Permanent state of euphoria, future approval of Sequenced Drug Regimens

[Bltucka]

I would like to discuss possible methods of developing a sequenced drug regimen to keep one in a euphoric state. This is meant to be a therapeutic regimen to treat certain mental illnesses, not a recreational one (though any recreational experiences will be helpful for research purposes so please do include!) and this is purely an intellectual discussion.

Having experienced euphoria from medications in the past and having spoken to others who have experienced what they would consider euphoria from the same or other medications/substances, I think it is safe to say that medically induced euphoria varies in intensity and dare I say definition from person to person. If euphoria is in fact an exactly defined feeling or state...which I think is near impossible to do when you consider the complexity of the brain... then perhaps those like myself who functioned in a pleasant, highly productive, cheerful manor while experiencing this euphoria are the exception. While i can see the potential issues with elongating a state of euphoria in someone who can not function productively and/or interact appropriately due to the ways in which the euphoria inducing medication/substance has affected their brain (keeping in mind their are many different chemicals effecting many different areas of the brain that can create this "euphoria"...) ...What it may even come down to is whether euphoria was ever the appropriate term for what these people are/were experiencing as the actual definition of euphoria is (too effing short in my opinion) "a feeling or state of intense excitement and happiness." People have suggested that euphoria borders mania (but personally i think there is a broad spectrum) and because they feel it borders mania they believe it a dysfunctional state to be in (If we agree that being in a state mania is dysfunctional ((which again is subjective and falls on a spectrum)) I agree that someone in a euphoric state at the high end of that spectrum (bordering mania) could potentially be too dysfunctional to gain any therapeutic value from remaining in that state. And perhaps the route used to obtain that euphoria needs to be altered, and possibly that particular person may wind up never being able to function in a state of euphoria... which brings us to this post.


As far as addiction goes there is much more at play there. And I do not think repetitively seeking a euphoric state defines addiction! Firstly no one should be self medicating or attempting to maintain a euphoric state without a professional's help (or so i write ), and right now as far as i know, that is not an available treatment option for any form of mental illness. The point of the original post was to discuss ways in which this could be achieved hypothetically from a medical perspective as a treatment for anxiety, depression, ADHD/ADD or even bipolar... I'm not sure enough about the brain of a person suffering from other mental illnesses to list this as a hypothetical treatment option. In no way am i suggesting that anyone try this on their own.

I have had people say to me that anyone wishing to remain in a euphoric state must be an addict and must be stopped. My problem with classifying everyone who would like to continue through life in a medically induced euphoric state as an addict is that what is really being said there, is that everyone's brain reacts to every medication or substance in the same exact way. This I'm sure we can agree is not the case. If the person seeking to continue experiencing euphoria is dysfunctional, dangerous, or harming themselves while in that euphoric state (or if they are on an illegal recreational drug that is ruining/ endangering their life or someone else's ) then I would say that person may very well be an addict and probably would not be a candidate for what could be a very therapeutic treatment for someone else who tolerates the euphoric state better.


I do love reading everyone's take on this though so please do write back

Some things I would like to discuss are

-Mechanisms of action as pertaining to psychiatric drugs and
Ways in which we can rotate through medications/substances (or future ideas for medications (based on actual science ..not a hypothetical cure all magic pill lol) to continually elevate (or alter) known euphoria producing sectors of the brain.
-Any research done on this topic
-and personal opinions or experiences on the subject.


Below is a bit about me not related to the post. so stop here if you are only interested in original topic.
_________________________________________________________________________________________________________________________________

About me = 29 year old female, suffering with bipolar disorder, Anxiety, stage 4 endometriosis (inoperable due to excessive internal abdominal scaring from internal bleeding and multiple surgeries) ADHD...diagnosed and treated (and documented) as a child but forgotten about (bipolar was ALWAYS to blame ((despite my reminders of my childhood diagnosis of ADHD)) for my symptoms... according to a series of close-minded inattentive doctors who I have a hard time forgiving for destroying my life.

 

[Charles_Voynich]

I don't know if this is exactly what you're getting at, but there's been some talk in the medical community of not only using ketamine to treat acute, treatment-resistant depression, but also as a prophylactic for at-risk people. Not a lot is know at this point about the long-term effects of using ketamine in this way, but the research is definitely promising;

http://www.biologicalpsychiatryjournal.com/article/S0006-3223(15)00360-1/abstract

[h=3]Background[/h]Stress exposure is one of the greatest risk factors for psychiatric illnesses like major depressive disorder and posttraumatic stress disorder. However, not all individuals exposed to stress develop affective disorders. Stress resilience, the ability to experience stress without developing persistent psychopathology, varies from individual to individual. Enhancing stress resilience in at-risk populations could potentially protect against stress-induced psychiatric disorders. Despite this fact, no resilience-enhancing pharmaceuticals have been identified.


