The Impact of the Opioid Antagonist Naloxone on Experimentally Induced Craving in Nicotine-Dependent Individuals.

OBJECTIVE: Preclinical and clinical findings suggest a substantial association of the endogenous opioid system in nicotine dependence. The present study investigates the possible dose-dependent influence of naloxone, an unspecific opioid-receptor-antagonist, combined with cue exposure on the physiological state, locomotor activity, craving and the hypothalamic-pituitary-adrenal axis in nicotine-dependent humans. METHODS: Twenty nicotine-dependent, outpatient participants were deprived of nicotine for over 4 h, before receiving challenges with naloxone (1.6 mg or 3.2 mg q70 kg IV) or the placebo. Additionally, following drug administration, either smoking-related cues or neutral images were presented. Nicotine withdrawal was monitored by evaluating the following objective signs - skin conductance, heart rate, temperature, respiration, locomotor activity, cortisol, prolactin and ACTH levels as well as craving. RESULTS: With respect to subjective effects, participants administered a higher dosage of naloxone and those who were shown smoking-related cues were significantly less pleased (p = 0.019), felt more depressed (p = 0.033) and thought smoking would make them feel better (p = 0.028) than participants given naloxone and shown neutral cues. Participants given no naloxone but with smoking-related cues felt a higher urge to smoke than participants given naloxone and shown neutral cues (p = 0.042). Naloxone - in both dosages - also decreased the desire and intention to smoke in comparison to placebo. Compared to the placebo group, significantly higher cortisol, prolactin and ACTH values were observed after administration of lower and higher dosage of naloxone followed by smoking-related cues. CONCLUSION: Naloxone influenced nicotine withdrawal and strengthened significantly by cue exposure, both on objective measurement and on craving scales. These findings suggest an involvement of the endogenous opioid system in the development and maintenance of nicotine dependence.

Mental disorder, service use, and barriers to care among 500 homeless people in 3 different urban settings.

OBJECTIVE: To determine the standardized rates of mental disorder, health service use and barriers to care in a representatively diverse sample of homeless adults in three different sized urban centers in British Columbia, Canada. METHOD: Five hundred homeless adults from Vancouver, Victoria and Prince George were recruited. The MINI-International Neuropsychiatric Interview PLUS was used to determine current and lifetime rates of mental disorder, mental disorder episodes and suicidality. Health service use and barriers to care were recorded. RESULTS: Overall, 92.8 % of participants met criteria for a current mental disorder: 82.6 % for alcohol or drug dependence, 57.3 % anxiety disorder, 31.5 % mood disorder. Over half (53.4 %) met criteria for a concurrent disorder. Only 14.9 % had seen a psychiatrist and 12.7 % a mental health team in the year prior to the survey. Most common barriers included being poorly connected to the system of care and issues related to homelessness. Mental disorder rates across sites were high, however, differences were found that reflected the composition of the samples. CONCLUSION: Improving the mental health state of the homeless will require significant capacity for mental health and concurrent disorder programming that is tailored to the community it intends to serve. Demographic features of the population may help in directing assessments of need.

Mental disorders in ecstasy users: a prospective-longitudinal investigation.

OBJECTIVES: To investigate the relationship between ecstasy use and mental disorders in a representative sample of adolescents and young adults. METHOD: Data for this investigation were drawn from the Early Developmental Stages of Psychopathology (EDSP) study, an epidemiological-longitudinal study in which 14-24 year-olds were examined prospectively over a period of about 4 years. Results are based on N=2462 participants who completed the whole study period and for whom drug use behavior could be determined. RESULTS: (1). Ecstasy users, compared with non-users, were at significantly increased risk of DSM-IV substance related disorders, including alcohol use disorders (52.6 vs. 15.6%; OR=5.6, 95% CI=3.8-8.1). Further, ecstasy users also had a higher risk of alcohol use disorders, when compared with users of other illicit substances (52.6 vs. 40.3%; OR=1.7, 95% CI=1.1-2.4). (2). Ecstasy users had significantly higher rates for almost all DSM-IV mental disorders examined when compared with non-users (any non-substance use disorder: 68.7 vs. 44.5%; OR=3.1, 95% CI=2.1-4.4) and compared with users of other illicit drugs (any non substance use disorder: 68.7 vs. 55.5%; OR=1.8, 95% CI=1.2-2.6). (3). Ecstasy users also reported significantly higher rates of prescription medicine use, though they did not use more medical services than non-drug users. (4). Analyses of temporal patterns of ecstasy use and disorder onset revealed that the first use of ecstasy was secondary to the onset of DSM-IV mental disorders in the majority of cases. Still, subjects with mental disorders at baseline also showed a significantly increased risk for initiation of ecstasy use during the 4-year follow-up period. CONCLUSIONS: Care should be taken in cross sectional studies in interpreting mental disorder signs and symptoms merely as a consequence of ecstasy use, as ecstasy use might be associated with the use of multiple substances, and onset of mental disorder is more likely to precede rather than to follow use of ecstasy and related substances.

