Mescaline and regional cerebral blood flow

Duke University, Durham NC

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Abstract

The hypothesis for this study is that mescaline induced depersonalization will be associated with an increase in cerebral blood flow (CBF) in the anterior cingulate, and that altered time sense will be associated with decreased blood flow in the cerebellum. In previous studies done in our laboratory, tetrahydrocannabinol (THC) and marijuana have been found to produce altered time sense and depersonalization. The proposed project will enable us to find out whether mescaline-induced intoxication, altered time sense, depersonalization and euphoria involve the same brain regions found to be associated with similar phenomena induced by marijuana and THC. Hallucinogens and cannabis are not addictive to animals which indicates that these drugs involve reward mechanisms unique to humans. Thus, the study of humans is imperative to understand the neurobiological mechanisms for hallucinogen addiction. We will recruit normal, healthy volunteers with a history of exposure to marijuana or a hallucinogen, they must be right-handed individuals, they must be able to read and write English, be between the ages of 18-40, and sign an informed consent. We will exclude any volunteers who have any significant physical or psychiatric disorders - including drug abuse, a history of vascular disorders, history of psychoses or personality disorders, and any current use of any central nervous system (CNS)-acting medication. The subjects will come to the GCRC on two occasions, separated by a minimum of one week. On one visit the subject will receive the active drug and on the other visit they will receive a placebo. A urine drug screen will be done on all subjects, and pregnancy testing will be performed on all female volunteers. A baseline positive emission tomography (PET) scan will be done using radioactive water and the autoradiographic technique. No arterial puncture will be done. A catheter will be placed for 15O administration and for blood draws. We will be using the newer, non-invasive external lung-probe C 15O technique to determine the input function on the PET scans. This technique provides a scaling factor for the lung-probe measurement of the input function. This scaling factor is then applied to the subsequent 15O water scans. The subjects inhale a small amount of radioactive carbon monoxide, hold it in their lungs for 20 seconds then exhale; three 0.5 ml blood samples are then drawn for counts. After the baseline PET scans, the subjects will have administered to them a mescaline dose of up to 500 mg on one visit, and a placebo during the other visit. This will be administered in our laboratory in Duke South, then the subjects will be escorted back to the GCRC. The PET scans will be repeated three more times after the intoxication has reached it's peak, approximately 2-5 hours after administration. We are also going to have the volunteers undergo a fMRI (functional Magnetic Resonance Imaging) on each visit. They will be asked to identify faces or patterns on a computer while having the fMRI, which will give us the cerebral hemodynamic activity. They will do this after the final PET scans. Our lab personnel will escort the subjects to PET and to MRI, then back to the GCRC. Symptoms of intoxication (slight increase in pulse, blood pressure and body temperature, dilated pupils, transient psychotic symptoms with preservation of insight) usually disappear within 8-10 hours after ingestion; subjects will be discharged from the GCRC after all signs of intoxication have disappeared. DEA licensure has been obtained, and an IND number from the FDA, # IND 56,064, has been assigned to this protocol.