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Medicine

French Drug Trial Leaves One Brain Dead and Five Critically Ill (theguardian.com) 232

jones_supa writes: One person is brain dead and five others are seriously ill after taking part in a phase one drug trial for an unnamed pharmaceutical firm at the Biotrial clinic in France. In medicine, phase one entails a small group of volunteers, and focuses only on safety. Phase two and three are progressively larger trials to assess the drug's effectiveness, although safety remains paramount. The French health ministry said the six patients had been in good health until taking the oral medication. It did not say what the new medicine was intended to be used for, but a source close to the case told AFP that the drug was a painkiller containing cannabinoids, an active ingredient found in cannabis plants. Mishaps like this are relatively rare, but in 2006 six men fell ill in London after taking part in a clinical trial into a drug developed to fight auto-immune disease and leukaemia. All trials on the drug at the French clinic have been suspended and the state prosecutor has opened an inquiry.
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French Drug Trial Leaves One Brain Dead and Five Critically Ill

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  • Naughty cannabis (Score:2, Insightful)

    by Anonymous Coward

    Waiting for all the morons to blame cannabis. It's Friday, work's done, I'm stoned. Love you all x

    • Re:Naughty cannabis (Score:5, Informative)

      by Fwipp ( 1473271 ) on Friday January 15, 2016 @11:54AM (#51308019)

      The article clarifies:

      Touraine said the drug was meant to act on the body’s endocannabinoid system, which deals with pain. Earlier reports had suggested that the drug contained cannabinoids, an active ingredient found in cannabis plants, but the minister said it did not contain the drug or any derivatives of it.

      • Re: (Score:2, Funny)

        by cayenne8 ( 626475 )
        Why not just let people consume the plant pretty much in its natural state?

        That's been proven SAVE for centuries....

        • by SJHillman ( 1966756 ) on Friday January 15, 2016 @12:09PM (#51308159)

          It appears to alter the subject's ability to spell simple words, even when the word is emboldened and all caps.

        • Re:Naughty cannabis (Score:5, Informative)

          by Anonymous Coward on Friday January 15, 2016 @01:38PM (#51308981)

          Why not just let people consume the plant pretty much in its natural state?

          Because that the endocannabinoid system can't be fully manipulated in all ways possible by just using naturally occurring stashes of THC.

          The brain contains two primary receptors (CB1 and CB2) and a few minor G protein receptors as the trigger points of the endocannabinoid system.
          The remainder of that system is the parts of the brain that generate THC to fill those receptors.

          The system as a whole has a cascading effect on things in the brain everywhere from pain control to required memory forming processes to mood control.

          Cannabis as found in plants is of forms not generated in the brain, and typically only stimulate one of the two major receptors, and rarely the G protein receptors at all.

          From those that enjoy THC use recreationally, CB1 stimulation manifests as a "sleepy relaxed pain-killing high" where CB2 stimulation manifests as a "creativity and energy boost high"
          But other than various amounts of receptor stimulation and thus various "how high" levels, you don't get much more out of it than that.

          There are fully synthetic versions of chemicals designed specifically to stimulate both CB1 and CB2 (sometimes completely) as well as designed to hit the G protein receptors in various ways and by various methods.
          These chemicals are usually called "THC equivalents" but the vast majority are anything but equivalent when looking at what they do and how they go about doing it in comparison to natural THC.

          Did you know if you stimulate CB2 at 95%+, CB1 at anything over 50%, and block GPR18 uptake from the brains natural sources, you can induce a full sensory pathway failure for a few minutes?

          The chemical JWH-210 was designed to do just this, and in effect causes a 10-15 minute "trapped in" coma with all the effects of sensory deprivation and decoupling the differentiation between sensory input and your memories of past sensory input.
          The recreational crowd usually describes this as forced lucid dreaming.

