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Biomedical subjects

A H Oliveto

Publications and source records attributed to A H Oliveto.

At least 19 recordsLinked to original sources

Is dependence on one drug associated with dependence on other drugs? The cases of alcohol, caffeine and nicotine.

Several studies have correlated the use of one drug with that of another drug; however, whether dependence on one drug is associated with dependence on another drug, independent of any use/use association, is unclear. We asked 196 randomly-selected subjects the DSM-IV criteria for dependence as applied to alcohol, caffeine, and nicotine. Among ever users, the severity of alcohol vs nicotine dependence and alcohol vs caffeine dependence was related, but this relationship was weak (r = .22 & .31). Nicotine and caffeine dependence were not correlated. These results fail to confirm theories of commonality that hypothesize dependence on one drug predisposes to dependence on another drug.

Adult↗

Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone.

BACKGROUND: Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence. METHODS: This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10. RESULTS: In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence. CONCLUSIONS: Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.

Adult↗

Endorsement of DSM-IV dependence criteria among caffeine users.

The purpose of this article is to determine whether some caffeine users endorse clinical indicators of dependence and abuse. We asked 162 randomly-selected caffeine users generic DSM-IV criteria for dependence, abuse, intoxication and withdrawal pertaining to their caffeine use in the last year via a structured telephone interview. The prevalence of endorsement of dependence items was 56% for strong desire or unsuccessful attempt to stop use, 50% for spending a great deal of time with the drug, 28% for using more than intended, 18% for withdrawal, 14% for using despite knowledge of harm, 8% for tolerance and 1% for foregoing activities to use. Seven percent of users met DSM-IV criteria for caffeine intoxication and, among those who had tried to stop caffeine permanently, 24% met DSM-IV research criteria for caffeine withdrawal. Test-retest interviews for dependency agreed in 29/30 cases (97%). Eight expert substance abuse clinicians agreed with self-endorsed caffeine dependence 91% of the time. Our results replicate earlier work and suggest that a substantial proportion of caffeine users exhibit dependence-like behaviors. Further studies are needed to determine whether such users exhibit a clinically significant syndrome of drug dependence.

Adult↗

A randomized trial of buprenorphine maintenance for heroin dependence in a primary care clinic for substance users versus a methadone clinic.

PURPOSE: Buprenorphine is an alternative to methadone for the maintenance treatment of heroine dependence and may be effective on a thrice weekly basis. Our objective was to evaluate the effect of thrice weekly buprenorphine maintenance for the treatment of heroin dependence in a primary care clinic on retention in treatment and illicit opioid use. SUBJECTS AND METHODS: Opioid-dependent patients were randomly assigned to receive thrice weekly buprenorphine maintenance in a primary care clinic that was affiliated with a drug treatment program (n = 23) or in a traditional drug treatment program (n = 23) in a 12-week clinical trial. Primary outcomes were retention in treatment and urine toxicology for opioids; secondary outcomes were opioid withdrawal symptoms and toxicology for cocaine. RESULTS: Retention during the 12-week study was higher in the primary care setting (78%, 18 of 23) than in the drug treatment setting (52%, 12 of 23; P = 0.06). Patients admitted to primary care had lower rates of opioid use based on overall urine toxicology (63% versus 85%, P < 0.01) and were more likely to achieve 3 or more consecutive weeks of abstinence (43% versus 13%, P = 0.02). Cocaine use was similar in both settings. CONCLUSIONS: Buprenorphine maintenance is an effective treatment for heroin dependence in a primary care setting.

Adult↗

Hydromorphone-naloxone combinations in opioid-dependent humans under a naloxone novel-response discrimination procedure.

Naloxone-hydromorphone combinations were tested in participants trained to discriminate naloxone from placebo under a novel-response drug discrimination procedure while maintained on methadone. Naloxone alone produced dose-related increases in naloxone-appropriate responding, little or no "novel"-appropriate responding, and increases in opioid antagonist adjective ratings (n = 5). Hydromorphone alone produced dose-related increases in novel-appropriate responding, little or no naloxone-appropriate responding, and increases in opioid agonist adjective ratings (n = 6). When combined with naloxone, hydromorphone produced dose-related decreases in naloxone-appropriate responding and antagonist adjective ratings (n = 6). These findings are consistent with nonhuman data and suggest that this procedure may be useful as a human laboratory model of opioid withdrawal.

Adult↗

Effect of LAAM dose on opiate use in opioid-dependent patients. A pilot study.

