Oh "Doctor suspects", does he? This doctor suspects otherwise.

May 5, 2009

More Ecstasy users dead, this time in Edmonton.

Cassie, 14, and friend Ashley were at a Rock ‘n’ Ride Dance Party at West Edmonton Mall on April 24. They took some ecstasy but got so sick they had to be taken to hospital.
Her friend recovered, but Cassie died over the weekend.

Dammit! Did I mention I’m the parent of a nonzero number of mini-women? Dammit, dammit, DAMMIT!
and… it gets worse.

There was a prior pair of deaths at the Paul Band First Nation west of Edmonton:

Just last month, 14-year-old Leah House and 15-year-old Trinity Bird died in hospital after taking ecstasy along with seven other girls on the night of March 21.


As you might anticipate this is not news to Your Humble Narrator. I tend to keep tabs on the Ecstasy deaths and they pop up with regularity in the news.
In this case, I’m particularly exercised over an article which quotes Charles Grob, M.D. (UCLA page):

Charles Grob believes there is a strong chance that a deadly batch of adulterated pills is making the rounds in and around Edmonton, though health officials and law-enforcement groups have issued no such public warning.
Dr. Grob, a professor of psychiatry at UCLA, was the first U. S. researcher to conduct human tests of methylenedioxymethamphetamine, or MDMA, the technical name for Ecstasy, since it was outlawed in the U. S. in 1984. It is rare for anyone to “overdose” on the drug in its pure form, he said.
There are but a few dozen deaths linked annually with Ecstasy in North America; mostly, they arise from complications, such as pre-existing heart problems or hyperthermia that occurs when high, frenetic raver kids overheat themselves.
But three girls, all within a few weeks of each other, in the same vicinity, and none of whom were observed exercising hyper-actively, he says, is too unusual to be MDMA-caused. “I think there’s something else in those pills,” Dr. Grob says. “It would be awfully coincidental if all three of these teenage girls had congenital heart problems that had not been identified earlier. I’d put my money on a drug substitute.”

Here’s my take. We don’t bloody well know. Period. Until we have a comprehensive tox report showing what was and what was not in these kids’ bodies when they died. It is quite possible, however, that MDMA is indeed the primary cause.
Quoting from my prior post on this very topic:

Street ecstasy tablets are notoriously variable in psychoactive drug content. Structurally related compounds such as MDA, MDE and good ol’ Methamphetamine are commonly detected. Behaviorally related but structurally unrelated caffeine is also observed, as are a host of what might be “filler” compounds such as tylenol. Paramethoxyamphetamine (PMA) is a decent suspect as it does seem to exhibit a fairly steep dose-response function. Another way to look at this is a narrow recreational-index, i.e. the difference between the dose which produces the desired recreational effect and adverse consequences in a substantial fraction of the population is small.
Nevertheless, it is also the case that MDMA itself is capable of producing the types of lethal and near-lethal effects that are reported in Case Reports and the popular media. There are the occasional reports in which no other suspect drugs are reported. Moreover, resort to the animal research literature shows that under certain conditions, MDMA and MDMA alone is capable of causing death in mice, rats, dogs and nonhuman primates.

Now from this article we find:

The hospital did not find rat poison in the girls’ bloodstream and did find Ecstasy.

I’ll make the assumption here that they are talking about MDMA and that the hospital actually reported this as such. I can’t find much on the tox yet. Note, the users/fans/etc are all over this issue too.
I will renew my pleas for local authorities and the medical examiner, not to mention the sensation-seeking press, to do whatever they can to make full tox information available. “Rat poison”? Can we stay serious here people? This is public health. As I say fairly frequently, the Ecstasy user is comparatively sensitive to information on the likely risks of the drug. No, I’m not being naive. You can look at many, many user practices which are promulgated on advocacy/harm reduction websites and forums online and talk to your local users (do you talk with your undergraduates, professors?). Chill out rooms, tryptophan loading, various vitamin prescriptions, cautions on dose and frequency….you can draw direct links to available knowledge from Case Reports of medical emergency/death, on-site experience of harm reduction outfits and the preclinical research literature. Now, I’m not saying that stuff necessarily is helpful to avoid all potential adverse consequences, I’m just saying that the target audience is…receptive. And in the absence of information to the contrary, this population is going to go to the mat denying that it could possibly be MDMA itself that is the root cause of fatality.
I’m here to say that it is completely possible and there are features of this particular case that make my supposition even better supported than is usual when dissecting the available public press information. With respect to Dr. Grob’s and my competing suspicions let us note this:

Cassandra Williams, who died from pills bought at the mall party, reportedly took six; Trinity Dawn Bird and Leah Dominique House, from the Paul Band, reportedly took five each

and this:

The [Edmonton] ME’s office has found they can range anywhere from 50 to 1,000 milligrams per tablet.

