Roland R. Griffiths

Caffeinated energy drinks--a growing problem.

Since the introduction of Red Bull in Austria in 1987 and in the United States in 1997, the energy drink market has grown exponentially. Hundreds of different brands are now marketed, with caffeine content ranging from a modest 50 mg to an alarming 505 mg per can or bottle. Regulation of energy drinks, including content labeling and health warnings differs across countries, with some of the most lax regulatory requirements in the U.S. The absence of regulatory oversight has resulted in aggressive marketing of energy drinks, targeted primarily toward young males, for psychoactive, performance-enhancing and stimulant drug effects. There are increasing reports of caffeine intoxication from energy drinks, and it seems likely that problems with caffeine dependence and withdrawal will also increase. In children and adolescents who are not habitual caffeine users, vulnerability to caffeine intoxication may be markedly increased due to an absence of pharmacological tolerance. Genetic factors may also contribute to an individuals vulnerability to caffeine-related disorders including caffeine intoxication, dependence, and withdrawal. The combined use of caffeine and alcohol is increasing sharply, and studies suggest that such combined use may increase the rate of alcohol-related injury. Several studies suggest that energy drinks may serve as a gateway to other forms of drug dependence. Regulatory implications concerning labeling and advertising, and the clinical implications for children and adolescents are discussed.

Withdrawal syndrome after the double-blind cessation of caffeine consumption

BACKGROUND People who stop consuming caffeine may have symptoms, but the incidence and severity of caffeine withdrawal are not known. This study was performed to determine the effects in the general population of ending ones dietary intake of caffeine. METHODS We studied 62 normal adults whose intake of caffeine was low to moderate (mean amount, 235 mg--the equivalent of 2.5 cups of coffee--per day). They completed questionnaires about symptoms and tests of their mood and performance when consuming their normal diets (base-line period) and at the end of each of two two-day periods during which they consumed caffeine-free diets and under double-blind conditions received capsules containing placebo (placebo period) or caffeine (caffeine period) in amounts equal to their daily caffeine consumption. RESULTS More subjects had abnormally high Beck Depression Inventory scores (11 percent), high scores on the trait scale of the State-Trait Anxiety Inventory (8 percent), low vigor scores (11 percent) and high fatigue scores (8 percent) on the Profile of Mood States, and moderate or severe headache (52 percent) during the placebo period than during either the base-line period (2, 0, 0, 0, and 2 percent, respectively; P less than 0.05) or the caffeine period (3, 2, 2, 0, and 6 percent; P less than 0.05). More subjects reported unauthorized use of medications during the placebo period (13 percent) than during the caffeine period (2 percent, P = 0.017). Performance of a tapping task was slower during the placebo period than during the base-line and caffeine periods (P less than 0.01). CONCLUSIONS Persons who consume low or moderate amounts of caffeine may have a withdrawal syndrome after their daily consumption of caffeine ceases.

An automated version of the digit symbol substitution test (DSST)

An automated version of the Digit Symbol Substitution Test is described that employs a relatively inexpensive, commercially available microcomputer to present and score the task. Advantages of the automated DSST include: (1) objective scoring of both speed and accuracy of test performance, (2) printed copies of test scores, (3) convenient administration under standardized test conditions, and (4) the capacity for repeated assessment of an individual’s performance over time. Task performance data for individual subjects following doses of pentobarbital are presented; these data illustrate both the stability of task performance under constant conditions and the within-subjects sensitivity of task performance to experimental manipulations.

