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Hi there,

Well there's a legal Benzo where I live called Etizolam, which is technically not a benzodiazepine but a thienodiazepine, basically where the benzene ring of the molecule has been replaced by a thienophene ring.

From what I've read it is more selective to the alpha 2 subtype of the GABAA receptor, which means it should be more potent as an anxiolytic.

I have only tried it once but in EEG scans it has shown characteristic effects of tricyclic antidepressants, and has been reported to increase serotonin levels or possibly even act as a serotonin releasing agent, although this isn't confirmed i don't believe.

The fact it shows tricyclic antidepressant effects which means possible serotonin increase makes the therapeutic benefit in HPPD somewhat negligible I feel. Although increasing serotonin has helped some of our members so it depends on the person I guess.

Some interesting things ive found are:

No cognitive defects were reported in a 3 week dosage of 0.5mg a day compared to placebo, which is unusual for a benzo.

When multiple doses of etizolam were administered compared to lorazepam, lorazepam caused down regulation of alpha1 GABA sites whereas etizolam caused an increase in alpha2 GABA subtypes, almost reverse tolerance.

No tolerance to the anticonvulsant effect of etizolam was reported with long term administration compared to other Benzos.

Quote: 1. Patients with generalized anxiety disorder were either treated with Etizolam (0.5 mg), Alprazolam (0.5 mg), or Bromazepam (3 mg) twice a day. While all three drugs retained their effectiveness over 2 weeks, etizolam actually started to become more effective than the other benzos from to 2 weeks to 4 weeks (reverse tolerance in a way). The researchers also note antidepressant activity in etizolam not seen in the other two drugs tested.

This should mean in theory that Etizolam should cause less addiction and dependence, and due to reverse tolerance effect actually increases alpha2 GABAA subtypes, making more of the receptors available I believe.

It's an interesting thienodiazepine nonetheless.

One thing I will say is that the time I did try Etizolam i felt a lot more normal, more sedated than I usually would but a lot more normal. Cognition was actually improved dramatically, and it reduced visual snow by around 75 percent from a 1mg dose. Interestingly it didn't affect trails and tracers (possibly due to seretogenic activity) but completely removed after images. There was a definite lessening of DP/DR too, although I noticed colours looked more vivid on Etizolam for some reason.

This may be an excellent alternative to Clonazepam for some sufferers. Main metabolite has a half life of just under 9 hours.

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  • 4 weeks later...

No problem, it's strange isn't it! I can definitely vouch for that effect though as the more I've taken it the more effective it has become. The withdrawals are much gentler than other BZD's according to reports too.


Yeah it worries me a little too, although I've not been able to find any information on how this effect is mediated at all, which would be interesting to know.

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Have you seen any thorough reports of etizolam withdrawal (or lack thereof). Most I've seen were from relatively short-term use and thus fairly inconclusive.

I don't wish to get into a habit of using benzodiazepines (or analogues) on a daily basis, but it's always nice to as much as possible about the compounds one ingests (even if just as a means of convincing oneself not to over-indulge).


Personally I find that oxazepam is quite useful as an occasional anxiolytic (however the onset of action is impractically long, more than an hour) while alprazolam is of almost no use for me. I can feel anxious on alprazolam while being sedated and lethargic. As far as I know, this is quite uncommon(?). Oxazepam seems to relieve my visual symptoms a little, while alprazolam does absolutely nothing in this regard.

Next on my list to try are etizolam and clonazepam, in that order.

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On a slightly related note (sorry for derailing the thread slightly), I've stumbled upon what seems to be the holy grail of benzodiazepine pharmacodynamics, an article named An Updated Unified Pharmacophore Model of the Benzodiazepine Binding Site on ɣ-Aminobutyric Acida Receptors: Correlation with Comparative Models. I was able to download the full-text article with my university library account.


To moderators: I'm unsure if I'm allowed to share it here per the forum rules. If not, please delete the following link.

An Updated Unified Pharmacophore Model of the Benzodiazepine Binding Site on ɣ-Aminobutyric Acida Receptors: Correlation with Comparative Models

It would seem that some concentrated structure/activity analysis could lead to novel selective benzodiazepine agonists with less side-effects (I'd say that hypnotic action and memory impairment are clearly undesired side-effects in an anxiolytic or anticonvulsant medication! :-) )

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(unimportant rambling)

I apologize for spamming this thread somewhat, but novel, selective benzodiazepine agonists are highly interesting to me. Though I don't have a regular benzo habit - I try to keep it to approximately once per week, and I've never exceeded the equivalent of 10mg diazepam at any one time. I have, however, found them indispensable for stressful situations such as teaching and family get-togethers as my anxiety and feelings of "dissociation" spike in these situations.

