Ratings Of Drug Liking Research Articles

Human methadone self-administration: Effects of diazepam pretreatment.

The effect of diazepam on methadone self-administration was examined. Five methadone-maintained patients with a history of benzodiazepine abuse were recruited. Patients were stabilized on 80 mg of methadone per day. After stabilization patients participated in methadone self-administration sessions. During each session, 128 presses (fixed ratio 128) of 1 button delivered 10 ml of 0.054 mg/ml methadone solution. The same number of button presses on a 2nd button delivered 10 ml of vehicle. Forty-five min prior to the self-administration session, 0 (placebo), 5, 10, or 20 mg per 70 kg body weight diazepam was administered. Ratings of drug liking, goodness, strength, and high were collected 5, 30, 60, 90, and 150 min after the end of the self-administration session. Diazepam pretreatment significantly decreased the amount of methadone consumed. The 10- and 20-mg diazepam doses significantly increased reports of good, like, strong, and high.

Reinforcing effects of triazolam in sedative abusers: Correlation of drug liking and self-administration measures

Six male subjects with histories of sedative abuse were allowed to orally self-administer a maximum of 18 color-coded triazolam and placebo capsules during daily 3-h sessions. The schedule of reinforcement was a signaled fixed-interval 10-min schedule in which triazolam and placebo were concurrently available as mutually exclusive choices. Triazolam was shown to be a reinforcer in four of the six subjects. The two subjects who did not self-administer triazolam in preference to placebo also had lesser histories of drug dependence. Self-administration of triazolam (0.125 or 0.25 mg per capsule) was generally stable over 7–10 days. Manipulations of triazolam dose (0.0312–0.25 mg) per capsule in two subjects showed that the number of capsules self-administered was inversely related to capsule dose. Subject ratings of drug liking obtained from experimenter-administered doses of triazolam were correlated with self-administration behavior occurring 1–7 days later. Of the subject ratings, next day ratings obtained on the day after dosing resulted in significant correlations whereas same day ratings obtained while subjects were under the influence of triazolam did not. These results have important implications for abuse liability prediction and suggest that next day ratings have greater predictive validity than measures collected while subjects are under the influence of benzodiazepines.

Reinforcing and subjective effects of methylphenidate in humans.

This study assessed the reinforcing and subjective effects of methylphenidate in a group of 35 adults (15 females and 20 males) with no history of drug dependence. A discrete-trial choice procedure was used to assess the reinforcing effects of a single oral dose of methylphenidate selected to produce a moderate subjective response in each subject (range 20-40mg). A number of variables (gender, current and past drug use, personality, and baseline mood and arousal) were examined in an attempt to identify sources of variability in drug response. Methylphenidate was chosen on 28% of occasions. In the group as a whole, methylphenidate had no effect on ratings of drug liking, but did increase ratings indicative of "positive" mood, CNS stimulation and anxiety. Within-subject variability in methylphenidate choice was related to variability in subjective response to the drug across choice trials. Methylphenidate choice was also associated with between-subject differences in prior opioid use and several personality dimensions. When compared with the results of a prior study of the same design with d-amphetamine, these results suggest that methylphenidate produces a somewhat different profile of subjective effects, and may be a less efficacious reinforcer than d-amphetamine.

EFFECTS OF Δ9‐THC ON MARIJUANA SMOKING, DOSE CHOICE, AND VERBAL REPORT OF DRUG LIKING

The effects of delta 9-tetrahydrocannabinol content of marijuana on cigarette smoking, dose choice, and verbal report of drug "liking" by adult males living in a residential laboratory were investigated. Marijuana cigarettes were available during programmed intervals while subjects were engaged in recreational activities. The tetrahydrocannabinol content of the cigarettes remained constant each day, but was changed across days. Subjects provided written ratings of drug liking at the end of each day. In the first study, placebo or active (2.3% delta 9-tetrahydrocannabinol) marijuana cigarettes were available for 1-, 2-, or 3-day intervals at varying times of day. The number of cigarettes smoked was unrelated to tetrahydrocannabinol content, although verbal reports of drug liking were consistently higher when marijuana cigarettes containing tetrahydrocannabinol were smoked. In a second study, a choice procedure, consisting of four 3-day blocks of 2 sample days and 1 choice day, was used. On sampling days, subjects smoked cigarettes varying in tetrahydrocannabinol content (0.0, 2.0, and 3.5%, w/w); on choice days they were allowed to choose between the two previously sampled doses. The number of cigarettes was not consistently related to tetrahydrocannabinol content. Ratings of drug liking were increased when marijuana cigarettes contained tetrahydrocannabinol, but ratings of marijuana containing 2.0% and 3.5% of the compound were similar. In contrast, subjects consistently chose the 3.5% dose over either the 0.0% or 2.0% dose. Dose choice was more sensitive to tetrahydrocannabinol content than either reports of drug liking or numbers of cigarettes smoked.

