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Biomedical subjects

Robert O Pihl

Publications and source records attributed to Robert O Pihl.

At least 19 recordsLinked to original sources
PubMed2006

The dopamine D4 receptor gene and moderation of the association between externalizing behavior and IQ.

BACKGROUND: Dopaminergic neurotransmission is implicated in externalizing behavior problems, such as aggression and hyperactivity. Externalizing behavior is known to be negatively associated with cognitive ability. Activation of dopamine D4 receptors appears to inhibit the functioning of the prefrontal cortex, a brain region implicated in cognitive ability. The 7-repeat allele of the dopamine D4 receptor gene produces less efficient receptors, relative to other alleles, and this may alter the effects of dopamine on cognitive function. OBJECTIVE: To examine the influence of a polymorphism in the third exon of the dopamine D4 receptor gene on the association between externalizing behavior and IQ. DESIGN: In 1 community sample and 2 clinical samples, the presence or absence of the 7-repeat allele was examined as a moderator of the association between externalizing behavior and IQ; the strength of this effect across samples was estimated meta-analytically. PATIENTS: Eighty-seven boys from a longitudinal community study, 48 boys referred clinically for aggression, and 42 adult males diagnosed with attention-deficit/hyperactivity disorder. MAIN OUTCOME MEASURES: IQ scores and observer ratings of externalizing behavior were taken from existing data sets. RESULTS: Among individuals lacking the 7-repeat allele, externalizing behavior was negatively correlated with IQ (mean r = -0.43; P<.001). Among individuals having at least 1 copy of the 7-repeat allele, externalizing behavior and IQ were uncorrelated (mean r = 0.02; P = .45). The difference between these correlations was significant (z = -2.99; P<.01). CONCLUSIONS: Allelic variation of the dopamine D4 receptor gene appears to be a genetic factor moderating the association between externalizing behavior and cognitive ability. This finding may help to elucidate the adaptive value of the 7-repeat allele.

Adolescent↗
PubMed2006

Patterns of simultaneous polysubstance use in drug using university students.

Simultaneous polysubstance use (SPU) is a common phenomenon, yet little is known about how various substances are used with one another. In the present study 149 drug-using university students completed structured interviews about their use of various substances. For each substance ever used, participants provided details about the type, order and amount of all substances co-administered during its most recent administration. Alcohol, tobacco and cannabis were frequently co-administered with each other and with all other substances. Chi-squared tests revealed that when alcohol was used in combination with any of cannabis, psilocybin, MDMA, cocaine, amphetamine, methylphenidate (ps < 0.01) or LSD (p < 0.05) its initial use preceded the administration of the other substance. Paired samples t-tests revealed that when alcohol was used with cocaine (p < 0.01) or methylphenidate (p < 0.05) it was ingested in greater quantities than when used in their absence. Patterns of cannabis use were not systematically related to other substances administered. Finally, using one-sample t-tests, tobacco use was demonstrated to be increased relative to 'sober' smoking rates when used with alcohol, cannabis, psilocybin, MDMA, cocaine, amphetamine (ps < 0.001), LSD (p < 0.01) or methylphenidate (p < 0.05). Results suggest that many substances are routinely used in a SPU context and that the pattern in which a substance is used may be related to other substances co-administered.

Adolescent↗
PubMed2006

Psychostimulant users are sensitive to the stimulant properties of alcohol as indexed by alcohol-induced cardiac reactivity.

One indicator of increased sensitivity to alcohol-induced reward is a heightened heart rate (HR) increase following alcohol intoxication, a characteristic associated with increased alcohol-induced dopamine (DA) release. The goal of this study was to determine whether users of drugs known to induce DA release have higher HR increases after alcohol intoxication than never users have. Sixty-four men with known drug-use histories participated in an alcohol challenge in which HR was measured. Stimulant users had significantly higher ethanol-induced HR increases than never users had, although use of marijuana or hallucinogens was not associated with this marker. Stimulant users obtained superior Sensitivity to Reward scores (R. Torrubia, C. Avila, J. Moltó, & X. Caseras, 2001) compared with never users. Stimulant drug users may be more sensitive to the stimulating properties of alcohol, and this appears to be mediated by superior activity in the Behavioral Approach System (J. A. Gray, 1991).

