PT  - JOURNAL ARTICLE
AU  - Dajani, Esam Z.
AU  - Larsen, Kenneth R.
AU  - Taylor, John
AU  - Dajani, Noura E.
AU  - Shahwan, Thomas G.
AU  - Neeleman, Stephen D.
AU  - Taylor, Mark S.
AU  - Dayton, Merril T.
AU  - Mir, G. Nabi
TI  - 1′,1′-Dimethylheptyl-Δ-8-tetrahydrocannabinol-11-oic Acid: A Novel, Orally Effective Cannabinoid with Analgesic and Anti-inflammatory Properties
DP  - 1999 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 31--38
VI  - 291
IP  - 1
4099  - http://jpet.aspetjournals.org/content/291/1/31.short
4100  - http://jpet.aspetjournals.org/content/291/1/31.full
SO  - J Pharmacol Exp Ther1999 Oct 01; 291
AB  - 1′,1′-Dimethylheptyl-Δ-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°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 (ED50 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. The American Society for Pharmacology and Experimental Therapeutics