          The chemical AM-2232 stimulates CB1 partially and completely overloads CB2 beyond 100%, while also doing "something" to the Ki receptors previously thought unrelated to THC usage.
          It has been described as "Imagine the highest high you have had, and multiply that by a hundred. Once you are high enough, keep going because it doesn't stop there"

          The idea of AM was to provide pain control on the level of opiates, but without the dependency and withdraw issues opiates have. That part didn't quite work out in earlier versions of the chemical however (the withdraws were quite different from opiates, but there were still withdraws) and the chemical made a schedule 1 banned substance before further research could be done.

          None of this is possible to obtain from THC in naturally growing plants.
          The brain is much more complex than that, and can be "hacked" in many more ways and combinations using chemicals designed for that explicit purpose that have no naturally occurring equal.

          If you'd like to kill a couple days with further reading, I submit to you the following research:
          https://en.wikipedia.org/wiki/JWH-018 [wikipedia.org]
          https://en.wikipedia.org/wiki/List_of_JWH_cannabinoids [wikipedia.org]
          https://en.wikipedia.org/wiki/List_of_AM_cannabinoids [wikipedia.org]

        • Now where's the money in that?

      • Re:Naughty cannabis (Score:5, Informative)

        by fahrbot-bot ( 874524 ) on Friday January 15, 2016 @12:11PM (#51308165)
        Also reported in the NY Times [nytimes.com]:

        Contrary to several reports in the French news media, the drug was not a cannabis-based painkiller, Ms. Touraine said.

        • Simple misunderstanding. It wasn't a cannabis based drug, it was cannibal based.
      • by msobkow ( 48369 )

        As with all synthetic cannabis, side-effects may include death... :(

      • You really think that facts mean anything when it comes to drug hysteria? C'mon, how long have you been around?

      • by wjcofkc ( 964165 )
        Weed is for the devil, so let's make a synthetic version we don't really know anything about and see what happens! After all, the effects of marijuana have never been studied and are a complete unknown. Right?
      • by Holi ( 250190 )
        ABC, CBS, Bloomberg, Daily Mail, Verge, and many more have all reported incorrectly that it was a cannabis based drug.
    • by GuB-42 ( 2483988 )

      Not all cannabinoids are THC. In fact There is a whole market for synthetic cannabinoids as legal substitutes for marijuana, most of them much more dangerous than the real thing and usually made illegal as they gain popularity.
      Additionally, because THC is a well known natural substance, it is not patentable and the pharmaceutical industry doesn't like it. Should they make a drug containing cannabinoids, they are more likely to use a molecule that can be patented.

    • Waiting for all the morons to blame cannabis.

      API: Dozens of school children were murdered by a deranged gunman in YourCity, USA earlier today. Governor Dumbshit (R|D) deplored the loss of life, but reminding voters that "at least we can rest easy in the knowledge that the gunman's second amendment right to bear arms was in no way abridged." Early reports that the bullets contained cannabis, and that medical marijuana lies at the heart of the tragedy, have been debunked, although Governor Dumbshit (D|R) has promised voters a thorough investigation "to get to the real facts." After wiping drool from his chin, the Governor went on to say, "If cannabis bullets weren't responsible for the loss of life, then why did investigators feel the need to deny cannabis was involved? Clearly, where there's smoke, there's cannabis."

  • by xxxJonBoyxxx ( 565205 ) on Friday January 15, 2016 @11:52AM (#51308009)

    >> 1 dead 5 wounded in a drug trial

    That's why they call it a trial and limit who can be in it (so it's not 1,000 dead and 5,000 wounded).

    • I will be curious to hear some real facts come out about this ... brain death isn't a small mishap, it's a pretty serious reaction.

      One wonders what they were really given.

      If you have 90 random people smoke or ingest cannabis, I bet none of them would end up brain dead.

      • I am keeping an eye on these things as a chronic pain patient who is prescribed cannabis, but I am not 100% sure exactly WHICH drug this is about... It might have been BIA 02-093, aka Eslicarbazepine, from looking at earlier trials for painkillers by this company. Anyone know for sure?
        • TFA is short on facts, the claim it was cannabis derived is being rejected.

          Short answer, it doesn't look like anybody has said anything meaningful yet about the actual drug in question.

