Isolation and Pharmacological Evaluation of Minor Cannabinoids from High-Potency Cannabis sativa

J Nat Prod. 2015 Jun 26;78(6):1271-6. doi: 10.1021/acs.jnatprod.5b00065. Epub 2015 May 22.

Abstract

Seven new naturally occurring hydroxylated cannabinoids (1-7), along with the known cannabiripsol (8), have been isolated from the aerial parts of high-potency Cannabis sativa. The structures of the new compounds were determined by 1D and 2D NMR spectroscopic analysis, GC-MS, and HRESIMS as 8α-hydroxy-Δ(9)-tetrahydrocannabinol (1), 8β-hydroxy-Δ(9)-tetrahydrocannabinol (2), 10α-hydroxy-Δ(8)-tetrahydrocannabinol (3), 10β-hydroxy-Δ(8)-tetrahydrocannabinol (4), 10α-hydroxy-Δ(9,11)-hexahydrocannabinol (5), 9β,10β-epoxyhexahydrocannabinol (6), and 11-acetoxy-Δ(9)-tetrahydrocannabinolic acid A (7). The binding affinity of isolated compounds 1-8, Δ(9)-tetrahydrocannabinol, and Δ(8)-tetrahydrocannabinol toward CB1 and CB2 receptors as well as their behavioral effects in a mouse tetrad assay were studied. The results indicated that compound 3, with the highest affinity to the CB1 receptors, exerted the most potent cannabimimetic-like actions in the tetrad assay, while compound 4 showed partial cannabimimetic actions. Compound 2, on the other hand, displayed a dose-dependent hypolocomotive effect only.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesics
  • Animals
  • Cannabinoids / chemistry
  • Cannabinoids / isolation & purification*
  • Cannabis / chemistry*
  • Dose-Response Relationship, Drug
  • Dronabinol / analogs & derivatives
  • Gas Chromatography-Mass Spectrometry
  • Mice
  • Mississippi
  • Molecular Structure
  • Motor Activity / drug effects
  • Nuclear Magnetic Resonance, Biomolecular
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / metabolism

Substances

  • Analgesics
  • Cannabinoids
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • cannabiripsol
  • Dronabinol
  • delta(9)-tetrahydrocannabinolic acid