55 replies to this topic

[Michael Rian]

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[Rior]

Okay, some things need to be cleared up here. I of course thank those of you who are chiming in, but I see a lot misinformation going around here.

 

First off a note on who I am/why I should be listened to:

 

I've studied neuroscience on my own for about 6 years, and in school for about 3. I'll be graduating with a degree in neuroscience this spring, although my own personal research has certainly served a greater purpose for my education than that I've received in college. I say that based on the fact that my own personal research has acted as supplementation to the knowledge gained from school, which has allowed me to hone a much broader knowledge of neuroscience than school alone would teach me. (Which, has still been quite a lot.)

 

That said, there are of course still those out there who know neuroscience better than I.  If I am wrong in any way, please feel free to correct me. I won't take offense.

 

 

CLEARING UP WHAT NEEDS TO BE CLEARED UP:

 

Receptor downregulation:

 

This is the largest piece of incorrect information. Downregulation of serotonin receptors doesn't mean you are downregulating an actual receptor.  There is no such thing as a "downregulated single receptor."  "Downregulation" simply refers to the process by which the body is adapting to a change in homeostasis, by changing the density of something. This could be anything from: downregulation of serotonin production (the body is producing less serotonin as a result of overly-serotonergic events, this is 100% an acute side-effect that follows immediate MDMA use) to downregulation of serotonin receptors, aka, the body has reduced the number of serotonin receptors found on the post-synaptic dendrites (the spiny "receiving" end of a neuron, that allows production of excitatory/inhibitory post-synaptic potentials which then reach the soma [cell body of a neuron] which then determines whether or not enough EPSPs have been registered to elicit a full response and firing of that subsequent neuron with an electrical response down the axon.)  When post-synaptic serotonin receptors have been downregulated, their density is reduced. The receptors themselves are not individually "downregulated."  This means, as well, that serotonergic receptors are not exactly "damaged" by MDMA use. Rather, frequent MDMA use messes with the serotonin receptor system so much that the density of the receptors/production of serotonin are reduced.

 

Easymode:  

 

Individual receptors are not "downregulated." Serotonin receptor density as a whole is reduced when you refer to "serotonin receptor downregulation." "Serotonin downregulation" means a reduction in the production of serotonin itself.

 

Second: (in reference to post #29 by Charlotte8)

 

5-HTP is the precursor for production of 5-HT (aka, SEROTONIN! 5-HT is serotonin.) 5-HTP is serotonin, but phosphorylated (added phosphate...aka the "P" on 5-HTP)  There are no receptors for 5-HTP.  5-HTP is metabolized directly into serotonin.  Now, that said, there are also no "presynaptic serotonin nerve endings." This is not a thing. This does not exist.  There ARE presynaptic serotonin receptors, just as there are postsynaptic serotonin receptors. And your nerve ending is not damaged, unless you consider serotonin receptor density downregulation damage. Which, I guess, it kinda is.  But you're not seeing a breakdown of the membrane wall, or a breakdown of the pre-synaptic bouton. The cell itself (aka, the cell wall, membrane, etc) is not DAMAGED. Just the density of receptors kind of is.

 

IMPORTANT DISTINCTION: This is NOT to say that MDMA does not cause cell death. It can, and does. This is done by a factor called "apoptosis" though, which is otherwise known as programmed cell death.  This is how cells die. Your body tells them to die (in a way) in response to some variety of stimuli.  Apoptosis occurs in good ways (destruction of neuronal sequences associated with fear for certain things you shouldn't be afraid of, aka fear extinction) as well as bad ways (concussions induce apoptosis through excess glutamate release and subsequent glutamatergic excitotoxicity.) Another example is use of MDMA causing apoptosis. MDMA is a very strong stimulant in many ways.  Not just in the energy it brings, but a stimulant in how it forces serotonin release, as well as serotonin transporter inhibition, leaving so much excess serotonin in the synaptic cleft. It stimulates the serotonin system, and it does it very powerfully.  I don't know the full, exact mechanism for how excess serotonin causes apoptosis (I can tell you how glutamate does it...) but it is apoptosis nonetheless.  So what to get out of this: Apoptosis is a necessary process, however excess drug use can cause apoptosis in amounts you don't want.  Getting these lost neurons back is....very difficult. It's doable in the hippocampus with time, however if you've caused damage to the prefrontal cortex those neurons are much, much much harder to regenerate. So yes, long-term, frequent MDMA use can cause extreme neuronal damage and loss, and that damage may be hard or impossible to recover from.

