Acute behavioral and physiological effects of modafinil in drug abusers.

Modafinil, a novel stimulant, is effective in the treatment of excessive daytime sleepiness associated with narcolepsy. It is biochemically and pharmacologically distinct from prototypical stimulants such as D-amphetamine, cocaine, and methylphenidate. The present experiment was designed to assess the acute behavioral effects of oral modafinil, cocaine, and placebo in participants (n=9) with recent histories of cocaine use (i.e. positive urine for cocaine or benzoylecgonine during the initial screening interview). Drug effects were assessed with a battery of self-reported drug-effect questionnaires, performance measures, and physiological indices. Cocaine, but not modafinil, produced stimulant-like self-reported drug effects (e.g. increased ratings of High and Stimulated). Modafinil and cocaine dose-dependently increased heart rate and blood pressure. The results of the present study suggest that modafinil has minimal abuse potential, but should be viewed cautiously because of the relatively small sample size. Future studies should further characterize the abuse potential of modafinil using other behavioral arrangements, such as drug discrimination or drug self-administration. A full characterization of the abuse potential of modafinil will become important as the use of this drug increases.

Retrograde facilitation of memory by triazolam: effects on automatic processes.

RATIONALE: Retrieval processes have been implicated as a potential mechanism by which benzodiazepines can produce retrograde memory facilitation. OBJECTIVES: This study tested the degree to which benzodiazepine-induced retrograde facilitation of memory was due to an enhancement of automatic retrieval processes. METHODS: Forty healthy adults were randomly assigned to one of three dose conditions (double-blind), under which they received 0.0 mg (placebo), 0.125 mg, or 0.25 mg of the short-acting benzodiazepine triazolam (Halcion). Subjects studied a list of words just prior to dose administration. One hour after dose administration, subjects performed a word-stem completion task which tested their retrieval of the studied words. A process-dissociation procedure was used to estimate the degree to which retrieval was under the influence of memory processes that were automatic (i.e., unintentional) versus controlled (i.e., intentional). RESULTS: Subjects who received active doses of triazolam displayed a greater probability of using studied words as stem completions. Estimates of memory processes showed a greater influence of automatic influences during memory retrieval under triazolam doses. CONCLUSIONS: The findings indicate that retrograde memory facilitation following benzodiazepine administration does not necessarily reflect an improved ability to intentionally retrieve information but could instead reflect increased responsiveness to cues that automatically elicit retrieval of pre-drug information.

Alcohol effects on inhibitory and activational response strategies in the acquisition of alcohol and other reinforcers: priming the motivation to drink.

OBJECTIVE: Low doses of alcohol can increase (i.e., prime) operant responding for alcohol in social drinkers. The present study tested the degree to which alcohol increased subjects' responding for the drug by biasing their reward-acquisition strategies in favor of response activation, and away from inhibitory responding. METHOD: Thirty-two social drinkers received either a priming dose of alcohol (0.55 g/kg) or a placebo, prior to performing a stop-signal task to earn their choice of alcoholic drinks or alternative monetary reinforcers. RESULTS: When alternative monetary reinforcement was of low value, alcohol was chosen more often by subjects who received the priming dose versus those who received the placebo. The priming dose also affected reward-acquisition strategies. Subjects who received the priming dose obtained reinforcers by increased response activation and reduced response inhibition. By contrast, those who received the placebo obtained reinforcers via a combination of activational and inhibitory responding. CONCLUSIONS: The results of this study show that alcohol might affect cognitive processes involved in drug reinforcement. By combining traditional operant measures of drug reinforcement with tasks that assess cognitive processes, this research offers a promising new strategy to study the role of cognitive processes in the abuse potential of a wide range of drugs.

Behavioral pharmacological similarities between methylphenidate and cocaine in cocaine abusers.