Cassie’s mom, Angela Eyre, said her daughter’s friends told her she took six hits of E, and that the pills were what’s known as a triple stack, or three times the regular dosage.

That high end is really high from what I’ve read in published data. Much more common would be the 50-150 mg range per tablet. I do note that if the ME is going to talk to the press, perhaps he might have actual MDMA levels to discuss or at least follow up ? And levels of the major metabolites HMMA and HHMA and MDA would come in handy too. And perhaps they might go out and round up some street Ecstasy that looks like what the friends are reporting the girls to have consumed?
Never. The. Less. Dr. Grob. Five or six tablets? So we’re talking a low of 250 mg, very possibly 500 mg and potentially 750 mg? In teen girls, so my 50 kg lower bound on bodyweight is even more likely. Anywhere from 5 to 15 mg/kg ingested? Are you paying attention o ye denialists who think that preclinical doses are absurdly high? At least when it comes to certain studies in both monkeys and rats, these are mg/kg equivalent. We don’t even have to get into dose scaling / Pharm 101 issues.
Remember from Hardman et al, 1973 that the LD50 for intravenous administration in monkey is 22 mg/kg (95% CI 17-28) and in dog 14 mg/kg (8-17). Mechan et al. 2006 used much lower numbers, but a repeated oral dosing (at 3 hr intervals) paradigm pointed to a very similar ~25 mg/kg (cumulative) LD50. To me this is consistent with a couple of other studies showing a negligible difference between injected (typically IM or SC) and oral dosing for several types of outcomes. Admittedly there is not a huge comparative literature. But oral dosing does not offer some huge categorical protection. The second issue we need to think about is that LD50 is the dose that is lethal for half of the subject population. But we are not talking detached science here. We are talking about the life of a person here. We are talking outcomes in which the LD10, LD1 or even LD0.01 is important to know. One might easily assume that when an oral dose of 5-15 mg/kg is consumed, there are going to be tangible numbers of people for whom this is a life-threatening dose.
So Dr. Grob’s confidence that it couldn’t possibly be the MDMA at cause here seems unsupported to me.
As I’m already at Oracian lengths, one more thing. This article made another irritatingly stupid statement:

There are but a few dozen deaths linked annually with Ecstasy in North America; mostly, they arise from complications, such as pre-existing heart problems or hyperthermia that occurs when high, frenetic raver kids overheat themselves.

First of all, complications are exactly the point! I mean what does anyone every die of when a drug with other purposes is involved other than “complications”. Otherwise, the death would have to be the intentional result of, i.e., a single-purpose poison. The fact that the drug interacts with other factors, individual or circumstantial is assumed.
Pointing to MDMA as the causal agent simply means that said congenital heart defect or energetic dancing would not have resulted in medical emergency and/or death itself without MDMA being on board.
And this gets me into complicating pharmacology especially when it comes to alcohol (we need to consider specifically related but non-MDMA constituents of the “Ecstasy” tablets a bit differently). The denialists of Dr. Grob’s ilk like to point to evidence of alcohol consumption in the tox reports of Ecstasy-related deaths and claim that this exonerates MDMA as a causal agent. Again, the question is whether that level of alcohol would have been problematic without MDMA. Furthermore, we might ask if the clinical profile is most consistent with MDMA toxicity or most consistent with toxicity related to other causes.
And there is a list of clinical findings that is associated with MDMA toxicity, consistently, regardless of the dosing circumstances or other contributing factors. This includes evidence of seizure (strange dancing, movement and even “found collapsed”), hyperthermia, hyponatremia and then some other consequences. They are remarkably consistent factors involved in the Case Reports and media descriptions. The linking factor, of course, is the presence of MDMA in the blood. Circumstances such as elevated ambient temperature, constitutive defects, water consumption, dancing and even specific non-MDMA tablet constituents are less consistently associated.
But yeah, Dr. Grob, it has to be that other stuff. Couldn’t possibly be the single consistent factor which, oh by the way, produces these same physiological responses when administered in controlled laboratory studies. Naah, couldn’t be.