 

Easymode:

 

5-HTP only exists for the creation of serotonin (which is 5-HT). There are no "5-htp receptors." "Presynaptic serotonin nerve endings" also do not exist. There are some presynaptic serotonin receptors, but the pre-synaptic bouton (aka the place that releases neurotransmitters) will itself never be a "serotonin neuron/nerve ending."  Any damage caused to neurons is just either a reduction in receptor density, or death of the receptor altogether through a process known as apoptosis.

 

No cells "die" in the body (for the most part) simply by destruction of the cell membrane etc due to drugs. They are killed by the body itself, in a process known as "apoptosis" which is elicited by the body in response to a stimulus. The stimulus could be overuse of drugs. The stimulus could be a concussion. The stimulus could also be you realizing you don't need to be afraid of a certain thing (this is good apoptosis).  Apoptosis is bad, but also good and very necessary. It's how your body decides what should be a part of your personality, and what should not. Overuse of drugs throws off your homeostasis, and this causes your body to elicit apoptosis at a greater rate than you actually want.

 

 

THAT SAID, MY DISCUSSION ON YOUR CONDITION AND SUBSEQUENT RECOMMENDATIONS:

 

You have likely killed off a couple million neurons. You have trillions, but a couple million gone is obviously likely to make a noticeable effect. Those neurons that are left, are likely to be in slight disarray as they are "less commonly used" and not those that you have typically relied on in the past. Your intelligence will be lacking in comparison to who you were before. Your emotional state is also likely to be less adept at keeping you stable and happy.  You may suffer depression, as you ruminate over the fact that you've permanently damaged yourself and you'll never be the same. THIS LAST THOUGHT THOUGH, is the worst thing you can possibly do.  Of course, it's much easier said than done, to change yourself away from a mindset that you've permanently hurt yourself.  But convincing yourself of that is the worst possible thing you can do, as that forces you to continue in that mindset. Instead, you must understand that your brain, your mind, is different now. It is less malleable than it was when you were a teenager, as genetics have changed the rate at which your neurons multiply and connect, and the rate at which long-term potentiation is initiated. But, that said, it is still malleable nonetheless, and will remain so until the day you die. I promise you this.

 

Now, for how to address this unfortunate state:

 

Realize, first and foremost, that the damage is REPARABLE. However, it will TAKE WORK. Not "take this supplement" work.  Actual, mental work.  Your brain is like a muscle, in that the more you work it, the more you will strengthen good synapses and increase your mental quickness. You will also train yourself to be happy, which is very doable. It's a matter of causeing the good neurons  associated with a happy mental state to be strengthened, while reducing the use of "unhappy" neurons. This is an EXTREMELY simplistic way of saying it, but it works for the discussion.  This process will take a long time. Nothing you will come across will give you immediate change. No supplement, no drug, will immediately cause you to "jump back" into a perfect state of mind. It's like eating a fuck ton of protein, but not going to the gym.  You will gain nothing from supplement use alone. But, like protein while working out, supplements can help you.  A healthy diet will help you.  These will aid you in the workout that will be the workout you do for your mind.  These will quicken the process by which your brain changes and adapts in healthy ways, but you must work yourself out.  

 

Now, the list of supplements I list will likely be helpful, based on their mechanism of action, but I haven't put a ton of research into each individual supplement. There will likely be some that will aid you more, and some I'm missing. So for that I apologize. But, I recommend:

 

Bacopa Monnieri for it's serotonergic properties. I believe (my memory fails me) that has been seen to increase serotonin receptor density. This will help a little bit. 

 

Vitamin D because it's very likely you don't have enough of it, and it helps to support a strong mind.

 

Fish oil as it helps in the production of myelin for the protection of neurons, and will help your mind adapt. 

 

Magnesium L-Threonate or Memantine for its NMDA receptor antagonism. You need the L-threonate variety of magnesium if you're going to take it for mental purposes. Magnesium L-threonate has been seen in studies to cause an upregulation in dendritic extension in the hippocampus.  This will aid in increasing the connections between the neurons found in your hippocampus, the area of your brain associated with memory. I didn't fully read through your initial post, but I would certainly believe your memory is a little poorer following heavy MDMA use. Luckily for your, the hippocampus contains the highest density of NEURONAL STEM CELLS in your entire brain after you enter adulthood.  This means it is the easiest to regenerate.  Now, a note on both Mag L-threonate and Memantine (which I suppose I haven't spoken much of yet) is that in the INITIAL STAGES of taking either of these, your memory and thought processes are likely to be worse than they were prior to taking them.  I'll explain it this way: MDMA makes your serotonin system go into overdrive, which causes your brain to scale back your serotonergic stuff. Mag L-Threonate and memantine both act as antagonists at your NMDA receptors, causing you to be a little dumber in the short term....but your brain wants constant homeostasis! So, it adapts to your knew-found dumbness! It causes and upregulation in the production of glutamate and NMDA receptors, and also increases the rate at which your neurons connect. This is your brain's attempt at making up for your forced-upon-it dumbness. This results in greater clarity and greater memory after extended use (but only extended use), despite your initial brain fog and dumbness. I hope this makes sense.

