Life Sci. 2004 Aug 6;75(12):1513-22.
Ajulemic acid: A novel cannabinoid produces analgesia without a "high".
Burstein SH, Karst M, Schneider U, Zurier RB.
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St., Worcester, MA 01605, USA.
A long-standing goal in cannabinoid research has been the discovery of potent synthetic analogs of the natural substances that might be developed as clinically useful drugs. This requires, among other things, that they be free of the psychotropic effects that characterize the recreational use of Cannabis. An important driving force for this goal is the long history of the use of Cannabis as a medicinal agent especially in the treatment of pain and inflammation. While few compounds appear to have these properties, ajulemic acid (AJA), also known as CT-3 and IP-751, is a potential candidate that could achieve this goal. Its chemical structure was derived from that of the major metabolite of Delta(9)-THC, the principal psychotropic constituent of Cannabis. In preclinical studies it displayed many of the properties of non-steroidal anti-inflammatory drugs (NSAIDs); however, it seems to be free of undesirable side effects. The initial short-term trials in healthy human subjects, as well as in patients with chronic neuropathic pain, demonstrated a complete absence of psychotropic actions. Moreover, it proved to be more effective than placebo in reducing this type of pain as measured by the visual analog scale. Unlike the narcotic analgesics, signs of dependency were not observed after withdrawal of the drug at the end of the one-week treatment period. Data on its mechanism of action are not yet complete; however, the activation of PPAR-gamma, and regulation of eicosanoid and cytokine production, appear to be important for its potential therapeutic effects.
first mention that I can find.....
J Pharmacol Exp Ther. 1999 Oct;291(1):31-8.
1',1'-Dimethylheptyl-delta-8-tetrahydrocannabinol-11-oic acid: a novel, orally effective cannabinoid with analgesic and anti-inflammatory properties.
Dajani EZ, Larsen KR, Taylor J, Dajani NE, Shahwan TG, Neeleman SD, Taylor MS, Dayton MT, Mir GN.
International Drug Development Consultants Corporation, Long Grove, Illinois, USA. esamd@aol.com
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. |
