Reduced memory and attention performance in a population-based sample of young adults with a moderate lifetime use of cannabis, ecstasy and alcohol.

Regular use of illegal drugs is suspected to cause cognitive impairments. Two substances have received heightened attention: 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') and delta-9-tetrahydrocannabinol (THC or 'cannabis'). Preclinical evidence, as well as human studies examining regular ecstasy consumers, indicated that ecstasy use may have negative effects on learning, verbal memory and complex attentional functions. Cannabis has also been linked to symptoms of inattention and deficits in learning and memory. Most of the published studies in this field of research recruited participants by means of newspaper advertisements or by using word-of-mouth strategies. Because participants were usually aware that their drug use was critical to the research design, this awareness may have caused selection bias or created expectation effects. Focussing on attention and memory, this study aimed to assess cognitive functioning in a community-based representative sample that was derived from a large-scale epidemiological study. Available data concerning drug use history allowed sampling of subjects with varying degrees of lifetime drug experiences. Cognitive functioning was examined in 284 young participants, between 22 and 34 years. In general, their lifetime drug experience was moderate. Participants completed a neuropsychological test battery, including measures for verbal learning, memory and various attentional functions. Linear regression analysis was performed to investigate the relationship between cognitive functioning and lifetime experience of drug use. Ecstasy and cannabis use were significantly related to poorer episodic memory function in a dose-related manner. For attentional measures, decrements of small effect sizes were found. Error measures in tonic and phasic alertness tasks, selective attention task and vigilance showed small but significant effects, suggesting a stronger tendency to experience lapses of attention. No indication for differences in reaction time was found. The results are consistent with decrements of memory and attentional performance described in previous studies. These effects are relatively small; however, it must be kept in mind that this study focussed on assessing young adults with moderate drug use from a population-based study.

[AWMF-guideline: cocaine-, amphetamine-, ecstasy- and hallucinogen-related disorders]. / AWMF-Behandlungsleitlinie: Psychische und Verhaltensstörungen durch Kokain, Amphetamine, Ecstasy und Halluzinogene.

Actually, guidelines for treatment of substance-related disorders were written under the overall control of the DG-Sucht e. V. and the DGPPN e. V. This appears within the framework of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaft (AWMF). The leading objective of these guidelines is the description of the current scientifically proven and evidence-based medicine in addiction to derive recommendations to therapy. In this context, the guideline for treatment of cocaine-, amphetamine-, ecstasy-, and halluzinogen-related disorders is introduced.

Predictors for completing an inpatient detoxification program among intravenous heroin users, methadone substituted and codeine substituted patients.

Up to 1999 more opioid dependent patients in Germany were substituted with codeine or dihydrocodeine (summarised as codeine) than with methadone. The current retrospective study compares the differences in detoxification treatment outcome for codeine-substituted patients, methadone-substituted patients and patients injecting illicit heroin. The study is based on the medical records of 1070 patients admitted consecutively for opioid and polytox detoxification between 1991 and 1997. The main hypothesis was that injecting illicit-heroin users would complete detoxification treatment less often than codeine- or methadone- substituted patients, and that methadone-substituted patients who had received more structured treatment would complete more often than codeine-substituted patients who did not receive any structured treatment beyond the prescription of codeine. We analysed a number of demographic and drug related variables as possible predictors. Our bivariate analyses confirmed our main hypothesis: 50.4% (OR: 1.8) of the methadone-substituted patients, 45.5% (OR: 1.5) of the codeine-substituted patients and 35.9% (OR: 1 comparison group) of the injecting illicit-heroin users completed the detoxification program (P=0.006). This finding remained significant even after correcting for a number of confounders. Using stepwise multiple logistic regression analyses, we found age, education, history of imprisonment, regular contact with a counsellor, currently being on probation and reported plans for participating in an abstinence treatment program to be significant predictors of completing detoxification treatment. Although the current analysis did not rule out differences in pharmacological effects as a contributing factor, the results are consistent with an interpretation of a dose-response association between psychosocial/psychotherapeutic support and detoxification outcome. More psychosocial/psychotherapeutic support leads to better detoxification treatment response.

