ULTRASTRUCTURAL AND BIOCHEMICAL CHANGES IN CNS INDUCED BY MARIHUANA

Abstract

The effect of Δ9-tetrahydrocannabinol (THC) on some metabolic processes and cell structures in rat brain were studied in vitro and in vivo. The intracellular distribution and binding of labeled THC in brain tissue was also determined. The following results were observed:A.The incorporation of radioactive precursors into protein and nucleic acid of rat brain cortical slices was significantly inhibited by THC. The inhibition was age related, with the most marked effect being in the infant (3-day-old) rat.B.Acute administration of THC and other cannabinoids brought about morphological changes, viz. a reduction in the number of nuclear membrane-attached ribosomes (NMAR) in infant rat brain. The reduction of NMAR was dose and time related, and reversible. The pharmacologically active cannabinoids had a highly significant effect, but the pharmacologically inactive had only a slight effect. These ultrastructural changes are consistent with the biochemical effects of THC on protein and RNA synthesis.C.Following the administration of radioactive THC to lactating rats, THC and its metabolites were identified in the organs of suckling infants. The amount of cannabinoids transferred from the lactating mother to suckling infant produced a highly significant decrease of NMAR in brain cells, which was still detectable 24 h after the injection. The prolonged supply of THC and/or active metabolites from the milk probably accounted for this lengthy action.D.Intracellular distribution studies with labeled THC show highly preferential binding to particulate fractions in the brain cells, mainly the crude mitochondrial fraction. This localization is supported by electron microscope studies which show preferential binding of labeled THC to nerve endings.