Gaba receptors and Serotonin

Grateful 30 Apr 2016

Hello any insight you guys/girls have is very much appreciated. I have a friend who is deeply suffering from anxiety\depression. It seems to lift when he takes clonazepam but he knows that isn't the way to solve it. He had a bad experience on MDA(tested). And it left him with crippling anxiety. What kind of supplements should he use as he does not want to fall into the pharmaceutical trap. He knows that there are things on this earth that can and will heal him. Any insight is appreciated. He would only use pharmaceutical remedies aa a last resort. Thanks so much for reading.

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Doc Psychoillogical 01 May 2016

Anxiety and Stress

In rats given Melissa officinalis extract (9.32% Rosmarinic Acid) at 120-360mg/kg bodyweight for 15 days appeared to have anxiolytic effects in an open field test as well as an elevated maze test but not in a four-hole board test at the higher two doses (240mg/kg and 360mg/kg).[26] The anxiolyic effects (30-300mg/kg ethanolic extract) have in one study been comparable to 1mg/kg Diazepam when dosed over 10 days, and appeared to be more effective in females (with only 300mg/kg being statistically significant in males, but all doses being effective in female rats).[27]

One study has noted that inhalation of lemon oil vapor has exerted anti-stress responses, and that these effects were related to serotonergic signalling (particularly the receptor 5-HT1A).[28]

Two animal studies suggest anxiety reducing effects of oral Lemon Balm, with one noting that lemon vapor was also effective

In a clinical setting, an acute dose of 300 or 600mg Melissa officinalis prior to an acute stress test (DISS battery of tests[29] followed with Mood assessment via Bond and Lader VAS mood scales[30]) noted that the higher dose was associated with improved self-reported calmness, reduced alertness (increased after test) following the test while the 300mg dose failed to significantly modulate mood.[31] Another acute study noted that a Lozenge containing Melissa officinalis was able to induce brain wave alterations similar to that of standard anxiolytics.[32]

Can reduce anxiety when dosed acutely (single dose taken before stressor)

In humans consuming 300mg Melissa officinalis (7% Rosmarinic acid and 15% total hydrocinnamic acids) at breakfast and again before sleep for 15 days in an open-label trial, there appears to be general anxiolytic propeties in regards to anxiety-related eating problems (33% lower than baseline), emotional instability (7%), fatigue (18%), feelings of guilt (15%) or inferiority (18%), psychosomatic symptoms (33%) and intellectual disturbance (28%).[25]

Appears to reduce anxiety when taken over a period of time in humans (morning and nightly doses)

GABAergic mechanisms

In regards to GABA (primary sedative neurotransmitter), the methanolic extract appears to have GABAergic activity secondary to inhibiting the enzyme GABA transaminase (IC50 of 0.55+/-0.2mg/mL) to a greater degree than hexane (none detected), ethyl acetate (2.55+/-0.28mg/mL), and water extracts (0.82+/-0.03mg/mL).[23] The molecules that appear to be most active in this regard are Ursolic Acid (5.0+/-3.6% inhibition at 1µg/mL and 19.9+/-10.6% inhibition at 100µg/mL), oleanolic acid (20.2+/-11.1% at 10µg/mL), and Rosmarinic Acid (4.6+/-2.2% inhibition at 1µg/mL and 40.4+/-3.2% at 100µg/mL) while ursolic acid appeared to be slightly synergistic when paired with oleanolic acid.[23]

A reduced concentration of GABA transaminase has been noted in vivo following 50-200mg/kg oral ingestion in aged rats over 5 weeks, when the hippocampal dentate gyrus was removed and assessed.[24]

Appears to have GABAergic activity, although by a mechanism not common to other nutraceuticals (possible additive or synergistic possibilities that are not yet explored)

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iseethelight 01 May 2016

He has to try many supplements before he finds what works for him. It depends on what imbalance is causing his depression. Serotonin and gaba supplements may make him more depressed. Trial and error.

