Laugh? I nearly died.

March 10th, 2007 by Ben Goldacre in bad science, drurrrgs, scare stories | 62 Comments »

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.]


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62 Responses



  1. Robert Carnegie said,

    March 10, 2007 at 12:55 am

    of course this is the style of most communications about illegal drugs; they tell you it does terrible things to you, vaguely and unconvincingly, and they don’t address pros and cons of strategies other than “just say no”, which, however, is usually good enough for me. Aside from losing one’s mind, which one is fond of, there’s this business of dying. It’s also how I felt about rugby football at school. People die playing it – not for me.

    On the other hand, I admit news of the perils of a “four or fewer portions of veg. a day” habit hasn’t changed my lifestyle as much as the Powers that Be intended that it should.

    Strange, I missed the story, but nitrous oxide just came up in the forum anyway, I think. I know I saw it somewhere: “You could die” seemed a stronger consideration than “You could fall over.” In general anaesthetic someone stands over you watching the whole time to see that you don’t die. So not something to try by yourself.

    Do you have to break into the dentist to get it? Or can you make it at home? I don’t want details, I’m just intellectually curious.

  2. faddy said,

    March 10, 2007 at 1:02 am

    I had assumed this entry’s title was a reference to Medicine Balls…

  3. bfwallis said,

    March 10, 2007 at 2:10 am

    Do you have to break into the dentist to get it? Or can you make it at home? I don’t want details, I’m just intellectually curious.

    I’m pretty sure that it’s used in whipped cream cans in the U.S.

    Do you have canned whipped cream in the UK? I must admit that with the number of Sanisburyses I went into in the UK in 2002, I never noticed the presence or absence of canned whipped cream.

  4. Kimpatsu said,

    March 10, 2007 at 3:42 am

    Once again, the Guardian cut this article to ribbons when they ran it.

  5. AitchJay said,

    March 10, 2007 at 5:14 am

    Used in whipped cream in Australia too, so you use a Soda Stream or a whipped cream dispenser to use it. There were 24 hour service stations where I’m from that got fresh cupboards full of the canisters every Thursday – in time for the weekend drug binges. Not even the pretence that it was for legitimate use..

    Never heard of anyone dying, but if you want to hyperventilate with it, use a balloon – as soon as your muscles go loose you can’t hold it – much safer.

  6. doctormonkey said,

    March 10, 2007 at 5:35 am

    or you can call an ambulance and they dole the stuff out for pain lots…

    or you could have a baby…

  7. Gimpy said,

    March 10, 2007 at 7:46 am

    You can get canisters of NO from most wholesalers that supply the catering trade. It’s widely used in restaurants. All you need to inhale it is an adapted whipped cream canister. It gets boring after a while. Its something we did at school for a week or so until we found out where the ether was kept.

  8. JohnD said,

    March 10, 2007 at 8:38 am

    Ben,
    I won’t argue with you on the pharmacology, but you’re on dangerous physiological ground here.

    As I understand it, and I’m speaking as a horrified reader of other’s accounts, the practice of masturbating with a plastic bag over your head is intended to achieve a mild hypoxia that heightens the experience. A ‘high’. Reports show that this goes wrong from time to time, and people die. They die of hypoxia/anoxia, which means that their brains have been starved of oxygen.
    To do this with a flow of nitrous oxide into the plastic bag will wash the oxygen-containing air out of the bag, and replace it with a narcotic. This puts the practitioner into a similar position to a drunken driver – so incapable of recognising that they are in danger that they cause their own death.
    So the advice of the MHRA is correct – breathing pure nitrous oxide causes hypoxia and can kill you. To extend their caution to the dangers of falling down does seem to be unnecessary, else they would issue similar warnings against cooking sherry.

    And on the medical use of nitrous oxide. In every technique in which N2O is used, equipment and practice are directed at preventing the use of this gas without a safe addition of oxygen. Anaesthetic machines are built with mechanical interlocks so that the oxygen supply rises as the nitrous oxide is turned up. Women in labour and casualties in ambulances are offered Entonox, a cylinder of premixed 50% oxygen and nitrous oxide. And those in charge of such kit are trained and professional.

    Compare this with breathing NO2 from a plastic bag with some artificial ‘whipped cream’ squirted in it. The gas in the bag will be near 100% nitrous oxide. In these circumstances, to quibble about NMDA or B12 deficiency is trivial.

    John

  9. drduncan said,

    March 10, 2007 at 8:40 am

    Normally I would agree with Dr Goldacre, and I find this column very interesting, but this is something about which he is wrong.

    Nitrous Oxide is not safe. As an anaesthetist i use this drug on my patients almost every day. Whn used in this setting thegas has come from a medical gas suplier and is used through an anaethetic machine that has a hypoxic guard. This means the machine cannot actually give more than 75% nitrous. In this way, hypoxia is prevented in the patient.

    The nitrous oxide available in clubs is known as whippets. This is becuase it comes from the propellant used in the whipped cream cannisters. It is not medical grade. God knows what kinds of pollutants there are in there. Second, it is provided in balloons from a cannister that contain 100% nitrous oxide. THERE IS NO OXYGEN IN THESE BALLOONS. Third, the user inhales vital capacity breaths (big breaths) and thus inhales 100% nitrous. After a few breaths of this they will have completely deoxygentaed their lungs. Thus the ‘high’ from the nitrous is compounded by the ‘high’ of hypoxia. In addition, such a high dose of nitrous is actaully uite close to an anaestheic dose.