[h=3]Methods[/h]Using a chronic social defeat (SD) stress model, learned helplessness (LH), and a chronic corticosterone (CORT) model in mice, we tested if ketamine could protect against depressive-like behavior. Mice were administered a single dose of saline or ketamine and then 1 week later were subjected to 2 weeks of SD, LH training, or 3 weeks of CORT.


[h=3]Results[/h]SD robustly and reliably induced depressive-like behavior in control mice. Mice treated with prophylactic ketamine were protected against the deleterious effects of SD in the forced swim test and in the dominant interaction test. We confirmed these effects in LH and the CORT model. In the LH model, latency to escape was increased following training, and this effect was prevented by ketamine. In the CORT model, a single dose of ketamine blocked stress-induced behavior in the forced swim test, novelty suppressed feeding paradigm, and the sucrose splash test.


[h=3]Conclusions[/h]These data show that ketamine can induce persistent stress resilience and, therefore, may be useful in protecting against stress-induced disorders.

 

[jaiho]

A permanent state of euphoria isn't possible with drugs, what goes up must come down.
If you cycle multiple drugs of different mechanisms, they are all targeting the same pleasure centers, just via different mechanisms. The end result is a reduced pleasure response in everyday life, and eventually no drug will be able to activate euphoria/reward response.

The closest you could get is artificial happiness, high dose SSRI or high dose MAOIs with augmentation strategies to further dopamine transmission.

The only way to achieve it would be to get DBS (Deep brain stimulation) planted near the nac shell. There is no tolerance to electrodes stimulating the pleasure centers.

 

[sekio]

Permanent euphoria is not only counterproductive, it's not achievable due to the self-limiting nature of the reward circuitry in the NAcc (more euphoria = less effect of more dopamine release = harder to stay euphoric)

Balance in all things.... trying to stay doped up 24/7 will inevitably have negative side effects or will stop working entirely.

 

[Bltucka]

A permanent state of euphoria isn't possible with drugs, what goes up must come down.
If you cycle multiple drugs of different mechanisms, they are all targeting the same pleasure centers, just via different mechanisms. The end result is a reduced pleasure response in everyday life, and eventually no drug will be able to activate euphoria/reward response.

The closest you could get is artificial happiness, high dose SSRI or high dose MAOIs with augmentation strategies to further dopamine transmission.

The only way to achieve it would be to get DBS (Deep brain stimulation) planted near the nac shell. There is no tolerance to electrodes stimulating the pleasure centers.

A permanent state of euphoria isn't possible with drugs, what goes up must come down.
If you cycle multiple drugs of different mechanisms, they are all targeting the same pleasure centers, just via different mechanisms. The end result is a reduced pleasure response in everyday life, and eventually no drug will be able to activate euphoria/reward response.

The closest you could get is artificial happiness, high dose SSRI or high dose MAOIs with augmentation strategies to further dopamine transmission.

The only way to achieve it would be to get DBS (Deep brain stimulation) planted near the nac shell. There is no tolerance to electrodes stimulating the pleasure centers.

Hi I understand what you are saying. and thank you for writing!! I am going to be reading a lot more on DBS it is very interesting... It seems like you already understand what I am trying to describe , but if i worded it wrong, to be clear I was referring to switching from targeting one euphoria producing site to another while also changing the mechanism of action if needed to preserve or assist in the replenishment of the previously "treated" area. Assuming the euphoria experienced was comparable as well as tolerated, would it be possible to induce euphoria via say an increase in serotonin through ___ mechanism until depletion caused the treatment to be ineffective, and then begin to target another neurotransmitter like dopamine in a way that would not effect serotonin levels therefore allowing the body time to replenish it's serotonin , or are you saying that this would cause long term damage to the body's ability to produce serotonin/dopamine etc naturally- permanently?

Also haven't MAOIs been linked to just that... permanently low levels of serotonin / dopamine (I've read conflicting studies on this) ? I always wondered why they were not being used as frequently , I know they do interact with many things making them a complicated medication to take if you don't pay attention to what you are ingesting (guilty) ... 20ish, 15ish years ago they were quick to prescribe MAO inhibitors, lately not so much.

