Peter Wennberg

Effects of naltrexone on the subjective response to amphetamine in healthy volunteers.

Abstract: While dopaminergic mechanisms in amphetamine-taking behavior have been extensively studied, the contribution of the endogenous opioid system is less clear. We assessed the effects of an opioid antagonist, naltrexone (50 mg), on the subjective response to an oral dose of dexamphetamine (30 mg) in 12 healthy volunteers in a double-blind, placebo-controlled design. Volunteers received a total of 4 combinations of the study preparation (placebo-naltrexone, placebo-amphetamine) over 4 occasions with 1-week intervals. The primary objective of the study was to evaluate the effect of pretreatment with naltrexone on the subjective response to amphetamine. This was measured using a Visual Analog Scale, assessing the subjective effects over 7 hours. The secondary objective was to measure the effects of naltrexone on behavioral and physiologic responses to amphetamine. This was measured by blood pressure, heart rate, skin conductance, and speed of reading at the end of each session. Amphetamine produced significant effects on subjective arousal when compared to placebo after 1 hour (P < 0.001) and continued to be evident until 7 hours. Pretreatment with naltrexone significantly attenuated the subjective effects of amphetamine (P < 0.05), and this effect was time-dependent with a reduction from the 3-hour time point. Naltrexone did not influence the behavioral and physiologic effects of amphetamine in this sample. The results provide preliminary evidence that naltrexone may reduce the reinforcing effects of amphetamine via modulation of the opioid system. The potential of naltrexone as an adjunct pharmaceutical for the treatment of amphetamine dependence is promising and needs to be investigated further.

Alcohol use, heavy episodic drinking and subsequent problems among adolescents in 23 European countries: does the prevention paradox apply?

AIMS According to the prevention paradox, a majority of alcohol-related problems in a population can be attributed to low to moderate drinkers simply because they are more numerous than heavy drinkers, who have a higher individual risk of adverse outcomes. We examined the prevention paradox in annual alcohol consumption, heavy episodic drinking (HED) and alcohol-related problems among adolescents in 23 European countries. DESIGN AND SETTING Survey data from the 2007 European School Survey Project on Alcohol and Drugs (ESPAD) among 16-year-old students were analysed. PARTICIPANTS A total of 38,370 alcohol-consuming adolescents (19,936 boys and 18,434 girls) from 23 European countries were included. MEASUREMENTS The upper 10% and the bottom 90% of drinkers by annual alcohol intake, with or without HED, and frequency of HED, were compared for the distribution of 10 different alcohol-related problems. FINDINGS Although the mean levels of consumption and alcohol-related problems varied largely between genders and countries, in almost all countries the heavy episodic drinkers in the bottom 90% of consumers by volume accounted for most alcohol-related problems, irrespective of severity of problem. However, adolescents with three or more occasions of HED a month accounted for a majority of problems. CONCLUSIONS The prevention paradox, based on measures of annual consumption and heavy episodic drinking, seems valid for adolescent European boys and girls. However, a minority with frequent heavy episodic drinking accounted for a large proportion of all problems, illustrating limitations of the concept. As heavy episodic drinking is common among adolescents, our results support general prevention initiatives combined with targeted interventions.

Alcohol habits in Sweden during 1997–2005 measured with the AUDIT

This study aimed to describe changes in Swedish alcohol habits during a period of “harmonization” with European Union alcohol policy. Three random samples collected during the years 1997 (n=997), 2001 (n=893) and 2005 (n=914) were compared. Alcohol habits and hazardous consumption was measured with the AUDIT (Alcohol Use Disorders Identification Test) distributed to the respondents by post. Results were somewhat diverse, but significant changes in alcohol habits occurred among two subgroups of the population: for women and the age group between 28 and 60 years, AUDIT scores peaked in 2001. The results are discussed in relation to the changes made in Swedish alcohol policy during the investigation period.

Internet-based assessment and self-monitoring of problematic alcohol and drug use

A Swedish web-based service (www.escreen.se) offers self-assessment and self-monitoring of alcohol and drug use via on-line screening with the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders Identification Test (DUDIT) as well as in-depth risk assessment using extended versions of both tests (Alcohol-E and DUDIT-E). Users receive individualized feedback concerning their alcohol and drug consumption and can follow their alcohol and drug use over time in personal diagrams and by writing in an electronic diary. This study describes user characteristics, service utilization patterns, and psychometric test properties for 2361 individuals who created a valid account over 20 months starting in February 2007. Problematic alcohol use according to AUDIT criteria was indicated for 67.4%, while 46.0% met DUDIT criteria for problematic drug use. Men and women accessed the service equally, with a mean age of 23 years. Internal consistency reliability figures were 0.90 for 1846 first-time AUDIT users and 0.97 for 1211 first-time DUDIT users; among 213 second-time AUDIT users reliability was 0.93, and 0.96 for 97 second-time DUDIT users. Internet-based alcohol and drug monitoring could function as a self-help tool or as a complement to substance abuse treatment.

An open clinical trial of naltrexone for amphetamine dependence: compliance and tolerability.