 

Cerebrolysin or other neurogenic compounds.  CBL is a fantastic substance for causes neuronal regeneration. It's used following concussions in other countries, as it's been found to mitigate something like 90% of damage caused by concussions if used within a couple hours of the incident. It's packed full of neurotrophic factors (NGF, BDNF, others) as well as about 13 necessary amino acids (the BUILDING BLOCKS of neurons) necessary for the correct production of neurons. Yes, you need to inject it intramuscularly. I've done it before. I have a fear of needles, but I got over it. You have one life after all, why not force yourself to man up and grab life by the horns. Honestly, I don't have a tremendous amount of respect for those dealing with major brain problems who are unwilling to try and beat their fear of needles if it meant drastically improving their quality of life....forever. If you fear needles, deal with it and figure it out. If you're one of those that feint, or have actual reactions in regards to needles that make it difficult, then I'm sorry...that does actually suck.  But if you're just simply like "oh, needles? Nah, brah, that shit's not for me. I know I'm essentially mentally retarded and this could help me a bunch, but I just don't feel like it cuz it involves needles and needles hurt and they're scary."  Don't be that guy.  I know I spent the majority of this particular informational post discussing the needle part...but CBL is probably the single greatest supplement/drug you could possibly administer if you're looking to regenerate yourself.

 

Now, these are the supplements I recommend for recovery from your situation. Naturally, I also highly suggest a very healthy diet. A strict diet. In particular, make sure you are tracking your necessary vitamins and minerals. You need to make sure you are maintaining the correct building blocks for the recreation of your healthy brain.

 

As for the ACTIONS YOU NEED TO TAKE:

 

You need to exercise your mind. You need to engage in healthy, stimulating habits to force your brain to strengthen good, strong connections.  These things are pertinent to your recovery:

 

Exercise.  Exercise has been found to elicit a massive benefit for your mind.  It has been hailed as one of the greatest things you could ever possibly do for yourself in stimulating the production of neurons and their connections. Weight lifting will be very good for you for the sake of confidence and also eliciting a positive hormonal response, however I believe it's also highly necessary to engage in strong cardio. For the sake of rebuilding neurons, I believe cardio is actually more necessary than weight-lifting.  I remember reading a study on this, but I don't really feel like finding it right now as I'm tired. So you can take my word for it, or not. I remember reading that moderate cardio elicits a very strong increase in endogenous neurotrophic factors, versus mild cardio and heavy cardio, which both induce less of a neurotrophic response.  I can't define what "moderate" means for you. If you really want me to, ask nicely and I'll be happy to figure it out. I'm just tired right now and getting progressively more tired as I type this post, so I'm skimping out there.

 

Meditation.  Meditation is far better than anything else you could possibly do in terms of recovering your brain from damage. It causes highly noticeable changes in gray matter density in the areas of your brain that tend to matter most (dorsolateral prefrontal cortex, other areas of the PFC....your hippocampus and general limbic system)  It is difficult to practice at start, because you likely won't notice anything profound. It will take usually about 2 weeks of solid meditation practice to notice anything drastic or profound. What will typically occur is an incredible state of calmness and clarity, that will last for literally hours after you're finished meditating. It may last all day. But, it is a drastic and extraordinary change in your state of consciousness that will put you into a much healthier mental state than you were prior.  You will be happy. That happiness will last. But the benefits of meditation really only occur after long-term practice. That said, I said you have to work for your repair. You are not one of these lucky people who didn't damage their brain through extensive MDMA use.  You did, and now you have to pay the price, by working to recover. Meditative practice is not easy at first. It might even be frustrating, as you won't notice anything after your initial practice. But keep at it. Eventually, it will hit you like a ton of happy, fluffy bricks, and you'll realize what you're really experiencing. When you get into a solid meditative practice, on top of keeping up with exercise and a healthy diet, you will notice changes and you will notice them quickly. Far, far far far far quicker than you ever would through supplementation alone, or even anything else minus meditation. Meditation is the cornerstone to the mental work you are required to do.  It is imperative for a strong, much quicker recovery.  Your life will become meditation. You will learn to love it, and you will appreciate it. But you must do it. 

