Biomedical subjects

Richard W Foltin

Publications and source records attributed to Richard W Foltin.

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

"Tasting and wasting" behavior in non-human primates: aberrant behavior or normal behavior in "times of plenty".

The purpose of this study was to develop a foraging model that engenders large meals. Eight free-feeding baboons were first given periodic access to a chocolate sugar-coated candy (M & Ms) and then a jelly sugar-coated candy (Skittles). Baboons had access to food 24 h each day, but they had to complete a two-phase operant procedure in order to eat. Responding on one lever during a 30-min appetitive phase was required before animals could start a consumption phase, where responding on another lever led to food delivery, i.e., a meal. 3 days a week for 8 or 9 weeks baboons received candy during the first meal and then food pellets were available: a 2 month interval when only pellets were available separated periods of candy access. All baboons ate as much candy in the single candy meal as they did pellets throughout the remainder of the day. Beginning week 5 of M & M access, five baboons began to waste a large number of M & Ms by spitting them out. Baboons wasted few Skittles or pellets. Pellet intake was less, but total caloric intake was greater on days that animals had access to either candy. Pellet, but not candy eating varied between males and females: males began eating pellets sooner in the day, ate more pellet meals and more pellets. Periodic access to a preferred candy food engendered large amounts of candy consumption in all baboons, and periodic access to M & Ms engendered food tasting and wasting behavior in 5 of 8 baboons.

Animals↗

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

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

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

Adult↗

PubMed2006

Pharmacokinetics of repeated doses of intravenous cocaine across the menstrual cycle in rhesus monkeys.

Numerous studies in rodents suggest that there are sex differences in response to cocaine that are related to fluctuations in the ovarian hormones of females. Given that female rhesus monkeys have menstrual cycles that are remarkably similar to those of humans, they provide an ideal laboratory animal model for assessing the effects of cocaine across the menstrual cycle. The present study assessed the effects of 4 injections of intravenous (i.v.) cocaine (0.00, 0.25 or 0.50 mg/kg), spaced 15 min apart, in 4 female rhesus monkeys. Each monkey was tested with each dose during 4 phases of the menstrual cycle: menses, midfollicular, periovulatory and midluteal. Estradiol and progesterone levels were measured each session before cocaine administration to verify phase of the menstrual cycle. Cocaine and cocaine metabolite levels were measured 5 min after each cocaine dose and 5, 15, 30, 45, 60 and 120 min after the last cocaine dose. Similarly, levels of luteinizing hormone (LH) and prolactin levels were measured before, 5, 15, 30, 45, 60 and 120 min after the last cocaine dose. Cocaine and metabolite levels increased as a function of dose, but there were minimal differences across the menstrual cycle following repeated injections of cocaine. With a few exceptions, LH levels decreased as a function of time within the session, with no differences as a function of cocaine dose. Cocaine produced transient increases in LH levels during the luteal phase, with maximal levels occurring after the second cocaine injection. Lastly, cocaine substantially decreased prolactin levels across all menstrual cycle phases. Taken together, these data indicate that any behavioral differences observed either across the menstrual cycle or between males and females, are probably not related to alterations in the pharmacokinetics of cocaine across the menstrual cycle.

Animals↗

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

Exogenous progesterone attenuates the subjective effects of smoked cocaine in women, but not in men.

In a previous study, we showed that the positive subjective effects of cocaine were higher during the follicular phase compared to the luteal phase of the menstrual cycle. The purpose of the present study was to determine if exogenously administered progesterone during the follicular phase in females would attenuate the response to cocaine compared to the normal follicular phase, thus making the response to cocaine similar to the luteal phase. To address the role of sex differences, males were also administered exogenous progesterone during one inpatient stay. In all, 11 female and 10 male non-treatment-seeking cocaine smokers participated. Females had three inpatient stays: one during a normal follicular phase, one during a normal luteal phase, and one during a follicular phase when exogenous progesterone was administered. Males had two inpatient stays: one when exogenous progesterone was administered and the other when placebo was administered. During each inpatient admission, there were four smoked cocaine administration sessions: participants were administered six doses of cocaine (0, 6, 12, or 25 mg cocaine base) at 14 min intervals. Smoked cocaine increased heart rate, blood pressure and several subjective effects such as 'good drug effect' and 'drug quality' cluster scores. Administration of progesterone during the follicular phase in women attenuated the positive subjective effects of cocaine, whereas only minimal changes were observed in men. These results indicate that progesterone modulates the response to cocaine in women and suggests that fluctuations in endogenous progesterone levels account for some of the sex differences observed in humans.

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

Baclofen decreases feeding in non-human primates.

