Biomedical subjects

S D Comer

Publications and source records attributed to S D Comer.

At least 19 recordsLinked to original sources

PubMed2001

Buprenorphine sublingual tablets: effects on IV heroin self-administration by humans.

RATIONALE: Studies have shown that buprenorphine, a partial mu opioid agonist, effectively reduces heroin taking. While previous research with buprenorphine utilized a liquid formulation, a tablet formulation is proposed for clinical use. However, because recent research suggests that the liquid and tablet differ in bio-availability, it is unclear what dose of the buprenorphine tablet effectively antagonizes the reinforcing effects of heroin. OBJECTIVE: The present study was designed to compare the effects of two sublingual doses of buprenorphine maintenance on heroin self-administration. METHODS: Eight heroin-dependent men participated in a 6-week, double-blind, placebo-controlled inpatient study to evaluate the reinforcing effects of intravenous heroin (0, 6.25, 12.5, 25 mg) during maintenance on 8 or 16 mg sublingual buprenorphine. Participants first sampled the available dose of heroin, and then were allowed to respond under a progressive ratio schedule for either heroin or $20. For each heroin dose, one sample session and three choice sessions occurred. Two sessions per day were conducted. A sample session was followed by the first choice session on one day, and the second and third choice sessions occurred on the following day. These sessions were conducted while participants were maintained on daily doses of 8 or 16 mg buprenorphine (3 weeks each). RESULTS: Relative to placebo, 12.5 and 25 mg heroin produced significant increases in break point values under both maintenance dose conditions. The mean break point value for 12.5 mg heroin was significantly lower under 16 mg buprenorphine, compared to 8 mg. CONCLUSIONS: These results demonstrate that the reinforcing effects of heroin were not fully antagonized by these doses of the tablet formulation of buprenorphine, and that 16 mg buprenorphine reduced heroin self-administration relative to 8 mg.

Administration, Sublingual↗

PubMed2001

Bupropion SR worsens mood during marijuana withdrawal in humans.

RATIONALE: Symptoms of withdrawal after daily marijuana smoking include increased ratings of irritability and depression. Similar mood symptoms are reported by cigarette smokers during nicotine abstinence. OBJECTIVE: Given the successful use of sustained-release bupropion in treating nicotine dependence, this study investigated how maintenance on bupropion influenced symptoms of marijuana withdrawal compared to maintenance on placebo. METHODS: Marijuana smokers (n=10) were maintained outpatient on active (300 mg/day) or placebo (0 mg/day) bupropion for 11 days, and were then maintained inpatient on the same bupropion dose for 17 days. For the first 4 inpatient days, participants smoked active marijuana [2.8% delta9-tetrahydrocannabinol (THC)] 5 times/day. For the remaining inpatient days, participants smoked placebo marijuana (0.0% THC) 5 times/day. Participants were then maintained outpatient on the alternate dose of bupropion for 11 days, followed by a second inpatient residential stay, paralleling the first. Medication administration was double-blind. Mood, psychomotor task performance, food intake, and sleep were measured daily during each inpatient phase. The order of active and placebo bupropion maintenance was counterbalanced between groups. RESULTS: Bupropion had few behavioral effects when participants smoked active marijuana. During placebo marijuana smoking, i.e., active marijuana withdrawal, ratings of irritability, restlessness, depression, and trouble sleeping were increased by bupropion compared to placebo maintenance. CONCLUSIONS: These data suggest that bupropion does not show promise as a potential treatment medication for marijuana dependence.

Adult↗

PubMed2001

Effects of repeated oral methamphetamine administration in humans.

RATIONALE: Although methamphetamine use has increased over the past several years, few studies have evaluated the effects of repeated methamphetamine administration in humans. OBJECTIVES: Because methamphetamine is often taken in a pattern of repeated use followed by a period of abstinence, the present study sought to evaluate the effects of repeated methamphetamine administration in humans. The hypothesis was that tolerance would develop to methamphetamine's effects. METHODS: Seven normal, healthy volunteers participated in a 15-day residential study. Participants completed subjective-effects questionnaires and psychomotor performance tasks repeatedly throughout the experimental day. Oral methamphetamine (5, 10 mg BID) was administered on days 4-6 and 10-12; placebo was administered on all other study days. RESULTS: Relative to placebo baseline, only two "positive" subjective ratings ("I feel a good drug effect" and "I feel high") were significantly elevated, and only on the 1st day of methamphetamine administration. In contrast, numerous "negative" ratings, including "I feel..." "a bad drug effect," "dizzy," and "flu-like symptoms" were elevated on the 3rd day of methamphetamine administration. Total caloric intake decreased and sleep was disrupted after methamphetamine administration, relative to baseline. CONCLUSIONS: The pattern of methamphetamine's positive subjective effects were altered with chronic administration such that tolerance, or a decreased effect, occurred after repeated administration. In contrast, methamphetamine's negative subjective effects increased over days. These results suggest that in this population of normal volunteers, the abuse liability of oral methamphetamine is relatively low.

