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The anxiolytics thread


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#1 medievil

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Posted 08 March 2013 - 12:20 AM

Basicly i want to set up threads simular to the wiki templates like this:

But with our own experiences, or reasons why something would be anxiolytic, we got a sedative thread, a stimulant thread too, so tought this was a good idea to add.

For me i mostly suffer from avpd and anxiolytics for me are things that take out amphetamine anxiety, mostly benzo's or phenibut.

I know scienceguy has a thread about this but he was very discriminative against several options wich id like to discuss too.

Im gonna make myself a cup of chamomile but i think for me it was mostly placebo, perhaps with piperine it works better?

Magnolia bark and mulungu have been said to be simular to a diazepam tablet and from what ive read are the most potent anxiolytic herbs.


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Posted 08 March 2013 - 02:06 AM

From my own experiences.. and staying strictly within the bounds of anxiolytics and not sedatives that mask anxiety.. I've had success with Ashwagandha, L-Theanine, CDP-Choline, 5-HTP, L-Tryptophan, Deprenyl, Oxiracetam, Magnesium, Theobromine, and others I can't think of at the moment.

Ashwagandha can be sedating but not always. Deprenyl was calming yet stimulating. Rhodiola is my absolute favorite anxiolytic but it's also an amazing mood boost for me. I seem to respond well to MAOI's.

I'd like to point out that most of these were only short term anxiolytics for me. The absolute most success I've had with anxiety was not with supplements but with cognitive behavioral therapy. The short term success of the supplements listed above were probably attributed to placebo.

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#3 medievil

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Posted 08 March 2013 - 02:10 AM

Yes CBT should not be underestimated as a effective treatment for anxiety.

#4 medievil

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Posted 08 March 2013 - 02:37 AM

Id like to try GABOB its a gaba and GHB agonist, GHB agonists are anxiolytic for me (amisulpiride, prechloperazide, etc).

#5 Thorsten3

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Posted 08 March 2013 - 10:52 AM


Some obscure French drug that operates on certain non addictive (so they tell us), sub unit of the benzo receptors. It doesn't interact with the GABA receptors directly, but is another anxiolytic.

I've tried it, and when used on its own it does work for GAD. It's not that bad, although comes with absolutely no mood elevating effects whatsoever. It feels like a mild benzo without the mood elevation.

It won't be of interest to the OP, but others might want to try it if their anxiety is that bad.

I also want to try tofisopam, at some point.

#6 medievil

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Posted 08 March 2013 - 11:03 AM

I wanted to post about both myself actually, and they do intrest me very much haha.

#7 medievil

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Posted 08 March 2013 - 11:08 AM

Allways worrying about getting benzo's in time, withdrawals if you cant its serieusly pissing me off so a non addictive thing that works would be perfect. I even consider valproic acid and want clozapine around in case i end withdrawing again as that seems the best emergency med for that.

Edited by medievil, 08 March 2013 - 11:12 AM.

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#8 medievil

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Posted 08 March 2013 - 12:42 PM

Honokiol and magnolol increase the number of [3H] muscimol binding sites three-fold in rat forebrain membranes in vitro using a filtration assay, by allosterically increasing the affinities of low-affinity sites.

Squires RF, Ai J, Witt MR, Kahnberg P, Saederup E, Sterner O, Nielsen M.


Center for Neurochemistry, The Nathan Kline Institute for Psychiatric Research Orangeburg, NY 10962, USA. lajtha@nki.rfmh.org


