Δ9-tetrahydrocannabinol (THC) is present in the body between smoking sessions in occasional non-daily cannabis users.

BACKGROUND: THC can be measured in blood up to a month after last intake in heavy cannabis users. The cognitive deficits during abstinence have been hypothesized to be at least in part due to residual THC in brain. To which extent THC accumulation will occur after occasional cannabis use has gained limited attention. We aimed to predict THC-levels between smoking sessions in non-daily as well as daily cannabis users and to compare these predictions with published THC levels. METHODS: Predictions were based on pharmacokinetic principles on drug accumulation after repeated dosing, applied to different cannabis smoking patterns, using data from a three-compartment model for THC pharmacokinetics and results on the terminal elimination half-life of THC in humans. We searched the literature for THC measurements which could be compared with these predictions. We found no such results from controlled studies of long-term repeated cannabis consumption of known THC amounts. Thirteen published studies contained, however, enough information on cannabis use and results from THC-measurements to make tentative comparisons with the predictions. RESULTS: The predictions of THC-plasma levels present after different cannabis smoking patterns assuming terminal elimination half-lives of THC of 21.5 h or longer, had some support in published THC levels measured in individuals self-reporting their cannabis consumption. We found no consistent discrepancies between the predictions and reported THC plasma levels after non-daily or daily cannabis use. The predictions indicate that THC might be present in plasma between smoking sessions above usual analytical limits when smoking every third and second day, and at lower levels after once weekly smoking. CONCLUSIONS: The study indicates that THC might be present continuously even in non-daily smokers at low levels, even if the smoking occasions are separated by a week. This is different from alcohol, where ethanol has disappeared after a day. From a toxicological point of view the persistance of THC in the brain, raises questions whether this should be given more attention as with other toxicological thinking where long-term presence of bioactive substances gives rise to concern. There are some uncertainties in this analysis, and controlled studies on THC-accumulation accompanying different use patterns seem warranted.

Diagnostic tests and treatment procedures performed prior to cardiovascular death in individuals with severe mental illness.

OBJECTIVE: To examine whether severe mental illnesses (i.e., schizophrenia or bipolar disorder) affected diagnostic testing and treatment for cardiovascular diseases in primary and specialized health care. METHODS: We performed a nationwide study of 72 385 individuals who died from cardiovascular disease, of whom 1487 had been diagnosed with severe mental illnesses. Log-binomial regression analysis was applied to study the impact of severe mental illnesses on the uptake of diagnostic tests (e.g., 24-h blood pressure, glucose/HbA1c measurements, electrocardiography, echocardiography, coronary angiography, and ultrasound of peripheral vessels) and invasive cardiovascular treatments (i.e., revascularization, arrhythmia treatment, and vascular surgery). RESULTS: Patients with and without severe mental illnesses had similar prevalences of cardiovascular diagnostic tests performed in primary care, but patients with schizophrenia had lower prevalences of specialized cardiovascular examinations (prevalence ratio (PR) 0.78; 95% CI 0.73-0.85). Subjects with severe mental illnesses had lower prevalences of invasive cardiovascular treatments (schizophrenia, PR 0.58; 95% CI 0.49-0.70, bipolar disorder, PR 0.78; 95% CI 0.66-0.92). The prevalence of invasive cardiovascular treatments was similar in patients with and without severe mental illnesses when cardiovascular disease was diagnosed before death. CONCLUSION: Better access to specialized cardiovascular examinations is important to ensure equal cardiovascular treatments among individuals with severe mental illnesses.

Undiagnosed cardiovascular disease prior to cardiovascular death in individuals with severe mental illness.

OBJECTIVE: To examine whether individuals with schizophrenia (SCZ) or bipolar disorder (BD) had equal likelihood of not being diagnosed with cardiovascular disease (CVD) prior to cardiovascular death, compared to individuals without SCZ or BD. METHODS: Multivariate logistic regression analysis including nationwide data of 72 451 cardiovascular deaths in the years 2011-2016. Of these, 814 had a SCZ diagnosis and 673 a BD diagnosis in primary or specialist health care. RESULTS: Individuals with SCZ were 66% more likely (OR: 1.66; 95% CI: 1.39-1.98), women with BD were 38% more likely (adjusted OR: 1.38; 95% CI: 1.04-1.82), and men with BD were equally likely (OR: 0.88, 95% CI: 0.63-1.24) not to be diagnosed with CVD prior to cardiovascular death, compared to individuals without SMI. Almost all (98%) individuals with SMI and undiagnosed CVD had visited primary or specialized somatic health care prior to death, compared to 88% among the other individuals who died of CVD. CONCLUSION: Individuals with SCZ and women with BD are more likely to die due to undiagnosed CVD, despite increased risk of CVD and many contacts with primary and specialized somatic care. Strengthened efforts to prevent, recognize, and treat CVD in individuals with SMI from young age are needed.