Caffeine physical dependence: a review of human and laboratory animal studies

Although caffeine is the most widely used behaviorally active drug in the world, caffeine physical dependence has been poorly characterized in laboratory animals and only moderately well characterized in humans. In humans, a review of 37 clinical reports and experimental studies dating back to 1833 shows that headache and fatigue are the most frequent withdrawal symptoms, with a wide variety of other signs and symptoms occurring at lower frequency (e.g. anxiety, impaired psychomotor performance, nausea/vomiting and craving). When caffeine withdrawal occurs, severity can vary from mild to extreme (i.e. incapacitating). The withdrawal syndrome has an onset at 12–24 h, peak at 20–48 h, and duration of about 1 week. The pharmacological specificity of caffeine withdrawal has been established. The proportion of heavy caffeine users who will experience withdrawal symptoms has been estimated from experimental studies to range from 25% to 100%. Withdrawal symptoms have been documented after relatively short-term exposure to high doses of caffeine (i.e. 6–15 days of ≥600 mg/day). Although animal and human studies suggest that physical dependence may potentiate the reinforcing effects of caffeine, human studies also demonstrate that a history of substantial caffeine intake is not a necessary condition for caffeine to function as a reinforcer. The similarities and differences between caffeine and classic drugs of abuse are discussed.

Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness

A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event. Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality – Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change.

Benzodiazepine self-administration in humans and laboratory animals – implications for problems of long-term use and abuse

Abstract Drug reinforcement may represent the primary behavioral-pharmacological mechanism underlying two types of problematic use of benzodiazepines – recreational abuse by polydrug abusers and inappropriate chronic use by patients. High dose polydrug abuse for the purpose of getting high is readily recognized as a significant social problem. Inappropriate chronic benzodiazepine use is more subtle but relatively common: for anxiolytics, 36% of past-year users (3% of the adult population in the US) report using these drugs for 4 consecutive months or longer. The risks of such long-term use are much better documented than the benefits. This paper provides a current review of various problems that have been identified with the long-term use and the recreational abuse of benzodiazepines, including memory impairment, risk of accidents, falls and hip fractures in the elderly, a withdrawal syndrome, brain damage, overuse in the elderly, overuse by chronic pain patients, overuse by alcoholics and recreational abuse among alcoholics and polydrug abusers. A comprehensive review of the literature on benzodiazepine reinforcing effects in humans and laboratory animals is also provided. Drug self-administration studies in humans and laboratory animals provide models of both types of problematic benzodiazepine use. Recreational abuse of benzodiazepines has been modeled in human research with polydrug abusers and in laboratory animal studies, which show that the reinforcing effect of benzodiazepines is intermediate relative to other sedative compounds and is increased in subjects with histories of previous sedative drug self-administration. The problem of inappropriate long-term use of benzodiazepines by people without histories of drug abuse has been partially modeled in human studies showing that benzodiazepines function as reinforcers in subjects with anxiety, insomnia, and histories of moderate alcohol consumption, and in preclinical studies showing stable, low-rate benzodiazepine self-injection with concurrent physical dependence under conditions of continuous availability. Both human and animal research suggests that the drug history and current behavioral context may be important in the establishment of benzodiazepines as reinforcers. Limited human and animal research provides little support for the common belief that physical dependence enhances benzodiazepine reinforcement.

Effects of mecamylamine on human cigarette smoking and subjective ratings

Multiple measures of cigarette smoking, subjective effect and physiological effect were collected during 90-min test sessions in normal volunteers. Before sessions subjects received oral doses of mecamylamine (2.5, 5.0, 10, 20 mg) or placebo. Each dose and placebo was given three times in a randomized block sequence. Mecamylamine increased several measures of cigarette smoking, including number of cigarettes, number of puffs per cigarette, and expired air carbon monoxide level. Mecamylamine also produced modest, dose-related decreases in standing blood pressure and increases in standing heart rate. The subjective effects produced by mecamylamine were not characteristic of those of psychoactive drugs. Mecamylamine appears to have increased cigarette smoking by decreasing the effective dose level of nicotine available from cigarette smoking.

Progressive-ratio performance maintained by drug infusions: comparison of cocaine, diethylpropion, chlorphentermine, and fenfluramine.

