Honokiol

[dopamimetic]

2-(4-hydroxy-3-prop-2-enyl-phenyl)- 4-prop-2-enyl-phenol (Wikipedia)

Cytotoxicity inhibition
One way that honokiol acts as a neuroprotective is through cellular regulation and subsequent inhibition of cytotoxicity. Two mechanisms used to achieve this inhibition are GABAA Modulation and Ca2+ Inhibition. Cytotoxicity inhibition may be the neuroprotective mechanism of honokiol. Honokiol has also been shown to inhibit repetitive firing by blocking glutamate.[23]

GABAA modulation
GABAA receptor binding sites
It is believed that honokiol acts on GABAA receptors similarly to benzodiazepines and Z-drugs. However, honokiol has been shown to achieve anxiolysis with fewer motor or cognitive side effects than GABAA receptor agonists such as flurazepam and diazepam. It has been shown that honokiol likely has a higher selectivity for different GABAA receptor subtypes and both magnolol and honokiol showed higher efficacy when acting on receptors containing δ subunits.[1] GABAA receptors control ligand-gated Cl− channels that can help increase seizure thresholds through the influx of chloride anions. Honokiol may also affect the synthesis of GABA. In a study where mice received seven daily injections of honokiol, researchers observed a significant increase in hippocampal levels of glutamate decarboxylase (GAD)(67) a precursor to GABA.[24]

Ca2+ inhibition
A high concentration of Ca2+ induces excitotoxicity which is believed to be the main mechanism behind movement disorders such as ALS, Parkinson's disease, and convulsive disorders like epilepsy. Honokiol disrupts the interfaces post synaptic density protein (PSD95) and neuronal nitric oxide synthase (nNOS).[1] PSD95 and nNOS coupling to the NMDA receptor causes a conformational change responsible for the intracellular influx of Ca2+ which could in turn be a pathway for neurotoxicity. Calcium overloading can also cause damage by over-activation of calcium-stimulated enzymes. Honokiol can reduce calcium influx through inhibition of the fMLP, AlF4−, and thapsigargin G-protein pathways.[20]

Interesting, potentially useful?

 

[Anonymous Dissident]

This was easily available in the not too distant past. I never got a lot of benefit from it, but I have a significant tolerance to GABA drugs. I got samples of this and hordenine with a botanical order years ago, but neither was anything special. I can't remember the doses off hand, but I'll try to find my notes on it. Theres a lot of info on this in the old E-Dot forums.

Edit: I remember there being quite a bit of debate about its neurotoxicity at high doses, but I don't know if that was ever empirically proven.

 

[dopamimetic]

Do you remember if and what mechanisms for toxicity had been speculated about?

Does an archive of this e-dot forum exist? Google found me nothing in a quick try.

Based on the pharmacology it rather looks like it'd protect against excitotoxicity / seizures by increasing GABA and limiting NMDA activity by modulating Ca2+ influx but always it's the dose making the poison I guess.. At least then it must show some efficacy which isn't always sure with plant based compounds.

The activity very distantly remembers me of riluzole, which is used in ALS and showed solid benefits with some mental problems but nobody has ever tried it because its stratospheric price..

 

[Anonymous Dissident]

I don't have time to dig through all of it tonight, but the E-dot forums have moved to entheogen-network.com

A quick search of honokiol brings up 150+ results. I'll try to find the debates about toxicity tomorrow, they were on a much more advanced forum thats now defunct iirc.

Hope this helps!

 

[Anonymous Dissident]

I'm having difficulty locating the info debating the toxicity of honokiol, with the exception of a brief reference on the Wiki page, but I still have a few sources to check. I'll find it if it's still out there...


Edit: I contacted an old associate to find out if an archive of the closed forum I'm referring to is available anywhere. Fingers crossed.

 

[polymath]

I think there must exist some plant terpene or other natural compound that has a concrete benzodiazepine-like effect (kavalactones seem to be closest to that at present), but honokiol/magnolol seem to be quite ineffective in practice.

 

[Anonymous Dissident]

I think there must exist some plant terpene or other natural compound that has a concrete benzodiazepine-like effect (kavalactones seem to be closest to that at present), but honokiol/magnolol seem to be quite ineffective in practice.

I can't remember the active chemicals contained in erythrina mulungu, but a tea of the bark is the closest thing I have experienced to an "ethnobotanical benzodiazepine", far more effective than kavalactones. Tread carefully though, coral tree species can be really, really toxic...

