Search PubMed⌕ Search

Biomedical subjects

T R Kosten

Publications and source records attributed to T R Kosten.

At least 19 recordsLinked to original sources
PubMed2001

Pathological gambling.

Explore the source record for details and available documents.

Disruptive, Impulse Control, and Conduct Disorders↗
PubMed2001

Effects of cocaine prior to and during bupropion maintenance in cocaine-abusing volunteers.

The effects of cocaine were examined prior to and during bupropion maintenance in nonopioid-dependent cocaine abusers. Prior to bupropion maintenance, subjects underwent an experimental session during which repeated cocaine doses (0, 50, 100 mg/70 kg) were administered intranasally. Then subjects were maintained on bupropion (150 and 300 mg per day) and underwent experimental sessions as before. Cocaine, regardless of bupropion, produced dose-related increases in several stimulant-like self-reports, performance and cardiovascular measures. Bupropion decreased POMS ratings of friendliness and vigor, regardless of cocaine dose. Bupropion enhanced and attenuated cocaine-induced increases in ratings on the LSD and BG subscales of the ARCI, respectively. These results suggest that bupropion does not alter the acute subjective or cardiovascular effects of cocaine in a robust manner.

Administration, Intranasal↗
PubMed2001

Quantitative medial temporal lobe brain morphology and hypothalamic-pituitary-adrenal axis function in cocaine dependence: a preliminary report.

Preclinical and clinical studies have shown that cocaine increases plasma adrenocorticotropin hormone (ACTH) and cortisol. Chronic elevation of plasma cortisol exerts direct toxic effects upon hippocampal neurons and exacerbates hippocampal damage resulting from ischemia and seizures. The authors tested for evidence of hippocampal damage in patients with chronic cocaine dependence. Medial temporal lobe and total brain volumes were quantified using magnetic resonance imaging (MRI) in 27 patients with cocaine dependence and 16 healthy subjects. Basal and ovine corticotropin releasing hormone (oCRH) stimulated ACTH and cortisol levels were also examined in a subset of 8 healthy and 9 cocaine dependent subjects after 21 days of abstinence. No evidence for decreased hippocampal or total brain volume in cocaine dependence was observed. Similarly, basal and oCRH stimulated ACTH and cortisol levels in cocaine dependent patients did not differ from those in healthy subjects.

Adrenocorticotropic Hormone↗
PubMed2001

Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.

Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the previous report and provides an additional objective measure for perturbation of noradrenergic and stress responses in these patients.

Acoustic Stimulation↗
PubMed2001

Neuroleptic use in the treatment of Post-Traumatic Stress Disorder.

BACKGROUND: There have been few studies of the use of neuroleptics in the treatment of Post-Traumatic Stress Disorder (PTSD). This study uses data from two large outcome studies to: (1) examine demographic and treatment characteristics associated with neuroleptic prescription in the treatment of PTSD, and (2) compare the outcomes of neuroleptic-treated patients with those not receiving neuroleptics. METHODS: A secondary analysis of an observational outcome study of 831 inpatients and 554 outpatients (all males) receiving treatment at the VA for combat-related PTSD was performed. Patients were classified as having either received neuroleptics during the following year or not. Sociodemographic characteristics, treatment and medication history and detailed information about PTSD symptoms were obtained at baseline and 12 months. First, the two groups were compared with respect to the demographic and clinical variables. We then conducted a series of separate paired t-tests to determine whether there was significant improvement from baseline to follow up in each group and a series of analyses of covariance that compared outcomes in the two groups, adjusting for baseline differences. RESULTS: Approximately 9% of inpatients and 10% of outpatients were treated with neuroleptics. Patients who received neuroleptics had both more psychiatric and more social impairment. They also demonstrated more severe PTSD (especially intrusive symptoms) despite having similar combat exposure. Outcomes after one year for the group treated with neuroleptics were not significantly different from the group not treated with neuroleptics. CONCLUSIONS: Neuroleptic use in the treatment of PTSD is targeted at more seriously ill patients and was not associated with substantial improvement.

Adult↗
PubMed2001

Quantitative morphology of the caudate and putamen in patients with cocaine dependence.

OBJECTIVE: Deficits in dopaminergic function may contribute to hypertrophy of striatal structures associated with typical neuroleptic treatment. In light of a body of research that has associated chronic cocaine use with extrapyramidal symptoms and striatal dopaminergic depletion, the authors looked for evidence of striatal dysmorphology in patients with chronic cocaine dependence. METHOD: Caudate, putamen, and total brain volumes were quantified by means of magnetic resonance imaging in 25 cocaine-dependent and 20 healthy subjects. RESULTS: Normalized caudate and putamen volumes were 3.40% and 9.18% larger, respectively, in the cocaine-dependent subjects. CONCLUSIONS: These observations suggest that deficits in dopaminergic function associated with cocaine dependence may contribute to striatal hypertrophy.

