title: Ajulemic acid (IP-751): synthesis, proof of principle, toxicity studies, and clinical trials.
abstract: Ajulemic acid (CT-3, IP-751, 1',1'-dimethylheptyl-Delta8-tetrahydrocannabinol-11-oic acid) (AJA) has a cannabinoid-derived structure; however, there is no evidence that it produces psychotropic actions when given at therapeutic doses. In a variety of animal assays, AJA shows efficacy in models for pain and inflammation. Furthermore, in the rat adjuvant arthritis model, it displayed a remarkable action in preventing the destruction of inflamed joints. A phase-2 human trial with chronic, neuropathic pain patients suggested that AJA could become a useful drug for treating this condition. Its low toxicity, particularly its lack of ulcerogenicity, further suggests that it will have a highly favorable therapeutic index and may replace some of the current anti-inflammatory/analgesic medications. Studies to date indicate a unique mechanism of action for AJA that may explain its lack of adverse side effects.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA. sumner.burstein@umassmed.edu
authors.forename: Summer
authors.initials: S
authors.lastname: Burstein
mesh_terms: D000328:Adult; D000700:Analgesics / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001169:Arthritis, Experimental / Q000188:drug therapy; D002186:Cannabinoids / Q000737:chemistry; D045744:Cell Line, Tumor / Q000187:drug effects; D017322:Clinical Trials, Phase II as Topic; D016207:Cytokines / Q000502:physiology; D004311:Double-Blind Method; D013759:Dronabinol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000188:drug therapy; D005260:Female; D005756:Gastritis / Q000139:chemically induced; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D015394:Molecular Structure; D009437:Neuralgia / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D051381:Rats
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002186:Cannabinoids; D016207:Cytokines; D013759:Dronabinol; C471849:lenabasum