No Responses Yet to “Oh "Doctor suspects", does he? This doctor suspects otherwise.”

  1. D. C. Sessions Says:

    DM, I know you try hard and I really do appreciate it, but this was not remotely Oracian.
    Then again, that’s quite a bar.


  2. Those are *really* high doses.


  3. kerri Says:

    Why in the world would anyone take 6 pills? These girls must have done this a lot to be needing the “6 pill” dose. What else did they have in their bodies. This tox report is important. overindulgent.


  4. Matthew Says:

    I’m no MDMA expert, but I seem to remember that MDMA can raise core body temperature. The argument (as I remember it, but I’m sure DM can explain) is that dancing, not drinking enough water, drinking alcohol and taking MDMA all contribute to MDMA related death. The presence of alcohol certainly does not exonerate MDMA as a causal agent, but it does suggest that excessive dancing, alcohol consumption, and dehydration (let alone any pre-existing heart problems) are equally causal agents in that death. The fact that there are so few deaths surrounding MDMA consumption, and the vast majority of those also involve “complicating” factors seems to suggest (to me) that MDMA is not particularly toxic as a single agent.


  5. DrugMonkey Says:

    Matthew @#4:
    These are some theories, yes. From my perspective those potential contributors are common enough, and the MDMA-related emergency/death uncommon enough, that we are still looking for consistent factors. In short, dancing, slight dehydration and co-administration of other drugs are no guarantee of getting into trouble, the flip side is that avoiding these is no guarantee of safety.
    There’s another biggie you missed. Although I don’t know that much about salt balance physiology, for sure hyponatremia is a frequent mention in case reports. It seems to me to be more common in the female ones but that’s a subjective call. MDMA appears (see Wolff et al, 2006 for one study) to increase ADH/AVP secretion which would cause the kidney to retain water. And of course there are the factors (including intentional reaction to the ‘dehydration’ theory) which induce users to drink excess(?) water. But one might presume these more general circumstances would affect a lot of people that don’t get into trouble.
    So what is it? A perfect storm of circumstances? maybe. An underlying individual difference (or several) that we don’t understand yet? Something to do with chronic use, tolerance and sensitization (that coma guy I posted on awhile ago)?
    Isn’t science fun?


  6. bill Says:

    “Rat poison”? Can we stay serious here people?
    I’m told that street drugs are sometimes cut with strychnine, which to many people is “rat poison”. My guess is that’s what the reporter was thinking of.


  7. bill Says:

    Huh? What ate the rest of my comment? I said something like:
    I’m told street drugs are sometimes cut with strychnine, which is supposed to intensify the high (allowing the dealer to include less of the actual drug). I guess that’s the “rat poison” the reporter is talking about.


  8. Dr. Feelgood Says:

    How do they do their tox tests? Does it just show positive for amphetamines or do they do a mass spec analysis?…..hmmm. I agree with you DM, there is no evidence for an adulterant,however, what is the real story? Were they not getting an effect of taking two, then they took two more and no dice, and then more? If it was that pattern, it may very well be PMA. If they were just young fucktards and downed six pills up front, then MDMA could easily be the culprit….Hell if you took 6 triple doses of aspiring you could die just as quick. The only thing you should take that much of is my scholarly opinions… 😛 No…that might cause an O.D. as well.
    Doc F


  9. Dr. Feelgood Says:

    aspiring – g = ASPIRIN…


  10. I, too, am the parent of a non-zero number of mini-women and several other mini-women who frequent our house are likely to all end up together at parties like that in the not-so-distant future. I’ve also gotten very interested in the risks of recreational drugs use, especially after a comment I got on the poppy seed tea death of a University of Colorado student – a parent whose son died six years ago wrote in and, most relevant to this story, hosts a website that includes his son’s tox report showing that opiate alkaloids were the primary cause of death.
    I’m very disappointed in Dr Grob because high-profile cases like this will have a huge impact on how MDMA risks are viewed by the public and, more importantly, by high school and college kids. I dabble in this media stuff and a responsible professional will think very, very carefully about the content and implications of their commentary.
    I don’t wish to make accusations but, as a scientist, let me propose a hypothesis. Perhaps a person who is the “first U.S. researcher to conduct human tests of methylenedioxymethamphetamine, or MDMA,” may have a conscious or unconscious bias, or even vested professional and/or financial interest, in spinning information on the safety of MDMA.
    I also cannot emphasize strongly enough DM’s call for restraint on unfounded speculation until the pills and the blood of the victims can be rigorously analyzed. If local authorities in Edmonton cannot find a qualified analytical laboratory with a rapid turnaround and international expertise in the area, I may be able to make one or two suggestions of US labs with such capabilities.


