Lisuride - Liquid Lisuride For Lab/R&D

[DaveFoster]

I tried to post this but forum has made it really ******* hard, it's frustrating. @haidut have you considered posting to multiple forums, or do you have a deal with charlie or some ***t? I don't hate him or anything but I am so sick of the internet. I'm out of energy for this ***t.

Anyway, I seriously believe lisuride could have major value as a regulator of circadian rhythms. 5-ht2c agonists apparently can emulate light signals: Serotonin 5-HT2c agonists mimic the effect of light pulses on circadian rhythms. - PubMed - NCBI And I've noticed personally that (although I did not enjoy lisuride's acute effects) lisuride seemed to improve ability to wake up at the right time. This has given it more value over time than metergoline, and I think that taking metergoline (or SSRIs) without lisuride to balance it out could be an error.

Agomelatine is a potential candidate for this argument: although the melatonin receptor agonism is obviously a strongly confounding factor, the 5-HT2c antagonism (as it's taken before bedtime) also suggests something for lisuride's usefulness. Agomelatine: A Novel Antidepressant

I would posit lisuride's ability to stimulate 5-HT2c while simultaneously making up for in dopamine agonism through other receptors, might make it a great candidate for fixing circadian rhythm issues.

If you took lisuride in the morning, and then took a combination of either agomelatine or GHB or baclofen (GHB is more physiologicially more appropriate than baclofen) and 5-alpha-DHP in the evening for the allopregnanolone, and at least 1-2 grams of glycine, could have potential solve anyone's circadian issues. To be clear the nighttime drug may require a combination of GABA-a and GABA-b drugs to be truly effective, as hinted by (this is about sleep paralysis in muscles during REM, however I think the interpretation is likely to extend to the other sleep mechanisms): Identification of the Transmitter and Receptor Mechanisms Responsible for REM Sleep Paralysis

(Although agomelatine has a rather good profile with non-5-HT2b-agonism, it can still give elevated liver enzymes)

I think lisuride could be an interesting pharmalogical alternative to agomelatine if used in the morning,.

The 5-HT7 receptor also has implications in circadian rhythms (and depression.)

@haidut

Do you know the approximate half-life of lisuride with SFA esters as a solvent? I'm calculating an equivalent 0.1 mg oral dosage with the different steady-state pharmacokinetics taken into account.

Also, do you think lisuride could cause serotonin syndrome in combination with other serotonergic antidepressants?

"...LSD and the novel ergot derivative lisuirde produced this syndrome in rats. These drugs possess both serotonergic and dopaminergic properties. Since changes in dopaminergic function have also been reported to affect the so-called serotonin syndrome, it was not clear how the two ergot drugs acted to produce this syndrome. The syndrome produced by pargyline and 5-hydroxytryptophan methyl ester was blocked by haloperidol, methysergide, parachlorophenylalanine, and alpha-methylparatyrosine; these treatments failed to block the effects of lisuride. Metoclopramide did not block the syndrome produced by either lisuride or pargyline plus 5-hydroxytryptophan methyl ester. Methysergide partially blocked the behavioral effects of LSD; pretreatment with either haloperidol or metoclopramide potentiated and prolonged the behavioral effects of LSD. The results suggest that dopaminergic modulation of the serotonin syndrome occurs before the serotonin receptor involved in this behavior. Also, the differences between LSD and lisuride may be relevant to their different psychopharmacological properties."

Reference: Lisuride and LSD: Dopaminergic and serotonergic interactions in the “serotonin syndrome”​

 

[haidut]

The 5-HT7 receptor also has implications in circadian rhythms (and depression.)

@haidut

Do you know the approximate half-life of lisuride with SFA esters as a solvent? I'm calculating an equivalent 0.1 mg oral dosage with the different steady-state pharmacokinetics taken into account.

Also, do you think lisuride could cause serotonin syndrome in combination with other serotonergic antidepressants?

"...LSD and the novel ergot derivative lisuirde produced this syndrome in rats. These drugs possess both serotonergic and dopaminergic properties. Since changes in dopaminergic function have also been reported to affect the so-called serotonin syndrome, it was not clear how the two ergot drugs acted to produce this syndrome. The syndrome produced by pargyline and 5-hydroxytryptophan methyl ester was blocked by haloperidol, methysergide, parachlorophenylalanine, and alpha-methylparatyrosine; these treatments failed to block the effects of lisuride. Metoclopramide did not block the syndrome produced by either lisuride or pargyline plus 5-hydroxytryptophan methyl ester. Methysergide partially blocked the behavioral effects of LSD; pretreatment with either haloperidol or metoclopramide potentiated and prolonged the behavioral effects of LSD. The results suggest that dopaminergic modulation of the serotonin syndrome occurs before the serotonin receptor involved in this behavior. Also, the differences between LSD and lisuride may be relevant to their different psychopharmacological properties."

