There are a million heroin users in the US, and the UK has Europes highest rate of use. It is a huge problem. But can there be a chemical answer to a social issue?
The effect of heroin has been described as a warm blanket on the brain. Within seconds of the drug entering the bloodstream, it hits receptor molecules in the brains neurons that induce a surge of euphoria, followed by a prolonged sense of tranquillity. Yes, it feels good and thats the problem.
But what if you took heroin and felt nothing? What if there was a treatment that cancelled its effects on the brain? Who then would bother to take it?
That prospect is raised by the development of a vaccine against heroin. Researchers in California recently announced a vaccine that can block the narcotic effects of heroin in mice and monkeys, and they say that human clinical trials are on the horizon. The idea is that a single shot of the vaccine could nullify its mind-altering effect for several weeks at a time, potentially breaking the cycle of drug use. A vaccine works by cancelling out expectancy, says behavioural psychologist John Marsden in the addictions department of Kings College London. The user knows that theres no point in taking the drug to get the hit he or she craves, and so they stop trying.
But a heroin vaccine is controversial. Some say that breaking the habits of addicts is more than a matter of stopping the drug from working you need to address the underlying reasons for drug abuse. A heroin vaccine might find a role in combating the epidemic of drug use, but its no panacea.
Heroin and other opioid drug use is a devastating social problem, and in many places its getting worse. The number of heroin users in the US tripled to one million between 2003 and 2014, and heroin abuse is estimated to cost the US around $50bn a year. Deaths from overdose have tripled in the past 15 years, and injection of the drug has spread HIV and other diseases transmissible through blood. About eight in every 1,000 Britons are high-risk opioid users the highest ratio in Europe.
Describing drug abuse as an epidemic is already to imply that it is a kind of disease. And indeed that is how it is regarded by medical organisations such as the American Medical Association; the US National Center on Addiction and Substance Abuse in New York calls it a complex disease of the brain and body. After all, like many other diseases it can be inherited: genetic factors seem to account for as much as half of the risk that an individual will develop drug addiction.
If addiction is a disease, then talk of treating it with a vaccine perhaps sounds a little less strange than it might at first seem. In this case, though, the vaccine wouldnt be doing what it normally does, which is to stimulate immunity to an agent of disease such as a virus. Instead, it would inhibit the effects of the addictive substance.
Vaccines against addiction have been discussed for decades. There was some research into a heroin vaccine in the 1970s, but more effort was put into developing vaccines against nicotine and cocaine in the mid-1990s but it all came to nothing. As with any vaccine, the general idea is to administer a chemical, called a hapten, that, when carried by a larger molecule such as a protein, stimulates the bodys immune system to produce antibodies: protein molecules that recognise and stick to the hapten. By using haptens that closely resemble the disease agents, the hapten-carrier combination can train the body to fight off the real thing. This immune response is often boosted by secondary chemicals called adjuvants in the vaccine.
The early work on a heroin vaccine was abandoned in favour of other treatments. Replacement therapies use regulated, less dangerous opioid drugs such as methadone to wean users off heroin without nasty withdrawal symptoms. And there are drugs that can also block heroins psychotropic effects, in particular naltrexone. Unlike a vaccine, which would deliver long-term immunity to the opioid, blockers such as naltrexone have to be taken regularly typically as daily pills and so they depend on the user having the discipline and motivation to do so. Naltrexone is also used to treat alcohol addiction, as it can reduce the pleasant feelings of intoxication and reduce craving.
But naltrexone can introduce complications of its own. It has some side effects including tiredness, anxiety and gastrointestinal disorders. And some users, finding that heroin had no effect, simply tried taking a larger dose to overcome the inhibition. This led to some instances of fatal overdoses in Australia, where naltrexone was administered by a surgical implant that the users could not regulate themselves.
Pharmaceutical chemist Kim Janda of the Scripps Research Institute, a biomedical research centre in La Jolla, California, felt that, despite the lack of previous success, the vaccine approach to addiction was worth pursuing. Some of that earlier work, he says, was not careful and tried to rush things through. The researchers didnt do their homework.
For one thing, he says, the vaccines for nicotine and cocaine used poorly designed haptens and adjuvants, so they didnt induce effective blocking in most patients during clinical trials. Whats more, it was a mistake to think that the drug itself was the right target: the heroin molecule is not the active agent: it is a prodrug, a substance that breaks apart in the body to produce the agent that latches on to and activates receptors in the brain. The hit is delivered by the closely related opioid morphine, into which heroin is degraded in the body. But heroin is more effective than morphine because, unlike morphine, it can pass relatively easily from the bloodstream into the brain.
So the vaccine needs to raise antibodies not just to heroin but to morphine, Janda says and also to another opioid called 6-acetyl morphine, an intermediary in the conversion of heroin to morphine.
He and his co-workers have carefully crafted all aspects of their vaccine: hapten, carrier and adjuvant. They have tested their best formulation on mice and rhesus monkeys, finding that it can block the effects of heroin for at least eight months if administered by injection every three months or so.
