18 replies to this topic

[Heisenburger]

I’d like to compile a list of anxiolytic substances that have no addictive potential, but actually have some tangible effect. Here are the ones which I have tried, and the effects I’ve observed from taking them:

 

Tofisopam—an obscure and difficult to obtain benzodiazepine. From what I’ve read, it is only marketed in Bulgaria, but may be available in other Eastern European countries. It has two unusual properties: it is the only benzo that currently exists that has stimulant properties, and according to Wikipedia, is believed to be completely non-addictive (although the wiki article says that more research is needed in this area). I’ve taken it about 50 times, and it definitely does have a reasonably strong effect. Another unusual property of this drug is that effective doses are in the 100-milligram range, as opposed to traditional benzodiazepines in which a standard benzodiazepine equivalent is in the 0.5 to 1.0 milligram range. A benzodiazepine equivalent is the amount of a substance that produces a response equal to 10 milligrams of diazepam.

 

Hydroxyzine—an antihistamine that has stronger sedative effects than other antihistamines such as Benedryl or doxylamine. Judging from anecdotes posted on anxiety forums, most people don’t get much effect from it, if any. A few fortunate individuals have a strong anxiolytic response to it. I appear to be one of these fortunate few, as I’ve found it be a reasonably effective anxiolytic.

 

GTS-21 My personal favorite, and a compound which I currently believe is the strongest anxiolytic I’ve ever taken that does not have any psychoactive effect. Its major drawbacks are its price and the fact that only a handful of nootropics vendors currently carry it in stock. In my personal experience though, a 100-milligram dose has such a strong anxiolytic effect that I would easily equate it to two milligrams of Valium or a pediatric dose of Xanax.

 

I’ll add other random thoughts and observations as I think of them. Can anybody add to this list with compounds that they have personally had experience with?

[Avocet]

Interesting - thanks for sharing.

 

Would you say any of these would be helpful for insomnia?  I'm waking up every morning at 3am with horrific anxiety and can't get back to sleep.  I like the sound of the GTS-21 - is this freely available?

[psychejunkie]

Buspirone --- a 5HT(1)A partial agonist and D2, D3, D4 antagonist which usually used as Anxiety Disorder medication. Specially if combined by Melatonin Extended-Release. It also have Anti-Depressant effects after 5-6 weeks of treatment.

[psychejunkie]

Interesting - thanks for sharing.

 

Would you say any of these would be helpful for insomnia?  I'm waking up every morning at 3am with horrific anxiety and can't get back to sleep.  I like the sound of the GTS-21 - is this freely available?

 

Hydroxyzine helps with Insomnia, OTC and easy to get.

Buspirone + Melatonin TR is what I take often before bed; this combination has both anxiolytic and sedative effects.

 

Edited by psychejunkie, 19 June 2016 - 08:59 AM.

[Heisenburger]

Would you say any of these would be helpful for insomnia?  I'm waking up every morning at 3am with horrific anxiety and can't get back to sleep.  I like the sound of the GTS-21 - is this freely available?

 

I don’t think any of the three things I listed would help you much—they’re just not strong enough. That’s the problem with anxiolytic medications—the ones that work well are all hideously addictive, and the ones which are not hideously addictive don’t work very well. They just sort of ‘take the edge off’ instead of squashing anxiety like a bug like benzos do.

 

GTS-21 is expensive and difficult to obtain. There are only three companies that I am currently aware of who sell it: reChem in Canada, Transhuman Technologies, and Cerebral Health. I recently spearheaded the first group buy of this substance here on this message board, and it sold like hotcakes. I bought 50 grams from a Chinese manufacturer and sold almost all of it the first day. If there’s enough interest, I might be willing to do it again, but so far only a couple of people have contacted me asking for more.