Adult↗

PubMed2001

The NMDA antagonist memantine attenuates the expression of opioid physical dependence in humans.

RATIONALE: Preclinical observations suggest that NMDA receptor-mediated glutamatergic neurotransmission is involved in the expression and maintenance of opioid dependence. OBJECTIVE: The present study evaluated whether memantine, the clinically available non-competitive NMDA receptor antagonist, decreases naloxone-precipitated withdrawal in morphine-dependent humans. METHODS: Eight heroin-dependent, non-treatment seeking, inpatient participants were stabilized on a fixed dose of morphine (30 mg PO qid). Subsequently, they received a series of challenges with naloxone (0.4 mg, IM) and the severity of opioid withdrawal was monitored. Either placebo or memantine (60 mg PO) was given 6 h before each naloxone challenge. A modified multiple baseline, across-participants design was used to evaluate the effects of memantine on the severity of naloxone-precipitated opioid withdrawal. RESULTS: Naloxone increased ratings and produced physical changes consistent with opioid withdrawal. Memantine attenuated the severity of opioid withdrawal as assessed with the Clinical Institute for Narcotic Withdrawal Scale scale. Withdrawal was significantly reduced when naloxone was administered at 6 and 52 h after memantine, but not when administered 126 h (5 days) after memantine. Medication effects, assessed 5 h after memantine administration and before naloxone administration, included significant increases in ratings of "strong" and "good" drug effect, and "I feel sedated", "mellow", and "high". CONCLUSIONS: Memantine attenuated the expression of opioid physical dependence in humans, indicating that glutamatergic neurotransmission at the NMDA receptor site contributes to the maintenance of opioid dependence. This finding suggests that memantine may be a useful adjunct in the treatment of opioid dependence.

Adult↗

PubMed1999

Abstinence symptoms following oral THC administration to humans.

Symptoms of dependence and withdrawal after the frequent administration of high doses (210 mg/day) of oral delta9-tetrahydrocannabinol (THC) have been reported, yet little is known about dependence on lower oral THC doses, more relevant to levels attained by smoking marijuana. In a 20-day residential study, male (n = 6) and female (n = 6) marijuana smokers worked on five psychomotor tasks during the day (0915-1700 hours), and in the evening engaged in private or social recreational activities (1700-2330 hours); subjective-effects measures were completed 10 times/day, and a sleep questionnaire was completed each morning. Food and beverages were available ad libitum from 0830 to 2330 hours. Capsules were administered at 1000, 1400, 1800, and 2200 hours. Placebo THC was administered on days 1-3, 8-11, and 16-19. Active THC was administered on days 4-7 (20 mg qid) and on days 12-15 (30 mg qid). Both active doses of THC increased ratings of "High," "Good Drug Effect," and "Willingness to Take Dose Again" compared to baseline (days 1-3). THC also increased food intake by 35-45%, and decreased verbal interaction among participants compared to placebo baseline. Tolerance developed to the subjective effects of THC but not to its effects on food intake or social behavior. Abstinence from THC increased ratings of "Anxious," "Depressed," and "Irritable," decreased the reported quantity and quality of sleep, and decreased food intake by 20-30% compared to baseline. These behavioral changes indicate that dependence develops following exposure to lower daily doses of THC than have been previously studied, suggesting that the alleviation of abstinence symptoms may contribute to the maintenance of daily marijuana use.

Administration, Oral↗

PubMed1999

Abstinence symptoms following smoked marijuana in humans.

Symptoms of withdrawal after oral delta9-tetrahydrocannabinol (THC) administration have been reported, yet little is known about the development of dependence on smoked marijuana in humans. In a 21-day residential study, marijuana smokers (n = 12) worked on five psychomotor tasks during the day (0915-1700 hours), and in the evening engaged in recreational activities (1700-2330 hours); subjective-effects measures were completed 10 times/day. Food and beverages were available ad libitum from 0830 to 2330 hours. Marijuana cigarettes (0.0, 1.8, 3.1% THC) were smoked at 1000, 1400, 1800, and 2200 hours. Placebo marijuana was administered on days 1-4 . One of the active marijuana doses was administered on days 5-8, followed by 4 days of placebo marijuana (days 9-12). The other concentration of active marijuana cigarettes was administered on days 13-16, followed by 4 days of placebo marijuana (days 17-20); the order in which the high and low THC-concentration marijuana cigarettes were administered was counter-balanced between groups. Both active doses of marijuana increased ratings of "High," and "Good Drug Effect," and increased food intake, while decreasing verbal interaction compared to the placebo baseline (days 1-4). Abstinence from active marijuana increased ratings such as "Anxious," "Irritable," and "Stomach pain," and significantly decreased food intake compared to baseline. This empirical demonstration of withdrawal from smoked marijuana may suggest that daily marijuana use may be maintained, at least in part, by the alleviation of abstinence symptoms.

