11 replies to this topic

[Luntai]

Hi guys.

I read somewhere (and I just can't find it!) that it is possible to help the brain with supplements and/or super food to regenerate receptors or releaser capacity of eg. seretonin, rather than just feeding it and over time building tolerance. Is this intro understandable?

The point is to help the brain to naturally produce this in a larger degree, naturally, without needing to supply it.


One of the reasons for this is harm reduction after MDMA trips or others. I worry that this not only depletes the receptors and their ability to absorb, as well as the body's capacity or ability to make these neurotransmitters.

Personally I've also experienced a lot of depression and is still struggelig with this.

Cannabis, but especially MDMA, has been a very good help and MDMA made me wanna try again (Warning: MJ can worsen depression by making already experiences stronger if used wrong). I didn't really experience the bad comedown others suggested and felt this great afterglow afterwards. Therefore I'm trying to seek as much info about harm reduction as I can, my first meet with molly will not be the last. I don't want to deplete my brain/receptors.


So, do you think it's possible to regenerate receptors? And is there anything else relevant you can think of? I'm a fan of natural stuff. I'd be happy to learn more and hear corrections, I am just a person who reads a lot on the internet.

Edited by Luntai, 03 September 2014 - 07:42 AM.

[Area-1255]

To "rebuild" receptors you have to understand the main signaling compounds that lay the groundwork for "receptors" in the first place.

For example, Testosterone in proper ratio with estrogen will facilitate Dopamine (D2) receptor expression. Due to brain testosterone being converted somewhat into estrogen, endogenous/exogenoue Estrogen can't cross the Blood-Brain-Barrier as readily and thus Testosterone is responsible (ultimately) for effects of brain estrogen. (!) (!) (!)

 

Neurosteroids, Vitamin D, histamine status and many more all contribute to one's neurochemical profile.

 

Vitamin D is positively correlated with higher dopamine and serotonin levels; this is thought to be due to Vitamin D's action on NT hydroxylase enzymes.(!) (!)

Tryptophan Hydroxylase and Tyrosine Hydroxylase are the rate-limiting enzymes determining production of neurotransmitters from amino acids. (!)

Other enzymes involved in central NT activity include decarboxylase's. Decarboxylase can not be generalized, as each NT's decarboxylase enzyme seems to shuttle things in a different direction.

 

Glutamate Decarboxylase (GAD) converts Glutamate into GABA. (!)

Histidine Decarboxylase    (HDC) converts histidine into histamine. (!)

DOPA Decarboxylase shuttles dopamine into the periphery, leaving less effects in the brain. However, it shows minor positive effects on other rate limiting enzymes. (!)

 

 

Edited by Area-1255, 03 September 2014 - 08:04 AM.

[Flex]

Thats right.

Its not everything about the receptors.

Lesser Dat (Dopamine transporter) and/or lesser Vmat2 decrease dopamine to a very good extend.

(Afaik PKC, which is glutamate driven, inhibits the reuptake on the DAT)

See this interresting article:

Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo

http://www.pnas.org/...7/9977.abstract

So Vmat2, Dat, Gdnf, Bdnf and TH are such important that they are constantly mentioned in the parkinson research.

 

The only thing what pops in my mind for now is CDK5. Although I´m not 100% sure whether it increases Dopamine receptor expression,

it decreases at least the expression when activated.

Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream Signaling

http://www.plosone.o...al.pone.0084482

 

And acetyl-carnitine affects CDK5 and increases Dopamine in the nucleus accumbens permanently

Repeated acetyl-l-carnitine administration increases phospho-Thr34 DARPP-32 levels and antagonizes cocaine-induced increase in Cdk5 and phospho-Thr75 DARPP-32 levels in rat striatum.

http://www.nature.co...l/4000805a.html

 

EDIT :

Phosphatidylserine is a supplement that increases the gene expression of proteins that are implicated in Parkinson

http://www.israel21c...insons-disease/

So it would´nt hurt to take it. The only thing is that PS inhibits Platelet factor (?) 1 or 3.

I´ve forgott it, Anyway be carful when using it with other bloodthinning stuff and better dont overdose it.

 

Edited by Flex, 03 September 2014 - 06:02 PM.

[Ames]

Worrying about depleting brain receptors is a bit silly when doing MDMA. That's a bit like asking what supplements to take to reduce lung damage so that you can look forward to voluntarily rushing into a buring building next week. If you don't want to do brain damage, then don't do it. The brain damage is unnavoidable. It's also extensive, despite the common starry-eyed ridiculous rationalizations of people who enjoy its properties.