    I am not against recreational drugs, I am against anti-drug rhetoric that is not founded in any factual basis. I find it odd that cocaine is still used medicinally in ENT surgery, yet according to many papers, 1 dose can change your limbic system or life and make you an addict. How these 2 states can co-exist is beyond me. In this case though, I believe the MHRA have a point. Perhaps I could apply to my local ethics commitee and do some arterial blood gas sampling in volounteers who have inhaled balloons of N2O….

  10. JohnD said,

    March 10, 2007 at 8:42 am

    ERRATA!
    Sorry – should be N2O, not NO2 in last para.
    My fingers type faster than my brain.
    John

  11. drduncan said,

    March 10, 2007 at 8:49 am

    CORRECTION – I should say Nitrous oxide in clubs is not safe.

  12. BobP said,

    March 10, 2007 at 9:06 am

    In defence of Ben – I think his grouse is against sloppy wording in the MRHA press release, who ought to know better.

    On the other hand, the MHRA release had the desired effect of hitting the headlines and hopefully reminding people who supply or use N2O what naughty boys they are. They could have isseud a nerdy version, but it would have been ignored.

  13. Jut said,

    March 10, 2007 at 9:23 am

    I thought that a plastic bag on your head and inhaling a gas that was “not oxygen” was a fairly well known suicide method…was this an accidental death or suicide?

  14. drduncan said,

    March 10, 2007 at 9:44 am

    Ben has essentially said that the issue of hypoxia is irrelevant. He has said this to a wide audience. This is incorrect and incredibly dangerous. Inhaling several breaths of any gas that is not oxygen will lead to hypoxia. Conpounding that hypoxia with feelings of being ‘high’ make the situation potentially fatal. Combine that with ecstacy, cocaine, poppers, ketamine, GHB, 2CB, cannabis and whatever else the kids are doing these days in a club and you have a potentially lethal combination. N2O also supports combustion so having people smoking around it is as stupid as having people smoke around balloons containing 100% oxygen.

    There are a myriad of reasons why this drug is dangerous in a club, and that is what Ben should have been saying.

    Long term effetcts of bone marrow suprrssion and B12 problems only come after prolonged use (which is why it generally isn’t used for longer than 2 hours in theatres).

  15. Gimpy said,

    March 10, 2007 at 9:52 am

    drduncan with respect any drug used long term is going to have side effects. My recreational use of nitrous oxide was restricted to a couple of deep breaths rather than continuous breathing from a balloon. This was probably the equivalent of letting all the air out your longs and holding your breath for about a minute. Surely this is not dangerous? I should point out that I haven’t touched the stuff in nearly 10 years so am not seeking a guide to safe nitrous oxide use. :)

  16. banshee said,

    March 10, 2007 at 9:58 am

    Heh.

    The MHRA knowing better?

    Think about the recent volte face on the cardiac toxicity of the anti-depressant venlafaxine (it was but now it isn’t) or the interesting extrapolation from a single study over 3 months to risks over a year for stroke and other cerebrovascular events in dementia from a couple of selected antipsychotics…….

    I’m sure there are other examples from other fields.

    Nope. And FOI doesn’t work here either – everything is commercially sensitive. Well, Okay – the things I tried to find out about and the attitude was “we know something you don’t – but we’re not telling you”

    b

  17. Paul Crowley said,

    March 10, 2007 at 9:58 am

    Many thanks to JohnD and DrDuncan for discussing the dangers in more detail. It’s pretty obvious that putting a plastic bag over your head isn’t a wise move. However, I’m not sure I understand the dangers you’re trying to explain in the setting where N2O is usually recreationally used.

    The difference between administering N2O in a medical context for anasthesia and self-administration from a balloon is similar to the difference between being suffocated and holding your breath. In one instance, you don’t have control over what’s happening to you, and if it’s too much it can kill you through hypoxia. In the other instance, if hypoxia starts to set in you will be unable to continue. You’ll exhale, or you’ll drop the balloon, and your normal automatic breathing mechanism will cut in, restoring blood oxygen levels.

    “Whipped cream” N2O canisters contain pressurized gas; there’s no separate propellant. Since obviously they are meant for food use, they probably do not contain deadly poison.

    Contrary to what BobP asserts, lots of recreational drug users care deeply about the safety of what they do, and if there’s good evidence of a real safety risk I’d like to propogate that far and wide because it will make a real difference to behaviour. But I’ve read both comments several times now, and I’m still not seeing what danger recreational N2O use poses that holding your breath does not pose.

  18. drduncan said,

    March 10, 2007 at 10:02 am

    after 2 deep breaths of 100% oxygen, your end expired nitrogen is approximately half what it is when breathing room air. Although not very accurate, it would be reasonable to extroplate that and say that after 2 deep breaths of 100% N2O your end expired oxygen would be about half what it is normally. I suspect this would lead to a significant drop in alveolar oxygen tension and therefore a significant reduction in the arterial oxygen tension. Otherwise known as hypoxia. breathing steadily from a ballon rather than deep breaths would lead to a slower drop in the oxygen levels, but a drop nonethelss.

    How can you say that breathing a gas with no oxygen in it is not dangerous?

    Letting all the air out of you lungs and holding your breath for a minute WILL lead to hypoxia. Try it with you finger on a saturation probe. I sometimes do it at work when I am bored. After about 45 seconds the numbers start to fall. Combine falling numbers with fdallking body, potentiual head injuries and other recreational drugs and you have problems.

