100ug of LSD for ADHD, daily

[LSD for ADHD]

Hi,

I've been researching LSD and its positive effects for those with ADHD.

I would like to ask about opinions and any studies that show a correlation between LSD and a reduction in the severity of ADHD symptoms. I have researched some studies of epigenetic effects of LSD on dopamine receptors and transporters through 5-HT2A receptor downregulation. Perhaps more importantly to the reduction of the severity of ADD/ADHD symptoms is to glutamergic effects of 5-HT2A downregulation in the PFC. Many people think that it's dopamine that causes a reduction in ADHD severity; but, glutamatergic signalling is also as important.

I came across some anecdotal evidence that the main metabolite of LSD (2-oxo-3-hydroxy-LSD (O-H-LSD)) is actually a long-lasting metabolite of LSD with significantly more potent dopaminergic activity than the parent compound.

What I have done in regards to, what I believe, positive evidence and effects of LSD on ADHD (depression/anhedonia/alteration in default network activity from a resting state to a more proactive one) is to titrate my doses of LSD so as to not experience the hallucinogenic effects, while leading to persistent down-regulation of 5-HT2A receptors in the PFC as to facilitate glutamate activity, and thus leave the dopaminergic activity of LSD intact without psychedelia. My further hope, though not substantiated by scientific studies although I ask for your input on the matter, is that the metabolite of LSD would also contribute to pro-dopaminergic activity.

You might say that people already do this by microdosing; but, I'm taking this a step further. My idea is to persistently administer LSD (100ug daily) in doses that do not cause psychotropic effects while maintaining the positive effects for ADD/ADHD/depression/anxiety.

I'm just wondering if psychosis can be exacerbated due to constantly taking LSD in those doses, despite developing what some call "tolerance", whereas this "tolerance" would be sought after by me by not trying to trip.

My motivation for doing this is to rather take something that is cheap, natural, and by all means more healthy than amphetamines, derivatives, or methylphenidate, which act directly on dopmaine in a rather nasty fashion if you understand.

 

[nintey]

you're an idiot

 

[Hodor]

My motivation for doing this is to rather take something that is cheap, natural, and by all means more healthy than amphetamines, derivatives, or methylphenidate, which act directly on dopmaine in a rather nasty fashion if you understand.

How the hell is LSD "natural"? LSD is semi-synthetic.

Also, daily administration of ergot derivatives might lead to cardiac valvulopathy in the long run (ergoline-based anti-migraine and anti-parkinsonian drugs have mostly been withdrawn from the market for this reason).

 

[LSD for ADHD]

How the hell is LSD "natural"? LSD is semi-synthetic.

Sorry, what I meant was that it feels natural.

Also, daily administration of ergot derivatives might lead to cardiac valvulopathy in the long run (ergoline-based anti-migraine and anti-parkinsonian drugs have mostly been withdrawn from the market for this reason).

You know, my options are to either treat my ADD or not. So, I'm left with a handful of options. Actually, one. To increase dopamine via reuptake inhibitors or releasing agents. However, LSD presents another alternative here due to increasing dopamine levels possibly through a handful of mechanisms while being an agonist/partial agonist on important receptors pertaining ADHD. If cardiac valvulopathy is a potentially harmful side effect rather than have the side effects of stimulants, which feel very unnatural, then I'll take the rather minimal risk and comparatively much more worthwhile option of using LSD if possible.

Besides, none of the points I brought up has been even mentioned or questioned.

 

[Weltmeister]

this wont work long term. tolerance to LSD develops extremely quickly

 

[LSD for ADHD]

this wont work long term. tolerance to LSD develops extremely quickly

Depends on what you mean by tolerance here. Yes, the 5-HT2A receptors responsible for the hallucinogenic effects do downregulate insanely fast along with upregulated equally fast. However, the point is to persistently downregulate 5-HT2A receptors, while allowing LSD to be a partial agonist on D1/2 receptors, along with its more potent metabolite.

 

[Weltmeister]

AFAIK LSDs dopaminergic effects are heavily dependant on 5HT2A activation sensitizing dopamine receptors AND direct dopamine receptor agonism

 

[LSD for ADHD]

AFAIK LSDs dopaminergic effects are heavily dependant on 5HT2A activation sensitizing dopamine receptors AND direct dopamine receptor agonism

Yeah, so the question is something like, what are the effects of persistent stimulation of 5-HT2A receptors... on glutamate activity, dopaminergic tone, receptor sensitivity.

