Does nicotine affect D2 receptor upregulation? A case-control study.

OBJECTIVE: Nicotine has a powerful preventive effect on neuroleptic-induced dopamine D2 receptor upregulation in the rat. The aim of this human positron emission tomography (PET) study was to compare upregulation in a smoker and a non-smoker, both of whom had received haloperidol for the same duration of time. METHOD: Two subjects who had been treated for 16 years with a constant dose of haloperidol were scanned after temporary haloperidol withdrawal, using [11C]-raclopride. RESULTS: The non-smoker, who had received a dose of 10 mg/day, showed a D2 upregulation of 98% and developed severe and persistent symptoms of tardive dyskinesia (TD) upon withdrawal. The chronic smoker, who had been treated with 40 mg/day, displayed a D2 upregulation of 71% and did not develop TD. CONCLUSION: These human observations agree with animal data which showed that nicotine can decrease neuroleptic-induced D2 receptor upregulation. This property of nicotine may play a protective role in movement disorders whose pathophysiology involves D2 receptor hypersensitivity.

Increased dopamine D2 receptor binding after long-term treatment with antipsychotics in humans: a clinical PET study.

RATIONALE: Dopamine D2 receptor upregulation in the striatum is regularly seen in response to the administration of traditional antipsychotics in animal experiments. This is associated with hyperactivity and, for this reason, D2 receptor upregulation has long been postulated as central to tardive dyskinesia (TD). OBJECTIVE: Using positron emission tomography (PET), the present study attempted to determine whether antipsychotic-induced D2 receptor up-regulation also occurs in humans. METHODS: The long-term effects of traditional and novel antipsychotics on dopamine D2 receptors were investigated in nine subjects meeting DSM-IV criteria for schizophrenia who were deemed eligible for temporary treatment washout. Subjects had been treated with traditional antipsychotics (haloperidol n=3, perphenazine n=1) and novel antipsychotics (risperidone n=3, olanzapine n=2) in the moderate to high dosage range. Fourteen days after treatment withdrawal, the binding potentials (BPs) of dopamine D2 receptors were measured using 11[C] raclopride. The obtained BPs were compared to the BPs from antipsychotic-naive control subjects with schizophrenia. RESULTS: There was a significant increase in the D2 BP in both groups combined that reached 34%. The increases in the D2 BPs in the groups treated with conventional and novel antipsychotics were 37% and 31%, respectively. Significantly, the patients showing the highest degree of D2 receptor upregulation (98%) developed severe and persistent TD shortly after being started on a new antipsychotic with low affinity for D2 receptors. CONCLUSION: This study demonstrates for the first time, using in vivo neuroreceptor imaging, that dopamine D2 receptor binding is increased after long-term treatment with antipsychotics in humans. The data suggest that both traditional and novel antipsychotics with high affinity for dopamine D2 receptors are associated with a substantial increase in D2 receptor binding. The present data in humans agree well with animal data that implicate D2 receptor-mediated mechanisms in motor hyperactivity.

Diagnostic subgroups within a sample of comorbid substance abusers: correlates and characteristics.

Patients seeking treatment at the Addiction Research Foundation for a substance problem but who also reported psychiatric symptomatology were referred to the Mental Health Unit. Following a clinical psychiatric interview, these patients were categorized into one of six diagnostic subgroups based on the presence of DSM-III-R psychiatric disorders: mood, anxiety, psychotic, organic, Axis-II, and adjustment. A control group of patients referred to the Mental Health Unit but not diagnosed with a psychiatric disorder was also included. These groups were compared on several demographic, substance use, and psychiatric variables. Patients assigned a diagnosis of organic (substance-induced) and Axis II disorders were found to have more severe substance use histories, alcohol-related consequences and longer treatment histories. Patients with a diagnosis of adjustment disorder appeared to be functioning relatively better. Implications of studying the heterogeneity of comorbidity are discussed.

The impact of depression on the outcome of addictions treatment.

The objectives of this study were to examine the prevalence and presentation of depression among patients with substance use disorders, and to explore the relationship between depression and the outcome of addictions treatment. Seventy-five patients were consecutively recruited upon entering addictions treatment, and were assessed by clinical and semi-structured interviews, Hamilton Rating Scale for Depression, Global Assessment Scale, and Beck Depression Inventory. At intake, 22.4% of patients had primary depressive disorders, 8.4% had substance-induced depressions, and 5.6% had mixed features of primary and substance-induced depressions. Female and alcoholic patients were more likely to suffer from both primary and substance-induced depressions. At 3 months, 93.3% of patients were reinterviewed. Depressed patients had longer duration of abstinence and greater decreases in symptomatology. Patients with substance-induced depression achieved almost complete discontinuation of primary substance use. Depression had a significant impact on addictions treatment outcome, but many important predictors of outcome have not yet been identified.

Family history of alcoholism and the mediation of alcohol intake by catalase: further evidence for catalase as a marker of the propensity to ingest alcohol.

