Biomedical subjects

M W Fischman

Publications and source records attributed to M W Fischman.

At least 55 records · Page 3Linked to original sources

PubMed1997

Are choice and self-administration of marijuana related to delta 9-THC content?

The effects of delta 9-tetrahydrocannabinol (THC) content on choice marijuana, number of marijuana cigarettes smoked, and ratings of marijuana's effects were examined in 6 adult male marijuana smokers during a residential study consisting of four 3-day blocks of 2 sample days and 1 choice day. Days were divided into 6.5-hr work and social-access periods, beginning at 1000 and 1700. On sample days, marijuana cigarettes containing different THC concentrations (0.0% vs. 3.5% and 2.0% vs. 3.5% THC) were smoked at least once during each period. On choice days, independent choices between previously sampled marijuana cigarettes were made during each period. A maximum of 8 cigarettes could be smoked per day, and drug ratings were obtained after each period. Only choice behavior was sensitive to changes in THC content, whereas only the number of smoked marijuana cigarettes was related to context (i.e., work and social-access period).

Adult↗

PubMed1997

Effects of d-amphetamine on task performance and social behavior of humans in a residential laboratory.

Six healthy adult male volunteers lived for 11 days in a residential laboratory. Acute effects of d-amphetamine (0, 5, or 10 mg/70 kg) on performance of tasks, social interaction, and self-reports of drug effects were measured. Each day, participants engaged in a 6.5-hr work period and a 6.5-hr recreation period. Beverages containing d-amphetamine or placebo were consumed daily before the work period and before the recreation period. d-Amphetamine increased response rate without affecting accuracy on some tasks. d-Amphetamine increased the proportion of time spent engaging in verbal interaction during the first but not the second week of study. No changes in self-reported drug effects were observed. Thus, d-amphetamine improved performance in the absence of stimulant-like subjective effects. This differentiation between performance and subjective effects confirms the importance of determining the effects of drugs on a range of behaviors.

Adult↗

PubMed1997

Effects of caffeine withdrawal on humans living in a residential laboratory.

Caffeine withdrawal was examined in caffeine-dependent humans living in a residential laboratory. Ten men and 2 women who reported daily caffeine consumption participated in a 17-day study. From 1000-1700, participants worked on computerized tasks assessing memory, vigilance, and psychomotor skills, with a 1-hr break for lunch. From 1700-2330, participants engaged in private or social, recreational activities. Subjective-effects measures were completed 10 times per day. Participants were maintained on caffeine (100 mg 3 times a day at 0945, 1345, and 1745), except on days 5-6 and 12-13, when caffeine was replaced by placebo. Caffeine abstinence selectively influenced subjective effects without altering social behavior or performance on tasks assessing memory, vigilance, and psychomotor skills. Furthermore, the effects of caffeine on food intake were enhanced after 2 days of caffeine abstinence.

Adult↗

PubMed1997

A laboratory model of cocaine withdrawal in humans: intravenous cocaine.

Seven adult intravenous (IV) cocaine users completed a protocol investigating changes in behavior after the self-administration of cocaine. During sessions, the participants could self-administer up to 6 doses of IV cocaine (32 mg/70 kg) twice each day. Both 2- and 3-day binge conditions were tested. At 39 hr after the 3-day but not the 2-day binge of cocaine use, total Beck Depression Inventory scores were increased and participants reported increased ratings of Irritable and decreased ratings of I Want Cocaine. Exposure to stimulus cues associated with IV cocaine increased ratings of I Want Cocaine during periods of abstinence after both 2- and 3-day binges and increased ratings of Depressed only after the 3-day binge of cocaine use. The cessation of binge cocaine use produced modest changes in mood and cocaine craving that were related to the length of the binge and varied as a function of time since last cocaine use. Responsiveness to cocaine cues also varied as a function of the length of the previous cocaine binge.

Adult↗

PubMed1997

The effects of a monetary alternative on marijuana self-administration.

The availability of alternative reinforcers can reduce drug self-administration. This 21-day residential study investigated the effect of monetary alternatives on marijuana self-administration. Three female and four male participants performed computer tasks (baseline) in the morning before smoking a sample marijuana cigarette (0.0, 1.8, or 3.9% delta 9-tetrahydrocannabinol (THC) and receiving the sample alternative ($5.00 voucher). In the afternoon, participants had five opportunities to choose either the marijuana cigarette sampled earlier or a voucher for $5.00. Participants were required to meet a criterion level of task performance to obtain each choice. The monetary performance criterion varied from day to day (80, 100, or 120% of baseline); the marijuana performance criterion remained constant at 100% of baseline. Choices were delivered in the evening, after task completion. Marijuana choice varied as a function of THC concentration and criterion to earn money. Active marijuana was always chosen more often than placebo, and active and placebo marijuana were chosen over money when the criterion to earn money was high. Task performance improved when criteria were imposed, even after participants had smoked the sample marijuana cigarette. Subjective ratings of drug effects increased with increasing THC concentration, but did not predict choice. The availability of a monetary alternative was effective in shifting choice to self-administer marijuana, and marijuana choice was sensitive to contingency manipulations. The results further indicate that contingency manipulations may override the performance-impairing effects of marijuana observed in other studies.