 

I use etizolam for insomnia, as it seems to be the least of all evils. It’s an addictive benzodiazepine analog, but the nice thing about it is that it is much, much harder to get addicted to than traditional benzos such as Valium and Xanax. You can go a lot longer before addiction kicks in, and the withdrawal is not nearly as bad as benzo withdrawal. I take it almost every night, along with glycine, prazosin, and melatonin. The combination of these four compounds together is a very effective cure for insomnia. Last year I experienced a blessed period where I actually went almost two whole months without a single nocturnal awakening, which based on my history is absolutely astounding. That has never happened to me before in my entire adult life.

 

Maybe hydroxyzine would help with your insomnia. Unfortunately it’s prescription only in the United States. Recently my anxiety got so bad it was impacting my performance at work, so I had no choice but to go seek medical treatment. Having just moved to a new city, I didn’t know where to go so I just Googled for the nearest urgent care and went there. I suggested a three-week supply of Xanax and one of the SSRIs which have demonstrated benefits for anxiety such as Paxil or Cymbalta. No dice. All I got was “we don’t prescribe benzodiazepines or antidepressants here, but here’s a piddly amount of hydroxyzine and a referral to a clinical psychologist.” So that was a complete wash. But at least the hydroxyzine helped. It actually worked fairly well. But I’m not going to go back there again and plunk down $134 just to have my intelligence insulted and be given another six-day supply of the stuff. AllDayChemist has it for 13 cents a tablet; I’ll just buy more from them. Before I moved to this new city, I had a wonderful urgent care facility that I had been going to for years. They were the cheapest in town, and they had no problem giving me reasonable amounts of Xanax. They could see from my refill history that I wasn’t abusing it, so they never batted an eyelash when I asked for more. Hopefully I can find somebody like that where I live now.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

[Heisenburger]

I’m looking into an experimental drug called Aloradine. Somebody sent me a PM about it last night, and from the link he sent me it seems to have real promise. I’ll read up on it and see what I can find out. If it looks like something worth pursuing, maybe HHD can synthesize some for us.

[Heisenburger]

I mentioned to the person who told me about Aloradine that I am beginning to despair that an effective but non-addictive and non-psychoactive anxiety drug will ever be developed within my lifetime. It’s going to be such a tough nut to crack that I believe that we’ll have humans on Mars before it happens. I found this very lengthy paper (it’s a .pdf) on the subject of anxiolytic drug discovery which details the progress that science has made in this area during the past half century:

 

50 years of hurdles and hope in anxiolytic drug discovery

 

So far I’ve just skimmed it, so I’m not in a position yet to say whether it backs up my assertion or refutes it, but I’m hoping it will refute it. I’d like to believe that that there’s reason for optimism. Meanwhile, the hydrozyzine is still working well. I’m trying to decide right now whether or not to try the polypharmacy approach and use all three drugs simultaneously. If I do, I’ll report back in a couple of months with the results and my subjective impressions.

 

[Reformed-Redan]

I’m looking into an experimental drug called Aloradine. Somebody sent me a PM about it last night, and from the link he sent me it seems to have real promise. I’ll read up on it and see what I can find out. If it looks like something worth pursuing, maybe HHD can synthesize some for us.

That's interesting. I've been researching 3β-androstenol and think it's a good candidate to look into. But, is hard to get.

 

PEH is another option I've been looking towards for a while already.

 

Cheers.

[Heisenburger]

PEH is another option I've been looking towards for a while already.

 

What is PEH? I’d like to see what I can find out about it.

 

Edit: Phenylethylidenehydrazine, the primary metabolite of Nardil. Yes, looks like it could be an astonishing thing, but I’m getting conflicting information about it. Strangelove mentioned it in a PM to me a few months ago. The conflicting information I’m seeing is about how hard it is to synthesize, with some people saying it’s an easy synth, and some people saying that it’s such a difficult synth that that’s the only reason it isn’t already available. What’s the straight dope on the matter? Somebody (can’t remember who) told me that he had contacted Wuhan HengHeDa about it, but they said that it was too difficult for them to pull off. So the only option right now is to take the parent molecule, but the side effects are so horrific that most people would prefer to drink straight bleach than ingest Nardil.

