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Help me understand some LSD facts mechanism of action ect.

G

Godzilla

Bluelighter
Joined
May 4, 2010
Messages
397
I have just started reading about LSD, very interesting. I plan on reading more and gaining a more in depth knowledge of LSD.

My question is since LSD is a agonist at the 5ht receptors it can cause down regulation. (correct???) and the down regulation can cause higher tolerances. Possibally depression with long term frequent use. (related to downregulation of 5ht receptors.) The good thing is that you are not depleting your natural serotonin stores.

While MDMA causes depleation of your serotonin stores from the neuron (correct?)
So I figure abuse of MDMA can cause depression or (loss of magic) because your natural serotonin stores can be completely used. or gone. Plus you can have down regulation related to the chronic flood of serotonin on the receptors.

Ok am i understanding this???
How often is if safe to use LSD???
Are there any people on here that have used it 2-3 times a month for long periods of time. What are the long term effects of use and abuse. When is LSD use considered abuse. I know the common thing is to wait 1-2 months between MDMA trips what about LSD??? Thanks
 
I have a friend who used LSD about 2-3x per month for at least a 6 month period, he is just fine. Abuse generally just means the point where it starts affecting other parts of your life negatively, which it never did for him. He never developed any issues from psychedelic use besides minor HPPD. He trips 1x a year now roughly, his period of use was about 2 years ago.

I haven't used LSD to that extent but I did spend one summer where I tripped at least ten times over a period of 12 weeks. A few different research chemicals, mushrooms, LSD all in high doses. It probably won't kill ya but from my experience there are lots better things you can do with your life than trip weekly or even every other week. This period of my use is mostly what I attribute my cessation of psych use to. Stopped being novel I guess.

Long term effects probably won't be much unless you have a latent MI that could be brought out/precipitated. Otherwise you just stand a good chance of developing psych-burnout, aka Watts quote where you get the message and hang up the fone.
 
Thanks for any and all input.
Another thing i want to mention is that I used to drink almost everyday.(tequilla) Then I went into smoking weed almost everyday. While I was smoking i totally quit drinking and now I actually hate alcohol.

Then about one month ago I quit smoking pot.
I have smoked twice in one month.

Im not looking for an alternative to alcohol or weed Im just wondering if I were to do LSD at a low dose once or twice a month what would the long term affects be??

I realize that with any of the above substances I am doing harm to my body. I just seem to hate alcohol and everything that has to do with it. I hate how society deems it to be socially acceptable. It is horrible how many problems stem from alcohol. Unwanted pregnancies, car crashes, liver disease., fights, ect ect. We just dont see this happening as frequently with other drugs. Dont get me wrong being addicted to any substance is a serious problem and has serious consequences. (got off the subject) :)

Anyway is it safe to use LSD 2-3 times a month?
What are long term effects of using LSD at this frequency?
 
LSD is one of the safest drugs out there, assuming you dont already have pre-existing psychiatric problems. That being said, there is little point in doing low doses, it will quickly lose the magic, just as with MDMA, although for different reasons.

just my 2 cents
 
I be honest i just really like the feeling of low dose LSD. I dont need to be completely out of this world. (been there done that) I like to be able to function if needed. I allways try to get as far away from my family and responsibilities if im going to trip but I still need to be functional if there is an emergency
 
Godzilla said:
My question is since LSD is a agonist at the 5ht receptors it can cause down regulation. (correct???) and the down regulation can cause higher tolerances. Possibally depression with long term frequent use. (related to downregulation of 5ht receptors.)
Click to expand...

No, for two reasons.
First of all, LSD only has significant affinity for the 5HT2a and 5HT2c receptors, not all serotonin receptors. Those two receptors activate quite different effector pathways than, say, 5HT4 or 5HT5a receptors.
Secondly, research has shown that serotonin and LSD affect 5HT2a receptors quite differently from one another, and that they probably activate different effector pathways.

For a more in-depth review of current knowledge on, I suggest you take a look at this brilliant, albeit somewhat dated, article from The Heffter Review:
Serotonin Receptor Signaling and Hallucinogen Action

Actually, recent research has shown that LSD and other compounds with similar action might actually have a positive effect on depressed patients, and we are beginning to understand the neurobiology behind that fact. I read a paper on that recently, that I can try to find for you if you are interested. :)
 
there is a short term tolerance with LSD that some think is related to a downregulation of 5-ht2a receptors, but i don't know if there is any reliable evidence to back that up. The Hoffman collection at erowid is a great place to do some reading of legitimate research on LSD & other psychedelics as well. There are many, many psychedelics that are 5ht2a agonists, in fact some would probably say that its a requirement for a substance to be considered "classically" psychedelic.
 
Oh yeah, I hope that it didn't sound like I was denying that there is some tolerance buildup! I just don't think that there is a link between LSD tolerance and depressive symptoms :) .

By the way, the hypothesis that the tolerance is due to 5HT2a receptor downregulation has one "flaw": If that was the case, how would one explain that some other 5HT2a agonists do not exhibit decreased activity when one has a high LSD tolerance? :)
 
I would be interested in links or any info on LSD and its mechanism of action.
I would love to see if there were any strudies conducted on long term use.
I will look into those hefftner papers.
Culpepers you make a great argument. So they have actually given someone with a known tolerance to LSD a different 5ht2a agonist and they exhibited a normal response.
So the question is are there different intercellular processes that are happening with different 5ht2a agonist.
(please dont bash me Im trying to understand)
 
I think that what you mean when you say intra-cellular processes is what neurobiologists call effector pathways - i.e. the mechanism that is activated by some receptor. All that is talked about in the Heffter article mentioned above, but in short: Yes, we have pretty good evidence that different agonists can cause receptors to behave differently (which was not previously thought to be the case). As is mentioned in the Heffter article, we now know that multiple effector pathways can couple to a single receptor type, meaning that this one receptor can respond to stimuli in more than one way.
For instance, the 5HT2a receptor behaves quite differently depending on whether the agonist is serotonin or, for instance, the psychedelic DOI.

