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Biomedical subjects

Carl L Hart

Publications and source records attributed to Carl L Hart.

At least 19 recordsLinked to original sources
PubMed2007

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↗
PubMed2006

Smoked cocaine self-administration by humans is not reduced by large gabapentin maintenance doses.

Previously, we reported that gabapentin, a lambda-aminobutyric acid (GABA) agonist, significantly reduced "positive" subjective effects of cocaine without reducing cocaine self-administration. We speculated that the gabapentin doses used in that study were too low to detect subtle shifts in the reinforcing effects of cocaine. Thus, the present study examined the effects of larger gabapentin maintenance doses on cocaine-related effects, including self-administration. During this 48-day double-blind, crossover design study, the effects of gabapentin maintenance (0, 2400, 3200 mg/day) on response to cocaine (0, 12, 25, 50 mg) were investigated in six cocaine-dependent individuals not seeking treatment for their cocaine use. Active cocaine significantly increased choice to self-administer cocaine, subjective-effect ratings (e.g., "Good Drug Effect"), blood pressure, and heart rate. Gabapentin did not decrease cocaine self-administration, cardiovascular measures, or most subjective effects of cocaine. These data agree with findings from a clinical trial examining the effects of similar gabapentin doses on cocaine use by treatment-seeking cocaine-dependent individuals and suggest that gabapentin does not show promise as a treatment medication for cocaine dependence.

Adult↗
PubMed2006

Effects of baclofen on cocaine self-administration: opioid- and nonopioid-dependent volunteers.

Preclinical and clinical studies suggest that GABAB receptor agonists selectively decrease cocaine use. The behavioral mechanism for the interaction between baclofen and cocaine in humans is not known, nor have its effects been characterized in individuals dependent on both cocaine and methadone. The objective of this study is to determine how maintenance on baclofen influences smoked cocaine's reinforcing and subjective effects, mood and cocaine craving prior to and after the initiation of cocaine use in cocaine-dependent volunteers with and without concurrent opioid dependence. Nontreatment-seeking volunteers (10 nonopioid dependent; seven methadone maintained), residing on an in-patient research unit for 21 days, were maintained on each baclofen dose (0, 30, 60 mg po) for 7 days. A smoked cocaine dose-response curve (0, 12, 25, 50 mg) was determined twice: on days 3-4 and days 6-7 of each baclofen maintenance condition. Cocaine sessions began with a sample trial, when participants smoked the cocaine dose available that session, and five choice trials, when participants chose between smoking the available cocaine dose or receiving one 5 dollars merchandise voucher. The results show that in the nonmethadone group, baclofen (60 mg) decreased self-administration of a low cocaine dose (12 mg). In the methadone group, baclofen decreased craving for cocaine. In both groups, baclofen decreased cocaine's effects on heart rate. Baclofen did not alter cocaine's robust subjective effects (eg 'High,' 'Stimulated') for either group. The results from this laboratory study appear consistent with clinical evidence showing that baclofen decreases cocaine use in nonopioid-dependent patients seeking treatment for cocaine dependence. The distinct pattern of effects in methadone-maintained participants suggests baclofen may not be effective in opioid-dependent cocaine users.

Adult↗
PubMed2006

Substance use and psychosocial outcomes following participation in residential laboratory studies of marijuana, methamphetamine and zolpidem.

RATIONALE: Non-therapeutic research with drugs of abuse in humans is important for a more comprehensive understanding of substance abuse and for the development of more effective treatments. However, the administration of substances from drug classes with abuse potential to human volunteers raises ethical questions regarding potential risk to study volunteers. OBJECTIVE: The purpose of this study was to assess the psychosocial functioning and reported drug-taking behavior of volunteers before and after participating in a residential laboratory study, during which either marijuana, methamphetamine or zolpidem was administered. METHODS: Twenty-two volunteers were administered Addiction Severity Index (ASI) interviews at intake and approximately six months following their study participation. RESULTS: No significant differences between intake and follow-up assessments were found on any ASI composite or drug/alcohol-taking variable. CONCLUSION: These preliminary data suggest that participation in residential laboratory studies involving the administration of drugs from classes with abuse potential does not alter subsequent psychosocial functioning or reported drug use.

Alcoholism↗
PubMed2005

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↗
PubMed2005

Increasing treatment options for cannabis dependence: a review of potential pharmacotherapies.