 

Good brain games/mental work.  

 

Read books, read books that require mental work and focus. They will be hard at first, and get easier with time. You will find your reading speed quickening, especially when combined with the other good practices outlined above. You will see your vocabulary increase, you will see your thinking speed increase in fluidity.

 

Use the dual-n-back game you may have heard about. Use it daily. This will increase your working memory, aka your ability to hold multiple working thoughts at once and be able to manipulate them.

 

Other good stuff. Insert good mental work stuff here.  Basically anything hard on you mentally.

 

 

THE SINGLE MOST IMPORTANT THING TO REMEMBER WHILE YOU ENGAGE IN THESE ACTIVITIES:

 

This recovery will TAKE TIME. It will not be instantaneous, nor will it even be quick. It will be difficult (mostly at first), and it will certainly be frustrating. You may not see any benefits after 2 weeks of constant work. You might not even see them very much after a month. But 2 months? 3 months? 6 months?  If you kept up these healthy practices and proper supplement use for a full year, I bet you would quite literally be back as strong a mental state as you held before. It won't be the same mental state as who you were prior to your MDMA use. You will absolutely be a different person, but you will be happy, and you will be mentally strong (and likely physically ) The longer you keep up practice of these healthy practices, the greater benefits you will reap. If you keep these practices up consistently and for long enough, it is almost certain that you will be in a stronger, better mental state than you were even PRIOR to MDMA use. You will be smarter than many others, wiser as well. As you've been through the ringer, and you've recovered. You will understand the mind to a much greater extent than most others, as you've seen its lower depths of anguish, as well as its higher branches of beauty.  But, most importantly: RECOVERY WILL TAKE WORK. I CANNOT emphasize this enough. You will need to work, and you'll need to push yourself consistently. It will be hard in the beginning, but easier with time and practice.  If you do not work, you will likely never recover fully until genetic engineering or other major drug inventions come out...and even then, you will ABSOLUTELY, POSITIVELY not benefit in the same way that you would by engaging in the work necessary.

 

 

FINALLY, A PERSONAL ANECDOTE ON MY OWN LIFE AND WHY I EVEN BEGAN STUDYING NEUROSCIENCE: You may draw a couple parallels to your story, albeit differently.

 

I have endured about 6 concussions over the course of my life. I have lost about 80-90% of my sense of smell, my vision isn't what it used to be (one concussion literally swelled my occipital lobe and made me completely, 100% blind for 3-4 hours) my shortterm memory is/was shit, my long-term memory isn't/wasn't great either, and my cleverness is nearly half what it used to be.  My word recall is fairly shot in comparison to what it used to be, my general ability express myself on the whole isn't phenomenal in comparison to who I used to be. These concussions occurred in my teenage to late teenage years, allthewhile I was constantly smoking weed (I don't have anything against adults using weed, but after learning quite a lot, I believe it is extremely irresponsible for adolescents to habitually use weed. This weed smoking certainly didn't help my concussive recovery.)  

 

Essentially, I turned myself into a fragmented version of who I once was. I'm sure you obviously relate. This loss of myself is what encouraged me to study neuroscience. It is the constant desire to improve, to regain what I have lost. And I have. I have regained much of what I've lost, through constant work. I am still not quite at 100% where I used to be, but I am excelling in other ways. My motivation is stronger. My willpower is stronger. My knowledge is much stronger.  It's all about working, and understanding that there's beauty in the process.  Though my concussions have taken much away from me...they've inspired my fascination and dedication to neuroscience, and have given me the purpose of self-improvement in my life.  I have improved my condition dramatically, and I know you can too with dedication and work.

 

You've got a long, long road ahead of you, but I welcome you to the beginning of that path.

 

If you have any other questions, please let me know.

 

I started this post with literally just the intentions of correcting misinformation...but figured I might as well continued onward. I hope it has helped, and I hope you give it a chance to read through all of this.

 

 

Edit: After a couple edits I've realized my writing is shit when I'm tired. So I apologize for any grammatical errors or what have you, I'm exhausted after moving apartments all day.

Edited by Rior, 14 August 2014 - 08:26 AM.

[medicineman]

There are several things you should consider....

Receptor down regulation does not = receptor damage. who ever said that is a idiot.

MDMA it self has no toxicity at normal doses, but what is toxic is its MDA metabolite due to metabolism. therefore it has the potential to cause oxidative stress.

