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Increasing evidence indicates that chronic stress, such as social isolation, plays an important role in the development of a variety of psychiatric and somatic disorders. Meanwhile, chronic stress imposed by prolonged isolation and confinement in the spacecraft is also one of the major concerns for the health of future interplanetary space travelers. Preclinical studies suggest that the peripheral endocannabinoid (eCB) system is involved in the regulation of the stress response and eCB signaling is implicated in the pathogenesis of stress-related diseases. However, there are only few human studies addressing this topic, of which most focusing on patients who have already developed a certain type of disorder. It remains unknown whether chronic stress may affect eCB signaling in healthy humans. A 520-d isolation and confinement study simulating a flight to Mars provided an extraordinary chance to study the effects of prolonged stress in healthy humans. During the study period, the participants lived in confinement and could not meet their families, friends, or strangers for more than 500 days. We examined the impact of chronic exposure to isolation and confinement through monitoring their psychological state, brain cortical activity, sympathetic adrenal–medullary system response and eCB signaling response. We observed reduced positive emotion ratings, decreased brain cortical activities and high levels of catecholamine release, indicating that prolonged exposure to isolation and confinement stressors may bring about changes both psychologically and physiologically. Importantly, for eCB signaling response, blood concentrations of eCB 2-arachidonoylglycerol (2-AG), but not anandamide (AEA), were significantly reduced (p < 0.001), suggesting that dysregulation of 2-AG signaling might be specifically implicated in the response to chronic stressors.;

The endocannabinoid system has been implicated in the regulation of the stress response, fear memory formation, and inflammatory processes. Posttraumatic stress disorder (PTSD) can result from exposure to extreme stress and is characterized by strong, associative memories for the traumatic events experienced. Furthermore, an elevated physical disease risk has been observed in PTSD, likely to be mediated by inflammatory processes. Therefore, altered endocannabinoid regulation can be expected in individuals with PTSD. However, attempts to assess PTSD-associated differences in the endocannabinoid system from human blood samples have provided inconsistent results, possibly due to fluctuating levels of endocannabinoids. In hair, these neuromodulators are accumulated over time and thus give access to a more stable and reliable assessment. We therefore investigated PTSD-associated differences in hair concentrations of endocannabinoids (N-acyl-ethanolamides palmitoylethanolamide [PEA], oleoylethanolamide [OEA] and stearoylethanolamide [SEA]) in 38 rebel war survivors from Northern Uganda suffering from PTSD and N=38 healthy rebel war survivors without current and lifetime PTSD. PTSD diagnosis and symptom severity were assessed in structured clinical interviews employing the Posttraumatic Diagnostic Scale (PDS). A significant group difference was observed for OEA, with PTSD patients showing reduced hair concentrations. Regression analyses further revealed strong negative relationships between all investigated N-acyl-ethanolamides and symptom severity of PTSD. The observed reductions in endocannabinoids might account for the increased inflammatory state as well as for the failure to extinguish fear memories observed in PTSD. Our findings add to the accumulating evidence suggesting the endocannabinoid system as a target for pharmacological enhancement of exposure-based psychotherapy for PTSD. published

The introduction of the upcoming instrumentation liquid chromatography–mass spectrometry (LC–MS) into the field of forensic toxicology was primarily focused on crucial substances, undetectable by current analytical techniques. Typically, polar substances (which cannot be derivatised properly) thermolabile and high molecular weight compounds were first targets of the analytical technique. Successful application of LC–tandem mass spectrometry (API 2000, Applied Biosystems) in multiple reaction monitoring (MRM) mode to the identification of alprazolam (>1 pg/mg), dothiepine (>0.4 pg/mg) and piritramide (>2 pg/mg) in hair is presented in this paper. Moreover, the quantification of cocaine and benzoylecgonine was performed in the grey zone of suspicious hair samples (66 cases with positive response below cut-off in immunoassay screening but negative GC–MS confirmation). A high correlation between both techniques and a reliable substance confirmation by LC–MS–MS could be verified down to cocaine concentrations of 20 pg/mg in hair. An extension of the concept of MRM experiments to larger groups of analytes was attempted successfully. An adaptable combination of experiment modules (e.g. stimulants, narcotics, benzodiazepines, antidepressants/neuroleptics) to screening methods provides an efficient tool for a sensitive and specific systematic toxicological analysis (STA) in ‘general unknown’ cases.

Anabolic steroids usually undergo a complex metabolism which is mainly dependent on structural variation and application pathway. In contrast to doping analysis, where the presence of a prohibited substance constitutes a doping offence without regarding the origin or application, in forensic cases any information related to anabolic steroids may be required to evaluate the cause of death, liability of defendants, or self-consumption. 19-Norsteroids proved to be appropriate model compounds for the investigation, because of their prevalence in recent doping cases, analytical and biochemical similarity to endogenous steroids, well explored biochemistry, and the availability of numerous reference standards. Typical urinary metabolites are conjugates of terminal biotransformation products like norandrosterone–glucuronide, which are relatively unspecific and do not reveal details about administration time, pathway, dosages or structural details. Therefore, metabolic patterns in blood, hair and sweat were examined to study metabolism, distribution and incorporation behaviour of the steroids and hence the traceability in the respective matrices. Concentration profiles of the steroids in blood and the resulting bioavailability show distinct particularities after oral or transdermal application of steroids. Oral application of steroid precursors is followed by extensive first pass biotransformation of the steroid to inactive metabolites, while transdermal administration appears to be an efficient pathway, leading to effective and durable concentrations of active steroids in blood. Due to the mutual similarity of metabolic patterns in hair and sweat corresponding to the regional presence of sweat and sebum glands, steroid incorporation appears to proceed mainly via sweat absorption.

The first official report on the organization, analytical methodologies, and the results of the doping control analysis performed by the International Olympic Committee (IOC)-accredited Doping Control Laboratory of Athens, Greece, during the 6th World Championships of Athletics, held in Athens on 1–10 August 1997, is presented. The significance of the various analytical parameters of the doping control is shown. The results include 20 positive cases, of which two were detected in screening procedures and confirmed exclusively by high resolution mass spectrometry. The screening results and analytical data on the excretion of a new black-market doping agent, phenylpiracetam or carfedon, which was unknown in the literature, are also presented.