(end unimportant rambling)


From reading the Etizolam Experiences thread over at drugs-forum (and a similar thread at a Danish board) I've noticed that experiences differ widely with regards to the degree of sedation and hypnotic action of etizolam, though there seems to be a consensus that it is strongly anxiolytic. There seems to be some disagreement with regards to development of tolerance as well, with some users reporting requiring a quick escalation in dose.


Another point of disagreement is the degree of selectivity of etizolam. Wikipedia states:

"Similar to other benzodiazepines, etizolam binds unselectively to benzodiazepine receptor subtypes."

However, the reference for this claim is the following article: Pharmacological characterization of the novel anxiolytic beta-carboline abecarnil in rodents and primates. Upon skimming this article I'm unable to find any justification for the statement - if anyone else feels like looking through it I would be much obliged :-) 

I'm very skeptical about such a statement until I see some actual receptor affinities, since complete non-selectivity is, to my knowledge, highly unusual. This would, as far as I understand, mean that the equilibrium constant for the formation (or dissociation) of etizolam+receptor complex had to be the same for all receptor subtypes, which I find find highly improbable from a purely steric point of view, so to say. I may be wrong, however, since I have not studied pharmacology!

Sam93: Do you have a reference for your claim of αselectivity?  I'd be very interested in collecting some sound pharmacological data on etizolam (and perhaps other benzodiazepine agonists), with the assistance of anyone who wants to chime in :-)

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It is? I can access it just fine - that's strange. 

I'll skim it through tomorrow.. though BZD's are not my specialty, so to speak :)

Thanks! Only do it if/when you feel like it, mate :)

I'm at a friend's place - he's asleep by now, and I'm studying benzodiazepine receptors on a chocolate high :D I probably should be getting home...


On a slightly related note, it is a shame that abecarnil is so hepatoxic. It seems like such a perfect candidate for a non-sedating, non-hypnotic anxiolytic. It is apparently a highly selective benzodiazepine agonist exhibiting much less potential for physical dependence and withdrawal symptoms. In fact there are several candidates for HPPD-friendly benzo work-alikes. Ideally, the way I see it, we would have a benzo that is non-sedating and non-hypnotic while retaining anxiolytic and anti-convulsant activity (clonazepam is generally accepted as a good anti-convulsant benzodiazepine, I would think that this is part of the reason why it is the preferred benzodiazepine for many HPPD sufferers).

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I'm confused... How do they derive a statement for Etizolam from an article about Abecarnil?
edit: Yeah I can't find any justification for that statement from that article either.. Also checked what beta-CCE and ZK-93426 were, but they're not Etizolam. Maybe hit up wiki and change to "citation invalid" or something?

BTW the link only works if you're coming from the youknowwhere website. Try this instead for those who can't access it.

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Thanks for reading it :-) I can see a few statements in the article which could be misinterpreted if one were very sloppy, especially the part where they speak of selectivity towards BZ receptors in the cerebellum as opposed to those in the spinal cord.

In fact, the way I read the article, there is some indication that etizolam induces much less motor impairment at effective doses. Look:
"Abecarnil did not induce any impairment of the motor performance of mice in the traction test up to 100 mg/kg, p.o. (Fig. 6). On the other hand, the tested BZs impaired the motor performance, giving rise to the ED50 value of 20 mg/kg, p.o. for etizolam, 9.1 mg/kg, p.o. for diazepam and 8.4 mg/kg, p.o. for clotiazepam"
The ED50 is the dose which induces a given effect (here; motor impairment) in 50% of the population. We see that more etizolam, compared to diazepam, is required (in mice) to induce motor impairment. This is quite significant, seeing as how etizolam is clearly a much more potent anxiolytic than diazepam, meaning that it would presumably induce very little motor incoordination at therapeutic dosages. Not that I ever personally found this to be a big problem at therapeutic dosages of benzodiazepines, anyway, but it seems indicative of selectivity.

Yeah, I probably should update the wiki article. A shame it has already been quoted so many places on the web. Also, note how the quote begins "Similar to other benzodiazepines...", implying that etizolam is a benzodiazepine.

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And thus the drawbacks of Wikipedia become apparent :)
What you quoted does indeed suggest that Etizolam has focal effect. How this correlates to receptor binding specificity/selectivity, I'm not sure. i.e. Because there's more Etizolam needed to induce motor-impairment, needn't necessarily equate to selectivity.. Couldn't it be a matter of (dynamic) binding affinity possibly with some wicked dose-dependent effect curve (thinking back to Piracetam here)? Not too sure on this though, and less about whether it makes sense at all, haha! Just saying: other things could be at play. After all, certain subtypes  are more abundant in certain areas than others, etc.etc.etc. yet that type of information (distribution of receptors and their subtypes in specific regions) is particularly hard to find, especially subtypes. Or so I've found it to be in my searches (believe I was trying to find out about the distribution of the M1 mAChRs). In any case.. yeah I'd just stay away from obscure benzo's regardless haha! But that's just me. Then again, finding a better alternative to Clonazepam (which seems to be used by many if not most HPPD'ers) is definitely necessary. 