What you can do is take Agomelatine routinely, and Noopept. Tianeptine also restores post synaptic receptor sensitivity; and Agmatine or memantine can restore receptor sensitivity and density

if repair is what you are concerned about then dont waste your money on all these exotic supplements. Take good antioxidants, like Vitamin C, Gamma-tocopherol, Alpha-Lipoic Acid (these 3 time release), BioPQQ, Ubiquinol......
You can also potentially undertake a Ketogenic diet. ketones are extremely neuroprotectant. under ketosis your brain uses ketones as a substrate for energy, glycolysis is significantly reduced. therefore significant decreases in oxidation due to glucose metabolism. ketosis also increases endogenous glutathione production. remember the brain uses 20% of the bodies entire metabolism, therefore it is always in oxidative damage/repair. we need to get 'damage' out of that and the only way is through a ketogenic diet.

take these steps and you'll be back to normal

Hi Advanc3d,

I have emailed several professors on the topic and they said that what I am suffering with can no longer be because of receptor downregulation - due to the length of time it has been.
They said the receptors would have been downregulated - but they would have upregulated themselves over weeks or months. I have been like this 6 years. I was hoping and praying it was downregulation - but it appears it can't be and it is actual damage. :(

I have been told my an expert on MDMA that it is the 5-htp nerve endings (presynaptic) that are damaged - not the receptors.

Ketogenic diets are awesome - I already try to follow the 'Bulletproof Diet' by Dave Asprey. Thank you for your comment though - I was not aware of how it benefited then brain in this way.

There is no "damage", you are being misinformed. and if there was, the body contains an infinite mechanisms of counter regulatory measures, whether it be pre-synaptic or post synaptic, they can self regulate and increase or decrease output to compensate considering every neurotransmitter sets have autoreceptors and inhibitory and excitatory roles. also take note that users of heavy methampethamine usage got 90-98% regeneration of nerve conductivity (either from higher output due to compensation or from more being produced via growth factors) after 18months of abstinence.

there is no 'evidence' of 5-htp nerve ending damage from MDMA in humans (but rather from its metabolite MDA, which can be reduced by taking enzyme inhibitors). possibly with rats and monkeys but they use doses surpassing possible doses used in humans to prove a concept. rats have metabolites of MDMA that do not exist in humans. most of the rat studies are MDMA injection in to the brain as well.

other scenario is, you have had bad batches of proposed MDMA that contained highly neurotoxic byproducts that weren't washed out when it was made.

we might not have brain samples, but we know MDMA/ecstasy users (retrospectively of course) consistently score worse on certain measures of cognition.

[Advanc3d]

 

 

 

There are several things you should consider....

Receptor down regulation does not = receptor damage. who ever said that is a idiot.

MDMA it self has no toxicity at normal doses, but what is toxic is its MDA metabolite due to metabolism. therefore it has the potential to cause oxidative stress.

What you can do is take Agomelatine routinely, and Noopept. Tianeptine also restores post synaptic receptor sensitivity; and Agmatine or memantine can restore receptor sensitivity and density

if repair is what you are concerned about then dont waste your money on all these exotic supplements. Take good antioxidants, like Vitamin C, Gamma-tocopherol, Alpha-Lipoic Acid (these 3 time release), BioPQQ, Ubiquinol......
You can also potentially undertake a Ketogenic diet. ketones are extremely neuroprotectant. under ketosis your brain uses ketones as a substrate for energy, glycolysis is significantly reduced. therefore significant decreases in oxidation due to glucose metabolism. ketosis also increases endogenous glutathione production. remember the brain uses 20% of the bodies entire metabolism, therefore it is always in oxidative damage/repair. we need to get 'damage' out of that and the only way is through a ketogenic diet.

take these steps and you'll be back to normal

Hi Advanc3d,

I have emailed several professors on the topic and they said that what I am suffering with can no longer be because of receptor downregulation - due to the length of time it has been.
They said the receptors would have been downregulated - but they would have upregulated themselves over weeks or months. I have been like this 6 years. I was hoping and praying it was downregulation - but it appears it can't be and it is actual damage. :(

I have been told my an expert on MDMA that it is the 5-htp nerve endings (presynaptic) that are damaged - not the receptors.

Ketogenic diets are awesome - I already try to follow the 'Bulletproof Diet' by Dave Asprey. Thank you for your comment though - I was not aware of how it benefited then brain in this way.