Homeless and incarcerated: an epidemiological study from Canada.

BACKGROUND: Incarceration and homelessness are closely related yet studied rarely. This article aimed to study the incarcerated homeless and identify specific vulnerabilities, which rendered them different from the nonincarcerated homeless. It also aimed to describe the homeless population and its significant involvement with the criminal justice and enforcement system. METHODS: Data were derived from the British Columbia Health of the Homeless Study (BCHOHS), carried out in three cities in British Columbia, Canada: the large urban center Vancouver (n = 250), Victoria (n = 150) and Prince George (n = 100). Measures included socio-demographic information, the Maudsley Addiction Profile (MAP), the Childhood Trauma Questionnaire (CTQ) and the Mini International Neuropsychiatric Interview (MINI) Plus. RESULTS: Incarcerated homeless were more often male (66.6%), were in foster care (56.4%) and had greater substance use especially of crack cocaine (69.6%) and crystal methamphetamine (78.7%). They also had greater scores on emotional and sexual abuse domains of CTQ, indicating greater abuse. A higher prevalence of depression (57%) and psychotic disorders (55.3%) was also observed. Risk factors identified which had a positive predictor value were male gender (p < .001; odds ratio (OR) = 2.8; 95% confidence interval (CI): 1.7-4.4), a diagnosis of depression (p = .02; 95% CI: 1.1-4.4) and severe emotional neglect (p = .02; 95% CI: 1.1-3.2) in the childhood. CONCLUSION: Homeless individuals may be traumatized at an early age, put into foster care, rendered homeless, initiated into substance use and re-traumatized on repeated occasions in adult life, rendering them vulnerable to incarceration and mental illness.

Effects of irritability on craving before and after cue exposure in abstinent alcoholic inpatients: experimental data on subjective response and heart rate.

OBJECTIVE: Irritability is often linked with problem drinking. The aim of this study is to examine the possible influence of irritability on craving induced by a cue-exposure paradigm. METHODS: 30 male abstinent alcoholic inpatients of the Psychiatric Hospital of Munich University, Germany gave answers to a series of personality questionnaires. Results of this study concerning the impact of aggressivity on craving for alcohol has recently been published. In this study, the subjects were subdivided into a low- and a high-irritable group based on their scores on the irritability subscale of the Buss-Durkee Hostility Inventory and were exposed to alcohol cues. Craving was measured by means of the Alcohol Craving Questionnaire (ACQ) and Visual Analogue Scales (VAS). The heart rate was also assessed throughout the whole process. ANCOVA for repeated measurement was employed to evaluate the data - irritability disposition as the between-subject factor and the experimental manipulation (absence vs. presence of alcohol cues) as the within-subject factor. RESULTS: Major findings are: (1). main effects of irritability on 'emotionality', 'purposefulness', and 'expectancy' of the ACQ as well as on 'craving for alcohol' of the VAS were significant; (2). cue exposure also exerted a significant main effect on 'craving for alcohol' of the VAS and on the heart rate after the presentation of alcohol cues; (3). on 'compulsivity' of the ACQ and 'intention to alcohol intake' of the VAS; there was a significant interaction between irritability and cue exposure. The high-irritable alcoholics, compared with their statements in the baseline, tended to report a higher control over alcohol intake and a lower intention to alcohol use after cue exposure. However, after confrontation with alcohol stimuli, their low-irritable counterparts reported a much lower control and a slightly higher intention than they did in the baseline. CONCLUSIONS: The results of this study indicate that induced craving in hospitalized alcohol addicts probably varies with the magnitude of their irritability; it might make patients more aware of their vulnerability to alcohol, help them develop more differential coping strategies and improve medical therapy against alcohol craving.