Personally, I've never heard of bad effects from persistent 5-HT2A partial agonism.

 

[Weltmeister]

Probably because it has never been studied. At least not that im aware. Also I highly doubt there will be too many studies about the effect of taking hallucinogenic doses of LSD every day on ADHD

 

[sekio]

100ug LSD per diem seems too much. You'll get tolerant quite rapidly and your sleep quality will probably suffer.

LSD is pretty selective for 5ht2a and is not much of a dopaminergic at normal doses IIRC too. Not directly at least. It does bind for quite a long time.

 

[sean107]

Maybe try 20 micrograms to 25 micrograms? Tolerance develops much less rapidly at microdose amounts of LSD. However it does still effect sleep quite a bit.

 

[Solipsis]

13-OH-LSD, a metabolite, is supposed to be only dopaminergic as its effects can be blocked by an antidopaminergic ligand. It is also supposed to be quite potent. Unfortunately I'd like some more confirmation from Nichols about this cause it seemed like it was still a going-on piece of research and I can't find anything on it since then.

You don't need to take it daily for the 5-HT2a downregulation benefits and the supposed dopaminergic effects are too sketchy (psychosis liable, anxiogenic etc) to apply for ADHD. D2 agonism doesn't seem useful the way dopamine release or dopamine reuptake inhibition is??
Yes, the serotonergic effects are supposedly necessary to sensitize the dopaminergic system so if you grow tolerant to the serotonergic effects you will lose that sensitization.
However it's pure speculation as far as I am aware, that this sensitization is essential for the - also speculative - effects of 13-OH-LSD.

Also, the fibrosis causing effects on 5-HT2b would make something like LSD potentially (probably even? but a bit hard to calculate) harmful for your heart and lungs among other tissues if you take it daily as opposed to weekly/less-than-weekly.

Nice try, but no cigar

 

[IamaBonobo]

You need to do a lot more research because this is such a dumb idea for too many reasons to count. Have you ever even tried LSD @ 100µg? There's no way this would work, and even if it did it would still be a terrible idea.

 

[Solipsis]

Apparently dosage was 'titrated', although somehow apparently down as a form of microdosing with tolerance. The idea is not *that* terrible if you just expect tolerance to help you avoid psychedelic effects and also assuming that takes care of all other risks like psychosis, which is what is asked about here.

But yeah unfortunately still quite a number of flaws - my perspective on that listed the flaws ^^.

IME (i have ADD and ASD) lsd does relieve my issues, so I like to use it semi-weekly, which is sort of consistent with the idea that such a frequency gives you tolerance in the meanwhile, and the downregulation involved in that also is responsible for these therapeutic effects.

So: it does work but I don't really see a way around taking a psychedelic dose semi-weekly to produce this tolerance. You don't really want to take it more often to "maintain your tolerance" without having to trip so to speak. I also think that low-ish doses like 60 ug would produce less tolerance than higher doses, but I don't think it's "the higher the better" either. Basing my view on this on the assumption that tolerance is both a measure for therapeutic potential (although nobody said linearly) and can be felt by the diminishing returns.

No point in trying to improve on this, certainly not by being wasteful and risking various issues. I have no idea if the TS is actually trying to avoid tripping for whatever reason.

I'm seriously due for another session, it's been too long and I am noticeably worse off right now than after a trip.

 

[LSD for ADHD]

13-OH-LSD, a metabolite, is supposed to be only dopaminergic as its effects can be blocked by an antidopaminergic ligand. It is also supposed to be quite potent. Unfortunately I'd like some more confirmation from Nichols about this cause it seemed like it was still a going-on piece of research and I can't find anything on it since then.

Yeah, I'm assuming you're referring to this video:
https://www.youtube.com/watch?v=ZJtdZUy1LYE&feature=youtu.be&t=43m39s

You don't need to take it daily for the 5-HT2a downregulation benefits and the supposed dopaminergic effects are too sketchy (psychosis liable, anxiogenic etc) to apply for ADHD. D2 agonism doesn't seem useful the way dopamine release or dopamine reuptake inhibition is??

That's probably true; but, unknown until we know the binding profiles of the most predominant metabolites of LSD. I don't think D2 binding is psychosis liable due to newer gen antipsychotics working as D2 partial agonists to stabilise aberrant D2 activity in schizophrenics. I would even hypothesise that LSD, taken continuously, could serve as an antipsychotic.

