TY - JOUR
T1 - Δ9-cis-Tetrahydrocannabinol
T2 - Natural Occurrence, Chirality, and Pharmacology
AU - Schafroth, Michael A.
AU - Mazzoccanti, Giulia
AU - Reynoso-Moreno, Ines
AU - Erni, Reto
AU - Pollastro, Federica
AU - Caprioglio, Diego
AU - Botta, Bruno
AU - Allegrone, Gianna
AU - Grassi, Giulio
AU - Chicca, Andrea
AU - Gasparrini, Francesco
AU - Gertsch, Jürg
AU - Carreira, Erick M.
AU - Appendino, Giovanni
N1 - Publisher Copyright:
© 2021 The Authors. Published by American Chemical Society and American Society of Pharmacognosy
PY - 2021/9/24
Y1 - 2021/9/24
N2 - Thecis-stereoisomers of Δ9-THC [(−)- 3 and (+)- 3 ] were identified and quantified in a series of low-THC-containing varieties ofCannabis sativaregistered in Europe as fiber hemp and in research accessions of cannabis. While Δ9-cis-THC ( 3 ) occurs in cannabis fiber hemp in the concentration range of (−)-Δ9-trans-THC [(−)- 1 ], it was undetectable in a sample of high-THC-containing medicinal cannabis. Natural Δ9-cis-THC ( 3 ) is scalemic (ca. 80-90% enantiomeric purity), and the absolute configuration of the major enantiomer was established as 6aS,10aR[(−)- 3 ] by chiral chromatographic comparison with a sample available by asymmetric synthesis. The major enantiomer, (−)-Δ9-cis-THC [(−)- 3 ], was characterized as a partial cannabinoid agonist in vitro and elicited a full tetrad response in mice at 50 mg/kg doses. The current legal discrimination between narcotic and non-narcotic cannabis varieties centers on the contents of “Δ9-THC and isomers” and needs therefore revision, or at least a more specific wording, to account for the presence of Δ9-cis-THCs [(+)- 3 and (−)- 3 ] in cannabis fiber hemp varieties.
AB - Thecis-stereoisomers of Δ9-THC [(−)- 3 and (+)- 3 ] were identified and quantified in a series of low-THC-containing varieties ofCannabis sativaregistered in Europe as fiber hemp and in research accessions of cannabis. While Δ9-cis-THC ( 3 ) occurs in cannabis fiber hemp in the concentration range of (−)-Δ9-trans-THC [(−)- 1 ], it was undetectable in a sample of high-THC-containing medicinal cannabis. Natural Δ9-cis-THC ( 3 ) is scalemic (ca. 80-90% enantiomeric purity), and the absolute configuration of the major enantiomer was established as 6aS,10aR[(−)- 3 ] by chiral chromatographic comparison with a sample available by asymmetric synthesis. The major enantiomer, (−)-Δ9-cis-THC [(−)- 3 ], was characterized as a partial cannabinoid agonist in vitro and elicited a full tetrad response in mice at 50 mg/kg doses. The current legal discrimination between narcotic and non-narcotic cannabis varieties centers on the contents of “Δ9-THC and isomers” and needs therefore revision, or at least a more specific wording, to account for the presence of Δ9-cis-THCs [(+)- 3 and (−)- 3 ] in cannabis fiber hemp varieties.
UR - http://www.scopus.com/inward/record.url?scp=85112359989&partnerID=8YFLogxK
U2 - 10.1021/acs.jnatprod.1c00513
DO - 10.1021/acs.jnatprod.1c00513
M3 - Article
SN - 0163-3864
VL - 84
SP - 2502
EP - 2510
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 9
ER -