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2C-E and Quetiapine (Seroquel)

Holy_cow

Holy_cow

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Nov 29, 2007
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I'm taking 600mg of Quetiapine (Seroquel) at 22:00 every night for about 6 month as a sleeping aid. It works very well for this purpose, and unlike with other hypnotics, it remained effective long-term and no tolerance developed. The side effects (rapid heart beat, orthostatic hypotension, clogged up nose) dissapeared over time. I'm getting a long, good sleep and wake up refreshed and without any hangover.

Quetiapine is known to be an antagonist of 5-HT2A receptors (Ki 82nM) but has little effect on 5-HT2C receptors (Ki 1500nM). The hallucinogenic effects of compounds like 2C-E or LSD are thought to be mediated by activation of 5-HT2A receptors. Agonists, but also antagonists, cause desensitation of this receptor (http://www.ncbi.nlm.nih.gov/pubmed/11805206).

I was interested in finding out if a 5-HT2A/C agonist (2C-E) would still cause the typical hallucinogenic/psychedelic effects after chronic pretreatment with Quetiapine.

Thus, today at 13:30 (15.5 hours after the last dose of Quetiapine), I took a dose of 22mg of 2C-E, which is a dose that can be expected to be definitely psychoactive, according to PIHKAL.

It's now 16:00 (T+2:30), and the only effects of the 2C-E I've noticed are a slight, brief gastric discomfort and a slight psychostimulant-like effect with some slight anxiety. There are no hallucinogenic/psychedelic effects, which I have experienced with 2C-E previously, before I commenced Quetiapine treatment.

Conclusion: Chronic pretreatment with the 5-HT2A antagonist Quetiapine anihilates the hallucinogenic/psychedelic effects of the 5-HT2A agonist 2C-E. It is reasonable to assume that this effect will also occur under the treatment with other atypical antipsychotics with 5-HT2A antagonists effects, such as Risperidone, Olanzapine or Clozapine. Psychedelics are without effect under the chronic treatment with atypical, 5-HT2A antagonistic antipsychotics. Furthermore, these findings support the notion that hallucinogenic/psychedelic effects are caused by activation of the 5-HT2A receptor, which gets desensitized not only by agonists, but also by antagonists. The slight residual effects of the non-selective 5-HT agonist 2C-E may be mediated by activation of 5-HT2C and possibly 5-HT3 receptors.
 
Well, yes, but it wasn't so clear if chronic pretreatment, rather than acute cotreatment, with Quetiapine would affect the "trip".

While chronic pretreatment probably causes desensitation of the 5-HT2A receptor (i.e induces tolerance), acute cotreatment will obviously competitively antagonize the effects of a 5-HT2A agonists by competing for the binding site, just how acute Naloxone antagonizes µ opioids. But while chronic pretreatment with Naloxone/Naltrexone reduces tolerance (i.e. sensitizes receptors) to µ opioids, 5-HT2A antagonists seem to desensitize the receptor (i.e increase tolerance) towards agonists.

Btw, cotreatment with a 5-HT2A agonistic psychedelic and a low, threshold dose of a non-competitive NMDA antagonist (tried with MK-801) prevents 5-HT2A receptor desensitation (i.e. development of tolerance) by the agonist. Also, 5-HT2A agonists prevent the neurotoxic effects of NMDA antagonists.
 
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Olney's lesions, caused in rodents and monkeys by pretty much all tested non-competitive NMDA antagonists (PCP, Ketamine, MK-801, DXM, N2O, even memantine) in neuroprotective or dissociative doses. There's now evidence that prolonged Ketamine in clinically used doses is also neurotoxic in humans. I remember a recent study where they found convincing evidence of neurotoxicity in post mortem human brains after Ketamine treatment, but can't find the reference off hand. Search PubMed for "Olney NMDA" if you want to find out more. For the prevention of NMDA antagonist neurotoxicity by 5-HT2A agonists see http://v3.espacenet.com/publication...NR=5902815A&DB=EPODOC&locale=en_EP&CC=US&FT=D
 
I find it very interesting that chronic pretreatment with an antagonist would desensitize the receptor. Are you sure that all of the seroquel was cleared from your system when you took the 2-CE. I know it has a short half life but 600mg is a large dose, maybe you should have waited longer. Also, was it the extended release form?
 
This is exactly what I'd expect to happen with this combo. The effects of the 2c-e would be greatly diminished due to the 5-ht2a antagonism. As 2c-e's fairly safe, one could up the dose, or abstain from seroquel to negate these effects.
 
wait, why would you take DA inhibitor just to get some sleep? am i the only one who thinks thats a bad idea?
 
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