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Drug that hits alcohol serotonin receptor

Synaps3

Bluelighter
Joined
Sep 14, 2011
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I am looking for a drug that hits the same serotonin receptor site as alcohol. After doing a lot of research, I am unable to find exactly what serotonin receptors ethanol hits and if there are any drugs that hit the same receptors. I am a bit of an alcoholic and the main reason I drink is because of depression. I'd really like to find another drug that would give a similar antidepressant effect as alcohol. I am not looking for something super euphoric and I'm not looking for something like an SSRI either. It amazes me how hard it is to find a drug that makes you less depressed, but isn't super euphoric or shitty like an SSRI. Why is there nothing like this?
 
I wasn't aware that alcohol had significant serotonin effects, it does hit a lot of other things though and among the other targets that are thought to be responsible for its effects are GABA mediated and for that I would look into baclofen, it has also found a niche as a treatment for alcoholism.
 
Indeed ethanol seems to be a 5-HT3 positive modulator - didn't know that, just read on wikipedia (unfortunately no reference and could be wrong). But even if it is true, it's a minor component. The main effects are mediated over GABA-A (positive modulation) and NMDA (negative) receptors, and it hits some other things like calcium channels and adenosine, even nicotinic acetylcholine receptors. This broad spectrum makes it such a dirty drug - and of course the metabolism which generates toxic products.

There are some interesting proposed cleaner 'synthetic booze' molecules originating from the Z-drugs ... pagoclone comes to my mind, but there are better ones. Unfortunately they are not available yet, all you possibly can get is some obscure RC. The available Z-drugs are strongly sedating, with zolpidem (and possibly zaleplon, no experiences with this one yet) being the most interessant - but it's either genetically and/or sex-dependent (zolpidem appears to affect women quite stronger). I don't get any nice effects out of it besides just heavy sleepiness, while I've watched others to become heavily euphorically drunken-alike from just one or even a half of a zolpidem pill! Jealous ... %)
 
The positive effects are ALL mediated by GABA - I know from experience.
 
Acohol also metabolises to acetaldehyde which mediates opioid receptors.

Ethanol (EtOH) alters neural activity through interaction with various neurotransmitters and neuromodulators. The endogenous opioid system seems to play a key role in the activities of EtOH, since the opioid antagonist naltrexone (ReVia) attenuates craving. We have investigated the transcriptional regulation of opioid system genes in response to EtOH exposure for up to 96 h in human neuroblastoma SH-SY5Y cells using quantitative real-time polymerase chain reaction. We observed a significant decrease in the expression of opioid peptide precursors (proopiomelanocortin, proenkephalin, and prodynorphin) and of the kappa opioid receptor after 48 and 72 h of EtOH exposure (10 and 40 mM). These alterations were not present when the EtOH metabolism was blocked by 4-methylpyrazole. To evaluate whether the effects evoked by EtOH were possibly due to the first product of EtOH metabolism, cells were exposed to 0.4 mM acetaldehyde. We observed the same pattern of changes for prodynorphin, proenkephalin, and the kappa opioid receptor as after 72 h exposure to EtOH. These results contribute to our understanding of EtOH action at a cellular level and provide evidence of the role of acetaldehyde in mediating some of the EtOH-induced effects.


http://www.ncbi.nlm.nih.gov/pubmed/17934066
 
Alcohol is a depressant that is of course used by many depressed people, but that does not make it an anti-depressant. Any sedative may buy you temporary relief that way (acting as GABAergics - look what clubcard posted), the effect on staying able to function can sometimes be questionable and most are addictive.

The Z-drugs are also quite dubious, some like zolpidem and zopiclone are quite selective as hypnotics. I think pagoclone is also being tested for stuttering. Unfortunately I believe that Z-drugs are found to be carcinogenic so that is hardly a step up from alcohol.

Acetaldehyde might act on receptors but it is quite toxic. Drinking alcohol regularly can apparently increase your cytokines etc by like 4x, your body reacts as if it is injured and inflamed - chronically...
Yeah there are RC alcohols that do not form aldehyde metabolites, but they are about as sketchy to use as GHB, I think (I tried 2M2B).

