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Ferulic acid, a natural NMDA antagonist and serotonergic antidepressant

ferulic acid nmda ht1a ht2a ht2c

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#1 sativa

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Posted 06 May 2016 - 09:38 PM


Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) is a chemical component that makes up the cell walls in plants.
 

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Two different isomeric forms of ferulic acid found in nature (a) cis conformation and (b) trans conformation of ferulic acid.

 

 

I have acquired 5g of pure ferulic acid to test its psychoactive activity. It's bioavailability seems to be sufficiently high and appears to be "safe for human consumption".

 

According to wikipedia, "The highest known concentration of ferulic acid glucoside has been found in flax seed (4.1 +/- 0.2 g/kg)."
 
One ferulic acid supplement contains 250mg per capsule (as Trans-Ferulic acid), with a suggested use (for dietary enhancement) of 1 to 2 tablets daily with meals. One capsule would thus be equivalent to 60g of flax seed - bear in mind that the ferulic acid will be "bound up" in a "cell matrix" (and so potentially reducing it's bioavailability) as opposed to free form aka pure ferulic acid powder.
 
 

It's pharmacology includes NMDA antagonsism and serotonergic activity - which results in an antidepressant effect likely involving the 5-HT1A and 5-HT2A serotonin receptors.

It also exhibits non steroidal anti-inflammatory activity (5-LOX/COX enzyme inhibition) as well as antioxidant, anti-diabetic and anti-cancer activity.

It has been used in purified form as a supplement for Alzheimer's.

Ferulic acid has been approved as an antioxidant additive and food preservative in Japan (Graf, 1992 and JFCRF, The Japan Food Chemical Research Foundation, 1996)

 

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Absorption & bioavailability info:
 

Ferulic acid is quickly absorbed from rat stomach as the free form and then conjugated mainly in liver.

Ferulic acid (FA) is one of the most abundant phenolic antioxidants in the human diet. Many studies have documented its beneficial properties.
...
These results indicate that FA can be quickly absorbed from the rat stomach, and then is likely metabolized mainly in the liver. Such novel information would be helpful in the use of FA as a nutrient supplement. For example, oral administration of FA in capsule form or in a form bonded with sugar esters may provide a more appropriate concentration of FA in the circulation

Source: www.ncbi.nlm.nih.gov/pubmed/15514279

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Absorption of ferulic acid from low-alcohol beer.

These findings are consistent with the uptake of ferulic acid from dietary sources, such as tomatoes, and suggest that ferulic acid is more bioavailable than individual dietary flavonoids and phenolics so far studied.

Source: www.ncbi.nlm.nih.gov/pubmed/10730826


Sources for general information:
http://www.sciencedi...215017X14000368



NMDA antagonism:



Potent protection of ferulic acid against excitotoxic effects of maternal intragastric administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain.

The present study was conducted to investigate a possible protection of ferulic acid against excitotoxic effects of maternal intragastric (ig) administration of monosodium glutamate (MSG) at a late stage of pregnancy on developing mouse fetal brain.
...
The results suggest that ferulic acid is a novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist and neuroprotector.

Source:
www.ncbi.nlm.nih.gov/pubmed/16257184


Serotonergic activity:
 

Ferulic acid exerts antidepressant-like effect in the tail suspension test in mice: Evidence for the involvement of the serotonergic system

Ferulic acid (4-hydroxy-3-methoxycinnamic acid) is a phenolic compound present in several plants with claimed beneficial effects in prevention and treatment of disorders linked to oxidative stress and inflammation. In this study, we aimed to verify the possible antidepressant-like effect of acute oral administration of ferulic acid in the forced swim test (FST)
...

Taken together, these results demonstrate that ferulic acid exerts antidepressant-like effect in the FST and TST in mice through modulation of the serotonergic system.

Source: http://www.sciencedi...014299912000039


Edited by sativa, 06 May 2016 - 10:16 PM.