    As I say, I may apply to the ethic committtee for approval. Clearly there are plenty of willing volunteers

  19. drduncan said,

    March 10, 2007 at 10:08 am

    many users take repeated deep breaths from a baloon, thus ‘deoxygenating’ their lungs. That is why it is dangerous. When you hold your breath you have a reservoir of oxygen in your lungs from the air you have been breathing to get you through the breath holding. You cannot completely empty your lungs, there is always a bit of gas left in it, the residual volume. If you have been breathing air this RV contains oxygen. If you have been breathing 100% N2O then the RV contains NO OXYGEN as it has been ‘washed out’ by the N2O and you become hypoxic.

  20. Gimpy said,

    March 10, 2007 at 10:24 am

    drduncan but are there any health concerns over hypoxia lasting a minute or two? Apart from falling over of course.

  21. Paul Crowley said,

    March 10, 2007 at 10:39 am

    drduncan – thanks for this clarification!

    As I say, I believe that if there are real dangers from normal recreational N2O use then many users *will* be interested and *will* modify their behaviour if necessary. So this is a real opportunity to discuss and understand what the real situation is. If you can make a clear case that they are underestimating N2O risks then you may find your words propogated far and wide, so I hope it’s worth your time to continue to participate.

    Are you concerned about the danger that people will drop dead on the spot, or that they will do themselves some gradual long-term damage? I find it hard to believe that someone who sits down to breathe N2O from a balloon will drop dead on the spot of hypoxia for the reasons I’ve outlined, so I’m guessing it’s the latter.

    What is the gradual long-term damage from hypoxia? Please make it clear the sort of likelihood assocated with the risks you describe: you can drop dead directly from Ecstacy toxicity, but the risk is extremely remote, so if long-term damage is more likely than that please try and put at least a rough figure on it.

    How does the hypoxia from recreational N2O use differ from “holding your breath” hypoxia? You mention that for N2O users the residual volume contains far less oxygen, but I would have thought that the point at which you were unable to interfere with your own normal breathing would be about the same. I can imagine that there would be a difference, but I don’t understand why the difference is so great that it would move an activity from safe to unacceptably risky.

    As I said, I believe most recreational drug users do care about the safety of what they do. However, they are used to the undeniable fact that over the decades, most of the safety warnings they’ve heard about what they do have been openly dishonest (consider eg the use of Leah Betts’s death in demonizing Ecstacy) or obviously facile, as per the MHRA warning that this column rightly ridicules. So in order to convince them of a real danger, assertion is not going to be enough; someone’s going to have to provide chapter and verse on all the details. If that person is you, you could be doing a great service to the health of thousands.

  22. mus said,

    March 10, 2007 at 10:54 am

    while we’re at anasthetics, how about this paper ( www.pnas.org/cgi/reprint/102/28/9790 ) leading to this ( www.cbc.ca/technology/story/2007/03/09/science-nervessound-20070309.html ) article? bad science at work, huh?

  23. drduncan said,

    March 10, 2007 at 11:08 am

    OK, I am a DJ as well as a doctor. I play house music and have been to plenty of clubs. Many of my friends take recreation drugsa and hold down very responsible jobs. I am in no way against recreation drug use. malignant hyperthermia and serotonin syndrome in MDMA toxicity are rare. Leah Betts died from a dilutional hyponatraemia brought on by drinking too much water (in line with government advice at the time). People drop dead from penicillin, nut allergies and anything other kind of toxin or drug (all drugs are toxins) without warning every day of the year. It is very sad but it won;t change behaviour. Please do not for one minute think I am jumping on a drugs are bad bandwagon.

    Over the last year I have notice din clubs in south london a proliferation of balloons being sold. My concern is that thelack of oxygen in these balloons ad the nature by which they are being inhaled will lead to hypoxia. I do not know whether any studies have been done to show the effects of repeated short term hypoxia (30 seconds – 2 mins) on cognitive function, myocardial function, or gut function. However, when you combine this hypoxia with the stimulant effect of MDMA / speed / cocaine and the increased myocardial oxygen demand that the stimulation brings about I suspetc you would be making life a little tough for the heart. I think the risk of an MI is 27 times normal in the hour after having a line of cocaine. Combine that with an induced hypoxia of up to 2 minutes and I think you are looking at potential trouble. Myocardial ischaemia and dysrhythmias are a distinct possibility.

    I have done aquick pubmed search but can;t find anything useful. Common sense dictates that hypoxia is bad. Just because the evidence isn’t there to say it is bad, it doesn’t mean it is not bad. What is needed is a study to determine the level of hypoxia and then further work to determine if this hypoxia is dangerous, especially in combination with the other drugs that are flying through peoples system.

    You are using the get out clause of ‘there is no evidence to say it is bad’. My response would be to show me the eveidence that it is safe when used in this context. That is how most drugs get a licence.

  24. Ben Goldacre said,

    March 10, 2007 at 12:03 pm

    hey

    drduncan

    stop a moment

    of course breathing nothing but 100% nitrous oxide will cause a transient hypoxia. i said the MHRA were stupid and wrong to say that the effect users experience is due to hypoxia. i explained why this is not the case. i explained the real pharmacology of nitrous (which is very interesting). i discussed the risks, and suggested harm reduction, and more than that, i discussed how best to communicate risks without telling obvious lies and sacrificing your credibility.

    nitrous is indeed a relatively safe drug – recreational deaths numbering “one or two” and with extra circumstances causing death from hypoxia like a plastic bag over head – but as i said, like all drugs, it does have attendant risks, and the question is how to manage and communicate those without losing credibility. the b12 depletion is a significant issue.

    please don’t make me go through and pull out all the quotes to “prove” that i wrote what i wrote. maybe you could read it again?