There is no "damage", you are being misinformed. and if there was, the body contains an infinite mechanisms of counter regulatory measures, whether it be pre-synaptic or post synaptic, they can self regulate and increase or decrease output to compensate considering every neurotransmitter sets have autoreceptors and inhibitory and excitatory roles. also take note that users of heavy methampethamine usage got 90-98% regeneration of nerve conductivity (either from higher output due to compensation or from more being produced via growth factors) after 18months of abstinence.

there is no 'evidence' of 5-htp nerve ending damage from MDMA in humans (but rather from its metabolite MDA, which can be reduced by taking enzyme inhibitors). possibly with rats and monkeys but they use doses surpassing possible doses used in humans to prove a concept. rats have metabolites of MDMA that do not exist in humans. most of the rat studies are MDMA injection in to the brain as well.

other scenario is, you have had bad batches of proposed MDMA that contained highly neurotoxic byproducts that weren't washed out when it was made.

we might not have brain samples, but we know MDMA/ecstasy users (retrospectively of course) consistently score worse on certain measures of cognition.

 

 

 

those studies are full of limitations..

 

Serotonergic system is partly responsible for cognition and it influences other systems such as dopaminergic and adrenergic systems as well as endorphins and vasopressin and a whole lot of others. imflamatory markers change in different areas of the brain, etc.. i can explain to you every part of it, but it is irrelevant... once abstinence is provided, these effects on learning are reversed. 

 

a lot of the MDMA users are not single drug users either, so it cannot be conclusive.

 

Worst cognition problems occur once someone comes off SSRI's for example...

[Advanc3d]

Okay, some things need to be cleared up here. I of course thank those of you who are chiming in, but I see a lot misinformation going around here.

 

First off a note on who I am/why I should be listened to:

 

I've studied neuroscience on my own for about 6 years, and in school for about 3. I'll be graduating with a degree in neuroscience this spring, although my own personal research has certainly served a greater purpose for my education than that I've received in college. I say that based on the fact that my own personal research has acted as supplementation to the knowledge gained from school, which has allowed me to hone a much broader knowledge of neuroscience than school alone would teach me. (Which, has still been quite a lot.)

 

That said, there are of course still those out there who know neuroscience better than I.  If I am wrong in any way, please feel free to correct me. I won't take offense.

 

 

CLEARING UP WHAT NEEDS TO BE CLEARED UP:

 

Receptor downregulation:

 

This is the largest piece of incorrect information. Downregulation of serotonin receptors doesn't mean you are downregulating an actual receptor.  There is no such thing as a "downregulated single receptor."  "Downregulation" simply refers to the process by which the body is adapting to a change in homeostasis, by changing the density of something. This could be anything from: downregulation of serotonin production (the body is producing less serotonin as a result of overly-serotonergic events, this is 100% an acute side-effect that follows immediate MDMA use) to downregulation of serotonin receptors, aka, the body has reduced the number of serotonin receptors found on the post-synaptic dendrites (the spiny "receiving" end of a neuron, that allows production of excitatory/inhibitory post-synaptic potentials which then reach the soma [cell body of a neuron] which then determines whether or not enough EPSPs have been registered to elicit a full response and firing of that subsequent neuron with an electrical response down the axon.)  When post-synaptic serotonin receptors have been downregulated, their density is reduced. The receptors themselves are not individually "downregulated."  This means, as well, that serotonergic receptors are not exactly "damaged" by MDMA use. Rather, frequent MDMA use messes with the serotonin receptor system so much that the density of the receptors/production of serotonin are reduced.

 

Easymode:  

 

Individual receptors are not "downregulated." Serotonin receptor density as a whole is reduced when you refer to "serotonin receptor downregulation." "Serotonin downregulation" means a reduction in the production of serotonin itself.

 

Second: (in reference to post #29 by Charlotte8)

 

5-HTP is the precursor for production of 5-HT (aka, SEROTONIN! 5-HT is serotonin.) 5-HTP is serotonin, but phosphorylated (added phosphate...aka the "P" on 5-HTP)  There are no receptors for 5-HTP.  5-HTP is metabolized directly into serotonin.  Now, that said, there are also no "presynaptic serotonin nerve endings." This is not a thing. This does not exist.  There ARE presynaptic serotonin receptors, just as there are postsynaptic serotonin receptors. And your nerve ending is not damaged, unless you consider serotonin receptor density downregulation damage. Which, I guess, it kinda is.  But you're not seeing a breakdown of the membrane wall, or a breakdown of the pre-synaptic bouton. The cell itself (aka, the cell wall, membrane, etc) is not DAMAGED. Just the density of receptors kind of is.

