Benzos How different are the (non)benzodiazepines from each other in terms of subjective effects?

[Sheeno101]

The main difference highlighted is often their strength and duration of action, but I'd be interested to know if people view their effects as distinct from each other or just different shades of the same drug.

The main reason I'm asking is that I have terrible sleep problems, and would love a drug to help me sleep every now and again. I've tried two benzoes on different ends of the spectrum, alprazolam and diazepam, and both make me feel tired and help me sleep, but invariably make me feel awful and slow the next day, so much so that I usually wish I'd not taken them and thus barely slept at all. Alprazolam particularly I've used a lot, as I have it in liquid form, and so have tried doses as low as 0.1 mg (the smallest dose I can take without having strong negative consequences the next day; even 0.3 mg will leave me feeling bad). Many describe alprazolam as the least likely to leave a hangover due to its short duration, but that is not the case for me. I've had much better luck with phenibut and GHB as sleep aids, but the former's duration is too long and the latter I don't often have. They at least allow me to feel refreshed the next day though, unlike these benzoes which might be even worse for my sleep architecture than antihistamines like promethazine.

Anyway, I was wondering if there's any point in my trying some new benzoes or nonbenzoes to see if any don't make me feel so bad the next day. I haven't tried any of the Z-drugs, so they are intriguing. Similarly, there are all these benzo-like drugs nowadays (e.g. etizolam) which I'm wondering could bring me more luck than alprazolam or diazepam. I don't know whether to view them all as unique drugs, or to decide that the world of allosteric GABA modulators probably isn't for me.

 

[Hodor]

Thienodiazepines like etizolam produce almost exactly the same effects as benzodiazepines. The thiophene ring fused to the diazepine is a bioisostere for the phenyl ring in a regular benzodiazepine, meaning their effects on your receptors will be almost exactly the same.

Zolpidem and zaleplon, at least, are popular with people having trouble falling asleep (as opposed to staying asleep) because they tend to be short-acting, and relatively selective at modulating the parts of the GABA receptor that make you fall asleep (as opposed to also hitting the anxiety-relieving/muscle relaxing subunits, as common benzos do). Zolpidem also seems much more likely than benzodiazepines to induce strange, dream-like hallucinations when one resists falling asleep, although this might vary from patient to patient.

Zopiclone is apparently significantly less selective for the sleep-inducing GABA receptor subunits than originally assumed. Basically, there is probably little benefit with choosing zopiclone over a short-acting benzodiazepine.

 

[Sheeno101]

Thanks Hodor. I might look into seeing if I can get zolpidem or zaleplon prescribed, just to see if they don't have the same negative after-effects as benzoes for me. Does eszopiclone have the same reduced selectivity as zopiclone when compared to zolpidem and zaleplon?

Do you think that it's a fair assumption that if alprazolam and diazepam don't agree with me in this way, that other benzoes will most likely be the same?

 

[Jekyl Anhydride]

If you are very sensitive to hangovers from as little as 0.1mg of Alprazolam, you might want to skip the gabaergics entirely and look into something like Ramelteon, which doesn't seem to have the same efficacy as the benzos or Z drugs, but is approved for long term use if it does work for you.

Aside from that maybe Melatonin as it's OTC in the states and quite benign. For the most part, prescription sedatives for sleep or anxiolysis are a short term solution at best and will eventually stop working without dose escalation leading to the original issue of hangovers, increased side effects and rebound insomnia upon cessation. Sometimes things like exercise during the day and/ or a soak in a hot tub before bed are better long term solutions.

Hope you find a solution and Welcome to BL Sheeno

 

[Sheeno101]

Thanks for the suggestion and the welcome Jekyl! Ramelteon I'd never heard of and it sounds very interesting - I had before wondered if there would be a drug that agonises melatonin receptors that isn't melatonin itself. I'll definitely look into it.

Melatonin I've used for some years, by ordering it from the states. Like every supplement I've used for sleep (magnesium glycinate being another very good example), what initially seemed like a godsend ended up waning in efficacy after a while. I still do take it, trying to keep my doses under 0.5 mg a night as recent literature recommends and not taking it every night, but it's not so helpful anymore. What is more helpful, as you identify, is exercise, alongside positive adjustments to sleep hygiene such as getting up at the same time every morning, but I still frequently struggle - which is why I'm looking for something to help on an irregular, only-when-necessary basis.

It's very likely that I should just avoid the GABAergics, or the GABA-A PAMs at least considering that I've had a lot of luck with phenibut and GHB, but I was just interested in others' experiences of the differences between them before discarding them as a group entirely. I still do get benefit from 0.1-0.2 mg alprazolam when used very occasionally after all, though I try and avoid taking it whenever I can. I will look into zolpidem or zaleplon for that purpose, along with ramelteon. Do you have any other non-GABA-A PAM recommendations as a sleep aid?

Also I will just say that I didn't entirely mean for this thread to be sleep advice, though what I have received thus far has been very much appreciated! I was also interested in the general perceived differences in the PAMs as a class. If some people dislike many of the drugs in the class but like one or two, then there could still be one out there for my purposes.

