PubMed Health⌕ Search

Biomedical subjects

Suzanne K Vosburg

Publications and source records attributed to Suzanne K Vosburg.

17 recordsLinked to original sources

Gabapentin does not reduce smoked cocaine self-administration: employment of a novel self-administration procedure.

Previously, we reported that gabapentin, a nonselective gamma-aminobutyric acid agonist, reduced 'positive' subjective effects of cocaine without reducing cocaine self-administration. We speculated that the self-administration procedure used in that study was not sensitive to subtle shifts in the reinforcing effects of cocaine. Thus, this study examined the effects of gabapentin maintenance on cocaine self-administration using a purchase-cocaine choice procedure. During this 48-day inpatient/outpatient study, nontreatment-seeking cocaine abusers (n = 12) were maintained on gabapentin (0, 600, 1200 mg/day); four doses of cocaine (0, 12, 25, 50 mg) were each tested twice under each gabapentin condition. All cocaine testing was conducted while participants were inpatients. Before the start of each session, participants were provided with 25 dollars (five 5 dollar bills, one for each choice opportunity) and smoked the 'sample' cocaine dose once. Subsequently, participants were given five opportunities to purchase the sampled dose of cocaine (at 5 dollars per dose) or to keep 5 dollars for that choice trial. Choice to self-administer cocaine increased significantly with escalating cocaine doses; gabapentin maintenance did not alter choice to self-administer cocaine. These results concur with findings from our previous investigations of gabapentin and with those from a clinical trial examining the effects of larger gabapentin doses on cocaine use by treatment-seeking cocaine-dependent individuals. Together, the data indicate that gabapentin does not show promise as a treatment medication for cocaine dependence.

Adult↗

Depot naltrexone: antagonism of the reinforcing, subjective, and physiological effects of heroin.

RATIONALE: Naltrexone is an opioid antagonist that is currently approved as a treatment for opioid and alcohol dependence. Although it is highly effective in completely antagonizing the effects of opioids, medication noncompliance is a difficult obstacle to treatment. Therefore, a sustained-release form of naltrexone may improve treatment outcome. OBJECTIVE: The present study was designed to evaluate the time course, safety, and effectiveness of a depot formulation of naltrexone (Depotrex). MATERIALS AND METHODS: Five heroin-dependent individuals participated in an 8-week inpatient study. After a 1-week detoxification period, the effects of a range of heroin doses (0, 6.25, 12.5, and 25 mg, i.v.) were examined. Participants then received 384 mg naltrexone base. The effects of heroin were again evaluated for the next 6 weeks. One dose of heroin was tested per day and the entire dose range was tested each week. Doses were administered in non-systematic order. During a morning sample session, participants received a dose of heroin and $20 and subjective, performance, and physiological effects were measured both before and after drug administration. During an afternoon choice session, participants were given the opportunity to choose the sampled heroin dose and/or amount of money using a modified progressive ratio procedure. RESULTS: Depot naltrexone antagonized both the reinforcing and subjective effects of heroin for 4-5 weeks. Subjective ratings of withdrawal were reduced after week 2 and throughout the remainder of the study. The effects of heroin on mean trough pupil diameter began to emerge by week 5. There were no clinically significant effects on respiratory or cardiovascular function. CONCLUSIONS: The present results extend our previous findings by showing that the reinforcing effects of heroin were reduced for 4-5 weeks after administration of 384 mg depot naltrexone.

Adult↗

Memantine increases cardiovascular but not behavioral effects of cocaine in methadone-maintained humans.

Previous work has suggested that maintenance on the noncompetitive N-methyl-d-aspartate (NMDA) antagonist, memantine, increased the subjective effects of smoked cocaine in experienced cocaine users. To determine whether this phenomenon occurs in opioid-dependent individuals, eight (seven male, one female) methadone-maintained cocaine smokers participated in a 47-day inpatient and outpatient study to assess the effects of memantine on smoked cocaine self-administration, subjective effects, and cardiovascular responses. The participants were maintained on memantine (0 mg and 20 mg daily) for 7-10 days prior to laboratory testing, using a double-blind crossover design. Under each medication condition during inpatient phases, participants smoked a sample dose of cocaine base (0, 12, 25, and 50 mg) once, and were subsequently given five choice opportunities, 14 min apart, to self-administer that dose of cocaine or receive a merchandise voucher (US 5.00 dollars). Each cocaine dose was tested twice under each medication condition, and the order of medication condition and cocaine dose were varied systematically. Memantine maintenance did not alter the subjective or reinforcing effects of cocaine. Several cardiovascular responses, however, including peak and initial diastolic pressures following cocaine, were significantly greater during memantine maintenance, although these elevations were not clinically significant. Taken together, these findings corroborate earlier data suggesting that this dose of memantine will not be helpful in the pharmacotherapy of cocaine abuse.