Yes, the serotonergic effects are supposedly necessary to sensitize the dopaminergic system so if you grow tolerant to the serotonergic effects you will lose that sensitization.
However it's pure speculation as far as I am aware, that this sensitization is essential for the - also speculative - effects of 13-OH-LSD.

From what I've read about 5-HT2A receptors, the more important factor than DA sensitization is its stimulatory activity on glutamate activity on PFC function (which is one of the ways DRA's and DRI's work, that is to increase activity of glutamergic activity in the PFC through dopamine stimulation), which overcomes the liability of having the nucleus accumbens activated and this leading to dependency. Quite an appealing and novel aspect for any potential ADHD drug nowadays given the propensity for abuse.

Also, the fibrosis causing effects on 5-HT2b would make something like LSD potentially (probably even? but a bit hard to calculate) harmful for your heart and lungs among other tissues if you take it daily as opposed to weekly/less-than-weekly.

There are ways to mitigate that, and besides, I'd rather take LSD than a SSRI for depression (as that's something that concerns me more than fibrosis due to the fact that SSRI's actually have a higher prevalence of cardiac complications than some 5-HT2b agonists). For the matter, isn't LSD a 5-HT2b partial agonist?

Nice try, but no cigar

Well, this is really cutting edge science. I don't think MAPS is even aware of the idea of taking large doses of LSD to induce the above-mentioned effects. I might just try and contact Nichols to see what the thinks. At the very least, you would be able to drastically reduce DRA/DRI consumption, as I think 4F-MPH is an ideal candidate for ADHD here to use, and plan to use in conjunction with LSD at minimal doses.

Thanks for entertaining the idea!


What further complicates the issue is that economically, the only viable LSD prodrug that can be obtained and self-administered nowadays is 1P-LSD, which may have its own unique metabolites.

 

[LSD for ADHD]

100ug LSD per diem seems too much. You'll get tolerant quite rapidly and your sleep quality will probably suffer.

LSD is pretty selective for 5ht2a and is not much of a dopaminergic at normal doses IIRC too. Not directly at least. It does bind for quite a long time.

Maybe try 20 micrograms to 25 micrograms? Tolerance develops much less rapidly at microdose amounts of LSD. However it does still effect sleep quite a bit.

I don't know if I got the point across; but, tolerance is something desirable here. Much like the adaptive changes that occur to SSRI drugs in treating depression. Who knows, maybe 5-HT2A levels are already too high in ADHDers, apart from depressed and suicidal people. *Goes back to studying the etymology of ADHD and its relation to 5-HT2A receptors.*

 

[LSD for ADHD]

So, I went ahead and contacted Dr. Nichols. Let's see what he thinks.

 

[Solipsis]

5-HT2A receptor populations are high in people with ASD but that is apparently in platelets and not sure about the rest, but it could match the glutamatergic involvement hypotheses.
Again: regarding safety it seems unreasonable to take a lot of LSD all the time when you can take a normal amount every once in a while - it works, what more do you want? I just don't think it's all that effective relatively speaking to keep up a tolerance that is already there.
How would you mitigate 5-HT2B agonism? Antagonism is not all that smart, I think that too can cause such problems in tissue formation.

What do you actually base on that LSD could be an anti-psychotic? By taking LSD daily you are still activating what 5-HT2A receptors you have which isn't what you want. Yet on the other hand, you are still producing tolerance so limited 5-HT2A populations will eventually lower your potential for 'sensitizing your DA system' if that is what you are after. The whole point is the in-between time of having tolerance. Not just reaching some new homeostatis with the LSD.
I don't see how any idea of it working for ADHD beyond those benefits from 2A downregulation has any substantiation. Meaning: I don't think the reasoning behind it is sound. No offense of course but it seems more like guesswork than cutting edge science to me.

What's more, that wouldn't be in proportion to the health / safety issues involved in this plan.

I expect Nichols to be very reserved about what we actually know about this, what conjecture is reasonable, and about the safety of taking a drug like this daily.

Partial agonist does not mean low efficacy - just lower than the endogenous ligand - serotonin - itself, which is setting the bar high. IIRC it is fairly effective on 2B and perhaps more importantly: it snags onto the receptor and binds for an extremely long time (like on 2A) which is unusual - I mean: what do we know about what that long-term activation means for the downstream effects? - and not something you want to do every day at full dosage, or mitigate casually. I am not an expert on physiology but if fibrosis is about the chronic development of tissue, it seems that you do not chronically want a significantly acting agonist nor antagonist influencing it.