 

IMPORTANT DISTINCTION: This is NOT to say that MDMA does not cause cell death. It can, and does. This is done by a factor called "apoptosis" though, which is otherwise known as programmed cell death.  This is how cells die. Your body tells them to die (in a way) in response to some variety of stimuli.  Apoptosis occurs in good ways (destruction of neuronal sequences associated with fear for certain things you shouldn't be afraid of, aka fear extinction) as well as bad ways (concussions induce apoptosis through excess glutamate release and subsequent glutamatergic excitotoxicity.) Another example is use of MDMA causing apoptosis. MDMA is a very strong stimulant in many ways.  Not just in the energy it brings, but a stimulant in how it forces serotonin release, as well as serotonin transporter inhibition, leaving so much excess serotonin in the synaptic cleft. It stimulates the serotonin system, and it does it very powerfully.  I don't know the full, exact mechanism for how excess serotonin causes apoptosis (I can tell you how glutamate does it...) but it is apoptosis nonetheless.  So what to get out of this: Apoptosis is a necessary process, however excess drug use can cause apoptosis in amounts you don't want.  Getting these lost neurons back is....very difficult. It's doable in the hippocampus with time, however if you've caused damage to the prefrontal cortex those neurons are much, much much harder to regenerate. So yes, long-term, frequent MDMA use can cause extreme neuronal damage and loss, and that damage may be hard or impossible to recover from.

 

Easymode:

 

5-HTP only exists for the creation of serotonin (which is 5-HT). There are no "5-htp receptors." "Presynaptic serotonin nerve endings" also do not exist. There are some presynaptic serotonin receptors, but the pre-synaptic bouton (aka the place that releases neurotransmitters) will itself never be a "serotonin neuron/nerve ending."  Any damage caused to neurons is just either a reduction in receptor density, or death of the receptor altogether through a process known as apoptosis.

 

No cells "die" in the body (for the most part) simply by destruction of the cell membrane etc due to drugs. They are killed by the body itself, in a process known as "apoptosis" which is elicited by the body in response to a stimulus. The stimulus could be overuse of drugs. The stimulus could be a concussion. The stimulus could also be you realizing you don't need to be afraid of a certain thing (this is good apoptosis).  Apoptosis is bad, but also good and very necessary. It's how your body decides what should be a part of your personality, and what should not. Overuse of drugs throws off your homeostasis, and this causes your body to elicit apoptosis at a greater rate than you actually want.

 

 

THAT SAID, MY DISCUSSION ON YOUR CONDITION AND SUBSEQUENT RECOMMENDATIONS:

 

You have likely killed off a couple million neurons. You have trillions, but a couple million gone is obviously likely to make a noticeable effect. Those neurons that are left, are likely to be in slight disarray as they are "less commonly used" and not those that you have typically relied on in the past. Your intelligence will be lacking in comparison to who you were before. Your emotional state is also likely to be less adept at keeping you stable and happy.  You may suffer depression, as you ruminate over the fact that you've permanently damaged yourself and you'll never be the same. THIS LAST THOUGHT THOUGH, is the worst thing you can possibly do.  Of course, it's much easier said than done, to change yourself away from a mindset that you've permanently hurt yourself.  But convincing yourself of that is the worst possible thing you can do, as that forces you to continue in that mindset. Instead, you must understand that your brain, your mind, is different now. It is less malleable than it was when you were a teenager, as genetics have changed the rate at which your neurons multiply and connect, and the rate at which long-term potentiation is initiated. But, that said, it is still malleable nonetheless, and will remain so until the day you die. I promise you this.

 

Now, for how to address this unfortunate state:

 

Realize, first and foremost, that the damage is REPARABLE. However, it will TAKE WORK. Not "take this supplement" work.  Actual, mental work.  Your brain is like a muscle, in that the more you work it, the more you will strengthen good synapses and increase your mental quickness. You will also train yourself to be happy, which is very doable. It's a matter of causeing the good neurons  associated with a happy mental state to be strengthened, while reducing the use of "unhappy" neurons. This is an EXTREMELY simplistic way of saying it, but it works for the discussion.  This process will take a long time. Nothing you will come across will give you immediate change. No supplement, no drug, will immediately cause you to "jump back" into a perfect state of mind. It's like eating a fuck ton of protein, but not going to the gym.  You will gain nothing from supplement use alone. But, like protein while working out, supplements can help you.  A healthy diet will help you.  These will aid you in the workout that will be the workout you do for your mind.  These will quicken the process by which your brain changes and adapts in healthy ways, but you must work yourself out.  

 

Now, the list of supplements I list will likely be helpful, based on their mechanism of action, but I haven't put a ton of research into each individual supplement. There will likely be some that will aid you more, and some I'm missing. So for that I apologize. But, I recommend:

 

Bacopa Monnieri for it's serotonergic properties. I believe (my memory fails me) that has been seen to increase serotonin receptor density. This will help a little bit. 