 

[Xorkoth]

Melatonin is pretty effective. I also find about 50mg of diphenhydramine quite effective. Also L-theanine (an amino acid), L-tryptophan (also an amino acid), and oleamide (also a rather harmless supplement rather than a drug) I find quite helpful. I withdrew from phenibut recently and to help me sleep I would take a cocktail of 50mg of diphenhydramine, 1 gram of L-theanine, 1 gram of L-tryptophan, 3-5mg of melatonin, and ~100mg of oleamide. It works quite well. These days when I have trouble getting tired I'll take a combo of L-theanine and oleamide. None of these things are habit-forming or dependence-producing and do not leave you with a hangover the next day (except diphenhydramine does give a little bit of a hangover).

Regarding your last point... I've only tried clonazepam, alprazolam, lorazepam, and etizolam. Of these, etizolam has by far the nicest effects IMO, and is also the best for sleep, it's fantastic for sleep in fact. However benzos really aren't my thing, I don't find them recreational at all. But etizolam comes the closest to being recreational for me, of what I've tried.

 

[Twilight222]

Thienodiazepines like etizolam produce almost exactly the same effects as benzodiazepines. The thiophene ring fused to the diazepine is a bioisostere for the phenyl ring in a regular benzodiazepine, meaning their effects on your receptors will be almost exactly the same.

Zolpidem and zaleplon, at least, are popular with people having trouble falling asleep (as opposed to staying asleep) because they tend to be short-acting, and relatively selective at modulating the parts of the GABA receptor that make you fall asleep (as opposed to also hitting the anxiety-relieving/muscle relaxing subunits, as common benzos do). Zolpidem also seems much more likely than benzodiazepines to induce strange, dream-like hallucinations when one resists falling asleep, although this might vary from patient to patient.

Zopiclone is apparently significantly less selective for the sleep-inducing GABA receptor subunits than originally assumed. Basically, there is probably little benefit with choosing zopiclone over a short-acting benzodiazepine.

?This is the guy you should have your ears WIDE open to. That’s droping some serious truth.

 

[Sheeno101]

Melatonin is pretty effective. I also find about 50mg of diphenhydramine quite effective. Also L-theanine (an amino acid), L-tryptophan (also an amino acid), and oleamide (also a rather harmless supplement rather than a drug) I find quite helpful. I withdrew from phenibut recently and to help me sleep I would take a cocktail of 50mg of diphenhydramine, 1 gram of L-theanine, 1 gram of L-tryptophan, 3-5mg of melatonin, and ~100mg of oleamide. It works quite well. These days when I have trouble getting tired I'll take a combo of L-theanine and oleamide. None of these things are habit-forming or dependence-producing and do not leave you with a hangover the next day (except diphenhydramine does give a little bit of a hangover).

Regarding your last point... I've only tried clonazepam, alprazolam, lorazepam, and etizolam. Of these, etizolam has by far the nicest effects IMO, and is also the best for sleep, it's fantastic for sleep in fact. However benzos really aren't my thing, I don't find them recreational at all. But etizolam comes the closest to being recreational for me, of what I've tried.

Belated thanks for the advice Shadowmeister. I've tried L-theanine and it doesn't do much for me, unlike many other people, and have also tried 5-HTP but never L-trytophan for serotonin-mediated sleep. I have been looking into oleamide and it's interesting how sedating some people find it, but the reports are very varied.


I spoke to my doc in the hopes of getting prescribed zolpidem for sporadic use, but as it is a controlled substance in the UK (I got the spiel about how it is "highly addictive" which seems a little dramatic) I was instead prescribed amitriptyline, a tricyclic antidepressant. I'm reading differing reports about it, with some of the more encouraging describing how it produces very restful sleep, but others seeming more concerning, with people outlining how they sleep for over 12 hours and feel zombified for days. Does anyone here have any experience of it? If so, what dose would you recommend for helping insomnia? I recently came off venlafaxine and am feeling good in myself, so don't want to be messing around with my neurochemistry too much for fear of imbalancing it all again...

 

[Xorkoth]

I have never tried amitryptaline but I hear it is a good sleep aid... also I believe it will not form dependence (but could be wrong) and it's definitely not recreational. Have you tried diphenhydramine, or doxylamine, these are over the counter (in the US anyway) antihistamines that produce marked drowsiness.

 

[Sheeno101]

I took the amitryptaline, first 10 mg, and after a few hours without sleep another 10 mg. Strange drug, it reduced my sleep onset by an hour or so but I was still lying in bed trying to sleep for about 4 hours, and in that time I felt quite "tired but wired"... physically exhausted but mentally very much awake. Don't feel bad today though after about 6 hours of sleep. I'm glad to have it for when I need it but definitely won't be taking it much. I also spoke to a different doc today and managed to get zoplicone prescribed (much more common in the UK than zolpidem), so hopefully I'll have some luck with that. Not looking forward to the old pennies taste in the mouth that many describe though!

And I haven't tried doxylamine Shadowmeister, but I have tried diphenhydramine and promethazine many times. Diphenhydramine to me is awful, even if it makes me sleep for 8 hours I'll always wish I hadn't taken it, makes me feel dreadful the next day! Promethazine is a little better but I still become quite sluggish/irritable the next day, so I feel like drowsy histamines in general don't agree with me, just like benzoes. Very possible that zoplicone won't either but there's only one way to find out!