Future drugs

All around the world, things are rapidly changing. There are signs the War on Drugs may be running out of steam, new technologies promise new treatment possibilities, and scientific developments may be altering the very nature of drugs themselves. Here in New Zealand, bold new policy initiatives mean the treatment landscape will soon look vastly different. Rob Zorn talks with a few experts about what we can expect to see over the next few years.

Future dug policy

Regulated cannabis use is now legal in two American states, and the signs are other states will follow. Does this amount to an undermining of America’s staunch prohibitionist stance? And what implications might that have for future international drug control policy?

It seems many of the hard lines in the War on Drugs are slowly turning into soft and widening cracks.

Holland’s regulated cannabis cafés have been famous for years, but other countries have gone much further.

Portugal, for example, has become the poster state for drug law reformers globally. In 2001, it decriminalised all drug possession for personal use, resulting in plunging HIV rates, more receiving addiction treatment and an overall decline in drug use.

Uruguay has announced plans to legalise state-controlled cannabis. Colombia’s and Guatemala’s presidents have called for a debate on legalisation to help reduce drug-related crime. Costa Rica has decriminalised personal use, and Brazil and Argentina have referenda coming up on whether to do the same.

Most shocking and perhaps most promising of all, however, were the referenda held in the November 2012 American elections that legalised cannabis in Washington and Colorado.

What’s remarkable about this is that America has long been the stronghold of global prohibitionist mentality. This is a country where more than a million people (up to half the prison population) are incarcerated for drug offences at any one time. In fact, until recently, prohibition has been embedded so deeply in the American psyche that openly supporting drug policy reform has been a complete non-starter for most politicians.

Director of the Global Drug Policy Program at the Open Society Foundation Kasia Malinowska-Sempruch says it can’t be emphasised enough that the changes in the successful states were not pushed through the legislature; they came from the voting public.

“Anyone who’s had a dinner table discussion about drug policy knows there is significant support for reform in America, and there’s a growing understanding that the War on Drugs has failed. The numbers show Americans aren’t just thinking about it any more. They are ready to cross the threshold now and actually do something.”

And ironically, it’s been America’s enthusiastic investment in the War on Dugs that has hugely contributed to changing public opinion.

Malinowska-Sempruch believes people are now starting to see that the epidemic of arrests, debilitating stigma, mass incarceration and disproportionate penalties have not achieved any of prohibition’s stated goals. And news stories about the savage drug war butchery that happens almost daily in places like Mexico are perhaps making many wonder whether those espousing alternatives are worth another listen

“They’ve also seen that the sky doesn’t necessarily fall when you introduce newdrug policy models,” Malinowska-Sempruch says.

“The cafés in Holland did not provoke a massive spike in drug use. In fact, lifetime cannabis use there is lower than for many European countries, and among 15 to 16-year-olds, it is much lower than in the US. Similarly, Portugal did not witness an explosion of drug use when it decriminalised.”

And what’s happened in Washington and Colorado may just be the tip of the iceberg. Oregon also had a referendum to legalise recreational cannabis use, which only narrowly failed. Rhode Island and Maine have signalled plans to introduce similar legislation, and California almost crossed the legalisation line with Proposition 19 during the November 2010 mid-term elections.

It is likely even more American states will now be emboldened to pursue their own policies, and perhaps most importantly, politicians will be less reticent about their support for a public health approach. How quickly reform will spread across the US remains to be seen, but there’s little doubt there will be increased pressure on the federal government to relax domestic War on Drugs policies at a national level.

In fact, says Malinowska-Sempruch, the response to Colorado and Washington from the White House will be interesting as cannabis use is still illegal under federal law.

“Will the federal government sue? Will the Drug Enforcement Administration start patrolling the streets of Denver and Seattle? That all seems pretty unlikely.”

The Obama administration is indeed in a difficult position. On the one hand, it is committed to prohibitionist UN drug conventions, but it also has a responsibility to uphold democratic change. If it does try to counter the Washington and Colorado referenda, its most likely approach will be to hold state officials criminally accountable for administering legalisation and regulation, but the changes in public opinion probably mean this will be an unpopular move.

America is also facing international pressure to relax its hardline approach at home. Colombia, Mexico and Guatemala have all called on the US to consider other approaches such as decriminalisation. These are producer or transit countries that have long been plagued by black market violence and crime as a result of illegal drugs largely destined for the US.