  25. Littleshim said,

    March 10, 2007 at 12:51 pm

    Why does everyone seem to think this article’s about hypoxia? For ease of reference, here’s a summary of each paragraph.

    1. This article is about recreational use of nitrous oxide
    2. Plastic bags pose a risk of suffocation
    3. All drugs carry risks; what are the risks of nitrous oxide?
    4. An MHRA press release says that nitrous oxide’s ‘rush’ comes from oxygen deprivation, which poses health risks such as falling down.
    5. Public health policies must be credible to the audience to be effective. This claim about the drug’s function is, rightly, unlikely to be believed.
    6. Nitrous oxide has both pain-relieving and ‘high’ effects that appear to use different pathways.
    7. The ‘falling down’ claim is trivial. Nitrous has a more significant side-effect of causing B12 deficiency through long-term exposure.
    8. B12 deficiency can be easily reversed.
    9. In conclusion, Ben recommends not making incorrect claims about a drug’s function (which is self-defeating), but presenting clear information on the risks and attempting to minimise harm.

    Please note that Ben does not discuss hypoxia. He doesn’t claim that it’s harmless, or irrelevant, or that it isn’t a risk when using certain methods to take this drug. JohnD seems to have started this (comment 8) but actually Ben doesn’t go into this aspect at all. The article is about the MHRA’s bad science. Their attempts to scare off nitrous users with misleading, patronising and untrue claims are self-defeating because people will see through them, and so the MHRA lose credibility.

  26. Andrew Clegg said,

    March 10, 2007 at 12:57 pm

    Well said Ben, it sounds like people are losing sight of the real point of the article, which is that the MHRA are effectively torpedoing their own safety claim by lying about how the drug works. (Maybe it’s an honest mistake… But when an agency responsible for drug safety makes claims about mode of action that are so absurd a computer nerd like me can spot them a mile off, it’s tantamount to lying.)

    Re. the point someone made about N2O promoting combustion and hence being a bad idea to use around cigarettes… I burst someone’s N2O balloon with a cigarette once (in a club) and there wasn’t a hint of a flame. He’d thrown my hat across the room moments earlier—it seemed like the best possible comeback.

    But of course that’s anecdotal.

    Does anyone know if there’s an increased level of risk associated with taking N2O and helium at the same time? Because there’s an unexploited market out there for squeaky-voiced hilarity, surely.

    Andrew.

  27. drduncan said,

    March 10, 2007 at 1:18 pm

    unfortunately the title in the guradian today is ‘Nitrous oxide starves the brain of oxygen? Don’t make me laugh ‘ Hypoxia is starving the brain of oxygen, so it is part of the article.

    As for it supporting combustion, it wouldn;t be very useful as a booster in cars if it didn’t. It is not explosive so it won;t explode, but it does support combustion bgetter than oxygen.

    Anyway, i’ll stop there.

  28. cedgray said,

    March 10, 2007 at 1:29 pm

    Sir Humphrey Davy, inventor of many useful items, had a serious laughing gas habit, which was almost certainly instrumental in his death. He even wrote a (rather poor) ode to the gas:

    “Yet are my eyes with sparkling lustre fill’d
    Yet is my mouth replete with murmuring sound
    Yet are my limbs with inward transports fill’d
    And clad with new-born mightiness around.”

  29. Andrew Clegg said,

    March 10, 2007 at 1:30 pm

    That’s something to blame the Grauniad’s subs for then, not Ben!

    Andrew.

  30. Dr Aust said,

    March 10, 2007 at 1:32 pm

    So let me get this straight…. the MHRA’s statements about N2O are not very clear. On that at least we can all probably agree. As I understand what Ben is saying they don’t clearly make the point about what are risks of N2O per se, what are risks of acutely replacing O2 in your lungs with N2O, one breath from a bag vs two breaths, multiple breaths or re-breathing, long-term vs. short term risks of recreational N2O use, and so on.

    Of course, you can argue they have to balance “accurate info” with “clear easily understood message”. But then the counter-argument, derived esp. from work on drugs of abuse is “simple scary messages that are clearly at odds with people’s experience and lay knowledge are counter-productive”.

    Have I paraphrased all that right?

    BTW, as a professional physiology researcher / teacher (and other half to an ex-anaesthetics trainee) have been enjoying the blood gas discussion started by Dr Duncan (pace Ben), even if no-one else has. I think there’s definitely a study to be done there, Dr D, but of course there will be so many confounding effects that epidemiologically it would be hard to impossible to distinguish “direct N2O effects” from “tanked on other stuff” from “intermittent v. brief acute mild hypoxia”. And good luck getting an Ethics Ctte to approve your interventional study making healthy young volunteers honk N2O, or making them repeatedly acutely hypoxic… You should see the crap we have to go through regulations-wise to do lab classes where we make even ONE medical student mildly hypoxic (hardly ever below 90% Hb satn).

    Occurs to me that there are a large population of people who have intermittent acute hypoxia… those with obstructive sleep apnoea.. but of course they are mostly middle aged or older and overweight, so not all that comparable to young and healthy (in a general sense) clubbers.

  31. PK said,

    March 10, 2007 at 1:41 pm

    If you strap a bag around your head (with or without N2O) you’re an idiot, and the guy probably deserves a Darwin Award. Having said that, kids do experiment with drugs, and they should be taught the basic principles of safe drug use. The sooner Western society relaxes about recreational drug use, the better.

