TY - JOUR
T1 - Conversion of cannabidiol to Δ9-tetrahydrocannabinol and related cannabinoids in artificial gastric juice, and their pharmacological effects in mice
AU - Watanabe, Kazuhito
AU - Itokawa, Yuka
AU - Yamaori, Satoshi
AU - Funahashi, Tatsuya
AU - Kimura, Toshiyuki
AU - Kaji, Toshiyuki
AU - Usami, Noriyuki
AU - Yamamoto, Ikuo
N1 - Funding Information:
Acknowledgments A part of this work was supported by the “Academic Frontier” Project for Private Universities from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (2005–2009).
PY - 2007/6
Y1 - 2007/6
N2 - Cannabidiol (CBD), a nonpsychoactive cannabinoid, was found to be converted to 9α-hydroxyhexahydrocannabinol (9α-OH-HHC) and 8-hydroxy-iso-hexahydrocannabinol (8-OH-iso-HHC) together with Δ9-tetrahydrocannabinol (Δ9-THC), a psychoactive cannabinoid, and cannabinol in artificial gastric juice. These cannabinoids were identified by gas chromatography-mass spectrometry (GC-MS) by comparison with the spectral data of the authentic compounds. Pharmacological effects of 9α-OH-HHC and 8-OH-iso-HHC in mice were examined using catalepsy, hypothermia, pentobarbital-induced sleep prolongation, and antinociception against acetic acid-induced writhing as indices. The ED 50 values (effective dose producing a 50% reduction of control; mg/kg, i.v.) of 9α-OH-HHC and 8-OH-iso-HHC for the cataleptogenic effect were 8.0 and 30.4, respectively. 8-OH-iso-HHC (10 mg/kg, i.v.) produced a significant hypothermia from 15 to 90 min after administration, although 9α-OH-HHC failed to induce such an effect at the same dose. However, both HHCs (10 mg/kg, i.v.) significantly prolonged pentobarbital-induced sleeping time by 1.8 to 8.0 times as compared with the control solution with 1% Tween 80-saline. The ED50 values (mg/kg, i.v.) of 9α-OH-HHC and 8-OH-iso-HHC for the antinociceptive effect were 14.1 and 39.4, respectively. The present study demonstrated that CBD can be converted to Δ9- THC and its related cannabinoids, 9α-OH-HHC and 8-OH-iso-HHC, in artificial gastric juice, and that these HHCs show Δ9-THC-like effects in mice, although their pharmacological effects were less potent than those of Δ9-THC.
AB - Cannabidiol (CBD), a nonpsychoactive cannabinoid, was found to be converted to 9α-hydroxyhexahydrocannabinol (9α-OH-HHC) and 8-hydroxy-iso-hexahydrocannabinol (8-OH-iso-HHC) together with Δ9-tetrahydrocannabinol (Δ9-THC), a psychoactive cannabinoid, and cannabinol in artificial gastric juice. These cannabinoids were identified by gas chromatography-mass spectrometry (GC-MS) by comparison with the spectral data of the authentic compounds. Pharmacological effects of 9α-OH-HHC and 8-OH-iso-HHC in mice were examined using catalepsy, hypothermia, pentobarbital-induced sleep prolongation, and antinociception against acetic acid-induced writhing as indices. The ED 50 values (effective dose producing a 50% reduction of control; mg/kg, i.v.) of 9α-OH-HHC and 8-OH-iso-HHC for the cataleptogenic effect were 8.0 and 30.4, respectively. 8-OH-iso-HHC (10 mg/kg, i.v.) produced a significant hypothermia from 15 to 90 min after administration, although 9α-OH-HHC failed to induce such an effect at the same dose. However, both HHCs (10 mg/kg, i.v.) significantly prolonged pentobarbital-induced sleeping time by 1.8 to 8.0 times as compared with the control solution with 1% Tween 80-saline. The ED50 values (mg/kg, i.v.) of 9α-OH-HHC and 8-OH-iso-HHC for the antinociceptive effect were 14.1 and 39.4, respectively. The present study demonstrated that CBD can be converted to Δ9- THC and its related cannabinoids, 9α-OH-HHC and 8-OH-iso-HHC, in artificial gastric juice, and that these HHCs show Δ9-THC-like effects in mice, although their pharmacological effects were less potent than those of Δ9-THC.
KW - 8-Hydroxy-iso-hexahydrocannabinol
KW - 9α- Hydroxyhexahydrocannabinol
KW - Acid-catalyzed cyclization
KW - Antinociceptive effect
KW - Cannabidiol
KW - Δ-Tetrahydrocannabinol
UR - http://www.scopus.com/inward/record.url?scp=34249795493&partnerID=8YFLogxK
U2 - 10.1007/s11419-007-0021-y
DO - 10.1007/s11419-007-0021-y
M3 - Article
AN - SCOPUS:34249795493
SN - 1860-8965
VL - 25
SP - 16
EP - 21
JO - Forensic Toxicology
JF - Forensic Toxicology
IS - 1
ER -