Increase in diagnosis of depressive disorders contributes to the increase in antidepressant use in adolescents.

OBJECTIVE: To study if the observed increase in use of antidepressants (AD) among adolescents may be explained by higher incidence of depressive disorder diagnosis, increasing treatment of other mental disorders or more liberal prescribing practice. METHODS: We used three different study populations of girls and boys aged 13-17 years in Norway: 1) individuals who were diagnosed with depressive disorders in primary health care, 2) individuals who were diagnosed with depressive disorders in secondary health care; 3) individuals who were dispensed ADs as recorded in the prescription database. Dataset 2) and 3) were linked. RESULTS: Incidence of depressive disorders increased from 2010 to 2015 both in primary and secondary health care, especially in girls. One in four girls with incident depressive disorders was prescribed ADs and this proportion was stable over time. Among girls treated with ADs the proportion with a diagnosis where AD treatment is indicated increased from 61.1% to 66.0%. Furthermore, the proportion with moderate or severe episodes of major depressive disorders was stable and high, 72.9% in 2014. CONCLUSION: The only issue studied that could explain increasing AD use in girls was increasing incidence of depressive disorders. Most adolescents with incident diagnosis of depressive disorders were not treated with ADs.

Diagnostic and genetic overlap of three common mental disorders in structured interviews and health registries.

OBJECTIVE: To investigate whether diagnostic data from structured interviews, primary care and specialist care registries on major depressive disorder (MDD), anxiety disorders (AD) and alcohol use disorder (AUD) identify the same individuals, yield comparable comorbidity estimates and reflect the same genetic influences. METHODS: Registry data from primary and specialist care were available for 11 727 twins and diagnostic interview data for 2271 of these. We used logistic regression analyses and biometric modelling to investigate the overlap between the data sources. RESULTS: Most individuals meeting diagnostic criteria at interview were not registered with a corresponding diagnosis. The rates of registration were higher for MDD (36% in primary care and 15% in specialist care) and AD (21% and 18%) than for AUD (3% and 7%). Comorbidity estimated as odds ratios, but not as polychoric correlations, was higher in the registries than in the interviews. Genetic influences on the disorders were highly correlated across data sources (median r = 0.81), bordering unity for MDD and AD. CONCLUSION: Prevalence and comorbidity estimates differ between registries and population-based assessment. Nevertheless, diagnoses from health registries reflect the same genetic influences as common mental disorders assessed in the general population, indicating generalizability of aetiological factors across data sources.

A comparison between wastewater-based drug data and an illicit drug use survey in a selected community.

BACKGROUND: Estimations of drug use are mostly based on population surveys that can suffer from response biases. The current study evaluates using wastewater-based epidemiology (WBE) for assessing illicit drug use by comparing wastewater data with that from a population survey. METHODS: Introductory letters (29,083) were sent to inhabitants of Lier, Belgium, asking them to participate in an online survey study. Participants were asked to indicate their drug use in the past week for a 12-week period (September-November 2014). Concomitant wastewater samples were collected from the associated wastewater treatment plant in four bi-weekly periods. Samples were analyzed using solid-phase extraction and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). RESULTS: On average, 263 (1%) inhabitants filled out the questionnaire each week. According to the survey results, cannabis was the most used drug, followed by amphetamine, cocaine and methylenedioxymethamphetamine (MDMA). Wastewater data corroborated these results. Cocaine, amphetamine and MDMA showed a significant difference between days of the week. The four sampling periods differed significantly from each other for cocaine, amphetamine and methadone. CONCLUSION: Observed drug consumption patterns from survey and wastewater data match national and international data. Wastewater analyses confirm that WBE can be reliably used to confirm patterns and trends in drug use. Future studies should focus on identifying the most opportune sampling period giving the most reliable estimates of drug use and use smaller, contained communities such as festivals or prisons if methodology allows.

Investigation of agreement between wastewater-based epidemiology and survey data on alcohol and nicotine use in a community.