The authors conducted a 16-week study with nine opioid-dependent individuals (six male; four white/two African American/three Hispanic; age 36.8 +/- 2.2 years). Participants were assigned to either a low-dose (165 mg/week; n = 5) or high-dose (330 mg/week; n = 4) Levo-alpha-acetylmethadol (LAAM) condition according to a randomized, double-blind, within-subjects crossover design, such that they were inducted onto one maintenance dose for 4 weeks and then were crossed over to receive the converse for 4 weeks. Subsequently, individuals underwent detoxification from LAAM. Eight of nine participants completed the study protocol. The proportion of urine samples positive for opiates was 0.22 +/- 0.08 and 0.53 +/- 0.12, under the high- and low-dose conditions, respectively (F = 11.8; P = 0.01). These results show that LAAM dose regimen affects the degree of abstinence from opioids.

Adult↗

Effects of d-amphetamine and caffeine in humans under a cocaine discrimination procedure.

This study examined further the pharmacological specificity of an oral cocaine discriminative stimulus in humans. Five male cocaine-abusing volunteers (two African-American/three Caucasian) were trained to discriminate between a low dose of cocaine hydrochloride (80 mg/70 kg, p.o.) and placebo. Once the criterion for discrimination was met (i.e. > or = 80% correct responding for four consecutive sessions), dose-effect curves were determined for the dopamine reuptake inhibitor cocaine (20, 40, 80, 120 mg/70 kg, p.o.), the indirect dopamine agonist d-amphetamine (5, 10, 20 mg/70 kg, p.o.) and the adenosine antagonist caffeine (150, 300, 600 mg/70 kg, p.o.). Cocaine, d-amphetamine and caffeine each produced dose-related increases in cocaine-appropriate responding. Each compound produced at least a trend towards increases in a few stimulant-like self-reports and vital signs. When the relationship between cocaine-appropriate responding and self-reports were examined, cocaine and d-amphetamine, but not caffeine, had a similar profile of significant associations between discriminative performance and stimulant-like self-reports. These results suggest that, although the cocaine discriminative stimulus (80 mg/70 kg) is not specific only to stimulants with primarily dopaminergic actions, its pharmacological specificity may be more clearly defined when the relationship between discrimination and self-reports is examined.

Adult↗

Caffeine self-administration in humans: 1. Efficacy of cola vehicle.

Eight exclusive cola drinkers in Experiment 1 (mean caffeine intake = 157 +/- 74 mg/day) and 16 drinkers of both cola and coffee in Experiment 2 (mean caffeine intake = 579 +/- 201 mg/day) underwent 6 independent, double-blind weekly trials. Each trial began with a randomized cross-over sampling period of 1 day of access to noncaffeinated cola and 1 day of access to caffeinated (33 mg/8 oz) cola. During the subsequent 1- or 2-day test period, participants had unlimited concurrent access to the 2 colas. Reliable caffeine self-administration occurred in 2 of 8 participants in Experiment 1 and in 4 of 16 participants in Experiment 2. Self-reported drowsiness, fatigue, and headache were higher when participants received only placebo colas in Experiment 2, but not Experiment 1. Caffeine self-administration via cola occurs both among people whose primary source of caffeine is cola and among those whose primary source of caffeine is coffee.

Adult↗

A systematic survey of caffeine intake in Vermont.

Detailed data were collected on lifetime caffeine intake from 202 Vermont residents using a random-digit dial telephone survey. The sample appeared representative and test-retest reliability of caffeine intake was high (r = .95). Almost all participants (96%) had ever used and most (83%) presently used one or more caffeinated beverages weekly. The average caffeine intake was 186 mg/day. Many caffeine users (61%) used caffeinated beverages other than coffee. Current caffeine intake was a poor measure of lifetime intake. For example, among ever-users of caffeine, 41% had stopped at least 1 type of caffeinated beverage and 14% had stopped caffeine altogether. Cessation was mostly due to health concerns and unpleasant side effects. It was concluded that simply asking about "usual" coffee use is a poor and biased estimate of lifetime caffeine use. Thus, prior findings that caffeine is not associated with medical or behavioral disorders may represent false-negative results.

Adolescent↗

Functional antagonism of the caffeine-discriminative stimulus by triazolam in humans.