Adolescent↗
PubMed2006

Intoxicated behavioral disinhibition and the heart rate response to alcohol.

This study examined the association between the heart rate (HR) response to alcohol intoxication, which is thought to reflect sensitivity to alcohol-induced reward and alcohol-induced behavioral disinhibition. High- and low-HR responders to alcohol participated in a go/no-go task, under sober and intoxicated conditions. Errors of commission on this task have previously been related to behavioral disinhibition. High-HR responders made more intoxicated commission errors as compared with low-HR responders. High-HR responders also reported increased alcohol consumption, and controlling for the latter did not alter the significant association between high-HR responders and increased intoxicated errors of commission. These results are consistent with previous findings of an increased risk for addictive and disinhibited behavioral propensities in individuals with a high-HR response to alcohol intoxication.

Alcoholic Intoxication↗
PubMed2006

Heart rate response to alcohol and intoxicated aggressive behavior.

BACKGROUND: This study examined the elevated heart rate (HR) response to alcohol intoxication, thought to reflect an increased sensitivity to alcohol-induced reward, as a potential factor in the increased likelihood of alcohol-induced aggression. METHODS: Three groups, intoxicated high (n=37) and low (n=37) HR responders and sober controls (n=73), participated in a laboratory measure of physical aggression, the Taylor Aggression Paradigm. RESULTS: Results revealed that intoxicated high HR responders were more aggressive than the intoxicated low HR responders and sober controls. CONCLUSIONS: These findings are interpreted within a hypothetical model relating increased alcohol-induced aggression to a dysregulation in the motivational system responding to rewards.

Adult↗
PubMed2006

Differential effects of naltrexone on cardiac, subjective and behavioural reactions to acute ethanol intoxication.

OBJECTIVE: Alcohol may have psychomotor stimulant properties during the rising limb of the blood alcohol curve at commonly self-administered doses. Increased heart rate (HR) immediately after alcohol consumption may serve as an indicator or marker of such properties, which appear to be potentially opiate-mediated and dopamine-dependent. Naltrexone, an opiate antagonist, has been used successfully in the treatment of alcoholism and may produce its therapeutic effects through its effects on alcohol metabolism or by blocking alcohol's rewarding effects. We hypothesized that, if naltrexone blocks the psychomotor stimulant properties of ethanol, then it would decrease or eliminate the HR increase associated with acute alcohol intoxication and that this would be independent of any effect on alcohol metabolism. METHODS: Twenty male subjects were administered placebo and alcohol (1.0 mL 95% USP ethanol/kg body weight) in a laboratory setting on one day and naltrexone (50 mg) and alcohol on another (counterbalanced). We assessed all subjects for a change in HR and for a subjective and behavioural response from 35 to 170 minutes after drug or alcohol administration. RESULTS: The placebo and alcohol mix produced a significant mean HR increase from baseline (F(1,95) = 46.01, p < 0.0001, Cohen's d = 0.62), while naltrexone and alcohol did not (nonsignificant). The significant effects of naltrexone on blood alcohol level did not account for the effect of naltrexone on alcohol-induced HR change but did account for alterations in subjective and behavioural response to alcohol. CONCLUSIONS: Naltrexone appears to substantially reduce the HR increase that is characteristic of alcohol intoxication. This finding appears to lend moderate support to the notions that, first, naltrexone has differential effects on alcohol reactions and, second, that it specifically blocks the acute psychomotor stimulant properties of alcohol.

Adult↗
PubMed2005

Nicotine increases alcohol self-administration in non-dependent male smokers.

BACKGROUND: Alcohol and tobacco are commonly co-administered, yet little is known about the effects of acute nicotine administration on alcohol consumption in humans. This study sought to determine how nicotine delivered by tobacco smoke influences alcohol intake in humans using a double-blind placebo controlled repeated measures design. METHODS: During two randomized 120 min sessions 15 male occasional smokers smoked four nicotine-containing or four de-nicotinized cigarettes at 30 min intervals. Throughout the session, subjects could earn units of their preferred alcoholic beverage and glasses of water using a progressive-ratio (PR) task. RESULTS: Wilcoxon signed-rank tests indicated that nicotine increased alcohol self-administration in a significant proportion of participants (P or=0.16). A two-way ANOVA supported this observation further, and, compared to de-nicotinized cigarettes, the nicotine-containing cigarettes increased PR breakpoints for alcohol but not water, as reflected by a Cigarettex Beverage interaction (P<or=0.055). CONCLUSIONS: The present data suggest that acute nicotine administration increases alcohol consumption in at least a subset of smokers.