Six human participants with recent histories of cocaine use were trained to discriminate 200 mg oral cocaine hydrochloride. A range of doses of oral cocaine (50-300 mg), methylphenidate (15-90 mg), triazolam (0.125-0.75 mg), and placebo were then tested to determine whether they shared discriminative-stimulus and participant-rated effects with 200 mg cocaine. Cocaine and methylphenidate dose-dependently increased cocaine-appropriate responding, produced prototypical stimulant-like participant-rated drug effects (e.g., increased participant ratings of Drug Liking), and increased heart rate and blood pressure. Triazolam produced low levels of cocaine-appropriate responding and impaired performance. Thus, consistent with previous studies, humans can reliably discriminate oral cocaine. Consistent with in vivo behavioral neuropharmacological data, the discriminative-stimulus, participant-rated, and physiological effects of oral cocaine and methylphenidate were similar.

Reinforcing and subject-rated effects of methylphenidate and d-amphetamine in non-drug-abusing humans.

The reinforcing effects of methylphenidate (20-40 mg), d-amphetamine (10-20 mg), and placebo were assessed in eight healthy, non-sleep-deprived, non-drug-abusing outpatient volunteers. A modified progressive-ratio schedule was used to assess drug reinforcement in which a sampling session always preceded a self-administration session. During sampling sessions, volunteers received a drug dose to acquaint them with the drug effects. Drug doses were administered in eight identical capsules (i.e., each capsule contained 12.5% of the total dose). During self-administration sessions, which generally were conducted the next day, volunteers were given eight opportunities to work on a computer and could earn all, or some, of the capsules that were administered the previous day. To earn the first capsule, volunteers had to click a computer mouse 50 times. The number of clicks required to earn each additional capsule doubled (i.e., 100, 200, 400, 800, 1,600, 3,200, and 6,400 clicks). The dependent measure on this task was the break point (i.e., the last ratio completed). To characterize more fully the behavioral effects of methylphenidate and d-amphetamine, a battery of subject-rated drug-effect questionnaires, performance tasks, and physiologic measures was also used. Both doses of d-amphetamine increased the break point significantly above placebo levels, whereas only the high dose of methylphenidate did so. Break-point values for the doses of methylphenidate and d-amphetamine that maintained the greatest responding did not differ significantly. Methylphenidate and d-amphetamine produced some stimulantlike subject-rated drug effects (e.g., increased ratings of "drug liking"). These data suggest that methylphenidate, like d-amphetamine, can function as a reinforcer under a modified progressive-ratio schedule and, by inference, has at least some abuse potential in healthy, non-sleep-deprived, non-drug-abusing volunteers.

Assessing the abuse potential of methylphenidate in nonhuman and human subjects: a review.

Methylphenidate (MPH) is widely used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children, adolescents, and adults. Methylphenidate is clearly effective for the treatment of ADHD, but there is controversy as to whether it has significant abuse potential like other psychostimulants (e.g., D-amphetamine and cocaine). In general, the drug is believed to be abused at rates much lower than those for other stimulants. The present review examines studies that investigated the behavioral pharmacological profile of methylphenidate and discusses how results from these studies address its abuse liability. Using MEDLINE search terms methylphenidate, drug discrimination, reinforcement, self-administration, subjective effects, subject-rated effects, abuse potential, and abuse liability, along with a review of the references from identified articles, 60 studies were located in which the reinforcing, discriminative-stimulus, or subjective effects of methylphenidate were directly assessed in nonhumans or humans. Forty-eight (80.0%) of the studies reviewed indicate that methylphenidate either functions in a manner similar to D-amphetamine or cocaine (e.g., functions as a reinforcer, substitutes fully in drug discrimination experiments), or produces a pattern of subjective effects suggestive of abuse potential. The results are discussed as they pertain to factors that may account for the apparent discrepancy in abuse rates between methylphenidate and other stimulants, including characterization of actual abuse rates, defining abuse and misuse, pharmacokinetic factors, and validity of abuse liability assays.