Adult↗

PubMed1997

Choice between money and intranasal heroin in morphine-maintained humans.

Five morphine-maintained individuals participated in an inpatient study evaluating the effects of a monetary alternative ($10, $20, $40) on intranasal (i.n.) heroin (placebo, 12.5, 25, 50, 100 mg) self-administration, using a procedure in which subjects chose between money and heroin. Each money amount was tested in combination with each heroin dose. Subjects responded under a progressive-ratio schedule (PR 50, 100, ..., 2800); the PR value increased independently for each option. Subjective, performance, and physiological effects were also measured during each session. Heroin breakpoint values increased in a dose-related manner, relative to placebo, when $10 or $20 was available. In contrast, only the highest dose produced a heroin breakpoint value that was significantly different from placebo when $40 was available. Heroin also produced dose-related increases in several ratings of drug effect, including "I feel ..." "a good drug effect", "high", "mellow", and "stimulated". These effects were not significantly affected by the alternative money condition. These results demonstrated: (1) the dose-related reinforcing effects of i.n. heroin in opioid-dependent individuals; (2) that i.n. heroin self-administration can be modified by the availability of an alternative reinforcer (i.e. money); and (3) that self-reported drug effects can be differentiated from drug self-administration.

Administration, Intranasal↗

PubMed1997

Binge cocaine self-administration by humans: smoked cocaine.

Tolerance develops to the cardiovascular and subjective effects of intravenous cocaine during single self-administration sessions, but diminishes within 3 h after the session ends. To examine whether a similar pattern of tolerance occurs to smoked cocaine, seven adult 'crack' cocaine users completed a protocol investigating changes in behavior during the repeated self-administration of smoked cocaine. During sessions, participants could self-administer up to 6 doses of smoked cocaine (50 mg per dose), one every 14 min. Both two- and three-day binge conditions were tested. During the two-day binge, a 2.5 h cocaine self-administration session began at 1200 h and again at 1600 h on two consecutive days, while during the three-day binge, self-administration sessions occurred at 1200 h and 1600 h on three consecutive days. The first one or two cocaine doses in each session increased cardiovascular and subjective effects ratings; subsequent cocaine inhalations during the session did not increase these measures further, suggesting the development of acute tolerance to these effects. Ratings of 'I want cocaine' decreased slightly across three days of repeated smoked cocaine self-administration, while anxiety scores increased slightly across three days, suggesting that some effects of smoked cocaine may persist beyond a binge.

Adult↗

PubMed1997

A protocol to switch high-dose, methadone-maintained subjects to buprenorphine.

Buprenorphine (BUP) is an alternative to methadone (METH) maintenance. However, there are few studies on the switching of patients from METH to BUP. Eighteen volunteers who had been maintained on METH for 1-19 years were recruited for a residential cocaine self-administration study. All subjects were maintained on 60 mg METH for up to 1 1/2 weeks before the 7-day changeover (60, 40, 30, 30, 0 mg METH; 4, 8 mg BUP). Fifteen subjects successfully completed the transfer from METH to BUP, experiencing moderate withdrawal symptoms, as measured by the Subjective Opiate Withdrawal Scale (SOWS). Withdrawal symptoms were the highest during the first assessment of the day, at the time of BUP administration. SOWS scores returned to baseline 4 days after the switchover. This study demonstrates that within a supportive inpatient setting, research volunteers can be rapidly switched from high-maintenance doses of METH to BUP with an acceptable degree of tolerability.

Adult↗

PubMed1997

Behavioral effects of alprazolam in humans.