Adolescent↗
PubMed2005

Patterns of simultaneous polysubstance use in Canadian rave attendees.

The aim of this study was to examine rave-related polydrug drug use and to determine if patterns of substance use were associated with previous rave attendance. One hundred and eighty-six rave attendees (50% female) representing a wide range of ages (16 to 47 years; mean=23.5, sd=5.15) and levels of rave attendance experience (1 to 400 events) completed structured interviews in Montreal, Canada between November 2002 and September 2003 about their rave attendance patterns and their use of various licit and illicit substances at the most recently attended event. On average, participants reported using 2.5 different psychoactive substances (excluding tobacco) at the most recent event attended. Cannabis, alcohol, MDMA (ecstasy), amphetamine, cocaine, ketamine, and GHB were the most frequently reported substances, and details about their orders of administration, dosages, and patterns of co-administration are presented and discussed. The total lifetime number of raves attended by participants varied considerably (mean=48.6; sd=69.7; median=25), and there was a positive correlation between the number events attended and number of substances used at the most recent event attended (p<0.001). Analyses revealed that individuals reporting the use of ketamine, GHB, and/or cocaine at the most recent event had attended significantly more events than nonusers even when controlling for various demographic variables. A subset of respondents (n=27) completed a second interview to determine the reliability of their responses. Results indicated that respondents could reliably recall details about which drugs were used, the total doses administered, as well as order of drug administration.

Adolescent↗
PubMed2005

Characteristics of methylphenidate misuse in a university student sample.

OBJECTIVE: Methylphenidate (MPH) is a prescription stimulant drug with known abuse potential; however, little is known about its patterns of misuse or the characteristics of its abusers. METHODS: A sample of 50 university students reporting MPH misuse and 50 control subjects matched for age, sex, and ethnicity completed structured face-to-face interviews about their MPH and other drug use. For each substance ever used, they provided information regarding routes of administration and other substances ever coadministered, as well as details about the most recent administration. MPH users provided additional information about their reasons for use and, in 36 cases, about how they obtained the drug. RESULTS: Relative to control subjects, those who misused MPH were more likely to have used various other prescription and nonprescription stimulant drugs over their lifetime, and most MPH users reported mixing the drug with other psychoactive substances. Of the MPH sample, 70% reported recreational use of the drug, while 30% reported that MPH was used exclusively for study purposes. Relative to those using it exclusively for study, recreational users were more likely to report using MPH intranasally, as well as coadministering MPH with other substances. Most of those who reported their source of MPH obtained it from an acquaintance with a prescription. CONCLUSIONS: Those who misuse MPH are more likely than their peers to misuse various other substances, and MPH misuse frequently occurs in the context of simultaneous polydrug use. Because the primary supply of inappropriately used MPH appears to be prescribed users, efforts should be directed toward preventing its diversion.

Adolescent↗
PubMed2004

The hedonic response to cigarette smoking is proportional to dopamine release in the human striatum as measured by positron emission tomography and [11C]raclopride.

Positron emission tomography and [11C]raclopride were used to assess the dopaminergic response to cigarette smoking in ten smokers. Nicotine-deprived smokers were scanned twice on separate days. In one condition, participants smoked their usual brand of cigarettes while in the scanner and in the other condition they remained nicotine abstinent. On each day, subjects monitored the hedonic properties of their experience as well as their levels of craving. Initial analyses revealed no significant differences between the conditions in [11C]raclopride binding potential (BP) in the caudate, putamen, or ventral striatum. Because previous research suggested that drug-induced dopamine transmission is related to levels of craving and/or hedonic drug effects, the relationship between these variables and [11C]raclopride BP was examined. Craving levels were reduced by smoking but were not systematically related to BP change. However, the hedonic response to smoking was correlated with BP reduction in the caudate (P < 0.001) and posterior putamen (P < 0.05) but not in the ventral striatum. Post hoc analyses revealed that only five of the ten smokers reported mood-elevating effects in response to the smoking procedure. In these subjects, smoking was associated with decreased [11C]raclopride BP in the caudate. On the other hand, among subjects that reported a diminished mood response to smoking there was an increase in BP in the caudate and putamen. These results suggest that pleasurable drug experiences are associated with increased dopamine transmission in the dorsal striatum while unpleasant experiences may be related to decreased dopamine release in this region.

