Abstract
907
Objectives: Salvia divinorum, a mint plant originally used by the Mazatecs of Oaxaca, Mexico in spiritual ritual, has gained popularity as a legal hallucinogen in the United States and Europe. Salvinorin A, the psychoactive component is neoclerodane diterpenoid with 7 stereocenters, C23H28O8, and a potent κ-opioid agonist. When smoked, it causes visual hallucinations in seconds lasting only minutes. Part A: To label salvinorin A with carbon-11 and determine pharmacokinetics in baboon brain using positron emission tomography (PET). Part B: To observe changes in glucose metabolism in behaving rats given salvinorin A using small animal PET.
Methods: Part A: Salvinorin A was isolated from S. divinorum plants. The C(2) acetyl group was removed by methanolysis under basic conditions forming salvinorin B that was subsequently labeled with [11C]-acetyl chloride. PET studies were performed in 6 adult female baboons. Part B: Two groups of freely behaving rats were given salvinorin A (2.0 mg/kg i.p.) or vehicle then FDG, 15 min later. After 45 min, rats were anesthetized and their brains were imaged using small animal PET. SPM was used to determine group differences.
Results: Part A: [11C]-salivorin A crosses the BBB reaching 3.3% of the ID within 40 s and clears rapidly (t1/2 = 8 min); logD 2.34; PPB 16.1% free; [11C]-salvinorin A is distributed throughout the brain with a high concentration in the cerebellum and cortex; [11C]-salvinorin is metabolized through at least two pathways. Part B: Increases in FDG metabolism were observed in the auditory and visual cortex, periaqueductal gray, among others. Decreases were observed in the striatum and medial brainstem.
Conclusions: The pharmacokinetics kinetics of salvinorin A in the brain match its duration when abused.
Research Support: DOE-OBER, NIH, Goldhaber Fellowship
- Society of Nuclear Medicine, Inc.