Neck radiographs in croup syndrome

The hallucinogenic tryptamines DMT and 5-MeO-DMT in ayahuasca have little effect when taken orally unless co-administered with MAO inhibitors, which block their breakdown. A radiolabeled form of 5-MeO-DMT, [11C]MeO-DMT, was developed and injected into pigs for PET brain imaging. The tracer showed substantial brain uptake, with highest binding in the basal forebrain. Self-displacement studies indicated displaceable binding throughout the brain but not entirely in the ventral striatum. Ketanserin, a serotonin 5HT2 receptor antagonist, did not displace binding, excluding these receptors as the site of hallucinogenic action. MAO inhibition with pargyline reduced specific binding by 30% and slowed plasma metabolism, confirming MAO's role in the tracer's cerebral binding.

Study at a glance

Abstract

1141 Objectives: The ayahuasca effect refers to the potentiation of action of hallucinogenic tryptamine alkaloids by co-administration of a plant extract containing MAO inhibitors, especially the beta-carboline harmine. The hallucinogenic tryptamines in the ayahuasca drink are primarily DMT and 5-MeO-DMT, the same tryptamines in extracts of Bufo skin, and the snuff yopo, another South American hallucinogenic plant extract. DMT and/or 5-MeO-DMT have little effect by oral administration; however concomitant MAO inhibition is said to increase their psychotropic effects by interfering with first-pass metabolism of orally administered agents. MeO-DMT has previously been prepared as [11C]-methyl amine (Berger et al., 1978), which is very vulnerable to metabolism by N-demethylation or by oxidative deamination; the present ligand allows the tracing of deaminated metabolites. To provide the basis for modeling the ayahuasca effect, we have developed a radiosynthesis for [11C]MeO-DMT, and mapped its uptake in brain of pigs using positron emission tomography (PET). Methods: Nine pigs were injected with [11C]MeO-DMT and then PET scanned, three of which received cold MeO-DMT in self-displacement studies, three got ketanserin and three received pargyline in blocking experiments before second scan. Results: There was substantial uptake of [11C]MeO-DMT in brain of living Danish Landrace/Yorkshire pigs, with a mean of the voxel-based distribution volume, Vd, for the whole brain at 3,9±0,9 mL/g, with highest binding in the basal forebrain of all nine pigs examined. Self-displacement studies with cold MeO-DMT at 2 mg/kg (N=3) revealed displaceable binding throughout brain, but did not displace entirely the [11C]MeO-DMT binding in ventral striatum. There was no discernible displacement with ketanserin (1 mg/kg, i.v.), an antagonist of serotonin 5HT2 receptors, However, treatment with pargyline (3 mg/kg) caused a 30% decrease in specific binding in all three pigs, suggesting that MAO contributes significantly to the cerebral binding of the ligand. The pargyline treatment increased the area under the curve of untransformed [11C]MeO-DMT in plasma, and reduced the apparent rate constant for plasma metabolism (k0) by 50%. Since first pass metabolism is likely to be reduced following intravenous tracer injection, we are currently testing effects of pargyline on the cerebral uptake of [11C]MeO-DMT administered by the intraperitoneal route to rats. Conclusions: The present results indicate that [11C]MeO-DMT is a promising tracer for PET investigations of an important class of hallucinogens, further demonstrating that 5HT2 receptors can be excluded as the site of central hallucinogenic action.