[Therapeutic strategies and help in chronic alcoholism]. / Therapeutische Strategien und Hilfen bei chronischen Alkoholikern.

Chronical alcoholics are a challenge in therapy, especially if they have an adverse course of illness and treatment as well as multiple resulting somatical and neurological diseases. In German treatment of alcoholics the term 'chronisch mehrfach geschädigte Alkoholkranke' (chronically multiple affected alcoholics) has been established, describing patients with severe somatical and psychological disorders as well as social, professional, financial or legal problems. Permanent or even temporary abstinence is hard to achieve for these patients. They are usually found in psychiatric hospitals rather than in addiction wards, but also in social services or even prisons. Rehabilitation is possible in mental state hospitals that accept patients with dual diagnosis, sometimes even in special wards. Psychiatric co-morbidity in alcoholics is often underestimated. This is most important for psychotic illness, as well as other psychic diseases. A special problem is posed by delinquent patients that often have to be treated while in a penal institution. Some of the follow-up studies done on that have shown relatively good results in patients in penal institutions, but further studies are needed. As of yet, recent treatment options in pharmacotherapy to prevent alcoholic relapse are not sufficiently used. Anti-dipsotropics or so-called anti-craving-agents like acamprosate and naltrexone are primarily given to increase the rate of abstinence but could successfully be used in a harm reduction strategy (less drinking, shorter relapses).

Dynorphin A (2-17) attenuates the unconditioned but not the conditioned effects of opiate withdrawal in the rat.

OBJECTIVES: An unbiased place preference conditioning procedure was used to examine the influence of the non-opioid peptide, dynorphin A 2-17 (DYN 2-17), upon the conditioned and unconditioned effects of opiate withdrawal in the rat. METHODS: Rats were implanted SC with two pellets containing 75 mg morphine or placebo. Single-trial place conditioning sessions with saline and the opioid receptor antagonist naloxone (0.1-1.0 mg/kg; SC) commenced 4 days later. Ten minutes before SC injections, animals received an IV infusion of saline or DYN 2-17 (0.1-5.0 mg/kg). Additional groups of placebo- and morphine-pelleted animals were conditioned with saline and DYN 2-17. During each 30-min conditioning session, somatic signs of withdrawal were quantified. Tests of place conditioning were conducted in pelleted animals 24 h later. RESULTS: Naloxone produced wet-dog shakes, body weight loss, ptosis and diarrhea in morphine-pelleted animals. Morphine-pelleted animals also exhibited significant aversions for an environment previously associated with the administration of naloxone. These effects were not observed in placebo-pelleted animals. DYN 2-17 pretreatment resulted in a dose-related attenuation of somatic withdrawal signs. However, conditioned place aversions were still observed in morphine-pelleted animals that had received DYN 2-17 in combination with naloxone. Furthermore, the magnitude of this effect did not differ from control animals. CONCLUSIONS: These data demonstrate that the administration of DYN 2-17 attenuates the somatic, but not the conditioned aversive effects of antagonist-precipitated withdrawal from morphine in the rat. Differential effects of this peptide in modulating the conditioned and unconditioned effects of opiate withdrawal are suggested.

NMDA receptor challenge with dextromethorphan - subjective response, neuroendocrinological findings and possible clinical implications.

