psychedelics with tricyclic medication?

[timsul999]

so the med I'm taking is clomipramine; acts as a serotonin antagonist and blocks serotonin transport.
5-HT2A receptor (Ki = 36 nM)
5-HT2C receptor (Ki = 65 nM)
5-HT3 receptor (Ki = 85 nM)
5-HT6 receptor (Ki = 54 nM)
5-HT7 receptor (Ki = 127 nM)

looking up the pharmacology for the drug i'm taking, 25i-nbome, primarily acts on the 5-HT2A receptor.
what happens when antagonists and agonists are combined? will the clomipramine totally negate it, or just change the effects somehow?
another concern is since clomipramine acts as a anti-histamine and 25i has some histaminergic activity, would cause any undesirable/dangerous side-effects?

 

[Transform]

Though 25I is about 1000x more affinate for 5HT-2a, I would still expect the effects to be completely or almsot completely blocked. Seroquel is less affinate than both and I'm sure I've read about it being successfully used to abort NBOMe trips.

Even if that wasn't the case, the more important issue would be whether or not it's wise to take powerful psychoactive drugs while receiving treatment for psychological illness. While in some cases psychedelics can be quite pleasant with no aftereffects, they can also make such issues much worse.

 

[RobotRipping]

i think it would block 25i almost completely, i remember a post saying that 25i isn't actually so specific to hit just the 5ht2-a receptor but cant remember the details. I can tell you that seroquel and hydroxyzine will murder a trip. I once took hydroxyzine to balance out the anxiety and ruined my trip. Others have reported the same. Seroquel and hydroxyzine are 5-ht2a antagonists among other things, also anithistamines so they aren't dangerous to mix, just pointless, unless you want to come down from a trip pretty quickly.

I don't know the ki value (or what it would mean other than binding affinity lol) for 25i at 5-ht2a but there's no doubt, it's going to block some if not all of the effects.

one thing though, seroquel doesn't kill the stimulation for some reason even though it's a dopamine antagonist as well. I don't know why that happens. I'd take 50-75mg to come down from a trip and would just end up staying awake through it and would get really fucked up from it for some reason.

some/most tricyclics have MAOI activity too, isn't that correct? so i'd be cautious in mixing them just for that reason tho your medication in particular may pose no issue in that regard, just something to keep in mind, if that's true in the first place.

 

[kidklmx]

Might the NBOMe overpower the anti-psychotic? I think the Ki value for the NBOMes at 5HT2A is below 1nM IIRC, but that's probably not how receptor binding works (I know nothing in this field, though I like to read about it)

Here's that thread you were looking for, RoboRipping (turns out it was 25B-Nbome, but then again, that's probably not how it works)

 

[timsul999]

damn, waste of 20 bucks. imma take a gram and see how it goes anyway, not expecting much though. definitely not willing to taper myself off of clomipramine just to try psychedelics. oh well.

 

[Transform]

Please say you meant a mg.

 

[RobotRipping]

i'd be willing to wager he meant mg, as a gram certainly costs more than 20 dollars.

and thanks kidklmx; been looking for that thread for a while.

I guess OP can look at that chart and see how it compares to the AP he's on. The best effects usually come from 5ht2-a though, but you still may feel something. Though 25i's binding affinity at 5ht2a isn't listed there, we can assume the ki value is pretty damn low. Enough to overpower an AP? i don't think it's the same as bupe bumping other opiates off receptors because it has a higher binding affinity, as it's a partial agonist and not an antagonist. It'd be like taking an opiate that couldn't be countered by naloxone in overdose or something, which i'm sure is possible in theory anyway. Need pharmacology degree

 

[Lady Codone]

I used to take Anafranil and found it to be one of the most soul-killing drugs ever. Not sure how it would interact w/ recreational drugs, but I imagine it would dull the effect somewhat. Start with a low dose and don't take the two at the same time.

 

[timsul999]

I used to take Anafranil and found it to be one of the most soul-killing drugs ever. Not sure how it would interact w/ recreational drugs, but I imagine it would dull the effect somewhat.

gotcha, you mention this because of serotonin syndrome? anyways, eh... i definitely feel a bit of derealization on it. still function and feel normal though. i take a smaller dose (100 mg) and doc wants me to go up. should I?

so it's final 5ht antagonists kill psychedelics & entactogens? that rules out about 99% of rcs then.
I don't know shit about ki values - is it the lower value is the more binding affinity it has for the receptor?

btw doesn't make any difference but what I'm on is technically not an AP, and definitely doesn't share the completely obliterating, zombifying effects of seroquel or zyprexa.

kinda tentative on taking this now.

 

[rpm]

so it's final 5ht antagonists kill psychedelics & entactogens? that rules out about 99% of rcs then.

Not all antagonists. Fluoxetine definitely doesn't kill psychedelic experiences (at least with acid, mushrooms or 2ce). I know this because I have two friends who are on it and we often trip together. This is probably because it is very selective for the 5-HT2C receptor alone, and has weaker affinity for the other 5-ht receptors. Those girls always seem quite hardcore though - might just be how they are but they always want more when it comes to acid and mdma, when I'm going "actually this is about the level I want". So that might be effect of the meds.

 

[timsul999]

i believe prozac is just a reuptake inhibitor. it doesn't antagonize the receptor itself, but just blocks the serotonin transporter. I honestly don't really know what i'm talking about, but this seems to matter with the difference with how aps and sri antidepressants effect psychedelics. whereas antipsychotics negate them entirely, antidepressants have either an enhancing/diminishing effect that's pretty much all subjective to the user.

 

[rpm]

i believe prozac is just a reuptake inhibitor. it doesn't antagonize the receptor itself, but just blocks the serotonin transporter. I honestly don't really know what i'm talking about, but this seems to matter with the difference with how aps and sri antidepressants effect psychedelics. whereas antipsychotics negate them entirely, antidepressants have either an enhancing/diminishing effect that's pretty much all subjective to the user.

Yeah, point taken, it's main mechanism of action is reuptake inhibition. It also is a 5-hc antagonist. From wiki

Fluoxetine's mechanism of action is predominantly that of a serotonin reuptake inhibitor.[80][81] Fluoxetine delays the reuptake of serotonin, resulting in serotonin persisting longer when it is released. Fluoxetine may also produce some of its effects via its potent 5-HT2C receptor antagonist effects.[82] In addition, fluoxetine has been found to act as an agonist of the σ1-receptor, with a potency greater than that of citalopram but less than that of fluvoxamine. However, the significance of this property is not fully clear.[83][84]

.

Also

from here. But yeah, it's antagonistic properties are week in comparison to tricyclics, thus why it doesn't kill psychedelic experience. But it's still an antagonist, so not all antagonists stop psycs.