Six healthy male volunteers (aged 21-31 yr) were trained to discriminate between the methylxanthine caffeine (320 mg/70 kg, p.o.; e.g. drug A) and placebo (drug B). Then dose-effect curves were determined for triazolam (0.1-0.56 mg/70 kg), alone and in combination with the caffeine training dose (n = 6), buspirone (1.0-32.0 mg/70 kg), alone and in combination with the caffeine training dose (n = 4), and caffeine (56-560 mg/70 kg), alone and in combination with a selected dose of triazolam (n = 5). Triazolam blocked the discriminative effects of the caffeine training dose in a dose-related manner in five out of six subjects; whereas buspirone did so in only one out of four subjects. Different doses of caffeine alone generally produced dose-related increases in caffeine-appropriate responding; when administered concomitantly with triazolam, the caffeine dose-effect curve shifted significantly to the right. Triazolam and caffeine, but not buspirone and caffeine, generally produced significant interactions on several self-report and psychomotor performance measures. These results indicate that, at the doses tested, the caffeine discriminative stimulus can be blocked, at least partly by triazolam, but not by buspirone, which is consistent with the pharmacological actions of these compounds.

Adult↗

A pilot study of primary-care-based buprenorphine maintenance for heroin dependence.

The treatment of heroin dependence with opioid maintenance has traditionally employed methadone and more recently buprenorphine administered in traditional drug treatment settings. In this pilot study we evaluated buprenorphine maintenance for the treatment of heroin dependence in a program administered by primary-care providers in a primary-care setting. Seven patients were admitted to this nonblinded open-label pilot study and were offered 6 months of primary-care-based buprenorphine maintenance. Buprenorphine was administered in doses of 16 mg on Monday and Wednesday and 32 mg on Friday. Patients were seen weekly by primary-care providers and attended self-help meetings. Of the seven patients admitted to the study, five (71%) completed the 6-month pilot study and two (29%) were removed from the study. Urine toxicology data showed that the majority of urines tested were clear of opioids in four out of five patients who remained in treatment. These results suggest that primary-care-based opioid maintenance using buprenorphine shows promise as a new approach to the treatment of heroin dependence.

Adult↗

Discriminative stimulus, self-reported and cardiovascular effects of orally administered cocaine in humans.

This study evaluated whether an oral dose of cocaine can serve as a discriminative stimulus in humans. Four male and one female cocaine-abusing volunteers (ages 26-41 years) were trained to discriminate between cocaine HCl (80 mg/70 kg p.o.) and placebo. Once the criterion for discrimination was met (i.e., > or = 80% correct responding for four consecutive sessions), dose-effect curves were determined for orally administered cocaine (20, 40, 80 and 120 mg/70 kg), intranasally administered cocaine (20, 40, 80 and 120 mg/70 kg) and the benzodiazepine triazolam (0.25 and 0.50 mg/70 kg p.o.). All five subjects met the criterion for the cocaine-placebo discrimination within four to seven sessions. Novel cocaine doses by either the oral or intranasal route of administration generally produced dose-related increases in cocaine-appropriate responding, whereas triazolam produced predominantly placebo-appropriate responding. Cocaine by both routes produced qualitatively similar increases in stimulant-like self-reports, blood pressure and heart rate, whereas triazolam produced increases in sedative-like ratings and no changes in cardiovascular measures. Throughout dose-effect curve determinations, the training dose of cocaine and placebo continued to be identified correctly in four of five subjects (range, 75-100% correct responding). These results suggest that orally administered cocaine (80 mg/70 kg) is discriminable from placebo, has behavioral effects that are qualitatively similar to intranasal cocaine and does not show cross-generalization to a pharmacologically dissimilar compound.

Administration, Intranasal↗

Effects of diazepam and hydromorphone in triazolam-trained humans under a novel-response drug discrimination procedure.

Seven healthy normal male and female volunteers (21-31 years) were trained to discriminate between the benzodiazepine triazolam (0.32 mg/70 kg, PO; e.g., drug A) and placebo (e.g., drug B) under a three-choice, instructed novel response drug discrimination procedure. Once the criterion for discrimination was met (i.e., > 85% correct responding on four consecutive sessions), dose-effect curves were determined for triazolam (0.1-0.56 mg/70 kg), the benzodiazepine diazepam (10-32 mg/70 kg) and the opioid agonist hydromorphone (1-6 mg/70 kg). Subjects met the criterion for discrimination within four to six sessions. Triazolam and diazepam produced dose-related increases in triazolam-appropriate responding and no novel-appropriate responding at any dose tested. In contrast, hydromorphone generally increased novel-appropriate responding in a dose-related manner with placebo-appropriate responding and some triazolam-appropriate responding at intermediate doses occurring also. Triazolam and diazepam produced qualitatively similar increases on several measures of sedative drug effects; hydromorphone increased ratings of "like novel" and sedative-like effects in subjects who discriminated hydromorphone as novel relative to those who did not. These results indicate that the novel response drug discrimination procedure enhances the specificity of the triazolam-placebo discrimination.