How much this internal and external pressure will affect the international drug control policy stage, where America has such a strong and conservative voice, is presently anybody’s guess. But at the very least, Malinowska-Sempruch speculates it should encourage the sort of debate that has been suppressed until now.

“It’s been bottled up for so long, and perhaps now these initiatives will set off lots of calls for discussion at state, federal and international levels. There isn’t a country on earth that hasn’t been affected by bad drug policies,” she says.

Mike Trace, Chair of the International Drug Policy Consortium, says America’s prohibitionist influence has been slowly waning in the face of undeniable successes in places like Portugal.

“But with public opinion changing and the Latin American countries saying they’ve had enough, America’s certainty has now become irreversibly fractured. It’s going to be difficult to continue pushing such a hard and simplistic line when your own people and neighbours are all saying something different.”

Nevertheless, Trace doubts there will be an immediate global rush towards something like the Portuguese model.

“There are plenty of states, such as Russia and some Asian countries, still wanting to eradicate their way out of this social problem, so I think we’re yet a long way from finding the sort of consensus that will result in worldwide drug policy reform.

“One thing we could get broader agreement on is moving away from arrests and harsh punishments for people who use drugs. We are seeing a growing consensus that the money used for incarcerating and punishing users is not at all money well spent.”

And while hardliners remain, UN leadership seems well aware there is a new global mood for change. Trace says a General Assembly Special Session on global drug control strategy, originally scheduled for 2019, has been rescheduled for 2016.

“At the UN, where everything happens at a snail’s pace, bringing something forward by three years amounts to great urgency.”

So what happens during the years leading up to 2016 will be really important. Organisations like the International Drug Policy Consortium will be doing what they can to influence UN leaders and ambassadors towards a more enlightened approach, but the future of global drug policy may well depend significantly on just what America does next.

Future treatments

If there’s one thing we know about future addiction treatment in New Zealand, it’s that things will be very different – and perhaps in unexpected ways. Resources will be tight and demand will be high, but could new advances in computerised treatment be the answer to all our problems?

Co-chair of the National Committee for Addiction Treatment Robert Steenhuisen says government policy released during 2012 presents a pretty bold vision for New Zealand’s mental health and addiction sectors that will require innovation in how future treatment needs are met.

“The first thing that becomes abundantly clear is that we will need to do much more with the same or fewer resources,” he says.

“Increasing younger and older populations, ethnically diverse groups and the knowledge that alcohol and drug problems have a significant impact on other sectors like education, health, welfare and justice mean demand for services is only going to increase.

“In fact, Health Workforce NZ predicts a doubling in required treatment over the next decade. But this is all occurring against a background of increased demands for accountability and efficiencies, and there will only be a modest increase in funding. We simply have to find ways to be much more efficient.”

Traditionally, addiction services have understood their target as being the 3 percent of the population most impacted by mental health and addiction problems, but Steenhuisen says a new ‘whole of population’ approach will mean a reorientation towards earlier intervention and a much broader focus on the wider impact of substance abuse.

You’d have to wonder how the New Zealand treatment sector is going to cope.

One way might be by embracing new developments in interactive computerised technology being used to augment conventional treatment overseas and providing enhanced outcomes and more efficient use of counsellor time.

For example, computer-based training for cognitive behavioural therapy (CBT4CBT) developed by Yale University’s School of Medicine, uses videos, quizzes and games to help patients recognise and avoid situations that put them at higher risk of using and to teach skills for refusing drugs and coping with cravings.

CBT4CBT trialled well, with 66 percent of participants returning drug-free urine samples for longer, as opposed to 47 percent who did not use CBT4CBT. In the trial, it was used with patients before their twice-weekly sessions with counsellors, and its developers suggest it works so well because it helps patients focus on their most acute problems when they meet with clinicians.

The Community Reinforcement Approach Plus Vouchers programme (CRA+), developed by the National Development and Research Institute in the US, also uses videos, quizzes and games to teach abstinence and life skills, such as self and financial management.

However, CRA+ can also interface directly with a clinic’s urinalysis equipment. It analyses samples and prints out motivational monetary vouchers where they are negative. If samples are positive, it identifies the drug traces present and goes through interactive exercises with the patient to assess the circumstances of their drug taking and develops a personalised plan to help the patient avoid using in future.