 

That being said, keep in mind that MDMA is a type of methamphetamine. Memantine has been shown to prevent serotonin induced hyperthermia in the brain during MDMA use, and 5-HTP preloading consistenly will attenuate amphetamine induced neurotoxicity. In my opinion, this is 5-HTPs primary neurotportective effect. It protects dopaminergic neurons. I like the 50mg dose every few days, as that provides a nce dompanine boost for me and noticeably reduces motor neuron symptoms. Any more than that tends to blunt a dopaminergic rebound for me and can lead to strange emotional effects. However, take more if you want to feel what taking too much may do. That might be worthwhile to get a feel for it. Also, everyone likely has their own best dose with 5 HTP. Just watch the potnetial for nausea at higher doses. Go slow.

 

Enhancing your natural and sober mood will provide you with far more life pleasure in the long run, especially when you consider that MDMA induced brain damage can potentially provide you with decades of sub-optimal function and depressed mood not to metion, perhaps, unforseen diseases later in life. However, I know that people have to find their own truth, and need to bottom out in their own way. I would recommend a decade of heavy cannabis use to burn yourself out on before I would recommend even a short period of MDMA use.

 

If you want to look into something else, then search fro the tagsync neurofeedback threads, save $2,000, buy the equipment, and then have a targeted high tech method of improving your natural brain function for as long as the equipment functions. Or take up skydiving.

Edited by golgi1, 04 September 2014 - 06:22 AM.

[Area-1255]

Worrying about depleting brain receptors is a bit silly when doing MDMA. That's a bit like asking what supplements to take to reduce lung damage so that you can look forward to voluntarily rushing into a buring building next week. If you don't want to do brain damage, then don't do it. The brain damage is unnavoidable. It's alos extensive, despite the common starry-eyed ridiculous rationalizations of people who enjoy its properties.

 

That being said, keep in mind that MDMA is a type of methamphetamine. Memantine has been shown to prevent serotonin induced hyperthermia in the brain during MDMA use, and 5-HTP preloading consistenly will attenuate amphetamine induced neurotoxicity. In my opinion, this is 5-HTPs primary neurotportective effect. It protects dopaminergic neurons. I like the 50mg dose, as that provides a nce dompanie boost for me and noticeably reduces motor neuron symptoms. Any more than that tends to blunt a dopaminergic rebound for me and can lead to strange emotional effects.

5-HTP doesn't have dopaminergic effects; on the contrary they are anti-dopamine.

Though some receptors of serotonin may promote dopamine activity, the vast majority don't - and emotional blunting is not uncommon but ubiquitous with artifical (or excessively natural) serotonin boosting.

5-HT1A receptors for example, pre-synaptically are "autoreceptors" that act to inhibit serotonin release and firing.

The post-synaptic 1A receptors are neuroendocrine modulators, mainly promoting beta-endorphin, prolactin and corticosteroid synthesis.

They are also highly inhibitory on both GABA and Dopamine, as well as histamine and NMDA - mainly in the paraventrical nucleus (PVN).

There a few reasons that is bad.

1.) The PVN containing neurons act as both fast-action-potentials and are crucial in regards to motor speed and cognitive functioning. 

2.) This specific region and the inhbition thereof, will produce negative hormonal effects and summon a heavy suppression of your libido and general desire to do anything worth doing.

 

Agonizing (stimulating) 5-HT1A receptors on the other hand will promote dopamine in the nucleus accumbens, and probably in the prefrontal cortex as well - but although this can potentially be helpful in some cases, the negative over riding effect seen by upstream neurons largely short-circuits the temporary benefits. Maybe not immediately, but eventually 5-HT1A activity will cause intellectual deficits. Hence why chemicals that are 5-HT1A antagonists ; may be used and are being investigated for, Alzheimer's and Dementia, they promote acetylcholine and glutamate release (5-hT1A blockers). (!) (!) (!)

 

5-HT1A blockers can also treat and / or cure SSRI-induced sexual dysfunction, with or without type 2A/C antagonists, or any other serotonin antagonist for that matter. 

 

5-HT1A blockade will also lead to a reduction in cortisol, prolactin, ACTH etc

5-HT1A blockade POTENTIATES long-term growth because it leads to increases in histamine, NMDA, testosterone,DHEA, glutamate, acetylcholine etc..

 

Besides the H(3) histamine receptor, 5-hT1A receptor is overlooked and is another piece of garbage in the human biochemistry that is passed off as having immense benefits which are really illusions. 

 

I can tell you firsthand that the best I have ever felt is when 5-ht1a receptors were blocked and histamine H3's are blocked.

