Scopolamine as antidepressant; pharmacology details?

[MiaouMixe]

I have severe anhedonic depression. This is not a consequence of drug/ supplement use as I have never done any; legal or illegal. I'm just trying to feel better. You lovely folks are very knowledgeable, and most importantly open minded. I'm not against pharmacological treatment options, but the "standard" antidepressants leave much to be desired and may even be contributing to the chronicity of depressive disorders.

I'm a fan of the glutamatergic experiments (ketamine, ECT, etc) but would like to minimize risk. I found this interesting study on regular old scopolamine (nausea drug) where they had good results. It is thought that abruptly nuking muscarinic cholinergic receptors somehow affects glutamatergic receptors downstream. Results are felt a few days after the dose; you're not meant to feel fantastic on the active dose phase. I know this approach is not ideal, but it could be easy to replicate if I can obtain said seasickness patches. I've had some luck with regular Benadryl (at normal sleep doses) and REM deprivation, so I think I might be particularly responsive to this. The scopolamine doesn't even require any gigantic doses! Might as well, you know?

ANYWAYS: my main question is what scopolamine derivatives would give me the same effect, and how would I go about translating dosages? I'm not going to attempt anything IV, but I'm thinking a skin patch would be similar. Would an oral drug work? What about scopolamine butylbromide or hydrobromide? Other compounds/derivatives? Can some inactive ingredient affect the outcome? It's gotta make it into my brain in one piece and appropriate amounts.

Thanks.

 

[Apurplenugfish]

If you want to look into alternative treatment which I highly recommend and am doing myself, I'd look into the use of psychadelics to help with psychological disorders such as depression...I would specifically recommend micro-dosing LSD or Psilocybin mushrooms. If you are willing and open minded about going on a trip to solve your depression under guidence from someone likeminded I think you can benefit greatly. Scopolamine is a terrible drug and I fail to see how anyone can benefit from it...not to mention it's dangerous.

 

[serotonin2A]

I don't really understand your logic here. You think that established antidepressants have drawbacks. Why in the world would you think scopolamine would be a better alternative? Anticolinergics were used for depression in the 1950s but nobody wanted to take them because they have intolerable side effects. And that was during a period when there were few alternatives. People litterally chose to remain depressed so they could avoid scopolamine.

So now there are many alternatives with few side effects, and you want to search out scopolamine?

 

[dopamimetic]

I'm a fan of the glutamatergic experiments (ketamine, ECT, etc) but would like to minimize risk.

I really share the opinion of serotonin2A here.. while the glutamatergic pathway certainly is very promising and intriguing, and you indeed might be right on that there's an interconnection with mACh receptors somewhat, the last thing you (or anyone - I really don't get it why anticholinergics are abused, but everyone is different of course) probably want to do in terms of safety and side effects is doing something like scopolamine. Strong anticholinergics have been linked to the development of dementia!

If you're unsatisfied with the currently available antidepressants (which I can understand as I am too), you're really better off trying straight something adjusting glutamate and/or dopamine. For anhedonic depression, low-dose methylphenidate (or isopropylphenidate, if you're open to research chemicals- it has less side effects and is patented already) in combination with memantine (low-affinity NMDA antagonist) might be very promising. You'll get some glutamate inhibition, less or no tolerance to the phenidate & increased dopamine.

Or, if anxiety, dysphoria / sadness are your main problems, the cough suppressant dextromethorphan can be very interesting in therapeutic dosages (just as those used for cough, or maybe slightly higher, but less is more!). It combines the ketamine-antidepressant mechanisms with those of a SSRI (and maybe even something unique to it, in that it additionally regulates glutamate and is neuroprotective) in a somewhat safe way. And it's OTC! (It might make you somewhat tired and maybe a bit nauseous in the first days until your brain adjusts, but it's much better tolerated imho than the average SSRI.)

Also you can add light stimulants (caffeine, isopropylphenidate in 5mg dosages - methylphenidate is not recommended because it's too strong on norepinephrine) to the DXM for energy.

At least for me it works like nothing else currently!

--

And last but not least we have these AMPA positive modulators like unifiram and sunifiram, or the older but very safe piracetam. For some they are very motivating, antidepressant and even anxiolytic. Others, like me, don't tolerate them but I'll have to research more.

--

Edit: But the study you've linked is indeed interesting, especially as it's from 2012...

Moreover, our results complement the previously reported findings that cholinergic enhancement using physostigmine induces symptoms of depression in currently manic individuals with BD and worsens symptoms in patients with unipolar depression.

Determination of the optimal schedule of administration and the potential long-term use of scopolamine as an antidepressant agent requires further study, particularly because potential adverse effects include confusion and delirium.

 

[Apurplenugfish]

Bottom line is the risk isn't worth the reward and I can look into further alternatives that would be good I could suggest LSD very strongly. Changed my life and cleansed my soul, I found purpose and in turn permanently solved my heavy depression.