BACKGROUND/AIMS: Alcohol and nicotine are the two most used substances world-wide and associated with increased burden of disease. Since surveys on substance use may be difficult due to response biases, wastewater-based epidemiology (WBE) was developed as a more objective measure of nicotine and alcohol use. This study compares estimates of nicotine and alcohol use from a wastewater sampling campaign in a medium-sized Belgian city with a concurrently executed population survey. METHODS: 29,083 letters about participation in an online survey study on weekly alcohol and tobacco use were sent to the inhabitants of Lier, Belgium. Wastewater samples were collected from the associated treatment plant in four bi-weekly periods. Samples were analyzed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Ethylsulfate was used as alcohol biomarker and cotinine and trans-3'-hydroxycotinine as nicotine biomarker. RESULTS: 263 (1%) surveys were filled out on average per week. According to survey data, alcohol and nicotine were used less than in the rest of Belgium and this was matched by the wastewater data. Nicotine use, but not alcohol use, showed a significant variation over the sampling periods. Both nicotine and alcohol showed increase use during the weekend while only alcohol showed a different use pattern throughout the week. CONCLUSION: No correlation between WBE and survey data could be demonstrated, possibly due to small sample sizes. However, this study shows that weekly trends in alcohol and nicotine use can be quickly detected from wastewater analysis and the occurrence of major events such as festivals can be identified.

Changes in cognitive function during psychogeriatric treatment in relation to benzodiazepine cessation.

INTRODUCTION: The aim of this study was to investigate cognitive functions after admission to a geriatric psychiatric hospital, and to study the short-term effects of cessation of benzodiazepine use on cognitive functions. METHODS: Details of benzodiazepine use and serum concentration measurements were recorded on admission. The Hopkins verbal learning test, the Stroop test, Digit Vigilance Test and the Mini Mental Status Examination were performed on admission, and after 4 weeks of hospitalization. Test results were compared for the total group of patients, as well as for benzodiazepine "continuers" and the "quitters". RESULTS: For all patients (n=224), improved performances were observed in 10 out of 12 cognitive tests. Significant improvements were seen in 4 out of 12 tests. Benzodiazepine "quitters" improved significantly more than the "continuers" (p=0.027) only on the Hopkins verbal learning test, delayed recall performance. DISCUSSION: Among elderly psychiatric patients, cognitive function improved slightly during the 4 weeks of hospital treatment, but only for one of the memory tests, the improvement was related to the cessation of benzodiazepine treatment.

A clinical study of the cognitive effects of benzodiazepines in psychogeriatric patients.

Previous studies have shown cognitive impairment in long-term benzodiazepine users compared to non-users. However, little is known about such effects in a population of geriatric psychiatry patients. The aim of this study was to identify differences between benzodiazepine users and non-users on standardized tests of the cognitive fields of learning and memory, executive functions and vigilance, at admittance to a department of geriatric psychiatry.Hopkins verbal learning test, Stroop test and digit vigilance test were performed in all patients. Test performances were compared between benzodiazepine users (n=168) and non-users (n=73). A multiple linear regression model was used, adjusting for different baseline characteristics (years of education, dementia and depression).No significant differences in test results were found between benzodiazepine users and non-users on 11 out of 12 cognitive tests results. On one of the 12 test results (time used on the digit vigilance test), benzodiazepine users showed better performance compared to non-users (ß=-0.20, p=0.032). This finding was not statistically significant after Bonferroni correction for multiple testing.This study of geriatric psychiatry benzodiazepine users did not reveal cognitive impairment compared to non-users on the cognitive areas tested. Other possible negative consequences of benzodiazepine use should, however, also be considered when prescribing drugs to older patients.

The relationship between socio-economic status and antidepressant prescription: a longitudinal survey and register study of young adults.

AIMS: The current study examines the relationship between socio-economic status (SES) and antidepressant prescription among young adults and investigates mechanisms that could explain such a potential social gradient. METHODS: Longitudinal survey data from a population-based Norwegian sample (N = 2606) was collected in four waves over a 13-year period. The data were linked to register data on antidepressant prescription and several indicators of SES (education, income, social or unemployment benefits, disability or rehabilitation benefits and parents' education). RESULTS: Apart from parents' education, all indicators of low SES were related to higher rates of antidepressant prescription. A part of the relationship between SES and antidepressant prescription was due to low SES being related to higher levels of anxiety and depression. Moreover, low SES was related to more frequent use of mental health services, which again was related to higher rates of antidepressant prescription. Both contact with physicians and other mental healthcare professionals accounted for some of the relationship between SES and antidepressant prescription. CONCLUSIONS: The study provides information about mechanisms involved in the relationship between low SES and antidepressant prescription. More research is needed about whether a comparable social gradient in antidepressant prescription is also to be found outside the Nordic countries.