          • by Dogers ( 446369 )

            And they probably won't either, in order to protect the investment they've put in it so far..

        • It probably hasn't been determined yet, but I'd like to know where the problem ultimately lies: Is it actually in the formulation of the drug, or was it mis-manufactured, mis-administered, or simply contaminated at some point?
      • At least not from a single dose.

        I do know a few potheads, though, and "brain dead" is a pretty good description....

      • by Megol ( 3135005 )

        If one of them is allergic it could happen. It may be what killed this brave* test pilot.

        (* I really think he/she was, taking a risk for potentially improving the world)

    • by vux984 ( 928602 ) on Friday January 15, 2016 @12:08PM (#51308145)

      Exactly right. And its also exactly right that the prosecutors office investigate to make sure that all protocols were followed.

      This sort of thing is rare because the protocols to get a drug approved for human testing generally work. We know occasionally there will be events like this and its a risk we take. But in an event like this we need to establish that nobody was playing fast and loose with the protocols. Make sure data wasn't faked, make sure anything that might have predicted this wasn't suppressed or concealed, make sure the test subjects were being properly monitored, etc.

      • by lgw ( 121541 )

        This sort of thing is rare because the protocols to get a drug approved for human testing generally work.

        They work well enough that I'd be surprised if this was the result of corner-cutting on the research. I think it's more likely that something went wrong in the preparation.

    • We can prevent this from happening again if we eliminate the onerous regulatory requirements to perform drug trials.

      (note: joke)

  • "the drug was a painkiller containing cannabinoids" the french ministry of health says no cannabinoids was involved:

    http://www.liberation.fr/franc... [liberation.fr]

    The drug is about treating anxiety.

  • One thing's for sure (Score:5, Informative)

    by Nidi62 ( 1525137 ) on Friday January 15, 2016 @11:55AM (#51308029)
    You know the other 2 are suddenly REALLY happy they got the placebo
    • You know the other 2 are suddenly REALLY happy they got the placebo

      Expect that in Phase 1 trials, no one is given a placebo. The purpose of Phase 1 trial is testing for safety, not efficacy, and is given to a very small number of healthy test subjects.

      • by Nidi62 ( 1525137 ) on Friday January 15, 2016 @12:16PM (#51308229)

        You know the other 2 are suddenly REALLY happy they got the placebo

        Expect that in Phase 1 trials, no one is given a placebo. The purpose of Phase 1 trial is testing for safety, not efficacy, and is given to a very small number of healthy test subjects.

        It has been reported in several media outlets that 6 were given the trial medication and 2 were given placebos in this particular round. In all around 90 people have participated in the Phase 1 trial so far, The article in the summary specifically states that some of the 90 were given placebos while the rest were given differing strengths of the drug. Everything I've read states that this particular round used the highest concentration of the drug and implies that with the other rounds the dosage increased with each round. So sounds like they were trying to find a maximum safe dosage. Basically they were looking for side effect or potential harm, in which case you certainly need a placebo group in each round to determine a baseline. And I would say they were wildly successful at determining the dosage at which the drug is unsafe.

      • Re: (Score:2, Interesting)

        by Anonymous Coward

        Expect that in Phase 1 trials, no one is given a placebo.

        This is entirely incorrect.

        Dose-ranging [wikipedia.org] is usually a phase I or early phase II clinical trial. Typically a dose ranging study will include a placebo group of subjects, and a few groups that receive different doses of the test drug. For instance, a typical dose-ranging study may include four groups: a placebo group, low-dose group, medium-dose group and a high-dose group.

      • Re: (Score:2, Informative)

        by Anonymous Coward

        According to French website Figaro [lefigaro.fr],

        [C]es essais de phase 1, après avoir été menés sur des chimpanzés, ont débuté le 9 juillet 2015 dans les locaux de Biotrial. 128 hommes et femmes participent aux essais. 90 personnes se sont vu administrer cette molécule à des doses variables, les autres ont pris une dose placebo , a indiqué la ministre.