  32. stever said,

    March 10, 2007 at 2:34 pm

    using balloons is probably the safest way to use the gas in its pure form. It is naturally self limiting since feinting – not unheard of with nitrous – would lead to normal breathing and blood oxygen would rapidly return to normal (unlike bag over head, mask, or in sealed car methods which have led to deaths, albeit small numbers). Im not aware of any deaths from use with ballooons. You have to work very hard or be extremely irresponsible/stupid to do yourself signinficant harm with balloons. people who have developed problems from long term use have been mostly medical proffessionals who have consumed massive doses over prolonged periods, using masks. This is very different from occassionally doing a couple of balloons at a party – which would describe the vast majority of recreational use (it also remains very expensive – £2 a balloon in clubs, 50p if done privately – for a minute or twos effect)

    If someone did feint – as rational beings, next time they did it they would do so more carefully and safely, just as they would with overdrinking or spinning out on weed. If someone is told about the dangers and ways to use it safely in the first place the risks would be reduced even more. This would be an obvious benefit of the required proper regulation/licensing of vendors/health and safety infrastructure – rather than another couterproductive prohibition.

  33. Steevl said,

    March 10, 2007 at 3:42 pm

    drduncan’s concerns might be warranted if nitrous really was used in the way he describes, but the fact is, it really isn’t. It’s simply not possible to spend 2 minutes breathing 100% nitrous. Any more than 20 to 30 seconds with your lungs full of nitrous will get you so high that you can no longer remember to hold your breath, and start breathing normally again. If you see anyone using nitrous for longer periods than this (*especially* if they remain standing), then they are taking in a pretty good proportion of normal air with every lungful. If they take repeated deep breaths from a balloon, they are either taking deep breaths of normal air in between, or taking the deep breaths quickly and repeatedly, so the situation is little different to simply taking one deep breath.

    Using nitrous from a dentist’s tank (or worse, tanks obtained from car mechanics or ice cream vans) with a mask attached to the face, or set off in a sealed car, is a serious, serious danger. But breathing from balloons is no different to holding your breath.

    I’m a bit confused as to why drduncan is so hysterical about the danger of short term hypoxia from nitrous use, but admits to inducing it in himself by holding his breath just because he is bored.

  34. jackpt said,

    March 10, 2007 at 4:48 pm

    I don’t advocate drugs, but I do believe that people should be able to make an informed choice if they’re going to partake in them. I think one of the tragedies of anti-drug campaigns is that by presenting risks as definitely-maybes they have the counter-productive effect of contradicting peoples’ personal experience. If anything, after reading the resulting articles generated by the MHRA press release, people are going to engage in riskier behaviour than before because know they know that official information is all bunk. Of course it isn’t – but people do have a tendency of A is untrue therefore B, C, D, E, F are untrue.

    However, I have noticed at least one story a year that covers people dying from NO2. Although they all seem to be cases where people have ripped-off (or ‘borrowed’) medical NO2 and forgotten that it should be mixed with oxygen. Or used it in a confined space without adequate air or ventilation. That’s a different risk profile from casual use with balloons. The MHRA could have done a better service by advising on its interactions and who would be at risk from its usage (should some people with certain health conditions avoid it? etc.).

  35. Dr Aust said,

    March 10, 2007 at 4:56 pm

    Breath-holding and breathing in a gas mixture other than air aren’t really comparable.

    The “weird feeling” you get on holding your breath, or on re-breathing air from a bag, is much more to do with CO2 levels in your body going UP than with the O2 level going DOWN. Anyone keen to read loads about the physiology of breath-holding can try:

    ep.physoc.org/cgi/content/abstract/91/1/1

    Physiologically, for most things to do with breathing, your body is much more sensitive (in terms of detecting and responding to the change) to moderate increases in CO2 than to moderate falls in O2. The review above quotes:

    “During breath-holding, the arterial …partial pressure of oxygen PaO2 falls below its normal level of ~100 mmHg and that of carbon dioxide PaCO2 rises above its normal level of ~40 mmHg. At breakpoint from maximum inflation in air [i.e. holding your breath after taking a maximal breath of air in] the PaO2 is typically 62 ± 4 mmHg, while the PaCO2 is typically 54 ± 2 mmHg.”

    This change in O2 ON ITS OWN (i.e. without any change in CO2) would not change your breathing much, if at all.

    [This in part is why hypoxia is dangerous... you are not well-designed to detect it. Hence all the stories about WW2 pilots at altitude or with shot-out oxygen bottles passing out and crashing their planes. If there is no concomitant CO2 increase to "alert" your body, you aren't aware of the dropping O2 levels until you are nearly gone.]

    In the breath-holding example, the increase in CO2, in contrast, WOULD have a big effect on its own. The COMBINATION of the changes in both gases actually has a bigger effect than either alone. So… if holding your breath for a long time makes you feel light-headed and gives you a headache I would say it is much more to do with the raised CO2 than with cerebral hypoxia.

    If you breathe in a gas other than air or O2 – like N2O – the O2 level in your blood may fall a bit (as there is less O2 in your lungs), but the CO2 will not rise since you are still able to blow out CO2. So I would predict little “blood gas level-related weird feeling”. Of course, if you take more, and deeper, breaths of the non-air gas, or hold your breath in between breathing from the bag, you will get progressively more hypoxic. Physiologically it would be interesting to know how much, if Dr Dunc is still anxious to do the experiments..