Glutamatergic NMDA receptors are believed to play a major role in the pathophysiology of numerous neuropsychiatric disorders including substance use and schizophrenia. Neuropharmacological studies measuring subjective response, psychopathology and biological parameters are helpful in studying pathophysiology of these disorders. We report preliminary data of a placebo-controlled double-blind challenge study in recently detoxified alcoholics (n = 20) and healthy controls (n = 10) using the non-competitive NMDA antagonist dextromethorphan. Findings suggest that dextrometorphan can produce ethanol-like subjective effects in both alcoholics and controls and induce a mild form of craving in alcoholics only. The results of this study give further support to the hypothesis of glutamatergic NMDA receptors mediating much of ethanol's psychotropic effects. Possible clinical implications of these findings are discussed.

Phytohemagglutinin-stimulated calcium signal in lymphocytes of alcoholics before, during and after detoxification.

Acute and chronic exposure to ethanol influences intracellular calcium homeostasis via NMDA receptors, direct regulation of calcium channels or the phosphoinositide pathway. To explore the influence of alcohol withdrawal on calcium metabolism, we have investigated the resting and phytohemagglutinin (PHA) stimulated [Ca2+]i in lymphocytes of 10 alcoholics before, during and after withdrawal. Our findings suggest that both compartments of the PHA-stimulated signal are affected in alcoholics, with flattening of the initial peak and sustained calcium influx, as long as severe vegetative signs are present. MANOVA results showed significant interaction effects for both measurement points, for the initial peak, 40 s after stimulation (P = 0.05), and especially for the sustained influx at the end of the observation period (P = 0.001). The detailed mechanisms of this disturbed calcium homeostasis need further investigation.

Age-specific patterns of hallucinogen use in the US population: an analysis using generalized additive models.

Although there has been growing concern in recent years about an escalation in the use of LSD and other hallucinogens, little is known about the distribution of the use of these drugs in the United States population. In order to fill this gap, we used generalized additive models to analyze data from the 1988, 1990, and 1992 National Household Survey on Drug Abuse, to compare the age-specific prevalence of hallucinogen use by level of socio-economic indicators. In addition, we used survival analysis to compare patterns in the onset of use. Use of hallucinogens in the past year was highest at the age of 19 years for each of the NHSDA surveys, but use was not linked to enrollment in school at this age. Past year prevalence was highest among whites and respondents with high family income. The onset of hallucinogen use was most likely to occur between ages 15-19 years, regardless of birth cohort. These results indicate a stable pattern since hallucinogens were made widely available in the late 1960s, in which the transition from adolescence to adulthood has been the period of highest risk for hallucinogen use.

Role of delta-opioid receptors in mediating the aversive stimulus effects of morphine withdrawal in the rat.

An unbiased place preference conditioning procedure was used to examine the role of delta-opioid receptors in mediating the aversive effects of opioid withdrawal. Rats were implanted s.c. with two pellets each containing placebo or 75 mg morphine. Single-trial conditioning sessions with saline and the opioid receptor antagonists naloxone (0.001-1.0 mg/kg, s.c.), naltrindole (0.01-3.0 mg/kg, s.c.) or naltriben (0.01-3.0 mg/kg, s.c.) commenced 4 days later. During these conditioning sessions, physical signs of withdrawal were also quantified. Tests of conditioning were conducted on day 5. Naloxone in doses of 0.01-1.0 mg/kg produced significant conditioned place aversions in morphine-implanted animals. A dose of 0.01 mg/kg produced few physical withdrawal signs whereas higher doses resulted in marked wet dog shakes, body weight loss ptosis and diarrhea. No such effects were observed in control (placebo-implanted) animals. Administration of the selective delta-opioid receptor antagonists naltrindole and naltriben produced dose-related place aversions in morphine-implanted animals. The magnitude of these effects did not differ from that observed with naloxone. The minimum effective doses of naltrindole and naltriben were 0.1 mg/kg. Doses of 0.1-1.0 mg/kg produced few, if any, somatic signs of withdrawal whereas higher doses of these antagonists only produced diarrhea and wet-dog shakes. Other withdrawal signs were absent. In contrast to the opioid receptor antagonists tested, the dopamine D1 receptor antagonist SCH23390 failed to produced conditioned place aversions or physical signs of withdrawal in morphine-pelleted animals. These data demonstrate that the selective blockade of either delta- or mu-opioid receptors is sufficient to induce conditioned aversive effects in morphine-dependent animals. They also indicate that physical symptoms associated with precipitated morphine withdrawal differ depending upon the opioid receptor antagonist employed.

