LOS ANGELES -- The Food and Drug Administration has fast-tracked human tests of what may be the first cure for methamphetamine addiction. The drug also may be the first non-opiate drug treatment for heroin and opiate addiction.
In a recent trial, UCLA researchers administered the drug Ibudilast, or MN-166, to 11 non-treatment-seeking meth addicts. The trial, the first of three phases of Ibudilast human testing required for FDA approval, was meant to test the safety of the drug taken in combination with meth. Researchers said the treatment appears to have passed the safety test and eased the addiction.
"Very preliminary results would indicate that Ibudilast may dampen craving and improve cognitive functioning," said Dr. Aimee Swanson, co-investigator on the trial and research director at the UCLA Center for Behavioral and Addiction Medicine.
Researchers have been trying to develop medication to treat meth addiction for more than 20 years. There were about 439,000 meth abusers in the U.S. in 2011, according to the Substance Abuse and Mental Health Services Administration's national survey. Meth addiction cost the country an estimated $23.4 billion in 2005 alone, according to a RAND Corp. study.
The only options right now for meth addicts seeking recovery are counseling, an in-patient rehab center or Narcotics or Crystal Meth Anonymous. These treatments don't work for many people, Swanson said.
"When we see people come to participate in the trial, it's really their last resort," Swanson said. "Many of them can no longer hold down a job, they have strained relationships with family members. Gone went the cars, gone went the business, gone went the house, gone went the kids. The main focus of this person's life is using meth."
The need for another option is dire, Swanson said. "It seems cruel and unusual to just leave them hanging." The FDA fast tracks treatments for serious or life-threatening conditions that demonstrate the potential to address unmet medical needs. The designation may lead to expedited regulatory review.
Ibudilast may prevent the activation of certain cells in the central nervous system, called glial cells, which have been linked to drug dependence, researchers said. "When you're on meth, your whole brain is saying, 'I need meth,'" Swanson said. "If you could block meth from interfering with glial, it would allow the messages that you would like to be sending and receiving to actually get to your brain."
"You could say, 'You know, rather than calling my dealer right now, I'm going to say no,'" Swanson said.
The 11 meth addicts, all paid volunteers, were housed in a hospital unit and were not allowed to leave for three weeks. They were intravenously injected with meth two or three times a week while they were treated with Ibudilast. Researchers determined that the combination was safe and will now move on to phase two of the trial, which will be funded by federal government research institute the National Institute on Drug Abuse.
Ibudilast was developed in Japan and has been marketed there and in Korea since 1989 to treat asthma and post-stroke complications. MediciNova, a biopharmaceutical company based in San Diego, Calif., licensed Ibudilast in 2004 as a potential treatment for multiple sclerosis. In 2005, the company partnered with NIDA and with other researchers to test the drug on animals, mostly mice and a few monkeys, that were addicted to meth.
The second phase of the UCLA study, expected to begin mid-summer, will be a 12-week trial of 140 treatment-seeking human meth addicts. Half the volunteers will take Ibudilast twice a day, and the other half will take a placebo. They will visit the trial unit three times a week for drug-craving monitoring, urine drug screens and medication adherence monitoring. The researchers said they hope the addicts taking Ibudilast will have reduced meth cravings and improved sobriety rates.
MediciNova, the only U.S. company with rights to Ibudilast, was founded in 2000 as a spinoff of a midsize pharmaceutical company in Osaka, Japan, that specializes in treatments for cardiovascular disease. MediciNova has rights to Ibudilast and other commercial drug candidates through alliances primarily with various Japanese pharmaceutical companies. None of MediciNova's products have been approved for U.S. sale. Its current CEO is Dr. Yuichi Iwaki, also a professor of urology and pathology at the USC Keck School of Medicine.
The UCLA study is small, "so it remains to be seen whether these findings hold up in larger studies where its effectiveness will be established," said Dr. David Sack, psychiatrist and CEO of Promises addiction treatment centers.
"Nevertheless the importance of this finding cannot be overstated," Sack added, saying there is "an urgent national need" for such a drug in clinical practice. "There are no effective treatments for amphetamine dependence despite more than a generation of research."
UCLA researchers said they expect the results of the 12-week phase-two trial to be released in early 2015. If the results are positive, there would be a larger phase three study and possible FDA approval by 2018.
TREATING HEROIN AND OPIATE ADDICTIONS
Ibudilast may also be the first non-opiate drug treatment for heroin and other opiate addictions. A team at Columbia University partnered with the National Institute on Drug Abuse and MediciNova to conduct a phase-one trial last year with 30 paid heroin addicts who lived in a hospital under supervision for three weeks.
The addicts were given morphine for two weeks and then a placebo for one week. Some of the participants, all sick from withdrawal symptoms, were given Ibudilast and others were given a placebo. If at any point withdrawal symptoms became unbearable, the participants were allowed to drop out.
The Ibudilast appeared to work. "The high dose of Ibudilast significantly reduced a subset of withdrawal symptoms," said Dr. Sandra Comer, professor of clinical neurobiology in Columbia's Department of Psychiatry and lead researcher on the trial, funded by the NIDA.
Recovering opiate addicts are currently treated with other opiates, such as methadone or buprenorphine.
"The problem with some of the opiate treatments for opiate addiction is that some people become dependent on the new opiate," said Johnson, chief scientific officer at MediciNova. "In some cases, it takes them years to finally get off the opiate." He added that even prescribed opiates are still dangerous, citing reports of individuals overdosing on the prescribed opiate meant to treat opiate addiction.
The researchers have begun conducting phase two of the trial on 24 non-treatment seeking heroin and prescription opiate addicts confined to a hospital unit for six weeks. The addicts will be stabilized on morphine for a few days, then slowly tapered off of the drug. Half will be given Ibudilast, and half will be given a placebo.
As the participants experience withdrawal symptoms, they will be given a choice between a dose of oxycodone, $20 or part of both. For example, a participant can choose to receive $10 with half of the oxycodone dose. Researchers said they hope the participants on Ibudilast will have reduced opiate cravings and will choose money over the opiate. The researchers said they plan to have results of the phase-two trial by the end of the year.
Ibudilast may also accelerate the pain-killing effects of opiates, so that opiates can be taken in lower doses. To test this, Columbia researchers gave participants in their phase-one trial high doses of oxycodone once at the end of the first week and once at the end of the second week. Both times, they put the patients' hands in freezing cold water. The individuals who were on Ibudilast in addition to oxycodone reported lower pain levels.
"If you can achieve good pain relief, with a lower side effect incident, that would be really beneficial for patients," Comer said. "There are all kinds of side effects of opiates like constipation, nausea and sedation. In addition, patients can become tolerant to opiates." Lower doses of prescribed opiates also lessen the risk of patients becoming addicted.