Pretreatment with hydromorphone, a mu-opioid agonist, does not alter the acute behavioral and physiological effects of ethanol in humans.

BACKGROUND: Endogenous opioid systems are thought to mediate at least some of the behavioral effects of ethanol. Opioid antagonists, like naloxone and naltrexone, decrease ethanol self-administration under a variety of conditions in different species of laboratory animals (e.g., rodents and nonhuman primates). Opioid agonists, like morphine, also alter ethanol consumption. However, the dose-response functions for opioid agonists are complex in that low doses increase ethanol self-administration, whereas moderate to high doses decrease ethanol self-administration. The results of prospective human laboratory studies that assessed the behavioral effects of ethanol after pretreatment with an opioid antagonist are mixed. The aim of the present study was to assess the acute subject-rated effects of ethanol (0, 0.5, and 1 g/kg) after pretreatment with hydromorphone, a mu-opioid agonist. METHODS: In the present experiment, the acute subject-rated, performance-impairing, and physiological effects of ethanol (0, 0.5, and 1 g/kg) were examined after pretreatment with hydromorphone (0, 1, and 2 mg), a mu-opioid agonist, in nine healthy volunteers. Volunteers received one of the nine possible ethanolhydromorphone combinations during each of nine experimental sessions. RESULTS: Ethanol produced prototypical subject-rated drug effects (e.g., dose dependently increased ratings of "high"), impaired performance, and increased heart rate. Hydromorphone pretreatment generally did not significantly alter the subject-rated, performance-impairing, or physiological effects of ethanol. CONCLUSIONS: The results of the present experiment suggest that hydromorphone pretreatment does not significantly affect the subject-rated effects of ethanol. Future human laboratory studies should test higher doses of hydromorphone. Future studies also might use more sophisticated behavioral procedures like self-administration, or perhaps drug discrimination, to determine if opioid agonists can modulate the behavioral effects of ethanol in humans.

Triazolam impairs inhibitory control of behavior in humans.

This study tested the effects of the sedative-hypnotic drug triazolam (Halcion) on the ability to inhibit behavior in humans. Thirty adults practiced a stop-signal task that measured their ability to inhibit and activate behavioral responses on a choice reaction time task. Equal numbers of participants (i.e., n = 10) then received either 0.25 mg, 0.125 mg, or 0 mg (placebo) of triazolam under double-blind conditions and performed the task intermittently over a 3-hr period. In accord with the hypothesis, triazolam reduced response inhibitions and increased the time required to inhibit a response. The drug also slowed the activation of responses. The findings contribute to the understanding of the basic behavioral mechanisms by which sedative-hypnotic drugs can produce states of behavioral disinhibition in some individuals.

Discriminative-stimulus effects of zolpidem, triazolam, pentobarbital, and caffeine in zolpidem-trained humans.

Six non-drug-abusing humans were trained to discriminate 15 mg zolpidem in the present experiment. After participants acquired discrimination, a range of doses of zolpidem (2.5-15.0 mg), triazolam (0.0625-0.3750 mg), pentobarbital (25-150 mg), caffeine (100-600 mg), and placebo were tested to determine whether they shared discriminative-stimulus effects with 15 mg zolpidem. The participant-rated and performance-impairing effects of zolpidem, triazolam, pentobarbital, and caffeine were assessed concurrently. Triazolam and pentobarbital dose dependently increased zolpidem-appropriate responding. Caffeine occasioned low levels of zolpidem-appropriate responding. Zolpidem, triazolam, and pentobarbital, but not caffeine, generally produced a similar constellation of participant-rated drug effects (e.g., increased scores for the Pentobarbital, Chlorpromazine, and Alcohol Group subscale on the Addiction Research Center Inventory) and dose dependently impaired performance. These results suggest that humans can reliably discriminate zolpidem. Despite its unique benzodiazepine-receptor binding profile, the discriminative-stimulus, participant-rated, and performance-impairing effects of zolpidem are similar to those of the barbiturates and benzodiazepines.