Inhalants to heroin: a prospective analysis from adolescence to adulthood.

Recent cross-sectional studies have indicated that inhalant use might be a vulnerability marker for the development of heroin use. This study is the first prospective investigation of the hypothesized association between early inhalant use and later heroin use. Analyses were conducted using longitudinal data from a community sample of Woodlawn (an all African American community on the South side of Chicago). Six-hundred subjects participated in both the adolescent and the adult assessments (approximately ages 16 and 32, respectively). Youths with a history of inhalant use by age 16 were over nine times more likely to begin heroin use by age 32, even when other plausible risk factors for the development of heroin use were held constant (RR = 9.3; 95% C.I. = 1.3 - 51.3). These findings add to and are consistent with prior cross-sectional evidence from data based on treatment samples and national survey data. The results from this longitudinal assessment support the idea that youthful inhalant use should be regarded as a vulnerability marker for the development of more serious drug use involvement in the form of heroin use.

Degree of acculturation and the risk of crack cocaine smoking among Hispanic Americans.

Epidemiologic data from three national surveys conducted in 1988, 1990, and 1991 were used to investigate the association between acculturation and use of crack cocaine among Hispanic Americans living in the United States. Poststratification and conditional logistic regression were used to hold constant shared aspects of neighborhood environment, age, sex, and education. The analyses showed a strong inverse relationship between degree of acculturation and crack smoking among Mexican Americans (relative odds = 0.12, 95% confidence interval = 0.04, 0.34) but not among other Hispanics in the study population. This observed variation within the US Hispanic American population deserves special attention in future research.

Suspected determinants of enrollment into detoxification and methadone maintenance treatment among injecting drug users.

Our primary aim in this study has been to evaluate selected conditions thought to influence the entry of injecting drug users (IDU) into detoxification and methadone maintenance programs, making use of a prospective study design to strengthen a cross-sectional investigation of these conditions. To begin our investigation, we analyzed cross-sectionally gathered data on 2879 IDUs who had been recruited through extensive community outreach efforts and who were interviewed at the time of recruitment. We then tested our hypotheses about suspected determinants of entry into treatment by analyzing prospectively gathered data on 1039 active drug users who had no recent history of being treated for drug problems. Among these 1039 IDUs (a subset of the initial cross-sectional sample), 144 entered a detoxification program between their recruitment interview and their next follow-up interview, conducted about six months after recruitment (range: 3.5-9.5 months) and 64 entered a methadone maintenance program during that observation interval. Using multiple logistic regression analyses, we found that a recent drug overdose, relatively higher frequency of injecting drugs, and a history of prior arrest or treatment were independent predictors of entry into detoxification. Being married or living with a partner, being female, a lengthy duration of drug use (> 10 years), and a history of prior treatment were independent predictors of entry into methadone maintenance. These findings shed light on what appears to be a different profile of suspected determinants of entry into a detoxification treatment versus methadone maintenance treatment, and help to clarify some potential differences between treated and untreated drug users that ought to be considered when evaluating results of investigations with IDU participants recruited solely from treatment settings.

The association between sniffing inhalants and injecting drugs.