  11. Lab Lemming Says:

    Assuming that Dr. Grob did actually publish MDMA research, it might be worthwhile looking up his papers, comparing the doses he used in controlled settings to what these girls took on a big night out, and writing a brief but pointy letter to the editor.


  12. It is worth asking the question whether these deaths could have been avoided if MDMA were legally available, and thus users could be assured of ingesting a known dose of a known compound, and not an unknown dose of who-the-fuck-knows-what.


  13. David Says:

    a fascinating phenomena about ecstasy is that it’s adverse histological effects, in animals (where this can be tested) seem to be amplified by coincident loud noise. Noise potentiates MDMA induced changes in the striatum (brain nucleus) and in the heart. A medline search for “ecstasy noise” should find about a half-dozen papers on this topic.
    so to physiProf’s comment, it may be that even if legal, MDMA may be inherently dangerous in the setting in which it is used.


  14. Toweet Says:

    Virtually anything taken at the wrong dose can cause death.


  15. bsci Says:

    Virtually anything taken at the wrong dose can cause death.
    I think you’re missing one of the points here. There is a potentially lethal dose of MDMA and there are dose metrics for MDMA where it can interact with other factors in a lethal manner. If key spokespeople act as apologists and say the deaths aren’t due to MDMA, they are hindering research and public education that will help us understand what those doses are. Publishing the detailed results of the tox screens (with the surviving family’s permission) would go a long way to increasing our understanding and combatting misinformation.


  16. bill r Says:

    This is insane – you simply show your ignorance of what is really out there.
    An ecstacy pill with 250mg of active MDMA is not seen, period. The 80s are dead and gone.
    You can easily check online to determine the average MDMA content of “good” pills (pillreports.com). In short, it’s roughly ~75 mg. 125 mg of active MDMA would be considered a very high quality pill, and is seen rarely.
    There is zero chance these girls took anywhere over 250mg of MDMA, much less 500mg or 750mg. You simply can’t get that amount of MDMA on the market unless you are a “drug gourmet” with good connections.
    These deaths are a result of adulteration/substitution. MDMA is simply too expensive and too rare.
    PMA is the best guess.


  17. DrugMonkey Says:

    bill r, you seem to be missing the point that these girls were reported to have consumed 5-6 tablets. At the lower end of about 50 mg of MDMA / tab, this would be 250-300 mg total MDMA consumed. If they were 100 mg tabs, then 500-600. If 150 mg (seen, but I agree rarer) we’re up to 750-900 mg.
    Now, of course these could have been unusually low-content tabs, less than 50 mg. Sure.
    All I’m pointing out here is that there is very good reason, based on the available evidence and the most-likely tablet concentrations, that these girls took a relatively large dose. Also, that MDMA has estimates for the LD50 in animal models and that it is possible, especially with dose scaling Pharm101, that these girls consumed something close to that known lethal range.
    Thus it is not at all reasonable in this case to argue that it was something other than a direct result of MDMA itself that caused the deaths.


  18. DSKS Says:

    “MDMA appears (see Wolff et al, 2006 for one study) to increase ADH/AVP secretion which would cause the kidney to retain water. And of course there are the factors (including intentional reaction to the ‘dehydration’ theory) which induce users to drink excess(?) water. But one might presume these more general circumstances would affect a lot of people that don’t get into trouble.”
    This was what reportedly killed Leah Betts, which lead to a change in safe-use advocacy policy. Not that a helpful solution was really put forward other than “Drink water in reasonable quantity and try to piss regularly”. I ditched that youthful experiment myself because the stuff gave me lower back pain, which just kicked in my inner hypochondriac. Believe it or not, even on mdma you can start to feel vulnerable and stupid standing at a urinal for 10 min trying to piss because you’re convinced that your kidneys are about to explode.


