Cannabinoids: influence on neurotransmitter uptake in rat brain synaptosomes

S. P. Banerjee, S. H. Snyder, R. Mechoulam

Research output: Contribution to journalArticle

Abstract

The authors examined the effect of Δ1 tetrahydrocannabinol (Δ1 THC) and 12 of its derivatives on the uptake of 3H labeled norepinephrine (NE), dopamine (DA), serotonin (5HT) and γ aminobutyric acid (GABA) into synaptosomes in homogenates of various regions of rat brain. Δ1 THC inhibits the accumulation of NE and 5 HT into hypothalamic preparations and DA into the corpus striatum with K(i) values of about 12 to 25 μM while GABA uptake into cerebral cortical preparations is inhibited less (K(i) = 140 μM). The affinities of Δ6 THC, 7 hydroxy Δ1 THC, 7 hydroxy Δ6 THC and cannabidiol for 5 HT, NE and GABA transports are similar to values for Δ1 THC, while cannabigerol, cannabinol and Δ6 THC 7 oic acid have substantially less affinity. Thus, hydroxylation of C 7 in Δ6 THC does not alter inhibitory potency, but its oxidation to an acid and aromatization of ring A greatly reduce affinity. The hydroxyl at C 31 of ring C is critical for inhibition of NE, 5 HT and GABA uptake, since its acetylation of methylation abolishes activity. Inhibition of NE, DA, 5 HT and GABA uptake by all cannabinoids examined is noncompetitive. Only about 1% of Δ1 THC and Δ6 THC and 5% of cannabidiol are fully soluble under our experimental conditions.

Original languageEnglish (US)
Pages (from-to)74-81
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume194
Issue number1
StatePublished - Dec 1 1975

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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