        "The phase-1 tests, after having been done on chimpanzees, started on July 9 2015 at Biotrial. '128 men and women participated in the tests. 90 were administered the drug at different doses, while the others took placebo', said the minister (of Health, Marisol Touraine)"

    • You know the other 2 are suddenly REALLY happy they got the placebo

      actually, they were all taking the placebo. the first person fell down a flight of stairs after "feeling dizzy" and four behind him suddenly felt dizzy too falling down atop the first. it seems odd and unbelievable until you find out they were all soccer players. [imgur.com]

  • Comment removed based on user account deletion
  • by Ecuador ( 740021 ) on Friday January 15, 2016 @11:59AM (#51308069) Homepage

    I thought it went "Blame Canada".

    But if it was natural cannabinoids we have to "congratulate" the lab for producing something deadly from a relatively benign plant...
    Also, I am curious how this can happen. Before starting such trials they are supposed to give huge doses of the "new" stuff to some unfortunate non-human mammals. I didn't know there could be a fatal compound that is non-fatal for e.g. rats in larger doses (if it was, it would have raised many flags I assume).

    • While we're not likely to know the details for a while yet, I wonder if it might not have had something to do with trying to create a synthetic or artificial version that does the same thing, in order to get around drug war paranoid reactions to the "natural" version. It's always struck me as ridiculous that society tends to be so averse to the idea that something beneficial could also be pleasant, so we have to strip one from the other. I wouldn't be surprised in the least if doing that sort of thing led t
      • And, really, if you're trying to test this ... do a bloody honest test.

        You do an study in which one group is (placebo|synthetic) and another group which is (placebo|pot).

        If you're trying to test a lab-made version of it, you should also be testing the real thing to prove you're doing better.

        Nobody will let you run that test, but I'm betting anxiety among your group with the pot goes down, unless someone has too much and has an unpleasant ride. I'm also betting absolutely ZERO of your pot users end up brain

  • I am always surprised they find people who willingly participate in drug trials, especially for something like a painkiller. Do we really need ANOTHER painkiller on the market?
    • by swb ( 14022 )

      Of course we do, all the truly effective ones now are opioids and they get you high, too, and our Calvinist morality and repressive drug control regime hates this, so we are desperately trying to find something, anything, that actually works as a painkiller without any euphoric side effects.

      True, there are some alternatives, but all the really heavy anti-inflammatories have nasty cardiovascular risks and the others, like gabapentin do some nasty things to neurotransmitters and really only have marginal effe

      • Re:Drug trials (Score:4, Insightful)

        by Tranzistors ( 1180307 ) on Friday January 15, 2016 @01:08PM (#51308689)

        > and our Calvinist morality and repressive drug control regime hates this

        Oh please! Problem with all current pain killers is that they are NOT EFFECTIVE for chronic pain. Opioids require ever bigger dosage to get the same effect, and your plan to "monitor their therapies" just mean that if the source of the pain is not dealt with, treatment will not be effective. But sure, blame Calvinists.

        • by swb ( 14022 )

          My understanding (and experience) with opioids is that the tolerance is mostly to the psychological effects, not the actual pain reduction.

          This was also my personal experience after an accident ripped my hand up, requiring half of a finger to be amputated and a bone fusion in the other finger.

          I got decent pain relief on a fixed quantity of oxycodone for about 4-5 months.

          Not sure if that counts as "chronic pain" but without oxycodone, my hand hurt like crazy until it had sufficiently healed. Maybe it's diff

          • I too am no doctor, but I have spent time under pain killers after surgery and if your case was anything like mine, the original source of pain became less and less intense. Like, if in the first week you would be on pain level 9 without medication, but after 10 weeks pain level would have dropped to level 5, and the required amount of morphine is the same, then you have developed some tolerance.

            I had to use morphine for couple of weeks and didn't even notice any withdrawal, but what I have gathered (anecdo

    • If it's one that has less addictive properties than opiates but similar efficacy then yes.
    • It's easy money. I know poor people who do this. It's kind of fucked up, but that's how it is.

