Peptides and neurotransmitters that would add to the reward of rewarding drugs

[MeDieViL]

Sex Reward and Peptides

Kinda follow up of my previeus thread (besides there are 2 kinds of rewards, euphoria and pleasure, as an example sex doesnt really cause euphoria it just feels fucking good, euphoric substances do also add pleasure(atleast they just make outside rewardingg things more fun like talking and dont induce pleasure on its own) tough so i suppose its connected for a part too.

"Last time I went through the literature it looked like a2 adrenoreceptors, and D2 were the main catecholamine receptors involved in it. However, 5HT, histamine, and more than a handful of peptides all seem to mediate the "enjoyment" of it. Things get really dirty really fast...'"

Off my sex thread, im mostly interested in things that add enjoyment rather then things that cause euphoria and make you act differened.

Im mostly interested in it for sex, as in the past it felt like a hour long lasting extremely good orgasm, now it just feels a bit better then normal, i want that shit back.

I made a general thread as i also noticed the enjoyment of other substances is reduced (togheter with euphoria tough) but my brain massively changed with going predromal shizo (where everything feels fucking massively good, shizo"s get excessive reward) but now it seems that its lower then it should be (also read that stabilised shizo's get a hypoactive response to amp).

So A2 receptors? agonist or antagonist? need some idea's then i can start experimenting%)

Its possible i might be happy with mdpv tough as that shit is great for sex, but somehow i think its also blunted like the rest and i havent experienced the true magic.

I know dxm completely takes the fun of sex, so i must try do something opposite of what it does whatever that would be.

I remember that the combo of 2CB and GBL induced massive MDMA like pleasure that was insane with not much euphoria however i cant get those substances at the moment but they def acted on some enjoyment targets.

The reward system is just so hard to understand, i wish they were right about da, but thats just the issue here it makes me want all this lol.

Also i suffer from severe anhedonia but i fucking love food showing that differened neurotransmitters/peptides induce reward for differened things.

We eat because food tastes good, and because we feel good after a meal. There may
be two separable systems for these two pleasurable aspects of eating. Belluzzi &
Stein (1977) proposed that brain opiates give the satisfaction that comes after
successful consummatory behavior. According to this view, opiates may be the
chemical basis of pleasure, the goal of drive reduction. Our task now is to figure out
which neurochemicals and which brain systems cause "drive induction" such as
appetite for food, and which give "drive reduction" such as satiation.

Just reading this paper, imagine tweaking reward so eating a meal causes more pleasure then a orgasm lol
http://www.bepress.com/cgi/viewcont...DRf3SCfuVPTufvlxA#search="rewarding peptides"

A gonadotropin-releasing hormone agonist (GnRH agonist) is an analogue that activates the GnRH receptor resulting in increased secretion of FSH and LH. Initially it was thought that agonists could be used as potent and prolonged stimulators of pituitary gonadotropin release, but it was soon recognized that agonists, after their initial stimulating action – termed a “flare” effect - eventually caused a paradoxical and sustained drop in gonadotropin secretion. This second effect was termed “downregulation” and can be observed after about 10 days. While this phase is reversible upon stopping the medication, it can be maintained when GnRH agonists use is continued for a long time.

d it stimulates a million
synaptic contacts in sensory and motor relays for sexuality. I would not be surprised
if it someday proved to modulate the rewarding incentives we feel during
intercourse and the satisfaction of orgasm. LHRH, in both men and women, has all
the earmarks of a "drive peptide" (Olds, 1977) for mating and reproduction.

Any anecdotes of it increasing sex reward?

 

[sekio]

as an example sex doesnt really cause euphoria it just feels fucking good

Sorry dude, euphoria is "the same thing as "feeling really good". Don't play these dumbass wrd games.

If you sit around and say "wah I have anhedonia, nothing is pleasurable" over and over, you're probably not going to feel a lot of pleasure from non-chemical sources.

The key here that most people seem to miss by a fucking mile is environment enrichment - if your day to day life is not rewarding to you, modify it until it is. Go read the RatPark study. Rats in shitty living conditions were quick to become morphine addicts but enriched-environment rats (and even the same morphine-addicted rats), when placed into an enriched environment, suddenly lose most of their addiction. Suprising but not totally unexpected.