Cocaine, diethylpropion, chlorphentermine, and fenfluramine were compared on a drug-maintained progressive-ratio procedure in baboons. Intravenous infusions of drug were contingent on completion of a fixed-ratio response requirement (fixed number of lever-press responses) with a 3-h time-out period following each infusion. Prior to testing each dose of drug, stable self-infusion performance was first established with 0.4 mg/kg cocaine when the fixed-ratio requirement was 160. Subsequently, a test dose of drug was substituted for the standard dose of cocaine. If the dose of drug maintained a criterion level of self-infusion performance (six or more infusions per day for 2 days), the ratio requirement was systematically increased every day until the ‘breaking point’ at which the self-infusion performance fell below a criterion level (one or zero infusionsper day). Fenfluramine did not maintain criterion self-infusion performance at any dose tested (0.02–5.0 mg/kg). The dose ranges of the other drugs that maintained maximum breaking points were 1.0–5.6 mg/kg for chlorphentermine, 1.0–3.0 mg/kg for diethylpropion, and 0.1–0.4 mg/kg for cocaine. Within-animal comparison of the maximum breaking points indicated that cocaine maintained the highest breaking points, followed in order by diethylpropion, chlorphentermine, and fenfluramine. The rank ordering of these drugs with the breaking point measure corresponds well with both the results of other animal experiments on measurement of reinforcing efficacy of these drugs and with the clinical information about the human subjective effects and abuse of these drugs.

Increased alcohol consumption, nonmedical prescription drug use, and illicit drug use are associated with energy drink consumption among college students

Objectives:This longitudinal study examined the prevalence and correlates of energy drink use among college students, and investigated its possible prospective associations with subsequent drug use, including nonmedical prescription drug use. Methods:Participants were 1060 undergraduates from a large, public university who completed 3 annual interviews, beginning in their first year of college. Use of energy drinks, other caffeinated products, tobacco, alcohol, and other illicit and prescription drugs were assessed, as well as demographic and personality characteristics. Results:Annual weighted prevalence of energy drink use was 22.6%wt and 36.5%wt in the second and third year of college, respectively. Compared with energy drink nonusers, energy drink users had heavier alcohol consumption patterns, and were more likely to have used other drugs, both concurrently and in the preceding assessment. Regression analyses revealed that Year 2 energy drink use was significantly associated with Year 3 nonmedical use of prescription stimulants and prescription analgesics, but not with other Year 3 drug use, holding constant demographics, prior drug use, and other factors. Conclusions:A substantial and rapidly growing proportion of college students use energy drinks. Energy drink users tend to have greater involvement in alcohol and other drug use and higher levels of sensation seeking, relative to nonusers of energy drinks. Prospectively, energy drink use has a unique relationship with nonmedical use of prescription stimulants and analgesics. More research is needed regarding the health risks associated with energy drink use in young adults, including their possible role in the development of substance use problems.

Multiple-choice procedure: an efficient approach for investigating drug reinforcement in humans.

Two experiments demonstrated the efficiency of assessing drug reinforcement in humans by using a novel multiple-choice procedure. The distinguishing characteristic of the procedure is that it arranges intermittent reinforcement for choices between pairs of potential reinforcers. The procedure has three key operations: (1) a subject is exposed to the potential reinforcers; (2) a subject then makes two or more choices on a questionnaire; for each choice, the subject is required to choose one of two potential reinforcers (e.g. drug vs. drug choices and/or drug vs. money choices); and (3) subsequently only one of the choices, randomly selected, is reinforced. In the present experiments, two variations of the multiple-choice procedure were evaluated in twelve male drug abusers. Both experiments assessed the reinforcing effects of three drug conditions (200 and 400 mg/70 kg pentobarbital and placebo) which were presented no more often than every other day. The experiments demonstrated dose-related choice of pentobarbital over money as well as choice of a higher dose of pentobarbital over a lower dose or placebo. Orderly data were generated with a single-session exposure to each drug condition. Multiple-choice procedures should have applicability, not only to the investigation of drug reinforcement, but also to the study of non-drug reinforcement in humans.