The purpose of this study was to examine, in healthy volunteers without histories of extensive sedative use, the acute behavioral effects of doses of alprazolam used in clinical applications. Subjects participated in daily sessions over 12 study days. They consumed a standard breakfast, received an oral drug dose (0, 0.25, 0.5, 1 mg) and completed performance tasks for 3 hours after dosing. Tasks included a digit-symbol substitution task, a repeated-acquisition of response sequences task, a differential reinforcement of low response rate task designed to monitor time estimation, a number recognition task, and a second-order repeated-acquisition of response sequences task. Each active dose was administered prior to two sessions, according to a randomized block design, and placebo sessions separated successive active-dose sessions. With the exception of the second-order repeated acquisition of response sequences task, dose-related changes in performance were observed during all tasks, but effects were significant only following the 1 mg dose. No drug-related changes were observed on visual-analog scale ratings of drug effect. The data indicate that the risk of adverse performance effects following use of alprazolam is related to dose, with risks increasing at doses at or above 0.5 mg.

Adult↗

PubMed1997

Behavioral contingencies modulate alprazolam self-administration by humans.

The effect of monetary contingencies on alprazolam self-administration was evaluated in seven male volunteers living in a residential laboratory. Drug administration occurred prior to an afternoon work session (13.00 h), and at the onset of an evening recreation period (17.30 h). On 'sample' days, participants were administered placebo or alprazolam (0.75 mg), and at the end of the afternoon work session, were told whether their task performance was 'better' or 'worse' than average. If they received 'better' feedback they earned $55, and if they received 'worse' feedback, they earned $15. On 'choice' days, participants chose to self-administer either alprazolam or placebo, with feedback occurring on two of the four choice days. Feedback was not actually linked to performance, but instead was pre-programmed. For one week, alprazolam administration was always associated with 'better' feedback on sample and choice days, and in the other week was associated with 'worse' feedback. When no feedback was delivered, alprazolam was self-administered equally often in the afternoon (57%) and evening (71%). When feedback was delivered, it significantly influenced the choice to self-administer alprazolam in the afternoon. 'Better than average' feedback resulted in alprazolam self-administration 57% of the time, but alprazolam self-administration decreased to 14% when it was associated with 'worse than average' feedback and reduced earnings. A similar pattern of effects has been reported for d-amphetamine. Thus, the self-administration of either a stimulant or a minor tranquilizer is significantly reduced when it is associated with a consequent loss of an alternative reinforcer, in this case money.

Adult↗

PubMed1997

Factors influencing marijuana self-administration by humans.

The self-administration of marijuana cigarettes varying in tetrahydrocannabinol (THC) content was measured by having participants choose between marijuana and an alternative reinforcer, i.e., snack food. Twelve marijuana users (eight men, four women), in groups of four, participated in a 16-day residential study. Each day, participants had the opportunity to choose repeatedly between a marijuana cigarette and a snack. The THC concentration of the cigarette changed each day (0.0, 2.2 or 3.9% delta 9-THC w/w), as did the number of snack items (one or two); each THC concentration was compared to each snack condition twice. Days were divided into a work period (09.15-16.45 h), comprising performance and subjective-effects tasks, and a recreation period (17.15-23.30 h). Each day at 10.00 h, participants "sampled" a marijuana cigarette containing the delta 9-THC concentration available that day, and selected the number of snack items available that day. Six "choice" trials occurred from 14.00-19.00 h, when participants responded under a modified progressive ratio schedule for either marijuana or snacks. At 18.15 h, participants could participate in a 10-min math task, in which each correct answer earned $1.00. Cigarettes containing 2.2 or 3.9% delta 9-THC were self-administered more often than placebo. The only other factor influencing marijuana choice was the opportunity to earn additional money, with participants choosing not to smoke immediately before the math task. By the end of the study, active marijuana had smaller effects on ratings of "high", "stimulated," and "good drug effect." These data demonstrate that: (a) delta 9-THC is an essential reinforcing component of marijuana; (b) marijuana use may be manipulated by monetary contingencies; and (c) tolerance may develop more readily to marijuana's subjective effects than its reinforcing effects.

Adult↗

PubMed1996

Crack cocaine and cocaine hydrochloride. Are the differences myth or reality?