This study examined how the GABA(b) agonist baclofen (0.5-5.6 mg/kg, p.o.), reported to increase food intake in rodents, affected the appetitive and consummatory aspects of feeding of non-human primates. Baboons had access to food 24 h each day, but they had to complete a two-phase operant procedure in order to eat. Responding on one lever during a 30-min appetitive phase was required before animals could start a consumption phase, where responding on another lever led to food delivery, i.e., a meal. Responding during the appetitive phase resulted in presentations of food-related stimuli only. Baclofen increased the latency to the first meal and decreased both appetitive and consummatory behavior. At the largest dose, baclofen induced emesis, indicating that the effects were due to malaise rather than a specific motivational action. In contrast, the positive control diazepam (GABA(a) agonist, 1.0-2.0 mg/kg, i.m.) decreased the latency to the first meal and increased both appetitive (P < 0.07) and consummatory behavior. Although the baclofen-induced decrease in appetitive behavior replicates data obtained in rodents, the baclofen-induced decreases in consummatory behavior do not. The findings suggest that the effects of large doses of baclofen in non-human primates may, in part, be due to non-specific behavioral disruptions.

Animals↗

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

Effects of sibutramine on the appetitive and consummatory aspects of feeding in non-human primates.

This study examined how sibutramine (0.06-4.0 mg/kg, i.m.), a clinically effective weight-loss medication which increases extracellular serotonin and norepinephrine levels, affected the appetitive and consummatory aspects of feeding of non-human primates. The effects were compared to the effects of the positive control dexfenfluramine (2.0-6.0 mg/kg, p.o.), which primarily increases extracellular serotonin levels. Baboons had access to food 24 h each day, but they had to complete a two-phase operant procedure in order to eat. Responding on one lever during a 30-min appetitive phase was required before animals could start a consumption phase, where responding on another lever led to food delivery, i.e., a meal. Responding during the appetitive phase resulted in presentations of food-related stimuli only. Sibutramine increased the latency to the first meal of the session in females, and decreased consummatory behavior without affecting other appetitive behavior in males and females. In contrast, dexfenfluramine, increased the latency to the first meal of the session, and decreased both appetitive and consummatory behavior in males and females. The behavioral mechanism by which sibutramine decreases food intake is distinct from other anorectic drugs, including dexfenfluramine, that have been tested in this paradigm.

Animals↗

PubMed2005

Dronabinol and marijuana in HIV(+) marijuana smokers: acute effects on caloric intake and mood.

RATIONALE: No studies to date have directly compared the tolerability and efficacy of smoked marijuana and oral dronabinol in HIV(+) marijuana smokers. OBJECTIVES: The aim of this study was to compare dronabinol (0, 10, 20, 30 mg p.o.) and marijuana [0.0, 1.8, 2.8, 3.9% Delta(9)-tetrahydrocannabinol (THC)] in two samples of HIV(+) marijuana smokers: those with (n=15) and those without (n=15) a clinically significant loss of muscle mass (<90% body cell mass/height), which is one component of AIDS wasting. METHODS: Mood, physical symptoms, self-selected food intake, cardiovascular data, and cognitive task performance were measured before and repeatedly after dronabinol and marijuana administration in eight 7-h sessions. Marijuana and dronabinol were administered in randomized order using a within-subject, staggered, double-dummy design. RESULTS: As compared to placebo, (1) marijuana (1.8, 2.8, 3.9% THC) and the lower dronabinol doses (10, 20 mg) were well tolerated (e.g., few physical symptoms, significant increases in ratings of "good drug effect") in both groups of participants; the highest dose of dronabinol (30 mg) was poorly tolerated in a subset of participants; (2) marijuana and dronabinol significantly increased caloric intake in the low bioelectrical impedance analysis (BIA) group but not in the normal BIA group; and (3) drug effects on cognitive performance were minor. CONCLUSIONS: These data suggest that for experienced marijuana smokers with clinically significant muscle mass loss, both dronabinol (at acute doses at least four to eight times the current recommendation) and marijuana produce substantial and comparable increases in food intake without producing adverse effects.

Adult↗

PubMed2005

Response to cocaine, alone and in combination with methylphenidate, in cocaine abusers with ADHD.