Janda says that his vaccine can actually protect against a lethal heroin overdose, reducing the risk of a user taking a massive heroin dose to try to beat the block. He is now hoping to move to clinical trials in humans if he can find a supportive biotechnology company. Thats when well really find out if the treatment works.
Some specialists in drug addiction have cautiously expressed their approval. Vaccines prevent the high, says Eugenia Oviedo-Joekes of the Centre for Health Evaluation and Outcome Sciences in Vancouver, and not everyone is ready for that. Vaccines, like any other pharmacological treatment in addiction, will have only a modest and specific success.
Vaccines are meant to be used by people who want to quit taking drugs, agrees Janda. If you dont want to stop then nothing will help. The idea is that if they have a moment of weakness, they wont relapse and can continue with their therapy.
Marsden agrees that vaccines could be effective for a subset of drug users. Vaccine development is to be welcomed for people who are seeking relapse prevention therapy, he says. But I doubt they will be the end game that some might want to claim.
The limitations of the approach, though, get at the heart of drug addiction, Marsden says. Its not like the craving that tempts us towards the box of chocolates, but is a deep resetting of neurological pathways. Addiction recalibrates the brain so that the user remembers past drug experiences and feels compelled to seek out new ones, Marsden says.
Whats more, serious drug use is often a response to social and psychological trauma and pain a product of ones environment and experience. Its not a disease like looking down a microscope and seeing a bacillus, says Michael Kelleher of the Lambeth Addictions Consortium in south London. It affects the poorest and most deprived parts of society and takes away psychological distress. Well over half of the female clients at Kellehers Brixton-based centre have been sexually abused, hesays.
So many users are seeking an opioid high not simply to enjoy the euphoric experience but to escape from distress. Thats why Kelleher says that many clients prefer to accept a regulated substitute, such as methadone, that delivers a similar hit with less risk, than to take a blocking therapy such asnaltrexone.
Besides, there are plenty of other drugs that produce effects similar to heroins. A whole range of synthetic opioids is now available, says Kelleher. The user might just move to something stronger. Then the situation might be like the evolutionary arms race in the development of antibiotics: vaccines would keep having to adapt to the latest opioid.
I applaud the science, says Kelleher. It should definitely go forward, and who knows where these things end. But Id be cautious, especially in the light of experience with the cocaine vaccine. Addiction is littered with miracle cures which never quite lived up to their name.
Oviedo-Joekess colleague Kurt Lock in Vancouver, who has been working for 20 years on the frontline with people using street drugs in the city, agrees. Some users may not be ready for such a treatment, he says, because they may lack many of the basic life skills required to perform in society, and struggle with other issues such as anxiety, depression, anger and homelessness. It would be essential to have the proper care available to address those needs in a constructive way, he says, otherwise the situation may turn for the worse with the user switching to other substances or being at a greater risk of suicide.
Still, Lock too sees a role for a vaccine. Assuming that the heroin user is not in any way coerced into taking it, a vaccine sounds very promising, he says. Its essential that the patient be ready and willing to take it. If the vaccine is able to eliminate withdrawal symptoms and cravings, then there are opioid-dependent users positioned to take the next steps toward an alternative life without drugs who would likely do quite well with the vaccine.
A vaccine could be a good combination therapy with psychotherapy to look at the underlying issues, agrees Marsden. But Janda has no illusions of any miracle cure. Vaccines will be another tool in treating addiction, its as simple as that, he says.
He says he has received encouraging responses to his work from Francis Collins, the influential head of the US National Institutes of Health, as well as from the National Institute on Drug Abuse. They understand and appreciate what were doing, he says, but we need to get to clinical trials before they will commit.
Janda thinks that the idea of addressing addiction by nullifying drug effects could be applied very widely. We have looked at just about every drug you can think of, and the potential is there, he says. Last week his team announced in Nature a vaccine against the synthetic amphetamine-like stimulant fenethylline, which has created a widespread addiction problem in the Middle East. It was previously unknown which of the chemical agents into which the drug breaks down in the body was responsible for its mind-altering effects, but Janda and colleagues were able to identify the active molecules by using different hapten molecules to raise antibodies in mice in effect vaccinating them against each of the possible candidate chemicals in turn.
A vaccine is not the only way to block a drugs action. For nicotine, for example, Jandas team has been studying an enzyme that can break down the molecule before it delivers its alluring buzz. I think this enzyme could have a huge impact on nicotine cessation therapy, he says.
Smoking is of course also a potentially lethal addiction, and quitting can be very challenging. But heroin addiction is not only potentially more dangerous and damaging; it is also more closely linked to social and environmental factors that no medicine can remove.
In a way, then, a heroin vaccine might force us to confront some unpalatable truths. What might look from one angle to be a medical problem with a potential pharmaceutical fix is also an issue of social justice and inequality, and of responsible state intervention. Oviedo-Joekes says that many of the people she works with have a long history of marginalisation, and that the risk factors include not only poverty and lack of family support but also draconian drug policies that put people at higher risk. In other words, while pills, injections and vaccines might help individual users, drug abuse is a social disease for which we dont yet have a cure.
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