Effects of training dose on the relationship between discriminative-stimulus and self-reported drug effects of d-amphetamine in humans.

The aim of the present experiment was to examine the relationship between the discriminative-stimulus and self-reported effects of drugs in humans. To accomplish this aim, nine healthy adult volunteers (four females, five males) were trained to discriminate between placebo and 10 mg d-amphetamine (low-dose group) or 20 mg d-amphetamine (high-dose group). After acquiring the placebo-amphetamine discrimination, a range of doses of d-amphetamine (1.25-20 mg) was tested to determine if they shared discriminative stimulus effects with the training dose. Participants in the low-dose group exhibited a significant leftward shift in the dose-response function for discrimination performance, which is concordant with previous preclinical and human drug discrimination studies that assessed the effects of training dose. Consistent with the drug discrimination findings, participants in the low-dose group exhibited a significant leftward shift in the dose-response function for several self-reported drug effects (e.g., Like the Drug and Stimulated). However, several other self-reported drug effect items were not significantly influenced by training condition (e.g., Anxious/Nervous and Bad Effects). These results suggest that the discriminative-stimulus and self-reported drug effects of d-amphetamine overlap, but are not isomorphic. Furthermore, these results illustrate that behavioral history significantly influences subsequent drug effects in humans.

A follow-up study of the acute behavioral effects of benzodiazepine-receptor ligands in humans: comparison of quazepam and triazolam.

Quazepam, a trifluoroethylbenzodiazepine hypnotic, and triazolam, a triazolobenzodiazepine hypnotic, differ in terms of their benzodiazepine-receptor binding profile. Previous studies have suggested that quazepam produces less performance impairment than triazolam. Whether these effects are due to differences between quazepam and triazolam in terms of their benzodiazepine-receptor binding profile or to the testing of insufficient doses is unknown. The present study compared the acute behavioral effects of triazolam (0.1875, 0.3750, and 0.5625 mg), quazepam (30, 60, and 90 mg), and placebo in 12 healthy humans using a within-subjects, placebo-controlled, crossover design. Quazepam and triazolam produced comparable dose-dependent performance impairment and increased ratings of drug effect and drowsy. Quazepam, but not triazolam, increased ratings of dizzy/light-headed, performance impaired, and sleepy. Triazolam, but not quazepam, increased ratings of high. Thus, across a sufficient range of doses, the performance-impairing effects of quazepam were similar to those of triazolam. By contrast, quazepam and triazolam produced somewhat different constellations of participant-rated drug effects. These differential drug effects may be attributable to differences between quazepam and triazolam in terms of their benzodiazepine-receptor binding profile.

Acute behavioral effects and abuse potential of trazodone, zolpidem and triazolam in humans.

The present study examined the acute behavioral effects and abuse potential of three drugs commonly used to treat sleep disorders, trazodone, zolpidem and triazolam, and placebo in ten male volunteers with histories of alcohol and drug abuse. Trazodone (100, 200 and 300 mg), a triazolopyridine antidepressant, was included because antidepressants are being used more frequently to treat sleep disorders, but it is unclear whether they have a distinct behavioral pharmacologic profile relative to benzodiazepine hypnotics. Zolpidem (15, 30 and 45 mg), an imidazopyridine hypnotic, was tested because it is the most commonly prescribed hypnotic and purportedly has a unique benzodiazepine-receptor binding profile. Triazolam (0.25, 0.5 and 0.75 mg), a triazolobenzodiazepine hypnotic, was included as the standard component because previous laboratory studies have demonstrated that it has at least some abuse potential. Trazodone, zolpidem and triazolam generally produced comparable dose-related increases in scores on the PCAG scale of the ARCI, which suggests the doses tested were equivalent on some behavioral dimension. The effects of trazodone on subject-rated items thought to measure abuse potential (e.g., subject ratings of Willing to Take Again) were less than those observed with triazolam. Zolpidem and triazolam produced comparable effects on these measures. The highest dose of zolpidem, but not triazolam, increased ratings of Like Drug, Happy, Good Effects, Friendly, Elated, Carefree and Bad Effects. Triazolam and zolpidem produced dose-dependent impairment on all of the performance tasks. Trazodone impaired performance on some, but not all, of these tasks. Consistent with the pharmacokinetics of these compounds, the time-action functions of trazodone, zolpidem and triazolam were similar on these measures. These data suggest that trazodone has less abuse potential than triazolam, and may be a viable alternative to benzodiazepine hypnotics in individuals with histories of alcohol or drug abuse. By contrast, despite its unique neuropharmacological profile, the acute behavioral effects and abuse potential of zolpidem are comparable to those of triazolam.