Self-administration of pentobarbital in light and moderate alcohol drinkers

Preference for a moderate dose of pentobarbital was assessed in light and moderate alcohol drinkers using a double-blind, placebo-controlled laboratory choice procedure. Sixteen light drinkers (less than six alcoholic drinks per week) and 13 moderate drinkers (six or more drinks per week) participated in a seven-session study in which they first sampled capsules containing pentobarbital (150 mg) or placebo and then chose and ingested the capsule they preferred. Subjective and behavioral measures were obtained at regular intervals during each session to characterize the drug's effects. Both groups chose pentobarbital less often than placebo: Mean pentobarbital choice in light drinkers was 20.8% and in moderate drinkers was 38.5%. Pentobarbital choice and drug liking ratings were highest among male moderate drinkers but still did not exceed placebo levels. The drug did not increase scores on standardized measures of drug euphoria, even among the most frequent choosers or the heaviest alcohol consumers. The results extend previous reports showing that individual without histories of drug abuse, even those who are moderate consumers of alcohol, do not self-administer sedative/anxiolytic drugs or experience their effects as euphorigenic.

Subjective, Behavioral, and Physiologic Responses to Intravenous Dezocine in Healthy Volunteers

Dezocine is an agonist-antagonist opiate that acts at the mu receptor, and is used for management of pain. Monkeys will readily press a lever to receive an injection of dezocine, and in former opiate addicts dezocine produces positive subjective effects similar to those of morphine. It is not clear, however, what its subjective effects are in people who do not have a history of opiate abuse. To answer this question, a within-subjects design was used in which 10 normal healthy volunteers (six men, four women) were injected with 0, 2.5, 5.0, and 10 mg/70 kg of dezocine in a double-blind fashion. Subjects completed several questionnaires (e.g., Addiction Research Center Inventory) commonly used in abuse liability testing before and at periodic intervals for up to 5 h after drug injection. We also assessed psychomotor performance (e.g., eye-hand coordination) and several physiologic measures (e.g., pupil size, respiration rate) at these times. Dezocine produced increases in ratings of drug liking (P less than 0.001), as well as other subjective effects that might be considered as pleasant ("good mood," "drunken," "coasting," "happy" ratings) (all P less than 0.05). At the same time, the drug had effects (increased dysphoria and sedation) that typically are not reported by addicts. Dezocine produced psychomotor impairment and miosis (constriction of the pupils) in a dose-dependent fashion. The observation that dezocine produces euphoria and increased drug-liking ratings in individuals without histories of drug abuse suggests that hospitals and surgicenters should have strict accountability procedures with this drug.

Diazepam and triazolam self-administration in sedative abusers: concordance of subject ratings, performance and drug self-administration

The reinforcing effects of diazepam (DZ), triazolam (TZ) and placebo were examined in eight male subjects with histories of sedative abuse. DZ (40 or 80 mg), TZ (1.0 or 2.0 mg) and placebo were each individually available for oral self-administration using a double-blind within-subject design. After an initial sampling exposure, subjects could self-administer a single dose of drug on each of 6 days by completing a progressively increasing bicycle riding requirement. All subjects initially self-administered DZ and TZ but a decreasing number of subjects continued to self-administer drugs on the remaining days; there was no difference between DZ and TZ in the total number of self-administrations. Placebo was self-administered only by one subject on two occasions. Performance measures showed that TZ produced greater memory impairment than DZ and that DZ produced residual psychomotor impairment on the next day. With repeated dosing, evidence of tolerance was seen for both drugs on psychomotor and memory performance and subject ratings of drug liking. A few modest correlations of drug self-administration and subject-ratings were obtained, suggesting some correspondence of subject verbal and drug self-administration behaviors, but these measures did not covary in a completely consistent manner.

