Science paper Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

[ermit]

It contains very interesting table figures giving the binding of Psilocin, DMT and LSD to 5-HT and other monoamine receptors

Link:

Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) ...

www.ncbi.nlm.nih.gov

Abstract:
Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce remarkably similar subjective effects in humans, and induce cross-tolerance. The phenylalkylamine hallucinogens are selective 5-HT2 receptor agonists, whereas the indoleamines are relatively non-selective for serotonin (5-HT) receptors. There is extensive evidence, from both animal and human studies, that the characteristic effects of hallucinogens are mediated by interactions with the 5-HT2A receptor. Nevertheless, there is also evidence that interactions with other receptor sites contribute to the psychopharmacological and behavioral effects of the indoleamine hallucinogens. This article reviews the evidence demonstrating that the effects of indoleamine hallucinogens in a variety of animal behavioral paradigms are mediated by both 5-HT2 and non-5-HT2 receptors.

PDF:

 

[ermit]

The LOWER the Ki for a particular drug at a particular receptor, the STRONGER its binding affinity for that receptor.

DMT:

Binding of DMT to 5-HT receptors

Binding site​	Ki (nM)​
​
5-HT1A​	183​
5-HT1B​	129​
5-HT1D​	39​
5-HT1e​	517​
5-HT2A​	127​
5-HT2B​	184​
5-HT2C​	360​
5-HT5a​	2135​
5-HT6​	464​
5-HT7a​	206​

Data from: Keiser et al., 2009

Source:

Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) ...

www.ncbi.nlm.nih.gov

Psilocin:

Binding of psilocin to 5-HT and other monoamine receptors

Binding site​	Ki (nM)​
​
SERT​	3801​
5-HT1A​	567.4​
5-HT1B​	219.6​
5-HT1D​	36.4​
5-HT2A​	107.2​
5-HT2B​	4.6​
5-HT2C​	97.3​
5-HT3​	> 10,000​
5-HT5​	83.7​
5-HT6​	57.0​
5-HT7​	3.5​
α1A​	> 10,000​
α1B​	> 10,000​
α2A​	1379​
α2B​	1894​
α2C​	> 10,000​
β1​	> 10,000​
D1​	> 10,000​
D2​	> 10,000​
D3​	2645​
D4​	> 10,000​
D5​	> 10,000​
H1​	304.6​

Data from the NIMH Psychoactive Drug Screening Program (PDSP).

Source:

Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) ...

www.ncbi.nlm.nih.gov

LSD:

Binding of (+)-LSD to 5-HT and other monoamine receptors

Binding site​	Ki (nM)​
​
5-HT1A​	1.1​
5-HT1B​	3.9​
5-HT1e​	93.0​
5-HT2A​	3.5​
5-HT2B​	30.0​
5-HT2C​	5.5​
5-HT5a​	9.0​
5-HT6​	6.9​
5-HT7​	6.6​
α2​	37​
β1​	140​
β2​	740​
D1​	180​
D2​	120​
D3​	27​
D4​	56​
D5​	340​
H1​	1540​

Data from: Nichols et al., 2002 and Marona-Lewicka and Nichols, 1995 (α2)

Source:

Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) ...

www.ncbi.nlm.nih.gov

 

[Kobranek]

That's why I love combining LSD, Psilocybin, and DMT! Hit all the receptors.

100 mcg LSD + 45 mg psilocybin + at the 0300 hour vape 25-30 mg DMT = WWWOOOOWWWWW smoalk more dmt!

 

[Nydex]

That's why I love combining LSD, Psilocybin, and DMT! Hit all the receptors.

100 mcg LSD + 45 mg psilocybin + at the 0300 hour vape 25-30 mg DMT = WWWOOOOWWWWW smoalk more dmt!

Now that sounds like a proper good time if I've ever heard one! Gotta try it sometime, but I first have to extract myself some psilocybin because I'm not the biggest fan of eating fruiting bodies in combination with LSD which already has a certain amount of body load for me and it doesn't feel nice for me to have anything in my stomach when peaking on it.