Haha just some thoughts, don't know if they're accurate. I haven't gone that in-depth on this particular subject as you have. Also, you know, the fogging fog!
And yes indeed, removing the word "other" from that sentence would resolve any possible implications of the sorts.

I'm not that up-to-date on stuff lately though. Figured I would take a break after the Coluracetam document (fucking drained my brain that stuff), so I did.
What say you on other Clonazepam alternatives?

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I'll probably respond to your post little-by-little (feeling a little low on energy at the moment - I'm trying out the beta blocker propranolol (for "mini-panic attacks"), something I'm likely to start a topic about at some point :) ).


Dynamic binding affinity; Are you talking about dose-dependent changes in affinity? I must admit that this is not something that I'm familiar with  - what would be the mechanism? :-)

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I'm gonna be quite frank here: I had very little of a clue what the hell I was talking about haha!
But it wouldn't surprise me if dynamic binding affinities can happen. Point was more that there could be more in the process involved than solely selectivity. Wouldn't know the mechanism of that though! Just a thought.

Ahh good luck on the propranolol   :) Should be somewhat helpful I suppose.

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My train of thought was this:

Imagine for a moment that etizolam has no affinity for non-benzodiazepine receptors. We know that different aspects of benzodiazepine activity is mediated through different receptor subtypes. If etizolam exhibits an effect profile which is different from largely non-selective agonists, then it must be selective, by one mechanism or another. Whether it is ''tissue-selective'' (my own word... i.e. binds to benzodiazepine receptors in certain areas of the body) or subtype-selective is not so clear. Perhaps my reasoning is flawed?


The fact that etizolam seems to have some monoaminergic effects as well complicates the situation, needless to say! :)


Off topic

(wrt propranolol: Yes, this is my second day of low-dosing (5mg). It seems to be pretty efficient at lessening anxiety spikes. It doesn't do anything for baseline anxiety, but simply knowing that I'm not going to panic is somewhat comforting.)

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Hi there,


I found that information in a study, it is saved on my computer somewhere but I don't have access to my computer at the minute so I'll have to copy a brief portion found on google.


However, the major difference [between other benzos] is in selective and high affinity binding to the alpha2 subunit of postsynaptic GABAA receptor subtype. This alpha2 subunit activation results in specific anxiolytic effect. Further, [etizolam] is suggested to possess less potential for causing "rebound anxiety" on drug withdrawal because it does not cause alpha4 subunit upregulation as compared to lorazepam. (I'll get the proper study to you when I have my laptop back :) )


I'm not too sure what is meant by pre and post synaptic receptors. I have a rough idea but perhaps somebody would be so kind as to tell me, for instance, what the difference would be in blocking pre synaptic / post synaptic calcium channels?


There is sound evidence however, that etizolam upregulates alpha 2 subtypes, so maybe this was mistaken for Etizolam being more selective for A2 when in actuality the A2 subtypes were simply getting upregulated with use.


What I'd like to find out, and what has not been studied, is the fact that Etizolam shows TCA properties. How would a Benzo raise levels of SE and NE? I know Clonazepam reduces the binding affinity of 5HT so I suppose it's not impossible.


It's a very interesting compound anyway. I use this as I find it much more effective than Clonazepam, and there is a distinct mood lift not seen with other Benzos in my experience. In addition, I have had no issues with tolerance and have never had to raise my dose any to achieve the same effects.


I used it for a solid week once and it definitely became more effective the more I used it, so the upregulation of A2 receptors must have something to it.


Sorry if this post didn't make much sense, I'm a bit tired haha.

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Tired here as well, but IIRC generally speaking post-synaptic receptors are for furthering the signal transmission, whereas pre-synaptic receptors are for "keeping score"/feedback which then continues to regulate the production of the agonist. Thus, blocking presynaptic receptors would... *crank* upregulate production of the agonist/transmitter, and blocking postsynaptic receptors would impede signal transduction cascade or whatever the fancy you'd like to call it :) And the latter might also cause for receptor (density) modulation over the long-term.

A bit vague, sorry!

Note: Don't quote me on this.. This is just off the top of my head, which needless to say may be distorted information haha!

