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Biomedical subjects

Carl L Hart

Publications and source records attributed to Carl L Hart.

28 records · Page 2Linked to original sources
PubMed2003

Methamphetamine attenuates disruptions in performance and mood during simulated night-shift work.

RATIONALE: Increased sleepiness while working and sleep disruptions are common complaints among shift workers. Consequently, shift workers may be more susceptible to diminished performance and work-related accidents. OBJECTIVE: To examine the effects of the central nervous system stimulant methamphetamine on psychomotor task performance, subjective effects, and food intake during shift work under laboratory conditions. METHODS: Seven participants completed this 23-day, within-participant design, residential laboratory study. They received a single oral methamphetamine dose (0, 5, 10 mg) 1 h after waking for three consecutive days under two shift conditions: (1) during the day shift, participants performed computerized psychomotor tasks from 0830 hours to 1730 hours and went to bed at 2400 hours and (2) during the night shift, participants performed tasks from 0030 hours to 0930 hours and went to bed at 1600 hours. Shifts alternated three times during the study; shift conditions were separated by an "off" day during which participants were not on a schedule and data were not collected. RESULTS: When participants received placebo, psychomotor task performance and subjective effects were disrupted during the night shift, relative to the day shift. Changing shift conditions did not alter food intake significantly. Methamphetamine reversed performance and subjective-effects disruptions, and decreased food intake during the night shift. CONCLUSION: These data indicate that shift changes produce performance impairments and mood alterations, and that a single low to moderate dose of methamphetamine attenuates many shift change-related disruptions in performance and mood.

Adult↗
PubMed2003

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↗
PubMed2003

The effects of venlafaxine on the subjective, reinforcing, and cardiovascular effects of cocaine in opioid-dependent and non-opioid-dependent humans.

The effects of maintenance on venlafaxine, which blocks both norepinephrine and serotonin reuptake, on the response to smoked cocaine (0, 12, 25, or 50 mg) in 7 opioid-free and 7 methadone-maintained cocaine abusers was examined during a 42-day study. Participants received venlafaxine (225 mg daily) and placebo as part of a double-blind crossover design. Cocaine significantly increased heart rate, blood pressure, cocaine choice, cocaine ratings, and ratings of positive subjective effects (e.g., "I feel high") in both groups. Venlafaxine significantly decreased the subjective effects of cocaine by 10-20% without affecting cocaine choice or cardiovascular response in both groups. Although the reduction in cocaine's effects was small, further studies using a longer venlafaxine maintenance period or a larger venlafaxine dose are warranted.

Adult↗
PubMed2003

Zolpidem-related effects on performance and mood during simulated night-shift work.

The effects of zolpidem, a nonbenzodiazepine hypnotic, on psychomotor task performance, subjective effects, and food intake were examined during simulated shift work. Seven participants completed this 23-day, within-participant design, residential laboratory study. They received a single oral zolpidem dose (0, 5, or 10 mg) 1 hr before bedtime for 3 consecutive days under 2 shift conditions: day shift and night shift. When participants received placebo, next-day performance and subjective effects were disrupted, and food intake was decreased during the night shift. Zolpidem improved subjective reports of sleep quality and, to a lesser extent, next-day performance. Next-day mood, however, was worsened by zolpidem. Food intake was unaffected by zolpidem. These data indicate that shift changes produce performance impairments, mood alterations, and decreases in food intake, and that zolpidem attenuates some shift-change-related disruptions.

Adult↗
PubMed2002

Nefazodone decreases anxiety during marijuana withdrawal in humans.

RATIONALE: Symptoms of marijuana withdrawal include increased irritability, depression and anxiety, and decreased sleep quality. Nefazodone, which is an antidepressant with sedative properties, may attenuate symptoms of marijuana withdrawal. OBJECTIVE: The present within-subject, placebo-controlled study investigated the effects of nefazodone during marijuana withdrawal. METHODS: Marijuana smokers [ n=7; averaging 6.0 (+/-1.3) marijuana cigarettes/day, 6.4 (+/-0.4) days/week], not seeking treatment for marijuana use, were maintained on two doses of nefazodone (0, 450 mg/day) for 26 days each. Each maintenance condition began with an outpatient phase (9 days) and continued with an inpatient phase (17 days) in a residential laboratory. Marijuana was smoked 5 times per inpatient day at 1000, 1300, 1600, 1900 and 2200 hours. On days 1-4 (baseline), the first four marijuana cigarettes were placebo (0.00% THC), while the final marijuana cigarette was active (3.04% THC). On inpatient days 5-8, only active marijuana was smoked, while on days 9-16, only placebo marijuana was smoked. Mood, psychomotor task performance, food intake and sleep were measured daily. The order of maintenance dose was counterbalanced between groups. RESULTS: Nefazodone maintenance did not alter the acute effects of active marijuana as compared to placebo nefazodone maintenance. During marijuana withdrawal, nefazodone decreased ratings of "Anxious", and "Muscle Pain", while having no effect on the marked increase in ratings of "Irritable", "Miserable" or decreased sleep quality. CONCLUSIONS: Nefazodone decreased certain marijuana withdrawal symptoms, but participants still reported substantial discomfort. These data provide further evidence of marijuana withdrawal, and highlight the need for more marijuana treatment options.