Attention deficit hyperactivity disorder (ADHD) is prevalent in adult cocaine abusers. Yet, it remains to be determined how the response to cocaine differs in cocaine abusers with ADHD compared to cocaine abusers without ADHD. Further, since ADHD is commonly treated with stimulants, such as methylphenidate (MPH), it is important to examine whether MPH maintenance alters the response to cocaine in cocaine abusers with ADHD. Thus, the first phase of this study compared the response to cocaine in adult cocaine abusers with ADHD to those without ADHD. The second phase assessed the effects of oral sustained-release methylphenidate (MPH-SR) maintenance (40 and 60 mg) on the response to cocaine only in those with ADHD. Cocaine abusers with ADHD (N=7) and without ADHD (N=7) who were not seeking treatment remained inpatient initially for 1 week, when the effects of cocaine alone were tested (Phase 1). Cocaine abusers with ADHD remained inpatient for an additional 3 weeks, during which the effects of cocaine during oral MPH-SR maintenance were tested (Phase 2). During cocaine fixed dosing sessions, participants received four injections of i.v. cocaine (0, 16 or 48 mg/70 kg), spaced 14 min apart. During cocaine choice sessions, participants had a choice between receiving i.v. cocaine (16 or 48 mg/70 kg) or two tokens, each exchangeable for 2 US dollars. Subjective effects related to ADHD symptoms (e.g. ratings of "Able to Concentrate") were significantly lower in cocaine abusers with ADHD compared to those without ADHD when placebo cocaine was administered. Active cocaine produced similar increases in cardiovascular and positive subjective effects in both groups and there was no difference in cocaine choice between the two groups. These data suggest that the response to cocaine is not different between cocaine abusers with ADHD compared to those without ADHD. When the cocaine abusers with ADHD were maintained on MPH-SR, cardiovascular effects were increased, however, this did not warrant termination of any test session. Maintenance on MPH-SR decreased some of the positive subjective effects of cocaine. Further, maintenance on a high dose of MPH-SR decreased cocaine choice. Thus, oral MPH-SR is safe in combination with repeated cocaine doses and decreases some of the positive and reinforcing effects of cocaine in cocaine abusers with ADHD.

Administration, Oral↗

PubMed2005

Smoked cocaine discrimination in humans: effects of gabapentin.

Gamma-aminobutyric acid (GABA) agonists, such as the GABA analogue, gabapentin, may provide new avenues for pharmacological treatment of cocaine dependence. The purpose of this study was to develop a smoked cocaine drug discrimination procedure in humans to test the effects of gabapentin maintenance on the discriminative stimulus, subjective, cognitive and cardiovascular effects of smoked cocaine. Eight male, nontreatment-seeking, cocaine-dependent volunteers, residing on an inpatient research unit for 47 days completed a within-subjects, counter-balanced design. Participants learned to discriminate between cocaine (25 mg) and placebo, and once the criterion for discrimination was met, smoked cocaine dose-effect functions (0, 6, 12, 25 and 50 mg) were determined under three gabapentin maintenance conditions (0, 600 and 1200 mg/day po). The highest dose of gabapentin tested (1200 mg/day) decreased the discriminative stimulus effects of cocaine (6 mg), decreased cocaine craving by 41-53% following cocaine administration (6 and 12 mg), and increased heart rate following either placebo or cocaine (12 mg) administration. Gabapentin did not significantly affect psychomotor task performance or the subjective effects of cocaine. Although the direction of gabapentin's effects was appropriate for a potential treatment medication, i.e., a decrease in cocaine-elicited craving and a decrease in cocaine's discriminative stimulus effects, these effects were limited to low doses of cocaine. The results suggest gabapentin may not produce effects sufficiently robust to be clinically useful, at least at this dose regimen.

Administration, Inhalation↗

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

Effects of dietary and pharmacological manipulations on appetitive and consummatory aspects of feeding in non-human primates.

This study examined how pharmacological and behavioral manipulations affect appetitive and consummatory aspects of feeding of baboons. Baboons have access to food 24 h each day, but they must complete a two-phase operant procedure in order to eat. Responding on one lever during a 30-min appetitive phase was required before animals could start a consumption phase, i.e. a meal, where responding on another lever led to food delivery. Responding during the appetitive phase resulted in presentations of food-related stimuli only. Decreasing session length, increased appetitive behavior and increased meal size. Limiting the number of meals to a single 90 min meal each day but increasing the number of food pellets the animals received increased the size of meal, but did not increase appetitive behavior. These findings suggest that time since the previous meal has a greater effect on appetitive behavior than the size of the previous meal. Amphetamine (AMPH), which increases dopamine, decreased food intake at doses that did not affect appetitive behavior, indicating that appetitive and consummatory aspects of eating can be pharmacologically differentiated. Increasing how frequently animals could earn food-related stimuli in the appetitive phase and food in the consummatory phase increased both appetitive and consumatory behavior. Under these conditions, AMPH nearly doubled appetitive behavior at doses that decreased food intake by nearly 50 percent. When animals had one meal, of self-determined duration, meal size increased without affecting appetitive behavior, further demonstrating that appetitive behavior can be independent of the size of the previous meal and not predictive of the size of the subsequent meal. Under these conditions, AMPH decreased food intake at doses that did not affect appetitive behavior. In contrast, dexfenfluramine (DFEN), which increases serotonin, decreased both appetitive and consumatory behavior. Thus, it is possible to independently manipulate the appetitive and consummatory aspects of eating using both pharmacological and behavioral interventions indicating that it may be possible to develop medications that selectively affect appetitive or consummatory aspects of eating.

Amphetamine↗

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↗