Despite the fact that rates of cannabis dependence have increased substantially over the past several years, there are no medications approved for the treatment of cannabis dependence. This paper reviews data from recent research on cannabinoids that may be relevant for the development of pharmacotherapies for cannabis dependence. Included in the discussion are findings from studies that have assessed the ability of medications to ameliorate cannabis-related abstinence symptoms in laboratory animals and human research participants. Data from studies that have investigated the effects of pharmacological agents on cannabis self-administration are also reviewed because these data may provide information critical for informing relapse prevention medication development efforts. The majority of published studies evaluating cannabis pharmacotherapies have focused on decreasing withdrawal symptoms: a growing number of medications reduce symptoms in laboratory animals, but the majority of these medications have not been tested in humans. Fewer studies have assessed the effects of potential cannabis treatment medications on cannabinoid-related reinforcing effects. In laboratory animals, only the CB1 cannabinoid antagonist rimonabant has shown promise. In humans, this medication has not been tested on cannabis reinforcing effects. To date, no medication has been shown to alter cannabis self-administration by humans.

Drug Therapy↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2005

Sleep quality deteriorates over a binge--abstinence cycle in chronic smoked cocaine users.

RATIONALE: In cocaine dependent individuals, changes in subjective and objective sleep quality accompany their characteristic binge-abstinence cycle. Preliminary studies suggest that sleep quality may decline with prolonged abstinence. Reported here are results of the most extensive study to date on sleep abnormalities during cocaine binge and confirmed abstinence under controlled conditions. OBJECTIVES: The purpose of the current study was to use an experimental, inpatient model of the cocaine binge and abstinence cycle to examine the course and magnitude of sleep disturbances during cocaine use and abstinence. METHODS: Five inpatient non-treatment seeking cocaine users completed 3 baseline days of drug abstinence followed by 3 days of medically monitored "binge" cocaine use, and then 15 days of drug abstinence. Physiological sleep was recorded with polysomnography and the Nightcap ambulatory monitor, while subjective sleep was assessed by questionnaire. RESULTS: Across 3 days of binge cocaine use and 15 subsequent days of confirmed drug abstinence, mean sleep duration, efficiency and latency changed in the direction of poorer sleep quality. In contrast, subjective reports of sleep quality remained unchanged across the same period. CONCLUSIONS: Physiological sleep quality deteriorated from days when cocaine was used across the first 2 weeks of confirmed drug abstinence. In contrast, subjective reports of sleep quality remained unchanged across the same period. We postulate that this dissociation between objective and subjective sleep quality results from a cocaine-use related disruption of the sleep homeostat. Worsening sleep quality during cocaine abstinence may contribute to the risk of relapse and its treatment may offer novel therapeutic strategies for cocaine dependence.

Adult↗
PubMed2005

Combined effects of methamphetamine and zolpidem on performance and mood during simulated night shift work.

Individuals who work irregular or rotating shifts often use stimulants and sedatives to offset shift-change-related mood and performance decrements. During this simulated shift work study the acute effects of the stimulant, methamphetamine were examined, and the effects of the hypnotic, zolpidem, and the combination were assessed during the shift after drug administration. Eight volunteers completed this 21-day, within-participant, residential laboratory study during which they received a single oral methamphetamine dose (0 or 10 mg) 1 h after waking, i.e., before task performance, and a single oral zolpidem dose (0 or 10 mg) 1 h before bedtime under 2 shift conditions: day shift and night shift. When participants received placebo at both dosing times, performance on some psychomotor tasks (e.g., the digit-symbol substitution task) and on some measures of mood (e.g., ratings of "Energetic") were disrupted during the night shift, relative to the day shift. Methamphetamine alone eliminated virtually all shift-related disruptions, while zolpidem alone and the drug combination produced few effects. These data indicate that shift changes produce performance impairments and mood alterations that are improved by a single low to moderate dose of methamphetamine. Zolpidem, given alone or in combination with methamphetamine, did not alleviate most shift-change mood and performance effects.

Adult↗
PubMed2005

Cognitive performance by humans during a smoked cocaine binge-abstinence cycle.

Five cocaine-dependent individuals completed a 22-day inpatient study of sleep and cognition. Following 3 days of drug-free baseline, participants underwent 3 days of twice-daily smoked cocaine base self-administration (6 50-mg doses, 14 minutes apart), followed by 15 days of abstinence. Each morning and afternoon, the CDR repeatable, multiple-version, computerized cognitive battery (whose stability following practice has been documented) was administered. During abstinence, performance deteriorated on vigilance tasks (especially reaction time) as well as on immediate and delayed verbal recognition tasks but not on working memory tasks. Declines were most evident in the afternoon. Data suggest that abstinence can unmask cognitive deficits induced by chronic cocaine use and circadian factors may mediate their severity.