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#2 sativa

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Posted 07 May 2016 - 08:01 PM

Underlying pathways involved in antidepressant effects:

Involvement of PKA, CaMKII, PKC, MAPK/ERK and PI3K in the acute antidepressant-like effect of ferulic acid in the tail suspension test

Ferulic acid is a phytochemical compound naturally present in several plants and foods that is approved as an antioxidant additive and food preservative.

It exerts a beneficial action in chronic mild stress-induced depressive-like behavior and produces an acute antidepressant-like effect in the tail suspension test (TST) through the activation of the serotonergic system.

This study was aimed at investigating the possible involvement of signaling pathways in the antidepressant-like effect
...
The results demonstrated that Ferulic acid exerts antidepressant-like effect in the TST in mice, through the activation of signaling pathways related to neuroplasticity, neurogenesis and cell survival.

Source:
www.sciencedirect.com/science/article/pii/S0091305712002419



Non steroidal anti-inflammatory properties:

Nonsteroidal anti-inflammatory drugs such as ferulic acid ... especially inhibit the lipoxygenase and/or the cyclooxygenase pathways and consequently prevent the formation of inflammatory mediators

Source: iovs.arvojournals.org/article.aspx?articleid=2123585



Use of ferulic acid as a supplement:

Effects of ferulic acid and Angelica archangelica extract (Feruguard) in patients with Alzheimer's disease

Feruguard is a health food supplement composed of ferulic acid extracted from rice bran and garden angelica obtained from Angelica archangelica. In recent years, Feruguard has been reported to be effective against the core symptoms and behavioral and psychological symptoms of dementia (BPSD) of Alzheimer disease (AD) and dementia with Lewy bodies (DLB).

Source: www.alzheimersanddementia.com/article/S1552-5260(10)01948-5/abstract



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#3 sativa

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Posted 07 May 2016 - 08:06 PM

From the comments section of http://theness.com/n...eimers-disease/ -

One of the keys to Alzheimer’s disease is the peroxynitrite-mediated tyrosine nitration of NMDA receptors–this is what allows the disease to progress even when other pathways that initially triggered the disease are cut off.

Peroxynitrite interacts with the NMDA receptor leading to nitration of the tyrosine residues present on the NMDA receptor subunits. This nitration is an irreversible reaction that leads to a constant potentiation of synaptic currents, calcium influx, and ultimately excitotoxicity [97;98; 99]. [the reaction may actually be reversible].

I can now make this point with almost absolute certainty, if you scavenge peroxynitrites and in the process inhibit NMDA receptor activation (and subsequent excitotoxicity), you effectively treat Alzheimer’s disease.

Eugenol in rosemary and other essential oils (lemon balm bay laurel, clove, etc.) via aromatherapy.

Eugenol protects neuronal cells from excitotoxic and oxidative injury in primary cortical cultures.

http://www.ncbi.nlm..../pubmed/9147382

In Vitro Activity of the Essential Oil of Cinnamomum zeylanicum and Eugenol in Peroxynitrite-Induced Oxidative Processes

http://pubs.acs.org/...rnalCode=jafcau

Effect of aromatherapy on patients with Alzheimer’s disease
Methods:  After a control period of 28 days, aromatherapy was performed over the following 28 days, with a wash out period of another 28 days. Aromatherapy consisted of the use of rosemary and lemon essential oils in the morning, and lavender and orange in the evening.

Conclusions:  In conclusion, we found aromatherapy an efficacious non-pharmacological therapy for dementia. Aromatherapy may have some potential for improving cognitive function, especially in AD patients.


Eugenol in essential oils and ferulic acid and syringic acid in ginseng inhibit NMDA receptor activation in at least two ways (metal chelation may be a third one): They inhibit tyrosine phosphorylation of NMDA receptors by removing phenolic groups from tyrosine and they reverse tyrosine nitration of NMDA receptors by producing water through the scavenging of peroxynitrites

(ONOO- + 2H+ + 2e-=H20 + NO2- and Protein-Tyr-NO2 + H2O –> Protein-Tyr-H + H+ + NO3-)

Hydrogen donation from phenols also helps to partially reverse oxidation.

