I apologize; normally I don't like to post without linking to full articles of my sources, but bluelight's attachment mechanism works about as well as 5-IAI and there are no good PDF hosts on the entire Internet (seriously I checked because I have that problem a lot). On the other hand, I'm glad I get to have a real argument for once.
Since the case reports are usually based on objective signs, not symptoms, it's not clear that some patients didn't experience headache (many patients were unresponsive or incoherent so it isn't clear what they experienced). Most NBOMe overdose victims are hypertensive so you might predict that some would show headache due to the rise in cerebral blood pressure, but that doesn't seem to happen.
Vasoconstriction has never been reported in NBOMe intoxication. See the footnote.
NBOMe may have other effects that block headache symptoms. In any event, less that 50% of patients with cerebral vasoconstriction syndrome show signs of headache.
Patients with cerebral vasoconstriction leading to seizures?
Does that really prove anything? 5-HT2A agonists induce vasoconstriction and cause vasculopathy in overdose. People have literally lost limbs after overdosing on DOB and BR-Dragonfly due to vascular spasm. NBOMe is shorter acting so it might not kill tissue so readily, but it is hard to believe that it acts differently from all other 5-HT2A agonists.
People have lost limbs after overdosing on
other drugs. Also source on the limb part.
https://en.wikipedia.org/wiki/Bromo-DragonFLY#Pharmacology
"...is most accurately described as a non-subtype selective 5-HT2 agonist, as it is actually twice as potent an agonist for 5-HT2C receptors as for 5-HT2A..."
"A 39-year-old previously healthy man experienced diffuse, progressive, peripheral arterial spasm
36 hours after the ingestion of concentrated high-grade 4-bromo-2,5-dimethoxyamphetamine. "
What happens 36 hours after you take DOB? The acute effects have mostly worn off. Why does DOB cause vasospasm only after it leaves this man's system? I don't know why he had a diffuse peripheral vasospasm, but it probably wasn't caused by DOB doing anything directly.
Um. Images of the article are now
available here on imgur, so if anyone can read Swedish I'd be much obliged.
(not relevant)
Um, is there an article nearby that I can actually read? One that suggests the 5-ht2a receptor is in any way responsible for vasoconstriction?
The metabolic acidosis could be due to hyperthermia and agitation, and I was under the impression that is why amphetamine produces metabolic acidosis.
Lactic acidosis is the interesting question. Metabolic acidosis could be caused by many things, but the blood pH was unremarkable here anyway: cases 1 (pH 7.2), 2 (pH 7.3), and 4 (pH 7.33) show acidosis (pH <7.35), but 2 and 4 are just past the threshold, and 3 (pH 7.48) actually has alkalosis (pH >7.45). It seems highly unlikely that such mild acidosis is related to organ failure.
LSD has been associated with cerebral vasoconstriction syndrome:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002654/
LSD causes cerebral vasoconstriction via activation of the 5-ht1b and 5-ht1d receptors, which is the (presumable) basis of its antimigraine efficacy. But that article doesn't say anything about LSD.
I'm afraid that isn't true about 25I-NBOMe. It shows virtually the same selectivity as DOB and 2C-B, and it definitely activates 5-HT2C.
http://www.ncbi.nlm.nih.gov/pubmed/25547199
for antagonist labeled receptors, Ki = 0.52 nM (5-HT2A) vs. 0.69 nM (5-HT2C)
for agonist labeled receptors, Ki = 0.16 nM (5-HT2A) vs. 0.50 nM (5-HT2C)
I'm aware that there were a few initial reports indicating that 25I-NBOMe was moderately selective but that wasn't borne out by further investigation. Otherwise there would have been no need to develop drugs like 25CN-NBOH.
There is always a need for more publications; even this selectivity (vs agonists) is a factor-of-10 different from what I linked to for Br-DFLY. It's not exactly reasonable to choose the only assay that agrees with your preconceptions, either. Different assays have found different selectivities. Also, people die in mostly the same way with the decidedly more selective 25C-NBOMe:
http://informahealthcare.com/doi/abs/10.3109/15563650.2014.909932
Notably, Case 2 had rhabdo; "CT scan of the brain was unremarkable. "; this
article you posted told me that's the first thing you do in RCVS (though RCVS is chronic).