Earlier studies have suggested that catalase activity (CA) may represent a biological marker of alcohol intake in animals and in humans. An initial study was designed to rule out the possibility that CA is induced as a function of acute alcohol intake. Subjects (n = 80) were presented with either an alcohol (0.5 g/kg of body weight) or control solution, and asked to provide four 100-microliters blood samples at 0.0, 0.5, 2.0, and 24.0 hr. Results showed no differences in CA between individuals who had received alcohol, and controls, even when the effects of previous drinking history were covaried out. This lack of effect of acute alcohol intake on the possible induction of CA further supported the notion that CA may be a viable marker of alcohol intake, rather than the converse. In the second study, the relation between CA and alcohol intake was investigated in individuals with a family history (FH) of alcoholism (FH+), and in those without a family history of alcoholism (FH-). Subjects (n = 607) completed the Michigan Alcoholism Screening Questionnaire, the MacAndrew Scale, and the Concordia University Alcohol Screening Questionnaire; answered questions concerning their FH for alcoholism; and provided a 100-microliters blood sample. Results showed that FH+ individuals had higher mean CA compared with FH- individuals. When individuals with FH+ were compared with those with FH-, differences in the pattern of relation between CA and alcohol intake were observed. Although a significant relation between CA and alcohol intake was obtained for both FH- and FH+ individuals, this relation was significantly higher (p < 0.001) for individuals with FH+.(ABSTRACT TRUNCATED AT 250 WORDS)

Cue-evoked arousal in cocaine users: a study of variance and predictive value.

Thirty-six cocaine abusers in treatment and 16 non-using controls were exposed to visual cocaine cues; measurements included changes in skin conductance and a rating of psychological arousal (persisting cocaine thoughts and images during the 24 h following the experiment). The GSI score of the HSCL-58 was used as an indicator of psychological distress. Probands showed arousal responses significantly higher than the controls. Skin conductance readings correlated positively with HSCL-58 scores and with severity of craving in the week prior to the trial. Unexpectedly, they correlated negatively with duration of cocaine use and did not vary as a function of the severity of cocaine addiction or the duration of cocaine abstinence prior to the test. Neither cocaine addiction measurements nor arousal responses were found to predict cessation of use (a minimum of 3 months of sustained abstinence) 1 year after the test.

Cocaine problems in the coca-growing countries of South America.

The problems of cocaine present a rather particular profile in the Central Andes region from which this drug originates. On the one hand there is a relatively harmless pattern of use (coca leaf chewing) in the countries concerned which minimizes the drug's most hazardous properties. On the other hand the region suffers from some of the most severe cocaine-related problems to be observed anywhere: (a) easy access to the newer, highly toxic preparations of the drug (such as coca paste) and a rapid growth in the number of new users; (b) the abandonment of certain traditional and essential agricultural activities in favour of the more profitable coca leaf production; (c) the severe ecological damage being caused in the coca growing areas; and (d) the establishment of a powerful coca trade economy which is subverting the very fabric of society and is creating corruption, lawless violence and political anarchy.

The role of medical schools in the prevention of alcohol-related problems.

There is agreement that physicians can play a major role in the prevention of alcohol problems among their patients and that medical schools should prepare physicians for this role by teaching three major subject areas: knowledge, attitudes and clinical skills. Despite this agreement and the acknowledged high prevalence of alcohol problems in clinical populations, medical school coverage of these problems is not proportional to their importance. Barriers to adequate coverage of alcohol problems are traditional attitudes, confusion as to whether such problems are "medical" and lack of adequate faculty role models. These problems could be remedied by encouragement and training of interested faculty members, establishment of substance abuse centres in university medical schools, integration of alcohol-related material with relevant topics in all departments and inclusion of alcohol-related questions on medical qualifying exams.

The social complications of chronic alcohol abuse: relative influence of family history and severity of alcohol dependence.

Alcoholics with a family history of the disease are said to present more severe consequences than alcoholics without such a history. This study examined the frequency distribution of severe alcohol dependence and police arrests for public drunkenness across samples of alcoholics with (n = 77) and without (n = 37) a family history of alcoholism. Both the percentage of subjects presenting severe dependence and the history of police arrests were greater in the positive family history group, but these differences did not reach conventional levels of statistical significance. However, results of logistic regression analyses demonstrate that male sex, younger age and, above all, severity of alcohol dependence, are better correlates of the occurrence of police arrests than is the subject's family history of alcoholism. The picture presented by this sample of outpatient alcoholics appears to qualify some currently held assumptions of the influence of family history on the phenomenology of alcoholism.

Screening for alcoholism among alcohol users in a traditional Arab Muslim society.

The Short Michigan Alcoholism Screening Test (S-MAST) was applied to 140 alcohol users in the traditional Muslim society of Kuwait. One hundred were confirmed alcoholics and 40 were self-disclosed social drinkers in the community. The questionnaire significantly discriminated between the groups. Its sensitivity level was 100% and its specificity 82.5%. Although all except one of the S-MAST items elicited significant differences between the groups in question, it appears that the particular sociocultural conditions of the setting may influence the validity of some of them.

Cannabis affects the severity of schizophrenic symptoms: results of a clinical survey.

Data on the history of cannabis use and a spot urine test for cannabinoids were obtained for 137 schizophrenics in treatment. Subjects who were using cannabis during the 6-month observation period presented with a significantly higher degree of delusional and hallucinatory activity than those who did not. Moreover, the group using cannabis made a higher average number of visits to the hospital during the same period. The status of cannabis use appeared to contribute to such variance more than did other relevant factors (age, stage of the illness, amount of medication prescribed, occasional use of other psychoactive substances).