1. The bark of the root and stem of various Magnolia species has been used in Traditional Chinese Medicine to treat a variety of disorders including anxiety and nervous disturbances. The biphenolic compounds honokiol (H) and magnolol (M), the main components of the Chinese medicinal plant Magnolia officinalis, interact with GABA(A) receptors in rat brain in vitro. We compared the effects of H and M on [3H]muscimol (MUS) and [3H]flunitrazepam (FNM) binding using EDTA/water dialyzed rat brain membranes in a buffer containing 150 mM NaCl plus 5 mM Tris-HCl, pH 7.5 as well as [35S]t-butylbicyclophosphorothionate (TBPS) in 200 mM KBr plus 5 mM Tris-HCl, pH 7.5. H and M had similar enhancing effects on [3H]MUS as well as on [3H]FNM binding to rat brain membrane preparations, but H was 2.5 to 5.2 times more potent than M. 2. [3H]FNM binding. GABA alone almost doubled [3H]FNM binding with EC50 = 450 nM and 200 nM using forebrain and cerebellar membranes, respectively. In the presence of 5 microM H or M the EC50 values for GABA were decreased to 79 and 89 nM, respectively, using forebrain, and 39 and 78 nM, using cerebellar membranes. H and M potently enhanced the potentiating effect of 200 nM GABA on [3H]FNM binding with EC50 values of 0.61 microM and 1.6 microM using forebrain membranes, with maximal enhancements of 33 and 47%, respectively. Using cerebellar membranes, the corresponding values were 0.25 and 1.1 microM, and 22 and 34%. 3. [3H]MUS binding. H and M increased [3H]MUS binding to whole forebrain membranes about 3-fold with EC50 values of 6.0 and 15 microM. Using cerebellar membranes, H and M increased [3H]MUS binding approximately 68% with EC50 values of 2.3 and 12 microM, respectively. Scatchard analysis revealed that the enhancements of [3H]MUS binding were due primarily to increases in the number of binding sites (Bmax values) with no effect on the high affinity binding constants (Kd values). The enhancing effect of H and M were not additive. 4. [35S]TBPS binding. H and M displaced [35S]TBPS binding from sites on whole rat forebrain membranes with IC50 values of 7.8 and 6.0 microM, respectively. Using cerebellar membranes, the corresponding IC50 values were 5.3 and 4.8 microM. These inhibitory effects were reversed by the potent GABA(A) receptor blocker R5135 (10 nM), suggesting that H and M allosterically increase the affinity of GABA(A) receptors for GABA and MUS by binding to sites in GABA(A) receptor complexes. 5. Two monophenols, the anesthetic propofol (2,6-diisopropylphenol, P) and the anti-inflammatory diflunisal (2',4'-difluoro-4-hydroxy-3-biphenyl carboxylic acid, D) also enhanced [3H]MUS binding, decreased the EC50 values for GABAin enhancing [3H]FNM binding and potentiated the enhancing effect of 200 nM GABA on [3H]FNM binding, although enhancements of [3H]MUS binding for these monophenols were smaller than those for H and M, using forebrain and cerebellar membranes. The enhancing effect of P and D on [3H]MUS binding were almost completely additive. 2,2'-biphenol was inactive on [3H]MUS and [3H]FNM binding. These, and other preliminary experiments, suggest that appropriate ortho (C2) and para (C4) substitution increases the GABA-potentiating activity of phenols. 6. The potentiation of GABAergic neurotransmission by H and M is probably involved in their previously reported anxiolytic and central depressant effects.

one anecdote indicates it also acts as a gabab PAM massively potentiating phenibut, ive been mostly impressed by this stuff for this purpose. (from what ive read) seems like the only true benzo alternative compared to valerian and shit.

Edited by medievil, 08 March 2013 - 12:48 PM.

#9 medievil

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Posted 08 March 2013 - 03:30 PM

Wow check this thread:

First of all, herbs against anxiety are always a short-time support and not a sole solution. One must work on it, sometimes with sports, sometimes with meditation. Always think "what's the worst that could happen?".

Some anxiolytic herbs (they act on different neurotransmitter-systems):
Paeonia lactiflora- root
Paeonia moutan- root (very active)
Cyperus rotundus- rhizome
Corydalis yanhusuo- root (very active)
Tilia tomentosa (and other Tilia sp.)- flowers
Hypericum perforatum- herb (highly active)
Magnolia officinalis- bark
Passiflora incarnata- leaves (methanol-extracts are highly active)
Salvia miltiorrhiza- root
Valeriana wallichii- root
Evolvulus alsinoides- herb (very active)
Ptychopetalum uncinatum / olacoides- wood
Bacopa monnieri- herb
Rhodiola rosea- root
Erythrina mulungu (highly active)
Eriocephalus africanus- herb
Marsilea minuta- leaves (also has anti-aggressive activity but acts on Serotonin-receptors)
Clerodendrum philippinum syn. C. fragrans- flowers (very active)
Abelmoschus moschatus- seeds
Mumio (Artsch- and Mineral)
Salvia rutilans syn. S. elegans- herb
Chondrodendron tomentosum- bark
Trichosanthes kirilowii- fruit
Albizia julibrissin- leaves, bark and flowers (very active)
Clitoria ternatea- leaves (very active)
Convolvulus pluricaulis syn. C. microphyllus- leaves (very active)
Piper methysticum- root
Sceletium tortuosum- herb