If you have burned your mind out so badly that even sex, good food etc do not even produce the slightest hint of good feelings you should look into being treated for major depressive disorder, perhaps with MAOIs. It's not normal to live your life with no pleasure at all.

You should not be looking for chemical substances to "enhance reward" because you'llcome right back to the simple fact that chemical dependence doesn't solve shit. You'll fidn some expensive reward enhancer and then end up right back where you started when it loses efficacy.

Seriously investigate your diet, excercise, lifestyle, and any concurrent medication you're taking. Don't assume that because you're not hugry after your third Big Mac of the day, that you're getting all your nutrients. Break out of routine and do something nice for others. See how that feels.

 

[MeDieViL]

Sorry dude, euphoria is "the same thing as "feeling really good"

This is not true at all, euphoria does bring a good feeling but it can be limited and the enjoyment can purely come from the happyness.

if your day to day life is not rewarding to you, modify it until it is.

Anhedonia means that you are unable to feel pleasure, that some idiots say that boredom is anhedonia is nothing to do with me, i have a very active life where i do things, am surrounded by people i like, can listen to music, go out to events etc however with anhedonia all those things are unpleasant as there is no reward whatsoever, if you have sex and dont feel anything enjoyable thats anhedonia, if you have sex and find it boring because its not like on meth thats a differened story.

when placed into an enriched environment, suddenly lose most of their addiction. Suprising but not totally unexpected.

When i fix my anhedonia its obvious i can still be bored and in a boring environment id prob go for drugs too, but add a group of enjoyable ppl and things to do then i could forget about the drug too, this the difference btw boredom and anhedonia, too many bored idiots claim that its the same as being anhedonic, its a fact that life doesnt give you pleasure, you have to do fun things.

If you have burned your mind out so badly that even sex, good food etc do not even produce the slightest hint of good feelings you should look into being treated for major depressive disorder, perhaps with MAOIs. It's not normal to live your life with no pleasure at all.

I dont suffer from depression, i am perfectly happy even tough i suffer from anhedonia but since i can fix that issue i see no reason to be depressed.

You should not be looking for chemical substances to "enhance reward" because you'llcome right back to the simple fact that chemical dependence doesn't solve shit. You'll fidn some expensive reward enhancer and then end up right back where you started when it loses efficacy

Tolerance can be prevented with nmda antagonists (look up my thread about that) and breaks, again im not looking to be high just be able to enjoy normal rewarding activitys and a substance on a level where id still be bored if i dont do anything.

The brains reward mechanism can be malfunctioning, simular to how people can lack happyness its diff from ppl expecting too much reward, i apreciate the most little reward but its not there and it feels unbearable, differened from being bored where there is a bit off reward and isnt as bad.

Seriously investigate your diet, excercise, lifestyle, and any concurrent medication you're taking. Don't assume that because you're not hugry after your third Big Mac of the day, that you're getting all your nutrients. Break out of routine and do something nice for others. See how that feels.

That is all optimal, its mostly caused by GBL abuse wich permantly downregulated myreward receptors, i actually used it for anhedonia but before that the issue wasnt as bad and the level of reward was simular to being bored rather then being extremely unpleasant as it is now.

Permanent reward downregulation can be prevented with amp so its a good solution.

 

[MeDieViL]

It's not normal to live your life with no pleasure at all.

Thats exactly the problem, its not that i expect too much reward from life.

 

[MeDieViL]

I developped predromal shizophrenia where pure anhedonia is a commen symption as the brain processes unpleasant feelings in the wrong brainarea wich are more important for survival, leaving no room for the induction of pleasure if im correct.

Taking a high naltrexone dose can show you that a simple brain malfunction can make it possible to lack reward even without depression or something simular.

 

[Renz Envy]

GnRH just stimulates testosterone production and I have dabbled with it before. It causes a fast peak in testosterone and it is hardly noticeable. It is good for getting HPTA function back to normal post steroid use, however it will not get your testosterone levels high enough or long enough to cause a major change.