Adult↗

PubMed1999

Comparison of intravenous and intranasal heroin self-administration by morphine-maintained humans.

Eight heroin-dependent individuals, maintained on divided daily doses of oral morphine, participated in a 2.5-week inpatient study comparing the effects of intranasal (IN) (placebo, 12.5, 25, 50, 100 mg) and intravenous (IV) (placebo, 6.25, 12.5, 25, 50 mg) heroin. Each morning, participants received $20 and a sample dose of heroin, and each afternoon they had the opportunity to self-administer all or part of the morning heroin dose or money amount. Participants responded under a modified progressive-ratio schedule (PR 50, 100, 200, 400, 800, 1200, 1600, 2000, 2400, 2800) during a ten-trial self-administration task. During each trial, participants could respond for 1/10th of the heroin dose or 1/10th of the money amount. The total amount of heroin and/or money chosen during the self-administration task was given at the end of the task. Thus, participants received drug and/or money twice each day: once during the morning sample session and once during the afternoon self-administration session. Participants received IV solution and IN powder simultaneously during each dosing; only one route contained active drug. Heroin produced dose-related increases in break point values by both routes of administration. Although IV heroin was approximately four-fold more potent than IN heroin, the maximal break point values for both routes were not significantly different. A similar difference in potency between the IV and IN routes was found for several ratings of subjective effects (e.g., "I feel a good drug effect," "I feel high"), but maximal subjective ratings were lower for IN compared to IV heroin. These results suggest that the reinforcing efficacy of heroin is similar by the two routes of administration, but that IN heroin is less potent than IV heroin. The results also underscore the importance of evaluating drug self-administration in the evaluation of the abuse liability of drugs.

Administration, Inhalation↗

PubMed1999

Fluoxetine-maintained obese humans: effect on food intake and body weight.

The effects of fluoxetine on food intake, body weight, and mood of obese individuals was examined in a 16-week inpatient/outpatient study. Six male and eight female obese volunteers began the study (four male and five females completed all phases of the study). They lived in a residential laboratory during three one-week inpatient periods separated by a 5-week and an 8-week outpatient period. Following an initial 4-day placebo baseline, participants were maintained on fluoxetine (60 mg/day) for the remainder of the study. Food intake parameters (total daily energy intake, macronutrient intake, mean number of eating bouts, interbout interval), body weight, subjective effects, and task performance were measured several times during the day during inpatient periods; food intake questionnaires were completed daily during the outpatient periods. Fluoxetine significantly reduced daily energy intake derived from fat, carbohydrate, and protein by decreasing the mean number of eating bouts per day throughout the study. No other food intake parameter was affected. Body weight was significantly reduced after 7 weeks, but not after 16 weeks of daily fluoxetine administration. These results indicate that fluoxetine reduced food intake for at least 16 weeks in nondepressed obese individuals without specifically affecting carbohydrate intake. Weight that was lost during the first few weeks of daily fluoxetine administration was subsequently regained even though food intake remained reduced. Therefore, fluoxetine maintenance does not appear promising as a sole long-term therapy for obesity.

Adult↗

PubMed1998

Effects of an alternative reinforcer on intravenous heroin self-administration by humans.

Five heroin-dependent research volunteers, maintained on divided daily oral morphine doses, participated in an inpatient study designed to evaluate intravenous (i.v.) heroin self-administration when money ($10, $20 or $40) was concurrently available. Each morning participants received a single injection of heroin (placebo, 6.25, 12.5, 25, or 50 mg/70 kg, i.v.) and each afternoon, they had the opportunity to self-administer all or part of the morning dose. Participants responded under a progressive-ratio schedule (50, 100, ..., 2800) during a 10-trial self-administration task. During each trial, participants could respond for 1/10th of the sampled heroin dose or 1/10th of a single money value. The progressive-ratio value increased independently for each option. The total amount of heroin and/or money chosen during the self-administration task was administered at the end of the task. Heroin dose-dependently increased ratings of 'good drug effect' and 'high', impaired task performance and decreased pupil diameter and blood oxygen saturation. Heroin also dose-dependently increased progressive-ratio break point values, which varied as a function of the alternative money amount. Consistent with previous studies, the present results demonstrate that alternative reinforcers, depending on magnitude, are effective in reducing heroin use in opioid-dependent individuals.