Some plants with compounds, acting on Benzodiazepine-receptors:
Salvia miltiorrhiza- root
Perovskia abrotanoides- leaves (contains Miltirone like Salvia miltiorrhiza)
Salvia canariensis- herb (Galdosol)
Hieracium pilosella- herb
Scutellaria laterifolia- herb
S. barbata- herb
S. baicalensis- herb
Hypericum perforatum- herb
Cyperus rotundus- rhizome
Sesbania grandiflora- flowers
Boerhaavia diffusa- herb (Hypoxanthine also regulates cortisol and because of this a stress-regulator)
Leptospermum scoparium- leaves and honey (Manuka)
Clitoria ternatea- leaves
Tilia tomentosa- flowers
T. platyphyllos- flowers
T. argentea- flowers
Scoparia dulcis- herb
Paeonia lactiflora- root
Paeonia moutan- root
Stachytarpheta cayennensis- leaves
Clerodendrum philippinum- flowers
Hypericum hircinum- herb
Rubus brasiliensis

... with actions on other GABA-subtypes:
Ziziphus spinosa- seeds
Z. jujuba. seeds and fruit
Valeriana officinalis- root
V. mexicana- root
V. celtica- root
V. wallichii- root
Nardostachys jatamansi- root
N. chinensis- root
Sclerocarya birrea ssp. caffra
Cissus quadrangularis- stalks
Angelica sinensis, polymorpha, pubescens- roots
A. dahurica (also acts on GABA-Transaminase)
Ligusticum chinense- root

Comparison of the binding affinity (IC50) on the Benzodiazepine-receptor:

Diazepam… 0,03-0,05 μM (Mindestdosis: 1-2mg)
Flurazepam…0,17 μM
Amentoflavone… 0,006-0,014 μM –Ki: 0,037 μM (main constituent in Dioon edule)
Agathisflavone… Ki: 0,028 μM (Biapigenine) …in Bauhinia vahlii, Rhus pyroides, ...
Xenovulene A… 0,04-0.05 μM (in the fungus Acremonium strictum)
Mayumbine... 0,076 ± 0,0035 μM (in Rauvolfia vomitoria and Corynanthe mayumbensis)
Miltirone…... 0,3 μM (part. agonist. diterpene from Salvia miltiorrhiza; NMDA-R.-Antagonist)
Skullcapflavone (Neubaicaleine)…0,36 μM (auch Ki) (a Flavon from Scutellaria baicalensis)
Phellopterine… 0,4-0,68 μM ~ 0,36 μM (a part. agonist. Furanocumarine from Angelica dahurica)
Hispiduline… 0,8-1 μM –according to other data 1,3 μM
Galdosol… 0,8 μM (a diterpenoide from Salvia officinalis and S. canariensis)
Chrysine (5,7-Dihydroxyflavone)… 2 μM (in Passiflora- species, Diazepam is only 40x as strong)
5,7-dimethoxyflavone… 2,1 μM (in Manuka respectively Leptospermum scoparium)
Wogonine…3-3,6 μM
5-hydroxy-7-methoxy-6-methylflavone... 3,3 μM (in Manuka resp. Leptospermum scop.)
Galangine-3-methylether… 3,5 μM (in galgant- resp. Alpinia galanga- root)
Isoginkgetine… 4-5 μM (a flavone from Ginkgo)
Ginkgetine (Amentoflavone-7,4'-dimethyl ether) … 5 μM (a flavon from Ginkgo)
7-Methoxyrosmanol …7,3 μM
Byakangelicol… 8 μM (a furanocumarine from Angelica dahurica)
Isoquercetine… 10μM
Baicaleine…10,1- 13,1 μM –Ki: 13,1
Imperatorine… 12,3 μM (a part. agonist. furanocumarine from Angelica dahurica and A.sinensis)
Oroxyline… 14,6 μM (also Ki) (in Scutellaria baicalensis)
Cirsiliol…Ki: 20μM at Typ I- BZD- R. (like Zolpidem and displaces Zolpidem)
Tanshinone IIA …20μM (from Salvia miltiorrhiza- root; and also an NMDA-R.-Antagonist)
Scutellarine…21 μM
Apigenine… 30 μMaccording to other data 3 μM (in camomile, parsley and many other herbs)
Carnosolic acid… 33 μM
Luteoline… 49 μM (in Passiflora incarnata, Scoparia dulcis, among others)
Carnosol… 57 μM
α-Casozepin… 88μM (in the casein-fraction of cow-milk)
Kaempferol… 93μM (Ki)
Baicaline…137 μM
Cirsiliol…Ki: 200μM
Acacetine… 3500μM
Epinepetalactone…? (Nepeta sibthorpii)
Ajmalicine (= Raubasine)…?
Cryptotanshinone…? (from Salvia miltiorrhiza- root; and also NMDA-R.-Antagonist)

