The Pharmacokinetics of THC in fat and brain: Resulting functional responses to marihuana smoking

A pleasant sensory perception (PSP), the high of THC or of marihuana consum ption, is a consistent functional response to this drug only manifested by man, and which occurs concurrently with an increased heart rate. However, i t has not been possible to relate consistently magnitude and duration of th ese functional markers to THC plasma concentration, whatever the route of a dministration. A re-analysis of all the available clinical and experimental data reporting the pharmacokinetics and storage of THC in tissues in funct ion of time, have indicated that the discrepancies between functional respo nses and plasma molecular THC concentration may be accounted for by the pha rmacokinetics of THC. The instant uptake and unlimited storage of THC by ne utral fat limits the molecular concentration of the drug present in the pla sma to a level which does not exceed 6 x 10(14) molecules/ml. The physicoch emical nature of the membrane lipid bilayer (of the blood-brain barrier) wi ll restrict the access of THC into the bilayer receptors and its: reactive enzymes. The PSP and increased heart rate of marihuana is correlated with t he molecular concentration of THC in the bilayer (blood-brain barrier) of t he order of 10(12)-10(14) molecules/ml. This number in turn would be relate d to the number of functional THC receptor sites in the lipid bilayer. THC would exert its functional properties on PSP and heart rate through a molec ular transmission to specific receptor site and bilipid layer physicochemic al interations. Rapid uptake and slow release of THC in fat associated with a rate-limited uptake into brain may be a general philogenetic mechanism w hich would protect brain function from prolonged exposure to xenobiotics li ke THC and other fat soluble drugs. Copyright (C) 2001 John Wiley & Sons, L td.