Reference: Lisuride and LSD: Dopaminergic and serotonergic interactions in the “serotonin syndrome”​

I think the trial with transdermal patch for lisuride showed half life of about 6 hours. The oral half life may be short but the effects are long lived as people have shared, which suggests that lisuride's metabolism in tissues is slow so one should not rely only on the half life to gauge the dose.
The issue with serotonin syndrome was discussed earlier in this thread. All ergot derivatives, with the notable exception of metergoline and methysergide, can cause serotonin syndrome when combined with serotonergic chemicals like SSRI or MOA-A inhbitors. The lisuride doses in that study are high - i.e. the dose on which the researches settled as being able to produce serotonin syndrome was equivalent to 0.08mg/kg for a human, so between 5mg and 8mg for an adult human. Clinically used doses of lisuride are in the 100mcg - 200mcg range.

 

[Wagner83]

I think the trial with transdermal patch for lisuride showed half life of about 6 hours. The oral half life may be short but the effects are long lived as people have shared, which suggests that lisuride's metabolism in tissues is slow so one should not rely only on the half life to gauge the dose.
The issue with serotonin syndrome was discussed earlier in this thread. All ergot derivatives, with the notable exception of metergoline and methysergide, can cause serotonin syndrome when combined with serotonergic chemicals like SSRI or MOA-A inhbitors. The lisuride doses in that study are high - i.e. the dose on which the researches settled as being able to produce serotonin syndrome was equivalent to 0.08mg/kg for a human, so between 5mg and 8mg for an adult human. Clinically used doses of lisuride are in the 100mcg - 200mcg range.

Wouldn't be simply that since it shifts the organism in a particular direction the downstream effects of its use may be more longer lasting?

 

[haidut]

Wouldn't be simply that since it shifts the organism in a particular direction the downstream effects of its use may be more longer lasting?

Yes, that too.

 

[DaveFoster]

I think the trial with transdermal patch for lisuride showed half life of about 6 hours. The oral half life may be short but the effects are long lived as people have shared, which suggests that lisuride's metabolism in tissues is slow so one should not rely only on the half life to gauge the dose.
The issue with serotonin syndrome was discussed earlier in this thread. All ergot derivatives, with the notable exception of metergoline and methysergide, can cause serotonin syndrome when combined with serotonergic chemicals like SSRI or MOA-A inhbitors. The lisuride doses in that study are high - i.e. the dose on which the researches settled as being able to produce serotonin syndrome was equivalent to 0.08mg/kg for a human, so between 5mg and 8mg for an adult human. Clinically used doses of lisuride are in the 100mcg - 200mcg range.

Thank you. Mirtazapine has isolated instances (usually in the elderly) for causing serotonin syndrome, and many reports online detail people's combination of mirtazapine with LSD, although LSD has different effects from those of lisuride.

 

[Terma]

What happened and why would people prevent you form posting positive reviews?

What about timing your meals, macronutrients, blocking blue light, reading instead of using computers in the evening, going to bed and waking up at the same time everyday?

I made a thread about it... Nevermind, the entire internet has been painful lately, people overcomplicate it and it drives me up the wall.

I'm way past life adjustments, all that plus Redshift on 4 machines, etc. Too many health problems, some undiagnosed. Most likely part immune and you not only can need strong substances to offset that but I'm convinced you need several in combination or you're wasting your time. I had significant improvements using 5-a-DHP and a combination of progesterone and opioids (opioids increase 5-AR and fifty other things), but sleep quality over quantity is a major issue lacking and there are a couple pathways none of these things address.

The 5-HT7 receptor also has implications in circadian rhythms (and depression.)

That's correct, someone else just brought that up, that was pretty psychic. Was interested in that one for awhile but didn't get far in terms of therapy. I guess it's another reason to avoid megadosing metergoline, or rather an argument to use it but in very controlled doses in the morning combined with enough lisuride (that's making stupid assumptions about their interactions, but they did feel decent together). The other antagonist is amisulpride but it wasn't clear if the low doses (which don't have the dopamine antagonism) have any effect through 5-HT7. These tend to have long half-lives which is a problem and where others like lisuride or baclofen have appeal. (Then there is oleamide as agonist or somewhat but I'll let someone else talk about that)

 

[DaveFoster]

Blossom has reported no withdrawal symptoms even from taking lisuride for several months consecutively.

