Party’s Over: Mephedrone Causes Memory Impairment

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Happy Pills

Photograph by Son of Groucho

Mephedrone (4-methylmethcathinone) is a fairly new “party” drug that has exploded in popularity over the last few years. On the street, it has a variety of names: Drone, M-Cat, Bubbles, Meow. It’s also a frequent ingredient in the drug mixes sold as “bath salts” or “plant food”. And now we’ve shown it causes memory impairment.

The subjective experience of being on mephedrone is something like a mix between MDMA (“ecstasy”) and methamphetamine or cocaine. It’s stimulating, euphoric, touch-enhancing (“entactogenic”) and very, very moreish.

One of the big problems with newly emerging drugs is that we know virtually nothing about them. Many thousands of people are regularly consuming mephedrone, but up until now the scientific community has had no idea about whether or not this might be damaging people.

But this is starting to change. A new paper by my colleagues and I at the University of Sydney, published in PLoS ONE today, provides the first demonstration under controlled laboratory conditions of lasting cognitive damage induced by mephedrone.

What we did

Two groups of laboratory rats were given a daily dose of mephedrone for ten days. The brains from the first group were examined shortly after their final dose of the drug, while the second group went back to their home cages for a month of drug-free healthy living.

The first set of brains provided some useful information about how mephedrone acquires its hook. Mephedrone has sharply contrasting effects on the serotonin and dopamine neurotransmitter systems.

One hour after their final dose, the rats had greatly reduced levels of serotonin in their brains, but increased levels of the molecules that serotonin breaks down into. On the other hand, dopamine levels were increased while their breakdown products were reduced.

It looks like mephedrone is inducing a sharp and sudden release of serotonin, which is then rapidly metabolised. With dopamine, the results suggest that mephedrone may be acting to reduce the rate at which this neurotransmitter is broken down, causing it to persist in the brain for longer.

This matches up with what we’ve been hearing from users. Serotonin is associated with the euphoric effects of drugs; dopamine is connected to their potential for addiction.

Taking a dose of mephedrone usually results in a brief but intense wave of euphoria (driven by the sudden serotonin rush) which is then followed by a longer period of stimulation and a strong craving for more (courtesy of the dopamine effect).

The intensity of mephedrone’s impact also suggests that too much of the drug is quite likely to have unfortunate consequences on the serotonin system.

This is particularly worrying because of the connection between serotonin and depression. Scientists from the UK are reporting alarmingly high numbers of suicides among fatalities connected to mephedrone.

Powers of recognition

With the second group of rats, their drug-free holiday was followed by a series of behavioural tests. One test in particular raised the alarm: the “novel object recognition test”.

Rats are curious little critters: they’re scavengers whose survival depends on making use of every food source available.

Because of that, they have a natural tendency to explore and investigate new things. In the scientific journals, they call this “neophilia”: rats like new stuff.

If you’re careful, you can make use of this characteristic in order to test rats’ memories. First, put your rats in a space with two identical things that they haven’t seen before.

It doesn’t matter much what you use: something like a clean coffee cup or a Rubik’s cube will do just fine.

After you’ve let your rats get familiar with the first pair of objects, you send them back to their home cage for however long it is that you want to test their memory. Then you bring them back to the same space where they first saw the two objects.

But instead of having two identical objects, they’re now faced with a pair of different things: one of them is the same item they saw earlier, while the other is new.

If their memory is intact, they’ll spend most of their time checking out the new thing. But if their memory is fried, then both objects are “new”, and they’ll split their time 50-50 between the two.

That’s exactly what our University of Sydney team found with the rats given mephedrone a few weeks earlier. The group of animals that had been on the highest dose of the drug split their time equally between the new and old objects, showing clear signs of memory impairment.

The dose they had received was designed to be roughly equivalent to what human users might consume over a night out, once you adjust for the differences between human and rat metabolism.

Damage and limitations

Our result confirms some earlier hints of memory impairment in human mephedrone users, and is the first time that a laboratory experiment has shown that mephedrone-induced impairment can persist for more than a few days.

However, we still don’t have any idea of the mechanisms involved. Dopamine and serotonin levels checked out as normal in the forgetful rats, but there is much more to the chemistry of memory than these two players. We also don’t know if the impairment is permanent or just persistent, and whether there’s anything that we can do to fix it.

When it comes to mephedrone, there’s still plenty more work to do.

Further reading:

By Craig Motbey, University of Sydney

Craig Motbey received funding from an Australian Postgraduate Award and the Australian Institute of Nuclear Science and Engineering.

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