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S J Heishman

Publications and source records attributed to S J Heishman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Laboratory validation study of drug evaluation and classification program: ethanol, cocaine, and marijuana.

The Drug Evaluation and Classification (DEC) program is used by police agencies to determine if individuals are behaviorally impaired because of drug use, and, if impaired, to determine the class of drug(s) causing the impairment. Although widely used, the validity of the DEC evaluation has not been rigorously tested. The primary goal of this study was to determine the validity of the variables of the DEC evaluation in predicting whether research volunteers had been administered ethanol, cocaine, or marijuana; a secondary goal was to determine the accuracy of trained police officers (Drug Recognition Examiner, DRE) in detecting whether subjects had been dosed with ethanol, cocaine, or marijuana. Community volunteers (n = 18) with histories of drug use received ethanol (0, 0.28, 0.52 g/kg), cocaine (4, 48, 96 mg/70 kg), and marijuana (0, 1.75, 3.55% THC) in a double-blind, randomized, within-subjects design. A single drug dose or placebo was administered during each of nine experimental sessions, and blood samples were obtained before and periodically after dosing. With the exception of marijuana, plasma drug concentration was at or near the observed maximum during the DEC evaluation. The ability of the DEC evaluation to predict the intake of ethanol, cocaine, or marijuana was optimal when using 17-28 variables from the evaluation. When DREs concluded impairment was due to drugs other than ethanol, their opinions were consistent with toxicology in 44% of cases. These findings suggest that the DEC evaluation can be used to predict accurately acute administration of ethanol, cocaine, or marijuana, and that predictions of drug use may be improved if DREs focused on a subset of variables.

Adult↗
PubMed1993

Performance, subjective, and physiological effects of nicotine in non-smokers.

Sixteen human volunteers with little or no experience using tobacco participated in one 4.5-h experimental session in which they were administered three doses of nicotine polacrilex gum (0, 2 and 4 mg) in ascending order at 90-min intervals. Physiological, subjective, and cognitive performance measures were assessed before and after each dose. Nicotine produced dose-related increases in heart rate and blood pressure and decreases in skin temperature. Nicotine also increased subjective ratings of dose strength and negative effects and decreased ratings of desire to repeat the same dose. There were dose-related trends toward decreased accuracy and increased response time on 3 of the 4 cognitive tests. These data do not support the hypothesis that nicotine enhances cognitive functioning in non-smokers.

Adult↗
PubMed1992

Stimulus functions of caffeine in humans: relation to dependence potential.

The interoceptive stimulus functions common to drugs of dependence include positive subjective effects, discriminative functions, and reinforcing functions. Data from studies measuring these stimulus functions constitute the objective assessment of a drug's dependence potential. This paper reviews the subjective effects, discriminative stimulus, and reinforcing stimulus functions of caffeine in humans to assess the dependence potential of caffeine. The stimulus effects of caffeine are compared with those of d-amphetamine, a prototypic CNS stimulant that has been studied under similar conditions, to evaluate the relative dependence potential of caffeine. Finally, caffeine's effects are evaluated in terms of generally accepted criteria for defining drug dependence. It is concluded that caffeine partially meets the primary criteria of drug dependence: 1) the majority of caffeine use is highly controlled, but not compulsive; 2) caffeine is psychoactive; and 3) caffeine functions as a reinforcer under certain conditions in humans, but not in animals. Caffeine thus has limited dependence potential. Additionally, although caffeine shares stimulus functions with d-amphetamine, it does so under limited conditions and should be considered to have a relatively lower dependence potential.

Caffeine↗
PubMed1992

Marijuana smoking: effect of varying delta 9-tetrahydrocannabinol content and number of puffs.