If depletion was a long term or permanent response to continually raised neurotransmitter levels... Has anyone found any studies on reversing this drug induced depletion? If i find any studies worth posting I will add them.

 

[jaiho]

are you saying that this would cause long term damage to the body's ability to produce serotonin/dopamine etc naturally- permanently?

Pretty much this, yes. The brain is always trying to reach homeostasis, the body treats drugs as poison, fighting against them & trying to rid them from your body as quickly as possible.
Drugs of euphoria basically trick the brain into releasing chemicals, which have downstream effects of activating pleasure response.

So eventually your pleasure center will no longer respond to pleasure when you continue cycling between drugs. You could probably maintain a weekend of euphoria each week or two, using things like Phenibut, Amphetamines, opiates or psychedelics, but not daily.

MAOIs are the only anti depressant that lift mood in people who aren't depressed. They increase all three neurotransmitters. You can also augment NRI based drugs to MAOIs to eliminate the need for the diet.
They don't interact with many drugs, you only need to worry about SRIs and releasers.

With DBS you can control the power output of the electrodes to your reward centre. Increasing the voltage on the remote equals more pleasure, and happiness. People report finding new love for music they never were interested in before DBS.

https://www.theguardian.com/music/2014/may/27/johnny-cash-deep-brain-stimulation-urge-listen

 

[Seppi]

Permanent euphoria is not only counterproductive, it's not achievable due to the self-limiting nature of the reward circuitry in the NAcc (more euphoria = less effect of more dopamine release = harder to stay euphoric)

Balance in all things.... trying to stay doped up 24/7 will inevitably have negative side effects or will stop working entirely.

^ Re: what Sekio said.

 

[Bltucka]

I don't know if this is exactly what you're getting at, but there's been some talk in the medical community of not only using ketamine to treat acute, treatment-resistant depression, but also as a prophylactic for at-risk people. Not a lot is know at this point about the long-term effects of using ketamine in this way, but the research is definitely promising;

http://www.biologicalpsychiatryjournal.com/article/S0006-3223(15)00360-1/abstract

This is also very interesting!! Thank you so much for sharing

 

[Charles_Voynich]

Just to be clear, I wasn't suggesting that was a way to achieve a "permanent state of euphoria". However, in my mind, I feel like if I could live every single day free of any kind of depression, with my memory and critical thinking skills all working at 100% of their capacity, I'm pretty positive I would essentially feel high all the time. At the end of the day, chemically-induced happiness is great, but I would personally prefer that my happiness and satisfaction was due to me perceiving the world with the most clarity, rather than with the least.

 

[Bltucka]

Just to be clear, I wasn't suggesting that was a way to achieve a "permanent state of euphoria". However, in my mind, I feel like if I could live every single day free of any kind of depression, with my memory and critical thinking skills all working at 100% of their capacity, I'm pretty positive I would essentially feel high all the time. At the end of the day, chemically-induced happiness is great, but I would personally prefer that my happiness and satisfaction was due to me perceiving the world with the most clarity, rather than with the least.

I agree! Personally I am happy with the way my mind is functioning on my current medications (finally). I obviously do not experience any euphoria...And any that I have experienced in the past was clearly from starting the Adderall. This is what got me thinking about the potential benefits that this could have for others.
________________
Also to everyone,
So many researchers are working on a cure for Parkinson's disease... and whether or not you are going to develop PD, permanent decreases in Dopamine (among others ((Seratonin, Glutamate)) do occur with age. Future cures for this may also be able to consistently replenish dopamine levels for the purpose discussed. At the moment all I have found is this http://www.nejm.org/doi/full/10.1056/NEJM200103083441002#t=article which is obviously too invasive for the purpose of artificial happiness lol (unless transplanting an excess amount would somehow allow for longer durations of euphoria) Not to go all sci-fi on everyone lol - but in many films/shows the idea of controlling the masses by inducing a permanent state of bliss...or euphoria is presented. I imagine that our government would be interested in this knowledge

 

[Seattle_Stranger]

I want to know more about this "electrodes stimulating pleasure centers with no tolerance buildup".

I can see it now...

It's the year 2050, you can home from a long day of work, you sit down, you put on your shiny new HighHat(tm), set the dial to "chillax", and enjoy hours and hours of wave after wave of euphoric pleasure. If you think any human being would ever remove this hat, you're nuts. That would be the last generations of human beings to ever reproduce.