Adult↗
PubMed2002

Effects of the NMDA antagonist memantine on human methamphetamine discrimination.

RATIONALE: The discriminative stimulus effects of N-methyl- D-aspartate (NMDA) antagonists have been assessed in laboratory animals. To date, no published study has assessed their ability to alter methamphetamine-related discriminative stimulus effects in humans. OBJECTIVE: This study investigated the discriminative stimulus, subjective (e.g. "Good Drug Effect"), psychomotor performance, and cardiovascular effects (e.g. blood pressure) of oral methamphetamine following acute oral memantine (a non-competitive NMDA antagonist) in humans. METHODS: Initially, participants were trained to discriminate 10 mg methamphetamine from placebo using a standard two-response procedure (drug versus placebo). Then, the effects of memantine (0, 40 mg) on methamphetamine discrimination were examined across several methamphetamine doses (0, 5, 10, 20 mg) using a novel-response procedure (drug versus placebo versus novel). RESULTS: Following placebo pretreatment, 10 mg methamphetamine produced 99% methamphetamine-appropriate responding and placebo produced 75% placebo-appropriate responding. Following memantine pretreatment, participants responded as if they had been given a novel compound, although memantine did not significantly alter most subjective-effects ratings following methamphetamine. Memantine alone produced "positive" subjective effects and novel drug-appropriate responding. CONCLUSION: These data indicate that the memantine-methamphetamine combination produced novel discriminative stimulus effects and that memantine produced some stimulant-like subjective effects.

Adult↗
PubMed2002

Comparison of smoked marijuana and oral Delta(9)-tetrahydrocannabinol in humans.

RATIONALE: Although smoked marijuana contains at least 60 cannabinoids, delta(9)-tetrahydrocannabinol (delta(9)-THC) is presumed to be the cannabinoid primarily responsible for many marijuana-related effects, including increased food intake and subjective effects. Yet, there has been no systematic comparison of repeated doses of oral delta(9)-THC with repeated doses of smoked marijuana in the same individuals. OBJECTIVE: To compare the effects of oral delta(9)-THC and smoked marijuana in humans under controlled laboratory conditions. METHODS: Eleven healthy research volunteers, who reported smoking an average of six marijuana cigarettes per day, completed an 18-day residential study. Marijuana cigarettes (3.1% delta(9)-THC, q.i.d.) were smoked or delta(9)-THC (20 mg, q.i.d.) was taken orally using a staggered, double-blind, double-dummy procedure for three consecutive days. Four days of placebo administration separated each active drug condition. Psychomotor task performance, subjective effects, and food intake were measured throughout the day. RESULTS: Relative to placebo baseline, oral delta(9)-THC and smoked marijuana produced similar subjective-effect ratings (e.g., "high" and "mellow"), although some effects of smoked marijuana were more pronounced and less prone to the development of tolerance. Additionally, participants reported "negative" subjective effects (e.g., "irritable" and "miserable") during the days after smoking marijuana but not after oral delta(9)-THC. Both drugs increased food intake for 3 days of drug administration, but had little effect on psychomotor performance. CONCLUSION: These results indicate that the behavioral profile of effects of smoked marijuana (3.1% delta(9)-THC) is similar to the effects of oral delta(9)-THC (20 mg), with some subtle differences.

Administration, Oral↗
PubMed2002

Effects of oral THC maintenance on smoked marijuana self-administration.

Studies have shown that the Delta(9)-tetrahydrocannabinol (Delta(9)-THC) concentration in marijuana cigarettes is an important factor for the maintenance of marijuana self-administration. Yet, the impact of oral Delta(9)-THC treatment on marijuana self-administration is unknown. Because other agonist therapies have been demonstrated to be effective for the treatment of substance use disorders, the objective of this study was to evaluate the influence of oral Delta(9)-THC maintenance on choice to self-administer smoked marijuana. During this 18-day residential study, 12 healthy research volunteers received one of three doses of oral Delta(9)-THC capsules (0, 10, 20 mg q.i.d.) for 3 consecutive days, followed by 3 consecutive days of matching placebo. The order of active Delta(9)-THC administration was counterbalanced. Each morning, except on days 6, 12, and 18, participants smoked the 'sample' marijuana cigarette (1.8% Delta(9)-THC w/w) and received a $2 voucher (redeemable for cash at study's end). Following the sample, volunteers participated in a four-trial choice procedure during which they had the opportunity to self-administer either the dose of marijuana they sampled that morning or to receive the $2 voucher. Relative to placebo Delta(9)-THC maintenance, participants' choice to self-administer marijuana was not significantly altered by either of the two active Delta(9)-THC maintenance conditions. Some 'positive' subjective drug-effect ratings following the sample marijuana cigarette were reduced: by day 3 of active oral Delta(9)-THC maintenance, participants' rating of 'Good Drug Effect' and 'High' were significantly decreased. Smoked marijuana-related total daily caloric intake was not significantly altered under any maintenance conditions. Finally, the effects of smoked marijuana on psychomotor task performance were only minimally affected by oral Delta(9)-THC maintenance. These data indicate that participants' choice to self-administer marijuana was unaltered by the oral Delta(9)-THC dosing regimen used in the present investigation.

Administration, Oral↗