 

[Cotcha Yankinov]

^I'm curious about the difference between taking a blotter once a week for 10 weeks vs. once a day for 10 days.

It could be that once 5-HT2B activates fibroblasts they start producing fibrosis slowly at first, and they then become more efficient at producing fibrosis the longer a specific fibroblast is activated. Essentially there could be a ramping up period...

 

[LSD for ADHD]

5-HT2A receptor populations are high in people with ASD but that is apparently in platelets and not sure about the rest, but it could match the glutamatergic involvement hypotheses.
Again: regarding safety it seems unreasonable to take a lot of LSD all the time when you can take a normal amount every once in a while - it works, what more do you want? I just don't think it's all that effective relatively speaking to keep up a tolerance that is already there.
How would you mitigate 5-HT2B agonism? Antagonism is not all that smart, I think that too can cause such problems in tissue formation.

Idk, it hasn't been tried, but I'm pretty interested in trialling it for some period. I could probably do a month and then report back here with my findings. Anyone willing to fund my experiment or provide me with some cheap 1P supplier? Preferably the higher doses the better for increased metabolites. I have a supplier for 100x100ug for 125 USD of 1P-LSD, pure and trustworthy.

What do you actually base on that LSD could be an anti-psychotic? By taking LSD daily you are still activating what 5-HT2A receptors you have which isn't what you want. Yet on the other hand, you are still producing tolerance so limited 5-HT2A populations will eventually lower your potential for 'sensitizing your DA system' if that is what you are after. The whole point is the in-between time of having tolerance. Not just reaching some new homeostatis with the LSD.
I don't see how any idea of it working for ADHD beyond those benefits from 2A downregulation has any substantiation. Meaning: I don't think the reasoning behind it is sound. No offense of course but it seems more like guesswork than cutting edge science to me.

Not really. Cutting edge, because AFAIK nobody has tried this yet or has the balls to take LSD in high doses every day, or at least every other day depending on the pharmacokinetics of the metabolites. Here is a paper you might find interesting.

The activation of 5-HT2A receptors in prefrontal cortex enhances dopaminergic activity.

My rationale is that persistent D2 partial agonism by LSD is theoretically the same or similar as the persistent D2 partial agonism of the newer AAP's like Abilify, Brexpiprazole, Vraylar.

What's more, that wouldn't be in proportion to the health / safety issues involved in this plan.

I don't think there are many cases of fibrosis due to LSD use. Not least documented ones. Again, I'm really not into the fear mongering about ergolines and fibrosis, not at the doses and half life of LSD (a couple hours), whereas the receptor docking on the important targets in the CNS is much longer and important than in platelets.

I expect Nichols to be very reserved about what we actually know about this, what conjecture is reasonable, and about the safety of taking a drug like this daily.

I think he has a lot of faith in the safety of LSD in contrast to NBOMe's and other partial agonists. The literature on LSD is extensive, and there's still a lot of research out there from the military that hasn't been released; but, also hasn't provided evidence that LSD is as toxic or dangerous as people may think.

Partial agonist does not mean low efficacy - just lower than the endogenous ligand - serotonin - itself, which is setting the bar high. IIRC it is fairly effective on 2B and perhaps more importantly: it snags onto the receptor and binds for an extremely long time (like on 2A) which is unusual - I mean: what do we know about what that long-term activation means for the downstream effects? - and not something you want to do every day at full dosage, or mitigate casually. I am not an expert on physiology but if fibrosis is about the chronic development of tissue, it seems that you do not chronically want a significantly acting agonist nor antagonist influencing it.

There's also higher partial agonism on 5-HTA1, which is probably even more imporatnt and beneficial for a multitude of disorders. There's a complex interaction between 5-HT2A and 5-HTA1 receptors that cause reciprocation of the effects. Downstream effects of 5-HT2A activation affects the following receptors: https://en.wikipedia.org/wiki/5-HT2A_receptor#Distribution

Furthermore, I don't see what's wrong with killing 2 birds with one stone here. 5-HT2A agonism or partial agonism is known to reduce rather significantly depression and anxiety, which are comorbid with ADHD.