Pharmos initiates CB2-selective drug trial
cannabinor, a CB2-selective synthetic cannabinoid drug candidate.
The trial aims to assess the drug's potential as a treatment for
neuropathic, inflammatory, visceral, and post-surgical pain.
The compound class holds great promise for a variety of applications in human health as CB1 and CB2 cannabinoid receptors in the brain and immune system play an integral role in nociception, inflammation and autoimmunity. The hope is that successful phase I trials will open the door to phase II testing in pain indications around year-end or early 2006.
The trial will enrol up to 48 healthy male subjects in a randomised, double blind, placebo controlled, intravenous, escalating single dose study. It is expected that the phase I cannabinor trial will be completed by the end of 2005.
"Initiating clinical development of compounds that work preferentially on the CB2 receptor is an important milestone. We hope that cannabinor will become an anti-pain drug that addresses unmet patient needs," said Haim Aviv, chairman and CEO.
CB1 receptors are found mainly in the central nervous system, and their activation leads to the psychotropic and cardiovascular effects of cannabis. CB2 receptors are found primarily in peripheral immune cells, and their activation has been shown to modulate inflammatory and immunoregulatory pathways.
In models of noxious, neuropathic, inflammatory, visceral, and post-surgical pain, the analgesic activity of cannabinor was comparable to reference agents tested including morphine and a variety of NSAIDs.
Involvement of the CB2 receptors in the drug candidate's mechanism of action is supported by observations that specific CB2 antagonists modulate cannabinor's analgesic and anti-inflammatory activities.
Howard Grossberg, vice president of drug development for Pharmos said: "The scientific community has suggested for years that substances similar to or derived from marijuana, known as cannabinoids, could treat pain."
"Now, studies show that cannabinoids directly interfere with pain signalling in the nervous system. Compounds that display high affinity for the CB2 receptor may offer avenues for harnessing the analgesic effect of CB-receptor agonists while avoiding the psychotropic and other adverse events seen with cannabinoid structures," he added.
Tolerance to narcotics such as morphine can be a clinical problem, with patients requiring steadily increasing doses to maintain therapeutic effect. A drug that remains effective without increasing dosage would be a valuable advance in treating severe pain.
Characteristically, cannabinoid compounds are lipophilic, a property making it difficult to formulate these compounds for oral administration. Importantly, cannabinor is water-soluble, and in animal models where the drug was administered orally, significant efficacy was measured.
Thus, preliminary evidence suggests that oral administration may be feasible as development proceeds.
In addition, increasing evidence has shown that cannabinoids have a number of useful functions in autoimmune disease including altering the balance between TH1 and TH2 lymphocytes in a favourable fashion as well as modulation of macrophage function and activation of MAP kinase.