Edited by Heisenburger, 24 June 2016 - 10:15 PM.

[Reformed-Redan]

 

PEH is another option I've been looking towards for a while already.

 

What is PEH? I’d like to see what I can find out about it.

 

Edit: Phenylethylidenehydrazine, the primary metabolite of Nardil. Yes, looks like it could be an astonishing thing, but I’m getting conflicting information about it. Strangelove mentioned it in a PM to me a few months ago. The conflicting information I’m seeing is about how hard it is to synthesize, with some people saying it’s an easy synth, and some people saying that it’s such a difficult synth that that’s the only reason it isn’t already available. What’s the straight dope on the matter? Somebody (can’t remember who) told me that he had contacted Wuhan HengHeDa about it, but they said that it was too difficult for them to pull off. So the only option right now is to take the parent molecule, but the side effects are so horrific that most people would prefer to drink straight bleach than ingest Nardil.

 

It's a hard synthesis. I believe the purification of the compound is the hardest part. That's what I got from THT when I requested that they synth it.

 

Anyhow, what about Sleank or Proproten? Those are pretty effective, especially the Tenoten.

[Reformed-Redan]

Have you tried Bromantane or Tianeptine? Since your a responder to GTS-21, and since GTS-21 likely normalizes (potentiates) NMDA currents along with DA normalizing activity (PAM) through a7n receptors, I think tianeptine might be worth a shot.

 

Also, Nardil isn't that bad. It's a gold standard for social anxiety for a reason.

[Junk Master]

Honestly, if you are having that much trouble with anxiety (and I've been there, believe me...), you might want to consider long term Phenibut use.  You seem like the kind of responsible person who will not redose and is not seeking a "high," and in my case I've found no need to increase my phenibut dose past 500-750 mg per day over a two week period, then have had no problem with tapering off for months at a time.  At the very least, 500-750 mg of phenibut on an occasional basis absolutely obliterates social anxiety for me without causing sedation.  I've also never had the same "high" from taking it that I did the very first time and am actually thankful for that!

 

Granted, Phenibut is not a substance to be taken lightly, and I'm aware of all the horror stories out there etc.  But it is dirt cheap and OTC.

 

Another option IMO would be a very low dose of Clonazepam.  I can take .5 mg a day for a week or two and only experience a day or two of insomnia upon cessation.

 

Keep in mind, however, I was also able to quit every single SSRI I've tried cold turkey with very few sides, and was also able to quite Effexor and Pristiq without nary a brain zap...

 

What I do know is long term social anxiety is a huge detriment to energy and cognition!  Those who have never experienced it long term have no idea just how draining, and how enervating it can be.

 

As always, I wish you the best of luck!

[Heisenburger]

Interesting experience last night: my anxiety has been completely under control for about two weeks now. I’ve been taking three 25-milligram tablets of hydroxyzine a day, very small amounts of an obscure benzodiazepine called flutoprazepam, and limiting my coffee consumption to no more than 24 ounces of standard-strength coffee per day. (I should clarify; flutoprazepam is obscure in the United States, but not in Japan, where it is where it is a common and highly sought-after drug.) Anyway, last night about 10 o’clock I suddenly felt a resurgence of my anxiety. I found this puzzling at first, since I had been so successful at keeping it under control. But then I discovered that I had forgotten to take my afternoon (second) dose of hydroxyzine. The stuff really works, at least for me. I’m fortunate that it does work for me. I have two coworkers who also have anxiety disorders, and both of them have been prescribed hydroxyzine to treat it. Both of them have reported that it had absolutely no effect on them at all.

[Mind_Paralysis]

I'm surprised that no one's mentioned it yet, but SNRI's were recently found through meta-reviews, to actually be the best anxiolytic medication in common use - it even trumps benzos after a certain time-threshold!

Here, have a look at this:

www.ncbi.nlm.nih.gov/pubmed/25932596

Depending on your neural profile I'd recommend either Duloxetine or Venlafaxine - the proof is in the pudding.

