10.1021/acs.jnatprod.9b00876.s001 Pasquale Linciano Pasquale Linciano Cinzia Citti Cinzia Citti Livio Luongo Livio Luongo Carmela Belardo Carmela Belardo Sabatino Maione Sabatino Maione Maria Angela Vandelli Maria Angela Vandelli Flavio Forni Flavio Forni Giuseppe Gigli Giuseppe Gigli Aldo Laganà Aldo Laganà Carmela Maria Montone Carmela Maria Montone Giuseppe Cannazza Giuseppe Cannazza Isolation of a High-Affinity Cannabinoid for the Human CB1 Receptor from a Medicinal <i>Cannabis sativa</i> Variety: Δ<sup>9</sup>‑Tetrahydrocannabutol, the Butyl Homologue of Δ<sup>9</sup>‑Tetrahydrocannabinol American Chemical Society 2019 CB 2 receptors cannabinoid Medicinal Cannabis sativa Variety Δ 9 THCB Cannabis sativa variety spectroscopic UV Human CB 1 Receptor homologue CB 1 receptor FM ECD K i THC-like binding affinity NMR nM CBDB HRMS IR butyl 2019-12-31 13:38:29 Journal contribution https://acs.figshare.com/articles/journal_contribution/Isolation_of_a_High-Affinity_Cannabinoid_for_the_Human_CB1_Receptor_from_a_Medicinal_i_Cannabis_sativa_i_Variety_sup_9_sup_Tetrahydrocannabutol_the_Butyl_Homologue_of_sup_9_sup_Tetrahydrocannabinol/11482215 The butyl homologues of Δ<sup>9</sup>-tetrahydrocannabinol, Δ<sup>9</sup>-tetrahydrocannabutol (Δ<sup>9</sup>-THCB), and cannabidiol, cannabidibutol (CBDB), were isolated from a medicinal <i>Cannabis sativa</i> 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 Δ<sup>9</sup>-THC, Δ<sup>9</sup>-THCB, showed an affinity for the human CB1 (<i>K</i><sub>i</sub> = 15 nM) and CB2 receptors (<i>K</i><sub>i</sub> = 51 nM) comparable to that of (−)-<i>trans</i>-Δ<sup>9</sup>-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 Δ<sup>9</sup>-THCB in order to reveal possible analgesic and anti-inflammatory properties. The tetrad test in mice showed a partial agonistic activity of Δ<sup>9</sup>-THCB toward the CB1 receptor.