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long term amphetamine use altering the effects of psychedelics.

pr0d1gy

pr0d1gy

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Hopefully this question is ADD appropriate.

I just wanted some opinions about a question of mine that has recently come up. After about 5 years of no recreational drug use, I recently decided to try some 25i-nbome. Based on the experiences of close friends, I had the expectation that this was a chemical that had a strongly mood altering aspect. After about 8 experiences in 6 months, I have not personally found any mood alteration. I realize that any drug will produce different effects in individuals, but the absolute lack of mood alteration is astonishing. I've found this to be a wonderfully visual compound; yet every time I have tried it, I just end up in a slightly darker mood waiting for the effects to end so I can go to sleep.

I've been on a rather low dose of amphetamine for about 4 years. Is it possible that the alteration of my neurochemistry this amphetamine use has caused may be playing a role in the strange way I respond to 25i? I thought there might be some association between the fact that 25i's effects are significantly modulated through 5-ht2a and the fact that 5-ht2a modulates dopamine neurons. My thinking was that I may be resistant to any euphoric effects from 25i as a result of my amphetamine use possibly altering the way dopamine neurons would be indirectly modulated by strong 5-ht2a agonism. To me this seems possible if in fact, 5-ht2a's modulation of dopamine plays a significant role in the mood altering effects of this drug.

I'd appreciate any feedback. I'm actually in med school but obviously this sort of stuff is way above me. I've totally given up on this material and tossed it. I'm not going to be messing around with this or any other psychedelics for quite a while; still any answers or feedback would probably be enlightening :D

PS. sorry if I butchered neurochemistry.
 
well first off, in general, plain stims and psychedelics don't mix mindset wise most of the time. They clash and you end up pretty much feeling too odd to do much, ime. So, your prescription could be be changing the mind set, or your prescription has made the effects of 5ht2a agonism on mood seem like nothing to your brain compared to the amphetamine(downregulation and such). In general plain amphetamines will crush mood/emotional aspects and enhance visuals while serotonin releasing amphetamines/etc(methylone,mdma,4-fa..) will also enhance mood instead of clashing with it leaving you in a weird mood.

all just my experience
 
It's doubtful - amphetamine does not produce cross tolerance with psychedelics like DOx, LSD, psilocin. The two drugs work on mostly different receptor systems anyway.

The 25x-NBOMe series of compounds has not been around for very long, no more than 5 years, and the activity has nowhere near the level of study that LSD recieved.

That said, they are presumably much more selective for 5-HT2a, which is just one of the many sites that psychedelics hit. Most psychedelics actually have a fairly broad spectrum of activity - few are totally selective for one receptor. 5-HT1a/b/d, 5-HT2b/c, and the other 5-HT sites (3, 7) in particular are affected depending on the drug.

As a rough rule of thumb, here are some correlations I have noted.
5-HT1a agonists seem to be serenic/anti-anxiogenic, and may play a part in the powerful "magic" response to drugs like MDMA and 5-MeO-DMT
5-HT2a agonists seem to be predisposed to "visual" effects more than "mental" - i.e. external sensory gain.
5-HT2b and c agonists are also hallucinogenic to my knowledge (mescaline & some 2c- drugs like 2c-e has significant activity at 5-ht2b, more than at 5-ht2a). 5-HT2c is structurally similar to 5-HT2a and most drugs that are active at one site, also are active at the other. The rumor I have heard is that 5-HT2c agonism leans more towards "mental" and anxiogenic effects. Psilocin is a noted 5-HT2c agonist.
5-HT3 is found in the gut, agonism can cause gas, cramps, vomiting.
5-HT7 is a target of some drugs like LSD and helps regulate mood.

I think your experiences stem from the fact that 25I-NBOMe is just much more selective of a psychedelic than the "classics".
 
Hopefully you can give me some MCAT tips lol, I write in a month!

Well my guess is similar to yours: there may be some sort of "downregulation" of various receptors involved downstream of 5HT2A/C agonism. IIRC 5HT2A and possibly 5HT2C agonists generally increase NE, DA, and glutamate neurotransmission which your body may already adapted to due to long term amphetamine treatment. If memory serves 5HT2A is also heavily involved in stimulant "liking" -we all know how fast that goes away- so it may be a functional change in the signalling pathway(s) and/or expression of the receptor.

I've had friends note the same thing, but they've been on stimulant medications for at least a decade now.
 
Epsilon Alpha said:
Hopefully you can give me some MCAT tips lol, I write in a month!

Well my guess is similar to yours: there may be some sort of "downregulation" of various receptors involved downstream of 5HT2A/C agonism. IIRC 5HT2A and possibly 5HT2C agonists generally increase NE, DA, and glutamate neurotransmission which your body may already adapted to due to long term amphetamine treatment. If memory serves 5HT2A is also heavily involved in stimulant "liking" -we all know how fast that goes away- so it may be a functional change in the signalling pathway(s) and/or expression of the receptor.