    Anyway, I guess what all this is leading to is that the “makes you feel drunk” effect of N2O, to which any woman who’s had a baby (like Mrs Dr A) will testify, is highly unlikely to be due to hypoxia…. which is where we came in. Or put another way, hypoxia IS dangerous, but as several people above have pointed out, you would have a job to get hypoxic enough for long enough breathing N2O from a bag.

    As Dr Dunc can confirm, the time when hypoxia is really dangerous is with a person who has passed out (bash on head, booze, drugs….). When unconscious the person may “kink” /block their windpipe, so like breath-holding but now without the body being able to respond to “protect the airway”. This is why all the first aid advice stresses recovery positions and making sure the airway is clear.

  36. amoebic vodka said,

    March 10, 2007 at 4:58 pm

    How does the hypoxia from recreational N2O use differ from “holding your breath” hypoxia?

    The hypoxia is the same, but the ability for you to notice it is very different. The body really is quite insensitive to falling levels of oxygen in the blood — the first sign of hypoxia is often passing out.

    However, the body is very sensitive to the levels of carbon dioxide in the blood. Where any gas replaces oxygen in normal air — whether that’s nitrogen or anything else, the amount of carbon dioxide stays the same as in normal air. However, if you hold your breath (or rebreathe air or even oxygen), the amount of carbon dioxide rises in the air in your lungs and your blood. Your body notices it and responds by making you hyperventilate — hold your breath for a bit and the urge to breathe becomes very strong. It is very noticeable.

    If anyone’s ever been the subject of physiology experiments rebreathing oxygen, it really is quite an odd sensation. You aren’t hypoxic as the oxygen levels are still above normal air, but you end up hyperventilating and after long enough, start turning blue.

  37. TheMole said,

    March 10, 2007 at 7:18 pm

    “As for it supporting combustion, it wouldn;t be very useful as a booster in cars if it didn’t. It is not explosive so it won;t explode, but it does support combustion better than oxygen.”

    Well, not exactly – at normal temperatures it doesn’t combust, but when you heat it to the temperatures found inside a car engine it decomposes into nitrogen and oxygen gases, releasing 3 moles of gas for every 2 moles of N2O, which makes it useful as a car booster in 2 ways – the gas pressure on the piston is higher, and the extra oxygen means you can burn more of the fuel.

    I’ve never tried nitrous, but a quick google reveals a few sites and a lot of ebay sellers selling N2O for whipping cream with suspicious “now, you’d never do anything naughty with this, because its really only for whipping cream” type disclaimers. While selling boxes of 600 refill bottles for a toy-sized cream whipper. Hmm.

  38. Martin said,

    March 10, 2007 at 8:12 pm

    Apologies for going off-topic, but I drove an ice cream van for a summer during Uni. (I now hate Teddy Bear’s Picnic!)

    My Mr Whippy machine had an air compressor; it didn’t use nitrous oxide. Is this a new thing, and does it alter the taste of the ice cream?

  39. raygirvan said,

    March 10, 2007 at 9:26 pm

    My Mr Whippy machine had an air compressor; it didn’t use nitrous oxide. Is this a new thing, and does it alter the taste of the ice cream?

    It’s not used for ice cream: that (and conventional whipped cream) is beaten to froth it up with air. The deal with nitrous oxide is that it’s a neat trick to make a froth without beating. Nitrous oxide, being fat-soluble, is dissolved in the cream under pressure. When it comes out of the can, the cream foams up with nitrous oxide bubbles coming out of solution.

  40. CDavis said,

    March 11, 2007 at 12:57 am

    A friend bequeathed me a 5-ft N2O cylinder after his attempts to make his Alfa break the sound barrier just blew up its engine. It sat in the corner of my flat for years, with occasional visitors and me sucking on the spout for fun every now and then. No-one died.

    I’m pleased to hear that the chemistry is more complex than just oxygen exclusion. For me the stuff often produced weird religious hallucinations, in which I became aware of a vast unseen observing presence etc. Presumably temporal lobe effects or summat, but whatever it is, I think they should give god-botherers the antidote.

    CD

  41. Robert Carnegie said,

    March 11, 2007 at 1:47 am

    I decided, for abstract curiosity, to look up online “How is nitrous oxide prepared”. As it’s a sensitive topic I won’t provide a hyperlink or credit, or the method (as pointless as it is to be coy), but I read, “The preparation is dangerous because of N2O’s tendency to explosively decompose into nitrogen and oxygen at high temperatures. N2O manufactured this way should NOT be inhaled, because it is contaminated with NO2, a corrosive, irritating gas that can cause permanent lung and genetic damage!”

    Also I didn’t notice here: “A rapid expansion of nitrous oxide can cool it enough to cause frostbite. People doing whippets have actually frozen their lips, tongues, or vocal cords- and under the anaesthetic influence of nitrous oxide, the damage is done before any pain is felt. Nitrous oxide has also been linked to birth defects, nerve damage, and permanent organ damage.” Apart from the freezing, is that all the vitamin B12 thing?? Or another little outbreak of Bad Science in a site concerned more with inorganic chemistry academically than with biological effects… but huffing laboratory supplies is a “do not do”.

    Btw, I’ve read at least a couple of Isaac Asimov murder stories set in university chemistry departments – Asimov was a chemist academically – where the detective is appalled by being told that anyone could pick up a thousand poisons from the department shelves. Things may have been tightened up since those days. If the story turns on science then I think it is technically science fiction.

  42. drduncan said,

    March 11, 2007 at 1:37 pm

    who remmebers Ben’s excellent articles on the omega 3 experiments. Lot’s of pseudoscientists putting forward half baked evidence for their trial in northumberland. Ben quite rightly rebuffed it by explaining that these trials were anecdotal and taken out of context.