The Video Doctor is part of a computerised program called Positive Choice, which has been trialled at five clinics in the San Francisco area. Clients log in to Positive Choice in a private area of the clinic. If they report drug taking or some other risky behaviour, such as unprotected sex, the Video Doctor appears and makes a brief intervention by selecting the most appropriate from a large store of files and video clips.

After their Video Doctor session, the client receives a printout out summarising the main points covered along with some suggested next steps. Their physician receives a summary of their risky behaviours, suggested counselling approaches and a list of appropriate treatment centres.

Video Doctor’s proponents say one of its strengths is that it overcomes factors that may impede assessment and counselling such as discomfort with talking about sexual practices and drug use and patients’ fear of stigma.

The Dartmouth Psychiatric Research Center in New Hampshire has produced a range of internet and mobile phone technologies that also offer evidence-based psychosocial interventions including goalsetting and monitoring, drug use analysis, self-management, drug refusal skills, problem solving and counselling. They are currently developing a model especially for people with co-existing problems.

Along with cost savings, computerised interventions promise to increase access to treatment because counsellors who delegate some of their routine clinical functions to computers will be able to schedule more patients. But how likely is it this sort of technology will catch on in New Zealand and what sort of difference could it make here?

According to National Addiction Centre Deputy Director Fraser Todd, these interventions can be as effective as one-to-one counselling for people with mild to moderate problems, and the cost savings and efficiencies they bring make their use here inevitable.

“An awful lot of treatment could be delivered using computers. In fact, there’s not a lot that can’t,” he says.

“I suspect they could even make clinicians redundant for a wide range of problems.”

What Todd means is that a person with mild to moderate needs may not need to see a clinician or may not need one right away, because they could receive computer-based treatment supervised by someone differently qualified. A nurse with general skills, for example, could work through a programme with a drug-dependent person and rely on the software for the in-depth knowledge about drugs and counselling required.

“It won’t work for everyone, and we’re always going to need clinicians for more serious cases, but I can see a real shifting of roles occurring in the future, especially towards primary care, as computerised interventions become more mainstream,” he says.

While there has been some work done in New Zealand’s addiction treatment sector around computer-based education programmes, it is unlikely we’ll be developing anything of our own to rival overseas interventions any time soon. And there’s probably no need to.

Todd believes we should simply buy the software from overseas developers, most of whom, he says, would be willing to supply modified versions that are culturally appropriate for New Zealand.

“The Dartmouth program, for example, sell for about the cost of two clinicians’ annual salaries. And when you think about the efficiencies and cost savings involved, buying them just makes good sense on all sorts of levels.

“But the question this raises, of course, is what are we going to do with all our surplus clinicians?”

And yes, he’s serious. Computer-based interventions could downsize the need for clinicians so much that a lot could find themselves out of work.

“Sure, this stuff is still in its infancy, even in the States, but it’s the sort of thing that will take off very quickly. There’s a real risk that some enthusiastic government is going to do the maths, see the potential savings and try to put this in place here overnight.

“It’s really important we take the time to implement it properly, say over 3–5 years, and that the government works with the treatment sector to make sure risks like this are managed.”

And, of course, computerised interventions will never be the answer to all our problems. In fact, they are likely to introduce a few new ones, and New Zealand having to deal with having too many treatment specialists will be a very unique problem indeed.

Future drugs

Wouldn’t it be great if you could enjoy the pleasures of alcohol without all the negatives, such as hangovers, liver cirrhosis and drunk-driving convictions? Professor David Nutt thinks current scientific ability to target specific areas of the brain means such a drug may not be too far off and that ‘synthetic alcohol’ could also function as an effective treatment tool for alcoholism. And if we can make synthetic alcohol fly, what else might we be able to do?

Medical problems associated with alcohol are increasing alarmingly in the developed world. Deaths from liver disease are rising rapidly and may soon overtake heart disease as the biggest killer.

In fact, a recent assessment of drug-related health hazards in the UK scored alcohol as the worst drug overall. It is so toxic that, if introduced today, it would be among the most controlled of substances. And it is a poison without an antidote.

Alcohol is metabolised into acetaldehyde, which literally pickles the liver (and other organs) over time, leading to acute illness and death.