I experimented with LECOZOTAN (an experimental 5-hT1A antagonist) and I can easily say that it the SINGLE MOST POTENT NOOTROPIC/ANTIDEPRESSANT compound I have ever found (besides betahistine and other H3 antagonists).

 

 

http://www.ncbi.nlm....pubmed/12183221

http://www.psyneuen-...0088-9/abstract

http://www.oxfordsch...0118-chapter-11

http://www.google.co...tents/US7425558

http://www.ncbi.nlm....cles/PMC446220/

Edited by Area-1255, 04 September 2014 - 06:37 AM.

[Luntai]

Thanks for the replies. Although I don't understand much, it goes a bit too deep. So I'm not sure what to make of this now. :P

I haven't replied to the rest here. I read it several times, but honestly I don't know what to answer to it because it's over my knowlegde. I am a bit confused. :P

Worrying about depleting brain receptors is a bit silly when doing MDMA. That's a bit like asking what supplements to take to reduce lung damage so that you can look forward to voluntarily rushing into a buring building next week. If you don't want to do brain damage, then don't do it. The brain damage is unnavoidable. It's also extensive, despite the common starry-eyed ridiculous rationalizations of people who enjoy its properties.
 
That being said, keep in mind that MDMA is a type of methamphetamine. Memantine has been shown to prevent serotonin induced hyperthermia in the brain during MDMA use, and 5-HTP preloading consistenly will attenuate amphetamine induced neurotoxicity. In my opinion, this is 5-HTPs primary neurotportective effect. It protects dopaminergic neurons. I like the 50mg dose every few days, as that provides a nce dompanine boost for me and noticeably reduces motor neuron symptoms. Any more than that tends to blunt a dopaminergic rebound for me and can lead to strange emotional effects. However, take more if you want to feel what taking too much may do. That might be worthwhile to get a feel for it. Also, everyone likely has their own best dose with 5 HTP. Just watch the potnetial for nausea at higher doses. Go slow.
 
Enhancing your natural and sober mood will provide you with far more life pleasure in the long run, especially when you consider that MDMA induced brain damage can potentially provide you with decades of sub-optimal function and depressed mood not to metion, perhaps, unforseen diseases later in life. However, I know that people have to find their own truth, and need to bottom out in their own way. I would recommend a decade of heavy cannabis use to burn yourself out on before I would recommend even a short period of MDMA use.
 
If you want to look into something else, then search fro the tagsync neurofeedback threads, save $2,000, buy the equipment, and then have a targeted high tech method of improving your natural brain function for as long as the equipment functions. Or take up skydiving.

It's not silly. I'm trying to research harm reduction here, which tells you I care about my health, but also tells you: I am a psychonaut who is greatly interested in this stuff. Mostly I take stuff to improve and learn about myself, but no one can say it ain't fun too.

MDMA has been a great help getting me in the right direction and realising what is important for happiness. It was a immensely great experience which I want to do again. I'm taking supplements to reduce liver damage, brain damage and so on and want to know more. Since it's such a good help for me and such an great experience I of course want to do it again.

I had a look at this site: www.rollsafe.org It mentiones a lot of harm reduction tips.

Yeah. That's what I wanna do (enhancing sober mood), I have this rule to wait at least 3 months between each roll, but in practice it will be at least 6-10 months.

Tagsync neurofeedback sounds interesting. Is that a way of mapping brain activity and understanding how it works and then try to alter this? Correct me if I'm wrong.

[Ames]

5-HTP doesn't have dopaminergic effects; on the contrary they are anti-dopamine.

Though some receptors of serotonin may promote dopamine activity, the vast majority don't - and emotional blunting is not uncommon but ubiquitous with artifical (or excessively natural) serotonin boosting.

 

I know that emotional blunting is common. That's what I stated, and that's what occurs with any experimentation of serotonin promoting agents in excess quantities. This is common knowledge.

 

Let me ask you a question. If a substance protects against amphetamine induced neurotoxicity, protects dopmainergic neurons, promotes dopamine release, and enhances sexual function and drive in small doses, would it be categorically safe to say that it enhances dopaminergic function?

 

I would say that this specific action profile better adheres to a responsible semantic categorization of "dopamine enhancing" then do most molecules that are commonly accepted as dopamine enhancing. This is because 5-HTP seems to enhance dopamine through a protective and upregulating role rather than as a direct agonist leading to eventual down-regulation. In other words, at a specific correct dose and frequency, 5-HTP seems to upregulate dopamine function. However, experientially, that correct dose and frequency window is sensitive in terms of realizing an upregulation effect that surpasses mere preservation of function in the face of neurotoxicity. Even 50 mg too much can suppress dopamine for days, in my experience. Once you know what dopamine suppression and dopmine enhancement feel like, it's quite easy to identify what is going on. That being said, a relative overdose likely still has robust protective effect on dopaminergic neurons in the presence of strong dopamine agonists such as anything in the amphetamine class.

