Cannabinoids: influence on neurotransmitter uptake in rat brain synaptosomes

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

Research output: Contribution to journalArticlepeer-review

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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