And alcohol has a number of more immediate effects because it affects so many different GABA neurotransmitters, of which there are many subtypes, in the brain. These effects include loss of inhibition, memory impairment, sedation, relaxation and interrupted motor neuron control.

Professor David Nutt, former advisor to the UK Government on drug policy, thinks it is high time we used what we know about neurons and how to target them to develop safer, alternative intoxicants that deliver the same results as alcohol but without the harms.

He suggests that, with current knowledge, it would be possible to develop a substance that targeted the GABA neurotransmitter subtypes that affect relaxation and intoxication in the brain in the same way as alcohol but do not affect, for example, the subtypes controlling memory or steadiness.

Furthermore, the benign effects of consumption could be reversed by antidotes. He points out that antidotes already exist for some of the effects of benzodiazepines, which stimulate GABA action in much the same way as alcohol. If adapted for alcohol, this would mean, effectively, you could ‘take a pill’ after indulging in a heavy drinking session and be perfectly safe driving home.

And of course, other benefits to synthetic alcohol would include that it doesn’t target neurons associated with addiction and that it would not break down into toxic acetaldehyde and slowly but surely kill your liver and you. “Considering its obvious benefits in reducing harm, synthetic alcohol is bound to happen in the future,” Professor Nutt says.

“What’s probably making this unviable at the moment is the implicit assumption by the public and legislators alike that alcohol is a foodstuff rather than a drug. Current regulations mean that replacing alcohol with a ‘real drug’ would be challenging. It might have to pass the same safety hurdles as medicines rather than the much lower hurdles for foods.

“But if governments signalled they wanted a safe alternative to alcohol, I am sure the combined skills of the pharmaceutical industry and academia could rapidly produce viable candidates.”

Nutt admits synthetic alcohol would not quickly become a ready substitute for the average drinker. Those who enjoy going out to a wine bar or who like a few ‘brews with the bros’ are not going to see a flavoured cocktail with added artificial alcohol as an attractive alternative.

But for those whose purpose in drinking is primarily to get drunk rather than to savour deep cherry undertones or the light refreshing bitterness of Pacifica hops, it might be just what the doctor ordered. Quite literally.

While ordinary members of the public could conceivably choose to take synthetic alcohol to a party rather than their usual six-pack – sober drivers, for instance, or those with a big day at work tomorrow – its most immediate benefits are for those in treatment or needing to reduce the harms associated with their consumption.

Being non-addictive and far less physiologically destructive, synthetic alcohol could be used as replacement therapy in much the same way methadone is used for those addicted to heroin and other opiates. So, synthetic alcohol as an approved medication could be a first step towards mainstream acceptance, once governmental red tape is overcome.

Eventually, those whose alcoholism is only in early stages could be encouraged towards a synthetic alternative, and some may avoid what might have been an inevitable addiction by choosing it early on.

Nutt first proposed the notion of synthetic alcohol in 2004, and the idea is catching on. A 2008 Sigma Scan (by the UK Government Office for Science) predicted the advent of just such a drug. In fact, it went much further, suggesting enhancement through lifestyle drugs may well become the norm in the future as we get better at targeting certain receptors in the brain.

‘Cogniceuticals’ could improve memory, our ability to learn and even our decision-making abilities. ‘Emoticeuticals’ could enhance our responses in private life or in challenging work situations, such as those that demand high motivation. ‘Sensoceuticals’ might enhance pleasure by restoring or accentuating the senses. Special sleep drugs could condense a refreshing night’s sleep into a few hours or allow us to skip bed altogether with no ill effects.

These futuristic drugs are almost exciting as flying cars, jetpacks and meals in a pill, but no doubt they will come with a raft of challenges and ethical implications that governments will need to sort through.

“In the meantime, though,” says Nutt, “governments should be doing all they can to expedite production of substances like synthetic alcohol. What’s at stake for them here is a future with fewer substance-addicted citizens.”

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Getting your anti-drug shot

Their kids starting smoking is every parent’s nightmare. Most will dabble with cigarettes at some stage, and many will become addicted.

Wouldn’t it be great if we could just have our kids vaccinated for nicotine (or any other drug – like methamphetamine, for example) at the same time they get their shots for measles, mumps and rubella?

Well, a study published in Science Translational Medicine in June 2012 claims just such a thing is not only possible, it already exists.