Methoxyphenols such as eugenol, ferulic acid, and syringic acid are particularly good antioxidants because the methoxy group increases the hydrogen donating and electron donating capacity of phenol groupls

Nitration and oxidation leads to the death of neurons via NMDA receptors and the subsequent production of peroxynitrites.

Nitration and oxidation also inhibit the regeneration of neurons in the hippocampus, inhibit the synthesis and release of neurotransmitters involved in short-term memory, sleep, mood, social recognition, and alertness, alter tau proteins which inhibits the transport of nutrients and neurotransmissions in the brain, and limit the flow of blood and the transport of glucose in the brain which can lead to apathy, wandering, and delusions.

I cannot help it that some of the best compounds for partially reversing oxidation and nitration come from plants. Produce a better synthetic antioxidant if you can.

Not all of this works perfectly, I understand that. Eugenol is a stimulating oil that increases the release of norepinephrine and high levels of norepinephrine can contribute to anxiety and hallucinations in some people with Alzheimer’s disease. The cognitive benefits derived from eugenol are offset by increased anxiety which may lead to the greater use of benzodiazepines such as Ativan which further lowers cognition. Ginseng can increase blood pressure and anxiousness. On the other hand substances high in ferulic acid can improve neuropsychiatric behavior in people with Alzheimer’s disease, dementia with Lewy Bodies, and frontotemporal lobe dementia.


Edited by sativa, 07 May 2016 - 08:14 PM.


#4 sativa

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Posted 07 May 2016 - 08:26 PM

Eugenol protects neuronal cells from excitotoxic and oxidative injury in primary cortical cultures.

We examined the neuroprotective efficacy of eugenol against N-methyl-D-aspartate (NMDA)-, oxygen-glucose deprivation-, and xanthine/xanthine oxidase-induced neurotoxicity in primary murine cortical cultures.

Eugenol (100-300 microM) attenuated NMDA (300 microM)-induced acute neurotoxicity by 20-60%. At the same concentration range, eugenol also inhibited NMDA (300 microM)-induced elevation in neuronal 45Ca2+ uptake by 10-30%. In the oxygen-glucose deprivation (50 min) neurotoxicity, eugenol (100-300 microM) prevented acute neuronal swelling and reduced neuronal death by 45-60% in a concentration-dependent fashion. Oxidative neuronal injury induced by xanthine/xanthine oxidase was also significantly reduced (75-90%) by eugenol (100- 300 microM) addition.

These results suggest that eugenol may play a protective role against ischemic injury by modulating both NMDA receptor and superoxide radical.

Source: http://www.ncbi.nlm..../pubmed/9147382


Edited by sativa, 07 May 2016 - 08:27 PM.


#5 sativa

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Posted 15 May 2016 - 06:19 PM

Ferulic acid affects cell cycle:

FA has also shown to affect cell cycle, by increasing proliferation of neural stem/progenitor cells in vitro and in vivo. It has also been reported to ameliorate the stress-induced depression-like behavior in mice (Yabe et al., 2010)



#6 sativa

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Posted 15 May 2016 - 07:46 PM

Ferulic acid is potentiated nicely by Rhodiola rosea (1% salidroside, 1% rosavin, 40% polyphenol extract).

I had 250mg Rhodiola at 12pm, and .6g ferulic acid orally at 6pm.

Edited by sativa, 15 May 2016 - 07:52 PM.


#7 ceridwen

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Posted 15 May 2016 - 09:52 PM

Feruguard causes cardio respiratory arrest.
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#8 sativa

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Posted 16 May 2016 - 01:49 PM

Feruguard causes cardio respiratory arrest.


Maybe that's due to the Angelica archangelica component.

Sodium ferulate (SF), the sodium salt of ferulic acid, is a drug used in traditional Chinese medicine for treatment of cardiovascular and cerebrovascular diseases and to prevent thrombosis.