    Read the above posts again. They are mainly anecdotal. Someone’s mate’s cylinder sitting in the corner of the room is hardly level 1 evidence.

    Show me the evidence IT IS SAFE IN CLUBS and I will be quiet. The evidence that it is safe comes from medical experiments where there is controlled amounts of oxygen in the gas mixture, something that is not happening in clubs. They are simply not comparable situations. This is a point Ben has made himself over and over again in relartion to the fish oil ‘trials’.

    This is not anti-drugs. I just feel that the evidence presented to say it is safe is wrong. I am in full agreement that the MHRA statement is partially incorrect (although I maintain hypoxia does produce a high – auto-erotic asphyxiation anyone…). This column is supposed to be about robust reporting and I’m afraid has fallken rather foul of itself on this occassion. The title on the guardian page is also completely incorrect, as Ben himself agrees that there is likey to be a hypoxia and therefore the brain does indeed startve itself of oxygen.

    mattson.creighton.edu/N2O/ – go to this page and look at the bit about wooden splint test for N2O. If that is not supporting combustion I’m not sure what is.

  43. Robert Carnegie said,

    March 11, 2007 at 3:02 pm

    Auto-erotic asphyxiation is another case where the reported pleasure “high” isn’t only due to hypoxia. Hypoxia on its own surely isn’t that wonderful or else the people who have suffered it accidentally surely would have noticed a change – such as in hypothermia where you start to feel too warm, although at that point your critical judgment usually is impaired already. You may or may not think to yourself, “Uh-oh, I feel warm and I know I’m freezing, the hypothermia must be dangerously advanced.”

    We’d have people just suffocating themselves or each other for the high, rather than suffocating themselves or each other during sexual intercourse. Without the sex it’d be less messy. You’d go into a bar at lunch and order a pillow held over your face for ninety seconds to set you up for the afternoon, or maybe your job isn’t as dull as mine.

    I haven’t looked into the sex thing, it seems bloody silly, but I suppose the sexual use of strangulation may be of a piece with other physical sensations of distress or discomfort or pain that are perceived as pleasure – up to a point – as sexual arousal progresses. For some people, still, there’s also an element of guilt in sex… it’s complicated. And there may be a unique role of hypoxia but there are other ways to achieve that – then again if it’s a matter of breathing a gas other than oxygen or CO2 (or air containing one or other of those) then that is more inconvenient to arrange than using a plastic bag.

    Now I have no idea whether N2O is safe in clubs. It seems a damn silly idea to me. As for the law… perhaps it wants looking at. But I think we should be specific about what actually does and doesn’t happen when someone is dosed or self-doses with N2O.

  44. Ben Goldacre said,

    March 11, 2007 at 4:39 pm

    oh for christs sakes drduncan,

    you’re seriously stretching it here, like no-one i’ve seen before.

    you’re hanging your whole argument that I have said something wrong on some sub-editors headline on my column in the guardian.

    you have to stoop to that, to get me saying what you want me to say, so that you can disagree with it.

    that is absurd.

    do you want me to reshash what i actually said, again, especuially for you, even though its written above, and other people have done that for you, as well as me?

    let me hold your hand, yet again.

    breathe deeply and try to pay attention.

    the effect of nitrous is not due to oxygen starvation, it is a drug effect. the mhra to claim otherwise make themselves look like buffoons. nitrous has some risks. they are not enormous. they should be honestly communicated and managed.

    you’re disagreeing with something, but it’s not with what i’ve written.

    for the love of god.

    i have not presented a gold standard essay on the relative risks or safety of nitrous, nor have i ever claimed to, that was completely not the point of what i wrote. i think it’s a pretty damning indictment of the lack of sophistication of our approach to drugs that no matter what anybody writes, somebody will come along and hysterically make it all about whether they are safe, attacking you for not saying it was dangerous frequently or prominently enough. this is like a totally topsy turvy witch trial.

    if you want to talk about nitrous causing hypoxia, that’s great. you’ve got a real bee in your bonnet about it. go for your life, write about it here, i’ll give you an audience.

    but you really seriously have to stop deliberately and repeatedly claiming i’ve said something i didnt because it’s rude, irritating, boring, repetitive, and twatty.

  45. drduncan said,

    March 11, 2007 at 6:00 pm

    i’m sorry if i appeared ‘twatty’ that was not my intention. i will retire beaten.

  46. Ben Goldacre said,

    March 11, 2007 at 6:09 pm

    i dont want anyone to retire beaten, it’s an interesitng question, but “This column is supposed to be about robust reporting and I’m afraid has fallken rather foul of itself on this occassion” on the basis of your interpretation of a headline and yuor own fascinatin with the risks of nitrous is patently absurd.

  47. kingshiner said,

    March 11, 2007 at 6:23 pm

    I’m quite sure the MHRA mean well, but they shouldn’t resort to misrepresenation of science. I’m sure you mean well too Drduncan, but nor should you… defending the MHRA statement as ‘partially correct’ by confusing a drug-induced high with a hypoxia-potentiated orgasm? Come on, you know these aren’t the same thing

  48. radar said,

    March 12, 2007 at 10:34 am

    Apropos to little that’s been said – all of this reminds me of something we used to do at school called the ‘Pilot’s Test’ (allegedly used by the RAF to simulate something or other). Now don’t try this at home kids. You crouch down and hold your knees up to your chest and take 30 really deep regular breaths. Then stand up and hold your breath. You will fall over and go all rushy, sometimes faint. My mate did it once in music lesson and smacked his head on a radiator – he took a couple of minutes to come round and we were shitting ourselves. Extra hard classmates would make someone ram them against a wall and compress their chest at the ‘standing up’ moment – guaranteed to make them pass out.