Adult↗

Assessment of cognitive functioning of methadone-maintenance patients: impact of adult ADHD and current cocaine dependence.

The purpose of this study was to determine if methadone-maintained patients (MMP) with cocaine dependence (CD) and/or adult Attention Deficit Hyperactivity Disorder (ADHD) exhibited compounded cognitive dysfunction associated with their poly-substance use and/or co-morbid psychiatric diagnoses. The sample consisted of 79 MMP (59% male, 51% Caucasian), maintained on methadone doses ranging from 40-130 mg/day, who were placed into one of four diagnostic categories: (1) a control group (no ADHD, no CD) (n = 24), (2) CD alone (n = 18), (3)ADHDalone (n = 18), and (4)ADHD+ CD(n = 19). The California Computerized Assessment Package (CalCAP) was administered to assess cognitive functioning requiring focused and sustained attention in a standardized fashion. There were no group differences on Simple Reaction tasks. Compared to the control group, the ADHD+ CD group was slower and less accurate on 33% of the Choice Reaction (CR) tasks. Specifically, individuals in the ADHD + CD group and the ADHD alone group performed significantly worse on tasks measuring attention and psychomotor responding. These tasks are associated with broader cognitive skills in working memory, language discrimination and flexibility of cognitive sets that may have implications for treatment outcome. Diagnostic services capable of identifying cognitive deficits among MMP with ADHD and/or CD are needed to maximize the likelihood of treatment success and to serve as an indicator for the efficacy of therapeutic approaches.

Adult↗

Modafinil attenuates disruptions in cognitive performance during simulated night-shift work.

Common complaints among shift workers are sleep disruptions and increased sleepiness while working, which may contribute to shift workers being more susceptible to diminished performance and work-related accidents. The purpose of this double-blind, within-participant study was to examine the effects of the alerting agent modafinil on cognitive/psychomotor performance, mood, and measures of sleep during simulated shift work. In all, 11 participants completed this 23-day residential laboratory study. They received a single oral modafinil dose (0, 200, 400 mg) 1 h after waking for three consecutive days under two shift conditions: day shift and night shift. Shifts alternated three times during the study, and shift conditions were separated by an 'off' day. When participants received placebo, cognitive performance and subjective ratings of mood were disrupted during the night shift, relative to the day shift. Objective and subjective measures of sleep were also disrupted, but to a lesser extent. Modafinil reversed disruptions in cognitive performance and mood during the night shift. While modafinil produced few effects on sleep measures during the night shift, the largest dose produced several sleep alterations during the day shift. These data demonstrate that abrupt shift changes produced cognitive performance impairments and mood disruptions during night shift work. Therapeutic doses of modafinil attenuated night-shift-associated disruptions, but the larger dose produced some sleep impairments when administered during day-shift work.

Affect↗

Desipramine treatment of cocaine-dependent patients with depression: a placebo-controlled trial.