Ferulic acid is present in many foods commonly eaten anyway.
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#9 gamesguru

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Posted 19 May 2016 - 12:11 PM

It just shows another benefit of plant-based diets.


"... it is envisaged that future investigations based on the present data will allow more clinically relevant herbs to be identified."
from, 'Current Evidence of Chinese Herbal Constituents with Effects on NMDA Receptor Blockade'

"The effects of several 5-HT1A agonists and excitatory amino acid antagonists were compared to the standard benzodiazepines, diazepam and chlordiazepoxide (CDP) in two assays predictive of anxiolytic activity, the social interaction and elevated plus maze procedures. Indicative of anxiolytic effects the 5-HT1A agonists, buspirone, gepirone and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) all significantly increased social interaction time and open arm exploration time in the social interaction and elevated plus maze procedures, respectively. Likewise, anxiolytic activity in these assays were also produced by the competitive N-methyl-D-aspartate (NMDA) antagonists, 2-amino-5-phosphonovaleric acid (AP-5), 2-amino-7-phosphonoheptanoic acid (AP-7), 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the non-competitive NMDA antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) while NMDA produced anxiogenic effects. Furthermore, the anxiolytic effects of these agents were of equal magnitude to the benzodiazepines. These two classes of compounds were differentiated in the yohimbine-induced seizure assay, with the NMDA antagonists dose dependently antagonizing seizures similar to the benzodiazepines while the 5-HT1Aagonists were inactive. These results suggest that the 5-HT1A agonists and the NMDA antagonists may be potential non-classical anxiolytic agents with different mechanisms of action."
from, 'Effects of 5-HT1A receptor agonists and NMDA receptor antagonists in the social interaction test and the elevated plus maze'


http://www.longecity...ntidepressants/

#10 thedevinroy

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Posted 20 May 2016 - 03:19 PM

I could have told you that NMDA antagonism was anxiolytic and anticonvulsant ... Although I wouldn't compare it to Valium or anything. That just makes your cells salty... :P

How does it feel to be on the ferugaurd?

Edited by devinthayer, 20 May 2016 - 03:20 PM.


#11 sativa

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Posted 20 May 2016 - 04:32 PM

How does it feel to be on the ferugaurd?


I haven't tried ferugaurd.

I have tried 98% ferulic acid powder at a dose of around .55g three times so far.

Initially standalone, and also combined with other things such as agmatine, kanna, alcohol, CBD hemp buds (only 0.02% THC), rhodiola.

So far, I like its effects. They seem to last at least till the next day. Here is a quote I wrote on another forum about ferulic acids psychoactive effects:

Experience #1 - .6g pure ferulic acid powder

I'm not on any medication. Currently sober (cacao, hemp buds, tobacco, gynostemma extract and black seed oil consumed earlier today)

23:23 - swallowed .6g ferulic acid with water on an empty stomach. Started watching a comedy/action film.

23:50 - mood definitely elevated, laughing out loud frequently, feel slight heaviness and detachment from body.

00.00 - Ongoing feeling of excitement. Definate CEV

00:15 - I feel content. Very easy to overcome craving for ginger biscuits and dark chocolate. Body "high" is definitely present, there is a sensation of "inner movement" - similar to that from ketamine.

00:30 - positive feeling of impending ongoing "glee"...

00:37 - take .95g agmatine sublingually (NMDA & alpha 7 nicotinic receptor antagonist, potentiation of CB1 and activity at 5-HT2A receptors). Body high sensations a lot stronger now.

01:25 - smoked hemp buds.
As you can see, I use pharmacologically synergistic combinations (and ensure low drug tolerances through "brain maintenance") which result in desired psychoactive effects, which doesn't require "potent" receptor activation. A nice benefit is that I can customise the psychoactive experience based on understanding of a substances pharmacology and brain chemistry. It's also fun to "play mad scientist" Stay safe though. Nothing silly or dangerous.