 

[Nagelfar]

I abused dicycloverine by taking an entire sheet issued me in the penitentiary, and it was *the one most single* dirtiest, pure body load toxic feeling "highs" I've ever had the displeasure to experience. First time I thought I took way too much and forced myself to vomit it shortly after dosing, forcing my hand into my throat in the 'swan' pecking eye-jab kung-fu hand form to induce gag-reflex so violently and enthusiastically (uncertain how well my imminent well-being could turn into an imminent question of my survival) so hard that I burst a blood vessel in my eye, making everyone on the tier think I got into a fight and having all the shock collars ask me "Who hit you? No man, serious, tell me" ("uh guy, don't ask, just know: I didn't get in any damned fight [except potentially between my own Dr. Jykell and Mr. Hyde being skittishly indecisive of who was meant to be on next]"). Due to the banality of prison daily life, I did the same thing again a month later, took less (but not much. meh.), and waited it out that time. Just made me feel like someone turned up the brightness on my internal subjective-observer of surrounding world screen to the point that permanent picture burn damage may have been being done to it on my unwarranteed cerebral-OS package I'm stuck with from the factory. Yeah, no bueno, uh, Bentyl.

 

[MiaouMixe]

You only take it for a few days!!!!!!! y'all didn't read my full post (though I guess I did ramble). No stickers for you :D

Jesus, of course taking an anticholinergic for a long time would suck.

Also this is not to get high. The dose would be less than that used for the indicated motion sickness purpose. Again, only for a few days. I really cannot think of a lower risk experiment. Trust me, I'm a complete chicken who hates risk!

It's also not about the ACh, but rather that downstream effect on glutamate receptors.

Now I wonder which scop derivatives and delivery methods would work...?

 

[serotonin2A]

Taking it just once wouldn't change the fact that it produces horrible side-effects. Have you ever taken scopolamine for motion sickness? Even that can make you feel like a zombie. The only reason people tolerate it is that motion sickness really really sucks.

 

[MiaouMixe]

I wake up every day debating whether or not to shoot myself in the head with a shotgun. I'm dying of boredom and apathy. I can google pictures of maggot infested diabetic foot ulcers for hours, and it won't budge my emotions a hair.I've been this way for 3 years.

I'm pretty sure a few days of dizziness, confusion and dry mouth, however uncomfortable, is a non-issue in comparison. Obviously I would stop the experiment if I got any truly dangerous reactions. I'd also avoid driving or operating machinery and all. Any drug has risks; you can have literally all the skin of your body melt off (Stevens-Johnson syndrome) from taking a Tylenol because of your pinkie-toe ache.

The antibiotics I got for a bacterial stomach ulcer were also unpleasant. I was puking every hour and had a 2 week long headache. Yet, no more infection now. Was it not worth it?

 

[dopamimetic]

Why don't you just try to directly adjust the glutamate system then with e.g. ketamine (proven to exhibit rapid acting antidepressant effects in many studies and led to the research about glutamate as a target for treating mental illnesses in general if I'm right), or OTC dextromethorphan <-- that's really powerful?

 

[serotonin2A]

I wake up every day debating whether or not to shoot myself in the head with a shotgun. I'm dying of boredom and apathy. I can google pictures of maggot infested diabetic foot ulcers for hours, and it won't budge my emotions a hair.I've been this way for 3 years.

I'm pretty sure a few days of dizziness, confusion and dry mouth, however uncomfortable, is a non-issue in comparison. Obviously I would stop the experiment if I got any truly dangerous reactions. I'd also avoid driving or operating machinery and all. Any drug has risks; you can have literally all the skin of your body melt off (Stevens-Johnson syndrome) from taking a Tylenol because of your pinkie-toe ache.

The antibiotics I got for a bacterial stomach ulcer were also unpleasant. I was puking every hour and had a 2 week long headache. Yet, no more infection now. Was it not worth it?

I'm not really sure of the issue then -- you seem dead set on trying scopolamine, so why are you asking for advice? I feel like the point you are missing is that scopolamine isn't a miracle antidepressant. It may be effective for some people but it wasn't the case that it works in all patients, and it's certainly not clear that it is as effective as conventional antidepressants. Not enough studies have been conducted to know how well it actually works.

If scopolamine works for you and you can tolerate taking it then that would be great. But is isn't a good solution for the vast majority of depressed patients.

 

[MiaouMixe]

Oh yes, Ketamine is on my radar but it is slightly really illegal (and I have zero sources for illegal things). I also don't have like $5,000 a session to give to a clinic to do it legitimately.