Adult↗
PubMed2001

Substance use disorders in patients with posttraumatic stress disorder: a review of the literature.

OBJECTIVE: Alcohol use disorders and other substance use disorders are extremely common among patients with posttraumatic stress disorder (PTSD). This article reviews studies pertaining to the epidemiology, clinical phenomenology, and pathophysiology of comorbid PTSD and substance use disorders. METHOD: Studies were identified by means of computerized and manual searches. The review of research on the pathophysiology of PTSD and substance use disorders was focused on studies of the hypothalamic-pituitary-adrenal axis and the noradrenergic system. RESULTS: High rates of comorbidity suggest that PTSD and substance use disorders are functionally related to one another. Most published data support a pathway whereby PTSD precedes substance abuse or dependence. Substances are initially used to modify PTSD symptoms. With the development of dependence, physiologic arousal resulting from substance withdrawal may exacerbate PTSD symptoms, thereby contributing to a relapse of substance use. Preclinical work has led to the proposal that in PTSD, corticotropin-releasing hormone and noradrenergic systems may interact such that the stress response is progressively augmented. Patients may use sedatives, hypnotics, or alcohol in an effort to interrupt this progressive augmentation. CONCLUSIONS: Vigorous control of withdrawal and PTSD-related arousal symptoms should be sought during detoxification of patients with comorbid PTSD and substance use disorders. Inclusion of patients with comorbid PTSD and substance use disorders in neurobiologic research and in clinical trials will be critical for development of effective treatments for this severely symptomatic patient population.

Adult↗
PubMed2001

Effect of opioid dependence pharmacotherapies on zidovudine disposition.

Injection drug users are frequently infected with human immunodeficiency virus (HIV) and receive opioid dependence pharmacotherapies and zidovudine (ZDV), the latter as a component of highly active antiretroviral therapy. We previously reported that methadone substantially increases ZDV concentrations. We now report on oral ZDV pharmacokinetics in 52 subjects receiving the opioid dependence pharmacotherapies l-alpha-acetylmethadol LAAM, buprenorphine, or naltrexone, and 17 non-opioid-treated controls. Relative to the area under the time-concentration curve (AUC) of ZDV in control subjects, no statistically significant differences in ZDV AUC were observed in participants treated with LAAM (p = .75), buprenorphine (p = .37), or naltrexone (p = .34). While methadone maintenance may result in ZDV toxicity and possibly require dose adjustments, other opioid pharmacotherapies should not produce ZDV toxicity.

Anti-HIV Agents↗
PubMed2000

Thrice-weekly versus daily buprenorphine maintenance.

BACKGROUND: Buprenorphine is a promising alternative to methadone or levo-acetyl alpha methadol for opioid agonist maintenance treatment, and thrice-weekly dosing would facilitate its use for this purpose. METHODS: After a 3-day induction, opioid-dependent patients (n = 92) were randomly assigned to daily clinic attendance and 12-weeks maintenance treatment with sublingual buprenorphine administered double blind either daily (n = 45; 16 mg/70 kg) or thrice weekly (n = 47; 34 mg/70 kg on Fridays and Sundays and 44 mg/70 kg on Tuesdays). Outcome measures include retention, results of 3x/week urine toxicology tests, and weekly self-reported illicit drug use. RESULTS: There were no significant differences at baseline in important social, demographic, and drug-use features. Retention was 71% in the daily and 77% in the 3x/week conditions. The proportion of opioid-positive urine tests decreased significantly from baseline in both groups and averaged 57% (daily) and 58% in 3x/week. There were no significant differences between groups in self-reported number of bags of heroin used for any day of the week, including Thursdays (48-72 hours following the last buprenorphine dose for subjects in the 3x/week condition), or in medication compliance (92%, 91%) and counseling attendance (82%, 82%). CONCLUSIONS: At an equivalent weekly dose of 112 mg/70 kg, thrice-weekly and daily sublingual buprenorphine appear comparable in efficacy with regard to retention and reductions in illicit opioid and other drug use. These findings support the potential for utilizing thrice-weekly buprenorphine dosing in novel settings.

Adult↗
PubMed2000

Disulfiram versus placebo for cocaine dependence in buprenorphine-maintained subjects: a preliminary trial.

