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  1. 5-HT2A
    A patent has been filed for a drug that produces some of ecstasy’s euphoric effects – and seems to put the brakes on boozing

    THINKING of taking a break from the booze? Many of us drink more than we probably should and wish we were better able to control our intake. Several drugs now in development could help us do just that.

    In 2012, alcohol played a part in 3.3 million deaths worldwide. Awareness campaigns and prevention services have done little to reduce the amount that people drink overall, and consumption has remained steady or increased around the world. The scale of the problem has led people, including David Nutt, a psychopharmacologist at Imperial College London, to want to try a different approach.

    Last month, a patent application was filed for a drug that is supposed to give people a pleasant intoxication as well as limit the amount they drink.

    In an unlikely marriage, the compound was created by the drug designer behind mephedrone, a now widely banned substance that has caused at least one death and been implicated in 13 others in the UK. The man, who has asked to be referred to by his pseudonym, Dr Z, initially intended his creation to be sold as a legal high. But after having discussions with Nutt and trying it on himself, he now plans to gift the patent to Nutt's charitable research group DrugScience, in the hope it will be used as a "binge mitigation agent".

    How it might finally be used will depend on the results of detailed testing – including how quickly it is absorbed and how it mixes with alcohol. But it might become something you'd take at the start of a night out, or perhaps even add to each drink.

    Nutt and Dr Z have called the new drug "chaperon". Its less catchy name is MEAI or 5-methoxy-2-aminoindane. Structurally, it is closely related to two drugs you can buy as a legal high in some places – MDAI and MMAI. Both were invented by David Nichols from Purdue University in West Lafayette, Indiana, and have some of ecstasy's euphoric effects.
    Unpredictable effects

    Nichols says chaperon also looks a bit like another drug, PMA, which is known to be highly toxic. And therein lies the risk: "There really is no good way to predict biological activity in a completely novel structure," he says. What it does to the brain is also hard to predict because small tweaks to a molecule can result in big changes to the neurotransmitters and pathways it acts on.

    So far no lab tests have been done on the substance, but Dr Z and about 40 other people have tried it. One of those people was me (see "A night on chaperon"). According to Dr Z, there have been no serious problems, although one person didn't enjoy the experience. Several others said it made them feel euphoric.

    The effects varied, but some of the experimenters reportedly lost the desire to drink. The effect didn't kick in immediately. The longest delay was 2 hours, and it took 5 hours before I felt like holding back on the booze – although this may have been because I took a very small dose to start with. This isn't necessarily a problem, says Dr Z, as long as people know that in advance so they don't keep taking it while waiting for it to work. However, he is concerned that the effect is so much like ecstasy: "Maybe the drug is too good?"

    Nutt doesn't think chaperon's ability to induce euphoria is necessarily an obstacle. There are other drugs that help people with alcohol problems to drink less or that act as a less harmful substitute – including some that Nutt is involved with (see "The alcohol fighters"). But most cultures around the world use drugs for pleasure, so a drug like chaperon could be a "win-win" situation, he says, acting both as a binge mitigator and providing some of its desirable effects.

    But "you need scientific tests", says Nutt. "Anecdotal evidence isn't enough." These would involve finding out what receptors it binds to, how it affects rats and working out a safe dosage profile, before raising funding to conduct clinical trials to see whether it really does reduce alcohol intake.

    David Caldicott from the Australian National University College of Medicine says the safety bar for new medicines is high – and even higher for recreational products.

    Caldicott is enthusiastic about the potential of a substance like chaperon, that has some of alcohol's desirable qualities, but he is worried about mixing drugs and alcohol: "From a harm minimisation perspective, mixing drugs and alcohol is never a good idea. It's one of the basic premises."

    Alex Wodak of the Australian Drug Law Reform Foundation says it is hard to predict what a drug will do when widely released. Its success will depend on whether it lowers people's intake of alcohol or simply adds another dimension to a night out.

    Of course, there's every chance the drug will simply be banned, like so many of Dr Z's creations. Nutt is philosophical. "Let's just hope they don't," he says. "We have to see this as an opportunity to reduce harms rather than a new drug that has hit the market."

    by Michael Slezak

    December 31, 2014



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