OBJECTIVE: To review and discuss the differences and similarities between the use of crack cocaine and cocaine hydrochloride; and to determine how these findings might affect policies on the imprisonment and treatment of cocaine users. DATA SOURCES: English-language publications were identified through a computerized search (using MEDLINE) between 1976 and 1996 using the search terms "smoked cocaine," "crack cocaine," "freebase," and "cocaine-base." In addition, manual searches were conducted on references cited in original research articles, reviews, and an annotated bibliography, and on selected journals. STUDY SELECTION: Only those articles that compared various routes of cocaine administration or types of cocaine (cocaine base or crack cocaine vs cocaine hydrochloride) were examined. DATA EXTRACTION: Studies were reviewed to obtain information on the composition of the 2 forms of cocaine, and the prevalence, pharmacokinetics and pharmacodynamics, abuse liability, pattern of use, and consequences across the various routes of cocaine administration and forms of cocaine. CONCLUSION: Cocaine hydrochloride is readily converted to base prior to use. The physiological and psychoactive effects of cocaine are similar regardless of whether it is in the form of cocaine hydrochloride or crack cocaine (cocaine base). However, evidence exists showing a greater abuse liability, greater propensity for dependence, and more severe consequences when cocaine is smoked (cocaine-base) or injected intravenously (cocaine hydrochloride) compared with intranasal use (cocaine hydrochloride). The crucial variables appear to be the immediacy, duration, and magnitude of cocaine's effect, as well as the frequency and amount of cocaine used rather than the form of the cocaine. Furthermore, cocaine hydrochloride used intranasally may be a gateway drug or behavior to using crack cocaine. Based on these findings, the federal sentencing guidelines allowing possession of 100 times more cocaine hydrochloride than crack cocaine to trigger mandatory minimum penalties is deemed excessive. Although crack cocaine has been linked with crime to a greater extent than cocaine hydrochloride, many of these crimes are associated with the addiction to cocaine. Therefore, those addicted individuals who are incarcerated for the sale or possession of cocaine are better served by treatment than prison.

Administration, Intranasal↗

PubMed1996

Effect of fluoxetine on food intake of humans living in a residential laboratory.

Ten male and one female normal-weight research volunteers, participating in a 16-day residential study, received oral fluoxetine (40 mg) or placebo at 0930 daily. Food intake, performance and subjective ratings were measured throughout the day. The interaction between fluoxetine and carbohydrate consumption was examined by providing subjects diets that engendered varied levels of carbohydrate intake. When subjects received placebo and had access to a regular diet, they consumed 3400 kcal day-1 (53% carbohydrate, 34% fat, 13% protein); and fluoxetine decreased caloric intake to 2770 Kcal, without affecting macronutrient contribution. Caloric intake (2730 Kcal; 67% carbohydrate) under the high-carbohydrate condition when subjects received fluoxetine was not different from intake under the regular-diet fluoxetine conditions. Subjects reported that the high-fat (low-carbohydrate) diet was less palatable and consumed 2975 Kcal under placebo conditions (35% carbohydrate); fluoxetine decreased caloric intake by an additional 400 Kcal without affecting macronutrient contribution. There was no evidence that carbohydrate intake modulated the effects of fluoxetine. Fluoxetine decreased food intake by decreasing the number of eating occasions. Performance and subjective measures were not significantly altered by fluoxetine compared to placebo. Thus, there was no evidence of a specific effect of fluoxetine on macronutrient consumption, nor were the effects of fluoxetine altered by the macronutrient composition of the available diet.

Adult↗

PubMed1996

Amphetamine self-administration by humans: modulation by contingencies associated with task performance.

The effect of task performance feedback and associated monetary earnings on drug self-administration were evaluated using eight subjects in a residential laboratory setting. The hypothesis was that if subjects believed that d-amphetamine impaired performance and reduced monetary earnings, d-amphetamine self-administration would decrease. Subjects performed computer tasks every day: on certain days that they received capsules, subjects were given bogus feedback regarding their performance ("better" or "worse" than average). On sample days, subjects were required to take d-amphetamine (10 mg BID) or placebo (0 mg BID) capsules. On choice days, subjects could choose between either d-amphetamine or placebo. Subjects received feedback on their task performance on 2 sample days and 2 of 4 choice days. Subjects received no feedback on the remaining two choice days. When subjects received no feedback, they chose d-amphetamine over placebo 78% of the time, and when they were given better feedback messages, they chose d-amphetamine 87.5% of the time. In contrast, d-amphetamine self-administration decreased significantly to 25% when subjects were told that it impaired their performance on work tasks and resulted in reduced earnings. In reality, d-amphetamine had little effect on work task performance. However, compared to placebo, d-amphetamine significantly increased subjective ratings of "Stimulated" and "Good Drug Effect" and significantly decreased ratings of "Tired" and "Sleepy." These results demonstrate that d-amphetamine served as a reinforcer under conditions in which drug self-administration did not influence monetary earnings, but that d-amphetamine self-administration could be modified by feedback/monetary earnings. Thus, contingencies associated with performance have important implications for drug use in the workplace.

Adult↗

PubMed1996

Effect of fenfluramine on food intake, mood, and performance of humans living in a residential laboratory.