Also very promising are the plant-compounds and endogene neurosteroids Allopregnanolone and Epipregnanolone, which act as very strong anxiolytics on GABA-barbiturate-receptors:
Allopregnanolone has strong narcotic, anxiolytic, antidepressive and socialising properties.
The sedative action of allopregnanolone through the barbiturate-GABA-receptor was only observed at low doses. High doses cause the opposite, which can create petulance by inhibiting GABA-receptors. Pregnanolones are much safer than barbiturates.

Allopregnanolone is found in the south-african plant Xysmalobium undulata (uzara- root), which is also used as sedative

The chaste tree (Vitex agnus-castus) contains a Allopregnanolone-precursor: Progesterone in its leaves:
The chaste tree is known as women's herb, but also for men it has healing and potential psychoactive (sedative, anxiolytic) properties. The plant has euphoriant, sedative, anxiolytic, aphrodisiac, antiinflammatory and analgetic actions.
The euphoriant action is mediated through dopaminergic diterpenes (rotundifurane, vitetrifoline, viteagnusine A), which also are responsible for aphrodisiac (hypersexuality) actions through agonistic actions on D2/D3- receptors. There was also found a definitive opioid action on mu-receptors.
The leaves (not the seeds) contain Progesterone, which is the precursor of the endogene neurosteroid Allopregnanolone in our body, which is the endogene neurotransmitter for the barbiturate-GABA-receptor.
The progesterone is active on itself, with anxiolytic actions among others. It is antagonistic on sigma-receptors.
The seeds of the chaste tree indirectly enhance endogene progesterone-levels.
Women use chaste tree- seeds for hormone-regulation.
The iridoids agnuside and aucubine have antiinflammatory, estrogenic and fungicide effects.


Gelsemium sempervirens
Posted Image
Posted Image
...is really a very dangerous plant, but as always its the dose which decides whether toxic or psychoactive / healing.
This climbing, aromatic plant is used in north- and central-america from indigenous peoples as narcotic. At higher doses it can cause hallucinations.
The main constituents, gelsemine acts pharmacologically contrary to strychnine and possibly could be used as antidote for it, because gelsemine acts also very potent on the glycine-receptors, but activating, while strychnine is a inhibitor on this receptors.
Newer studies reveal an interesting neuropharmacology: The activation of glycine-receptors with very small doses gelsemia-root promote the endogene allopregnanolone- production.
In my experience already a very small dose has pleasant relaxing and definite anxiolytic action. I used one tenth (1/10) of a tincture from safe 0,05g of the dried root.
BUT: The use (if at all) is only recommended with greatest precaution. It is really a very dangerous plant!

The benzodiazepines even were found in humans and plants:

Artemisia dracunculus (tarragon): 100-200 ng/g Delorazepam and 20-30ng/g Temazepam
Solanum tuberosum (potato)- herb: 60-70 ng/g Diazepam, 100-450 ng/g Temazepam and 0,06-0,97 ng/g Oxazepam
Triticum sp. (wheat): 1,6-4,4 ng/g BZDs (N-Desmethyldiazepam, Diazepam, Deschlordiazepam and iso-Diazepam)
human liquor: 1 ng/g Diazepam
human milk: 2 ng/g Diazepam
human serum: 0,001-0,032 ng/g N-Desmethyldiazepam, Diazepam and Oxazepam

To get one small dose delorazepam (0,5mg) one would need to extract 2,5-5kg tarragon-leaves...
To get one small dose temazepam (7,5mg) one would need to extract 16,6kg potato-herb...

Potent extracts of Papaver somniferum (not only opioid) and Nicotiana tabacum also show strong BZD-receptor- binding.

...a tryptic peptide from bovine α(s1)-casein also has benzodiazepine-like activity.
The precursor α(s1)-casein comprises approximately 40% of the casein fraction of cow's milk. Cow's milk also contains morphine, diazepam and opioid-peptides (caso-morphine among others) and has long been considered a tranquilizing beverage with a sleep-inducing and anxiolytic role.