Sure, that may be true in their series of case reports. But there have been more than 30 25I-NBOMe overdose cases described in the literature. What percentage showed elevated creatine kinase?
Well, now I'm 8 for 8.
But is muscle exhaustion the primary cause of the overdose syndrome or is it actually a result of hyperthermia, agitation, hypertension, and seizures? These two viewpoints are not necessarily incompatible but I'm trying to suggest that there are specific 5-HT2A-mediated effects that are likely to be involved.
The mechanism I suggested
is 5-ht2a specific. Vasoconstriction, on the other hand, is generally adrenergic.
5-HT2A receptors are expressed by neurons that control blood pressure and heart rate. Some of the tachycardia and hypertension may be due to fear, but 5-HT2A agonists increase blood pressure and heart rate in anesthetized animals. Psilocin probably isn't a good counter-example because it activates receptors (5-HT1A, 5-HT1B...) that block 5-HT2A effects, whereas NBOMe doesn't have that effect.
Source your claims; as far as I can tell they aren't true.
EDIT: 9 for 9.
http://www.fsijournal.org/article/S0379-0738(15)00116-4/abstract
"In the present case, a 22-year-old healthy male, with a short history of alcohol and recreational drug abuse died at a hospital after the nasal ingestion (“sniffing”) of 25C- NBOMe. The deceased and a friend purchased 25C-NBOMe on the internet and the drug was delivered in small transparent capsules containing small flakes. The friend reported that he and the deceased had been sniffing 25C-NBOMe on the preceding evening (between 8:00 and 10:00 pm). At approximately 9:30 pm, the deceased was talking incoherently, and at 10:15 pm, he was running around in his apartment pulling down curtains. At 11:00 pm, an ambulance was called because the deceased was hallucinating and had jerky movements and a clenched jaw. When the ambulance arrived three minutes later, he was unconscious (he scored 3 on the Glasgow Coma Scale (GCS)). At initial evaluation, the respiratory rate was 23 breaths per minute, blood pressure was 104/83, pulse was 100 bpm, and blood glucose was 13.3 mmol/L, and he exhibited mydriasis. He had convulsions that were treated with the intravenous administration of 10 mg diazepam with no effect. He was intubated at the scene and treated with 5 mg midazolam, 100 mg suxamethonium and 100 mg ketamine. The initial oxygen saturation level was 80%, but it was increased to 100 % by mechanical ventilation. An episode of ventricular tachycardia and atrial fibrillation was observed, and he was treated with 300 mg amiodarone. The transit time to the emergency department was approximately 30 minutes. The initial investigation at the emergency department revealed the following symptoms: hyperthermia with a core temperature of 40°C, pulse of 140 bpm, diffuse bleeding from all mucosa, respiratory and metabolic acidosis, rhabdomyolysis, high lactic acid, anuria and hyperkalemia (Table 1). His blood pressure was low at 70/45 mmHg, despite infusion of noradrenalin and phenylephrine. He was further treated with infusion of saline, human albumin, and sodium bicarbonate and blood transfusion. An additional dose of 15 mg diazepam was administrated, and the hyperkalemia was also treated. ECG showed inferior ST depression changes and increases in coronary biomarkers (Table 1). His head was actively cooled. He was transferred to the intensive care unit and held in an artificially induced coma and was additionally treated with fentanyl. His condition continued to deteriorate with disseminated vascular coagulation (DIC) (Table 1). Despite lifesaving treatment, he died at approximately 10:00 am the following morning of multi-organ failure and a clinical picture consistent with serotonin syndrome. The friend had none of these symptoms and reported having “a good trip” for 4-6 hours after sniffing the 25C-NBOMe."
Let's go back to the start. Why do I think the NBOMe deaths are different from the DOx deaths? Because they die differently. The DOx users die of cardiac effects, aspirated vomit, tissue necrosis; never kidney failure. And the NBOMe users -- the ones who die, at least -- consistently get rhabdomyolysis and lactic acidosis. And their muscle jerking doesn't resolve with diazepam... because it's downstream from the CNS? Just maybe?
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