Zaleplon and triazolam in humans: acute behavioral effects and abuse potential.

Zaleplon, a pyrazolopyrimidine that is under development as a hypnotic, produces its pharmacological effects at the benzodiazepine-recognition site on the GABA(A) benzodiazepine-receptor complex. Unlike most benzodiazepines, zaleplon binds selectively to the BZ1 (omega1) subtype of the benzodiazepine receptor. The present study compared the acute subject-rated effects, performance-impairing effects, and abuse potential of zaleplon and triazolam, a triazolobenzodiazepine hypnotic, in 14 healthy volunteers with histories of drug abuse. Zaleplon (25, 50, and 75 mg), triazolam (0.25, 0.5, and 0.75 mg) and placebo were administered orally in this double-blind, crossover study. Zaleplon and triazolam produced comparable dose-related effects on several subject-rated drug-effect questionnaires. Zaleplon and triazolam also produced comparable dose-dependent decrements on several performance tasks including balance, circular lights, digit-enter and recall, DSST, picture recall/recognition and repeated acquisition. Same-day and next-day subject-rated measures reflecting abuse potential (e.g., drug liking, good effects, and monetary street value) also suggest that zaleplon and triazolam were comparable. The only notable between-drug difference observed in the present study was that the time-action function of zaleplon differed from that of triazolam. The onset time, time to maximum drug effect, and duration of action were shorter with zaleplon than triazolam. Thus, despite its non-benzodiazepine structure and unique benzodiazepine-receptor binding profile, the behavioral pharmacological profile of zaleplon is similar to that of triazolam.

Acute physiological and behavioral effects of oral cocaine in humans: a dose-response analysis.

The present study was designed to assess the acute physiological and behavioral effects of a wide range of doses of oral cocaine HCL (placebo, 50, 100, 200, and 300 mg). Nine volunteers (eight males and one female) with recent histories of cocaine use resided on a general inpatient psychiatry unit while they participated. Drug doses were administered in a double-blind fashion under medical supervision, but for safety purposes, they were administered in ascending order. The physiological, subject-rated, and performance effects of oral cocaine HCL were assessed before drug administration and periodically afterwards for 5 h. Oral cocaine HCL increased heart rate and blood pressure as a graded function of dose, but the magnitude of these effects were not clinically significant. Oral cocaine HCL produced positive subject-rated drug effects (e.g. increased ratings of good effects, like drug, and willing to take again), but did not affect performance. Consistent with the pharmacokinetics of oral cocaine HCL, drug effects were generally discernible from placebo 0.5-1 h after administration, peaked approximately 1 h after administration, and progressively abated during the remainder of the experimental session. The results of this experiment demonstrate that across a six-fold range of doses oral cocaine HCL is well tolerated by individuals with recent histories of cocaine use and can be safely administered under controlled laboratory and medical conditions.

Naltrexone does not attenuate the acute behavioral effects of ethanol or pentobarbital in humans.

