Ibudilast, a drug compound developed by a pharmaceutical company in Japan and licensed to San Diego, Calif-based MediciNova, is being tested by UCLA addiction researchers as the first-ever pharmacotherapy for methamphetamine addiction.
A very few pharmaceutical firms have shown an interest in developing drugs to treat substance abuse. MediciNova is one of them.
MediciNova licensed ibudilast, or MN-166, from the Japanese firm Kyorin Pharmaceutical in 2004. MN-166 has been marketed in Japan and South Korea for the treatment of asthma and post-stroke diseases for decades. MediciNova scientists discovered independently ibudilast's modulation of the immune response, and suggested it had potential as a treatment for opioid and methamphetamine addiction.
Several addiction experts took notice, including scientists with the National Institute on Drug Abuse (NIDA). So far, NIDA has awarded four grants to addiction researchers studying ibudilast's potential as a treatment for methamphetamine abuse.
There are an estimated 1.2 million methamphetamine users in the United States, according to a survey by the Substance Abuse and Mental Health Services Administration (SAMSA). But there's currently no approved medication for methamphetamine addiction.
Michael Coffee, chief business officer for MediciNova, says the drug was recently found safe in a Phase 1b trial of 12 methamphetamine-sing volunteers and will advance to a Phase 2 trial by UCLA researchers by early 2013. MediciNova, which holds patent rights to the drug through 2028, is providing the drug product, stability testing of the drug and regulatory oversight with the FDA, says Coffee.
Columbia University is studying the drug's impact on heroin users, and UCLA's Center for Behavior and Addiction is following its Phase 1b safety trial with a Phase 2 efficacy trial. The randomized, placebo-controlled trial will enroll 140 treatment-seeking methamphetamine users for a 12-week period. Researchers, led by principal investigator Keith Heinzerling, MD, an addiction specialist with the UCLA Medication Development Unit for Stimulant Abuse, will observe the impact the drug has on methamphetamine abstinence during the final two weeks of treatment.
"It's very rare for a pharma to work on medication for addiction," says Heinzerling. "For some reason they don't see the market potential." However, he said, ticking off some statistics,10 to 15 percent of Americans have a problem with drugs or alcohol. That's 1-out-of-10 Americans during their lifetime. Only about 25 percent of substance abusers are able to master their addictions through counseling and behavioral modification alone.
There's another reason drug companies might want to take a second look at addiction drug development. "Increasingly, insurance companies are more willing to pay for treatment for drug and alcohol problems," says Heinzerling. " There's a growing body of evidence that shows ending addiction potentially reduces health care costs. People who abuse substances often end up in the emergency room or hospital." Clearly, it's cheaper in the long run to help them get off the substances.
”It's critical that we have collaboration with companies and NIDA,” says Heinzerling, but to date, few companies have shown an interest in developing medications that might help combat substance abuse. MediciNova has the understanding of the drug's mechanisms combined with "the vision and courage" needed to stay with the research and approval process, according to Heinzerling. "
A condition such as meth abuse could be considered similar to an orphan disease treatment since pharmaceutical companies don't want to devote resources to it.
With few exceptions, the private sector isn't investing in drug addiction research. Heinzerling's colleagues at the UCLA center are also studying Chantix's (varenicline) usefulness in helping methamphetamine dependent people. (Chantix is already FDA approved for smoking cessation. It is believed to work by blocking some of the brain's nicotine systems and stimulating the release of small amounts of dopamine.)
How Ibudilast Might Work on Methamphetamine Addiction
Methamphetamine and other stimulants cause an inflammatory reposes – they “ramp up” the immune system, says Heinzerling. Meth use use interferes with glial cell secretions associated with the inflammatory response. When glial cells are activated they secrete chemical messengers that disperse and affect neurons and other cells. Ibudilast interferes with the glial cell response and may help keep the inflammatory response in better balance.
In petri dishes, ibudilast increases the secretion of glial cell-derived neurotrophic factor (GDNF), a growth factor that the brain secretes in response to injury. Researchers believe GDNF could also help counteract the toxic affects of methamphetamine.
Unlike some other drugs used to replace one addictive drug for another (such as methadone for heroin) ibudilast shows no evidence of dependency or addiction, says Heizerling. There's no “high” associated with it.
When withdrawing from meth, users go into a “fog.” They have a lower attention span and lack of focus that can last several months or a year while abstaining. Because ibudilast is believed to modulate the glial cell response, people withdrawing from meth may not feel the withdrawal effects quite so deeply. The goal is to help them feel good enough to stick with a course of therapy while their body returns to balance, says Heinzerling.
Heinzerling cautions that patients battling substance abuse will not find a medication that acts as a “silver bullet” for their treatment. Medication can help but does not do the work for the patient.