BACKGROUND: We examined the effects of disulfiram versus placebo on cocaine dependence in buprenorphine-maintained subjects. METHODS: Opioid and cocaine dependent subjects (n = 20) were induced onto buprenorphine maintenance, then randomized to disulfiram (250 mg q.d. ; n = 11) or placebo (n = 9) treatment for 12 weeks. RESULTS: Groups were comparable at baseline on demographic measures and on baseline measures of drug-use severity. Fifteen subjects completed the study, including 8 subjects randomized to disulfiram (72.7%) and 7 subjects randomized to placebo (77.8%). The total number of weeks abstinent from cocaine was significantly greater on disulfiram versus placebo (mean +/- SD: 7.8 +/- 2.6 vs. 3.3 +/- 0.5, p <.05) and the number of days to achieving 3 weeks (24.6 +/- 15.1 vs. 57.8 +/- 7.7, p <.01) of continuous cocaine abstinence was significantly lower in disulfiram compared with placebo. The number of cocaine-negative urine tests during the trial were also higher on disulfiram (14.7) than on placebo (8.6); furthermore, subjects in the disulfiram group achieved consistently higher rates of cocaine-negative urine tests in each 3-week interval and the increase over time was faster in the disulfiram compared with placebo. CONCLUSIONS: This preliminary study suggests the potential efficacy of disulfiram versus placebo for treatment of cocaine dependence in buprenorphine-maintained patients.

Adult↗
PubMed2000

Significant interaction between clozapine and cocaine in cocaine addicts.

Because clozapine may be prescribed to cocaine abusing patients with schizophrenia, we studied cocaine-clozapine interactions in a controlled setting. Eight male cocaine addicts underwent four oral challenges with ascending doses of clozapine (12.5, 25 and 50 mg) and placebo followed 2 h later by a 2-mg/kg dose of intranasal cocaine. Subjective and physiological responses, and serum cocaine levels were measured over a total 4-h period. Clozapine pretreatment increased cocaine levels during the study and significantly increased the peak serum cocaine levels in a dose dependent manner. In spite of this elevation in blood levels, clozapine pretreatment had a significant diminishing effect upon subjective responses to cocaine, including 'expected high', 'high' and 'rush', notably at the 50 mg dose. There was also a significant effect upon 'sleepiness', 'paranoia' and 'nervous'. Clozapine caused a significant near-syncopal episode in one subject in the study, requiring his removal from the study. Clozapine had no significant effect on baseline pulse rate and systolic blood pressure, but it attenuated the significant pressor effects of the single dose of intranasal cocaine. These data suggested a possible therapeutic role for clozapine in the treatment of cocaine addiction in humans, but also suggests caution due to the near-syncopal event and the increase in serum cocaine levels.

Adult↗
PubMed2000

Effects of lamotrigine on behavioral and cardiovascular responses to cocaine in human subjects.

We evaluated the effects of acute pretreatment with lamotrigine, a putative glutamate release inhibitor, on the physiological and behavioral responses to intranasal cocaine in cocaine-dependent volunteers (N = 8). The study employed a double-blind, placebo-controlled, within-subject design. Subjects participated in six experimental sessions. On each study day, placebo, lamotrigine 125 mg, or lamotrigine 250 mg was administered orally in the morning, followed 2 hours later by intranasal cocaine 120 mg/70 kg or placebo. Measurements of heart rate and blood pressure were acquired, and subjects responded to mood state questionnaires at predetermined time intervals. Cocaine alone produced increases in heart rate, blood pressure, and several measures of pleasurable mood and drug effects. Lamotrigine alone produced a mild relaxing effect. Lamotrigine pretreatment altered neither the physiological responses nor the subjective ratings of cocaine's pleasurable or aversive mood effects.

Administration, Oral↗
PubMed2000

Sex differences in self-reported and physiological response to oral cocaine and placebo in humans.

Self-report and physiological data from 27 male and 8 female cocaine-abusing volunteers exposed to cocaine (80 mg/70 kg p.o.) and placebo were examined for sex differences in their responses. Females reported significantly greater baseline ratings on the Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) (sedation) and Lysergic Acid Diethylamide (LSD) (dysphoria) subscales of the Addiction Research Center Inventory-Short Form (ARCI) relative to males. In addition, females reported significantly greater ratings on the Visual Analogs Scales (VAS) Bad Drug Effects and Anxious/Nervous scales relative to males, regardless of drug. Cocaine produced greater increase in systolic blood pressure in males following cocaine, whereas females showed greater increases following placebo. These results suggest that a placebo control is necessary to determine sex differences in response to an active drug.

Administration, Oral↗