OBJECTIVE: The aim of this study was to test the hypothesis that desipramine would be an effective treatment in cocaine abusers with current depressive disorders. METHOD: This was a randomized, 12-week, double-blind, 'placebo-controlled trial of outpatients (N = 111) meeting DSM-III-R criteria for cocaine dependence and major depression or dysthymia (by SCID interview). Participants were treated with desipramine, up to 300 mg per day, or matching placebo. All patients received weekly individual manual-guided relapse prevention therapy. Weekly outcome measures included the Clinical Global Impression Scale, self-reported cocaine use and craving, urine toxicology, and the Hamilton Depression Scale (biweekly). Summary measures of mood and cocaine use outcome were compared between treatment groups with chi2- or t-tests. Dichotomous summary measures of depression response and cocaine response were the primary outcomes. Mixed effect models were also fit to explore the relationship of cocaine use to mood improvement and treatment over weeks in the trial. RESULTS: Desipramine was associated with a higher rate of depression response (51%, 28/55) than placebo (32%, 18/56) (p < 0.05), but treatment groups did not differ in rate of cocaine response. Depression improvement was associated with improvement in cocaine use. Desipramine was associated with more dropouts due to side effects and medical adverse events, while placebo was associated with more dropouts due to psychiatric worsening. CONCLUSIONS: Desipramine was an effective treatment for depression among cocaine-dependent patients. Improvement in mood was associated with improvement in cocaine abuse, but a direct effect of medication on cocaine outcome was not clearly established and rates of sustained abstinence were low. Future research should examine newer antidepressant medications with more benign side effect profiles and combinations of behavioral and pharmacological treatments to maximize effects on cocaine use.

Adult↗

Reinforcing effects of oral Delta9-THC in male marijuana smokers in a laboratory choice procedure.

RATIONALE: Oral Delta-9-tetrahydrocannabinol (Delta(9)-THC; Marinol) is medically available for the treatment of nausea associated with cancer chemotherapy and for wasting syndromes related to HIV/AIDS. Little is known about its reinforcing effects. OBJECTIVE: This study was conducted to characterize the reinforcing effects of oral Delta(9)-THC in experienced marijuana smokers under controlled laboratory conditions. METHODS: Ten healthy male marijuana users completed this 17-day residential study. On days 2, 6, 10, and 14, at 0900 h, participants received a "sample" oral dose of Delta(9)-THC (0, 10, 20 mg) and an alternative reinforcer, a 2 US dollars voucher (redeemable for cash at study's end). Over the next 3 days, they had 11 opportunities to self-administer either the sampled dose of Delta(9)-THC or to receive a 2 US dollars voucher. RESULTS: Participants chose active Delta(9)-THC (10 and 20 mg) more often than placebo (<two selections vs approximately four selections, respectively). However, they chose active Delta(9)-THC on less than 50% of choice opportunities. Both active Delta(9)-THC doses produced significant increases in "positive" subjective effects, impaired psychomotor performance, and increased heart rate, relative to the placebo conditions. CONCLUSION: These data indicate that oral Delta(9)-THC may have modest abuse liability in experienced marijuana smokers.

Administration, Oral↗

An evaluation of the reinforcing effects of memantine in cocaine-dependent humans.

The purpose of this double-blind, outpatient study was to evaluate the reinforcing and subjective effects of the uncompetitive N-methyl-d-aspartate (NMDA) antagonist memantine in cocaine-dependent humans. Eight participants (two females, six males) completed this study which consisted of three blocks of seven sessions; each block tested a different dose of memantine. During the first two sessions of each block, participants "sampled" the memantine capsule (10, 20, or 30 mg) and the placebo capsule that were available for the next five sessions. During the five subsequent sessions, participants had an opportunity to self-administer either the active or placebo capsule. Memantine was not reinforcing and subjective-effects ratings were not altered as a function of dose. Results suggest that these doses of memantine do not have abuse liability in cocaine-dependent individuals.

Adult↗

Utility of lead-in period in cocaine dependence pharmacotherapy trials.

We examined whether drug use behaviors during a 2-week lead-in for a pharmacotherapy trial were predictive of retention in treatment and of the level of cocaine use during the subsequent 12 weeks of treatment. Fifty cocaine dependent patients were grouped based on: (1) principal route of cocaine administration: intranasal versus smoking, and (2) level of cocaine use during the 2-week lead-in: high versus low. Results indicate that level of cocaine use during the 2-week lead-in was a significant predictor of cocaine use during the subsequent 12 weeks of treatment. Patients with reported higher level of use during the lead-in period were more likely to continue using cocaine during the treatment. Patients who used smoking as their primary route of cocaine use were more likely to drop out early in the treatment. Findings of this study suggest that route and level of cocaine use during lead-in be used as a covariate in models testing treatment effect.