  19. bill r Says:

    They consumed 5-6 tablets – which indicates that the MDMA content is very low. 125 mg of MDMA would absolutely floor a 50kg girl. 250mg wouldn’t make them sick, it’d cause them to pass out. The symptoms reported do not match the effects of these doses.
    The fact that they are sold as “triple stacks” makes it very obvious that these were adulterated. “Triple stacks” do not exist – they are a marketing term designed to gloss over the fact that you may feel different from a typical e pill.
    You have to consider the relative probabilities of
    1. Adulterated pills (extremely, extremely, extremely common. Nearly all pills are adulterated, and those bought by high schoolers will be bottom of the barrel scraps, even more likely to be terrible)
    2. Very very high quality pure MDMA pills. Very very very rare.
    If they took 5-6, then this is a corresponding drastic increase in adulterants. These adulterants (such as PMA) have a significantly different dose/response curve.
    So we have the possibility of:
    1. A large quantity of high quality MDMA absent adulterants, resulting in reaching the lower regions of the LD50 danger zone.
    2. A large quantity of pills containing adulterants, which easily reach and surpass the danger zone of PMA.
    We can argue about relative probabilities all day, but #2 is far far far more likely in my opinion. These are teenage girls with poor connections – they’re more likely to get shit pills than 125mg pure MDMA pills (which even experienced users have INSANE difficulty obtaining).


  20. DrugMonkey Says:

    Street Ecstasy is highly variable, both regionally and across time sure. But pill testing and police seizure sources suggest more like half of samples are only-MDMA.
    Disagree that 125 mg will floor everyone who tries it. Looking at both human lab studies and the clinical trials protocols this is nonsense. This is even before we know how many times these girls had tried Ecstasy and get into tolerance issues.
    Agreed that PMA would be my next bet but unless you know something about PMA in that market, no more likely than other nonMDMA contaminents.


  21. Agreed that 125 mg pure MDMA would not come close to flooring anyone, even if it was their first exposure.


  22. DrugMonkey Says:

    So I noticed that EcstasyData.org is back to testing again. (They seem to run out of funding periodically). For those who don’t know, this is an outfit that tests tablets submitted anonymously. Unfortunately there seem to be some legal issues that prevent actual content from being published but they do put ratios for tablets that contain multiple psychoactive compounds.
    If you wander over to the search page you can entertain yourself looking at just what psychoactive drugs show up in putative Ecstasy tablets. Relevant to this conversation, there does not appear to be a lot of PMA containing tablets being submitted for analysis.
    Do recall selection bias is rampant. You can do your own speculating about whether users would be more or less likely to submit tablets which appear to convey subjective experiences at odds with expectation for genuine MDMA.


  23. PalMD Says:

    Pardon the long comment, BroDrug:
    Several issues here.
    1) Morality of use: neutral more or less. It is possible to talk about the dangers of drug use without addressing it as a moral issue (as you always do). I think that advocates often confound criticism of the drug for criticism of the user.
    2) Ethics of the expert: As DrFreeRide points out, when an expert speaks, they better remember people are listening, and they better be careful of the consequences of their speech.
    3) Dangers of use: dangers of use are not defined solely by the dangers of the dose of the unadulterated substance. It is less relevant what the LD50 of pure MDMA is than the “intention to treat”. How a drug is used IRL is essential. If people typically use it with other substances, intentionally or otherwise; if additional behavioral risks of problems such as hyponatremia exist, or even the danger of, say, impaired driving—all these things contribute to the risk of a substance. If MDMA were used in a controlled environment and dispensed by a reliable laboratory, we would need to evaluate it somewhat differently.
    Of course, even with a controlled situation, idiosyncratic reactions are not uncommon, and people may die EVEN IF THEY DO EVERYTHING “RIGHT”.
    So, what are the risks vs. benefits of MDMA? Benefit: It feels good to take it. Further benefits: can be investigated scientifically.
    Risks: Death. Not a large risk, but a very, very bad outcome.
    I personally can’t see why anyone would advocate for its use. If studies eventually show safe and beneficial ways to use this drug, fine, but that is not the current state of our knowledge.
    Remember, this isn’t an issue regarding the morals of users, but the ethics of promoters.


  24. DrugMonkey Says:

    Risks: Death. Not a large risk, but a very, very bad outcome.
    And let us not overlook the other risks. Even long-abstinent former Ecstasy users are reasonably consistently found to have lasting affective and cognitive differences. There is also the exceptionally well characterized disruption of serotonergic function in animal models, a finding which has some support in human studies. Particularly in the case of affective disruption the connection makes a lot of sense. The cognitive symptoms (attention, verbal memory) are perhaps less clearly connected to the serotonin depletion, may have to look for other less well characterized consequences of MDMA exposure.
    As you might imagine, the synthetic conclusion that differences in affect or cognition in former Ecstasy users has something to do with MDMA itself is hotly contested by the MDMA fans.