Adult↗
PubMed2004

Heightened heart rate response to alcohol intoxication is associated with a reward-seeking personality profile.

BACKGROUND: The psychomotor stimulant theory of addiction posits that sensitivity to the positively rewarding properties of alcohol puts certain individuals at higher risk for alcohol abuse. A valid and reliable index of overactivation in the reward system has been a heightened baseline heart rate (HR) increase on the ascending limb of the blood alcohol curve. The main goal of this study was to investigate the relationship between this HR response and a questionnaire measuring sensitivity to reward and sensitivity to punishment. Additional goals included looking at (1). the association between a high HR response and various personality traits (hopelessness/introversion, anxiety sensitivity, impulsivity, and sensation-seeking) and (2). the relationship between these personality traits and stimulant use. METHODS: A total of 18 low- and 19 high-HR responders completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the Substance Use Risk Profile Scale (SURPS), and a modified version of the Addiction Severity Index. RESULTS: High-HR responders obtained significantly higher scores than low-HR responders on the sensitivity to reward scale of the SPSRQ, as well as increased sensation-seeking scores on the SURPS. High-HR responders were not at significantly higher risk of having used stimulants, but stimulant use was associated with higher impulsivity scores on the SURPS. CONCLUSIONS: Novelty/sensation-seeking is among the personality traits that have been linked to heavy alcohol use. This study suggests that reward sensitivity might mediate the relationship between this personality profile and drinking behavior.

Adolescent↗
PubMed2003

Alcohol promotes dopamine release in the human nucleus accumbens.

Microdialysis experiments in rodents indicate that ethanol promotes dopamine release predominantly in the nucleus accumbens, a phenomenon that is implicated in the reinforcing effects of drugs of abuse. The aim of the present study was to test the hypothesis in humans that an oral dose of ethanol would lead to dopamine release in the ventral striatum, including the nucleus accumbens. Six healthy subjects underwent two [(11)C]raclopride PET scans following either alcohol (1 ml/kg) in orange juice or orange juice alone. Subjective mood changes, heart rate, and blood-alcohol levels were monitored throughout the procedure. Personality traits were evaluated using the tridimensional personality questionnaire. PET images were co-registered with MRI and transformed into stereotaxic space. Statistical parametric maps of [(11)C]raclopride binding potential change were generated. There was a significant reduction in [(11)C]raclopride binding potential bilaterally in the ventral striatum/nucleus accumbens in the alcohol condition compared to the orange juice condition, indicative of increased extracellular dopamine. Moreover, the magnitude of the change in [(11)C]raclopride binding correlated with the alcohol-induced increase in heart rate, which is thought to be a marker of the psychostimulant effects of the drug, and with the personality dimension of impulsiveness. The present study is the first report that, in humans, alcohol promotes dopamine release in the brain, with a preferential effect in the ventral striatum. These findings support the hypothesis that mesolimbic dopamine activation is a common property of abused substances, possibly mediating their reinforcing effects.

Adult↗
PubMed2003

Exaggerated ethanol-induced cardiac reactivity as an indicator of increased risk for gambling.

Pathological gambling and alcohol dependence show a high rate of co-occurrence. Some individuals at risk for alcohol dependence display an exaggerated heart rate (HR) increase following alcohol consumption, a characteristic suggesting sensitivity to reward. This study examined whether exaggerated ethanol-induced cardiac reactivity was associated with increased gambling behaviors. One hundred five young men (M = 20.13 years, SD = 1.07) consumed 1 ml of ethanol (95% volume) per kilogram of body weight. HR was measured and participants completed the South Oaks Gambling Screen (SOGS; H. R. Lesieur & S. B. Blume, 1987). Those with higher intoxicated HRs reported significantly greater scores on the SOGS (p = .02). This suggests that ethanol-induced HR increase is a possible marker for addictive disorders.