 

[KyleKingsly]

Blossom has reported no withdrawal symptoms even from taking lisuride for several months consecutively.

Dave I've been meaning to talk to you about dopamine agonists (and metergoline) for a while, since I noticed that you seem to have a keen interest in them as I do. I saw Blossom's report and agree that anecdotally that seems promising, however, one report does not make this safe enough to use in my opinion. DAWS can "only" affect ~19% of dopamine agonist users (as seen in this review article Dopamine agonist withdrawal syndrome: A comprehensive review - ScienceDirect), and you have to keep in mind that for some users these changes are permanent. Dopamine agonists are incredibly powerful drugs that are generally reserved for people with very serious issues (Parkinson's) that have few better choices. They can induce epigenetic changes (that is, DNA changes) that will permanently change how you react to dopamine and cause long lasting or permanent fatigue, anxiety, lack of motivation, etc.

I've done my share of research chemicals and under-researched substances but I try to do my homework and be incredibly careful before I put anything in my body. As I see things right now, dopamine agonists are just to be dangerous to be using casually for purposes of motivation, confidence building, energy, etc. Trust me, I'm not happy about that because I was thinking that lisuride and ropinirole were magic bullet drugs that were going to fix all my problems, and they very well might temporarily, but not potentially not without making things far worse in the long run.

I do support @haidut selling this and will be interested to how he responds to this post, but I think that for most people this stuff is just too risky to be experimenting with. The fact that lisuride doesn't seem to induce withdrawal symptoms as much as other dopamine agonists and that there aren't really bad cases reported could very well be due to fact that this stuff hasn't really been sold on the market much, and so there are just fewer people testing it overall.

Instead of playing with fire, I recommend that people try mucuna pruriens (no more than a few times a week). It has its own risks, but seems far safer overall while still giving a nice dopaminergic boost. Y'all can also look into bromantane.

 

[DaveFoster]

Dave I've been meaning to talk to you about dopamine agonists (and metergoline) for a while, since I noticed that you seem to have a keen interest in them as I do. I saw Blossom's report and agree that anecdotally that seems promising, however, one report does not make this safe enough to use in my opinion. DAWS can "only" affect ~19% of dopamine agonist users (as seen in this review article Dopamine agonist withdrawal syndrome: A comprehensive review - ScienceDirect), and you have to keep in mind that for some users these changes are permanent. Dopamine agonists are incredibly powerful drugs that are generally reserved for people with very serious issues (Parkinson's) that have few better choices. They can induce epigenetic changes (that is, DNA changes) that will permanently change how you react to dopamine and cause long lasting or permanent fatigue, anxiety, lack of motivation, etc.

I've done my share of research chemicals and under-researched substances but I try to do my homework and be incredibly careful before I put anything in my body. As I see things right now, dopamine agonists are just to be dangerous to be using casually for purposes of motivation, confidence building, energy, etc. Trust me, I'm not happy about that because I was thinking that lisuride and ropinirole were magic bullet drugs that were going to fix all my problems, and they very well might temporarily, but not potentially not without making things far worse in the long run.

I do support @haidut selling this and will be interested to how he responds to this post, but I think that for most people this stuff is just too risky to be experimenting with. The fact that lisuride doesn't seem to induce withdrawal symptoms as much as other dopamine agonists and that there aren't really bad cases reported could very well be due to fact that this stuff hasn't really been sold on the market much, and so there are just fewer people testing it overall.

Instead of playing with fire, I recommend that people try mucuna pruriens (no more than a few times a week). It has its own risks, but seems far safer overall while still giving a nice dopaminergic boost. Y'all can also look into bromantane.

Thank you. I'm not combining it with mirtazapine regardless.

 

[ilikecats]

lol mucuna pruriens is not safe. Thats levodopa its neurotoxic. Just because its from a natural source doesn't mean its safer.

 

[KyleKingsly]

lol mucuna pruriens is not safe. Thats levodopa its neurotoxic. Just because its from a natural source doesn't mean its safer.

Trust me, I'd be the last to believe that natural inherently means safer; I really hate advocates of the frickin' appeal to nature fallacy and the "natural or nothing" people. I love my synthetic products too. However, the fact remains that many plants have synergistic collections of alkaloids that are safer than extracts/synthetic reproductions of isolated chemicals. Coffee, for example, has plenty of healthy antioxidants that are not found in caffeine itself, and so it's generally healthier to drink coffee over pure caffeine (not to say that caffeine is really unsafe.)