??:?? - ginger biscuits and dark chocolate all eaten

03:00 - Still noticeably inebriated. Very tired. Took 1.5g Magnesium Threonate sublingually, went to bed. Likely synergistic NMDA antagonsism from the magnesium.

12:00 - Wake up at midday feeling refreshed.

Antidepressant aftereffects were present today. A feeling of contentment, and no urge for biscuits and chocolate were experienced.


I've tried .55g ferulic acid two more times, both swished sublingually with water for ~10mins then swallowed. Effects crept up slowly for an hour or so, and lasted at least until the next day.

On both occasions a strong mood lift and general pleasant enjoyment was experienced and socialising was very very easy, as was laughter.

No aftereffects were noticed.


Edited by sativa, 20 May 2016 - 04:41 PM.


#12 thedevinroy

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Posted 20 May 2016 - 07:20 PM

You have to swish it? Or take it on an empty tummy?

Edited by devinthayer, 20 May 2016 - 07:20 PM.


#13 sativa

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Posted 20 May 2016 - 10:49 PM

You have to swish it? Or take it on an empty tummy?


No, I just did that to speed up/enhance absorption. I took it on a fairly empty stomach.

#14 thedevinroy

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Posted 21 May 2016 - 05:48 AM

Sounds easily absorbed and a great way to stave off the social anxiety. I took Memantine for a while, even whilst on Huperzine A. No euphoria or anything, just subsided the craziness from caffeine... less tense, less scatter brained, etc. The fact that it is a simple phenolic compound is really good for mood and the immune system.

Would you say it increased focus, motivation, thought speed, creativity, ability to shift attention, energy, passion, deeper REM, wittier conversation, funnier conversation, confidence, pride, or anything similar or opposite?


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#15 sativa

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Posted 21 May 2016 - 12:08 PM

Sounds easily absorbed and a great way to stave off the social anxiety.
...
Would you say it increased focus, motivation, thought speed, creativity, ability to shift attention, energy, passion, deeper REM, wittier conversation, funnier conversation, confidence, pride, or anything similar or opposite?

Regarding absorption, I first brushed my teeth and gums (with sodium bicarbonate) and swished the ferulic acid powder with 10ml colloidal gold, which, itself, contributes a noticeable background boost to many aspects including mood, strength, resilience etc. I'm used to colloidal golds effects so this allowed me to differentiate ferulic acids effects.

Ferulic definitely is good for social anxiety. I'm usually quite chilled but with hints of s.anxiety and ferulic definitely calmed it down.

It brings about a sense of almost serenity, it feels soft, cosy and easy going.

My general goal is to attain and maintain a so called "flow state" (kind of like the limitless effect except more tenable and wholesome, by this I mean emotional intelligence and not so much of a focus on ego) and I incorporate both a western and eastern approach to life and existence.

I mainly use plants (eg adaptogens, essential oils) but also synthetics (such as memantine, uridine) and vit & mineral supplements. Diet is fairly simple and 98% organic (w.rice, chestnuts, vegetables, nutritional yeast, pea protein powder, coconut/olive/hemp/FCL oil) and I place an importance in engaging a constant low level detoxification (by boosting it etc).

I don't have any underlying "diseases or conditions" to treat.

Regarding your list, many of these things I have picked up/learnt already. Bear in mind it was a while since I tried ferulic but I'll recall as best as I can!

∆ Increased focus - slightly
∆ Motivation - slightly
∆ Thought speed - tweaked, increased
∆ Creativity - slightly
∆ Ability to shift attention - prone to this anyway if the current task is not very "interesting". Ferulic didn't have a noticeable effect, perhaps I was more able to focus though, less straying.
∆ Energy - slightly
∆ Passion - yes
∆ Deeper REM - unsure, I occasionally take 2-3g glycine before bed. The one time I took ferulic before bed I had consumed many other psychoactives so I can't tell...
∆ Wittier conversation - yes.
∆ Funnier conversation - yes. Exploding with laughter, at my own humor and in general conversation. Made my jovial child like nature stand out even more.
∆ Confidence - yes. One time, chilling with a friend, she's quite attractive and another on a night out where alcohol was also consumed.
∆ Pride - no effect I could tell. I think pride is an aspect that is more under control of another part of me, one that ensures I am not overly prideful and keeps it in check. I perceive pride as being useful in small amounts but too much and ego is amplified which is not something "I" like.