The enzyme trypsin in the gastrointestinal tract hydrolyzes the α(s1)-casein to α-Casozepine, which significantly reduce epileptic symptoms, convulsions and anxiety. It has affinity for the BZD-subunit of the GABA-A- receptor.


#10 medievil

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Posted 08 March 2013 - 04:25 PM

Mulungu - Best sleep aid ever?

I tried mulungu for the first time recently, and I really enjoyed it! I purchesd some shredded bark at a local herb store which opened recently. I had been wanting to try it for a while, but it wasn't at the top of my list of things to order online. When I saw that it was available locally, I thought that I would give it a try.
For those who don't know, mulungu is a tree bark from south america, which is used as an anti-anxiety medication, sleep aid, and for relaxation. People have said that it is a good natural alternative to benzodiazepines like [color=#1B8EDE !important][background=transparent !important]valium[/background] or klonopin. I don't really care for those drugs, but do have problems sleeping periodically.
I did some brief research before brewing the tea. Dosage for the tea ranges from a gram or two to 10 grams. I weighed out 15 grams and added it to a pot of hot, but not boiling, water on the stove. I added some cinnamon, black pepper, cloves, and honey to improve the taste and hopefully potentiate the herb.
I split the tea into two cups, one for me, one for my brother. We started with a few sips each, and were pleasantly surprised by the mild taste. Within just a few minutes I was able to feel the tea, so I continued sipping until i finished half the cup. As we lay in bed watching a movie I felt blissfully relaxed and was content to lay there quietly. I ended up finishing my cup and basically nodding in and out out sleep for an hour or so until I fell completely asleep.[/color]
[color=#000000]The next day there was no residual ill effects, and I felt fine. I should add that I am on methadone maintainence, currently taking 85mg a day. I normally don't feel anything from this dose, but it may have added to the pleasurable effects of the mulungu. When I get paid, I will definitely be buying more of this stuff! Let me also add that even though I have a tendency to lack self control when it comes to drugs, I felt no compulsion to use the mulungu every day. I bought about 4 doses worht and consumed it over the course of a week. [/color]

Only posted half of what i want to post, good my brain is like a database lol, the dipyridamole cilltrex stack did wonders with learning stuff fast.

#11 leftside

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Posted 08 March 2013 - 05:35 PM

I also like Mulungu. I've only tried the extract. I'll have to get some of the herb and make a brew of 100g using my slow cooker.

#12 Multicultural Harmony

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Posted 26 November 2013 - 06:00 AM

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#13 Galaxyshock

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Posted 12 March 2024 - 06:42 AM

Bump to this thread. Was thinking about starting my own, but this appears a good starting point. It's been over 10 years, so I wonder what effective anxiolytics do we have in 2024?


Targeting the cannabinoidergic system seems like a very potential avenue. I'm looking at FAAH-inhibitors. I heard about URB597 getting a group buy done by some fellas but I haven't heard of anecdotes.


URB597(KDS-4103) is a relatively selective and irreversible inhibitor of the enzyme fatty acid amide hydrolase (FAAH).[1][2] FAAH is the primary degradatory enzyme for the endocannabinoid anandamide and, as such, inhibition of FAAH leads to an accumulation of anandamide in the CNS and periphery where it activates cannabinoid receptors. URB597 has been found to elevate anandamide levels and have activity against neuropathic pain in a mouse model.[3]

Preclinical studies have shown FAAH inhibitors to increase BDNF levels in the hippocampus and prefrontal cortex,[4] highlighting their potential in addiction treatment as "enviromimetics".[5] Indeed, Chauvet et al. found that chronic URB597 administration in rats "significantly reduces cocaine-seeking behaviour and cue- and stress-induced relapse".[6]

URB597 was at one point being developed by Kadmus Pharmaceuticals, Inc. for clinical trials in humans.[7]

→ source (external link)


Other targets of my interest:

  • metabotropic glutamate receptor antagonists / negative allosteric modulators
  • GABA-B positive allosteric modulators
  • Neurosteroids
  • Delta-opioid receptor agonists
  • substances that decrease neuroinflammation

And yeah let's not forget herbs, Magnolia bark indeed felt like a dose of a benzodiazepine without side effects, perhaps something I should give a new shot.

Also tagged with one or more of these keywords: anxiolytics

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