The purpose of this study was to determine marijuana dose-effects on subjective and performance measures over a wider dosage range than previously reported using technology which allowed for specification of both the volume and delta 9-tetrahydrocannabinol (THC) content of smoke delivered, and to relate these effects to plasma THC levels. Seven male community volunteers, who were moderate users of marijuana, smoked 4, 10 or 25 puffs from cigarettes containing either 1.75 or 3.55% THC on 6 separate days. Postsmoking plasma THC levels were systematically related to both number of puffs and cigarette THC content. Maximal THC levels occurred immediately after smoking and ranged from 57 to 268 ng/ml. These plasma levels provided a measure of systemic delivery when a known volume and THC content of marijuana smoke was inhaled. Orderly dose-related increases were also observed for heart rate, expired air carbon monoxide and subjective report of drug effects. The 25-puff, 3.55%-THC condition produced greater plasma THC levels than previously reported and reliably impaired performance on a battery of psychomotor and cognitive tasks with substantial individual differences noted in the degree of performance impairment. Puff number/THC content combinations producing comparable plasma THC levels resulted in similar subjective effects and performance impairment. This study provided a comprehensive assessment of the pharmacological effects of smoked marijuana over a wider and more precisely controlled dosage range than has been accomplished previously.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Discriminative stimulus effects of d-amphetamine, methylphenidate, and diazepam in humans.

Eight male community volunteers, who reported current psychomotor stimulant use, were trained to discriminate between the presence and absence of orally administered d-amphetamine 30 mg. During daily experimental sessions, in which a single drug dose or placebo was tested, physiological and subjective measures were assessed and subjects indicated their discrimination by responding on an operant color-tracking procedure. During four test of acquisition sessions, discriminative responding indicated that all subjects learned the discrimination, and d-amphetamine produced physiological and subjective effects typical of psychomotor stimulants. Generalization testing then followed in which dose-response curves were determined for the following drugs: d-amphetamine (3.75, 7.5, 15 and 30 mg), diazepam (5, 10, 20 and 40 mg), and methylphenidate (7.5, 15, 30 and 60 mg). d-Amphetamine and methylphenidate produced dose-related increases in d-amphetamine-appropriate responding, whereas no dose of diazepam substituted for d-amphetamine in any subject. d-Amphetamine and methylphenidate produced a similar pattern of subjective changes, including increased ratings of euphoria and drug liking and decreased sedation. In contrast, diazepam increased subjective scales of sedation and dysphoria. These results are consistent with similar studies testing animals and humans and demonstrate the utility of human drug discrimination research as an integral component of drug abuse liability testing.

Adolescent↗
PubMed1991

Human pharmacology and abuse potential of nalmefene.

Nalmefene hydrochloride was administered to six male volunteers with histories of opiate abuse using a double-blind, randomized, Latin square design to determine if it produced typical morphine-like effects. A comparison of physiologic and subject- and observer-reported effects was made between morphine, 15 and 30 mg given intramuscularly; nalmefene, 25, 50, and 100 mg given orally; and placebo. Drowsiness or sleepiness was the most common drug effect reported after the administration of each treatment. Only morphine produced miosis and increased subject-reported euphoria and "drug liking." Neither drug increased Addiction Research Inventory subscale scores measuring dysphoria or sedation or produced changes on the Profile of Mood States questionnaire. Adverse effects reported only after the administration of nalmefene included agitation/irritability and muscle tension; these did not appear to be dose related. The data indicated that nalmefene did not produce typical morphine-like effects and has no apparent abuse potential.

Adult↗
PubMed1991

Drug self-administration methods in abuse liability evaluation.

The human drug self-administration paradigm is an extension of the animal model developed in the 1960s. The paradigm can be used to investigate the determinants and correlates of drug-seeking and drug-taking behavior and has proven useful in the development of medications for treating drug dependence. This paper describes the basic components of the human self-administration model and discusses studies that illustrate some of its applications, including assessment of the reinforcing effects of drugs, analysis of behavioral and pharmacological mechanisms of drug self-administration and measurement of the abuse liability, behavioral toxicity, and aversive effects of drugs. Some of the strengths and limitations of using the paradigm with human research subjects are also presented. It is concluded that the drug self-administration model should not replace other measures of abuse liability testing in humans, but should be incorporated into comprehensive programs of drug abuse assessment wherever possible.

Drug Evaluation↗
PubMed1990

Acute and residual effects of marijuana: profiles of plasma THC levels, physiological, subjective, and performance measures.