The best sex I have ever had was on GHB, methamphetamine and a 500mg/week testosterone propionate dose. I do not advise using any of those drugs, especially not testosterone or meth.

That is all optimal, its mostly caused by GBL abuse wich permantly downregulated myreward receptors, i actually used it for anhedonia but before that the issue wasnt as bad and the level of reward was simular to being bored rather then being extremely unpleasant as it is now.

Permanent reward downregulation can be prevented with amp so its a good solution.

1) GBL abuse will down regulate your GHB receptor for a short amount of time which can cause a reduction of dopamine release, growth hormone release and oxytocin release. This is why you use GHB type drugs at most once a week.

2) 24-hour dosing of GBL/GHB will lead to excessive glutamate levels resulting in anxiety as your brain is severely starved of GABA. It is much like a very fast acting alcohol withdrawal.

3) Amphetamine is not a cure for anhedonia. It is, in fact, a major culprit. The word "Cure" indicates that amphetamine is going to heal your depression; it is a brain poison with short term benefits. It's not an antibiotic handling a bacterial infection.

4) There is ZERO proof in humans that amphetamines or GHB can permanently "down regulate" rather, destroy NT receptors for life. Read more threads about the neurotoxicity of amphetamines. You would be surprised how a month of abstinence can make you feel much better.

My credibility is in that both amphetamine and GHB are my favorite drugs. Especially in combination. I was an addict at one point to both and I see no difference in my ability to function now that I no longer chronically take them without self-control.

 

[Epsilon Alpha]

If you want to strive for a state of "perma-win" try tracking down "JoePedo" at zoklet or whatnot, he's the go to guy on that. Personally, I'm not going to advise you go blasting yourself with all sorts of drugs to try to elicit a certain response from a system we don't really understand.

Also its alpha2 antagonists which are mainly responsible due to increased noradrenergic transmission, but we (as far as I've read) have no clue what elicits arousal. Hell we're still working on the finer details of awake vs asleep. Not trying to sound like a negative Nancy, but we don't really know what to look for or even how to properly stimulate it if we found a target.

 

[MeDieViL]

Ill elaborate more later but first of all i dont have any depression, and indeed amp aint a cure atleast not simular to a antibiotic but more to something like a beta blocker that normalises a issue, it is not a culprut if it is combined with memantine for tolerance and a daily break every week is taken, many anecdotes support that amp can be used chronically on a daily basis for a variaty of issues without tolerance.

Yes amp induced downregulation reverses easy and wont indeed never cause permament anhedonia, the issue caused by g is not caused by receptor downregulation as the GHB agonist amisulpiride or the gabab agonist phenibut dont cause any relief, it doesnt have to destroy receptors either, it can induce long term changes like "amphetamine sensitization" wich is mostly permanent, most drugs cause permanent changes albeit you wont really notice much effects of that subjectively.

Ive had breaks of drugs for longer then a year so im well aware a simple break wont reverse the issue, that said its a obvious thing to try but either way my anhedonia before g was really bad too

If you want to strive for a state of "perma-win" try tracking down "JoePedo" at zoklet or whatnot, he's the go to guy on that. Personally, I'm not going to advise you go blasting yourself with all sorts of drugs to try to elicit a certain response from a system we don't really understand.

Also its alpha2 antagonists which are mainly responsible due to increased noradrenergic transmission, but we (as far as I've read) have no clue what elicits arousal. Hell we're still working on the finer details of awake vs asleep. Not trying to sound like a negative Nancy, but we don't really know what to look for or even how to properly stimulate it if we found a target.

Id totally agree, its not something special im looking for, rather want the original effects of amp back wich is prob more easy to do then trying something crazy looking giving food the reward of a orgasm or shit

"perma-win"
Haha its a fun thing to discuss about, what may theoretically be possible.

Im not thinking we can do much here apart from starting a interesting discussion, the thing i really want to do is described in the other thread, trying to get the sex reward back amp caused in the old days, as it originally did that and does for most it may be easy to figure out what causes is and eventually how to get it back.