I've never taken any pharmaceutical antidepressants and drink very very rarely. I occasionally smoke .3-4g of Nicotiana rustica tobacco (which is up to 20x stronger than regular tobacco) perhaps ~3.5 times a week, combined with CBD hemp buds (0.02% THC). This is a recent habit, I keep the nicotine habit "in check" with lobelia tincture.

Combinations with interesting neuropharmacological potential that I'd like to try:

Ferulic acid -

+Forskolin (cAMP, upregulate D2L receptor)

The forskolin-mediated hD2L receptor rise is dependent on de novo protein synthesis, a rise in cAMP levels, PKA activation, and, at least partially, PTX-sensitive G proteins.

+Kanna (50:1 extract, SSRI & possible serotonin VMAT activity, CB1 activity if unfermented, PDE4 inhibiton)
+Huperzine A
+Kava kava (home made extract and purchased extract paste, both effective and safe)
+Saffron (has NMDA, sigma and 5-HT activity IIRC)
+Syrian rue (has MAOB inhibition, 5-HT2A psychedelic activity, and AChE inhibition, NMDA antagonsism.)
+Lemon oil (5-HT3 antagonsism, HT1A agonism, AChE inhibition)
+Happiness tree (Albizia julibrissin, antidepressant via 5-HT1A and 5-HT2C)
+Datura stramonium seeds (full spectrum muscarinic antagonist, so be careful with dosage. Might result in interesting effects. This combo is purely experimental....)
+Celastrus Paniculatus - (NMDA antagonsism, AChE inhibition, dopamine TAAR agonism)

The Kanna, Syrian rue (low dose), Happiness tree and lemon oil combos have potential for great antidepressant effects.
Ferulic + Celastrus could be quite interesting too.

Ferulic acid combined with Gardenia jasminoides might be spectacular:

Rapid Antidepressant Activity of Ethanol Extract of Gardenia jasminoides Ellis Is Associated with Upregulation of BDNF Expression in the Hippocampus.

...
Here we investigated ethanol extracts of the constituent herbs of Yueju...

...we found that only Gardenia jasminoides Ellis (GJ) showed a significant effect.
...
These findings suggest that GJ has rapid antidepressant effects, which are associated with the elevated expression of BDNF in the hippocampus. In Yueju formula, Yue represents GJ, as thus our study demonstrates the primary role of GJ in rapid antidepressant efficacy of Yueju.



Some sort of ultimate antidepressant combo:

+ Ferulic acid (NMDA, 5HT)
+ Gardenia jasminoides (rapid BDNF upregulating antidepressant)
+ An AChE inhibitor:
---Celastrus - adds NMDA antagonsism and dopamine effects - stimulating.
---Taspine:

Taspine is an alkaloid which acts as a potent acetylcholinesterase inhibitor. https://en.m.wikiped...rg/wiki/Taspine

found in Croton lechleri aka dragon's blood. I have an extract arriving soon.
---Huperzine A - adds NMDA antagonsism

+ Vitamin E - lower prolactin
+ Kanna (preferably fermented) - mainly SSRI, PDE4 inhibiton.
+ optional low dose Syrian rue for potentiation. Might also enhance pineal endocrine function and enhance mitosis.

Edited by sativa, 21 May 2016 - 01:06 PM.


