np9b00876_si_001.pdf (2.54 MB)
Isolation of a High-Affinity Cannabinoid for the Human CB1 Receptor from a Medicinal Cannabis sativa Variety: Δ9‑Tetrahydrocannabutol, the Butyl Homologue of Δ9‑Tetrahydrocannabinol
journal contribution
posted on 2019-12-31, 13:38 authored by Pasquale Linciano, Cinzia Citti, Livio Luongo, Carmela Belardo, Sabatino Maione, Maria Angela Vandelli, Flavio Forni, Giuseppe Gigli, Aldo Laganà, Carmela Maria Montone, Giuseppe CannazzaThe butyl homologues of Δ9-tetrahydrocannabinol,
Δ9-tetrahydrocannabutol (Δ9-THCB),
and cannabidiol, cannabidibutol (CBDB), were isolated from a medicinal Cannabis sativa variety (FM2) inflorescence. Appropriate
spectroscopic and spectrometric characterization, including NMR, UV,
IR, ECD, and HRMS, was carried out on both cannabinoids. The chemical
structures and absolute configurations of the isolated cannabinoids
were confirmed by comparison with the spectroscopic data of the respective
compounds obtained by stereoselective synthesis. The butyl homologue
of Δ9-THC, Δ9-THCB, showed an affinity
for the human CB1 (Ki = 15 nM) and CB2
receptors (Ki = 51 nM) comparable to that
of (−)-trans-Δ9-THC. Docking
studies suggested the key bonds responsible for THC-like binding affinity
for the CB1 receptor. The formalin test in vivo was performed on Δ9-THCB in order to reveal possible analgesic and anti-inflammatory
properties. The tetrad test in mice showed a partial agonistic activity
of Δ9-THCB toward the CB1 receptor.