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Oh by the way StateOfRegret, if you're interested in a purely anxiolytic benzo with no sedation then look at Pyrazolam. It's almost purely an anxiolytic with anticonvulsion action too. If you look at the binding chart it is extremely selective for a2 and a3, particularly a2. It is also completely legal, in the UK anyway.


I've tried this myself.


Pyrazolam is a benzodiazepine derivative originally developed by a team lead by Leo Sternbach at Hoffman-La Roche in the 1970s.[1] It is mainly an anxiolytic, but it has also shown anticonvulsant and hypnotic effects.[2] Pyrazolam has no active metabolites[3] and has activity 12x stronger than diazepam while causing little ataxia and sedation. It is most selective for the α2 and α3 receptor subtypes.[4]

Binding data (GABA):[citation needed]

α1 3.84±0.25 α2 1.31±0.19 α3 1.48±0.21 α5 3.72±0.32    
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Somewhat off topic:
A very interesting model of nerve signal conduction (
the Soliton Model) is being developed at the Niels Bohr Institute of Theoretical Physics (where I study) which proposes that nerve signals are actually propagating density pulses associated with (as I understand it) some sort of phase transition. This model seemingly solves numerous problems with the "electrical" model of signal conduction and explains the (previously poorly understood) mechanism of action of numerous anesthetics.

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My experience was great, it is the only chemical I've ingested post-hppd that had a definite lessening effect on my DP/DR. Visuals were reduced a little and it completely eliminated any anxiety, it was impossible to get anxious actually.


It didn't feel like I took any thing at all, I just had no anxiety whatsoever, however, it did make me a little more nasty toward people which was a weird side effect.


And I'd assume that due to it's short half life (6 hours) and high binding affinity to a2 subtypes it would be very likely to cause rebound anxiety, this would be one to take sparingly in situations where one is likely to suffer from anxiety.


Etizolam is definitely the more interesting one. I swear by it. The only problem with it is if I take over 2mg (which reduces visuals and makes me feel quite normal) I just fall asleep.

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Thanks for sharing! The amnesic and hypnotic effects is my biggest "issue" with benzodiazepines (that and their tendency to cause dependence and withdrawals in the long run), since I'll mostly be using them for stressful situations at university such as teaching, presentations and days where my HPPD and associated anxiety is worse, for whatever reason. But being on the verge of falling asleep or forgetting things is, unfortunately, pretty unacceptable in those situations.

Oxazepam has had very few of those side-effects for me (I do not know why this is) while alprazolam is almost useless for me, since it doesn't relieve my anxiety very effectively and makes me very, very drowsy. I've even experienced worsened HPPD symptoms on alprazolam to the point that I was relieved when it stopped working!

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Etizolam definitely posesses hypnotic effects, however if I'm concentrating on something or socialising then those effects don't come into effect. It's when you have nothing to do that the hypnotic effects become noticable. That's only when I take 2mg however.


1mg of Etizolam is VERY nice though. Reduced visuals, completely eliminated anxiety and a huge relaxing mood lift, without the brain fog, confusion and 'flatness' of other Benzo's. Actually looking back I've been quite productive on Etizolam at times. Also the big one for me, no benzo hangover whatsoever and actually has a nice, warm, mood lifted afterglow. It is unlike any benzo or sedative I have ever taken.


The reports of tolerance usually stem from people of quite an abusive nature who really over do it. As can be seen from studies, there is reverse tolerance to the anxiolytic effects, or if you prefer, upregulation of alpha2 subunits, there is also no tolerance to the anticonvulsant effects as opposed to other benzodiazpines, and no cognitive decline associated with Etizolam. 


I'd rate it much higher than Clonazepam for sure.


Another note on the tolerance/addiction issue, I took Etizolam for 2 weeks straight, 1 to 2mg every day with no tolerance whatsoever, then for the next 3 weeks I took it maybe 3 or 4 times a week at the same dose, then stopped abruptly for over a week with no withdrawals or rebound anxiety whatsoever. I now take it once or twice a week with no problems.

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Wait.. forgive me if this sounds stupid, but is that in other words proposing that nerve signal transduction/conduction/propulsion/tranmission/whatever is mediated via some form of peristaltic movement?

odisa: Sorry, I didn't see your reply before :-/ But no, I don't see how you get the idea of peristalsis being involved. What you should imagine is, I believe, fluctuations in the density of the axon material propagating along the nerve fiber. No actual bulk movement of material is necessary for this density "pulse" to propagate. But once again, I haven't really studied the soliton model, and I have no knowledge of biophysics in particular  :-)


Sam93: Was 1mg your usual dose? I just took a little less than 0.5mg ~90 minutes ago, and I'm not feeling any different as far as I can tell. Less than with 7.5mg of oxazepam for sure.

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