 

5-HTP protects dopmainergic neurons, an action which has a dopaimine enhancing effect that, I suspect, would level out with chronic use. 5-HTP also has an initial HGH agonism effect that quickly ceases with chronic use. Therefore, it would likely be best to supplement with it intermittently every few days, and at a reasonable dose, to realize the dopamine enhancing effect. In fact, this is the exact effect that I get with intermittent use at relatively low doses. 100 mg suppresses dopamine for me, leading to depression and reduced sexual drive. 50 mg every few days mildly enhances mood, blunts anxiety (possibly the mechanism of mood enhancement - the anxiety suppression does increase with dose likely due to an increasing ability to block neurepinephrine production), mildly increases motivation, and markedly enhances sexual drive. Too much of it crushes motivation, energy, and sex drive. It also potently protects against excitotoxicity and the resultant inflammation, an issue that I currently have two decades of experience with. If a person does not have such an issue, then their experience with 5-HTP will likely be different. However, the OPs issue is that he is looking to protect against a stimulant rather than to solve for an energy deficit in the brain.

 

This paper confirms what I experience, and the 6 hour delayed rise in dopamine hints at an adaptive upregulation in my opinion. In my experience, 6 hours is subjectively how long it takes:

 

http://neurosciencem..._depletes-3.pdf

 

Single dose 5-HTP mediated GH release:

 

http://press.endocri...0/jcem-36-1-204

 

5-HTP supplementation delays ALS:

 

http://www.ncbi.nlm....pubmed/14527871

 

5-HTP supplementation reduces amphetamine self-administration in rats:

 

http://www.sciencedi...091305786903977
 

5-HTP reduces the undesireable locomotor effects of amphetamine:

 

http://www.ncbi.nlm....les/PMC3044786/

 

5-HTP enhances dopamine release in rats administered MDMA:

 

http://onlinelibrary...0243.x/abstract

 

A study that I have very recently read, but that I can now not seem to find, concluded that 5-HTP preserves motor neuron function. Though, you can infer that from some of the above studies.

 

 

 

OP, here is a study for you:

 

MDMA induces programmed death of human serotogenic cells and leads to long-term neuropsychiatric behaviors such as  panic and psychosis:

 

http://www.fasebj.or.../2/141.full.pdf

 

And it fucks your memory:

 

http://link.springer...3-1463-5#page-1

 

Not to sound too dick-ish, but you may be back on this board in a few years trying to work out how to handle your newfound anxiety and likely depression, as well as how to regain your lost healthy stress response. FYI, there isn't much help on here for those conditions nor memory loss. Good luck!

Edited by golgi1, 04 September 2014 - 06:07 PM.

[Flex]

You could aternatively try psylocibin

http://guardianlv.co...ster-headaches/

http://www.theguardi...reat-depression

 

If everything goes well, it anti-anxiety effects do supposedly last for 1 Year !

If not, You might become more anxious for 1 Year

 

No seriously, I´ve looked into http://www.rollsafe.org/

and I´m a bit sceptic whether Acetyl-carnitine, Magnesium and vitamin C  would be sufficient.

The problem with green tea is its advantage at the same time.

It thinns the blood potently because two green tea capsules from Olimp with 250mg and 55% EGCG are as strong as aspirine, if not even stronger

http://www.raysaheli.../catechins.html

 

5-ht on its self thickens it. But if You get a high blood pressure due MDMA and take then blood thinners,

it could be problematic.

Admittelyits just my theory, I actually dont know it.

Edited by Flex, 04 September 2014 - 10:21 PM.

[Luntai]

MDMA induces programmed death of human serotogenic cells and leads to long-term neuropsychiatric behaviors such as  panic and psychosis:
 
http://www.fasebj.or.../2/141.full.pdf
 
And it fucks your memory:
 
http://link.springer...3-1463-5#page-1
 
Not to sound too dick-ish, but you may be back on this board in a few years trying to work out how to handle your newfound anxiety and likely depression, as well as how to regain your lost healthy stress response. FYI, there isn't much help on here for those conditions nor memory loss. Good luck!

I appreciate the input. I'm all about getting your views of it, pro or against.