GABAergics are by any means not ideal for depression! Find out what the reason is for your depression and treat that problem...
 
2M2B carbamate has been/is being sold by the gram from a company that usually deals with bulk (1 tonne cubes) chemicals. Just the GABA part was JUST like alcohol but without 'the dark corners'. I cannot see someone taking it and turning into a complete twat.
 
I bought some 2m2b a few months ago after researching it. I should have made a trip report but never got around to it.
I will say be very careful if anyone(veterans included) plans on trying it.
If youre a drinker id recommend avoiding it because of the zeal alcohol can bring on, i.e: the want to get more drunk or sustain a drunk. You definitely CANT have a "drinking session" with it if youre one who likes to drink beer.
The initial come-up euphoria i would compare to G but besides that it seemed more of a "drunk and hard to function" high that didnt fade with food, water and sleep.
Plus BDO, GBL and GHB all taste like candy compared to it, if that tells u anything...
 
Hmm I've tried 2M2B once when they sold it from the UK, and don't have it as bad in memory ... GBL definitely tastes much worse, while pure GHB shouldn't have any real taste (or?).. the 2M2B has some chemical mint smell to it if I remember it correctly. The effects were alright but nothing special and not worth the money... but if it had been cheaper, it would have made a decent substitute because of the lack of hangover, toxicity and less dirty overall effects ...

But well, don't have that much experiences with GHB either. Somehow I felt that it was a bit ... cold, and mechanic, don't know. Many people seem to like it.
 
2M2B carbamate has been/is being sold by the gram from a company that usually deals with bulk (1 tonne cubes) chemicals. Just the GABA part was JUST like alcohol but without 'the dark corners'. I cannot see someone taking it and turning into a complete twat.

I thought that random carbamates can potentially be quite dangerous / toxic? ...

GHB / GBL were most of the time very warm for me, cozy and gregarious. But especially at lower doses effect on GHB receptors can give that effect, quite stimulating in a way.. it is only at high / full doses that the GABAergic action starts to dominate.

And yes, 2M2B smelled like mentholic campherous terpenes. Pure well-made GHB is mostly tasteless (not particularly disgusting as unreacted GBL can be), but still salty cause of the sodium and vaguely ychtious.
No I won't say 2M2B is particularly bad, I liked the lack of hangover, but it is also very easy to get wrecked (black hole!) cause of the potency - it can be like drinking half a bottle of vodka in one go - pretty dicey. Especially tricky for people who are careless or reckless.

I've been dependent on GHB but fortunately I never upped the dose compensating for tolerance.. so I could just stop and have a bad day or aid with something like gabapentin - and on one january 1st I just left it behind me without much thought. Strange, but glad I did not really go deep into the addiction upping the dose. Still, all that sodium!

Personally, since messing with GABAergics too much (benzos etc) and getting chronic withdrawal syndrome from that - anxiety insomnia the whole shebang... I am more careful and apprehensive about it - I never take superhigh doses of any such thing, and make sure to leave enough off days or weeks so that actual dependence doesn't return. It's worse than opioids to get addicted to IMO and I recommend huge caution with them.
 
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I am looking for a drug that hits the same serotonin receptor site as alcohol. After doing a lot of research, I am unable to find exactly what serotonin receptors ethanol hits and if there are any drugs that hit the same receptors. I am a bit of an alcoholic and the main reason I drink is because of depression. I'd really like to find another drug that would give a similar antidepressant effect as alcohol. I am not looking for something super euphoric and I'm not looking for something like an SSRI either. It amazes me how hard it is to find a drug that makes you less depressed, but isn't super euphoric or shitty like an SSRI. Why is there nothing like this?

I read your post and it reminded of a quote I use to hear a lot. Something about.. there will be no drug or alcohol that won't make your depression even worst. Something like that.

Whenever you reward yourself and artificially get endorphin produced, the further you are from the solution - so I've been told.
 
Just like with all other medicinal problems you have to get to the root of the problem instead of just fighting the symptoms. Anti depressants should only be used if the symptoms are unbearable and never as a long term treatment. I know theres also people that naturally have imbalances of neurotransmitters but those are a minority.