Adult↗
PubMed2003

Aggressiveness, family history of alcoholism, and the heart rate response to alcohol intoxication.

Some sons of male alcoholics (SOMAs) are characterized by an increased heart rate (HR) response to alcohol intoxication, which is thought to reflect increased sensitivity to alcohol-induced reward. Such a response has also been related to increased physical aggression. However, the confounding effect of aggression in SOMAs may be obscuring the interpretation of these findings. The HR response to alcohol was therefore assessed in 4 groups: high/low aggressive SOMAs and high/low aggressive non-SOMAs. Results indicate that aggressive SOMAs had the highest intoxicated HR response and that they reported the most alcohol consumption. This suggests that in some cases the high comorbidity between alcohol misuse and aggression is related to an increased sensitivity to alcohol-induced reward.

Adolescent↗
PubMed2003

Alcohol affects executive cognitive functioning differentially on the ascending versus descending limb of the blood alcohol concentration curve.

BACKGROUND: Executive cognitive functioning (ECF), a construct that includes cognitive abilities such as planning, abstract reasoning, and the capacity to govern self-directed behavior, has been recently researched as an antecedent to many forms of psychopathology and has been implicated in alcohol-related aggression. This study was designed to examine whether differential ECF impairments can be noted on the ascending versus the descending limbs of the blood alcohol concentration curve. METHODS: Forty-one male university students participated in this study. Twenty-one subjects were given 1.32 ml of 95% alcohol per kilogram of body weight, mixed with orange juice, and the remaining 20 were given a placebo. Participants were randomly assigned to either an ascending or descending blood alcohol group and were tested on six tests of ECF on their assigned limb. Subjective mood data were also collected. RESULTS: Intoxicated participants on both limbs demonstrated ECF impairment; the descending-limb group showed greater impairment than their ascending-limb counterparts. Intoxicated subjects were significantly more anxious at baseline than placebo subjects. The introduction of this covariate nullified any significant differences in subjective mood found on either limb of the blood alcohol concentration curve, but ECF impairments remained robust. CONCLUSIONS: Our results support the conclusion that alcohol negatively affects cognitive performance and has a differential effect on the descending versus the ascending limb of the blood alcohol concentration curve. The latter finding may have important ramifications relating to the detrimental consequences of alcohol intoxication.

Adult↗
PubMed2003

Familiality of heart rate and cardiac-related autonomic activity in five-month-old twins: the Québec newborn twins study.

The familiality of infant sleeping heart rate (HR) and cardiac-related autonomic activity, as indexed by spectral analysis of HR variability (HRV) and response to postural change, was investigated in 322 5-month-old twin pairs. The postural change elicited only minor changes in cardiovascular activity. As a result, analyses focused on supine cardiovascular activity. Multivariate genetic modeling indicated that individual differences in sleeping HR and high frequency (HF) HRV were determined by unique environmental and distinct additive genetic factors. These variables, along with low frequency (LF) HRV, were also affected by overlapping familial environmental influences. Familial influences in HF HRV were more pronounced for baby girls than boys. Estimates of relative LF and HF HRV were determined by common (familial) and unique environmental factors; familial influences on these estimates did not overlap with familial influences on sleeping HR.

Algorithms↗
PubMed2002

A longitudinal study of pain sensitivity and blood pressure in adolescent boys: results from a 5-year follow-up.

A growing literature has observed a significant reduction in pain sensitivity among hypertensive animals and humans. It is uncertain whether a reduced sensitivity to pain can be observed in nonnotensive individuals who go on to develop high blood pressure. Blood pressure (BP) was reassessed in one hundred fifteen 19-year-old boys initially tested at age 14, when they were also presented with a pain stimulus (mechanical finger pressure). Hierarchical regression analyses indicated that information regarding pain tolerance improved prediction of changes in systolic and diastolic blood pressure beyond that afforded by differences in BP at age 14, parental history of hypertension, and body mass index. These analyses suggest that pain sensitivity may be associated with physiological processes involved in the development of sustained high blood pressure.

Adolescent↗