    People who I know who occasionally do N2O describe something similar but with more giggling. Sounds rubbish to me…

    Aah the stupidity of youth. Apologies for off-topic ramblings down memory lane.

  49. Andrew Clegg said,

    March 12, 2007 at 11:10 am

    Robert, re. 41:

    I decided, for abstract curiosity, to look up online “How is nitrous oxide prepared”. As it’s a sensitive topic I won’t provide a hyperlink or credit, or the method (as pointless as it is to be coy)

    Umm… The page that you quoted about industrial N2O being contaminated with NO2 mentions the method and it sounds perfectly innocuous to me. I was expecting it to say they get it by bubbling nitrogen and oygen through rabbits’ livers in vivo or something from your, err, coy moment.

    Or did you just mean, you don’t want to give the kids ideas about trying this at home? Bit redundant since you can buy it all over the place.

    Which reminds me, TheMole (37) says:

    I’ve never tried nitrous, but a quick google reveals a few sites and a lot of ebay sellers selling N2O for whipping cream with suspicious “now, you’d never do anything naughty with this, because its really only for whipping cream” type disclaimers. While selling boxes of 600 refill bottles for a toy-sized cream whipper. Hmm.

    On Camden High Street there are vendors selling (along with really big rizlas and the last type of magic mushroom they forgot to ban) dispensers and refills labelled for catering use. Underneath a big picture of a heavily tattooed and pierced punk winking at the camera while he holds a balloon to his lips. Subtle :-)

    Andrew.

  50. BrickWall said,

    March 12, 2007 at 11:10 am

    I’ve always thought anyone engaing in auto-erotice asphyxiation is likely to be nuts as well as very sad – really, even if it worked doing that to yourself just for an improved wank?

    I wonder though if it really does work? I have this picture of these people trying it because they’ve been told it does and then assuming they have done it long enough for it to work properly until the time they do it a bit too long!!

    Any practitioners out there willing to explain the fun?

  51. BrickWall said,

    March 12, 2007 at 11:13 am

    Jeez my typing is all up the spout of course I meant to say, “assuming they HAVEN’T done it long enough for it to work properly” – Idiot!

  52. Dudley said,

    March 12, 2007 at 12:13 pm

    I was just wondering where you got “this picture” from…

  53. BrickWall said,

    March 12, 2007 at 1:41 pm

    Oh its not my picture, I just found it, its one of my mates’ brothers pictures actually, just kept it for a laugh etc.

  54. stever said,

    March 12, 2007 at 1:43 pm

    re Cdavies 40#

    its very much not recommended to use nitrous made for car engine systems. It apparently has additives in it that could be nasty. recreational use should be with product passed for human consumption, medical or catering.

  55. CaptainKirkham said,

    March 12, 2007 at 5:39 pm

    All I know about this is that there are few things sillier than watching people at a party breathe in and out of balloons. Honestly, it is one of those “reality check” moments. Also, it makes people’s lips go blue. Luvverly.

    But I have to say that this whole MHRA thing sounds like a typical (and typically pathetic) example of the “drugs are baaaaaad” instinct and will not be listened to one jot. It will not be trusted or taken seriously. One person dies because of a plastic bag over his head – honestly, that is not the least bit relevant to people sucking out of balloons using soda syphons.

  56. Robert Carnegie said,

    March 13, 2007 at 1:51 am

    Auto-erotic asphyxiation – en.wikipedia.org/wiki/Stephen_Milligan , possibly Michael Hutchence – I haven’t got straight whether Paula Yates thought he had or hadn’t. The question was suicide but I think it would have to count either way really?

    It appeared in an episode of [Six Feet Under] recently repeated – a stranger dies at the start of each show and ends up in the funeral parlour. In this case I think characters in the show argued whether it was an urban legend, and I believe they included the “bite on a piece of citrus fruit” part. Other tellers of the story seem to have been unsure of where to put that, so to speak.

    www.goaskalice.columbia.edu/1866.html (not really work safe, like that matters by now either) claims “between 500 and 1000 deaths occur annually in the United States from this”, which is citeless and vague.

  57. fridgemonkey said,

    March 13, 2007 at 1:55 pm

    Does anyone know if there’s an increased level of risk associated with taking N2O and helium at the same time? Because there’s an unexploited market out there for squeaky-voiced hilarity, surely.

    Unfortunately inhaling Nitrous from a balloon, which has just been dispensed under pressure from a cylinder or a whipped cream dispenser, chills the vocal chords [cos the gas is cold]. So the hight voice helium effect is cancelled out by the lowered voice from the cold N20.

    Apparently.

  58. Suzy said,

    March 13, 2007 at 10:46 pm

    Glad to see the Folate / B12 thing was sorted

  59. raygirvan said,

    March 15, 2007 at 1:03 am

    500 and 1000 deaths …citeless and vague

    True, but it’s not far different from the figure cited in an Andrew P Jenkins medical paper that’s easy enough to Google. Jenkins and others argue that it’s under-reported for various reasons, particularly in the case of teenage deaths where parents clean up the scene. The profile of potential cases commonly turns up in the papers: teenage male hanging that isn’t clear suicide (e.g. no note, no history of self-harm, no stressful circumstances) and the police find no evidence of foul play – investigation fizzles out into a coroner’s open verdict.

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