  25. Benefit: It feels good to take it. Further benefits: can be investigated scientifically.
    Risks: Death. Not a large risk, but a very, very bad outcome.

    On a risk-benefit analysis such as this, you are going to be requiring discouraging a vast array of everyday activities that people take totally for granted and don’t even think about.
    Climbing trees: Benefit: It’s fun. Risks: Death. DON’T CLIMB TREES!
    Wading in the surf: Benefit: It’s fun. Risks: Death. DON’T WADE IN THE SURF!
    Recreational sailing: Benefit: It’s fun. Risks: Death. DON’T SAIL!
    Do you see how your analysis that balances “only fun” versus some completely unquantified risk of death gets you absolutely nowhere that has any relevance to how people make risk-benefit calculations in every other area of life?


  26. BikeMonkey Says:

    Wading in the surf: Benefit: It’s fun. Risks: Death. DON’T WADE IN THE SURF!
    Oh c’mon.
    Body surfing is totes fun and lots of people like to do it in my location. The people tasked with some degree of insight and oversight of this recreation, the lifeguards, do not tell people to stay the hell out of the water.
    They caution people about the presence of riptides, when stronger than usual surf is a risk for weaker swimmers, the fact that you should bloody well know how to swim and the way to bodysurf properly so as to minimize risk of breaking your face on a steep beach.
    What they don’t do is say “Hey, the ocean is perfectly safe, nothing can possibly happen to you out there that is the fault of the ocean.”
    In fact nobody does, from the casual tourist to the surfers who get in the water every day of the year.
    So why are drug advocates so keen to deny any possible risk of their preferred substance?


  27. So why are drug advocates so keen to deny any possible risk of their preferred substance?

    This is quite the straw man. There are many people who have thought long and hard about drugs who seek nothing more than application of the same risk-benefit analysis that we apply to every other policy decision in society except for drugs (and sex and war) to drugs.
    Anti-drug crusaders enjoy doing battle against the few people who may be “keen to deny any possible risk to their preferred substance”, because it is easy and allows them to sound sensible while maintaining an opposite, but equally cartoonish, position of their own.
    In my opinion, scientists who really care about mitigating the societal harm caused by currently illegal drugs should stop arguing with the few “illegal drugs are totes harmless and awesome” wackaloons, and start engaging a comprehensive cost-benefit analysis that includes (1) costs-benefits of prohibition itself, (2) costs-benefits of the use of particular drugs, and (3) costs-benefits of restricting access to particular mind-altering substances in terms of the effects on seeking other mind-altering substances.
    No one with half a brain really thinks that any particular drug is “infinitely harmless and beneficial”, and arguing against those people instead of engaging a comprehensive cost-benefit analysis is pointless.


  28. DrugMonkey Says:

    Then there are vast numbers of people with less than half a brain. You should talk to some actual people in the target populations, adolescents and college kids, sometime and see what they think they know about drug harms and the basis for their behavior. Talk to random d00ds in your bar or coffee shop (as I did yesterday, as it happens). See how many drug advocate falsehoods are parroted versus how many exhibit an informed view of reality.
    Your “many people” may reflect a demographic that you inhabit but it is at complete odds with any representative slice of the drug using population and of the voting public for that matter.
    “cartoonish” is utter bullshit. I clearly delineate the scope of my discussion to whether or not there is harm and the nature of that harm. This is totally independent of your risk-benefit trope, civil liberties, legal/illegal or other discussions. At worst I insist that such policy/legal arguments do not misrepresent facts, reality and available knowledge when they resort to those areas in making the case.


  29. Risk-benefit analysis is a “trope”? HAHAHAHAHAHAHAHAHAHAHAHAH!


  30. PalMD Says:

    Internecine blogwar!!!!!