Three experienced marijuana smokers participated in four 2-day experimental sessions in which they smoked either 0, 1, or 2 marijuana cigarettes containing 2.57% delta 9-tetrahydrocannabinol (THC) at two different times on the first day. A battery of physiological, subjective, and performance measures was repeated throughout day 1 to assess acute effects and on day 2 to measure any residual effects of marijuana. Blood samples were also repeatedly collected to examine the relationship between plasma levels and pharmacological effects of THC. Acutely, marijuana increased heart rate and subjective ratings of drug effects and slightly impaired performance on a circular lights task in all subjects. Performance was also impaired (decreased accuracy and increased response time) on serial addition/subtraction and digit recall tasks on day 1 in two subjects. On day 2, tachycardia and subjective effects of marijuana were not observed. Performance remained impaired on the arithmetic and recall tasks on day 2, although the decrements were not as large as those observed on day 1. In general, plasma THC levels covaried with the other measures. These preliminary results suggest that marijuana can adversely affect complex human performance up to 24 hours after smoking.

Adult↗
PubMed1990

Acute opioid physical dependence in humans: effect of naloxone at 6 and 24 hours postmorphine.

Previous studies in our laboratory have documented the occurrence of naloxone-precipitated opioid abstinence from 45 minutes to 6 hours after acute morphine administration in humans. This study extended the morphine-naloxone interval to 24 hours and examined the effect of repeated naloxone challenges on withdrawal responses. Six male nondependent opiate users participated in eight experimental sessions in which they received single IM injections of morphine (18 mg/70 kg) followed 6 and 24 hours later by challenge sessions with IM placebo or naloxone (10 mg/70 kg). Naloxone challenge at 6 hours postmorphine reversed morphine-induced miosis and subjective reports of opiate symptoms, drug high, good drug effects, and drug liking. At 24 hours postmorphine, naloxone had no effect on these measures, which had returned to premorphine levels. However, at 6 and 24 hours postmorphine, naloxone precipitated subjective symptoms and observer-rated signs of opioid abstinence. When naloxone challenge at 24 hours was preceded by naloxone at 6 hours postmorphine, the magnitude of abstinence symptoms and signs was attenuated. These data suggest that morphine-induced adaptational changes underlying the development of physical dependence persist beyond other measureable agonist effects, and that these changes are disrupted or reversed by repeated antagonist administration.

Double-Blind Method↗
PubMed1990

Acute opioid physical dependence in humans: effect of varying the morphine-naloxone interval II.

Previous studies have demonstrated antagonist-precipitated withdrawal from 45 min to 24 hr after acute opioid administration in nondependent human subjects. The purpose of this study was to examine longer postagonist intervals and to determine the maximum interval between agonist administration and antagonist challenge at which precipitated withdrawal can be observed. During this study 6 nondependent male volunteers who reported using opiates an average of 4 times per week received naloxone challenges (10 mg/70 kg i.m.) at 6, 12, 24, 36, 48, 60, or 72 hr after single i.m. injections of morphine (18 mg/70 kg or 30 mg/70 kg). Each interval was tested independently in random order. Naloxone reliably precipitated withdrawal signs and symptoms at 6 and 12 hr postmorphine. Withdrawal symptoms were greatly diminished in intensity at 24-hr postmorphine and were not elicited at postmorphine intervals longer than 24 hr. Withdrawal precipitation persisted somewhat longer than pupillary constriction because pupils had returned to predrug diameters by 24 hr postmorphine but, generally, there appeared to be correspondence between offset of agonist effects and dissipation of precipitated withdrawal. This study extends observations about the time course of acute physical dependence effects which begin within minutes after acute morphine exposure, dissipate within 36 hr, are associated with the onset and offset of agonist effects and do not require chronic opioid administration.

Adult↗
PubMed1990

Low-dose caffeine physical dependence in humans.

This study investigated the effects of terminating low dose levels of caffeine (100 mg/day) in 7 normal humans. Substitution of placebo capsules for caffeine capsules occurred under double-blind conditions while subjects rated various dimensions of their mood and behavior. In the first phase of the study, substitution of placebo for 12 consecutive days resulted in an orderly withdrawal syndrome in 4 subjects which peaked on days 1 or 2 and progressively decreased toward prewithdrawal levels over about 1 week. Data from the remaining three subjects provided no evidence of withdrawal. In the second phase of the study, the generality of the withdrawal effect was examined by repeatedly substituting placebo for 100 mg/day of caffeine for 1-day periods separated by an average of 9 days. Despite differences within and across subjects with respect to the presence, nature and magnitude of symptoms, each of the seven subjects demonstrated a statistically significant withdrawal effect. Although the phenomenon of caffeine withdrawal has been described previously, the present report documents that the incidence of caffeine withdrawal is higher (100% of subjects), the daily dose level at which withdrawal occurs is lower (roughly equivalent to the amount of caffeine in a single cup of strong brewed coffee or 3 cans of caffeinated soft drink) and the range of symptoms experienced is broader (including headache, fatigue and other dysphoric mood changes, muscle pain/stiffness, flu-like feelings, nausea/vomiting and craving for caffeine) than heretofore recognized.

