1',1'-Dimethylheptyl-delta-8-tetrahydrocannabinol-11-oic acid: a novel, orally effective cannabinoid with analgesic and anti-inflammatory properties

J Pharmacol Exp Ther. 1999 Oct;291(1):31-8.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral
  • Analgesia
  • Analgesics / adverse effects
  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Cannabinoids / adverse effects
  • Cannabinoids / pharmacology*
  • Carcinoma, Basal Cell / chemically induced
  • Dimethyl Sulfoxide / adverse effects
  • Dimethyl Sulfoxide / pharmacology
  • Dronabinol / adverse effects
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacology
  • Drug Interactions
  • Indomethacin / pharmacology
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Pain Measurement
  • Rats
  • Rats, Wistar
  • Stomach Ulcer / chemically induced

Substances

  • 1',1'-dimethylheptyl-delta(8)-tetrahydrocannabinol-11-oic acid
  • Analgesics
  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cannabinoids
  • Dronabinol
  • Indomethacin
  • Dimethyl Sulfoxide