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OfflineInsultingLizard
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Registered: 01/04/20
Posts: 546
Last seen: 4 months, 11 days
Tolerance and downregulation * 1
    #27044871 - 11/18/20 05:11 AM (3 years, 2 months ago)

Sorry if this has been asked before. I searched but couldn't find anything relevant.
I was on my ride to work today and a question came up I didn't know the answer to. If psychedelic tolerance is the downregulation of serotonin receptors and the effects of psychedelics are caused by, essentially, the stimulation of those receptors, how come while your brain is on tolerance it's functioning normally? How is it able to perform its normal functions if serotonin regulates a host of background body functions, and how is it our perception is not "antipsychedelic", so to speak? Which I guess we could understand it to mean gray and dulled.


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OfflineJonBa
Hawaiian shirt weirdo

Registered: 05/14/19
Posts: 361
Last seen: 2 years, 4 months
Re: Tolerance and downregulation [Re: InsultingLizard]
    #27044886 - 11/18/20 05:39 AM (3 years, 2 months ago)

Good question, but I think the downregulation might be why you feel like sleeping for a full 2 days after a strong trip?  :uhoh:


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Life saved by DMT


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InvisiblefeeversM
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Registered: 12/28/10
Posts: 8,546
Loc: Flag
Re: Tolerance and downregulation [Re: JonBa] * 1
    #27044896 - 11/18/20 05:59 AM (3 years, 2 months ago)

Unless you do some serious damage with a heavy stimulant or something, there will always be enough functioning receptor sites to keep things running smoothly. Psychedelics latch on to a small subset of serotonin receptors


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OfflineInsultingLizard
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Registered: 01/04/20
Posts: 546
Last seen: 4 months, 11 days
Re: Tolerance and downregulation [Re: feevers]
    #27044923 - 11/18/20 06:23 AM (3 years, 2 months ago)

Quote:

JonBa said:
Good question, but I think the downregulation might be why you feel like sleeping for a full 2 days after a strong trip?  :uhoh:



It's weird, isn't it? I don't feel more sleepy, but if I do sleep I can easily sleep for two or three hours longer than usual. All the better for me, I'm usually sleep-deprived.

Quote:

feevers said:
Unless you do some serious damage with a heavy stimulant or something, there will always be enough functioning receptor sites to keep things running smoothly. Psychedelics latch on to a small subset of serotonin receptors



Is that so? Still, I can understand that it doesn't make a difference for normal body functions, but I'm surprised perception isn't altered post-trip.


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OfflinePandemoon
Ἧeẍeᾐmeḭsṫeŗ ͛
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Registered: 01/28/14
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Re: Tolerance and downregulation [Re: InsultingLizard]
    #27044927 - 11/18/20 06:28 AM (3 years, 2 months ago)

Isn't the so called "afterglow" an alteration of our perception? It can last for days, if not weeks.. especially after a heavy trip.

-


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OfflineInsultingLizard
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Registered: 01/04/20
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Last seen: 4 months, 11 days
Re: Tolerance and downregulation [Re: Pandemoon]
    #27044958 - 11/18/20 07:00 AM (3 years, 2 months ago)

Quote:

Pandemoon said:
Isn't the so called "afterglow" an alteration of our perception? It can last for days, if not weeks.. especially after a heavy trip.

-



I don't get an afterglow at all. For me, when the trip ends all subjective effects pass. With mushrooms anyway. With LSD I've noticed the day after I feel more relaxed than usual.


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InvisibleBarnaby
Interesting lifetime
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Registered: 12/13/17
Posts: 9,146
Re: Tolerance and downregulation [Re: JonBa]
    #27045150 - 11/18/20 09:24 AM (3 years, 2 months ago)

Who sleeps f80'sor two days after a "heroic dose"?  I take things to the limit, TAKE IT TO THE LIMIT!  That song makes me laugh but at least I have good drugs bad drugs I get. 

DARE growing up, never said anything useful, like heroin is worse than marijuana.  Learned the hard way with ice in a tub and the "doctor" as he is known, in prison last I heard from stealing and returning things then his girlfriend wanted to have sex with me and no way in hell.  But he shot me up and put ice under my balls.  Was really drunk and just said fine.  Lasted two seconds and I was out so I didn't get that bliss people talk about but not the addiction either.

I survived and puked up green and black shit in the morning.  Yes I was a young moron but it awakened me to so much as I am generation X and am a 80's kid, didn't know. Hence teach that and sex education in schools.  Thought I had herpes but just a long lasting rash after I saw a doctor and always wipe your area there with your towl.  Not Brazillian wax but still helps to clip it.

That new Borat movie made me laugh with the daughter of Borat and that scene with her bush grown out like that.  It was a merkin of course but the joke was great.  And the period part of it.  Wow.  Fertility rites. 

Jibberjabber  adopting a cat today.  Hooray for me!  Carrot juice and ginger and beers.  Is so strange thinking back on that movie how dumb rich people are in general.  How easily the are ignorant of so many things. 

I grew up in a Mormon family that went to shambles and living in Utah is interesting.  Everything is set up.  Jews get it.  Baptism, Mission, College and temple marriage, starter home, lots of kids, and blah.


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OfflineJonBa
Hawaiian shirt weirdo

Registered: 05/14/19
Posts: 361
Last seen: 2 years, 4 months
Re: Tolerance and downregulation [Re: Barnaby]
    #27045174 - 11/18/20 09:37 AM (3 years, 2 months ago)

Quote:

Barnaby said:
-stuff-




Pardon?


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InvisibleBarnaby
Interesting lifetime
Male

Registered: 12/13/17
Posts: 9,146
Re: Tolerance and downregulation [Re: JonBa]
    #27045177 - 11/18/20 09:39 AM (3 years, 2 months ago)

You are pardoned by the President.  Only way.


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OfflineInsultingLizard
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Registered: 01/04/20
Posts: 546
Last seen: 4 months, 11 days
Re: Tolerance and downregulation [Re: Barnaby]
    #27045284 - 11/18/20 10:32 AM (3 years, 2 months ago)

Well... Hope your cat has a long, happy life.


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Invisibleopenmind
curious
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Registered: 08/03/07
Posts: 13,876
Re: Tolerance and downregulation [Re: Pandemoon]
    #27045422 - 11/18/20 11:53 AM (3 years, 2 months ago)

Quote:

JonBa said:
Good question, but I think the downregulation might be why you feel like sleeping for a full 2 days after a strong trip?  :uhoh:






I don't feel like sleeping much the day(s) after a mushroom trip, sometimes maybe but that's not a typical aspect of mushrooms for me.....

...but after a strong LSD trip I do tend to be a bit sleepy headed and lethargic for the day or two after. I've always suspected this is because of LSD having more affinity for/action on dopamine receptors than mushrooms and the dopa system being a bit "down-regulated" the day(s) after.





Quote:

Pandemoon said:
Isn't the so called "afterglow" an alteration of our perception? It can last for days, if not weeks.. especially after a heavy trip.

-





I usually have a nice lingering afterglow with any psychedelic...tho some of the time I am feeling a bit sleepy/lethargic the days after a trip with LSD, I do still have a pleasant "glow" of sorts that sticks around for at least a day or a few.

I've always wondered what's going on with the "after glow" from a neuro/pharmacological perspective, considering that 5ht receptors and others are usually "down-regulated" (less sensitive than usual) the days after a trip.





-OM

.


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