Intravesical injection of THC analog efficacious for painfulbladders

May 21, 2006

Intravesical administration of liposomal ajulemic acid (IP-751)produces a positive response in laboratory animals and may beuseful in patients with painful bladder syndrome or interstitialcystitis, say investigators from the University of Pittsburgh.IP-751 is an analog of tetrahydrocannabinol (THC)-11-oic acid,which in turn is a metabolite of THC, the main psychotropic elementof cannabis.

Intravesical administration of liposomal ajulemic acid (IP-751) produces a positive response in laboratory animals and may be useful in patients with painful bladder syndrome or interstitial cystitis, say investigators from the University of Pittsburgh. IP-751 is an analog of tetrahydrocannabinol (THC)-11-oic acid, which in turn is a metabolite of THC, the main psychotropic element of cannabis.

"Anything to do with [marijuana] and its potential medicinal use is a political hot button," acknowledged lead researcher Michael B. Chancellor, MD. "Fortunately, we are talking here about a drug instilled only into the bladder. IP-751 is chemically synthesized in the lab and is based on the pharmacology of cannabis, but is not obtained from the plant in any way."

IP-751 is aqueously insoluble, prompting the investigators to formulate it into liposomes for intravesical administration. Female Sprague-Dawley rats were instilled with 0.5 mL of either saline or liposomal IP-751 for 30 minutes under anesthesia. Control rats received liposomes without the drug.

After 24 hours, the rats underwent continuous cystometrograms, again under anesthesia, while their bladders were filled with saline (0.04 mL/minute), followed by 0.125% acetic acid. The researchers then calculated percent reduction in intercontraction intervals (ICI) by acetic acid over baseline values.

Rats instilled with saline had a decrease in ICI of 83+/-6.4% after intravesical instillation of acetic acid, with the rats that received inert liposomes yielding about the same results. Rats instilled with liposomal IP-751, however, had a significantly decreased response of 24.7+/-6.4% following acetic acid infusion (p