Edit: (+)-11α-hydroxyerythravine and (+)erythravine are the active constituents iirc...

 

[allone]

the two VITAL things when it comes to those plant polyphenols (even lignans as this is termed); solubility solvents and bioavaibility percent in humans. im not sure whats best solvent for honokiol but i assume like 90% of what i read, probably few including ethanol, BUT NOT WATER! Basically, its already fucked up right here. The whole GABA influence, well, its soluble in methanol and ethanol and other alcohols, hmmm.... I wonder why would it have GABA effect....
ANYWAY, now, a third problem arises. Origin. It could come from anywhere at any time at any point without any control or tests. FDA doesnt give 2 fucks about testing supplements if they lie or not. they wait until people die and then they are like, HEY WE GOT A PROBLEM! but indepenent companies already do testings and guess what? MOST, maybe at least 75% of herbal supplements do not contain actual ingredients and are adulterated. Seriously, if you can adulterate typical foods, oils which people buy and consume on regular basis without any control, how difficult can it be to do that with herbs which FDA doesnt even understand what they are!
So, to sum this up. I think we are about LIGHT YEARS away from realizing if honokiol has any potential or not. Maybe we will touch MARS first.

 

[polymath]

I can't remember the active chemicals contained in erythrina mulungu, but a tea of the bark is the closest thing I have experienced to an "ethnobotanical benzodiazepine", far more effective than kavalactones. Tread carefully though, coral tree species can be really, really toxic...

Edit: (+)-11α-hydroxyerythravine and (+)erythravine are the active constituents iirc...

Thanks for mentioning this. Based on the Erowid reports, it looks like that is an effective sedative (enough to be dangerous to drive a car on).

 

[polymath]

I possibly shouldn't lift up this old thread, but I ordered some erythrina mulungu by mail on sunday and got it yesterday. It was in two plastic bags that had finely powdered sawdust on the bottom and less finely ground shreds of wood bark on top. When I kept some 5-10 grams in boiling water and drank the water extract after filtering, the effect was much like it's supposed to be according to this Erowid report:

Erythrina mulungu - Erowid Exp - 'Mellow Experience in Large Amounts'

An Experience with Erythrina mulungu. 'Mellow Experience in Large Amounts' by Brainiac

erowid.org

Bought a few cans of beer later yesterday, and after the coral tree tea even 4 beers felt more like 8. I don't have a very good recollection of going to sleep last night. When waking up with a bit of a hangover, the leftover mulungu water extract got me back to sleep really quickly.

The effect from the mulungu extract alone was much like what David Nutt's purported alcohol substitute is supposed to do, removing nervousness without excessive loss of control. The rosemary and lavender essential oils I mentioned months ago didn't have this much effect, especially after having used them a few times (they do, however, potentiate opiates a bit even after that).

Edit: the same amount doesn't make me feel intoxicated today, so there's same kind of acute tolerance as with benzodiazepines.

 

[emkee_reinvented]

I can't remember the active chemicals contained in erythrina mulungu, but a tea of the bark is the closest thing I have experienced to an "ethnobotanical benzodiazepine", far more effective than kavalactones. Tread carefully though, coral tree species can be really, really toxic...

Edit: (+)-11α-hydroxyerythravine and (+)erythravine are the active constituents iirc...

Long time ago I aquired Mulungu and its extract.

Without any verification assuming this was Mulungu. My experience was that it did what benzo's try to do.

Benzodiazepinen carry alot of side effects, that make them even sort of recreational. Mulungu seemed way more straight forward. At least as effective as a Benzo but no artificial sedation was noted.

 

[allone]

where do you guys get your mulungu from? god knows, i need something like this right now

 

[Anonymous Dissident]

where do you guys get your mulungu from? god knows, i need something like this right now

I obviously can't go into the specifics, but many reputable ethnobotanical vendors carry both the raw plant material and extracts.

 

[allone]

well, do you think the whole raw material is better? since extractions arent even sure what to look for

 

[polymath]

well, do you think the whole raw material is better? since extractions arent even sure what to look for

Keep it in a large amount of boiling water for a few minutes and drink the resulting "tea".

The first risk that came to my mind about erythravine was that being a nicotine receptor ligand it could act as a non-depolarizing muscle relaxant. That would also cause a feeling of clumsiness like benzos, and a large amount would cause paralysis of the respiration muscles and make you suffocate when fully conscious. It doesn't seem to be like that, though.