Ben Goldacre
Saturday March 10, 2007
The Guardian

Obviously nobody is more worried than I about the hippie crack epidemic: nitrous oxide – better known as laughing gas – has hit the news, after the death of a man with a plastic bag over his head, and a cannister of the drug connected to himself.

Now, I will never speak ill of the dead, and I feel very sorry for this poor man, but equally we must all take responsibility for our actions. Plastic carrier bags are a vital feature of the tramp-chic look I’ve been going with this season – or should I say decade – and to be fair, the one I’m currently carrying my laptop around in reads “plastic bags can be dangerous: to avoid suffocation keep this bag away from babies and children.”

Is there anything else to worry about with hippie crack? Because all drugs carry attendant risks, and it is only by clarifying those risks that we can decide how to manage them. Luckily the Medicines and Healthcare Regulatory Authority has put out a press release, which has manifested itself in various headline stories, mostly under headlines suggesting that nitrous is “no laughing matter”.

The MHRA say this: “Whilst the inhalation of nitrous oxide may be perceived by some as ‘harmless activity’ – there are a number of health risks associated with its inhalation. The ‘rush’ users experience is caused by starving the brain of oxygen. This can cause the user to collapse and injure themselves when falling.”

Now, to be effective, and persuade people to change their behaviour, in public health policy, it is generally considered that your message must be credible, and perceived by the recipient as applicable to their circumstances. This is relevant in campaigns on HIV or smoking for example. I suspect most hippie crack users will already have experimented with holding their breath, and will rightly conclude that their transcendant experience on nitrous is a drug effect; and that it’s an anaesthetic used in hospitals, and in childbirth, so the effect is probably not caused by starving the brain of oxygen; and that the MHRA, of all reputable bodies, is talking nonsense.

In fact, the pharmacology of nitrous oxide is fascinating, and a window onto how we deduce what drugs do in the brain. It seems to work on the NMDA neurotransmitter system, and on the opioid system. Animal models suggested that it might increase the release of opiate molecules made by your own body. To test whether opiates were responsible for the effects on humans, researchers gave nitrous, to people in pain, and then gave an opiate receptor blocker, to see if the analgesic effect was reversed, or changed: the analgesic effect was, but the subjective sensations of being “high” on nitrous were not, even at high doses, suggesting that this aspect of its effect must be mediated by a different neurotransmitter system. It seems likely that these effects are mediated by the NMDA system, perhaps similarly to ketamine. If all those politicians really were “experimenting with drugs” in their youth we’d know a lot more than we do.

But that’s a colossal diversion. Are there any real dangers with nitrous oxide? Well it’s fairly safe overall, and I suppose you could risk manage the “falling over” thing by “sitting down”, but it has been studied very closely for a long time – on account of its widespread medical use, and the worry about chronic low dose exposure for dentists and people who work in operating theatres – and it turns out that it does have a major side effect: it selectively oxidises the vitamin B12 in your body, and affects the folate levels too. Vitamin B12 is needed for a process called methylation, involved in making DNA amongst other things, and without it you have a tough time making new cells. I confess I find the nerdy details of why you get ill from things endlessly fascinating.

There are cases in the literature of people over-exposed to nitrous becoming dangerously B12 deficient, or as the MHRA describe it: “There are also long-term dangers to health (including bone marrow suppression, blood cell problems and poisoning of the central nervous system).” But having said that, in the literature it seems fairly clear that these very worrying effects are reversed simply by giving high dose vitamin B12 (which we also recommend for mothers with growing babies inside them).

This may be rather trendy and “harm reduction” of me, but if I was going to put out a press release on hippie crack, I would advise against using it, but I wouldn’t shoot down my credibility with primary school assertions about its mode of action on the brain, I would state the risks clearly, and if I thought the risks from, perhaps, B vitamin deficiency really were significant and worrying, then I might also mention the harm reduction strategies available, and start monitoring outcomes.

· Please send your examples of bad science to bad.science@guardian.co.uk

[Oh, somewhere in the mangle the paper’s version ended up half implying that B12 and folate might be the same thing, they’re not, although both may be affected by nitrous; longer and correct version of copy above etc.]