Five male and four female normal weight research volunteers, participating in 13-day residential studies, received oral fenfluramine (20, 40 mg) or placebo at 09:30 and 17:00. Food intake, performance, and subjective ratings were measured throughout the day. Carbohydrate intake was manipulated by providing lunch meals high (males: 120 g; females: 80 g) or low (males: 25 g; females: 16 g) in carbohydrate on 8 days; on the remaining days subjects self-selected lunch. Total caloric intake (approximately 2800 Kcal) did not differ among the low- and high-carbohydrate, and self-selected lunch conditions when subjects received placebo, indicating caloric compensation. Total carbohydrate intake was significantly less, however, when subjects consumed the low-carbohydrate lunch compared to the other lunch conditions. Fenfluramine significantly decreased total caloric intake (approximately 500 kcal) by decreasing meal size, not number, only when subjects consumed the low-carbohydrate lunch. Fenfluramine was only an effective anorectic drug when subjects consumed a lunch with fewer calories and a lower carbohydrate:protein ratio than self-selected baseline. Also, fenfluramine improved performance on a range of computer tasks and increased ratings of "Alert," "Friendly," and "Talkative," while decreasing ratings of "Tired" and "Irritable."

Adult↗

PubMed1996

Pattern of cocaine use in methadone-maintained individuals applying for research studies.

Twenty-three methadone-maintained individuals seeking admission into a cocaine study were interviewed using the Pattern-of-Drug-Use assessment. Sample characteristics included: 96% male, 91% Caucasian, and 36 +/- 5 mean years of age. Mean methadone dose was 81 +/- 20 mg. On average, subjects reported using greater than $200 or 5 grams of cocaine per week. "Binge/crash" cocaine use did not appear to be the typical pattern of use. However, during daily periods of cocaine use, repeated injections of large amounts of cocaine were taken, which may place patients at risk for medical complications. These findings emphasize the importance of developing novel treatment strategies to treat these dually-addicted individuals.

Adult↗

PubMed1996

Effects of methadone or buprenorphine maintenance on the subjective and reinforcing effects of intravenous cocaine in humans.

The effects of p.o. methadone or sublingual buprenorphine maintenance on i.v. cocaine self-administration and the response to experimenter-administered cocaine were evaluated in 12 methadone-maintained individuals. Participants lived in a clinical research center during the 4- to 5-week protocol. After stabilization on 80 mg/day methadone, half the participants were first tested during buprenorphine maintenance (8 mg/day with p.o. placebo) and half were first tested during methadone maintenance (60 mg/day with sublingual placebo). After testing on the alternate medication, all participants were returned to their entry level of methadone. Testing consisted of three daily sessions of fixed cocaine dosing (four injections; 0, 16 and 48 mg/70 kg) and three daily sessions of cocaine self-administration with a choice procedure (16, 32 and 48 mg/70 kg vs. $5). The transition from methadone to buprenorphine engendered moderate withdrawal symptoms (score of 12 on the subjective opiate withdrawal scale), which returned to base-line levels (score of 4 on the subjective opiate withdrawal scale) before testing during buprenorphine maintenance. Buprenorphine maintenance significantly reduced "I want cocaine" scores by 15% during fixed-dosing sessions. Subjective effects of fixed cocaine doses, including increased ratings of "high," "stimulated" and "good drug effect," were not affected by the maintenance medication. Heart rate was consistently 9 beats/min less, regardless of cocaine dose, during methadone maintenance. In comparison with methadone, buprenorphine maintenance decreased cocaine self-administration when 16- or 32-mg doses were available, but not when 48 mg was available. Thus, buprenorphine may have greater efficacy than methadone for controlling cocaine abuse among individuals dependent on opioids.

Adult↗

PubMed1995

Effect of amphetamine on human macronutrient intake.

Six male subjects participated in a 15-day residential study examining the effects of amphetamine on macronutrient intake. During the first 11 days, carbohydrate intake was manipulated by providing lunch meals high (155 g) or low (25 g) in carbohydrate. Subjects received oral d-amphetamine (5, 10 mg/70 kg, BID) or placebo. Total daily caloric intake was similar under both lunch conditions (approximately 3400/Kcal), but carbohydrate contributed more energy under the high-carbohydrate condition. Both doses of amphetamine decreased total caloric intake to approximately 2600 Kcal, by decreasing the number of eating bouts, without affecting macronutrient selection. During the last four days subjects received a higher daily dose of amphetamine (30 mg/70 kg in four doses) or placebo, and were allowed to self-select lunch. Although 30 mg amphetamine decreased intake of all macronutrients, the relative contribution of carbohydrate to total caloric intake was increased from 54% to 62%, while the contribution of fat was decreased from 32% to 26% and the contribution of protein was decreased from 14% to 12%. Thus, at a high dose, amphetamine altered the relative contribution of specific macronutrients to total caloric intake.

Adult↗