49 replies to this topic

[thedevinroy]

Please note that activation of the D4 dopaminergic receptor involved with ADHD causes a reduction in cAMP, NMDARs, GABARs, etc. and an increase in AMPARs. This is why Piracetam is useful for treating hyperactivity subtype. However, most forms ADHD are though to be from lower dopamine receptor activation, whether it be the D4 subtype or another inhibitory receptor like D2. The D4 receptor also receives norepinephrine and epinephrine.

More on D4 Receptor:
http://www.ncbi.nlm....les/PMC3009820/

In addition to NMDA antagonists, Ampakines, Dopaminergics, Noradrenergics, and Adrenergics, it is important to note that the GABA-A receptor is involved in inhibitory dopamine receptor activation. I realize GABA-A inhibition will cause convulsions if done improperly, so I'm not recommending anybody go out there and down a bunch of sage oil, zinc, and ginkgo. You will have one hell of a time explaining all this to your doctor.

What I am interested is starting a discussion on the topic.

Natural GABA Blockers:

• Zinc (also an NMDA antagonist and Melatonin co-factor)
• Bilobalide (found in Ginkgo Biloba)
• Thujone (found in Sage Oil Ethanol Extracts and Absynth)
• Picrotoxin (found in Anamirta cocculus)
• Bicuculline (found in Dicentra cucullaria, Adlumia fungosa, Fumariaceae, and Corydalis)
• Cicutoxin (found in water hemlock)

Nootropic Drug GABA Blockers:

• Cyclothiazide (also an Ampakine ... not sure of its availability in USA)
• Alpha-5IA (inverse agonist at GABA-A5, partial agonists at other subtypes)

Cyclothiazide used to be available in the USA as a diuretic and antihypertensive. Alpha-5IA is still in the research phase. I have not tried either, but would love to... so would love to.

Personally, I found Zinc + Ginkgo to be a great addition to Gotu Kola in fighting ADHD symptoms.

Edited by devinthayer, 17 November 2011 - 09:54 PM.

[thedevinroy]

Anyone try Sage Oil from an ethanol extract?

Seems ethanol is the best solvent for Thujone.

[thedevinroy]

I can't find any experiences whatsoever on Cyclothiazide. It seems it is too ancient of a drug to really be popular, but there are studies all over the place on it. It is an ampakine that pre-dates the original nootropic Piracetam by a year! It's lethal dose exceeds the weight of the rats and mice! I can't believe no one has ever tried this for cognitive benefits!

Outrageous. I'm calling pharmacies and my insurance company as soon as I remember to see if they stock it or cover it.

[sam7777]

I know sage essential oil had some sort of beneficial effect in me. I never really tried to test it consistently though.

[thedevinroy]

I know sage essential oil had some sort of beneficial effect in me. I never really tried to test it consistently though.

Awesome. It's also packed with Omega-3 (ALA) oil, too.

[thedevinroy]

I just want to add that Ginkgo in the realm of 2-3 pills (120mg of 24/6/5 extract) is pretty darn like a lot of Fish Oil on an empty stomach. That's the best thing I can compare it to. It sort of opens up your mind, and let's you think clearer. I haven't noticed any extreme flushing of skin, just a nice color. I'm a pretty pale face usually, so I'd compare it to coffee-face. It helps with motivation and focus a tad, too.

EDIT: And though it helps with energy, it does not increase hyperactivity. Good when Selegiline wears off to prevent crash. Seems to synergize well with 15mg of Zinc.

Edited by devinthayer, 18 November 2011 - 03:23 PM.

[thedevinroy]

Been doing some research on Sage oil. Seems that 12 drops is considered toxic (rats have died from use) which is funny since a serving is 2x that dose of sage oil 1:1 ethanol oil (example). The leading causes of GABA blockade are alpha-thujone and beta-thujone and their metabolites. They all act on GABA-A receptors (noncompetitive, picrotoxin site) and 5-HT3 receptors. It's half life is remarkably long (25+ hours) according to the facebook group and other users report long lasting effects, similar to THC use.

I wouldn't recommend long term use past a few drops a day if you are generally a lethargic, sedated, anxiety-free individual with no history of epilepsy or blood disorders.

[thedevinroy]

And I called my pharmacy about Cyclothiazide. They had no idea what I was talking about. They had me spell out the word.

[thedevinroy]

Anyone know where I can find a higher grade of Ginkgo than the 24/6/5 standardized extracts I see everywhere? Looking for higher Bilobalide content. This article claims to have found one with 5% bilobalide, but then doesn't state specifically what brand or where to find it other than Amazon... great help, smartass publications.