Assessing individual differences in ethanol preference using a cumulative dosing procedure

Preference for ethanol versus a placebo was assessed in 12 normal volunteers usina a cumulative dosing preference test. The test consisted of four sampling sessions followed by three choice sessions. During the sampling sessions subjects received either five cumulating oral doses of ethanol (0.1 g/kg per dose) or equal volumes of placebo, at 15-min intervals. Subjective and observer-rated drug effects, psychomotor performance, drug liking ratings, and breath ethanol levels were measured at regular intervals. During choice sessions, subjects first chose which of the two substances (drug or placebo) they wished to take and ingested one unit dose. Then, at 15-min intervals throughout the session, they could ingest up to ten additional unit doses of the same substance (i.e., up to 1.1 g/kg ethanol). On average, the subjects chose the ethanol-containing beverage on 75% of the choice sessions, and they self-administered a mean total dose of 0.8 g/kg per session. Subjects varied in the amount of ethanol ingested on choice sessions, and the amount they chose was related to their subjective responses to the drug during sampling. Subjects who chose the most ethanol, whereas the subjects who chose ethanol less frequently and ingested lower doses reported primarily sedative-like effects from the drug. The results demonstrate that the cumulative dosing procedure can be used effectively to evaluate drug preferences and dose preferences in normal volunteers.

Individual differences in the discriminative stimulus effects of d‐amphetamine in humans

AbstractThe discriminative stimulus (DS) and subjective effects of d‐amphetamine (AMP) were examined in male and female normal healthy adults. Subjects were trained to discriminate between oral AMP (10 mg) and placebo. Of the 100 subjects who underwent discrimination training, 53 reliably learned the discrimination. These “discriminators” (Ds) were compared with the 47 “nondiscriminators” (NDs) on a variety of measures. Ds and NDs did not differ qualitatively in their response to AMP. As a group Ds were more certain than NDs of their ability to discriminate between AMP and placebo and were more accurate in labelling AMP as a stimulant. AMP also had a greater effect for Ds than for NDs on ratings of drug liking and general activity level during the day. Although Ds generally showed a stronger subjective response to AMP, Ds differed significantly from NDs on only 4 of 18 mood scales affected by AMP (2 anxiety scales and analog ratings of “stimulated” and “high”). Ds did not differ from NDs on any of the following measures: body weight, gender, current or lifetime drug use, baseline mood state, subjective response to placebo, or a variety of personality traits. The results demonstrate considerable individual differences in sensitivity to AMP and suggest a relationship between the DS effects of AMP and specific mood states.

Discriminative stimulus effects of caffeine and benzphetamine in amphetamine-trained volunteers.

The discriminative stimulus (DS) and subjective effects of caffeine (100 and 300 mg, PO) and benzphetamine (12.5 and 50 mg, PO) were studied in 18 normal human volunteers trained to discriminate between d-amphetamine (10 mg) and placebo. d-Amphetamine increased ratings of drug liking and activity level and produced a profile of subjective effects characteristic of amphetamine and related psychomotor stimulants. The DS effects of d-amphetamine generalized only partially to caffeine and benzphetamine; mean percent d-amphetamine-appropriate responding was 42 and 58 after 100 and 300 mg caffeine, respectively, and 17 and 56 after 12.5 and 50 mg benzphetamine, respectively. Neither dose of caffeine affected ratings of drug liking or activity level, but 300 mg caffeine did produce a profile of subjective effects that partially overlapped with that produced by d-amphetamine. Benzphetamine 50 mg, but not 12.5 mg, increased ratings of drug liking and activity level and produced a profile of subjective effects qualitatively similar to, but weaker than, that produced by d-amphetamine. For both caffeine and benzphetamine, a close relationship was observed between their subjective effects and their ability to substitute for the DS effects of d-amphetamine. These results correspond well with findings obtained from similar studies conducted with laboratory animals, providing further support for the reliability and validity of human drug discrimination paradigms.