  31. defender of idiots Says:

    in defense of the doctor, he only indicated a betting preference (i’d put my money on..) would you really accept this wager with the doctor at even odds (or a proxy):
    case 1: the girl died from a drug subsitute (idiot wins)
    case 2: the girl died from MDMA (DrugMonkey wins)
    to sweeten the odds, we’d even give you the win if no specific contaminant is identified in a tox screen.
    Rants don’t interest me. Would you really take the bet?
    I don’t have a dog in this fight. But it seems that the probability of MDMA overdose is less than the probability of toxic substitute overdose. At least if I had to bet. [by the way, don’t do the drug, you can die either way]


  32. MarkH Says:

    I initially didn’t think what he said was that unreasonable based on any time you get a cluster of deaths from the drug you should consider poor quality even in a legal drug market. Considering a quick review of the literature, there are many descriptions of people dying from contaminated ecstasy, or to be fair, poison pills containing no MDMA.
    For instance this one. Although this study of MDMA purity in the UK suggests a lower prevalence of contaminated pills since the 1990s.
    Taking a look at a case report and review of the toxicity of the drug would suggest many other clinical findings that should be present in MDMA toxicity, which also seems to be somewhat idiosyncratic in terms of how people are poisoned by the drug. It seems to be some people are susceptible to a malignant hyperthermia no matter what the dose. Toxic reactions have been observed even within the typical “therapeutic” range of the drug. If anything this would make me even more scared to use the drug since rather than being related to dose, you’re playing Russian roulette when taking the drug, aside from possible contaminants.
    For an informative review see here, a paper describes cases of fatalities as follows:

    As noted earlier in this review, the usual “recreational” dose of MDMA or MDEA produces blood levels in the range of 100–250 ng/mL, or 100–250 µg (0.1–0.25 mg) per litre. Most of the cases of serious toxicity or fatality have involved blood levels ranging from 0.5 mg/L to 10 mg/L, that is, up to 40 times higher than the usual recreational range. However, some have had levels as low as 0.11–0.55 mg/L, that is, overlapping the “normal” range and a little above it. This is an important point, because it demonstrates the degree to which the seriousness of the effects can be dependent on environmental factors other than the drug concentration.
    All the fatal cases that have been located through a literature search are summarized in Appendix 1, which includes additional reference material167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182 (available on the CMAJ Web site at http://www.cma.ca/cmaj/vol-165/issue-7/ecstasyappendix.pdf). Most of these cases are associated with the use of MDMA, but a number are primarily associated with amphetamine, MDA, MDEA, MBDB and other amphetamine derivatives. They are included here to emphasize that the fatalities depend on mechanisms that are common to all the amphetamines and not specific to “ecstasy.” After eliminating, where possible, cases that are duplicates of the same cases already reported by other authors and cases involving only amphetamine or methamphetamine rather than the ring-substituted derivatives, the search indicates a total of 87 reported deaths involving “ecstasy” or related drugs, in which the primary cause of death appears to be as follows:
    · cardiovascular, including cerebrovascular 8
    · hepatic 4
    · cerebral, including hyponatremia 9
    · hyperpyrexic 30
    · misadventure (suicide, accident) 14
    · unknown — insufficient information 22

    Based on the data presented in this paper and elsewhere, Grob’s statement that OD from ecstasy is “rare in its pure form” certainly appears false. There is a toxicity specific to the drug, possibly with idiosyncratic ODs in a therapeutic or recreational range. In terms of suspecting a cluster, considering 0.5-2million tablets of X are taken weekly in Britain, he might not be far off the mark in being concerned about a contaminant. I would hope public health officials would work quickly to rule out such a risk.
    But is he a denialist? I don’t think so. So far, he’s just wrong. I think there’s a difference. Once he starts espousing theories about how the government is conspiring to spread fake reports of ecstasy deaths, or is falsifying research on its toxicity, then maybe I’d be concerned about denialism. As it stands, he seems out of touch with where the literature is since 1984. Don’t water down the term.


  33. becca Says:

    “There is also the exceptionally well characterized disruption of serotonergic function in animal models, a finding which has some support in human studies.
    How do you test this in human studies? It strikes me as immensely difficult to find an appropriate control group for “people motivated enough to feel good that they risk death” (although maybe CPP’s right and it would work to just take a look at tree climbers or something).
    I wonder if Ecstasy users long-term prospects for serotonergic function might not be quite as rosy as random controls.
    For that matter, you could probably say something snarky about the long-term cognitive prospects for someone who would take 6 hits.
    Anyway, one thing I would really like to see is a cost-benefit analysis of any drug use which attempts to model likelihood of seeking treatment for mental illnesses.
    “The people tasked with some degree of insight and oversight of this recreation, the lifeguards, do not tell people to stay the hell out of the water.”
    This is because it’s their job to make it safer for people to be in the water. It is not because they are not mortally afraid of you getting a spinal injury (ever watch a lifeguarding training vid?). NOW STOP DIVING IN THE SHALLOW WATER FUCKERS!!!!
    /ex-lifeguard rant