Adult↗
PubMed1990

Low-dose caffeine discrimination in humans.

A novel drug discrimination procedure was used to study the discriminability and subjective effects of caffeine in seven human volunteers who abstained from dietary sources of caffeine. Daily sessions involved p.o. ingestion of two capsules sequentially, one of which contained caffeine and the other placebo, under double-blind conditions. Each day subjects attempted to identify and were later informed which capsule contained caffeine and which contained placebo. All subjects acquired rapidly the initial discrimination (100 or 178 mg vs. placebo). Examination of progressively lower caffeine doses showed that accuracy and ratings of confidence in accuracy were increasing functions of dose. There were individual differences in the lowest discriminable dose: three subjects discriminated 56 mg, three discriminated 18 mg and one discriminated 10 mg. Discrimination accuracy was usually higher after the second capsule than after the first capsule. All subjects indicated that they believed that they made the discrimination predominantly on the basis of central effects of caffeine vs. placebo, such as changes in mood and socializing. Compared to placebo, 100 mg of caffeine increased ratings of alertness, well-being, social disposition, motivation for work, concentration, energy and self-confidence and decreased ratings of headache and sleepiness. This dose of caffeine also produced a large increase in a measure of "euphoria." The present study documents biological activity of caffeine at lower doses than heretofore recognized. The general approach to investigating the effects of low drug doses may have broad application in human psychopharmacology research for characterizing other subtle psychotropic effects.

Adult↗
PubMed1989

Effect of d-amphetamine, secobarbital, and marijuana on choice behavior: social versus nonsocial options.

The effects of oral d-amphetamine and secobarbital and smoked marijuana on human social conversation and preference for socializing were studied in three separate experiments. During experimental sessions, active drug or placebo was administered using an acute or divided dosing procedure. Subjects who received drug then engaged in a discrete-trial choice procedure in which they made a series of mutually exclusive choices between a social (talking with their nondrugged partner) and nonsocial (sitting quietly alone) option. Lapel microphones and voice operated relays measured seconds of speech. Subjects engaged in greater amounts of conversation and chose the social option more frequently following acute dosing of d-amphetamine and secobarbital compared with placebo. Acute administration of marijuana did not significantly affect social speech or choice behavior, producing slight decreases in both measures. Acute dosing of all drugs significantly increased subjective drug effect or drug high; however, only secobarbital affected the circular lights task, producing significant performance decrements. The shifts in preference toward the social option observed with d-amphetamine and secobarbital suggest that these drugs increased the reinforcing effects of socializing relative to sitting alone. This may be one mechanism by which psychoactive drugs facilitate social conversation.

Adult↗
PubMed1989

Effects of tetrahydrocannabinol content on marijuana smoking behavior, subjective reports, and performance.

This study investigated the smoking topography of marijuana and its effect on heart rate, subjective reports, and cognitive/psychomotor task performance. Male subjects (N = 12) with histories of moderate marijuana use smoked ad lib one cigarette containing 0, 1.3, or 2.7% delta 9-THC on separate days. Smoking topography measures revealed smaller puff and inhalation volumes and shorter puff duration for the high marijuana dose compared to the low dose. No other smoking behavior differed between the active doses. Heart rate was increased dose dependently over placebo levels. Active marijuana also increased subjective reports of drug effect over placebo, but not dose dependently. Significant memory impairment was observed on a forward and reverse digit span task, and performance was impaired on the digit symbol substitution task by the high, but not low, dose of marijuana. Performance on a divided attention task was not affected by marijuana. Thus, although subjects adjusted their smoking of cigarettes varying in THC content, dose-related effects of marijuana were obtained on several measures. The observed differences and individual variation in smoking topography measures suggest that precise control of smoking behavior would improve the accuracy of marijuana dose delivery.

Adult↗