July 10, 2010 A new compound similar to the active component of marijuana (cannabis) might provide effective pain relief without the mental and physical side effects of cannabis, according to a study in the July issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).
The synthetic cannabinoid (cannabis-related) compound, called MDA19, seems to avoid side effects by acting mainly on one specific subtype of the cannabinoid receptor. "MDA19 has the potential for alleviating neuropathic pain without producing adverse effects in the central nervous system," according to the study by Dr Mohamed Naguib of The University of Texas M.D. Anderson Cancer Center.
MDA19 Works on a Single Cannabinoid Receptor
The researchers performed a series of experiments to analyze the pharmacology and effects of the synthetic cannabinoid MDA19. There are two subtypes of the cannabinoid chemical receptor: CB1, found mainly in the brain; and CB2, found mainly in the peripheral immune system. Dr. Naguib's group has been doing research to see if the cannabinoid receptors -- particularly CB2 -- can be a useful target for new drugs to treat neuropathic pain. Neuropathic pain is a difficult-to-treat type of pain caused by nerve damage, common in patients with trauma, diabetes, and other conditions.
MDA19 was designed to have a much stronger effect on the CB2 receptor than on the CB1 receptor. In humans, MDA19 showed four times greater activity on the CB2 receptor than on the CB1 receptor. In rats, the difference was even greater. The experiments also showed that MDA19 had "protean" effects, so-called after the shape-shifting Greek sea god Proteus -- under different conditions, it could either block or activate the cannabinoid receptors.
In rats, treatment with MDA19 effectively reduced specific types of neuropathic pain, with greater effects at higher doses. At the same time, it did not seem to cause any of the behavioral effects associated with marijuana.
Potential to Develop Effective Pain Drugs that Avoid Side Effects The "functional selectivity" of MDA19 -- the fact that it acts mainly on the CB2 receptor and has a range of effects under differing conditions -- could have important implications for drug development. "[W]ith functionally selective drugs, it would be possible to separate the desired from the undesired effects of a single molecule through a single receptor," Dr. Naguib and colleagues write.
This means that MDA19 could be a promising step toward developing medications that have the pain-reducing effect of cannabinoids while avoiding the mental and physical side effects of marijuana itself. However, more research will be needed before MDA19 or other agents that act on the CB2 receptor are ready for testing in humans.
"These elegant studies by Professor Naguib demonstrate remarkable analgesic properties for this synthetic cannabinoid," comments Dr. Steven L. Shafer of Columbia University, Editor-in-Chief of Anesthesia &Analgesia. "The studies suggest a novel mechanism for this protean agonist. Although preliminary, these studies suggest that synthetic cannabinoids may be significant step forward for patients suffering from neuropathic pain."
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- Jijun J. Xu et al. Pharmacological Characterization of a Novel Cannabinoid Ligand, MDA19, for Treatment of Neuropathic Pain. Anesthesia & Analgesia, July 2010 vol. 111 no. 1 99-109 [link]
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