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

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.

>sigh<

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.”

AGGGGHH! Idiot!
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 LD_0.01 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.