If you want to strive for a state of "perma-win" try tracking down "JoePedo" at zoklet or whatnot, he's the go to guy on that. Personally, I'm not going to advise you go blasting yourself with all sorts of drugs to try to elicit a certain response from a system we don't really understand.

Epsilon you should know me by now that i allways start out with a optimistic view that things are possible, i am just as skeptical as alot of others, the only difference is that starting from a viewpoint that things may be possible it keeps you more interested in researching to see wheter it can actually happen, while i agree most things would be impossible, with the viewpoint that it probably would be impossible ppl wouldnt bother trying to get some results and potentially miss out on one little possibility out of the 100 we can achieve. My nmda antagonist thread is a good example, there were a ton of differened things that worked for tolerance in rodents, most people said they wont work in humans, but by beleiving in them all i ended up discovering nmda antagonists do really work (there were a few succesfull anecdotes too tough but its just an example where optimism is better then disregarding the possibility from the start)

Like quercetine wich works for tolerance in my case to stims, its only been shown in rodents to block opiate tolerance because of no depletion, but you also know no depletion helps tolerance for many things

Those things were alot simpler to come up with, but i made a ton of interesting discoverys just based on limited evidence wich is enough to prompt me to try stuff, such as discovering nefiracetam completely reverses all positive shizo symptions including ones by amp
Enyway enough stim induced ramblings lol

My credibility is in that both amphetamine and GHB are my favorite drugs. Especially in combination. I was an addict at one point to both and I see no difference in my ability to function now that I no longer chronically take them without self-control.

I was too and no matter how long abstinence G barely works anymore, causes brainzaps and complex partional seizures the whole time, easily 5 a day if i end up in a binge, it def damaged me.

 

[sekio]

Medevil, spend 5 to 10 minutes before you post composing your thoughts so you're not posting 5 times in a row.

PS you will never get the original effects of amphetamine back - ever.

 

[MeDieViL]

Medevil, spend 5 to 10 minutes before you post composing your thoughts so you're not posting 5 times in a row.

PS you will never get the original effects of amphetamine back - ever.

I still got most of the original amp effects, just make sure the receptors that downregulate stay upregulated with things like memantine, only need to figure out why the sex effects dimished.

I also blame the original amp effects for all that posts in a row haha.

 

[MeDieViL]

It does seem indeed that test cause reward, its easy to safely increase it with chronic clomid doses, wonder wheter it does it directly or releases some peptides or something.

Pheromones are rewarding too

What else? Think guys

 

[sekio]

Given that nobody's actually come up with a compound they can legitamitely call a Homo sapiens pheromone I think you're really scraping the bottom of the barrel.

Environmental enrichment is the only thing I can think of that reliably increases "reward". You may be searching down the wrong path if you're starting to go the androgenic route - lack of sex drive/energy can be horomonally linked.

 

[MeDieViL]

Given that nobody's actually come up with a compound they can legitamitely call a Homo sapiens pheromone I think you're really scraping the bottom of the barrel.

Environmental enrichment is the only thing I can think of that reliably increases "reward". You may be searching down the wrong path if you're starting to go the androgenic route - lack of sex drive/energy can be horomonally linked.

Im well aware that environmental enrichment increases reward, atleast it doesnt increase reward the human reward system is based on inducing reward based on certain things, such as conversing with someone, hijacking the system and inducing reward without things that are rewarding is not what im looking for.

 

[Raza]

Subject is relevant to my interests. I've often noted the same distinction between euphoria/mental pleasure/action-motivation flow and physical pleasure in sex (although they're definitely both highly involved), and sought to improve them separately. I do think they're highly intwined, though; at least one major contributor to pleasure sensitivity is the level of arousal you can sustain without hitting orgasm, which derives directly from mood/motivation factors.

Psychedelics that enhance tactile sensations are one road. Foxy, moxy, most of the 2C's. All round, I would say these are probably the safest and surest bet for a significant (but by themselves, in people not otherwise wired for strong sexual pleasure, not overwhelming) improvement.