A 5% extract would be nice...

Edited by devinthayer, 22 November 2011 - 10:02 PM.

[AbolishtheState]

Thujone may also be found in members of the genus Artemisia, such as Absinthe Wormwood (Artemisia absinthium). More on that after I provide some context.

About a year ago, I found myself in the depths of a deep depression (three words with the same root seems a bit redundant, but I digress) resulting from an unexpected move, which led to social withdrawal and self-imposed isolation. During this trough of my existence, I made some rather unwise decisions regarding recreational drug use; precipitated by immediate cessation of cannabis use after a year or so of chronic intake, due to lack of a "hook-up." In my desperate and foolish search for some substance to fill the void, I scoured Erowid and other internet resources for novel intoxicants that were relatively easy to acquire.

One such intoxicant with which I experimented was thujone from dried wormwood. The subjective "high" reported by fellow Erowid experimenters, which I experienced to some degree, was a "dollhouse effect" on the perception of reality. This was not a visual distortion, per se, but a tinge of unreality cast upon everything one sees; as if everything looked the same, yet seemed fake and contrived. These effects likely indicate derealization. From Wikipedia: "derealization is an alteration in the perception or experience of the external world so that it seems unreal. Other symptoms include feeling as though one's environment is lacking in spontaneity, emotional coloring and depth." [http://en.wikipedia....i/Derealization] I am not sure if derealization is a known symptom of GABA_A antagonism, but there seems to be a lot of anecdotal evidence suggesting the link. Some of the other symptoms I experienced were cardiac dysrhythmia, intense anxiety, and mild convulsions. I cannot report any cognitive enhancement or increased focus, but I was not looking for those effects and my trial was with a dose likely too large to produce those results. The following article is the only one I was able to find which tested the link between attention performance and thujone. The results seems contrary to your hypothesis, however, thujone was administered concurrently with alcohol; alleviation of ADD symptoms was not the study's purpose; and thujone has actions other than GABA_A antagonism, which may complicate its use in treating ADD.

Absinthe:' class='bbc_url' title='External link' rel='nofollow external'>http://www.thujone.info/thujone-absinthe-5.html']Absinthe: Attention Performance and Mood under the Influence of Thujone
by A. Dettling, H. Grass, A. Schuff, G. Skopp, P. Strohbeck-Kuehner and H-Th. Haffner
Published in Journal of Studies on Alcohol, September 2004
OBJECTIVE:
The aim of this study was to determine whether the impacts of absinthe on attention performance and mood were different from those
experienced with beverages that contain only alcohol. The ingredient causing absinthe's toxicity is believed to be thujone.
METHOD:
A total of 25 healthy subjects participated in the study. An attention performance test and two questionnaires testing different mood
dimensions were used. Three drinks with an identical amount of alcohol but with different amounts of thujone were offered.
RESULTS:
The results of the present study showed that the simultaneous administration of alcohol containing a high concentration of thujone had
a negative effect on attention performance. Under this condition, the subjects tended to direct their attention to signals in the central field
of attention and to neglect peripheral signals; the number of correct reactions decreased significantly in the peripheral field of attention,
and reaction time and the number of "false alarm" reactions increased significantly. The effects were most prominent at the time of the
first measurement. When the subjects were under the influence of alcohol or were administered both alcohol and a low thujone
concentration, these effects were not observed. The assessment of mood state dimensions showed that the anxiolytic effect of alcohol
was temporarily counteracted by a high thujone concentration.
CONCLUSIONS:
As they are apparently opposed to the effect of alcohol, the reactions observed here can be explained by the antagonistic effect of
thujone on the gamma-aminobutyric acid receptor. Similar alterations were observed for the other mood state dimensions examined.

→ source (external link)

[thedevinroy]

Thujone sounds like a trip indeed. Thank you for sharing that.

[nupi]

Tried it once (it's been legalized in Switzerland a couple of years ago). Garish taste and mainly got me drunk with some other weird effects on top of it. Overall, not enjoyable enough for me to ever bother with it again...

[AbolishtheState]

Tried it once (it's been legalized in Switzerland a couple of years ago). Garish taste and mainly got me drunk with some other weird effects on top of it. Overall, not enjoyable enough for me to ever bother with it again...

The taste is rather atrocious. It is probably one of the most bitter flavors to have ever fouled my tongue. Noopept and other bitter synthetics taste sweet in comparison.

Edited by AbolishtheState, 23 November 2011 - 05:00 AM.

