Is this a groundbreaking cure for opiates and 'benzos' addicts?

Australian doctor George O'Neil claims to have discovered a way to help addicts quit. But could it be derailed by his renegade approach?

Slow release: a client at the clinic shows his syringe infusion pump (David Maurice Smith/Oculi) (David Maurice Smith/Oculi)

Toru had always been an anxious child, but the problem worsened when he was 19 and attending college in Tokyo – he would feel his heart race every time that he had to present in front of his class – so a psychiatrist prescribed clonazepam, one of the drugs known as benzodiazepines (which also include Valium and Xanax).

Initially, Toru felt calmer. Soon, though, the drugs' potency began to wane and, after about a year, he quit taking them. His anxiety escalated. He stopped sleeping and began experiencing panic attacks, one so severe that he called an ambulance to take him to A&E. So Toru did the logical thing: he went back on the drugs.

Despite his struggles, Toru completed his degree and began working in IT. But he had developed a temper and struggled to hold down a job. At a particularly low point, he destroyed a computer and got fired. And then Toru stopped looking for work. Periodically, he would try to quit the meds, but the withdrawal symptoms always proved too severe.

Toru's mother, Machiko, was the first to realise how bad things were, but when she began calling his doctors, they stonewalled her. Finally, the pair went on a sort of extended drug treatment holiday, winding up in Brisbane, Australia. There, they met a doctor who said: "I would go directly to Dr George O'Neil."

George O'Neil is an unlikely saviour for the world's benzodiazepine addicts. A large man with a cherubic face, I first meet him at his summer home in Lancelin, about an hour's drive from Perth, where he and his family can congregate, away from his Fresh Start clinic. It's a safe haven from the deranged behaviour exhibited by some of the patients to whom he has devoted the last two decades.

Dr George O'Neil chats with a client about to receive an implant at his Fresh Start clinic in Perth (David Maurice Smith/Oculi)

O'Neil's quest began in the mid-1990s when a young woman asked for help with her husband, a heroin addict. Then 15 weeks pregnant, terrified about raising the child alone, she pleaded: "Surely there's something you can do." The woman was persistent and "very lovely", O'Neil remembers, and came back every month for a year and a half, begging for help.

O'Neil may have seemed an odd person for the woman to seek out. But she knew about his other life as a medical inventor, his best-known product being a catheter that halved the rate of urinary tract infections experienced by paraplegics; this was the money-maker that ultimately freed O'Neil to devote his life to addicts.

"In one short lifetime you could concentrate on 2,000 inventions," O'Neil tells me, but there's always one that really matters: "There's always a pearl." He found his in China, where he attended a talk on naltrexone, a drug that appeared to take the high out of heroin. It is a considerably more potent form of naxolone, which was already used to reverse opiate overdoses. He had his eureka moment, realised that tweaking blockers could rein in addicts' cravings, returned home and told the woman that he had figured out how to help her husband.

O'Neil's approach is beguilingly straightforward. Drugs known as "blockers" have been on the market for decades. At high doses, they reverse lethal overdoses, but patients undergo a rapid and excruciating detox. O'Neil suspected that, at extremely low doses, blockers could take the high out of opiates like heroin without causing agony.

Getting high requires fooling our bodies' cells. Normally, they keep things running smoothly through a system of keys and locks. "Keys" – hormones or neurotransmitters – gain access to cells by binding to specific receptors, or "locks". Drugs known as "agonists", including opiates and benzodiazepines, mimic these keys and essentially pick the locks. By contrast, "antagonists", or blockers, jam the lock – and take the high out of drugs. Why, reasoned O'Neil, would an addict continue taking a drug if it no longer feels good?

When O'Neil first started working with naltrexone, he offered it to patients as a daily pill. The formulation was too strong and triggered a rapid, painful detox. ("It half-killed me," an early patient told me.) Moreover, because forgetting or neglecting to take the pill was easy, staying on naltrexone required pure willpower. As Gary Hulse, a researcher at the University of Western Australia and one of O'Neil's long-time collaborators, puts it: "Why would any self-respecting heroin user take it?"

O'Neil set to work creating a method of delivery that the addict couldn't control, and developed slow-release pills, along with a medical device –almost like a Pez dispenser – to implant them. (These dispensers can last for almost a year and be re-implanted indefinitely.) Then, in the mid-2000s, he attended an addiction conference in London where he heard a talk by an Italian researcher, Gilberto Gerra, on flumazenil, a drug that seemed to block benzodiazepines in much the same way naltrexone blocks opiates. O'Neil was intrigued. He'd found his second pearl.

