the_integerian
Bluelighter
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While psilocybin tends to cause more relaxation
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Why does LSD tend to cause stimulation?
- Thread starter the_integerian
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mdmantpa
Bluelighter
IME they both stimulate the mind because of the way they make us process information, its almsot as if we are on overload mode. But it is true that LSD has a slight upper feel,idk why tho
Depends on what other receptors beyond 5HT2A it acts on, how it distributes itself in the body/brain, etc. But what else could we say in response to that? The details are unknown.
Until research on psychedelics is decriminalized and respectable, nobody (certainly nobody who is interested in psychedelics for their own sake) can do the really informative research that would lay bare the mechanism of psychedelic drugs and the means by which they produce all the subtly different effects that they do.*
I am aware of no typical psychedelic (5HT2A antagonist) which has been shown to exert stimulant effects via the same mechanism as typical stimulants (DA/NE release). (not counting psychedelic empathogens like AMT and MDA)
*Shulgin was a rare exception, but at that time the technology wasn't there, and he didn't have the funding even if it was, to investigate the receptor binding properties, which I think would have been very informative. Not that he would put much stock that anyway (and I see the merit in his point but the real fascinating part is in finding how the subjective effects and the receptor binding and other mechanical effects correlate)
Until research on psychedelics is decriminalized and respectable, nobody (certainly nobody who is interested in psychedelics for their own sake) can do the really informative research that would lay bare the mechanism of psychedelic drugs and the means by which they produce all the subtly different effects that they do.*
I am aware of no typical psychedelic (5HT2A antagonist) which has been shown to exert stimulant effects via the same mechanism as typical stimulants (DA/NE release). (not counting psychedelic empathogens like AMT and MDA)
*Shulgin was a rare exception, but at that time the technology wasn't there, and he didn't have the funding even if it was, to investigate the receptor binding properties, which I think would have been very informative. Not that he would put much stock that anyway (and I see the merit in his point but the real fascinating part is in finding how the subjective effects and the receptor binding and other mechanical effects correlate)
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^ I would agree man but there is only so much that your mindset can do, when you have such an absurd amount of energy, I don't think it's plausible that it's NOT the drug itself that is causing it, I'm not saying that it's impossible for anything other than the drug itself to cause it, I'm just saying it doesn't seem plausible to me
madswagga, I'm sorry but I'm gonna have to say that I don't see a mood releasing the amount of chemicals MDMA does all at once. maybe some kind of extreme situation like near death experiences, but if mood could cause the large chemical dump that mdmda does, we wouldn't need mdma anymore hahaha
j.zhivago
Greenlighter
I think mental and physical environments,dose of course too, determine such things. On several occasions(times with both substances) I enjoyed running around like some wild man breaking free.Other times,most frequently were spent cross-legged sitting in the dark.I think it just comes down to personal setting rather than the chemical itself.
Malice-
Greenlighter
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Since LSD itself comes from ergot, this would only make sense:
"Nevertheless, the pharmacologist H. H. Dale discovered that ergotoxine, besides the uterotonic effect, also had an antagonistic activity on adrenaline in the autonomic nervous system that could lead to the therapeutic use of ergot alkaloids. Only with the isolation of ergotamine by A. Stoll (as mentioned previously) did an ergot alkaloid find entry and widespread use in therapeutics. "
Also, this:
"I further employed my synthetic procedure to produce new lysergic acid compounds for which uterotonic activity was not prominent, but from which, on the basis of their chemical structure, other types of interesting pharmacological properties could be expected. In 1938, I produced the twenty-fifth substance in this series of lysergic acid derivatives: lysergic acid diethylamide, abbreviated LSD-25 (Lyserg-säure-diäthylamid) for laboratory usage.
I had planned the synthesis of this compound with the intention of obtaining a circulatory and respiratory stimulant (an analeptic). Such stimulating properties could be expected for lysergic acid diethylamide, because it shows similarity in chemical structure to the analeptic already known at that time, namely nicotinic acid diethylamide (Coramine). During the testing of LSD-25 in the pharmacological department of Sandoz, whose director at the time was Professor Ernst Rothlin, a strong effect on the uterus was established. It amounted to some 70 percent of the activity of ergobasine. The research report also noted, in passing, that the experimental animals became restless during the narcosis. The new substance, however, aroused no special interest in our pharmacologists and physicians; testing was therefore discontinued. "
-Albert Hoffmann, LSD: My Problem Child
I hope this helps.