I have (and am) already struggelig with depression, anxiety and fucked up child hood for many years now. My concentratiion and memory too, although my memory is actually pretty good. But the problem is finding the right memory and getting the brain to do what I want. I think it's years of misprogramming and undereating, living depressed, unstimulated, unhealthy and expecting perfection. Nuff about that.

My point is, should I be worried? I've done MDMA one time, ate/drank well, took vitamins, anti-oxidants and magnesium.


Maybe I'll just stick to herbs, LSD and magic mushrooms (haven't tried the last two)?

I've already experienced great results from nootropics and cannabis. I now learn better and can program and change. I also think that ego softening is great for me, although I was scared of this and thought it meant to remove what you've learned and get kinda empty.

Think I gotta start a new thread about this in particular before I start ramblin'.
 
 

You could aternatively try psylocibin
http://guardianlv.co...ster-headaches/
http://www.theguardi...reat-depression
 
If everything goes well, it anti-anxiety effects do supposedly last for 1 Year !
If not, You might become more anxious for 1 Year
 
No seriously, I´ve looked into http://www.rollsafe.org/
and I´m a bit sceptic whether Acetyl-carnitine, Magnesium and vitamin C  would be sufficient.
The problem with green tea is its advantage at the same time.
It thinns the blood potently because two green tea capsules from Olimp with 250mg and 55% EGCG are as strong as aspirine, if not even stronger
http://www.raysaheli.../catechins.html
 
5-ht on its self thickens it. But if You get a high blood pressure due MDMA and take then blood thinners,
it could be problematic.
Admittelyits just my theory, I actually dont know it.

Haha, know what you mean. I know it probably can't be compared, but bad (depressive) trips with cannabis has left me a bad period after, but I learned to avoid this. And it has tought me so much, I am now able to do small programming when sober. And good (fun, functional) trips gives me a good period after.

I feel that cannabis makes the brain more flexible, that it increases brain plasticity rather. That can explain why I am able to change my way of thinking and that for some it can worsen depression. Because it's ruled by your emotions, it doesn't make you either more or less depressed or happy. It depends on you. Anyone (dis)agree?

So yeah, I'll try magic mushrooms. I feel I gotta prepare myself though, because I know anxiety "attacks" is just terrible when sober, it gotta be total hell with shrooms. It can be truly hell with pot too, as I experienced after 1.2 grams in oil the first time, after 40 mins it hit us. Started great, ended in hell. Never experienced anything worse.


Again, not sure what to make of this. I think my MDMA use is on hold, and I'm thinking adaptogens, herbs and superfood will be a good way to go. I'm gonna try St. Johns Wort for depression.

Think I wanna start a thread about dealing with such, using drugs and herbs as tools and other experiences as well as mine. This forum the right place for this?

[Bateau]

Rhodiola and Bromantane are gonna be two of your best bets, Rhodiola having more significant effects on serotonin and bromantane having more significant effects on dopamine.

 

Rhodiola:

http://www.ncbi.nlm....pubmed/24323403

http://www.ncbi.nlm....pubmed/22921986

http://www.ncbi.nlm....pubmed/19403286

http://www.ncbi.nlm....pubmed/19260327

http://onlinelibrary...5.tb00073.x/pdf

http://cms.herbalgra...988ce0a6f627633

 

 

Bromantane:

http://www.ncbi.nlm.nih.gov/pubmed/10198757

http://www.ncbi.nlm.nih.gov/pubmed/15500036

http://www.ncbi.nlm.nih.gov/pubmed/16915929

http://www.ncbi.nlm.nih.gov/pubmed/17854844

http://www.ncbi.nlm.nih.gov/pubmed/20369592

http://www.ncbi.nlm.nih.gov/pubmed/20408420

[Bateau]

 

I experimented with LECOZOTAN (an experimental 5-hT1A antagonist) and I can easily say that it the SINGLE MOST POTENT NOOTROPIC/ANTIDEPRESSANT compound I have ever found (besides betahistine and other H3 antagonists).

 

 

 

What 5-ht1A and H3 antagonists have you experimented with besides Conessine, Betahistine and Lecozotan?

Edited by Bateau, 05 September 2014 - 05:39 PM.

[Area-1255]

 

 

I experimented with LECOZOTAN (an experimental 5-hT1A antagonist) and I can easily say that it the SINGLE MOST POTENT NOOTROPIC/ANTIDEPRESSANT compound I have ever found (besides betahistine and other H3 antagonists).

 

 

 

What 5-ht1A and H3 antagonists have you experimented with besides Conessine, Betahistine and Lecozotan?

 

WAY 100,635 and NAN 190, I liked those as well but they seemed to not last as long in terms of effect, for w/e reason.