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Psychedelic cross-tolerance?

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TheReadyAwakening

TheReadyAwakening

Jimmy
So I've heard a lot of contradicting opinions as to whether or not certain psychedelics provide a cross-tolerance between two different drugs. I'm sure there is some validity to this, and I'd like to know what, if there is any, scientific grounds support the idea.

I know that tryptamines and phenethylamines are pretty different, so I doubt there would be any cross-tolerance between say psilocybin and LSD. However, DMT and psilocybin have extremely close molecular structures, so it would make sense to have a cross-tolerance, yet apparently this is not accurate.

Anyone have some insight into this? Maybe set the record straight?
 
Just from anecdotal information and experience reports, I have heard that DMT taken during the peak of a psilocybin trip greatly enhances the psychedelic effects and should be done with a lot of caution exercised. I haven't so far heard of any reports of cross tolerance.

Though they are similar in molecule structure, they are so wildly different in effects the small difference makes a lot.

Though I haven't come across any concrete scientific explanation that I can link you to soz :c
But I'm sure someone else out on the nexus would have such info =)
 
I'm sorry, but I can't find sources for this information. But I've heard that the classical longer lasting hallucinogens like psilocybin mushrooms and LSD will create a medium-term tolerance lasting a few days that DOES affect DMT. However, DMT use does not appear to exert any tolerance effect against LSD or shrooms in any of the reports I've heard or read.
 
In my experience, DMT creates no cross tolerance with any of the classic psychedelics (and neither it builds tolerance itself). Mixed with mushrooms they definitely synergize. Mushrooms and LSD do create cross tolerance that lasts a couple of days. I wonder what are the pharmacological actions that explain this, because it can't be simple 5-HT2a signalling otherwise DMT would also create tolerance.
 
I wonder if the duration of exposure to the 5-HT2a agonism is part of the equation. Do tolerance effects occur when DMT is used with a RIMA so that it lasts for several hours, like shrooms or LSD?

Someone I know with cluter headaches reports that a small amount of psilocybin is enough to abort an entire cycle of cluster headaches and keep them from coming back for a month, whereas DMT will only abort a headache that is currently happening -- it won't prevent recurrence in the short-term or long-term. But he hypothesized that use of a longer lasting formulation, such as oral DMT + Caapi Copy, would produce results resembling those of shrooms.
 
Samadhi-Sukha-Upekkha said:
Do tolerance effects occur when DMT is used with a RIMA so that it lasts for several hours, like shrooms or LSD?
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Nope.. Take for example ayahuasca rituals that are often composed of subsequent dosages in the same night, and one definitely gets the effects increased and increased, no tolerance noticed. Even in specially long rituals this is still true. Also in rituals that happen in consecutive days, one still keeps getting just as much or even more effects. It's really peculiar! Any more ideas on what would be the reason for DMT's lack of tolerance as opposed to other psychedelics?
 
endlessness said:
Any more ideas on what would be the reason for DMT's lack of tolerance as opposed to other psychedelics?
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I would think it is because DMT is endogenous, so it is a normal procedure that some DMT is bound to the receptors in question. It makes no sense to get tolerance for something that your own body produces, that would mean you would have to produce more and more DMT in order to continue whatever role the substance have endogenously.
 
Not to hijak your thread or anything bro, but anyone know about x-tolerance bet. Lucy & 2CE? Just wondering for future dream reference.

-spiceworm
 
From SWIM's experience, the tryptamines and phenethylamines aren't too cross tolerant, but LSD and mushrooms are. Most tryptamines are with each other, and most phenethylamines are with each other. DMT is an exception, and he thinks ibogaine is too, although SWIM has very limited experience with ibogaine.

With DMT, for SWIM, he builds a rapid tolerance to it, when smoked, and getting a lot in fast seems to help him go further, but if he prolongs this he can't go as deep, it must be fast. It doesn't feel very cross tolerant with other tryptamines, however SWIM experienced less of a drastic change on psilocybin and DMT as he did on LSD and DMT..

Perhaps it's the MAOI that enables one to continue to take ayahuasca repeatedly with success.. It would seem with MAOI/RIMA action going on, your body isn't breaking it down, therefore you have no tolerance. That is pure speculation, but it seems to make some sense to me..

Now this is all just from his experimentations, so your mileage may vary..
 
SWIM experiences very strong cross-tolerance for mushrooms for 3-4 days after taking LSD. Noticeable but not as much cross-tolerance the other way around.
 
Virola78 said:
benzyme said:
rapid turnover.
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Pls tell us how this works..
I am very interested.

Or maybe you have a good link?
A quick google didnt get me anywhere...
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well, to put it simply, signal transduction is short-lived because dmt binds and is released from the receptor binding site relatively quickly. for this reason, downregulation isn't much of an issue, since tolerance builds and fades quickly.

as for psilocin and lsd, they have a higher binding affinity and signaling is more extensive, so downregulation is more noticeable
 
 
Only got threshold effects from spice the day after a shroom trip. 1/4 oz of cubes 2 days after lsd was more mild than an 8th normally. From experience, Psilocybin has cross tolerance with dmt and lsd.
 
I have experienced an enhancement and synergy of DMT when I drink Ayahuasca, eat mushrooms a few hours later, and then head off to hyperspace at the very end.

I ate mushrooms without Ayahuasca the other day, smoked probably 300mg of perfectly good changa, and was completely DENIED entry.

I was shocked and humbled. Either there is something else in a different variety of mushrooms, or the absence of the MAOI led to some kind of cross tolerance. I will never smoke after mushrooms again, as that was a horrendous waste of changa, unless Ayahuasca is also present. Holy cow!
 
Some people swear by smoking DMT with the mushrooms..endlessness has spoken to me about hwo good that combo is for him..but that with LSD and DMT he stays grounded, others swear by LSD and DMT..

I never tried it though..I have only smoked with ayahuasca. With mushrooms I cant bring myself to do it..how much are you eating? I have been taking about 5 grams once a week the last couple weeks, and that should blast off anyone if they are good cubes. Ayahausca never got me to the place that the mushrooms have been taking me lately. I would just take more mushrooms, and take them as a tea..if you take enough there is a point where you wont want a higher dose, trust me..it get realy realy weird.

I also dont get toleracne from psilocin the next day really, I can take it again with strong effects still..butby the third day I will need to wait a few days until I can go again.

I also have been noticing that theafter glow from mushrooms is much brighter and lasts longer than with ayahuasca for me..not sure why that is. After a mushoom journey I feel like everything is just pefect in my life for days..and especially for the next day or so..
 
dreamer042 said:
Mescaline and LSD-25 do have a cross tolerance.
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SWIM has not tried this himself because he’s never had the two at the same time to test it. But LSD is a super tolerance builder and tends to produce cross tolerance to other psychedelics more than the other way around. Mescaline tends not to produce much tolerance at all. You can take mescaline many days in a row, and unlike LSD, after the fourth day of consecutive use it still works nearly as well as it does on the first day. So I get the feeling that you will not get much tolerance to LSD by using mescaline first, but will get tolerance to mescaline by using first LSD. Does anyone have any experience with that?
 
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