"Nevertheless, the pharmacologist H. H. Dale discovered that ergotoxine, besides the uterotonic effect, also had an antagonistic activity on adrenaline in the autonomic nervous system that could lead to the therapeutic use of ergot alkaloids. Only with the isolation of ergotamine by A. Stoll (as mentioned previously) did an ergot alkaloid find entry and widespread use in therapeutics. "
Also, this:
"I further employed my synthetic procedure to produce new lysergic acid compounds for which uterotonic activity was not prominent, but from which, on the basis of their chemical structure, other types of interesting pharmacological properties could be expected. In 1938, I produced the twenty-fifth substance in this series of lysergic acid derivatives: lysergic acid diethylamide, abbreviated LSD-25 (Lyserg-säure-diäthylamid) for laboratory usage.
I had planned the synthesis of this compound with the intention of obtaining a circulatory and respiratory stimulant (an analeptic). Such stimulating properties could be expected for lysergic acid diethylamide, because it shows similarity in chemical structure to the analeptic already known at that time, namely nicotinic acid diethylamide (Coramine). During the testing of LSD-25 in the pharmacological department of Sandoz, whose director at the time was Professor Ernst Rothlin, a strong effect on the uterus was established. It amounted to some 70 percent of the activity of ergobasine. The research report also noted, in passing, that the experimental animals became restless during the narcosis. The new substance, however, aroused no special interest in our pharmacologists and physicians; testing was therefore discontinued. "
-Albert Hoffmann, LSD: My Problem Child
I hope this helps.
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Coolio
Greenlighter
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MDMA doesn't do that much to me anymore, as I've integrated the mindset into everyday sober reality.
madswagga
Bluelighter
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look into some biochemistry along with psychology. you'd be surprised at what the mind can do. remember when you pop a pill of ecstasy it isnt the mdma or meth that goes to your brain and you get high off of. its the chemicals and neurotransmitters your brain releases
Malice-
Greenlighter
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While increased extracellular serotonin, dopamine, and norepinephrine will definitely increase heart rate, there are other mechanisms as to how MDMA increases heart rate. The study was performed on rats, though.
![:\](https://bluelight.org/xf/BL_Images/Orig_Emoji/wrygrin.gif "wry grin :\")
Venrak
Bluelight Crew
Not to further derail this thread, but a while ago I found I could become euphoric by will alone; The sensation is similar to those produced by dopaminergic drugs and lasts for several minutes.
hamhurricane
Bluelighter
this is not true at all. there has been an enormous amount of research into the pharmacology of LSD and this research is ongoing. the short answer to the OPs question is that LSD has a higher affinity for dopamine receptors than any of the alkaloids found in psilocybe mushrooms. Psilocybin acts primarily on serotonin receptors but LSD binds potently to both dopamine and serotonin receptors (as well as several others) the unpleasant stimulating effect is hypothesized to be caused by the LSD metabolite 13-HO-LSD.
LSD has a biphasic effect - plasma levels of the parent compound drop off at about four hours but, it is thought, around that time the 13-hydroxylated metabolite comes into play binding more strongly to D2 receptors, which as far as we can tell does not feel especially good. like i said this research is ongoing and perhaps in the next few years more will be known about how 13-OH-LSD impacts the LSD experience.
Sandozer
Bluelighter
That's neato man! I've never heard of that metabolite before. I feel like a dumbass now. Pardon me if I don't understand but your saying that LSD metabolizes into 13-HO-LSD and then 4 hours in that metabolite binds to the D2 receptor?
If you could simplify that explanation for me by putting it into layman's terms that'd be great. Here's the graph. I couldn't find one for psilocybin/psilocin.
The Hof was searching for circulatory stimulants when he discovered LSD, but I have no clue why psilocybin has a different effect in the aspect of stimulation. That's a good question though.
You can't hassle the Hof.
But this question puzzles me. I never thought about it, then again, I haven't taken mushrooms for 3 years either.
love_sex_desire
Bluelighter
^^ I think the reason why psilocybin has a different effect in the aspect of stimulation is because of its primarily serotonergic activity. In very simplified terms it is the dopamine activity that causes LSD to be stimulating, and the serotonergic activity that causes LSD to be psychedelic. Since psylocibin causes lower levels of dopamine actvity compared to LSD, it is not stimulating like LSD.
olieroliepolie
Ex-Bluelighter
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I have took acid hundreds of times which i know probably sounds like im telling fibs lol, from 16-21 i took acid regularly and built up a tolerance where i had to consume 7 strawberrys to get a good trip. The reason why i stopped was i found that dosage overly stimulatiory on the body as in my eyes/ears/mouth and throat seriously feeling bad and i can only assume that i was being poisoned due to high toxicity. Since then i do not get much of a buzz using LSD which is a shame as i loved it in the past but i won't chance upping my dosage for reasons i posted above. Members should only use this one sparingly as not to lose the magic. Mushrooms on the other hand are not half as bad on the body when consuming massive doses and i can only assume that compared to LSD are not as toxic. I am more than likely going to be proved wrong on both counts hehehe...Sorry not really on topic.