  34. DrugMonkey Says:

    How do you test this in human studies?
    A couple of approaches. You round up similar people with similar lifestyles and uses of other drugs that don’t happen to take Ecstasy. You can also recruit users and stratify by exposure patterns in various ways to approximate a dose-response. It is never perfect, of course. Which gives the denialists plenty of grist to pretend that it is all meaningless.
    I wonder if Ecstasy users long-term prospects for serotonergic function might not be quite as rosy as random controls.
    of course. Which is why we need experimental laboratory studies to test the role of individual factors such as a specific recreational drug. There is also the expensive route of a large prospective study in humans like the one in the Netherlands. You get a huge sample of kids prior to the usual drug onset and follow them for years. pubmed de Win MM and you’ll find some initial reports


  35. becca Says:

    Mmmmmm cohort studies. Expense schmexpense.
    Re: the XTC toxicity study- I do wonder if people who haven’t started using Ecstasy by age 22 are typical of the average user (maybe in the Netherlands??). Is it totally IRB-impossible to do a cohort study starting with young teens?
    But in any event, I’ve never seen much reason to question the Dr. Drew claim that virtually every mind altering substance is more harmful if taken as an adolescent, so if anything that aspect of the design will underestimate the neurological issues caused by Ecstasy.
    AHAHAHAHHAHA The reply comment to the early report is FANTASTIC. Basically, after Win MM reported Ecstasy as impairing verbal memory, somebody else comes along and says maybe Ecstasy users scored more poorly out of test-anxiety… I found it vaguely reminiscent of stereotype threat literature. Oh, people are such twisty things to study…


  36. It strikes me as immensely difficult to find an appropriate control group for “people motivated enough to feel good that they risk death” (although maybe CPP’s right and it would work to just take a look at tree climbers or something).

    Wake the fuck up! Every single fucking day you risk death to do things that make you feel good.


  37. DrugMonkey Says:

    But is he a denialist? I don’t think so. So far, he’s just wrong. I think there’s a difference. Once he starts espousing theories about how the government is conspiring to spread fake reports of ecstasy deaths, or is falsifying research on its toxicity, then maybe I’d be concerned about denialism. As it stands, he seems out of touch with where the literature is since 1984. Don’t water down the term.
    Phew. I was starting to worry about you, agreeing with me and all in that comment up to this point.
    Look, I don’t think we really get as far establishing some gold standard, big “D” denialist category as we do pointing to the individual denialist tactics. Because ultimately that is all you have. You can establish track records until the cows come home and you still can’t prove that you know the state of a person’s mind and whether they are exhibiting genuine (if entirely unsupportable) belief versus a disingenuous stance.
    In the case of Grob, he does have a track record on a certain side. That would be the side of claiming that MDMA is harmless. To get there many of the advocates, including Grob in this instance, ignore, overlook or minimize the available data to a degree that I find unjustified as a legitimate scientific position.
    As one contrast, note that I go out of my way in these discussions to point out the rarity of medical emergency and death when it comes to MDMA use. I would have far less problem with advocates if they acknowledged that MDMA can in and of itself cause death at what appear in some cases to be doses which overlap with the so-called typical recreational range. Then if they want to go on about the cluster, fine.
    In this case, I might suspect a behavioral cluster. Suppose the MDMA supply in a certain subpopulation was exceptionally low-content for a substantial amount of time. The users might very well think that you have to take 5 tablets to get an effect and end up, for this history, taking only a dose that approximates the mean recreational dose for all world-wide consumers. Now if they unsuspectingly get supplied with a more normal-content tablet and continue their dosing behavior- bam. Cluster of unwittingly high dose consumptions. Nothing whatsoever to do with nonMDMA constituents.


  38. MarkH Says:

    Agreement or disagreement should only be dependent on the facts and the literature suggests the facts are simply not on Grob’s side. He made a very stupid statement. In isolation, this might just be ignorance, and I prefer to reserve the label for motivated purveyors of BS. However, if you are more familiar with a history of him refusing to accept the current consensus which describes a very clear toxicity, then he might very well be a crank. I really want to hear a conspiracy theory before I’ll call someone denialist though.


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