 

[Bltucka]

I want to know more about this "electrodes stimulating pleasure centers with no tolerance buildup".

I can see it now...

It's the year 2050, you can home from a long day of work, you sit down, you put on your shiny new HighHat(tm), set the dial to "chillax", and enjoy hours and hours of wave after wave of euphoric pleasure. If you think any human being would ever remove this hat, you're nuts. That would be the last generations of human beings to ever reproduce.

hahahaaa!

 

[jaiho]

It's used for treatment resistant depression mostly
But im sure the surgeons put in limits on the remote to stop you from always experiencing euphoria.
And then im sure there will be some hacker to find a way to get around it then find himself never leaving his room.

I want to know more about this "electrodes stimulating pleasure centers with no tolerance buildup".

I can see it now...

It's the year 2050, you can home from a long day of work, you sit down, you put on your shiny new HighHat(tm), set the dial to "chillax", and enjoy hours and hours of wave after wave of euphoric pleasure. If you think any human being would ever remove this hat, you're nuts. That would be the last generations of human beings to ever reproduce.

 

[luckys1evin]

I can sympathize Depression and the embarassing social anxiety for me, but you can have permanent Euphoria (Unless you wanna be a HARDcore doper). Again I relate Id like nothing more than not even Euphoria just a sense of well being like a single 10 Hydrocodone. If I took 1 three times a day I could stay in an almost Euphoric state, then what? Im addicted, probably broke maybe worse. Besides humans like any animal can stay in that state or our insticts would "rot". Think about it never having to react because youron cloud nine, Not to mention it takes BEING sober to appreciate the high right?

 

[luckys1evin]

Herion along with all drugs alchohal and nicotine OUT OF BUISS lol If permanent happiness were possible.

 

[luckys1evin]

To recieve "Pleasure " Your brain has to pump a chemical called Dopamine and Serotonin problem is (And this is why junkies look and act like they do after a 4 day upper) Their body has no more Dopamine to use. So keeep sniff lines wont help. Hell anything that causes u pleasure imagine a lil slightly /slowly refillable tank*** of "Feel good Chms" Once you over do it well you've prlly seee a crashing tweaker on tv or sum? He has no more Happy Chems so the rest in his brain dont know what to do exactly and act up a lil

 

[luckys1evin]

Just to be clear, I wasn't suggesting that was a way to achieve a "permanent state of euphoria". However, in my mind, I feel like if I could live every single day free of any kind of depression, with my memory and critical thinking skills all working at 100% of their capacity, I'm pretty positive I would essentially feel high all the time. At the end of the day, chemically-induced happiness is great, but I would personally prefer that my happiness and satisfaction was due to me perceiving the world with the most clarity, rather than with the least.<------ SOunds like Euphoria to me?

 

[Bltucka]

Hey lucky and everyone,

Yes I know what you mean... and yes I agree with all those who said that ups and downs are essential to recognizing and appreciating the happier times. But still in a modern world, safe in your home (or an institution for that matter) where instincts are not important or necessary, I can still see the therapeutic value for talk therapy sessions in people suffering with depression, ptsd, anxiety...

 

[Bravoncius Roxford]

Actually, euphoria is a very, very good thing. What is not good are pain, depression and anxiety. I do agree that intense euphoria is not only not physiologically sustainable but also not phsyically sustainable. But living in a state of mild euphoria isnot only physiologically possible but the single best thing you can wish for. Hpomaniacs not only never crash, but they also have better health and live longer than "normal" people. Roosevelt and physicist, Freeman Dyson, are examples of hypomaniacs that were very successful in life. Hypomaniacs, or euthymics, are the most blessed people in the World. They have in abundace that wich everyone wants: happiness. The only thing that really matters. Everything else we have and do are just means to that end, happiness. Euthymics already have it coded in their DNA - and the evidence is that hypomania, like melancholic depression, is largely genetic. Also, dopamine is not a pleasure chemical. It is merely related to wanting pleasure. Pure pleasure appears to be mediated by Mu opioid receptors and encocannabinoid recepotors.

 

[Cotcha Yankinov]

I'm not convinced that all chronic hypomanics don't have crashes, but I wonder if they tend to have overall more total positively valenced experience.

Or maybe euthymia necessitates some traits that lead to more suffering, in today's environment, wherein happiness is to some degree defined by behavior (and the resultant outcome), and the behavior of a euthymic can be dysfunctional in our societies.