Ibudilast: MediciNova's Meth Treatment Might Also Help Against Opioids
The small biopharmaceutical company MediciNova, located in San Diego, recently announced that the U.S. Food and Drug Administration has fast-tracked one of their top drug candidates, known as MN-166, for the treatment of methamphetamine addiction.
In the eyes of the FDA, MN-166 is considered a new molecular entity. But in reality, this drug has been on the market for other indications in Japan for more than 20 years, where it is known as Ibudilast and where it has established an enviable safety record.
"MN-166 is the same drug that is approved in Japan," says Michael Coffee, MediciNova's Chief Business Officer. "It is not an analog. The difference is that in Japan the dosage recommended is 30 mg per day. Our preferred dosing range, for all the indications we're working on, is 80-100 mg per day."
MN-166 Against Opioid Addiction
Those indications include addiction treatment beyond methamphetamine. The company also believes the drug has potential for treating opioid addicts as well.
Currently most standard treatments for opioid addiction themselves also harbor an opioid - like Suboxone and Methadone. While this appeals to some addicts, it does not appeal to others who want to begin an opioid-free life as soon as possible. So the first concern is whether this drug is an opioid.
Is MN-166/Ibudilast an opioid?
"Ibudilast is not an opioid," says Coffee. "It was originally developed as a non-selective phosphodiesterase (PDE) inhibitor for the treatment of bronchial asthma."
Ordinarily when we talk about pharmaceutical treatments for opioid addiction we talk in terms of opioid receptors in the brain, but that's not exactly the case here. Or at least it doesn't tell the whole story. While MN-166 does appear to respond to opioid receptors in the brain, it might have another trick up its sleeve.
Addressing withdrawal symptoms
Opioid addicts fear withdrawal over everything else; this fear is so great that it prevents many addicts from seeking treatment sooner. Therefore any opioid addiction treatment has to address, in some meaningful manner, the dreaded withdrawal syndrome: anxiety, crawling skin, diarrhea, nausea/vomiting, sweating, runny nose, dilated pupils, and the rest of the nightmare that is withdrawal.
In drugs like Suboxone, there is a partial opioid to feed those opioid receptors. If MN-166 is not an opioid, how can it contribute to blunting some of those symptoms? By blocking opioid-induced glial activation.
Glial Cell Attenuators
Glia likely compose about half the mass of the brain and are far more numerous than those better-known brain cells, neurons. Opioids increase the activation of glial cells, and it appears that they contribute to the reward pathways that make opioids so addictive. The more those pathways are illuminated, the greater the tolerance, and the higher the addict will dose to achieve the same high.
This is the genesis of dependence and addiction; now physiological changes are being made in the reward-happy brain to accommodate more and more of the drug that is activating the glial cell reward pathway.
Given this activation and given their abundance, they become a particularly attractive treatment target, but the treatment would need to attenuate this activity - in other words, inhibit it.
MN-166 appears to do this. The net effect is a decrease in withdrawal symptoms and, as importantly, a reduction in the cravings created by the influx of hungry reward pathways.
The Development Process
Currently researchers at Columbia University and the New York State Psychiatric Institute are conducting a Phase 2a clinical trial of MN-166 against opioid dependence.
Additionally, MediciNova is working with the U.S. FDA on developing future trial protocols in an effort to bring this drug to the U.S. market as soon as possible so that opioid addicts might finally have a non-opioid based treatment option when they decide they're ready to get clean.