I've tried 2 weeks of tianeptine, but it made me really depersonalized and worsened already serious insomnia. Apparently it was not even the direct NMDA antagonist I thought. There is evidence to support other glutamatergic drugs like riluzole and memantine, but I'd have a tough time selling that to a doctor. They're not direct antagonists either, but I take reversing amphetamine tolerance as evidence to their affecting the appropriate reward/motivation systems. I could just buy those online, I suppose (no penalty for possession). DXM is interesting, but I have yet to research how the SSRI bit affects the need to dose a bit higher than indicated. I'm looking for that permanent receptor magic, not to get high and temporarily feel great, only for it to stop working later (but not be able to go off without withdrawals). Plus, any withdrawal that leads to overactivation of glutamatergic systems could be directly brain damaging (that's why you don't do benzos or alcohol).

 

[MiaouMixe]

Re: serotonin2A,
yes, I'm set. That's why reading the question again would reveal that I'm looking for info on pharmacology of scop derivatives. I KNOW it is a long, shot, it's just too quick and easy an experiment to not try. I even explicitly stated how I did not think it was the answer to everything. It's such a longshot that I wouldn't even try it (despite said simplicity) if I hadn't had that unusually good reaction to Benadryl and REM deprivation.

 

[belligerent drunk]

I could understand if you were desperate after trying every conventional treatment available and now decided to go balls to the wall and do scopolamine because nothing else worked, but as I understand you haven't taken anything yet. So why are you so certain that THIS is what you really need? As everyone has stated, the probability that it will perform a miracle is so small compared to the obvious heavy side effects you're more than likely to suffer... I don't know, doesn't make sense to me. Try the standard antidepressants, believe me the side effects may be bad, but at least they're somewhat proven to work - trying scopolamine against depression is russian roulette.

EDIT: oh I see that you're set... well disregard my post then. I don't know much about derivatives of scopolamine.

 

[MiaouMixe]

I'm going to start giving out lollipops for excellence in reading comprehension :D

number of people that answered: 8
number of people that answered MY QUESTION: 0

 

[MiaouMixe]

I am thankful for any informed discussion though. It's good to have responses at all.

 

[neurotic]

You could try a dissociative RC if you've been wanting to try ketamine. No need for connects or even getting out of the house for that

 

[belligerent drunk]

So are you looking for scopolamine derivatives or any anticholinergics? Because as far as I know scopolamine et al aren't very common and I haven't really heard of more than atropine, benzatropine, scopolamine being used or produced, of the tropanes. Anyway, what exactly do you want to know about the pharmacology of said drugs? Considering that tropanes are probably hard to get, I'd probably start with/try diphenhydramine. It's not a selective anticholinergic, it also has antihistaminic properties, but maybe that'll work...

 

[dopamimetic]

I think one of these first-generation antihistaminics actually lead to the development of the SSRIs, don't remember if it was diphenhydramine or some other one ... but the antidepressant activity of choline antagonism is a really disputed matter.

Memantine you can get dirt cheap without prescription off some Indian online pharmacies, maybe Riluzole as well (but this one is more expensive and rare, I'm still looking for a good source for it because I'm quite interested in it too) as well as one of the bigger US nootropic vendors carries it in liquid form. And, like neurotic said, we have the dissociative RC's, although unfortunately the golden era of methoxetamine is over ... that new 2'-OxO-PCE might have good potential, but there are no real experience reports yet and it's always a game with fire when using new RCs, most are not that well synthed when they come from Asia ... and Ephenidine/Diphenidine etc. I wouldn't really recommend, from the general opinion, Ephenidine would be the best one maybe but they all have a disturbing stimulatory side to them which might be counterproductive for depression ... also they are quite short-lived. But I'd rather try Ephenidine before using Scopolamine! Or, as said, DXM. The SSRI side it has doesn't hurt really, it's qualitatively quite different from the average antidepressant and doesn't share these anxiogenic / suicidal adverse effects in my eyes, probably because the glutamate adjustment overpowers them ...

It's really shit that Ketamine is scheduled in so many countries ... it has real use for pain, anxiety and depression! (But we have something called the Darknet these days )

 

[belligerent drunk]

Anticholinergics aren't meant to be taken daily unless there is no other way, but I don't think that's what the OP wants. They want a one-off magical experience that will cure them for life. Well, at least they have hope, I'll give them that.

I can give my own experience with datura (atropine + scopolamine) as some input. I do have some sort of depression, but it hasn't been diagnosed yet because it seems to be more complicated than just that. Anyway, about 1.5 years ago I decided to experiment with datura and after titrating my dose up I had a borderline trip with all the classical symptoms of a low-end anticholinergic overdose. Apart from not being able to read for about 48 hours and feeling glad that I didn't die, it didn't do much. The experience itself was confusing: I was seeing bugs crawling on walls, said walls moved and so on. Now you say that the positive effects appear after; I didn't notice anything. Given, I wasn't even looking, but I'm sure if there was something to it then I would have noticed.

So maybe it's just skeptical me, but I think all taking an anticholinergic will do to you is shake some sense into you and maybe make you feel better because you're still alive. But in HR interests we'll try to answer as many questions to make your endeavors as harmless as possible, and maybe then you'll listen to the valuable advice other people are giving you here. NMDA antagonists.