Risk taking differences on a behavioral task as a function of potential reward/loss magnitude and individual differences in impulsivity and sensation seeking.

Although previous studies have shown that the Balloon Analogue Risk Task (BART; [Lejuez, C.W., Read, J.P., Kahler, C.W., Richards, J.B., Ramsey, S.E., Stuart, G.L., et al. (2002). Evaluation of a Behavioral Measure of Risk Taking: The Balloon Analogue Risk Test (BART). J Exp Psychol, Appl, 8, 75-84.; Lejuez, C., Aklin, W., Jones, H., Richards, J., Strong, D., Kahler, C.W., et al. (2003a). The Balloon Analogue Risk Task (BART) Differentiates Smokers and Nonsmokers. Exp Clin Psychopharmacol, 11, 26-33.; Lejuez, C., Aklin, W., Zvolensky, M., & Pedulla, C. (2003b). Evaluation of the Balloon Analogue Risk Task (BART) as a Predictor of Adolescent Real-world Risk-taking Behaviors. J Adolesc, 26, 475-479.]) can be used to index real-world risk-taking behavior, questions remain regarding how performance on the task may vary as a function of reward/loss value and how this relationship may differ as a function of relevant personality traits. The present study examined BART score at 1, 5, and 25 cents per pump and how this relationship differed at low and high levels of impulsivity and sensation seeking. Results indicated that riskiness on the BART decreased as reward/loss magnitude increased. Further, this decrease was most prominent in those low in Impulsivity/Sensation Seeking, whereas those high in Impulsivity/Sensation Seeking were largely insensitive to variation in reward/loss magnitude. Findings are discussed in terms of sensitivity to reward and loss, and how these processes can be studied further using the BART including extensions to cognitive modeling and the measurement of neurobehavioral functioning.

Delta9-tetrahydrocannabivarin as a marker for the ingestion of marijuana versus Marinol: results of a clinical study.

Delta9-tetrahydrocannabinol (THC), the main psychologically active ingredient of the cannabis plant (marijuana), has been prepared synthetically and used as the bulk active ingredient of Marinol, which was approved by the FDA for the control of nausea and vomiting in cancer patients receiving chemotherapy and as an appetite stimulant for AIDS patients. Because the natural and the synthetic THC are identical in all respects, it is impossible to determine the source of the urinary metabolite of THC, 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), in a urine specimen provided in a drug-testing program. Over the last few years there has been a need to determine whether a marijuana positive drug test is the result of the ingestion of marijuana (or a related product) or whether it results from the sole use of Marinol. We have previously proposed the use of delta9-tetrahydrocannabivarin (THCV, the C3 homologue of THC) as a marker for the ingestion of marijuana (or a related product) because THCV is a natural component of most cannabis products along with THC and does not exist in Marinol. We have also reported that THCV is metabolized by human hepatocytes to 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid (THCV-COOH); therefore, the presence of the latter in a urine specimen would indicate that the donor must have used marijuana or a related product (with or without Marinol). In this study, we provide clinical data showing that THCV-COOH is detected in urine specimens collected from human subjects only after the ingestion of marijuana and not after the ingestion of Marinol (whether the latter is ingested orally or by smoking). Four subjects (male and female) participated in the study in a three-session, within-subject, crossover design. The sessions were conducted at one-week intervals. Each subject received, in separate sessions and in randomized order, an oral dose of Marinol (15 mg), a smoked dose of THC (16.88 mg) in a placebo marijuana cigarette, or a smoked dose of marijuana (2.11% THC and 0.12% THCV). Urine samples were collected and vital signs were monitored every 2 h for a 6-h period following drug administration. Subjects were then transported home, were given sample collection containers and logbooks, and were instructed to record at home the volume and time of every urine collection for 24 h, and once a day for the remainder of a week (6 days). Subjects were also instructed to freeze the urine samples until the next session. All urine samples were analyzed by GC-MS for THC-COOH and THCV-COOH using solid-phase extraction and derivatization procedure on RapidTrace and TBDMS as the derivative. The method had a limit of detection of 1.0 ng/mL and 1.0 ng/mL for THCV-COOH and THC-COOH, respectively.

Reinforcing and subjective effects of diazepam in nondrug-abusing volunteers.

Preference for diazepam was assessed in 18 light and 12 moderate social drinkers using a cumulative dosing procedure. The 7-session procedure consisted of: 1) four sampling sessions, during which participants ingested color-coded capsules containing either diazepam (five 4-mg capsules administered at 30-min intervals; total dose 20 mg) or placebo, and 2) three choice sessions, during which they could ingest up to 7 capsules of their preferred color of capsule, each separated by 30 min. Subjective (mood) and behavioral (performance) measures were obtained throughout the 4-hour sessions. The light social drinkers chose diazepam over placebo on 66% of the choice sessions, and ingested a mean dose per session of about 16 mg. The moderate drinkers chose diazepam on 100% of the choice sessions, and ingested an average dose of 25 mg per session. Diazepam produced sedation in both groups, but in the moderate drinkers it also increased measures of subjective effects suggestive of "euphoria." The results indicate that diazepam can serve as a positive reinforcer under laboratory conditions in nondrug-abusing individuals who are moderate users of alcohol and other drugs. Greater reinforcing efficacy may be indicative of higher risk of abuse. The results illustrate the usefulness of the cumulative dosing procedure to measure both drug preference and dose preference.

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.

Risks and benefits of long-term benzodiazepine use.

Despite a sharp decline in the prescription of benzodiazepines during the past decade, reservations about their use have continued to escalate. This article presents converging data from three diverse sources: national survey data from consumers, laboratory data on the drug preferences of normal subjects, and a controlled clinical study of long-term diazepam treatment and withdrawal. These data suggest that (1) the risks of overuse, dependence, and addiction with benzodiazepines are low in relation to the massive exposure in our society; (2) benzodiazepine addiction can occur when doses within the clinical range are taken regularly over about 6 months; (3) many patients continue to derive benefit from long-term treatment with benzodiazepines; and (4) attitudes strongly against the use of these drugs may be depriving many anxious patients of appropriate treatment.

Behavioral and pharmacological treatment of cigarette smoking: end of treatment comparisons.

Success in a stop-smoking treatment program was compared in patients who received behavioral treatment alone (BT) or behavioral treatment plus Nicorette gum (NT). The proportion of nonsmokers at the end of the 10-week program was higher with the groups receiving BT (82%) than in those receiving NT (50%). While the groups differed in their initial tolerance levels and number of previous quit attempts, the data suggest that the addition of Nicorette gum did not confer a substantial advantage over BT alone.

Neuroleptic-induced "anhedonia" in rats: pimozide blocks reward quality of food.

The dopamine receptor blocker pimozide attenuated lever-pressing and running for food reward in hungry rats. In each case the characteristic behavior of pimozide-treated rats was the same as that of undrugged rats when reward was simply withheld. Drug-induced performance difficulties were ruled out by the presence of periods of normal responding in drug-treated animals. Pimozide appears to selectively blunt the rewarding impact of food and other hedonic stimuli.

Both positive reinforcement and conditioned aversion from amphetamine and from apomorphine in rats.

Rats learned to press a lever for intravenous injections of amphetamine or apomorphine. They also learned to avoid the taste of saccharin which was associated with experimenter-administered amphetamine or with self-administered apomorphine. Thus these, and presumably other, self-administered drugs serve as compound pharmacological stimuli, having both positively reinforcing and aversive properties.