting, to provide a single measurement within and across health and social systems, and to conduct treatment outcome evaluations. Moreover, having an available instrument makes it possible to develop longitudinal and transcultural research studies. For this reason, a French version of the Adolescent Drug Abuse Diagnosis (ADAD) was developed and validated at the University Child and Adolescent Psychiatric Clinic in Lausanne, Switzerland. This article aims to discuss the methodological issues that we faced when using the ADAD instrument in a 4-year longitudinal study including adolescent substance users. Methodological aspects relating to the content and format of the instrument, the assessment administration and the statistical analyses are discussed.

Effect of changes in the deuterium content of drinking water on the hydrogen isotope ratio of urinary steroids in the context of sports drug testing.

The hydrogen isotope ratio (HIR) of body water and, therefore, of all endogenously synthesized compounds in humans, is mainly affected by the HIR of ingested drinking water. As a consequence, the entire organism and all of its synthesized substrates will reflect alterations in the isotope ratio of drinking water, which depends on the duration of exposure. To investigate the effect of this change on endogenous urinary steroids relevant to doping-control analysis the hydrogen isotope composition of potable water was suddenly enriched from -50 to 200 0/00 and maintained at this level for two weeks for two individuals. The steroids under investigation were 5β-pregnane-3α,20α-diol, 5α-androst-16-en-3α-ol, 3α-hydroxy-5α-androstan-17-one (ANDRO), 3α-hydroxy-5β-androstan-17-one (ETIO), 5α-androstane-3α,17β-diol, and 5β-androstane-3α,17β-diol (excreted as glucuronides) and ETIO, ANDRO and 3β-hydroxyandrost-5-en-17-one (excreted as sulfates). The HIR of body water was estimated by determination of the HIR of total native urine, to trace the induced changes. The hydrogen in steroids is partly derived from the total amount of body water and cholesterol-enrichment could be calculated by use of these data. Although the sum of changes in the isotopic composition of body water was 150 0/00, shifts of approximately 30 0/00 were observed for urinary steroids. Parallel enrichment in their HIR was observed for most of the steroids, and none of the differences between the HIR of individual steroids was elevated beyond recently established thresholds. This finding is important to sports drug testing because it supports the intended use of this novel and complementary methodology even in cases where athletes have drunk water of different HIR, a plausible and, presumably, inevitable scenario while traveling.

Biological monitoring of exposure to solvents using the chemical itself in urine: application to toluene

Objective Biomonitoring of solvents using the unchanged substance in urine as exposure indicator is still relatively scarce due to some discrepancies between the results reported in the literature. Based on the assessment of toluene exposure, the aim of this work was to evaluate the effects of some steps likely to bias the results and to measure urinary toluene both in volunteers experimentally exposed and in workers of rotogravure factories. Methods Static headspace was used for toluene analysis. o-Cresol was also measured for comparison. Urine collection, storage and conservation conditions were studied to evaluate possible loss or contamination of toluene in controlled situations applied to six volunteers in an exposure chamber according to four scenarios with exposure at stable levels from 10 to 50 ppm. Kinetics of elimination of toluene were determined over 24 h. A field study was then carried out in a total of 29 workers from two rotogravure printing facilities. Results Potential contamination during urine collection in the field is confirmed to be a real problem but technical precautions for sampling, storage and analysis can be easily followed to control the situation. In the volunteers at rest, urinary toluene showed a rapid increase after 2 h with a steady level after about 3 h. At 47.1 ppm the mean cumulated excretion was about 0.005% of the amount of the toluene ventilated. Correlation between the toluene levels in air and in end of exposure urinary sample was excellent (r = 0.965). In the field study, the median personal exposure to toluene was 32 ppm (range 3.6-148). According to the correlations between environmental and biological monitoring data, the post-shift urinary toluene (r = 0.921) and o-cresol (r = 0.873) concentrations were, respectively, 75.6 mu g/l and 0.76 mg/g creatinine for 50 ppm toluene personal exposure. The corresponding urinary toluene concentration before the next shift was 11 mu g/l (r = 0.883). Conclusion Urinary toluene was shown once more time a very interesting surrogate to o-cresol and could be recommended as a biomarker of choice for solvent exposure. [Authors]

Adolescent substance-use assessment: methodological issues in the use of the ADAD (Adolescent Drug Abuse Diagnosis).

