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

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.

11 of 232 comments (clear)

  1. Re:Naughty cannabis by Fwipp · · Score: 5, Informative

    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.

  2. One thing's for sure by Nidi62 · · Score: 4, Informative

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

    --
    The only thing necessary for evil to triumph is for it to be pitted against a slightly greater evil
    1. Re:One thing's for sure by Anonymous Coward · · Score: 2, Informative

      According to French website Figaro,

      [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)"

  3. Re:Naughty cannabis by fahrbot-bot · · Score: 4, Informative
    Also reported in the NY Times:

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

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    It must have been something you assimilated. . . .
  4. Re:Naughty cannabis by orledrat · · Score: 5, Informative

    Endocannabinoid system is modulated by more than just THC, CBD and the regular ol' cannabinoids in ganja. It's a rather complex system whose functional mappings and tructure-activity relationships are not very well understood.. yet. It offers incredible potential for modulation, far beyond what cannabis can do, and I for one welcome our Pharma Overlords to throw their resources at these problems.. provided that they don't botch things up like this, for fucks sake.

  5. Re:Naughty cannabis by Anonymous Coward · · Score: 5, Informative

    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
    https://en.wikipedia.org/wiki/List_of_JWH_cannabinoids
    https://en.wikipedia.org/wiki/List_of_AM_cannabinoids

  6. Correlation... by Dunbal · · Score: 3, Informative

    Thus proving time and time again that mouse biochemistry != human biochemistry. "But it was working fine in the lab!"

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    Seven puppies were harmed during the making of this post.
  7. BIA 10-2474 by orledrat · · Score: 5, Informative

    The drug in question appears to be a FAAH inhibitor named BIA 10-2474.

    1. Re:BIA 10-2474 by pesho · · Score: 4, Informative

      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 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. Of course there is always the possibility that somebody screwed up the dosing and gave them more than they should have received.

  8. Re:The drug concerned by h4ck7h3p14n37 · · Score: 2, Informative

    I also believe BIA 10-2474 is the compound based on what I've been able to piece together via web searches.

    Here are the sources I located:

    http://www.biocentury.com/prod... http://www.insurancejournal.co...

    This is truly tragic, God help the people affected.

  9. Re:Naughty cannabis by h4ck7h3p14n37 · · Score: 4, Informative

    I don't know where you're getting your information, but it's not a good source. No one has ever died from consuming cannabis, yet you claim multiple people have. I'm curious, what were there names, where were these deaths reported?