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What depressants/hypnotics are not genotoxic or carcinogenic?

Tieeurrrop

Bluelighter
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Nov 19, 2018
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Reading around and almost every one I have come across are one or both.

Only the gaba b drugs like ghb and phenibut, baclofen seem to have a low toxicity in those areas (apart from pregablin and co which I read cause tumors) but I took them and have had a bad reaction to all of them where I get tons of watery discharge down my throat so I can't tolerate taking them as that effect is so irritating as to negate any sedative action.

All the benzoes seem to be one or both genotoxic or carcinogenic. Seems like an absolute minefield to find a substance that possesses neither of these qualities. I can't take a subtance and relax if it I know it is causing dna damage or carcinogenic.

I don't really know what else there is. There are the alcohols but they are terribly toxic by their nature. Alcohol, chloral hydrate and most likely all their relatives.

And don't you dare mention anti histamines, some of the most disgusting delerium inducing substances I have ever taken. Polar opposite of what I would consider relaxing.
 

dopamimetic

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Which antihistamines did you take?

My personal experience is that they vary greatly with side effects, and while they aren't exactly the most pleasurable sedatives, the sleep-inducing antidepressants like mirtazapine or trazodone (the latter making me dream weird stuff, not bad, just weird) have a much bigger window between the effective and the delirant dose than the old 1st-gen antihistamines like diphenhydramine, which also possesses strong anticholinergic activity.

Unrelated substance is clonidine, an anti-norepinephrinergic medication sold against high blood pressure but used rarely these days because it's heavily sedating / tiredness-inducing. Now gets re-used as a sleeping aid, especially for people with nightmares, in lower dosages it also helps against anxiety/agitation attacks but is more physically sedating than benzos, while not sharing their memory inhibition. Might help against manifestation of new anxieties when taken in moments of huge stress or traumatic incidences as (nor)epinephrine plays a main role in the selection of which memories get "burned in". Beta blockers are proven to help with this.

The Russian drug picamilon, which is N-nicotinoyl-GABA and thus just an amino acid and GABA, so (if I'm wrong please correct me, as always :) ) it'll hardly be genotoxic.. I've taken it and it works, 50mg (I think) weren't that strong but increasing dosage should make it a potent anxiolytic and sedative similar in effects to the benzos.

Then we have some natural drugs of course, piper methysticum aka kava kava (don't believe the hype about hepatotoxicity, this has been revised and probably came from an impure charge that was cut with synthetic ingredients to lower the costs.. with the result of having an EU-wide ban of anything more potent than homeopathics), then Erythrina mulungu, a Brazilian root that isn't that well researched afaik (just read that the seeds are used, yet do the headshops sell the root and according to reviews, it is active).

Also just found another paper about natural GABAergics: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023459/ which mentions Zizyphus jujuba var. spinosa, also the kava listed before.
Oh yes, passiflora - while being a weak one, the higher dosages are sedating nevertheless.


(passiflora incarnata, a bundle of piper methysticum roots and a mulungu tree; clonidine, picamilon, suvorexant and etifoxine)

Here you find an overview of GABA-A agonists: https://en.wikipedia.org/wiki/GABA_receptor_agonist

There's a new-gen hypnotic on the market in the states, suvorexant, which works by antagonizing orexin receptors. Wikipedia says the drug isn't recommended in people with liver impairment, yet nothing about being toxic on its own, so it might be about prolonged effects interfering with functioning on the day after.

An interesting non-benzo tranqulizier is etifoxine. There are some concerns about hepatotoxicity for that one too, yet it's labelled as very low incidence.
 
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Tieeurrrop

Bluelighter
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Nov 19, 2018
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It is pretty pointless knowing about very obscure substances which are not easily available. A tease even.

And yes I tried mulungu kava etc. Didn't like either. Kava feels ok but gave same negative reaction as the other gaba b drugs I mentioned before and mulungu was crap for falling asleep! I actually felt wired like I did when I would take valerian. Also did not settle well in the system and was just counting the hours for it to clear out.

I managed to access the study which speaks of genotoxic effects of benzoes.

Here is the title

Genotoxicity and carcinogenicity studies of benzodiazepines

Interested to hear what people say about the results of those tables (if you use the link provided for viewing in my other thread that dopamimetic gave and search by title). From what I can see they use massively larger doses than are used by humans but there are a couple of suitable looking subjects which showed lack of mutagenicity.

Alprazolam seems to show up negative (but they say equivocal in the tests) but I have also read around in my searches of it being positive but didn't investigate further so far as I was tired of researching by that time. Zolpidem sounds good in terms of short action and doesn't disrupt sleep architechture while also being one of the only ones in the study with was neither carcinogenic or mutagenic.

The graph in that study is very informative. I would be interested in hearing more discussion on the findings though as to the relative safety of given benzoes tested given the data shown in the tables. I mean there was only a couple they said definitely didn't show positive for either but I see a lot more negative results yet they say they didn't count for some reason or other like they didn't fit the current criteria for testing.
 

dopamimetic

Bluelighter
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Obscure substances? Clonidine is Rx in most countries. Suvorexant in the US. Picamilon can be ordered online. Etifoxine is available too on some of the same shops. Tiagabine can be ordered from French pharmacies with a Rx.
Besides that, it's NSPD here :)

Yeah would have been my gut feeling that benzo mutagenicity requires huge dosages, they are so widely used and addiction / long term use isn't new either, yet (afaik) they are considered safe and are used too in people with severe illness?

Read that they have been associated with weakening of the immune system, yet alprazolam interestingly enhances antibacterial activity.. https://www.ncbi.nlm.nih.gov/m/pubmed/1776530/

Zolpidem sounds good, short half life so it just makes you fall asleep without disrupting sleep architecture.
Unfortunately for me it is completely useless. Even 15mg lack any sedation. Years ago I used 5mg recreationally a few times, for its slightly intoxicating and anxiolytic effects.

Zopiclon on the other hand did work. And is the most extreme utterly bitter substance I know of. So much that even the traces of it reaching my taste receptors over bloodstream cause a change in taste..

Will get zaleplon soon, hopefully this one works. Pagoclone too but more for curiosity, it has been recommended as a recreational substitite for ethanol by some British professor, if I remember it correctly.
 

Abject

Bluelighter
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You ask for info and complain it's too obscure for you when you get it...
Benzos aren't hugely carcinogenic, especially the amount you'd be having your your issues
Cannabis isn't genotoxic afaik, have a bong and say thank you to dopa imo
 

Tieeurrrop

Bluelighter
Joined
Nov 19, 2018
Messages
56
Well now these seem pretty conclusive for xanax's lack of carncinogenicity and genotoxicity.



Although they don't detail the tests I imagine they are to be trusted and will have been peer reviewed?
 

Abject

Bluelighter
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I've never heard of benzos being classified as either, I'd say burnt toast would be more carcinogenic
 
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