The aim of the study was to assess the feasibility of naltrexone as a potential pharmacotherapy for amphetamine dependence. The study design was an open-label clinical trial with 20 amphetamine-dependent patients receiving 12 weeks of treatment comprised of naltrexone (50 mg) along with relapse prevention therapy. Patients were assessed weekly for adverse events and compliance to medication. Tolerability to naltrexone was measured by patients self-report and observed adverse effects along with plasma markers of hepatotoxicity. Compliance to treatment was measured by number of treatment days attended and by the presence of naltrexones metabolite, 6-β-naltrexol in urine. Majority of the patients tolerated the medication well, also during relapse. Mild headache, nausea and abdominal pain were reported (n=3) but subsided within 2 weeks. Plasma levels of hepatic markers did not reveal any significant increase from baseline. Eleven out of 20 patients complied with the treatment and there was a significantly higher proportion of positive tests of 6-β-naltrexol in urine among patients completing 12 weeks of treatment compared to those who did not (77% vs. 22%). The frequency and amount of amphetamine consumed was significantly lower during treatment compared with pre-treatment consumption (P<0.01). In conclusion, naltrexone was well tolerated with moderate rates of compliance, supporting the feasibility of investigating this compound in a larger placebo-controlled trial as a potential pharmacotherapy for amphetamine dependence.

Population screening of risky alcohol and drug use via Internet and Interactive Voice Response (IVR) : A feasibility and psychometric study in a random sample

BACKGROUND The wide accessibility of computer-based technologies like the Internet and Interactive Voice Response (IVR) systems raises the question of whether population survey data could be collected more easily and cheaply compared to using paper questionnaires. In the area of possibly stigmatized behaviors such as problematic alcohol and drug use, the question extends to whether the prevalence of such behaviors in the general population could be surveyed without compromising the quality of the data. AIMS This study compares Internet and IVR versions of the AUDIT and DUDIT with respect to: (1) response rate, (2) problematic alcohol and drug use and (3) reliability. METHOD 5000 individuals, randomly selected from the Swedish general population, were contacted via postal mail and invited to complete the AUDIT and DUDIT questionnaires via Internet or IVR. In total, 1861 (37.8%) participated in the study, 1089 via Internet and 772 via IVR. RESULTS The Internet administration mode yielded a higher response rate (38.1%) compared to the IVR mode (33.9%). When respondents were given a choice between Internet and IVR, a higher response rate resulted (43.2-46.6%). Problematic alcohol and drug use occurred among 21.1% and 2.8% of the sample, respectively, with no significant differences by administration mode. Both the AUDIT and DUDIT exhibited satisfactory reliability across administration modes, Cronbachs α 0.76/0.86. CONCLUSIONS Data quality does not deteriorate with computerized administration methods for the AUDIT and DUDIT in population studies but paper questionnaires should also be made available to respondents in order to maximize response rates.

Psychosocial characteristics at age 10; differentiating between adult alcohol use pathways: a prospective longitudinal study.

The objective of the present study was to relate psychosocial characteristics at age 10 to alcohol use pathways in adulthood up to age 36 using data from the male cohort (n = 122) of a longitudinal study. Psychosocial characteristics at age 10 were measured along five dimensions: parental socioeconomic status, intelligence, ability to concentrate, anxiousness, and school achievement. Subjects whose hazardous alcohol habits were limited to adolescence/early adulthood had parents with a significantly lower socioeconomic status compared to persistently hazardous alcohol consumers. In addition, two psychosocial configurations at age 10 were typically linked to future alcohol problems. One pathway included motivational difficulties in school and the second a general adjustment problem. The discussion relates these configurations to existing typologies and theories of development.

Alcohol Habits in Sweden during 1997–2009 with Particular Focus on 2005 and 2009, Assessed with the AUDIT: A Repeated Cross-Sectional Study

Aim: This study aimed to survey the changes in alcohol habits during a period with the European Union legal practices. Methods: Alcohol habits in Sweden were surveyed in the general Swedish population at four timepoints, in 1997, 2001, 2005 and 2009, using the 10-item AUDIT questionnaire. Design: Four separate randomly drawn cross-sectional samples of 1,250 individuals were surveyed at each timepoint. Results: An average of 70% of the sampled individuals responded to the AUDIT questionnaire. Men had higher total AUDIT scores than women in 2005 and 2009, but scores increased among women 61–71 years old and decreased among men 61–71 years old. Younger men and women 17–27 years old decreased their AUDIT-C consumption scores by almost 20% between 2005 and 2009. An analysis of problem drinkers (+8 for men/+6 for women) indicated that a larger proportion of elderly women drank moderately in 2009 compared with 2005, but fewer elderly women drank hazardously. Conclusions: Earlier increases in drinking levels between 1997 and 2001 may reflect a latent high demand that was restricted by low availability. When availability due to European Union harmonization increased, alcohol consumption followed suit. After a period of adaptation, alcohol consumption appears to have stabilized.

Psychological distress and functional impairment in patients with personality disorders

The study is aimed at investigating the impact of a personality disorder (PD) diagnosis, in terms of functional impairment and subjective distress, in order to better understand the burden of this diagnosis and its implications. Among the 462 consecutive psychiatric patients diagnosed with the DSM structured interview for Axis I, II and V diagnoses, almost 60% had PD. Patients with PD displayed considerable vulnerability and suffering in many domains, including finances and interpersonal relationships. Despite the educational and occupational similarities of PD patients and non-PD patients, the PD patients had more problems maintaining permanent job positions. They also had more symptomatic suffering and concerns about health than non-PD patients. Generally, the results were in line with findings in the literature but more thoroughly captured the challenges that PD patients face in various areas of life. Awareness of the frequent comorbidity of PD with Axis I disorders seems crucial in developing future treatment plans with an emphasis on psychosocial rehabilitation, vocational training and social support.

The Swedish version of the Outcome Questionnaire (OQ-45): Reliability and factor structure in a substance abuse sample

This study described the psychometric properties of the Swedish version of the Outcome Questionnaire (OQ-45.2) in a substance abuse sample (N=227). The test properties were satisfactory except for somewhat low internal consistency in the social role subscale. The results were similar to those obtained in other countries but systematic international comparisons are still lacking.