The same is true of Mucuna Pruriens - with powders from the whole plant or extracts of 5% L-Dopa or less, it seems to be relatively safe. The plant contains natural antioxidants that will mitigate the oxidative stress (the precursor to neurotoxicity) that pure L-dopa causes. Now I'm not claiming to be 100% sure that Mucuna Pruriens is completely safe, but there is always some risk with these less well known supplements and it does have a long history of human usage. Most of the danger of neurotoxicity comes from using high doses of isolated L-Dopa, as I understand things.

You can learn more here from this comprehensive study (notice how it describes L-Dopa as pro-oxidant and stress-inducing while Mucuna Pruriens itself is described as neuroprotective): The Magic Velvet Bean of Mucuna pruriens

 

[haidut]

Dave I've been meaning to talk to you about dopamine agonists (and metergoline) for a while, since I noticed that you seem to have a keen interest in them as I do. I saw Blossom's report and agree that anecdotally that seems promising, however, one report does not make this safe enough to use in my opinion. DAWS can "only" affect ~19% of dopamine agonist users (as seen in this review article Dopamine agonist withdrawal syndrome: A comprehensive review - ScienceDirect), and you have to keep in mind that for some users these changes are permanent. Dopamine agonists are incredibly powerful drugs that are generally reserved for people with very serious issues (Parkinson's) that have few better choices. They can induce epigenetic changes (that is, DNA changes) that will permanently change how you react to dopamine and cause long lasting or permanent fatigue, anxiety, lack of motivation, etc.

I've done my share of research chemicals and under-researched substances but I try to do my homework and be incredibly careful before I put anything in my body. As I see things right now, dopamine agonists are just to be dangerous to be using casually for purposes of motivation, confidence building, energy, etc. Trust me, I'm not happy about that because I was thinking that lisuride and ropinirole were magic bullet drugs that were going to fix all my problems, and they very well might temporarily, but not potentially not without making things far worse in the long run.

I do support @haidut selling this and will be interested to how he responds to this post, but I think that for most people this stuff is just too risky to be experimenting with. The fact that lisuride doesn't seem to induce withdrawal symptoms as much as other dopamine agonists and that there aren't really bad cases reported could very well be due to fact that this stuff hasn't really been sold on the market much, and so there are just fewer people testing it overall.

Instead of playing with fire, I recommend that people try mucuna pruriens (no more than a few times a week). It has its own risks, but seems far safer overall while still giving a nice dopaminergic boost. Y'all can also look into bromantane.

I am not aware of anybody using bromocriptine, cabergoline or lisuride that has experienced DAWS and I know of quite a few people who use these (mostly bodybuilders or other athletes that have high prolactin due to overexertion). Of course, that does not mean it is not an issue to be keep in mind and I may actually pull lisuride (and leave it as a custom order item only) at some point considering that metergoline seems to be a safer way to increase dopamine through pure serotonin antagonism.

 

[ilikecats]

@haidut lisuride>Metergoline any day of the week, twice on sundays. Also, let’s not forget that lisuride is Ray Peat approved while metergoline is not.

 

[Blossom]

Just ordered! I haven't used lisuride in years so I'm excited to see how my rat does on IdeaLabs lisuride.

 

[goodandevil]

@haidut lisuride>Metergoline any day of the week, twice on sundays. Also, let’s not forget that lisuride is Ray Peat approved while metergoline is not.

Ray said he's never tried metergoline, but he said it had a good reputation, but i for one would prefer that lisuride remain available.

 

[ilikecats]

@goodandevil oh gotcha. I was actually wrong btw, the source for my statement (metergoline being not "peat approved") was actually him talking about another drug and I just remembered it wrong. "I haven’t had any experience with ritanserin, don’t recommend it, and don’t recall discussing it." That's what I was thinking of. My bad

 

[goodandevil]

@goodandevil oh gotcha. I was actually wrong btw, the source for my statement (metergoline being not "peat approved") was actually him talking about another drug and I just remembered it wrong. "I haven’t had any experience with ritanserin, don’t recommend it, and don’t recall discussing it." That's what I was thinking of. My bad

Yeah he doesnt seem to like ritanserin. I think as many dopaminergics or anti-serotonin drugs as possible. Lisuride is extremely diffuclt to locate.

 

[ilikecats]

.

 

[Regina]

Ray said he's never tried metergoline, but he said it had a good reputation, but i for one would prefer that lisuride remain available.

+1. I prefer lisuride too!

 

[haidut]

@haidut lisuride>Metergoline any day of the week, twice on sundays. Also, let’s not forget that lisuride is Ray Peat approved while metergoline is not.

Noted, I meant I will just keep it off the website and only sell as a custom item.