Adult↗
PubMed2005

Gender effects following repeated administration of cocaine and alcohol in humans.

RATIONALE: Use of cocaine, alcohol, and the two drugs simultaneously is common and the risk of morbidity and mortality associated with these drugs is widely reported. This double-blind, placebo-controlled, randomized study examined gender differences in response to administration of these drugs alone and in combination. METHODS: Current users of cocaine and alcohol (n = 17) who met diagnostic criteria (DSM-IV) for cocaine dependence and alcohol abuse or dependence (not physiologically dependent on alcohol) and who were not seeking treatment for substance use disorders gave voluntary, written, informed consent to participate in three drug administration sessions:1) four doses of intranasal cocaine (1 mg/kg every 30 min) with oral alcohol (1 g/kg following the initial cocaine dose and a second drink at +60 min (120 mg/kg) calculated to maintain a plasma alcohol concentration of approximately 100 mg/dL; 2)four doses of cocaine and alcohol placebo; 3) cocaine placebo and alcohol. Pharmacokinetics were obtained by serial blood sampling, physiological measurements (heart rate and blood pressure) were obtained with automated equipment, and subjective effects were assessed using visual analog scales over 480 min. RESULTS: Responses to cocaine, alcohol, and cocaine-alcohol were equivalent by gender for most measurements. Women had higher heart rates following alcohol administration (p = .02). Women consistently reported higher ratings for "Feel Good:' a measure of overall mental/physical well-being, for all study conditions, reaching statistical significance for cocaine (p = .05) and approaching significance for alcohol administration (p = .1). CONCLUSION: Women showed equivalent responses to drug administration with the exception of perception of well-being, which was significantly increased for women. These findings may have implications for differential risk for acute and chronic toxicity in women.

Administration, Intranasal↗
PubMed2004

Gabapentin maintenance decreases smoked cocaine-related subjective effects, but not self-administration by humans.

Data from research with laboratory animals indicate that cocaine self-administration can be reduced by lambda-aminobutyric acid (GABA) agonists. Yet, the effectiveness of GABA agonists to decrease human cocaine self-administration has not been investigated under controlled laboratory conditions. The purpose of this study was to assess the effects of gabapentin, a GABA agonist, on cocaine-related behaviors, including self-administration, in human research participants under controlled laboratory conditions. During this 48-day double-blind, crossover design study, the effects of gabapentin (0, 600, and 1200 mg/d) maintenance on response to cocaine (0, 12, 25, and 50 mg) were investigated in seven cocaine abusers. Active cocaine significantly increased choice to self-administer cocaine, subjective-effect ratings (e.g., "Good Drug Effect"), blood pressure and heart rate (HR). Gabapentin did not reduce cocaine choice or cardiovascular measures, but it did decrease some subjective effects of cocaine (e.g., "Good Drug Effect" and "Anxious"). These data suggest that the cocaine-gabapentin combination was well-tolerated, and because some cocaine-related subjective effects were reduced by maintenance on relatively low gabapentin doses, future studies should test higher gabapentin doses.

Acetates↗
PubMed2004

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↗
PubMed2003

The effects of escalating doses of smoked cocaine in humans.

This study examined the effects of escalating doses of smoked cocaine in non-treatment-seeking cocaine users. Cocaine sessions were conducted twice per day for 3 consecutive days. During each session, one group of participants smoked a 12 mg cocaine dose, followed by a 25 mg dose, followed by four 50 mg doses at 14 min intervals (escalating-dose group); another group of participants smoked six 50 mg cocaine doses at 14 min intervals (fixed-dosing group). Cocaine produced dose-dependent increases in heart rate (HR), blood pressure, ratings of positive drug effect, e.g., "good drug effect", and ratings of cocaine dose, e.g., "liking", in the escalating-dose group. The 50 mg dose also increased these measures in the fixed-dosing group to a level that was not different than that observed following the initial 50 mg dose in the escalating-dose group. The largest effects of 50 mg cocaine were observed following the initial dose, with the latter 50 mg doses maintaining but not increasing these effects in both groups. The effects of cocaine in both groups were consistent for most measures within a day and between days. Resting baseline heart rate, blood pressure and cocaine craving were lower during the first session and higher thereafter. These results demonstrate that increasing the dose of cocaine during a bout, i.e., "binge", of cocaine use can increment the effects of cocaine, but administering the same cocaine dose maintains, but does not increment the effects of cocaine.

Adult↗