There is evidence that the use of inhalants might prove to be a modifiable risk factor for intravenous (IV) drug use, or possibly an important vulnerability marker. However, this evidence has come from studies using samples of convenience, such as a mixture of psychiatric patients, felons, and their relatives. If there is a link between these two different forms of drug-using behaviors, then a statistical association should be found in epidemiologic studies with rigorous sampling procedures--even after statistical adjustment for plausible confounding variables such as sex, age, socioeconomic status, and the use of drugs such as marijuana. To probe this suspected causal association, we analyzed epidemiologic data from the 1990 National Household Survey on Drug Abuse sponsored by the National Institute on Drug Abuse. The population for this survey consisted of all household residents aged 12 years and older in the conterminous United States, with respondents selected by probability sampling. A total of 9,259 respondents completed the confidential self-report interview conducted by trained interviewers; 192 persons reported a history of injecting drugs for nonmedical reasons (e.g., to get high), and 9,067 reported never injecting drugs. As hypothesized, inhalant use was found to be associated with injecting drugs (relative odds [RO] = 11.8). After adjustment for sex, age, race, socioeconomic status, and use of marijuana, inhalant users still were 5.35 times more likely than nonusers to have injected drugs (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of self-reported injection frequencies for past 30 days and 6 months among intravenous drug users.

In this study we compared two parallel self-reported measures that now are being used to assess the recent frequency of intravenous drug use. This study sample consisted of 926 HIV seronegative drug users recruited for participation in HIV research. During a standard interview with each drug user, we first asked about injections in the past 30 days, and then about injections in the past 6 months. The correlation between reports on the past 6 months and the past 30 days was appreciable when all injections were considered (Spearman correlation coefficient rho = 0.78). It increased when the sample was restricted to subjects who reported injections in the past month (rho = 0.88). This restriction resulted in a 15% reduction of the sample size, since 137 participants reported drug use in the previous 6 months but not in the previous 30 days. Concordance tended to be slightly higher for reported frequencies of heroin injections than for cocaine injections, and for men as compared to women. The observed levels of concordance indicate that in many instances both approaches can yield comparable results. Nevertheless the choice of 30 days recall vs 6 months recall must rest upon the specific research questions of each investigation.

[Evaluation of central and peripheral components of muscular fatigue in neuropathic and myopathic patients]. / Evaluación del componente central y periférico de fatiga muscular en pacientes neuropáticos y miopáticos.

In a group of patients chronically denervated and other with primary muscle involvement a search was made for mechanisms involved in the muscular fatigue. It was found that there was no major differences between patients chronically denervated and controls, while in those others with primary muscle disorders a loss of functional motor units during effort and a transient impairment of neuromuscular transmission play a role together with the central events normally occurring in fatigue.

[Evaluation of central and peripheral factors in muscular fatigue in patients with pyramidal lesions]. / Evaluación del factor central y periférico en fatiga muscular en pacientes con daño piramidal.

Muscular fatigue mechanisms were partially analyzed in patients with pyramidal lesions by using a computer device on line with a conventional electromyograph. Both the normal and the affected side were compared with control groups. The recordings were done throughout a ten minutes period and the maximal M wave was also measured at the starting and at the end of the procedure. The findings suggested that central events play a major role in the development of muscular fatigue in spastic muscles due to pyramidal damage.

Evaluacion del factor central y periferico en fatiga muscular en pacientes com dano piramidal. / Evaluation of central and peripheral factors in muscular fatigue in patients with pyramidal lesion

Para evaluar algunos de los componentes de la fatiga muscular en el dano piramidal, se selecciono un grupo de 15 pacientes con hemiparesia faciobraquiocrural de severidad variable, los cuales fueron sometidos a un esfuerzo muscular, durante el cual se evaluaron los cambios de la frecuencia y duracion de los potenciales positivos y negativos de EMG, asi como los sufridos por la onda paretico, el contralateral y en un grupo control de voluntarios sanos, comparandose los resultados de los 3 grupos. Las curvas de frecuencia y duracion del labo paretico, el sano y el control mantuvieron las mismas tendencias, asi como fue homologable el comportamiento de la onda M maxima en los 3 casos, lo cual indica que en la poblacion normal, bajo las presentes condiciones de estudio, es el factor central el condicionante principal en el desarrollo de fatiga muscular