But it's all in the article :)
 
Culpepers said:
Oh yeah, I hope that it didn't sound like I was denying that there is some tolerance buildup! I just don't think that there is a link between LSD tolerance and depressive symptoms :) .

By the way, the hypothesis that the tolerance is due to 5HT2a receptor downregulation has one "flaw": If that was the case, how would one explain that some other 5HT2a agonists do not exhibit decreased activity when one has a high LSD tolerance? :)
Click to expand...

I don't think there is a link between LSD & depressive symptoms either, excepting the odd idiosyncratic reaction of course. But those seem to be few & far between.

Well the cross tolerance seems to apply to all psychedelics, from anecdotal evidence anyway. Some people don't experience it, or experience it to a lesser extent than most, but those seem to be the exception rather than the rule.
 
I used lsd every weekend for a few months, I would take around four to six hits each time because of tolerance. The only negative effects I got from it were what I thought were symptoms of HPPD, but I'm not sure anymore. It cleared up after about 5 moths. So basically for five moths after I stopped taking LSD I continued to trip. It wasn't intense or anything. I would see auras around objects and walls would ripple, things like that. Every time I would smoke weed I would trip much like I had when I was on LSD, even when I drank alcohol I would get visuals. Its pretty safe in the long run but its a lot more fun if you only take it a few times a year.
 
any major dude said:
Well the cross tolerance seems to apply to all psychedelics, from anecdotal evidence anyway.
Click to expand...
From my own personal experience (and those of my friends) the 2C-X's do not exhibit any decreased activity even when taken a day or two after LSD or mushrooms (at a time when LSD or mushrooms would have virtually no effect). But that doesn't mean that it's like that for everybody, of course. Just everyone I know, oddly enough ;)
 
Godzilla said:
I would be interested in links or any info on LSD and its mechanism of action.
I would love to see if there were any strudies conducted on long term use.
I will look into those hefftner papers.
Culpepers you make a great argument. So they have actually given someone with a known tolerance to LSD a different 5ht2a agonist and they exhibited a normal response.
So the question is are there different intercellular processes that are happening with different 5ht2a agonist.
(please dont bash me Im trying to understand)
Click to expand...

LSD is probably the most well-researched psychedelic out there (unless you count cannabis). There have been tons of studies into its mechanism of action and effects of long-term use. A good place to start is the Erowid vault for LSD: http://www.erowid.org/chemicals/lsd/

To address what seem to be your main concerns so far: tolerance is usually only a major issue if you try to dose more than once a week. Dosing every couple weeks probably wouldn't cause much/any long-term tolerance build up. Even really excessive use doesn't cause serotonin depletion, receptor damage, or any of the other problems associated with overuse of drugs like MDMA. The main dangers of "abuse" are psychological: losing touch with day to day life, shirking real-world obligations to trip more often, having an intense bad trip, etc. It's perfectly possible to use LSD several times per month over a long timeframe without any negative physical effects. Since it's not physically damaging or addictive, I think "how much use is abuse?" can only be answered on a person-by-person basis.

There's also HPPD, which seems more common with heavier use, but we really don't know much about that. HPPD means you continue to get visual distortions long after the psychedelics wear off. Cases severe enough to get diagnosed are relatively rare.
 
I read the hefftner review. It really was an in depth look at the intracelular MOA. It brought back a lot of knowledge form grad school. Thanks. I really appreciate everyones input and will continue to research further into LSD. It is really interesting. Thanks again.
 
Great post Godzilla,

I'm glad I saw this because I was having a discussion with someone yesterday and they explained to me that they read somewhere that it's bad for you. I didn't really believe it because I've read so much about LSD and know that it isn't true, just didn't have anything on me at the time to back my side up.

Thanks again,

-djstrip
 
That is the problem with most people. They dont take the time to really research what drugs they are experimenting with. That is dangerous. Most people just believe what some ignorant person tells them and takes it for the truth. I wish more people would be a litttle more responsible. Plus this is extreamly interesting reading. IMO...
If people would do things a little more responsibally then there would not be so many laws governing our behavior and less problems with addiction ect
 
Godzilla: I completely agree! Good to see that someone is willing to do some studying. :)
 
rincewindrocks said:
LSD is one of the safest drugs out there, assuming you dont already have pre-existing psychiatric problems. That being said, there is little point in doing low doses, it will quickly lose the magic, just as with MDMA, although for different reasons.

just my 2 cents
Click to expand...

I'm curious as to why you think it will lose the magic? After several years of taking high doses, then a VERY long hiatus, I now generally only take low doses, and I still regularly get my ass kicked (my tolerance seems to have actually decreased, practically to the point where I see acid and start mildly tripping). Even when ass-kicking does not occur, I always experience low dose effects. I don't take LSD that often though - perhaps once every 2 months at most. I do find my recovery time is taking longer though - the day after I pretty much can't speak at all, to anyone.

Why exactly would it "lose the magic" if taken fairly regularly at low doses?
 
the day after I pretty much can't speak at all, to anyone.
Click to expand...
Could you elaborate on that? That seems like a somewhat disturbing after effect. I always feel open and content the day after a good acid trip.
 
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