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.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2751505/

1′,1′-Dimethylheptyl-Δ-8-tetrahydrocannabinol-11-oic Acid: A Novel, Orally Effective Cannabinoid with Analgesic and Anti-inflammatory Properties

  “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… .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.”

“1′,1′-Dimethylheptyl-Δ-8-tetrahydrocannabinol-11-oic acid (CT-3) is a novel cannabinoid with analgesic and anti-inflammatory activities. CT-3 is chemically similar to Δ-9-tetrahydrocannabinol (THC, dronabilone) and nabilone.”

“Analgesia is one of the most profound effects of THC in most species after its parenteral administration, and THC had shown equivalent potency to morphine in rats and mice in a variety of analgesic tests, including the tail-flick latency measurements. Several synthetic cannabinoids have also shown analgesic activities in animal models selective for detecting opiate analgesics.”

“The analgesic action of CT-3 is well confirmed in rats and in mice. Available evidence indicates that CT-3 exhibits two distinct pharmacological properties: an anti-inflammatory property occurring at a very low dose (ED50 = ∼0.1 mg/kg i.g.; and an analgesic property occurring at a higher dose (ED50 = ∼5 mg/kg i.g. and i.p.). The present results indicate that CT-3 is an orally effective analgesic drug, and acceptable pharmaceutical formulation of CT-3 would not require the adjuvant use of permeability enhancers to promote its bioavailability. CT-3 clearly warrants clinical development as an analgesic and anti-inflammatory drug.”

http://jpet.aspetjournals.org/content/291/1/31.long

Marijuana, inflammation, and CT-3 (DMH-11C): cannabis leads to new class of antiinflammatory drugs.

Abstract:

“CT-3, a synthetic derivative of a metabolite of marijuana, is being tested by arthritis researchers as a possible new anti-inflammatory drug. Early studies show that CT-3 may be effective without the gastric side effects of steroids and psychoactive effects of marijuana. The processes of inflammation may be important in the pathogenesis of HIV disease. Obtaining the medical benefits without the psychoactive effects of marijuana is also important, as the high associated with cannabis use can be debilitating. The drug is currently in early pre-clinical animal testing.”

http://www.ncbi.nlm.nih.gov/pubmed/11365002