p.s.. I found mushrooms the ultimate mood buzz, if on an evening outdoors i would feel endless energy and very strongly stimulated though in a focused way, like keeping it under wraps till that energy was needed. I would sprint for ages and felt like a could do anything physically. Other times chilling out with friends indoors with mellow tunes on the stimulation would not really be there or even feel it could be called on, at this time i would feel strongly empathy and a need to comunicate and share. Thinking back shrooms were the better of the two highs
p.p.s.. love,sex and desire i am not following you, lol
p.s.. I found mushrooms the ultimate mood buzz, if on an evening outdoors i would feel endless energy and very strongly stimulated though in a focused way, like keeping it under wraps till that energy was needed. I would sprint for ages and felt like a could do anything physically. Other times chilling out with friends indoors with mellow tunes on the stimulation would not really be there or even feel it could be called on, at this time i would feel strongly empathy and a need to comunicate and share. Thinking back shrooms were the better of the two highs
p.p.s.. love,sex and desire i am not following you, lol
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love_sex_desire
Bluelighter
In my limited understanding, dopamine is a neurotransmitter associated with stimulating effects, similar to adrenaline. It is the brain's reward system and is associated with stimulants such as cocaine and methamphetamine. These stimulating drugs act on the dopamine receptors by inhibiting the upregulation and increasing the release of dopamine and epinephrine, resulting in a stimulating effect.
Serotonin, from what I understand, is associated more with relaxed and euphoric properties, but also anxiety and stomach irritability (depending on which serotonin receptor is affected). There are many serotonin receptors and it has been found that the activation of the 2nd (a) serotonin receptor is intrinsically linked with psychedelics visual aspects. So from that understanding we can infer that both mushrooms and LSD activate the 2nd (a) serotonin receptor, called the 5-ht2a receptor because both drugs have the visual effects of traditional psychedelics.
Most drugs also effect other neurotransmitters and their receptors. LSD activates the dopamine receptor associated with stimulating effects at a higher affinity than mushrooms, thus we can infer that both mushrooms and LSD will have visual effects, but because of LSD's higher affinity for the dopamine receptors compared to mushrooms, we can infer that LSD will have more of a stimulating effect compared to mushrooms.
Summarized:
High affinity for the 5-ht2a receptor equates to classic psychedelic effects
Higher affinity for the dopamine receptors equates to more stimulating effects
I do not know much about brain chemistry so some of my wording may be incorrect, but I hope this clears up what you were not following.
From my understanding LSD is virtually non-toxic. The dose response curve is very safe in that an effective therapeutic dose is many times lower than fatal or toxic doses. Unless someone is taking doses of LSD many times higher than a normal psychedelic dose, toxicity should not be an issue.
Does anyone have any sources to back up this assumption that LSD is toxic?
Does anyone have any sources to back up my belief that LSD is almost completely non-toxic? I can't be bothered to dig anything up right now, but there are many studies indicating the physical safety of LSD.
From my research I have come to the conclusion that LSD is very safe physically. The only negative aspect of LSD is its intense effect on the psyche. LSD mainly effects the brain, in a very powerful and somewhat overwhelming way. The main danger with using LSD is not in its physical effects but in its mental effects. If someone with a family history of mental illness, or with diagnosed mental illness, or someone in the midst of emotional trouble, uses LSD irresponsibly there is a chance that they may experience a psychotic outbreak.
A friend of mine who did not reveal that he was diagnosed with schizophrenia as a teenager used 2C-E (a very powerful psychedelic similar to LSD) on a regular basis. After a bad trip where he was caught in a time loop when he tried 4-HO-DiPT for his first time he mistakenly decided to drop a large 22 mg dose of 2C-E a few days later and entered the exact same loop process that he had experienced on 4-HO-DiPT. The powerful mental effects of these psychedelics precipitated a psychotic reaction. He had to take a month long leave from work, but has since recovered, although he has now vowed to never touch chemicals again.
Other than the mental risks of LSD use in those who are not mentally sound, I know of no significant physical risks associated with the use of LSD. It does cause vasoconstriction, but luckily the dose for LSD is in the micrograms and is such a small amount that dangerous physical effects do not become an issue until one consumes many times the regular dose range of LSD.