#16 sativa

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Posted 21 May 2016 - 01:12 PM

(my post edit ability timed out)

Re Syrian rue:

Potential to enhance mitosis thanks to the alkaloid pinoline. A harmala compound also inhibits formation of endogenous kynurenic acid which is an antagonist at many important glutamate receptors including alpha 7 (see www.longecity.org/forum/topic/61506-a-greatly-overlooked-factor-for-cognitionclarity-kynurenic-acid-glycinesarcosine-users-read/)

#17 thedevinroy

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Posted 21 May 2016 - 01:21 PM

Thanks! It's a compound I looked into trying before. Crazy it has so many effects, but not too surprised either being that it is all the things I mentioned. By pride I meant pride in work. Apathy is a common occurrence of low brain functioning individuals, so pride in work is one of those things that counters apathy to a degree.


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#18 normalizing

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Posted 21 May 2016 - 01:47 PM

sativa you keep mentioning gardenia but you wont do it still



#19 sativa

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Posted 21 May 2016 - 01:47 PM

By pride I meant pride in work. Apathy is a common occurrence of low brain functioning individuals, so pride in work is one of those things that counters apathy to a degree.

Ah I see! Perhaps slightly but I can't be certain as I am quite methodical and perfectionist for a lot of things anyway!

sativa you keep mentioning gardenia but you wont do it still


Like I told you already, the opportunity hasn't presented itself. This time your tone (as read over the internet...) is a bit less off putting than the first time you bought this up - I tend to be put off doing something when someone is "harassing" me to do it. "Harassing" is definitely to strong a word, but it kind of works in this context.

Note I'm not offended by what you said, nor should you be of what I said. Just trying to express my reaction.

Edited by sativa, 21 May 2016 - 01:57 PM.


#20 thedevinroy

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Posted 21 May 2016 - 02:26 PM

(deleted witty comment)

Edited by devinthayer, 21 May 2016 - 02:27 PM.


#21 thedevinroy

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Posted 21 May 2016 - 02:36 PM

By pride I meant pride in work. Apathy is a common occurrence of low brain functioning individuals, so pride in work is one of those things that counters apathy to a degree.

Ah I see! Perhaps slightly but I can't be certain as I am quite methodical and perfectionist for a lot of things anyway!

sativa you keep mentioning gardenia but you wont do it still

Like I told you already, the opportunity hasn't presented itself. This time your tone (as read over the internet...) is a bit less off putting than the first time you bought this up - I tend to be put off doing something when someone is "harassing" me to do it. "Harassing" is definitely to strong a word, but it kind of works in this context.

Note I'm not offended by what you said, nor should you be of what I said. Just trying to express my reaction.

It was ambiguous in part too. I mean originally I thought to include it as pride in work, but thought maybe he can take a rough idea and expound on its different implications and possible meanings. However, I don't believe that is necessary, since you have stated several characteristics that are stronger in other aspects of the same function - confidence and passion. I was trying to get a feel for the effects in the general prefrontal cortex, basal ganglia, cingulate gurus, and temporal lobes. They all seem pretty enhanced.

Do any of these effects wear off sooner than others?

#22 sativa

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Posted 21 May 2016 - 02:42 PM

(deleted witty comment)


I present you a "Lol" for said witty comment heh.

Do any of these effects wear off sooner than others?


Oh gosh, considering the different psychoactive substances/supplements I combined with ferulic I have no idea of the timescale and timetable of the ferulic effects and when each wore off...

I did notice positive effects the day after, but this could be due to a combination of ferulic and other substances. The ferulic definitely resulted in positive after effects, which I don't usually get.

By the time the psychoactive effects of my ferulic & co combinations are decreasing, all the pharmacological properties have merged together making it quite hard to differentiate. I'm still learning what alteration of different receptors feels like. I've got a pretty good feel for NMDA antagonsism - usually produces green/red visual effects.

Edited by sativa, 21 May 2016 - 02:53 PM.


#23 thedevinroy

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Posted 21 May 2016 - 02:48 PM

(deleted witty comment)

I present you a "Lol" for said witty comment heh.

Do any of these effects wear off sooner than others?

Oh gosh, considering the different psychoactive substances/supplements I combined with ferulic I have no idea of the timescale and timetable of the ferulic effects and when each wore off...