Administration, Oral↗

PubMed1998

Effects of methysergide and loratadine on food intake, mood, and performance of humans living in a residential laboratory.

The effects of loratadine, a peripherally acting histamine (H1) antagonist, and methysergide, a serotonin (5-HT) antagonist, were evaluated in seven normal-weight, male research volunteers, participating in a placebo-controlled, double-blind, 17-day residential study. Participants received oral loratadine (10 or 20 mg), methysergide (4 or 8 mg), or placebo at 1000 and 1700 hours daily. Active drug was administered on Days 4, 5, 7, 8, 11, 12, 15, and 16; placebo was administered on all other days. Drug and dose order were counterbalanced across participants. Food intake, performance, and subjective ratings were measured repeatedly throughout the day. Loratadine had no effect on food intake, performance, or subjective ratings. In contrast, total caloric intake significantly decreased from approximately 3500 kcal during placebo administration to 3065 kcal on the first but not the second day of methysergide administration. Consumption of carbohydrate (p < 0.055), protein, and fat decreased on the first day of methysergide administration. This decrease in food intake was due to a decrease in meal size; the number of meals consumed was not affected. The proportion of calories derived from carbohydrates significantly increased on the first day of methysergide administration. Methysergide also significantly impaired performance of a psychomotor task on the first day of high-dose administration and increased ratings of several subjective measures, including "Vomiting," "Stomach Pain," and "Miserable." These results suggest that the anorectic effect occurred as a result of the somatic and mood changes produced by methysergide. In addition, the inability of loratadine to affect food intake indicates that antagonism of central histamine receptors may be responsible for the increases in food intake produced by other antihistamines (e.g., diphenhydramine).

Adult↗

PubMed1997

Alprazolam increases food intake in humans.

The present study investigated the effect of alprazolam on the pattern of food intake in seven male participants living in a residential laboratory for 17 days. A wide selection of meals, snacks and beverages was freely available. Capsule administration occurred at 1300 and 1730 hours. Food intake on days when alprazolam (0.75 mg) was administered (days 2, 11) was compared to days when no capsule (days 1, 9) or placebo (days 3, 10) was administered. Alprazolam increased total caloric intake by approximately 975 kcal from a baseline of 2800 kcal. Alprazolam increased the number of eating occasions occurring in the evening (1700-2330 hour), without altering the size of eating occasions (kcal), or the proportion of total calories derived from carbohydrate, fat and protein. These data demonstrate alprazolam's robust effects on food intake in humans.

Adult↗

PubMed1997

Cyproheptadine produced modest increases in total caloric intake by humans.

Four male and three female normal-weight research volunteers, participating in an 18-day residential study, received oral cyproheptadine (4 mg) or placebo at 0930, 1245, and 1730 hours daily. Food intake, performance, and subjective ratings were measured throughout the day. The interaction between cyproheptadine and carbohydrate consumption was examined by providing subjects diets that engendered varied levels of carbohydrate intake. Three diet conditions were tested for 6 days each: a regular diet, a low-carbohydrate (high-fat) diet, and a high-carbohydrate diet. Placebo was given on days 1, 2, 3, and 6, while cyproheptadine was given on days 4 and 5 of each diet condition. When subjects received placebo and had access to a regular diet, they consumed 2500 kcal/day (59% carbohydrate 28% fat, 13% protein). Total caloric intake decreased (p < 0.007) when subjects received placebo and had access to the low-carbohydrate diet (40% carbohydrate, 43% fat, 17% protein) and increased (p < 0.056) when subjects received placebo and had access to a high-carbohydrate diet (70% carbohydrate, 19% fat, 11% protein). Cyproheptadine significantly increased total daily caloric intake by 20%, to 3000 kcal, only under the regular diet condition. The increase in caloric intake was due to an increase in the number of eating occasions without a change in eating occasion size. Although subjects consumed more food under the regular diet and cyproheptadine condition, cyproheptadine had no effect on the relative contribution of macronutrients to total daily caloric intake. There was no evidence for a modulation of the food-intake increasing effects of cyproheptadine by the macronutrient mix of the available diet. Cyproheptadine also significantly altered self-reported mood: compared to placebo, cyproheptadine produced significant increases in ratings of "Tired", "Sleepy", "Headache", "Can't Concentrate", and "Bad Drug Effect" and decreases in "Alert". Furthermore, cyproheptadine produced small decrements in psychomotor task performance.

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

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

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

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↗