    • I volunteered in a drug trial around 1995 or so. Back then, it paid NLG 100 per day, or EUR 70 corrected for inflation. When you're in college, that's a lot of money, especially since you can study your quantum mechanics at the same time. There was a guy who was participating in studies all the time.

      It was a phase-2 trial though; the (benign) side effects were already known. Phase 1 and drugs with severe side effects paid better. And we were told what kind of medicine it was and what side effects to expect

  • This is a pretty interesting reminder that many drugs' mechanism of action aren't fully understood. Even those that are well known operate solely by suppressing or enhancing some specific chemical reaction chain, so in reality they're pretty blunt tools. It's really interesting to think about the drug discovery process; everyone assumes that they at least won't die if the drug has made it to human trials, but apparently that's not the case!

  • I know know, terrible insensitive joke.

  • I thought phase 1 is always on animal.... no?
  • Do they do animal testing with drugs like this on chimps or monkeys to ascertain this kind of safety ahead of time before giving it to humans?

    I would imagine they might have given it to rats just to make sure they didn't fall over dead immediately, maybe dogs, too, but I would expect that chimps would have a brain structure more similar to humans and might have been more revealing in safety of a drug like this.

    I can appreciate where some chimp experiments might be a bit harsh, but a pain killer that you hav

    • You can't use chimps unless there's reason to believe nothing else would be close enough. Monkeys ought to be just fine though...
    • Yes, it's written in the article, but wait, it's /. so you didn't read TFA...
    • Do they do animal testing with drugs like this on chimps or monkeys to ascertain this kind of safety ahead of time before giving it to humans?

      RTFA

    • There is a sequence of testing which is done on animals. I can't remember exactly how it goes, but I think it starts with mice and rats then moves up to rabbits and dogs (beagles, because the poor buggers are so docile). A whole host of tests are done and these are, unfortunately, necessary unless we want more things like this to happen. Tests can't catch everything, but they're better than nothing. It should be emphasized that these are safety tests, which are distinct from the research that needs to be do
  • Comment removed based on user account deletion
  • Correlation... (Score:4, Informative)

    by Dunbal ( 464142 ) * on Friday January 15, 2016 @02:08PM (#51309279)
    Thus proving time and time again that mouse biochemistry != human biochemistry. "But it was working fine in the lab!"
  • BIA 10-2474 (Score:5, Informative)

    by orledrat ( 3490981 ) on Friday January 15, 2016 @02:11PM (#51309309)
    The drug in question appears to be a FAAH inhibitor named BIA 10-2474 [wikipedia.org].
    • Re:BIA 10-2474 (Score:5, Informative)

      by pesho ( 843750 ) on Friday January 15, 2016 @04:41PM (#51310525)

      This is still a speculation. The drug does seem to be called BIA 10-2474, according to recruitment materials from the drug testing company. There is only circumstantial evidence that this is a fatty acid amide hydroxylase (FAAH) inhibitor. The speculations are based on patent filings [freepatentsonline.com] by the pharmaceutical company which ordered the trial (Bial) and the general description that the drugs was "meant to act on the body’s endocannabinoid system". FAAH is an enzyme that among other things degrades endocanabinoids. The rational is that if you slow the degradation of endocanabinoids you will experience less pain (works on mice). So far nobody who is in position to know it has made a statement as to the specific mode of action of the drug or its chemical structure.

      According to fairly vague statements it seems that they were doing a dose escalation study, where different groups of people are given increasing doses of the compound in order to determine the point where the side effects start to show up. The people who got injured were in the group that received the highest dose. Usually this is done very carefully so you can stop before the side effects become severe. However, the response to drugs is not always in linear relationship with the dose and a small increase over a certain threshold may produce very severe adverse effects. This is always worked out in advance on lab animals (mice, rats, rabbits, etc). In the patent application they only cite testing in mice. Subtle differences in the biology of lab animals and humans have caused at least one other clinical trial to turn into a disaster [nih.gov]. Of course there is always the possibility that somebody screwed up the dosing and gave them more than they should have received.

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