Effect of the market withdrawal of carisoprodol on use of other prescribed drugs with abuse potential.

Carisoprodol, a centrally acting muscle relaxant indicated for acute lower back pain, has been available in Europe and the United States since 1959. Studies indicating increased risk of abuse or addiction led to withdrawal of the drug from the market in Norway and other EU countries in 2008. In this nationwide longitudinal prescription study of 53,116 individuals in Norway, previous users of carisoprodol switched, to a limited extent, to other prescribed drugs with abuse potential after the withdrawal.

Norwegian version of the Mini-International Neuropsychiatric Interview: feasibility, acceptability and test-retest reliability in an acute psychiatric ward.

OBJECTIVE: To assess the feasibility, patient and clinician acceptability and test-retest reliability of the Mini-International Neuropsychiatric Interview (MINI) used by non-psychiatrists in an acute psychiatric ward. METHOD: Of 268 consecutive patients included in a cross-sectional study, 176 (66%) completed MINI, and were compared to patients not interviewed. Patients and clinicians were questioned about the interview, using Visual Analogue Scales (VAS). For 38 patients, test-retest reliability was assessed with Cohen's kappa and observed agreement. RESULTS: MINI was not feasible for all patients. Among factors associated with not being interviewed were early discharge, psychosis, substance use and involuntary admissions. Although evaluations by patients and clinicians completing the postinterview questionnaire varied, MINI was generally perceived as being useful and feasible. Psychotic symptoms were associated with a less positive experience with MINI for both patients and clinicians. In the test-retest analyses, kappa values indicated excellent agreement for six diagnoses, fair to good for six and poor for seven, whereas observed agreement was 75% or above for all disorders. CONCLUSION: Among patients admitted to an acute psychiatric ward willing and able to complete the interview, MINI was well accepted by patients and clinicians, and has moderately good test-retest reliability.

Road traffic accident risk in patients with diabetes mellitus receiving blood glucose-lowering drugs. Prospective follow-up study.

AIM: To investigate, at a national level, whether patients using insulin or oral glucose-lowering agents had an increased risk of road traffic accidents compared with non-users. METHODS: All Norwegians aged 18-69 years (3.1 million) were followed from April 2004 until September 2006. Information on drug prescriptions, road traffic accidents and emigration/death was obtained from the following population-based registries: the Prescription Database, the Road Accident Registry and the Central Population Registry. The exposure period was the time from the first prescription of insulin or oral glucose-lowering agent during the study period. The incidence of accidents in the exposed person-time was compared with the incidence of accidents in the unexposed person-time by standardized incidence ratio (SIR). RESULTS: During the study period, 20 494 road traffic accidents with personal injuries were registered in Norway. One hundred and eighty-three accidents were registered for insulin users not taking oral glucose-lowering agents and 219 for users of oral blood glucose-lowering drugs without insulin. The SIR (95% confidence interval) for all ages and both genders combined were: insulin 1.4 (1.2-1.6), oral glucose-lowering agents 1.2 (1.0-1.3) and users of drugs for peptic ulcer and gastro-oesophageal reflux disease (negative comparators) 1.3 (1.2-1.4). The highest SIRs were found among the youngest insulin users (18-34 years old). CONCLUSIONS: A slightly increased risk of being involved in a road traffic accident was observed for drivers prescribed insulin, while no increased risk was observed for drivers prescribed oral glucose-lowering agents. The increased risk observed for insulin users was similar to that observed for users of drugs for peptic ulcer and gastro-oesophageal reflux disease.

Fatal overdose of zopiclone in an elderly woman with bronchogenic carcinoma.

The death of a 72-year-old woman with respiratory debilitation due to bronchogenic carcinoma is described. She overdosed herself with probably 200 to 350 mg of zopiclone. Zopiclone, quantitated by HPLC in femoral postmortem blood, was found to be 1.9 mg/L (4.8 micromol/L). This level is higher than many other zopiclone fatalities reported. We report a case where only zopiclone was detected.

[Lou Andreas-Salome (1861-1937)--psychoanalytical and feministic contribution to understanding her biography]. / Lou Andreas-Salomé (1861-1937)--psykoanalytiske og feministiske bidrag til forståelsen av hennes biografi.