Benzodiazepines are among the most widely prescribed class of anti-anxiety drugs in the world. First introduced in the early 1960s, within a decade they had become the most widely prescribed class of all drugs in the world. Soon, however, signs began to emerge that they were far from benign. They have been linked to grogginess, cognitive impairment and dementia. Worse, addiction can set in within weeks, even at low doses, and the drugs can actually trigger the same conditions they're meant to control. Many countries now stipulate that they should be used for no more than four weeks, but such recommendations are frequently ignored.

PHREEEEE: the guiding principles of the Fresh Start clinic next to a painting of founder Dr George O'Neil's granddaughter (David Maurice Smith/Oculi)

Flumazenil was first identified as a benzodiazepine blocker in 1981 while scientists were actually trying to create an even faster-acting benzodiazepine. The drug had a half-life of just seven to 15 minutes, making it useful for quickly reversing an overdose – and America's FDA approved it for that very purpose in 1991. According to Gerra, it had the potential to become "the naltrexone of benzodiazepines".

Gerra's talk inspired O'Neil, who set to work developing a blocker for benzodiazepine addicts. He knew he wanted something long-acting and addict-proof, like the naltrexone implant, and initially patented a pump that delivered flumazenil intravenously over several days on an outpatient basis. But getting addicts to comply was difficult as the pump could be removed at will, so O'Neil created slow-release flumazenil tablets for an implant.

Jon Currie, director of the addiction medicine unit at Saint Vincent's Hospital in Melbourne, raves about both pump and implant. "I haven't done a gradual reduction of benzodiazepines in 10 years now," he says. "Flumazenil… has absolutely revolutionised the benzodiazepine withdrawal process." And so it was that, in January 2014, Toru and Machiko came to O'Neil; and in November I meet Toru in the small apartment he shares with his mother.

Now on his third implant, broad-boned, with a mop of thick black hair, Toru recounts his story in halting English. Returning home to face all the stressors that prompted him to take anti-anxiety meds in the first place scares him most, he says. His nurse, Noel Dowsett, adds: "His level of anxiety is really horrific, the most severe I've ever seen."

After 25 weeks without any benzodiazepines, Dowsett adds, Toru has managed to get his hands on some pills. However, O'Neil is unfazed. He says Machiko and Toru have been at loggerheads recently, and that it's good Machiko now needs to return briefly to Japan to renew her tourist visa. He hopes that Toru might stabilise while she's away – because getting off drugs is only the first step to recovery, a basic truth he's learned the hard way. Remember that woman, the one who got him into treating addiction so many years ago? O'Neil tells me that her husband stayed clean for 18 months before returning to heroin. His wife walked out. "And two days later, he killed himself."

Over time, O'Neil developed his own iteration of the 12-step programme called PHREEEEE (for pharmacology, home; relationships; environment; education; employment; entry to our community; and exit to where you live) and launched an empire of temporary detox houses, long-term facilities far from Perth (so addicts can recover away from their friends and dealers) and therapists.

Toru tried staying at Northam, a long-term clinic; but, isolated and overwhelmed, he soon returned to Fresh Start. It's where he now attends weekly therapy sessions (though any progress is hard won) and where I meet O'Neil one Wednesday morning. The waiting room is full and many patients loiter on the bench outside or squat under a nearby tree. To appease the area's otherwise well-heeled inhabitants, the building's exterior has been enlivened with enormous painted butterflies.

Small steps: naltrexone implants ready to be inserted into a client's abdomen to prevent opiates from binding with brain receptors (David Maurice Smith/Oculi)

O'Neil takes me on his rounds. An indigenous couple recount how they met during a stint at rehab, and the woman sobs when she tells O'Neil she has lost custody of her children. A young meth addict whose right arm is covered with an intricate dragon tattoo refuses any pain medications so that he can drive home immediately after receiving his naltrexone implant. I meet Vikki, a woman with purple hair and an easy laugh who shakes constantly, thanks to a side effect of the Seroquel that she takes to stay calm. O'Neil inserts another round of naltrexone into her abdomen, just below her navel: it's insurance against returning to heroin, Vikki says.