During the past twenty years, various instruments have been developed for the assessment of substance use in adolescents, mainly in the United States. However, few of them have been adapted to, and validated in, French-speaking populations. Consequently, although increasing alcohol and drug use among teenagers has become a major concern, the various health and social programs developed in response to this specific problem have received little attention with regard to follow-up and outcome assessment. A standardized multidimensional assessment instrument adapted for adolescents is needed to assess the individual needs of adolescents and assign them to the most appropriate treatment setting, to provide a single measurement within and across health and social systems, and to conduct treatment outcome evaluations. Moreover, having an available instrument makes it possible to develop longitudinal and trans-cultural research studies. For this reason, a French version of the Adolescent Drug Abuse Diagnosis (ADAD) was developed and validated at the University Child and Adolescent Psychiatric Clinic in Lausanne, Switzerland. This paper aims to discuss the methodological issues that we faced when using the ADAD instrument in a 4-year longitudinal study including adolescent substance users. Methodological aspects relating to the content and format of the instrument, the assessment administration and the statistical analyses are discussed.

A fatal overdose of cocaine associated with coingestion of marijuana, buprenorphine, and fluoxetine. Body fluid and tissue distribution of cocaine and its metabolites determined by hydrophilic interaction chromatography-mass spectrometry(HILIC-MS).

Chromatographic separation of highly polar basic drugs with ideal ionspray mass spectrometry volatile mobile phases is a difficult challenge. A new quantification procedure was developed using hydrophilic interaction chromatography-mass spectrometry with turbo-ionspray ionization in the positive mode. After addition of deuterated internal standards and simple clean-up liquid extraction, the dried extracts were reconstituted in 500 microL pure acetonitrile and 5 microL was directly injected onto a Waters Atlantis HILIC 150- x 2.1-mm, 3-microm column. Chromatographic separations of cocaine, seven metabolites, and anhydroecgonine were obtained by linear gradient-elution with decreasing high concentrations of acetonitrile (80-56% in 18 min). This high proportion of organic solvent makes it easier to be coupled with MS. The eluent was buffered with 2 mM ammonium acetate at pH 4.5. Except for m-hydroxy-benzoylecgonine, the within-day and between-day precisions at 20, 100, and 500 ng/mL were below 7 and 19.1%, respectively. Accuracy was also below +/- 13.5% at all tested concentrations. The limit of quantification was 5 ng/mL (%Diff < 16.1, %RSD < 4.3) and the limit of detection below 0.5 ng/mL. This method was successfully applied to a fatal overdose. In Switzerland, cocaine abuse has dramatically increased in the last few years. A 45-year-old man, a known HIV-positive drug user, was found dead at home. According to relatives, cocaine was self-injected about 10 times during the evening before death. A low amount of cocaine (0.45 mg) was detected in the bloody fluid taken from a syringe discovered near the corpse. Besides injection marks, no significant lesions were detected during the forensic autopsy. Toxicological investigations showed high cocaine concentrations in all body fluids and tissues. The peripheral blood concentrations of cocaine, benzoylecgonine, and methylecgonine were 5.0, 10.4, and 4.1 mg/L, respectively. The brain concentrations of cocaine, benzoylecgonine, and methylecgonine were 21.2, 3.8, and 3.3 mg/kg, respectively. The highest concentrations of norcocaine (about 1 mg/L) were measured in bile and urine. Very high levels of cocaine were determined in hair (160 ng/mg), indicating chronic cocaine use. A low concentration of anhydroecgonine methylester was also found in urine (0.65 mg/L) suggesting recent cocaine inhalation. Therapeutic blood concentrations of fluoxetine (0.15 mg/L) and buprenorphine (0.1 microg/L) were also discovered. A relatively high concentration of Delta(9)-THC was measured both in peripheral blood (8.2 microg/L) and brain cortex (13.5 microg/kg), suggesting that the victim was under the influence of cannabis at the time of death. In addition, fluoxetine might have enhanced the toxic effects of cocaine because of its weak pro-arrhythmogenic properties. Likewise, combination of cannabinoids and cocaine might have increase detrimental cardiovascular effects. Altogether, these results indicate a lethal cocaine overdose with a minor contribution of fluoxetine and cannabinoids.