I've had friends note the same thing, but they've been on stimulant medications for at least a decade now.
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Good luck! Hope you do well on it :)

Regarding what sekio said, that makes a lot of sense. I knew that amphetamine doesn't cause cross tolerance with DOx and I should have assumed that it would be the same case with Nbomes.
 
do you take your daily dose while on the psychedelic or take the psychedelic when your daily amphetamine is wearing off? it could be what the combo feels like to you, or the effect of taking a psychedelic when your amphetamine is wearing off and your mood is sombre
 
amphetamines will potentiate the effects of mdma i know molly has become popular but x is sometimes a combination of mdma and amphetamines that way you have a lot of energy plus your "euphoria" feeling same principle with cocaine as for other things i cant exactly say for sure but i do take vyvanse on a daily basis and i know shrooms and k still work very well granted with those two i have really only used them once my vyvanse is wearing off at the end of the evening ... just more of a nighttime thing i spose
 
This sounds counterintuitive, as you're probably abstaining from amphetamine while you take the psychedellic to not have interactions, but it may be wise to have *just* enough amphetamine so you don't have acute withdrawal of sorts, but not enough to give you even therapeutic benefit, really-- maybe, say, 5mg in the morning of Adderall or Dexedrine if you were to take the psychedellic at night. You'll mostly have it out of your system by then, but they'll still be a tiny amount left, being too soon to get acute withdrawal, which usually happens the day after last ingestion... on the other hand, if you're on a therapeutic amount of amphetamine, you'll get serious, and that seriousness will inhibit the psychedellic's effect-- serious in the sense you're uptight, and mood is all, well, uptight. That's the exact opposite of what you want to be on a psychedellic.

If you're predisposed to mental illness, you may want to not take a psychedellic-- it could induce psychosis. If you do take it, I advise a trip therapist type that can help you get into the right mindset. I know when I took coke a few times, I would initially be very anxious when it came on, until I sort of let myself go with it, and that brought about a pleasant, mild euphoria... so mindfulness is very important to establishing mood. I think you're underestimating the role expectation plays in psychopharmacology. It plays a huge role. I'd go with a trip counselor, focus on things like candles, music, being around good, positive, calming people, and eat a healthy, wholesome meal beforehand.
 
Has anyone else noticed long term stimulant treatment has changed any other drug responses for them?
Drank for the first time in a couple months on Canada day and I found I was much less sedated and euphoric than I remember it being like before. Still social and pleasant, but very different nevertheless.
 
When I quit after dosing 4-fa at 20-50mg/day for 2weeks or so, I had to take MORE benzos to stay out of withdrawal. I don't know if that was because the amphetamine w/d felt like benzo w/d as well or if it was synergistic with the effects that cause benzo w/d, but its kind of possibly related to your experience with alcohol. I also notice that I'm less likely to get overwhelmed on psychedelics and such.
 
Epsilon Alpha said:
Has anyone else noticed long term stimulant treatment has changed any other drug responses for them?
Drank for the first time in a couple months on Canada day and I found I was much less sedated and euphoric than I remember it being like before. Still social and pleasant, but very different nevertheless.
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was there speed in your system while you were drinking? or is it since quitting amphetamine?
 
You should be careful mixing amphetamines, even prescription dosage with a tolerance, with 25-I. It can be responsible for strong bouts of psychosis, rage, mania. Also, it can lead to an earlier onset of HPPD.
 
Epsilon Alpha said:
Has anyone else noticed long term stimulant treatment has changed any other drug responses for them?
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I used to be able to drink something like a Monster and not even feel it, but after a 2 years of taking RX'd Amps I can feel even small amounts of caffeine. I can actually say a Mountain Dew is too much for me now. It has what, like 54 mgs? I can only stomach to drink 1/4 of an energy drink as well. I think it's safe to say that Amps have made me hypersensitive to all stimulants now. I don't get it though.
 
Is there cross tolerance between 5-ht releasing drugs and 5-ht-agonists (e.g. via downregulatoin or sth else)?
 
Dysphoric said:
I used to be able to drink something like a Monster and not even feel it, but after a 2 years of taking RX'd Amps I can feel even small amounts of caffeine. I can actually say a Mountain Dew is too much for me now. It has what, like 54 mgs? I can only stomach to drink 1/4 of an energy drink as well. I think it's safe to say that Amps have made me hypersensitive to all stimulants now. I don't get it though.
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That's very similar my experience back when i was rolling. Coffee and or monsters / cokes anything with a decent amount of caffeine in it would make me fairly anxious / jittery. I would have to throw the drink out early because of it . It seems messing with strong stimulants make you hypersensitive to caffeine.
 
F1n1shed said:
That's very similar my experience back when i was rolling. Coffee and or monsters / cokes anything with a decent amount of caffeine in it would make me fairly anxious / jittery. I would have to throw the drink out early because of it . It seems messing with strong stimulants make you hypersensitive to caffeine.
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Hmmm, well caffeine and amphetamine have a well known synergy so that could be the case. However, I always though that perhaps amphetamine use reduced the amount of caffeine someone consumes. I know on my RX'd dose that I really cut back on my coffee drinking, and when it comes time for me to take an amp break my caffeine tolerance is so low I can get a substantial effect on half a small cup of coffee.

Does that kind of sound like your usage pattern?
 
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