Background: - Small differences in genes may alter responses to drugs. One gene that has different forms is the mu opioid receptor gene. People with one form of this gene are more sensitive to alcohol. People with a different form are sometimes more sensitive to pain. Morphine and other prescription pain pills produce pain relief by acting at the mu opioid receptor. Researchers want to see the effect of morphine on brain reward and subjective effects. Morphine is a strong but short-acting pain medication that is sometimes used for anesthesia during surgery. Objectives: - To compare the effect of morphine on brain measures of dopamine release using imaging. Eligibility: - Individuals between 21 and 55 years of age who have previously taken pain pills prescribed to treat pain from a medical or dental procedure. Design: - This study has a screening phase and a study phase. The screening phase involves one or two visits of 5 to 6 hours. The study phase consists of 4 study visits. Each study visit will take about 8 hours. - Participants will be screened with a medical and psychiatric history and physical exam. They will be asked about drinking and drug-taking history, and any family history of alcoholism or drug abuse. Blood, urine, and breath samples will be collected. - During the first study visit, an MRI scan may be performed, questionnaires completed, and a blood sample collected for genetic testing. - During study visit 2, participants will test their pain sensitivity by placing one hand in cold water. Pupil diameter will be measured after the sensitivity test. After a blood sample is taken, participants will receive the morphine or a salt solution. The sensitivity test and pupil diameter test will be repeated. Final blood samples will be collected. A brief physical exam will also be performed. - During study visits 3 and 4, participants will receive morphine or a salt solution during a PET scan. Questionnaires to assess subjective effects will be administered. Final blood samples will be collected. A brief physical exam will also be performed. - Participants will stay in the clinic until the effects of the drug have worn off after study visits 2, 3, and 4. - About 1 week after the study session, participants will have a follow-up phone call.
Name: Morphine
Name: Placebo
Description: Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2) 33, with cerebellum as the reference region. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
Measure: 11C Raclopride Binding Potential in Caudate Time: 90 minutes following injectionDescription: Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2) 33, with cerebellum as the reference region. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
Measure: 11C Raclopride Binding Potential in Nucleus Accumbens Time: 90 minutes following injectionDescription: Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2) 33, with cerebellum as the reference region. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
Measure: 11C Raclopride Binding Potential in Putamen Time: 90 minutes following injectionDescription: Binding potential measured using regions-of-interest analysis of PET data. Parametric Binding Potential (BPND) images were obtained using the Simple Reference Tissue Model 2 (SRTM2) 33, with cerebellum as the reference region. Reduction in raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of Dopamine (DA) release.
Measure: 11C Raclopride Binding Potential in Ventral Pallidum Time: 90 minutes following injectionDescription: Area under the curve of the subjective perception-time course - Feel Drug. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared instead. Possible range of values for the AUC are 0 to 5500.
Measure: Subjective Perception of Morphine Effect - Feel Drug Time: 60 minutes following injectionDescription: Area under the curve of the subjective perception-time course - Feel High. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared instead. Possible range of values for the AUC are 0 to 5500.
Measure: Subjective Perception of Morphine Effect - Feel High Time: 60 minutes following injectionDescription: Area under the curve of the subjective perception-time course - Like Drug. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared instead. Possible range of values for the AUC are 0 to 5500.
Measure: Subjective Perception of Morphine Effect - Like Drug Time: 60 minutes following injectionDescription: Area under the curve of the subjective perception-time course - Want More. Subjective responses as measured by the Drug Effects Questionnaire [DEQ]. The DEQ consists of simple, face-valid, visual analog scale (VAS) questions on which people report their subjective states after ingesting a substance. The analog scale of responses ranges from "not at all" to "extremely", and the numeric scale ranges from 0 to 100. Due to skewness of individual time points; areas under the curve for these ratings across individual time points (0, 10, 20, 30, 40, 50 and 60 min) were compared instead. Possible range of values for the AUC are 0 to 5500.
Measure: Subjective Perception of Morphine Effect - Want More Time: 60 minutes following injectionAllocation: Randomized
Crossover Assignment
There is one SNP
OPRM1 A118G SNP Effect on Striatal Dopamine Response to an IV Opiate. --- A118G ---
A functional ยต-opioid receptor (OPRM1) A118G single nucleotide polymorphism (SNP) has been associated with increased risk for heroin addiction in some studies. --- A118G ---
The objective of this study is to examine the role of the A118G OPRM1 polymorphism for responses to a challenge of an opiate (morphine) with regard to psycho-physiological variables measured in the laboratory and for brain dopamine release measured by [11C]raclopride PET. --- A118G ---