The aim of the present study was to determine whether naltrexone, an opioid antagonist, attenuates the acute subject-rated, performance-impairing and physiological effects of ethanol or pentobarbital. To accomplish this aim, two separate experiments were conducted. In Experiment 1, eight volunteers (one female, seven males) received ethanol (0, 0.5 and 1.0 g/kg) alone and in combination with naltrexone (0, 50 and 100 mg). In Experiment 2, eight different volunteers (five females, three males) received pentobarbital (0, 150 and 300 mg), alone and in combination with naltrexone (0, 50 and 100 mg). Subjects received one of the nine possible drug-naltrexone combinations under double-blind conditions during each of nine experimental sessions. Order of drug administration was mixed, and at least 48 h separated all sessions. In Experiment 1, subjects orally ingested ethanol 1 h after naltrexone. In Experiment 2, subjects ingested naltrexone 1 h after pentobarbital. The timing of drug administration was arranged so that the peak behavioral effects of ethanol or pentobarbital occurred so that across peak plasma levels of naltrexone. Drug effects were assessed before drug administration and periodically afterwards for 5 h using a battery of subject-rated drug-effect questionnaires and performance measures previously shown to be sensitive to the acute effects of ethanol. Ethanol and pentobarbital produced prototypical subject-rated drug effects (e.g. increased subject ratings of Drunk, Drug Liking, Elated and Good Effects) and impaired performance. Naltrexone did not produce significant effects on these measures. In other words, naltrexone did not attenuate the acute subject-rated and performance-impairing effects of ethanol or pentobarbital. The mechanism by which naltrexone exerts its clinical effect in the treatment of alcohol abuse/dependence remains unclear.

Comparison of acute behavioral effects of sustained-release and immediate-release methylphenidate.

The rate of onset of a drug's effect is an important determinant of its abuse potential. This experiment examined the acute behavioral effects of orally administered sustained-release methylphenidate (SR; 20-40 mg), immediate-release methylphenidate (IR; 20-40 mg), and placebo in 10 healthy volunteers. Drug effects were assessed before drug administration and periodically afterwards for 6 hr using drug-effect questionnaires and performance measures that are sensitive to the acute effects of stimulants. The IR formulation produced stimulant-like drug effects (e.g., increased ratings of "good effects") that generally varied as a function of dose and time. The SR formulation produced only transient effects on these measures. These findings are consistent with previous research on the influence of rate of onset using other drugs and suggest that the abuse potential of IR methylphenidate may be greater than that of SR methylphenidate.

Behavioral pharmacology of zolpidem relative to benzodiazepines: a review.

Zolpidem, an imidazopyridine that purportedly binds selectively to certain GABA(A) receptor subtypes, is the most commonly prescribed hypnotic. The present article critically reviewed the extant experimental literature to determine whether the behavioral pharmacologic profile of zolpidem also differs from that of benzodiazepines. Specific topics that are reviewed include: 1) reinforcing effects and abuse potential, 2) discriminative-stimulus effects, 3) subject-rated drug effects, 4) performance-impairing effects, 5) tolerance-producing effects, and 6) physiological dependence-producing effects. Studies that employed both nonhumans and humans are reviewed. Based on the available literature, the most parsimonious conclusion is that despite its unique neuropharmacological profile, the behavioral effects of zolpidem are generally similar to those of benzodiazepines. However, it is important to note the dearth of perspective, experimental studies that directly compared zolpidem and a benzodiazepine. Because of the clinical relevance and paucity of published studies, future research should focus explicitly on assessing the reinforcing effects, abuse potential, performance-impairing effects, tolerance-producing effects, and dependence-producing effects of zolpidem relative to a benzodiazepine. Important issues such as the selection of an appropriate comparison drug and subject population, and the doses tested needed to be considered in these future studies.

Buspirone is differentiated from diazepam in humans using a three-response drug discrimination procedure.