If you really are in desperate need of an antidepressant id recommend syrian rue since its cheap, legal and safe if you dont combine it with other drugs (including legal drugs like caffeine, alcohol and nicotine)
 
Unfortunately I believe that Z-drugs are found to be carcinogenic so that is hardly a step up from alcohol

Is this true? I havent come across it but am interested as my wife has been on Ambien for years. I will check but its late and was hoping for someone to do the work. :(
 
Is this true? I havent come across it but am interested as my wife has been on Ambien for years. I will check but its late and was hoping for someone to do the work. :(

Well, it's not really that simple to draw such conclusions perhaps - but this is still quite worrisome:
http://www.bluelight.org/vb/threads/395450-The-Z-drugs-as-carcinogens-(zolpidem-zopiclone-indiplon) >> read till the end especially

Addiction might be a much more acute and relevant problem for people going on these chronically. I'm not one to judge (I've self-medicated with benzos but the withdrawal syndrome took SO LONG) but the alternative to taking hypnotics would have to be very serious for the use to be responsible imho / imhe.
 
Thanks Solipsis. I feel slightly better reading that thread as not very conclusive but still worrisome. I imagine there is newer data. I will look when I can and update.
 
I think the populations of under-sleepers and over-sleepers have increased risk of mortality anyways, and also many people with insomnia really have sleep apnea so if the trials involved giving people with insomnia the z-drugs (which I'm curious if it was indeed people with insomnia without sleep apnea/upper airway resistance syndrome or just normal sleepers) then hypnotics likely pushed them further into low oxygen because of a reduced arousal related to low oxygen, and this is harmful and increases risk of mortality.

Hard to say what's going on with the animal experiments but I'd like to know if used in an animal model of insomnia because this should be about how hypnotics affect outcomes in short-sleepers, long-sleeping is known to be bad. Though we can't tell if sometimes people oversleep because they are "sick" and their bodies are trying to compensate or if it is part of the natural "dying process" to sleep more but generally under sleeping or over sleeping leads to high mortality.

I feel that for many reasons missing significant sleep or skipping a night completely should worry us much more than taking a newer hypnotic. Though I will say the M1 anticholinergics do cause very increased amyloid beta buildup and neurofibrillary tangles, and a increased risk of Alzheimer's accordingly. Benadryl is probably worse than the normal hypnotics.
 
The GABA-A subtype is specific to alcohol. Lose all the other effects and this just has the 'social lubricant' properties but without the 'dark corners'. People who admitted that they got mean when they drank were placid on QH-II-66 derivatives. Specifically

7-ethynyl-5-(2-fluorophenyl)-1-methyl-3H-1,4-benzodiazepin-2-one

Adding the alkyne is a bitch but I guess if you have a good relationship with your benzophenone supplier, they will make at reasonable cost.

I wouldn't expect LAZY CHEMISTS to make it.
 
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Indeed ethanol seems to be a 5-HT3 positive modulator - didn't know that, just read on wikipedia (unfortunately no reference and could be wrong). But even if it is true, it's a minor component. The main effects are mediated over GABA-A (positive modulation) and NMDA (negative) receptors, and it hits some other things like calcium channels and adenosine, even nicotinic acetylcholine receptors. This broad spectrum makes it such a dirty drug - and of course the metabolism which generates toxic products.

http://www.ncbi.nlm.nih.gov/pubmed/7694329?dopt=Abstract
When Wikipedia is disappointing for citations I refer back to here:
http://www.neurotransmitter.net/drugmechanisms.html

As for a gabaergic replacement, the only safe one I can think of is possibly Ashwagandha. Helps me quite a bit with anxiety and motivation in periods of stress.
 
Ethanol, like other CNS depressants activates gabaA receptors as its main target, but also affects calcium channels, sodium channels and possibly serotonin receptors, though there contribution to psychoactive affects of ethanol remains unknown.
 
Interesting, did you say you have tried zalaplon? according to Wikipedia, zalaplon isn't addictive, and withdrawal symptoms, if they develop are relatively mild.
 
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