 

[Transform]

Now that sounds like a proper good time if I've ever heard one! Gotta try it sometime, but I first have to extract myself some psilocybin because I'm not the biggest fan of eating fruiting bodies in combination with LSD which already has a certain amount of body load for me and it doesn't feel nice for me to have anything in my stomach when peaking on it.

This is what mushroom tea was invented for
Seriously, I love the combo of psilocin + LSD - one of these days I'll get to put the cherry on top and get it together enough for a dose of DMT when they've kicked in.

 

[Nydex]

This is what mushroom tea was invented for
Seriously, I love the combo of psilocin + LSD - one of these days I'll get to put the cherry on top and get it together enough for a dose of DMT when they've kicked in.

Indeed! I haven't tried mushroom tea, only fruit juice with blended up fruiting bodies. Does a tea extraction remove all the bits that cause most of the nausea and unpleasantness in the gut? Because that's my one and only gripe with mushrooms, otherwise the experience is phenomenally natural and beyond beautiful.

 

[Transform]

Indeed! I haven't tried mushroom tea, only fruit juice with blended up fruiting bodies. Does a tea extraction remove all the bits that cause most of the nausea and unpleasantness in the gut? Because that's my one and only gripe with mushrooms, otherwise the experience is phenomenally natural and beyond beautiful.

I may just be fortunate (although I've always had a 'sensitive stomach') - or it may be because I've often had liberty caps - but mushrooms never troubled my stomach. More often than not we'd brew mushrooms, but then eat the (twice) cooked fruiting bodies just to be sure.

Liberty caps are far daintier than most other species, so maybe this helps with digestibility. They're also highly amenable to rapid brewing. I'm pretty sure I've always cooked/brewed any cubensis I've had, dried or not, and Psilocybe cyanescens makes for a particularly fine miso soup.

Were the mushrooms you've had fresh, or were they dried? And what species were they? Both of these factors may impact how your guts respond, as potentially will your diet.

 

[Nydex]

Were the mushrooms you've had fresh, or were they dried? And what species were they? Both of these factors may impact how your guts respond, as potentially will your diet.

Dried Golden Teachers. Perhaps I just need to find a strain that's mellower in terms of body load, like Panaeolus sp.

 

[Transform]

There must be some kind of mycological resources for your part of the world - whether they mention local active species is another question entirely.

I get the impression that cubes rank low on the digestibility scale, so if you could find something native to your region there's a fair chance it might be gentler on your guts.

And we've veered somewhat off-topic. Must be your gastrointestinal serotonin receptor profile, what was I thinking?

 

[Nydex]

Oh, there are active species native to my area, for sure. I know for two of them - liberty caps and p. cyanescens (oh how I wish I found some of those!!!) - but I'm a bit on the fence in terms of wild foraging for obvious reasons. But yes, let's not steer too far away from this thread's point.

 

[doubledog]

Indeed! I haven't tried mushroom tea, only fruit juice with blended up fruiting bodies. Does a tea extraction remove all the bits that cause most of the nausea and unpleasantness in the gut? Because that's my one and only gripe with mushrooms, otherwise the experience is phenomenally natural and beyond beautiful.

Mushroom tea is much better in terms of digestion or stomach issues, but some unpleasantness is still there, as it is most likely caused by psilocin itself. As always, I would strongly recommend predosing any mushroom tea with harmala alkaloids, preferably extracted from caapi.

 

[Kobranek]

I may be lucky too with the nausea but lemon tek is where it's at for me and my golden teachers.

Love the cherry on top analogy Transform!

Recommend starting low when combining lsd and psilocybin. Maybe start with 50 mcg lsd + 1 gram mushrooms then 15-20 mg dmt. The timing is important when peaking or at the tail end of the trip. I feel that after the dmt the trip can seem like it subsides faster especially if timed at the tail end of the trip than usual since the intensity of the dmt can make lsd and psilocybin seem pale in comparison as crazy as it sounds.