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Grateful 01 May 2016

Thank you guys for the replys. It started after he took tested MDA and had a bad experience at the end which left him with crazy anxiety and paranoia. He was this way for about 3 weeks and got some phenibut. He didn't do enough research and started using it daily in which he felt mostly normal. After about 10-12 weeks the side effects were getting him bad like feeling withdrawal before his next dose and increased paranoia. He thought when people were laughing near him it felt like they were laughing at him. He did a half assed taper and got to one gram for about a week then jumped off cold turkey. He said that was one of the most painful experiences of his life where he was soaking the sheets almost everyday having to wash the covers. He was doing intense cardio for the 2 weeks he jumped off because he woke up in panic mode. It's been two months since and he is seeing improvement. He feels like it brought up some underlying OCD or something because in the mornings he gets obsessive thoughts about past failures and guilts. By the night time he feels a lot better and his sleep is pretty good sometimes a little broken but at like 6-7 hours most days. He started taking st Johns wort, myo inositol 16 grams a day, l theanine, 5 htp some days, and started food grade diatomaceous earth which is good for detox. He is seeing small improvements everyday just want some more insight. I heard about a RC ns-189 or something and was curious about that too.
Edited by Grateful, 01 May 2016 - 08:12 PM.

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sativa 03 May 2016

Before trying RC NS-189 try other neurogenesis substances - there are many such as coq10, turmeric, gotu kola...

Also I wouldn't really recommend pharmaceutical SSRI drugs...SSRI leads to long term serotonin receptor down regulation.

Happiness tree could be worth a try! -
www.planetherbs.com/specific-herbs/albizia-the-tree-of-happiness.html

Lemon oil is a nice antidepressant as mentioned above. Oxytocin release via 5-HT1A and 5-HT3 antagonsism all feel great...
Edited by sativa, 03 May 2016 - 12:47 PM.

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Brock 13 Aug 2016

Interestingly enough there is a plant that modeled the creation of the Pharmaceuticals your friend is trying to avoid. St. Johns wort flower was the foundation of prozac for it's ability to manipulate reuptake of neurotransmitters like seratonin and dopamine - the pleasure and happiness molecules. I did focus piece on the flower you can find here if your friend is interested in the natural rout. This is combination with tyrosine and acetyl carnitine would be ideal, both are cheap supplements to buy and are part of my personal stack every day. Mixed with a solid cup of coffee and you start your day refreshed and vibrant... trust me this will work if he has not already fell through the unfortunate rabbit hole of pharmaceuticals.

Article on st. johns wort > http://yoururbanalchemy.com/hypericum-flower-fight-mood-disorders/

Some more info on the best amino's I mentioned

Cheers!

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Flex 16 Aug 2016

Even if You dont like Doctors and the meds, better see an doctor. Could be that MDA caused a bleeding which could only be seen via a MRI and what not. just telling You a wild example.

try ziziphus jujuba aka Suan Zao Ren(the pin yin name) because it increases GAD 65/67 which increases the convertion of glutamate to GABA.

Magnolia extract (Hou pu) might help a bit but kava kava might be even better because its modulates the GABA receptors (IIRC).

other than that, I would look into cortisol/CRF altering stuff like St. john worth(though its afaik weak) Bupleurum chinense / Chai Hu

and especially regenerative stuff like fishoil more than 1g/d (supports), Rehmannia glutinosa (sheng di huang), ahswagandha extract, Jiaogulan (dopamine regeneration) and this thread:

Nogo-A inhibition and brain regrowth

http://www.longecity...th/#entry737252

and lots of sports to curb angiogenesis, Bdnf production and what not !!

However as far as I know, its not allways serotonergic damage because of MDA &etc. I heard it could be rather dopaminergic or general damage.

Time will tell. Meth addicts need 1-2 years of abstinence to recover from the damages. I guess it cant be generalized but Your friend should recover far better than them.

It could be that any expression of receptors has changed, either epigenetically or post-translational, in the case that he doesnt get better.

I´m no expert and the chances are imo not that big but I find, it has to be mentioned.

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Junk Master 16 Aug 2016

Though not MDMA induced, in my experience with anxiety and depression, the supplements that have been most useful are Magnolia Bark, Lemon Balm, and most of all Ashwagandha.

High doses of Inositol (12-18g) were very useful but I suffered mild gastrointestinal distress from said doses.

Other than that, why not continue with aerobic exercise and Clonazepam at low doses? Then over time begin to lower the dose of Clonazepam.

In my case, after trying Prozac, Zoloft, Wellbutrin, Lexapro, Effexor, and Pristiq; plus, Ambien, and Lunesta, I began with 1 mg of Clonazepam twice a day and also started Cognitive Behavioral Therapy. After a couple years of CBT, while continuing regular, aerobic exercise, I tapered off the Clonazepam until I now only take .5 mg as needed.

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