Substance P-like-immunoreactive sensory neurons in dorsal root ganglia of the chick embryo: ontogenesis and influence of peripheral targets.

The expression of substance P (SP) was studied in sensory neurons of developing chick lumbosacral dorsal root ganglia (DRG) by using a mixture of periodic acid, lysine and paraformaldehyde as fixative and a monoclonal antibody for SP-like immunostaining. The first SP-like-immunoreactive DRG cells appeared first at E5, then rapidly increased in number to reach a peak (88% of ganglion cells) at E8, and finally declined (59% at E12, 51% after hatching). The fall of the SP-like-positive DRG cells resulted from two concomitant events affecting a subset of small B-neurons: a loss of neuronal SP-like immunoreactivity and cell death. After one hindlimb resection at an early (E6) or late (E12) stage of development (that is before or after establishment of peripheral connections), the DRG were examined 6 days later. In both cases, a drastic neuronal death occurred in the ispilateral DRG. However, the resection at E6 did not change the percentage of SP-like-positive neurons, while the resection at E12 severely reduced the proportion of SP-like-immunoreactive DRG cells (25%). In conclusion, connections established between DRG and peripheral target tissues not only promote the survival of sensory neurons, but also control the maintenance of SP-like-expression. Factors issued from innervated targets such as NGF would support the survival of SP-expressing DRG cells and enhance their SP content while other factors present in skeletal muscle or skin would hinder SP expression and therefore lower SP levels in a subset of primary sensory neurons.

Anxiety and severity of illicit substance use in adolescence: Evaluating the mediating role of perceived coping styles

The purpose of this study was to examine whether coping styles (Active coping, Internal coping and Withdrawal coping) mediated the relationships between anxiety and severity of illicit substance use among a sample of 110 Swiss adolescents ages 12-19 (M=16.3, SD=1.66). The current study tested two competing models of anxiety on severity of illicit substance use. In the first model, we tested the direct effect of trait anxiety (STAI-Y anxiety score) on severity of illicit substance use (ADAD drug use severity rating), while in the second models we examined the mediating role of coping styles in the link between trait anxiety and severity of illicit substance use. Path models indicated that the associations between trait anxiety and severity of illicit substance use are partially mediated by active and withdrawal coping styles. Limitations of the findings and implications for prevention of substance use in adolescence are discussed.

Effectiveness of a brief integrative multiple substance use intervention among young men with and without booster sessions.

Brief interventions (BI) commonly employ screening and target a single substance. Multi-substance interventions are a more adequate reflection of risk behaviors in adolescents and young adults. Systematic screening complicates BI in many settings. The effectiveness of a voluntary multi-substance intervention among 19-year-old men and the incremental impact of booster sessions were analyzed. Participants were enrolled during mandatory army conscription in Switzerland. Compared with 461 controls, 392 BI subjects showed reduced substance use on 10 of 12 measures (4 tobacco, 4 cannabis, and 2 alcohol measures). Between-group effects were small and non-significant (except for cannabis use prevalence). Three-month booster sessions were not effective and even contraindicated. The usefulness of targeting multi-substances during BIs without prior screening depends on the value of small effects. The addition of booster sessions was not effective and therefore is not recommended.