GHB/GBL seems to cause a marked shift in physical pleasure sensitivity towards torso and genital areas. This is easiest to note when not having sex on it, but rather using it to try to sleep. Sensations of 'softness' of the sheets and body awareness shift away from head, hands, arms legs and feet and towards the groin, chest and stomach.

Going by the way NMDA antagonists (like DXM, but other dissosiatives do much the same) ruin sexual pleasure, and glutamate's strong involvement in peripheral feedback in general, I've thought to look there as well. However, my first and so far only experiment with Sarcosine and DAA for sex fell flat because the Sarcosine made me really drowsy, which I've since observed it does whenever I'm not above-baseline stimulated when I take it. I intend to continue this experiment, though.

Opiates, I am told, can really make every touch feel awesome. 'Course, general opioid agonists kind of overshoot the mark of improving sexual pleasure, and pay for the extra distance with a load of drawbacks. Oxytocin (which I suppose might be the opioid motivation peptide for social connectiveness) enhances the pleasure of touch, but in males not usually specifically in a sexual way. Still a good thing to add when you can get it. You need to get digging for the motivation peptide for sex... what did that paper suggest it was, something-hormone-releasing-hormone? Any way we can get at that stuff?

Also, I've read some stuff that points to the anterior insula as a brain region responsible for registering the physical pleasure from sex. Mindfulness meditation is known to improve sexual enjoyment, and enlarges this brain region in regular practitioners. Trying this, too, although I don't expect it to be among the early benefits (which have otherwise been a pleasant surprise).

 

[MeDieViL]

Psychedelics massively induce glut release, sarcosine and DAA is like taking 5HTP (will do shit compared to releasers). GHB also releases glutamate like amp wich all markedly increase sex pleasure.

 

[JackiesBabyy]

Psychedelics massively induce glut release, sarcosine and DAA is like taking 5HTP (will do shit compared to releasers). GHB also releases glutamate like amp wich all markedly increase sex pleasure.

I've read in many places amphetamine's increase in sexual pleasure was because of dopamine activating d2. If there's more mechanisms to it than that I'm interested imn knowing, though.

And what sekio said about Major Depressive Disorder is correct, it's a disorder and MAOIs are great at treating resistant forms of it where you're "always anhedonic". Have you been checked for it?

 

[MeDieViL]

I've read in many places amphetamine's increase in sexual pleasure was because of dopamine activating d2. If there's more mechanisms to it than that I'm interested imn knowing, though.

And what sekio said about Major Depressive Disorder is correct, it's a disorder and MAOIs are great at treating resistant forms of it where you're "always anhedonic". Have you been checked for it?

Im not depressed at all, in fact allways in a happy slightly hypomanic mood without any drugs.

 

[JackiesBabyy]

Im not depressed at all, in fact allways in a happy slightly hypomanic mood without any drugs.

I don't think you're sure what your emotions are...happy slightly hypomanic yet anhedonic. That's like saying "it's a freezing cold blistery day out there, but it's also slightly warm and comfortable.". I've had anhedonia due to my depression and since happiness is a form of pleasure and that goes against the definition of anhedonia, a lack of pleasure in life or activities. Maybe try using another word to describe it besides anhedonia.

 

[MeDieViL]

I don't think you're sure what your emotions are...happy slightly hypomanic yet anhedonic. That's like saying "it's a freezing cold blistery day out there, but it's also slightly warm and comfortable.". I've had anhedonia due to my depression and since happiness is a form of pleasure and that goes against the definition of anhedonia, a lack of pleasure in life or activities. Maybe try using another word to describe it besides anhedonia.

Ive had depressive episodes because of stim abuse before, trust me i know the difference btw depression and just anhedonia, also had a episode of atypical depression once.

I know it would be hard to understand if its connected to depression for you, but its like antidepressants inducing anhedonia for some i suppose.

 

[JackiesBabyy]

Ive had depressive episodes because of stim abuse before, trust me i know the difference btw depression and just anhedonia, also had a episode of atypical depression once.

I know it would be hard to understand if its connected to depression for you, but its like antidepressants inducing anhedonia for some i suppose.

Maybe, I just can't imagine being anhedonic without also being depressed at the same time because of it.