Thomas H. Kelly

The effects of repeated amphetamine exposure on multiple measures of human behavior.

Two groups of three healthy adult male volunteers (n = 6) participated in 15-day residential studies. Each study day was divided into a private work period (1000 to 1630), during which subjects had access to four work tasks, and a social period (1700 to 2330), during which subjects had access to a number of recreational activities available under social or private conditions. Occasionally during the study, access to high-probability activities was made contingent upon participating in low-probability activities. Tobacco cigarettes and food were available throughout each day (0900 to 2330). Each subject received active and placebo d-amphetamine doses (0 or 10 mg/70 kg) twice daily during two, three-consecutive-day intervals. Active and placebo dose intervals were presented in an alternating fashion, with order of exposure counterbalanced between groups. Amphetamine consistently decreased food intake, improved accuracy of performance on some work tasks, and increased verbal interaction and cigarette smoking. No tolerance to these effects was observed. Increases in VAS ratings of dose potency and liking, as well as stimulated and anxious, and decreases in sedated were observed during initial amphetamine exposure, but tolerance to these effects developed rapidly. The simultaneous measurement of multiple dimensions of human behavior establishes a profile of amphetamines effects which is useful for comparison with the behavioral profiles of other drugs, such as marijuana.

Effects of acute administration of diazepam and d-amphetamine on aggressive and escape responding of normal male subjects

Normal males participated in sessions providing two operant response options and were administered either diazepam (study I and II) ord-amphetamine (study II). The acute effects of diazepam on human aggressive responding, which ostensibly subtracted points from another person, were determined in study I. Study II was conducted to determine the extent to which social context and response consequence influenced diazepam (study I) andd-amphetamine (previous research) effects on aggressive responding. In study II, the other response option was escape responding which protected the subjects counter from point losses. Aggressive and escape responding were engendered by subtracting points from the subjects counter, and maintained by initiation of intervals free of point loss. Point subtractions were attributed to the other person (study I) or to a machine (study II). Responding to accumulate points exchangeable for money was available in both studies. Acute diazepam administration decreased aggressive responding in most subjects (study I), slightly increased escape responding (study II), and decreased responding to accumulate points. In study II,d-amphetamine increased both escape responding and responding to accumulate points. The effects ofd-amphetamine and diazepam were altered by the instructed source of point loss.

Effect of Meal Macronutrient and Energy Content on Human Performance

The effects of planned meals, varying in carbohydrate (CHO), fat and caloric content, on psychomotor performance by male subjects with unrestricted access to commercially-available foods was investigated in two residential studies. In the first study, two groups of three subjects (n = 6) completed psychomotor tasks before and after consuming a lunch consisting of 431 or 844 kcal, with caloric differences produced through covert changes in either fat or CHO content. The effects of each of four lunch conditions (low-fat, high-fat, low-CHO, high-CHO) were determined for three consecutive days. In the second study, two groups of three subjects (n = 6) received breakfast, lunch and an afternoon snack and completed psychomotor tasks after breakfast and lunch. Cumulative caloric content of the three eating occasions was approximately 700, 1200 or 1700 kcal (low, medium or high), again with differences resulting from covert changes primarily in either fat or CHO content. The effects of each of six food conditions were determined for two consecutive days. While changes in some aspects of performance were altered after meals, the effects were not related to the CHO, fat or caloric content of the meal. When subjects have unrestricted access to commercially-available foods, neither calories nor the relative fat or CHO content of normal meals influence human psychomotor task performance.

Are choice and self-administration of marijuana related to delta 9-THC content?

The effects of delta 9-tetrahydrocannabinol (THC) content on choice marijuana, number of marijuana cigarettes smoked, and ratings of marijuanas effects were examined in 6 adult male marijuana smokers during a residential study consisting of four 3-day blocks of 2 sample days and 1 choice day. Days were divided into 6.5-hr work and social-access periods, beginning at 1000 and 1700. On sample days, marijuana cigarettes containing different THC concentrations (0.0% vs. 3.5% and 2.0% vs. 3.5% THC) were smoked at least once during each period. On choice days, independent choices between previously sampled marijuana cigarettes were made during each period. A maximum of 8 cigarettes could be smoked per day, and drug ratings were obtained after each period. Only choice behavior was sensitive to changes in THC content, whereas only the number of smoked marijuana cigarettes was related to context (i.e., work and social-access period).

Multidimensional behavioral effects of marijuana

1. Five groups of three healthy adult male volunteers (n = 15), all reporting occasional, controlled marijuana use, gave written consent and participated in residential studies lasting 6 to 15 days. 2. Subjects smoked marijuana cigarettes (0, 1.3, 2.3 or 2.7% THC, w/w) at 0945, 1330, 1700 and 2030 every day, and each subject received both active and placebo marijuana cigarettes in 2-5 consecutive day phases, with placebo and active doses presented in an alternating fashion. 3. In comparison with placebo, active marijuana produced a variety of effects on measures of human behavior, including increases in food consumption and errors on psychomotor tasks, decreases in bouts of tobacco-cigarette smoking and verbal interactions and no changes in rates of task performance, time spent under social conditions or social cooperation. 4. Dimensions of human behavior were differentially sensitive to the effects of smoked marijuana. 5. The simultaneous measurement of multiple dimensions of human behavior is a useful procedure for determining dose potency following marijuana administration.