The discriminative stimulus effects of buspirone and diazepam were examined in 12 healthy volunteers using a three-response drug discrimination procedure and a within-subject design. During an initial sampling phase, the training drug conditions (placebo, 15 mg/70 kg buspirone, and 10 mg/70 kg diazepam) were identified to subjects by letter codes before oral drug administration. During a subsequent training phase, subjects earned money for correct drug identifications made two hours after drug administration. Ten out of 12 subjects acquired the three-response discrimination. When lower doses of buspirone (3.75 and 7.5 mg/70 kg) and diazepam (2.5 and 5.0 mg/70 kg) were tested in a subsequent generalization testing phase, both buspirone and diazepam produced dose-related increases in appropriate drug identifications, without significant cross-generalization. Analyses of standardized and unstructured self report questionnaires revealed that buspirone and diazepam produced different profiles of effects, and that buspirone was associated with a number of "negative" subject-rated effects including tension, nausea, and dizziness. These results demonstrate a distinct profile of discriminative stimulus and subjective effects for buspirone relative to diazepam which is consistent with its distinct pharmacological profile, and provide evidence for the sensitivity of the three-response drug discrimination procedure.

Pretreatment with isradipine, a calcium-channel blocker, does not attenuate the acute behavioral effects of ethanol in humans.

The acute subject-rated, performance-impairing, and physiological effects of ethanol (0, 0.5, and 1 g/kg) were examined after pretreatment with isradipine (0, 5, and 10 mg) in nine healthy volunteers. Volunteers received 1 of the 9 ethanol-isradipine combinations during each of nine experimental sessions. Ethanol alone produced prototypical subject-rated drug effects (e.g., increased ratings of "Drunk," "Good effects," and "Like drug") and impaired performance. Isradipine alone also produced significant subject-rated drug effects (e.g., increased ratings of "Drug effect," "Bad effects," "High," and "Stimulated"), but did not impair performance. Isradipine pretreatment generally did not significantly alter the subject-rated or performance-impairing effects of ethanol. Isradipine alone, but not ethanol alone, significantly decreased systolic and diastolic blood pressure. The ethanol-isradipine combinations generally produced significantly greater decreases in blood pressure than were observed with isradipine alone. Breath-alcohol levels were significantly lower after isradipine pretreatment, which suggests isradipine altered the bioavailability of ethanol. The present findings extend previous studies with humans that examined the behavioral effects of ethanol after pretreatment with other calcium-channel blockers, including nifedipine, nimodipine, and verapamil. Whereas the available studies suggest that calcium-channel blockers would not be useful pharmacological adjuncts in the management of ethanol abuse, more research is needed. Future studies should use self-administration and drug discrimination procedures adapted for use with humans to determine if calcium-channel blockers can attenuate any of the behavioral effects of ethanol.

Discriminative-stimulus and participant-rated effects of methylphenidate, bupropion, and triazolam in d-amphetamine-trained humans.

The discriminative-stimulus and participate-rated effects of a range of doses of d-amphetamine (2.5-20 mg), methylphenidate (5-40 mg), bupropion (50-400 mg), and triazolam (0.0625-0.5 mg) were tested in 5 humans trained to discriminate between oral d-amphetamine (20 mg) and placebo. d-Amphetamine and methylphenidate generally dose dependently increased drug-appropriate responding. Bupropion and triazolam on average occasioned less than or equal to 40% drug-appropriate responding. d-Amphetamine, methylphenidate, and bupropion produced stimulant-like participant-rated effects, while triazolam produced sedative-like effects. These results further demonstrate that the acute behavioral effects of d-amphetamine and methylphenidate overlap extensively in humans, which is concordant with preclinical studies. Bupropion produced some d-amphetamine-like, participant-rated drug effects but did not occasion significant levels of d-amphetamine-appropriate responding. These findings are concordant with previous findings of a dissociation between the discriminative-stimulus and participant-rated effects of drugs.