Over the years, O'Neil has experimented with naltrexone on opiate, meth, alcohol and gambling addicts. He suspects the drug can help over-eaters control their cravings and mitigate ADHD. Meanwhile, he's testing flumazenil on Parkinson's disease (it appears to reduce tremors) and hypersomnia. At one point, he puts me on the phone to a 71-year-old woman named Pat, a heavy smoker who – whenever she has the urge to light up – uses a flumazenil nasal spray that O'Neil invented.

However, this loose approach has made it hard for O'Neil to market his implants: "Naltrexone implants have not been approved for human use in Australia due to a lack of results from clinical trials," says the National Health and Medical Research Council website. And trials of flumazenil are even further behind. Meanwhile, O'Neil can only use his implants for research purposes, and is forbidden from advertising or actively recruiting new patients.

Some say that caution is warranted. Alex Wodak, president of the Australian Drug Reform Foundation, argues that blockers like naltrexone trigger too severe a withdrawal and even lead occasionally to death. But following protocol, O'Neil says, means prolonging patients' suffering. Besides, blockers square with his world view. He is deeply critical of any push to legalise marijuana, and he questions programmes that rely on methadone: "A 20-year-old [who's taking heroin every day] will become a 40-year-old who's taking methadone every day."

None the less, it's not entirely clear what, exactly, flumazenil is. Is it genuinely a blocker, or could it be on the side of the agonists? When Gilberto Gerra's patients experienced no hostility during withdrawal, he began to suspect that flumazenil calmed people by allowing some very limited benzodiazepine activity. His subsequent investigation found instances where neuropsychologists working with flumazenil had reached the same conclusion. And when he began publishing his findings in the early 1990s, a representative from the drug's manufacturer, Roche, actually called.

The drug, he agreed, was billed as a pure blocker to reverse a benzodiazepine overdose. But when Gerra told the rep that he believed the drug was a very weak benzodiazepine, the reaction was surprising. Gerra was told that Roche was looking into using flumazenil to treat epilepsy. And this was striking because the primary anti-epileptic medication at the time was Valium. "I said, 'Friends, if you are saying that you are experimenting with [flumazenil] as a weak anti-epileptic, you are admitting that this is being used like Valium, not a Valium antagonist,'" Gerra recalls.

More recently, O'Neil's associates at the University of Western Australia treated a woman for benzodiazepine addiction using flumazenil. Since she still experienced intense anxiety in certain situations, she was told to take a sublingual flumazenil tablet (another of O'Neil's inventions) every time she feels a panic attack coming on. "When you look at flumazenil," says Gary Hulse, "it's meant to be an antagonist, so it's meant to be neutral – no activity there at all. My observation is that it looks as though it may have agonist action. And then the question becomes: will it eventually be found to do the same things as the benzos? Could it itself be addictive?"

Maybe. And that's just one of George O'Neil's challenges. As it stands, the entire enterprise that he has built exists perpetually on the brink of financial ruin. Although he receives funds from various official and private sources, most of his patients are treated for free. And while the clearest way to make money would be for him to sell the patent on his implant – for which he has had lucrative offers – the thought makes him feel queasy. If drug addicts had to buy his treatment, he says, only three per cent of his patients would be able to afford the procedure. What he doesn't want is a "middleman" who is going to exploit addicts and make lots of money for himself.

Alternatively, O'Neil could push forward on the research front to legitimise his work. (He prefers to turn over his work to the UWA for them to judge what's most promising and to sort out the specifics.) But ironically, in outsourcing his larger research goals, he could actually bolster benzodiazepine use. Hulse's greatest hope is that, once proper dosage and delivery methods have been determined for flumazenil, doctors will feel comfortable prescribing benzodiazepines beyond a few weeks. Someone like Toru, for instance, could cycle on and off benzodiazepines without coming unhinged. And that, says Hulse, could revolutionise the use of benzodiazepines to treat anxiety.

As for Toru, he and Machiko fought about his benzodiazepine use for years. While she believed that even a single pill a day distorted his personality, he wasn't so sure. And now his life seems suspended. Without anti-anxiety medications that can work as well as benzodiazepines, his path to recovery remains murky. He fears returning to Japan, where all his stressors reached a head, yet he has struggled to learn English. And given his extreme social anxiety, he has met few people outside the rehab clinic.

As we speak, Machiko tries to reassure him. "Tapering off the medication is the first step," she says. "It takes some time, like language learning… And there is no silver bullet. You should be very, very patient."

This is an edited extract from an article originally published by mosaicscience.com