Adult↗

The effect of sertraline and environmental context on treating depression and illicit substance use among methadone maintained opiate dependent patients: a controlled clinical trial.

Psychiatric comorbidity, particularly depressive disorders, is associated with continued substance use and poor social functioning among methadone maintained patients. Evidence suggests similar neurochemical and environmental pathways may link the two disorders and it is reasonable to hypothesize that pharmacological and environmental factors play important roles in the treating comorbid depression and substance use. The present study tested the efficacy of sertraline for treating syndromally defined depressive disorders among non-abstinent methadone maintained opiate dependent patients. The moderating effects of environmental context on treatment outcome were also examined. Ninety-five patients were randomized in a 12-week, double-blind, placebo-controlled trial of sertraline, a serotonin-selective re-uptake inhibitor. There was no main effect of sertraline on either depression or substance use outcomes. However, sertraline demonstrated significant ameliorative effects on depression among patients with a more positive environment or less negative environment. The odds of being abstinent from heroin and cocaine were greater for patients on sertraline in environments with relatively less adversity. The findings support the hypothesis that contextual factors moderate the efficacy of pharmacological treatment for depression among methadone patients. They also suggest future research should examine a pharmacological treatment that is combined with a behavioral intervention targeting the accessibility of reinforcement or reducing the impact of aversive environmental interactions.

Adult↗

Impact of attention-deficit hyperactivity disorder and other psychopathology on treatment retention among cocaine abusers in a therapeutic community.

Although there are some data suggesting that individuals with depressive disorders may be more likely to remain in treatment than those without depressive disorders, it is less clear how well other psychiatric subgroups compare to those without psychiatric comorbidity. This sample is a follow-up study of 135 individuals who were admitted into a therapeutic community. Individuals with attention-deficit hyperactivity disorder (ADHD), other Axis I disorders (no ADHD), and no Axis I disorders were compared. Although individuals with other Axis I disorders had a strikingly low early drop-out rate, after a prolonged time in treatment, the drop-out rate increased substantially, such that these individuals were found to complete treatment at a lower rate (17%) than those with no Axis I disorders (29%). Furthermore, individuals with ADHD were less likely to graduate treatment than those with other Axis I or no Axis I disorders (0%, 9%, and 19%, respectively). Future investigations may be useful to determine whether pharmacologic or nonpharmacologic interventions might improve treatment outcome.

Adult↗

Marijuana withdrawal in humans: effects of oral THC or divalproex.

Abstinence following daily marijuana use can produce a withdrawal syndrome characterized by negative mood (eg irritability, anxiety, misery), muscle pain, chills, and decreased food intake. Two placebo-controlled, within-subject studies investigated the effects of a cannabinoid agonist, delta-9-tetrahydrocannabinol (THC: Study 1), and a mood stabilizer, divalproex (Study 2), on symptoms of marijuana withdrawal. Participants (n=7/study), who were not seeking treatment for their marijuana use, reported smoking 6-10 marijuana cigarettes/day, 6-7 days/week. Study 1 was a 15-day in-patient, 5-day outpatient, 15-day in-patient design. During the in-patient phases, participants took oral THC capsules (0, 10 mg) five times/day, 1 h prior to smoking marijuana (0.00, 3.04% THC). Active and placebo marijuana were smoked on in-patient days 1-8, while only placebo marijuana was smoked on days 9-14, that is, marijuana abstinence. Placebo THC was administered each day, except during one of the abstinence phases (days 9-14), when active THC was given. Mood, psychomotor task performance, food intake, and sleep were measured. Oral THC administered during marijuana abstinence decreased ratings of 'anxious', 'miserable', 'trouble sleeping', 'chills', and marijuana craving, and reversed large decreases in food intake as compared to placebo, while producing no intoxication. Study 2 was a 58-day, outpatient/in-patient design. Participants were maintained on each divalproex dose (0, 1500 mg/day) for 29 days each. Each maintenance condition began with a 14-day outpatient phase for medication induction or clearance and continued with a 15-day in-patient phase. Divalproex decreased marijuana craving during abstinence, yet increased ratings of 'anxious', 'irritable', 'bad effect', and 'tired.' Divalproex worsened performance on psychomotor tasks, and increased food intake regardless of marijuana condition. Thus, oral THC decreased marijuana craving and withdrawal symptoms at a dose that was subjectively indistinguishable from placebo. Divalproex worsened mood and cognitive performance during marijuana abstinence. These data suggest that oral THC, but not divalproex, may be useful in the treatment of marijuana dependence.