[Agent0023]

Selank.

 

Wikipedia: 

 

"In clinical trials, the drug has shown to provide a sustained nootropic and anxiolytic effect which is useful for the treatment of generalized anxiety disorder (GAD).^[1] Selank has an advantage over traditional anxiety treatments, such as benzodiazepines, as it has no sedating or negative cognitive side effects and no associated addiction or withdrawal problems."

 

Peptides are very different from neurotransmitter modulating drugs.  The effects can be very long lasting after a short course of use.

 

nootriment.com

What is Selank: Research into this Novel Nootropic Substance

Alexandr

Selank is one of the newer Nootropic substances to hit the market in recent years. It is considered to be heptapeptide and an accessory drug or substance which has anxiolytic (anti-anxiety) effects.

This supplement was developed at the Institute of Molecular Genetics of the Russian Academy of Science.

There is quite a buzz about this new drug for a number of potential benefits that could have a wide range of applications and uses. At the present time, Selank has completed stage III clinical trials in Russia and is awaiting the go-ahead for release to human use.

Selank is an analog of the spleen-produced peptide (peptide simply means a string of amino acids connected together) known as Tuftsin. This peptide is also considered to be immunomodulatory, or capable of improving and changing the immune system (for the better).

It is also closely related the prescription drug Semax, which was produced by the same institute and is currently approved for human use in Russia and Ukraine. There are a number of user and researcher reports indicating that Selank is a more effective alternative.

Edited by Senolytic Agent 0023, 18 July 2016 - 03:56 AM.

[Heisenburger]

I’ve found a new one—CBD oil. Don’t laugh; this stuff really works. The only problem is that I have to take a lot of it to see any effect, and that can get pretty expensive. But it has enabled me to sleep almost normally for four consecutive nights, which is pretty remarkable since I have been suffering from chronic insomnia for several weeks now. It is completely non-psychoactive; you can take it and go to work if you want to. It is also fantastically safe—they’ve done studies using children as test subjects. It produces a very nice sense of deep calmness, and about four hours later produces natural-feeling drowsiness followed by restful sleep. I’ve been taking it for several days now, and I would definitely recommend that anybody who suffers from anxiety and/or insomnia give it a shot.

[Agent0023]

Yeah golly CBD oil is expensive! CB2 stimulation by other means interested me and other herbs are cannabinergic and less costly. Clove oil, with it's caryophyllene content (1.7–19,5%) is an alternative and usually available on any pharmacy dental care shelf. Other essential oils contain this and cannabis-type terpenes and may be worth experimenting with. Ultrasonic essential oil diffusers can get the oil into room air. I've tried this. So far I see no downside, but without even a buzz to judge from it's hard to know how effective.

[Junipersun]

I'm also on the hunt for an effective, sustainable anxiolytic. My next trial will be Parnate, as the positive reports for social anxiety are remarkable. Also, I have some comorbid depression which is should help greatly. For now I think there is no single effective treatment for my anxiety which won't cause tolerance and addiction. So there are two options: Combine not-so-effective anxiolytics to get some synergistic effects. Memantine seems to work a bit, I'll maybe add kava kava extract and rosmarinic acid (a gaba-transmirase inhibitor). The second option is the old druggies dream: Receptor hopping. That means switching between effective anxiolytics/different mechanism of action on a daily basis. Kratom, Pregabalin and Benzos come to my mind. Still some days left for a week...

[fntms]

For those who react well to CBD oil, it might be worth trying palmitoylethanolamide (PEA), which acts on the same endocannabinoid receptors (but on more of those receptors, and more 'cleanly' cf peacure website for what it's worth, their product is good, I didn't check their science in detail, but PEA has been scientifically tested for pain management and depression also I think).
I have been taking 1.2g or so from different sources for a few weeks and I am now getting nice anxiolytic effects and improved sleep, as well as overall better mood with no noticeable side effects. I have even stopped tianeptine which was giving me too much stimulation and aggression (at least with the sulfate powders, even at low doses).