Adult↗

Caffeine self-administration and withdrawal: incidence, individual differences and interrelationships.

In four prior studies, caffeine (100 mg) self-administration was assessed by greater self-administration of caffeinated coffee than decaffeinated coffee and caffeine withdrawal was assessed by placebo substitution using six double-blind tests in each subject. This paper collates data across these studies to examine the incidence and predictors of the occurrence of caffeine self-administration and withdrawal. Caffeine self-administration occurred in 31% of subjects when a consistency criterion was used (n = 41) and 27% when a statistical criterion was used. Caffeine withdrawal occurred in 35% and 49% of subjects with each criteria (n = 37). Subjects who had withdrawal headaches and drowsiness were 2.3-2.6 times more likely to self-administer the caffeinated coffee. Several variables (e.g., average caffeine intake) did not predict caffeine self-administration or withdrawal.

Adult↗

Coffee and alcohol intake as predictors of smoking cessation and tobacco withdrawal.

In one study of 105 smokers who received physician advice plus placebo gum and in another study of 630 self-quitters, neither the presence or absence, nor amount of precessation alcohol, nor coffee intake, nor changes in alcohol or coffee intake postcessation, predicted relapse or most withdrawal symptoms. The one possible exception was that heavy caffeine and alcohol users reported a greater increase in hunger and craving postcessation; however, these effects were not consistent across measures, follow-ups, and studies. Our results are inconsistent with theories that caffeine intoxication from increased caffeine blood levels postsmoking cessation worsen tobacco withdrawal or that alcohol or caffeine use during initial abstinence from smoking increases relapse to smoking.

Adult↗

A novel-response procedure enhances the selectivity and sensitivity of a triazolam discrimination in humans.

Placebo-appropriate responding in drug discrimination can be difficult to interpret because such responding can indicate either the absence of any drug effect or the absence of a specific drug effect. This study addressed the overinclusiveness of placebo-appropriate responding by providing a response alternative for novel-drug effects (i.e., effects unlike the training stimuli). This "novel-response procedure" used instructions that indicated that only responses on a novel-appropriate manipulandum would be reinforced in the presence of novel drug effects. Four healthy male volunteers (ages 19-32) were trained to discriminate 0.32 mg/70 kg of triazolam from placebo. Then, dose-effect curves were determined for triazolam (0.1-0.32 mg/70 kg) and d-amphetamine (5 and 20 mg/70 kg) with a standard two-response procedure (drug vs. placebo) and the novel-response procedure. Triazolam produced dose-related increases in triazolam-appropriate responding with both procedures. d-Amphetamine produced predominantly placebo-appropriate responding with the two-response procedure and predominantly novel-appropriate responding with the novel-response procedure. Unexpectedly, the triazolam dose-effect curve obtained with the novel-response procedure was shifted to the left relative to the two-response procedure for discrimination measures. A similar effect was evident for both the triazolam and d-amphetamine dose-effect curves for some self-report measures. Because of the increased selectivity of placebo-appropriate responding and the increased potency of the drug stimulus, the novel-response procedure may represent a methodological advance for drug discrimination research.

Adolescent↗

Forced-choice versus free-choice procedures: caffeine self-administration in humans.

Methodological comparisons of procedures for drug self-administration are rare. In studies examining the reinforcing effect of caffeine in humans, caffeine self-administration usually has been inferred from performance under forced-choice procedures. In the present experiment, caffeine self-administration via coffee was compared under forced-choice and free-choice conditions; i.e., when subjects were and were not required to use a minimum number of coffees. Ten moderate coffee drinkers (2-7 cups/day) were assigned to forced- and free-choice conditions using a randomized cross-over design. Under each choice condition, subjects completed six independent, double-blind trials, consisting of a 2-day exposure period followed by a 2-day test period. During exposure, subjects consumed either decaffeinated or caffeinated (100 mg/serving) coffee on day 1 and the other coffee on day 2. During the test period, subjects had concurrent access to the same decaffeinated and caffeinated coffees. Under the forced-choice condition, subjects were required to drink at least four cups of coffee per day during the test period. Under the free-choice condition, subjects did not have a minimum-cup requirement. In general, the relative rate at which subjects self-administered caffeinated versus decaffeinated coffee was similar across choice conditions, even though subjects self-administered significantly fewer cups of both coffee types under the free-choice than the forced-choice condition. These results suggest that, at least for caffeine, forced-choice and free-choice procedures produce comparable results. Whether this finding generalizes to a context in which caffeine or another drug is more robustly self-administered, remains to be determined.

Adult↗