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Biomedical subjects

Leslie H Lundahl

Publications and source records attributed to Leslie H Lundahl.

5 recordsLinked to original sources

Negative cocaine effect expectancies are associated with subjective response to cocaine challenge in recreational cocaine users.

Although many studies have shown that cognitive effect expectancies are associated with drug use and drug treatment outcomes, few studies have compared effect expectancies with drug response following drug challenge. Healthy male and female volunteers (n=19, ages 21-35) who reported using cocaine 1-4 times per month completed the Cocaine Effect Expectancy Questionnaire (CEEQ: [Schafer, J. and Brown, S.A. (1991). Marijuana and cocaine effect expectancies and drug use patterns. Journal of Consulting and Clinical Psychology, 59, 558-565.]), were challenged with cocaine (0.9 mg/kg, i.n.), then completed a series of visual analog scales (VAS) and the Addiction Research Center Inventory (ARCI) at 15 min intervals for 3 h following cocaine administration. Significant positive correlations were found between global negative expectancies and peak responses on the VAS measures "Good," "Happy," "High," "Stimulated," and "Desire to Use Cocaine," and on the LSD subscale of the ARCI post-cocaine administration, and between global positive expectancies and the MBG subscale of the ARCI, and on VAS items "Anxious" and "Good" post-cocaine administration. Global positive expectancies also were positively correlated with peak systolic blood pressure, and global negative expectancies with peak heart rate after cocaine administration. These results suggest that negative and positive effect expectancies both play a complex role in the subjective experience of cocaine effects, and thus likely in the progression of non-use to recreational use, in the transition to abuse, and in individualized treatment strategies.

Adult↗

Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers.

OBJECTIVE: Preclinical investigations have established that methamphetamine (MA) produces long-term changes in dopamine (DA) neurons in the striatum. Human studies have suggested similar effects and correlated motor and cognitive deficits. The present study was designed to further our understanding of changes in brain function in humans that might result from chronic high dose use of MA after at least 3 months of abstinence. METHOD: Brain function in abstinent users was compared to controls using neuroimaging of monoamine transporters and cognitive assessment. Striatal levels of DA transporter (DAT) and vesicular monoamine transporter type-2 (VMAT2) were determined using [11C]methylphenidate and [11C]dihydrotetrabenazine positron emission tomography, respectively. Cognitive function was evaluated using tests of motor function, memory, learning, attention, and executive function. RESULTS: Striatal DAT was approximately 15% lower and VMAT2 was 10% lower in MA abusers across striatal subregions. The MA abusers performed within the normal range but performed more poorly compared to controls on three of the 12 tasks. CONCLUSIONS: Failure to find more substantial changes in transporter levels and neurocognitive function may be attributed to the length of time that MA users were abstinent (ranging from 3 months to more than 10 years, mean 3 years), although there were no correlations with length of abstinence. Persistent VMAT2 reductions support the animal literature indicating a toxic effect of MA on nigrostriatal nerve terminals. However, the magnitude of the MA effects on nigrostriatal projection integrity is sufficiently small that it is questionable whether clinical signs of DA deficiency are likely to develop.

Adolescent↗

Benztropine pretreatment does not affect responses to acute cocaine administration in human volunteers.

Benztropine (Cogentin ) was evaluated for its ability to block cocaine's physiological and subjective effects in humans. In healthy, recreational users of cocaine, placebo, or benztropine (1, 2, and 4 mg orally) was given 2 hr before subjects self-administered 0.9 mg/kg of cocaine intranasally. Measurements were made for 2 hr following cocaine administration, and plasma cocaine and cocaine metabolites were assayed. Cocaine produced typical increases in heart rate and alterations in self-reports measured by visual analog scales (VAS). Benztropine alone did not produce changes on any of these measures. Responses to cocaine with and without benztropine pretreatment were similar: benztropine did not change cocaine's effects. This study of one of the tropane-ring analogs that is approved for human use suggests this compound does not alter cocaine-induced effects, but just as importantly, does not produce any adverse behavioral or physiological effects. The exact therapeutic application of benztropine as a possible adjunct treatment for cocaine abuse in humans require further exploration.

Adult↗

Intravenous cocaine discrimination in humans.

Ten cocaine-dependent participants were trained to discriminate between intravenous saline and 20 mg/70 kg cocaine. During the first session, saline and cocaine injections were alternated twice, with each separated by 1 hr. The injections were identified by letter codes. During the next 3 sessions, 12 trials were conducted, with saline and cocaine administered 6 times each in pseudorandom order. Thirty minutes following each injection, participants were asked to identify the injection by letter code. Seven of the 10 learned the discrimination (at least 10 trials correct). To evaluate sensitivity, the investigators tested participants with different doses of cocaine in test sessions. In the next phase, methamphetamine (5 and 10 mg/70 kg) and pentobarbital (50 and 100 mg/70 kg) were given intravenously during test sessions to determine whether the discrimination exhibited pharmacological class selectivity. During the evaluation of sensitivity and selectivity, training sessions were interspersed. As dose of cocaine increased, the number of participants identifying the test dose as cocaine increased, demonstrating sensitivity. The higher doses of methamphetamine and pentobarbital substituted for cocaine. The physiological and subjective effects of cocaine and methamphetamine were stimulant-like and dose related. Pentobarbital produced no physiological changes but increased Visual Analog Scale ratings of Sedation, Good Drug Effect, and High. This failure to demonstrate pharmacological selectivity may be related to participants' learning a drug-vs.-no-drug discrimination, and thus it may be necessary to alter training procedures in future studies.

Blood Pressure↗

Effects of oral contraceptives on acute cocaine response in female volunteers.

A growing number of recent reports have demonstrated sex and menstrual cycle differences in the subjective, physiological and pharmacokinetic effects of stimulant drugs in humans. The present study was conducted to further investigate the relationship between gonadal hormones and cocaine effects by examining whether oral contraceptives (OCs) alter the acute effects of cocaine. Seven female volunteers, who were taking triphasic OCs and who were occasional users of cocaine, provided informed consent and participated in this placebo-controlled, four-visit study. Subjects were studied twice during days 6-10 of the menstrual cycle (equivalent to the follicular phase) and twice during days 21-28 of the menstrual cycle (equivalent to the luteal phase) and were challenged with an acute dose of intranasal (in) cocaine (0.9 mg/kg or placebo). There were no differences in cocaine-induced subjective, physiologic or plasma cocaine and metabolite levels during the times equivalent to the follicular and luteal phases of the menstrual cycle. Our findings provide evidence that OCs do not present an added risk of cocaine-induced cardiovascular effects and that exogenous administration of estrogen and progesterone at the physiologic doses found in OCs do not alter the subjective responses to acute cocaine.

Adult↗