1',1'-Dimethylheptyl-delta-8-tetrahydrocannabinol-11-oic acid: a novel, orally effective cannabinoid with analgesic and anti-inflammatory properties.
1',1'-Dimethylheptyl-Delta-8-tetrahydrocannabinol-11-oic acid (CT-3) is a novel cannabinoid that is under development by Atlantic Pharmaceuticals as an anti-inflammatory and analgesic drug. The objective of the study was to investigate the effects of CT-3 on overt symptom complex (Irwin's test), nociception, gastrointestinal (GI) ulceration, and pharmacological availability after intragastric (i.g.) and intraperitoneal (i.p.) administration. Analgesic studies were assessed in the hot-plate (55 degrees C) and the tail clip tests in mice and in the tail clip test in rats. In addition, pharmacological interaction of CT-3 with the solvent dimethyl sulfoxide (DMSO) was investigated in rats. In mice, CT-3 decreased spontaneous motor activity and induced dose-dependent, analgesic activity in the tail clip and hot-plate tests, with potency similar to morphine sulfate after i.g. and i.p. administration. However CT-3 showed more prolonged duration of analgesic action than morphine. In rats, CT-3 showed marked analgesia in the tail clip test and had similar i.p. and i.g. median effective dose (ED(50) values; 5 mg/kg). CT-3 was devoid of GI ulceration when administered with DMSO either acutely at doses below 100 mg/kg or chronically at a dosage of 30 mg/kg/day for 5 days. In contrast, indomethacin induced GI ulceration and deaths. The concurrent use of DMSO with CT-3 decreased its analgesic action, increased its adverse central nervous system effects, and induced GI ulceration. The evidence indicates that CT-3 exhibits a large dissociation between its anti-inflammatory/analgesic effects and its ulcerogenic actions. CT-3 warrants clinical development as a novel anti-inflammatory and analgesic drug.
Dajani
E Z
EZ
International Drug Development Consultants Corporation, Long Grove, Illinois, USA. esamd@aol.com
Larsen
K R
KR
Taylor
J
J
Dajani
N E
NE
Shahwan
T G
TG
Neeleman
S D
SD
Taylor
M S
MS
Dayton
M T
MT
Mir
G N
GN
D000284:Administration, Oral; D000698:Analgesia; D000700:Analgesics / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002186:Cannabinoids / Q000009:adverse effects / Q000494:pharmacology*; D002280:Basal Cell Carcinoma / Q000139:chemically induced; D004121:Dimethyl Sulfoxide / Q000009:adverse effects / Q000494:pharmacology; D013759:Dronabinol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D004347:Drug Interactions; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced
C113759:1',1'-dimethylheptyl-delta(8)-tetrahydrocannabinol-11-oic acid; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002186:Cannabinoids; D013759:Dronabinol; D007213:Indomethacin; D004121:Dimethyl Sulfoxide