[thedevinroy]

Haha not the experiences I would expect... do you think that a few drops over time do anything positive?

Edited by devinthayer, 23 November 2011 - 12:49 PM.

[AbolishtheState]

I meant to say in my first response that I still have some wormwood left. I would be willing to do some further experimentation, if you could recommend a target dose. Perhaps, you could procure some other GABA_A antagonists and we could do some trials.

[thedevinroy]

I meant to say in my first response that I still have some wormwood left. I would be willing to do some further experimentation, if you could recommend a target dose. Perhaps, you could procure some other GABA_A antagonists and we could do some trials.

Gorilla trial research! Well, if 12 drops of 25% thujone will cause neurotoxicity, what about 3 drops? I suggest that... unless you have powdered extract... in which case, I'd have to dig up how much thujone that is. ((12 / 28) * .25) / 4 = 0.0267857143 mL or about 26mg is in 3 drops of Sage oil. Whatever 26mg of thujone is in wormwood...

Zinc and Ginkgo are the only other readily available ones out there. However, they are entirely multi-functional GABA blockers. Ginkgo is more of a glycine antagonist. Zinc is also an NMDA antagonist and is used in activating B6, which is used in making melatonin from serotonin.

Edited by devinthayer, 23 November 2011 - 06:33 PM.

[AbolishtheState]

The only problem I foresee is that I have wormwood in whole herb form. It is not standardized so we would be guessing at the thujone content. That could certainly be dangerous and would not lend itself to accurate trials.

[matter_of_time]

dont know if it has something to do with gaba-a but after drinking to much alcohol beverage, I always feel the first hours in the morning ADD-free. Mostly just in a window of two hours and afterwards comes the man with the hammer.

[AbolishtheState]

dont know if it has something to do with gaba-a but after drinking to much alcohol beverage, I always feel the first hours in the morning ADD-free. Mostly just in a window of two hours and afterwards comes the man with the hammer.

After heavy GABA_A agonism--such as from drinking ethanol--one would assume there would be a rebound effect the next day, as the body down-regulates those receptors. Down-regulation might cause similar effects to GABA_A antagonism. If you experience alleviation of ADD symptoms during the rebound period, one might consider that anecdotal evidence of the link devinthayer suggested. Further investigation is merited, I feel.

[thedevinroy]

dont know if it has something to do with gaba-a but after drinking to much alcohol beverage, I always feel the first hours in the morning ADD-free. Mostly just in a window of two hours and afterwards comes the man with the hammer.

I think it does have to do with that. I notice the same thing when taking Valerian Root before bed. I believe it has to do with receptor regulation. Activation of GABA-A tends to reverse caffeine tolerance.

Edited by devinthayer, 23 November 2011 - 07:37 PM.

[thedevinroy]

dont know if it has something to do with gaba-a but after drinking to much alcohol beverage, I always feel the first hours in the morning ADD-free. Mostly just in a window of two hours and afterwards comes the man with the hammer.

After heavy GABA_A agonism--such as from drinking ethanol--one would assume there would be a rebound effect the next day, as the body down-regulates those receptors. Down-regulation might cause similar effects to GABA_A antagonism. If you experience alleviation of ADD symptoms during the rebound period, one might consider that anecdotal evidence of the link devinthayer suggested. Further investigation is merited, I feel.

http://www.shamansga...7-wormwood.aspx

I guess it can be anywhere between 0.5mg/g to 3mg/g. Assume the upper limit to be safe, and take 7 grams? That doesn't sound right... huh, I guess it is... damn, man. Won't that much give you gas?

[X_Danny_X]

i was reading some products about sage essential oil, it seems that it is basically applied through skin. ingested is dangerous according to the products directions.

is this true. i have adht/add and i am still searching for some products to help fight this problem.

[AbolishtheState]

dont know if it has something to do with gaba-a but after drinking to much alcohol beverage, I always feel the first hours in the morning ADD-free. Mostly just in a window of two hours and afterwards comes the man with the hammer.

After heavy GABA_A agonism--such as from drinking ethanol--one would assume there would be a rebound effect the next day, as the body down-regulates those receptors. Down-regulation might cause similar effects to GABA_A antagonism. If you experience alleviation of ADD symptoms during the rebound period, one might consider that anecdotal evidence of the link devinthayer suggested. Further investigation is merited, I feel.

http://www.shamansga...7-wormwood.aspx

I guess it can be anywhere between 0.5mg/g to 3mg/g. Assume the upper limit to be safe, and take 7 grams? That doesn't sound right... huh, I guess it is... damn, man. Won't that much give you gas?