The effects of d-amphetamine on food intake of humans living in a residential laboratory.

Two groups, each consisting of three normal weight, male research volunteers, lived continuously in a residential laboratory for 15 days. All contact with the experimenters was through a networked computer system and subjects behaviors, including food intake, were continuously recorded. During the first part of the day, subjects remained in their private rooms doing work activities. During the remainder of the day, they had the option to socialize with each other. A wide variety of food items were continuously available. Subjects controlled their own patterns of food intake, and could consume any item, or number of items, at any time during the day. Beverages containing d-amphetamine (10 mg per 70 kg) or placebo were consumed daily at 0930 and 1630 hrs. Amphetamine significantly reduced total daily caloric intake to about 70% of placebo levels. The reduction in intake was a consequence of a decrease in number of eating occasions per day; no changes in mean intake per occasion were observed. Amphetamine produced similar decreases in the daily number of snack and meal items, and in protein, fat, and carbohydrate intake. These results demonstrate that amphetamine has significant effects on human food intake, and the study of human feeding behavior under similar naturalistic conditions should provide important information about the behavioral actions of drugs affecting food intake.

Behavioral Response to Diazepam in a Residential Laboratory

Two groups of three healthy adult male volunteers without histories of sedative or other drug abuse participated in 15-day residential studies. Each day consisted of a private work period (10 AM to 4:30 PM), during which subjects participated in traditional laboratory performance tasks, and a social period (5 to 11:30 PM), during which subjects had access to recreational activities available under social or private conditions. Tobacco cigarettes and food were available throughout each day (9 AM to 12 PM). Diazepam (5 or 10 mg/70 kg) or placebo was administered orally twice daily in alternating three-consecutive-day intervals. Dosing order varied between groups. Diazepam had no effect on the total amount of time subjects spent in social conditions; however, the low dose increased verbal interaction, while the high dose decreased verbal interaction. Both doses disrupted performance on a second-order repeated-acquisition task but produced no effects on the other performance measures. Five of six subjects increased caloric intake following at least one dose, with the largest increases observed in subjects with the lowest baseline intake. Increases in subject reports of dose Potency and Sedated were also observed following the high dose. Diazepam doses routinely used in clinical settings influenced a variety of behaviors that are observed in the natural ecology, but not performance on accepted laboratory tasks.

Effects of nicotine gum and tobacco smoking on human avoidance responding

Three male smokers were exposed to a free-operant avoidance schedule in which a lever press postponed a point subtraction on a counter for twenty seconds. Subtractions were scheduled to occur every 5 seconds in the absence of lever presses. Prior to each experimental session the subject was administered varying amounts of nicotine via either chewing nicotine gum or smoking low or high nicotine yield cigarettes. Smoking cigarettes resulted in increased avoidance responding relative to baseline nonsmoking rates. Chewing nicotine gum did not produce changes in avoidance responding, however, nicotine blood levels produced by chewing nicotine gum were similar to levels produced by smoking cigarettes. The differential responding determined by route of nicotine administration is discussed and the implications for use of nicotine gum as an adjunct for smoking cessation is addressed.

The influence of social context and absence of Marijuana effects on human cooperative behavior

Five groups of three healthy adult males (n = 15) participated in experiments designed to investigate the effects of social and behavioral context on human cooperative behavior and to determine whether marijuana effects on cooperative behavior were influenced by these factors. Using a time-based contingency, participation on lower probability activities during 3-, 4-, or 6.5-hr sessions was maintained by points that were exchanged for time to engage in higher probability activities. High- and low-probability activities were maintained by paying subjects different amounts of money for working on tasks. Sessions were conducted in socially isolated rooms, and each subject chose whether points earned while engaged in lower probability activities would be equally distributed to all subjects (cooperation) or kept by each subject individually (noncooperation). Subjects could monitor each others’ choices by observing illuminated panels in their rooms. The number of points available for choosing the noncooperative option was manipulated across sessions. In addition, social interaction between subjects varied across studies. Cooperative and noncooperative choice patterns were similar across sessions for all three subjects in each study, as were total session earnings. Under conditions in which subjects could not interact, or could interact only minimally, choices for cooperative and noncooperative point-earning options were directly related to the number of points associated with the options. However, when subjects were allowed 6.5 hr of social interaction per day, between successive sessions, only the cooperative option was chosen, regardless of point conditions. Marijuana altered activity performance, but had no effect on choice patterns, or on session earnings, under any condition.