Oh bummer.

Yeah I deleted the witty comment based on your response. Figured it was in bad taste, but you still have a sense of humor I see.

#24 sativa

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Posted 21 May 2016 - 02:55 PM

Yeah I deleted the witty comment based on your response. Figured it was in bad taste, but you still have a sense of humor I see.

Well I actually never saw the comment of wit, but gave it a mental "lol", "in absentia".

To lol is to live, living necessitates lol. To live and not lol is not living. Do I digress??

Edited by sativa, 21 May 2016 - 03:01 PM.


#25 normalizing

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Posted 21 May 2016 - 06:30 PM

sative it shouldnt be offensive to you or me but to the people to which you still continue to recommend gardenia considering none of us have tried it yet. in my situation i cannot even afford any but you ordered from what i remember? anyway thats all, im just itching for report and i might act a bit aggressive about it too :)


Edited by normalizing, 21 May 2016 - 06:31 PM.


#26 sativa

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Posted 21 May 2016 - 07:56 PM

sative it shouldnt be offensive to you or me but to the people to which you still continue to recommend gardenia considering none of us have tried it yet. in my situation i cannot even afford any but you ordered from what i remember? anyway thats all, im just itching for report and i might act a bit aggressive about it too :)

Fair enough! Hmmm i still don't get why anyone should get offended because of that, if they were perhaps they might be overreacting!?! *shrugs*

I got it from a popular bidding site.

But ok OKKKKKKKK I'll try it ASAP ;)
My Tianeptine arrived earlier too.

Edited by sativa, 21 May 2016 - 07:57 PM.


#27 airplanepeanuts

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Posted 21 May 2016 - 08:16 PM

I have just glanced over this thread. Are you concerned about gardenia toxicity? http://www.ncbi.nlm....pubmed/22456001



#28 sativa

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Posted 21 May 2016 - 08:30 PM

I have just glanced over this thread. Are you concerned about gardenia toxicity? http://www.ncbi.nlm....pubmed/22456001:

The hepatotoxicity was associated with oxidative stress with decrease of total superoxide dismutase activity and increase of malondialdehyde concentration in rats' livers. Subchronic toxicity study showed geniposide did not cause hepatotoxicity at the doses of 24.3 and 72.9 mg kg(-1) orally for 90 days in rats. Thus, acute hepatotoxicity of geniposide at high doses was likely to be linked to oxidative stress, while geniposide at normal dose of 24.3 mg kg(-1) or less did not cause hepatotoxicity even in the repeated dosing study.

Not really. Its part of a traditional medicinal combination so for me, this adds credibility to its use and safety.

I maintain a healthy body and diet and regularly use adaptogens and other botanicals (eg milk thistle) which will all help to negate any potential hepatoxicity. I don't intend to take gardenia regularly neither.

More info on it's use and properties here: www.longecity.org/forum/topic/85615-natural-ketamine-for-depression/

Edited by sativa, 21 May 2016 - 08:32 PM.


#29 gamesguru

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Posted 21 May 2016 - 10:36 PM

some other natural NMDA antagonists...
lappaconitine blocks sodium channels, and kaitocephalin blocks AMPA

galantamine 3, huperzine 1
"The potential relevance ofNMDA receptor antagonist activity of huperzine A to the treatment of Alzheimer's disease is ..."

also apparently berberine and ibogaine

curcumin and some ergot alkaloid block glutamate release, which might have similar effects

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#30 sativa

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Posted 21 May 2016 - 10:43 PM

some other natural NMDA antagonists...
lappaconitine blocks sodium channels, and kaitocephalin blocks AMPA
...
also apparently berberine and ibogaine


Oh cool, interesting toxic substances with indirect glutamate activity!

And of course ibogaine is an NMDA antagonist! Have you ever tried it or full spectrum iboga extract? It's quite interesting and unique.





Also tagged with one or more of these keywords: ferulic acid, nmda, ht1a, ht2a, ht2c

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