Toxic substances in blood: an analysis of current recommendations under a Bayesian (decision) approach

This article extends existing discussion in literature on probabilistic inference and decision making with respect to continuous hypotheses that are prevalent in forensic toxicology. As a main aim, this research investigates the properties of a widely followed approach for quantifying the level of toxic substances in blood samples, and to compare this procedure with a Bayesian probabilistic approach. As an example, attention is confined to the presence of toxic substances, such as THC, in blood from car drivers. In this context, the interpretation of results from laboratory analyses needs to take into account legal requirements for establishing the 'presence' of target substances in blood. In a first part, the performance of the proposed Bayesian model for the estimation of an unknown parameter (here, the amount of a toxic substance) is illustrated and compared with the currently used method. The model is then used in a second part to approach-in a rational way-the decision component of the problem, that is judicial questions of the kind 'Is the quantity of THC measured in the blood over the legal threshold of 1.5 μg/l?'. This is pointed out through a practical example.

Need for informed consent in substance use studies--harm of bias?

OBJECTIVE: The aim of this study was to examine the differences between those who gave informed consent to a study on substance use and those who did not, and to analyze whether differences changed with varying nonconsent rates. METHOD: Cross-sectional questionnaire data on demographics, alcohol, smoking, and cannabis use were obtained for 6,099 French- and 5,720 German-speaking 20-year-old Swiss men. Enrollment took place over 11 months for the Cohort Study on Substance Use Risk Factors (C-SURF). Consenters and nonconsenters were asked to complete a short questionnaire. Data for nearly the entire population were available because 94% responded. Weekly differences in consent rates were analyzed. Regressions examined the associations of substance use with consent giving and consent rates and the interaction between the two. RESULTS: Nonconsenters had higher substance use patterns, although they were more often alcohol abstainers; differences were small and not always significant and did not decrease as consent rates increased. CONCLUSIONS: Substance use currently is a minor sensitive topic among young men, resulting in small differences between nonconsenters and consenters. As consent rates increase, additional individuals are similar to those observed at lower consent rates. Estimates of analytical studies looking at associations of substance use with other variables will not differ at reasonable consent rates of 50%-80%. Descriptive prevalence studies may be biased, but only at very low rates of consent.

Disease profiles of detainees in the Canton of Vaud in Switzerland: gender and age differences in substance abuse, mental health and chronic health conditions.

BACKGROUND: Literature on the disease profile of prisoners that differentiates by age and gender remains sparse. This study aimed to describe the health of correctional inmates in terms of substance abuse problems and mental and somatic health conditions, and compare it by gender and age. METHODS: This study examined cross-sectional data from the Canton of Vaud in Switzerland on the health conditions of detainees who were in prison on January 1, 2011 or entered prison in 2011. Health conditions validated by physician examination were reported using the International Classification of Diseases (ICD) version 10. The analyses were descriptive by groups of prisoners: the entire sample (All), Men, Older adults and Women. RESULTS: A total of 1,664 individuals were included in the analysis. Men comprised 91.5 % of the sample and had a mean age of 33 years. The other 8.5 % were women and had an average age of 39. Older adults (i.e., age 50 and older) represented 7 % of the total sample. Overall, 80 % of inmates were non-Swiss citizens, but the proportion of Swiss prisoners was higher among the older adults (51 %) and women (29 %). Overall, 41 % of inmates self-reported substance abuse problems. Of those, 27 % were being treated by psychiatrists for behavioral disorders related to substance abuse. Chronic infectious diseases were found in 9 % of the prison population. In addition, 27 % of detainees suffered from serious mental health conditions. Gender and age had an influence on the disease profile of this sample: compared to the entire prison population, the older inmates were less likely to misuse illegal drugs and to suffer from communicable infections but exhibited more problems with alcohol and a higher burden of chronic health conditions. Female prisoners were more disposed to mental health problems (including drug abuse) and infectious diseases. In terms of chronic diseases, women suffered from the same conditions as men, but the diseases were more prevalent in women. CONCLUSION: It is important to understand the different disease profiles of prisoners by gender and age, as it helps identify the needs of different groups and tailor age-and gender-specific interventions.