It might be worth trying. I could just start low and work my way up the dose range to ensure safety. I have plenty of natural GABAergics at my disposal if I feel I have overdone it. Would taking GABAergics reverse the effects of thujone, or would the GABAergics be blocked by the thujone?

Edited by AbolishtheState, 24 November 2011 - 12:34 AM.

[thedevinroy]

dont know if it has something to do with gaba-a but after drinking to much alcohol beverage, I always feel the first hours in the morning ADD-free. Mostly just in a window of two hours and afterwards comes the man with the hammer.

After heavy GABA_A agonism--such as from drinking ethanol--one would assume there would be a rebound effect the next day, as the body down-regulates those receptors. Down-regulation might cause similar effects to GABA_A antagonism. If you experience alleviation of ADD symptoms during the rebound period, one might consider that anecdotal evidence of the link devinthayer suggested. Further investigation is merited, I feel.

http://www.shamansga...7-wormwood.aspx

I guess it can be anywhere between 0.5mg/g to 3mg/g. Assume the upper limit to be safe, and take 7 grams? That doesn't sound right... huh, I guess it is... damn, man. Won't that much give you gas?

It might be worth trying. I could just start low and work my way up the dose range to ensure safety. I have plenty of natural GABAergics at my disposal if I feel I have overdone it. Would taking GABAergics reverse the effects of thujone, or would the GABAergics be blocked by the thujone?

Thujone is a noncompetitive antagonist, so it would completely block the effects at normal doses of GABAergics.

[thedevinroy]

i was reading some products about sage essential oil, it seems that it is basically applied through skin. ingested is dangerous according to the products directions.

is this true. i have adht/add and i am still searching for some products to help fight this problem.

Won't you smell like sage after that? Maybe you could put it in your deoderant.

Depends what type of ADHD you have... do positive modulating GABAergics make your symptoms better or worse?

[X_Danny_X]

..............

Edited by X_Danny_X, 27 November 2011 - 02:35 AM.

[X_Danny_X]

i was reading some products about sage essential oil, it seems that it is basically applied through skin. ingested is dangerous according to the products directions.

is this true. i have adht/add and i am still searching for some products to help fight this problem.

Won't you smell like sage after that? Maybe you could put it in your deoderant.

Depends what type of ADHD you have... do positive modulating GABAergics make your symptoms better or worse?

Well if I can ingest sage essential oil I would. I just dont know of a reliable product. Though it seems kind of dangerous to use.


I have no idea to tell you the truth. I didn't know of anything that I was taking (Food or Nootropics) that could be GABA inhibitors. I am right now taking 3 ritalin pills a day since my body I think is becoming tolerant of it. The ritalin are 20mg as I mentioned before. I am not too happy about using Ritalin since it shortens your life. I cant take a break from taking it right now since I am taking online college and going to work full time. I need the motivation it gives me.

[Healthy Tony]

I have been considering experimenting with this route of noots, but I have a few questions. First if a GABA agonist leads to rebound effects from downregulation wouldnt a short acting benzo such as ambien have this effect if taken at night? This seems logical yet contrary to research showing that benzos cause long term cognitive issues. Along similar lines of thought wouldn't the rebound of an antagonist be up regulation which would have undesirable effects?

[thedevinroy]

I have been considering experimenting with this route of noots, but I have a few questions. First if a GABA agonist leads to rebound effects from downregulation wouldnt a short acting benzo such as ambien have this effect if taken at night? This seems logical yet contrary to research showing that benzos cause long term cognitive issues. Along similar lines of thought wouldn't the rebound of an antagonist be up regulation which would have undesirable effects?

Benzos may make cognition worse, but there are some GABAergic herbs that tend to increase quality of sleep and have a much less duration of action that typical benzos. Skullcap and Valerian Root come to mind.

Withdrawals are plausible. Usually the net gain of a neurological system offset by a drug is not zero, and if so, not for a very long time. Lessening dosage may help lessen the progression of tolerance, and increasing dosage may help overcome tolerance. Either way, I'm willing to take my chances with nootropic doses of any GABA Blocker.

[Healthy Tony]

I feel like this may be something that may be best left to the scientific community. In my mind it seems like once said blocker wears off you would feel the rebound which would be sleepiness and fuzzy memory. But that contradicts the fact that downregulation causes memory impairment, so one would think that up regulation would have the opposite effect. This leads me to believe that perhaps GABA just needs to be balanced for optimal memory functioning. That being said I know little about the GABA system, so if someone could shed some light on the subject and explain this to me it would be much appreciated.