Lou (Louise) Andreas-Salomé's life and work has preoccupied many biographers. The interest may have be sparked by her liaisons with many of the greatest men of her time. She had an intimate relationship with Friedrich Nietzsche in a period of great change for him. She was Rainer Marie Rilke's mistress for several years. And she pursued a close friendship and working relationship with Sigmund Freud in the latter part of her life. But her significance goes beyond these associations. She was a celebrated novelist and essayist in her own right, with ten novels and more than 50 essays, also on psychoanalytical subjects. She has been viewed as femme fatale, opportunist, feminist, radical, liberal, but also as a significant contributor to psychoanalytical thought. There have been two biographical approaches: a psychoanalytical approach focusing on her loss of father-figures and later difficult relationships with famous men, and a feministic approach accusing psychoanalysts of not contributing to insight, but belittling Salomé's legitimate position. A fuller understanding may be obtained by integrating these two views.

[Centrally acting muscle relaxants and traffic hazards]. / Sentralt virkende muskelrelakserende midler i trafikken.

BACKGROUND: An increasing number of the centrally acting muscle relaxants were withdrawn from the Norwegian market during the 1988-98 period. The only drug in this group now marketed in Norway is carisoprodol. The National Institute of Forensic Toxicology in Norway analyses all blood samples from suspected drugged drivers. In later years there has been a marked increase in the number of blood samples testing positive for carisoprodol or meprobamate (the major metabolite). MATERIAL AND METHODS: 480 cases testing positive for central muscle relaxants in the years 1984-1998 were further studied. RESULTS: Compared with blood samples positive primarily for benzodiazepines, there were more women in the group (39% vs. 15%), and fewer drugs and less alcohol were detected. INTERPRETATION: The positive samples may indicate misuse or abuse due to the fact that high drug concentrations and concomitant use of benzodiazepines were frequent. This knowledge should have implications for doctors prescribing centrally acting muscle relaxants.

[Detection of zopiclone in many drivers--a sign of misuse or abuse]. / Zopiklonfunn hos mange bilførere--tegn på feilbruk og misbruk.

In 1998 zopiclone had a 42% share of the prescribed hypnotic drug market in Norway. The National Institute of Forensic Toxicology analyses all blood samples from suspected drugged drivers. The rise in zopiclone prescription was partly reflected in an increase in the number of drivers with zopiclone detected in the blood. We looked closer at the test results from 101 drivers with zopiclone detected in their blood in the January 1994 to April 1999 period. 60% had blood concentrations of zopiclone above the concentration observed after intake of therapeutic doses; 80% had higher blood concentrations than those expected 8 hours after intake of therapeutic doses. The majority of the drivers also tested positive for illegal drugs, prescription drugs with abuse potential, or alcohol. This indicates that zopiclone is misused or abused. Therefore the same caution should be applied when prescribing zopiclone as is applied when prescribing e.g. benzodiazepines.

[The bell tolls for Ernest Hemingway. Somatic, psychiatric and psychoanalytical aspects of his life and work]. / Klokkene ringer for Ernest Hemingway. Liv og forfatterskap i lys av somatikk, psykiatri og psykoanalyse.

This year, the centennial of Ernest Miller Hemingway's (1899-1961) birth is being celebrated. He committed suicide on July 2 1961, thus ending a crowded and turbulent life. He published seven novels and a number of short stories during his lifetime; four novels were published after his death. Millions of copies of his works have been sold and he is still one of the world most read authors. His simple, matter-of-fact and compressed style has had great influence on other authors. There has been enormous interest in the life and works of Hemingway. This paper addresses this interest and various aspects of Hemingway's life and tries to offer some explanations by looking at Hemingway's medical history, using some psychoanalytical approaches to his life and work.

[Adverse effects of zopiclone]. / Bivirkninger ved bruk av zopiklon.

In 1994 zopiclone (Imovane), a cyclopyrrolon, was introduced in Norway as a new kind of hypnotic. In 1996 zopiclone had a 26% share of the hypnotic market. This review of relevant literature has revealed a lack of documentation on the adverse effects of zopiclone. The similarities between zopiclone and benzodiazepine hypnotics are more striking than the differences. The bulk of comparative research has been carried out with triazolam, a drug taken off the Norwegian market in 1991. With zopiclone there is less inhibition of psychomotor function the day after intake than with flunitrazepam. Zopiclone causes less subjective "hangover" than nitrazepam, but there is a similar inhibition of psychomotor function the day after intake, and in some cases greater addictive potential.