According to Dr Ronald Crystal, Professor of Genetic Medicine at New York’s Weill Cornell Medical College, a vaccine can be created to prevent addiction to any substance, from nicotine to methamphetamine, for the rest of one’s life.

The vaccine works in exactly the same way as one used to prevent disease. A small amount of a specific type of drug is introduced to the body, causing the immune system to create antibodies. Before the drug can pass through the blood to the heart and brain, the antibodies destroy it, making it impossible for the user to feel the drug’s effects – a bit like what happens with varenicline tartrate (Champix).

The difficulty until now has been that molecules within addictive substances like cocaine, methamphetamine and nicotine are so small, they tend to be ignored by the immune system. To combat that, scientists created synthetic versions of the molecules and attached them to larger proteins, which makes them a little more noticeable. Finally, they add what is known as an ‘adjuvant’, a chemical mix created specifically to attract the immune system.

In Dr Crystal’s study, the process worked really well with mice. Scientists are now preparing to test the vaccine in rats and then primates before humans.

Addiction-proof painkillers

Opioid painkillers have long been a two-edged sword, and the world is full of people who once had chronic pain but now have addictions to their medication. For years, scientists have been trying to separate the pain-relieving characteristics of opioids from the addictive high they offer, and until now, most thought it impossible. A recent study published in the Journal of Neuroscience has found a drug that not only reduces the addictiveness of prescription painkillers but also boosts their effectiveness.

The drug, (+)-naloxone, is a molecular mirror image of the drug naloxone, which is used as an overdose antidote. In the study, scientists found that, when rodents were given a combination of (+)-naloxone and opioids, the drug seemed to prohibit the expected effects of the opioids.

When given an opioid such as morphine, test subjects displayed the usual characteristics of addiction, including self-administering the drug. However, when given a dose of (+)-naloxone with the opioid, the subjects exhibited no characteristics of addiction.

Lead author Dr Linda Watkins of the University of Colorado says she thinks that, when administered, the drug interacts with glia, immune cells that make up 90 percent of the brain. When standard opioids or painkillers are administered, glia enhance the activity of the neurons that respond to the drug. However, over an extended use of painkillers, they become increasingly active, reducing the drug’s pain-relieving effect and increasing tolerance. Ironically, as glia become more active, they also produce pain, effectively eliminating the painkilling effects of the opioid.

But when (+)-naloxone is introduced, it has an immediate calming effect on glia by blocking a type of receptor they contain. By calming the glia, less pain is caused, more is prevented, and negative effects such as addiction and tolerance are severely reduced.

Watkins isn’t yet ready to call the drug a success as positive results on humans are yet to be conducted. But lots of things that work on rodents can be made to work with humans so she admits to being excited at the new possibilities this discovery holds for the future of both pain relief and opioid addiction.

I-Sniffbot

Emergency and security services have always relied heavily on the sniffing abilities of dogs. From searching for disaster survivors to following the trail of wanted criminals, dogs have always done it best.

Their olfactory abilities have also done our canine servants proud in detecting illicit drugs and other unwanted substances at our borders, but Professor Ken Grattan of London’s City University believes we may now have an even better option. He heads a team developing the world’s first robot sniffer.

Nicknamed the cargo-screening ferret, the robot will have an artificial sense of smell capable of sniffing out any number of programmed odours. The sensors are made up of chemically coated optic fibres that would glow when contact is made with a targeted aroma.

While many would argue you can’t beat a dog’s natural sense of smell, Professor Grattan says a robot can do things no dog can. For example, dogs tire, get hungry, make mistakes and require the constant care of at least one trained professional. They also tend to slobber a bit and can be a bit pongy themselves. Robots, on the other hand, would be fully automated and capable of running for 24 hours a day without any need for reward or encouragement.

However, there are still drawbacks with the robot that would need to be overcome. For one, the robot would only be capable of detecting odours it had been programmed to identify. Replicating specific odours and programming robots to detect them is still tricky, and science is yet to match a canine’s natural sense of smell.

Further, robots aren’t yet able to detect the difference between a combination of smells, which means they would struggle to identify a programmed odour if one or more other odours were detectable at the same time.

And while it’s probably inevitable they’ll one day replace their canine counterparts, the robots probably won’t be anywherenear as cute.