Adult↗

Amantadine does not modulate reinforcing, subjective, or cardiovascular effects of cocaine in humans.

Data from several clinical studies have suggested that amantadine, which has dopaminergic agonist and glutamatergic antagonist effects, may be useful for the treatment of cocaine dependence. The interaction between amantadine and smoked cocaine was examined in 10 cocaine smokers (7 men, 3 women), who participated in a 26-day inpatient study. Participants were maintained on amantadine (0 and 100 mg bid) for 5 days prior to laboratory testing, using a double-blind crossover design. Under each medication condition, participants smoked a sample dose of cocaine base (0, 12, 25, and 50 mg) once, and were subsequently given five choice opportunities, 14 min apart, to self-administer that dose of cocaine or receive a merchandise voucher ($5.00). Each cocaine dose was tested twice under each medication condition, and the order of medication condition and cocaine dose varied systematically. Cocaine produced stimulant-like reinforcing, subjective, and physiological effects. Amantadine maintenance did not modify the choice to self-administer smoked cocaine. These findings, taken together with the decidedly mixed literature, suggest that amantadine (100 mg bid) will not have a role in the treatment of cocaine dependence.

Adult↗

Anxiety sensitivity among children of parents with anxiety disorders: a controlled high-risk study.

We investigated whether parental anxiety was related to anxiety sensitivity (AS) in offspring. Subjects were 261 offspring (aged 6-17 years) of parents with lifetime DSM-IV anxiety and/or mood disorders, and 79 offspring of parents with no lifetime anxiety, mood, or psychotic disorder. Parents and offspring were interviewed by blind clinicians. Children were administered the Child Anxiety Sensitivity Index (CASI). There were no significant differences between CASI scores of the offspring of parents with anxiety and/or mood disorders, and offspring of comparison parents. We conclude that parental anxiety or mood disorder does not predispose offspring to high anxiety sensitivity.

Adolescent↗

Pharmacotherapy for marijuana dependence: a double-blind, placebo-controlled pilot study of divalproex sodium.

There is a noticeable lack of targeted treatment options for marijuana dependence, in particular pharmacologic approaches. This is the first study evaluating a targeted pharmacologic approach for marijuana dependence. The goals of the study were to determine if such patients would seek pharmacologic treatment, whether these patients could be retained in treatment using a design previously developed for cocaine-dependent patients, and especially whether divalproex sodium showed promise as a treatment agent for marijuana dependence. We found that marijuana-dependent patients will seek treatment, and such patients can be adequately maintained in a pharmacologic trial. Regardless of treatment group, patients reported a significant reduction in their frequency and amount of marijuana use as well as a reduction in irritability. Given the lack of proven effective treatments for marijuana dependence, pharmacotherapies should be sought. The design of a preliminary clinical trial should include a psychosocial/behavioral intervention emphasizing motivation and medication compliance and a placebo control group.

Administration, Oral↗

Predictors of retention in naltrexone maintenance for opioid dependence: analysis of a stage I trial.

Behavioral naltrexone therapy (BNT) was developed to address the shortcomings of naltrexone maintenance for opiate dependence and improve compliance by integrating several empirically validated methods, including the use of a significant other to monitor compliance, voucher incentives, and motivational techniques. An uncontrolled Stage I pilot trial (N = 47) of BNT was conducted. Baseline demographic and clinical variables were evaluated as predictors of retention with univariate tests. Significant predictors were entered together into a multiple regression model. Poorer (shorter) retention in treatment was associated with methadone use and higher average bags per day of heroin. Other variables that became non-significant in multiple regression analysis included older age and depressive symptoms. Individuals with greater physiologic dependence and/or dependence on longer-acting opiates are at higher risk to drop out from naltrexone maintenance and may require a more gradual detoxification and more intensive behavioral therapy aimed at enhancing initial compliance.

Adolescent↗