 

Vitamin D because it's very likely you don't have enough of it, and it helps to support a strong mind.

 

Fish oil as it helps in the production of myelin for the protection of neurons, and will help your mind adapt. 

 

Magnesium L-Threonate or Memantine for its NMDA receptor antagonism. You need the L-threonate variety of magnesium if you're going to take it for mental purposes. Magnesium L-threonate has been seen in studies to cause an upregulation in dendritic extension in the hippocampus.  This will aid in increasing the connections between the neurons found in your hippocampus, the area of your brain associated with memory. I didn't fully read through your initial post, but I would certainly believe your memory is a little poorer following heavy MDMA use. Luckily for your, the hippocampus contains the highest density of NEURONAL STEM CELLS in your entire brain after you enter adulthood.  This means it is the easiest to regenerate.  Now, a note on both Mag L-threonate and Memantine (which I suppose I haven't spoken much of yet) is that in the INITIAL STAGES of taking either of these, your memory and thought processes are likely to be worse than they were prior to taking them.  I'll explain it this way: MDMA makes your serotonin system go into overdrive, which causes your brain to scale back your serotonergic stuff. Mag L-Threonate and memantine both act as antagonists at your NMDA receptors, causing you to be a little dumber in the short term....but your brain wants constant homeostasis! So, it adapts to your knew-found dumbness! It causes and upregulation in the production of glutamate and NMDA receptors, and also increases the rate at which your neurons connect. This is your brain's attempt at making up for your forced-upon-it dumbness. This results in greater clarity and greater memory after extended use (but only extended use), despite your initial brain fog and dumbness. I hope this makes sense.

 

Cerebrolysin or other neurogenic compounds.  CBL is a fantastic substance for causes neuronal regeneration. It's used following concussions in other countries, as it's been found to mitigate something like 90% of damage caused by concussions if used within a couple hours of the incident. It's packed full of neurotrophic factors (NGF, BDNF, others) as well as about 13 necessary amino acids (the BUILDING BLOCKS of neurons) necessary for the correct production of neurons. Yes, you need to inject it intramuscularly. I've done it before. I have a fear of needles, but I got over it. You have one life after all, why not force yourself to man up and grab life by the horns. Honestly, I don't have a tremendous amount of respect for those dealing with major brain problems who are unwilling to try and beat their fear of needles if it meant drastically improving their quality of life....forever. If you fear needles, deal with it and figure it out. If you're one of those that feint, or have actual reactions in regards to needles that make it difficult, then I'm sorry...that does actually suck.  But if you're just simply like "oh, needles? Nah, brah, that shit's not for me. I know I'm essentially mentally retarded and this could help me a bunch, but I just don't feel like it cuz it involves needles and needles hurt and they're scary."  Don't be that guy.  I know I spent the majority of this particular informational post discussing the needle part...but CBL is probably the single greatest supplement/drug you could possibly administer if you're looking to regenerate yourself.

 

Now, these are the supplements I recommend for recovery from your situation. Naturally, I also highly suggest a very healthy diet. A strict diet. In particular, make sure you are tracking your necessary vitamins and minerals. You need to make sure you are maintaining the correct building blocks for the recreation of your healthy brain.

 

As for the ACTIONS YOU NEED TO TAKE:

 

You need to exercise your mind. You need to engage in healthy, stimulating habits to force your brain to strengthen good, strong connections.  These things are pertinent to your recovery:

 

Exercise.  Exercise has been found to elicit a massive benefit for your mind.  It has been hailed as one of the greatest things you could ever possibly do for yourself in stimulating the production of neurons and their connections. Weight lifting will be very good for you for the sake of confidence and also eliciting a positive hormonal response, however I believe it's also highly necessary to engage in strong cardio. For the sake of rebuilding neurons, I believe cardio is actually more necessary than weight-lifting.  I remember reading a study on this, but I don't really feel like finding it right now as I'm tired. So you can take my word for it, or not. I remember reading that moderate cardio elicits a very strong increase in endogenous neurotrophic factors, versus mild cardio and heavy cardio, which both induce less of a neurotrophic response.  I can't define what "moderate" means for you. If you really want me to, ask nicely and I'll be happy to figure it out. I'm just tired right now and getting progressively more tired as I type this post, so I'm skimping out there.

 

Meditation.  Meditation is far better than anything else you could possibly do in terms of recovering your brain from damage. It causes highly noticeable changes in gray matter density in the areas of your brain that tend to matter most (dorsolateral prefrontal cortex, other areas of the PFC....your hippocampus and general limbic system)  It is difficult to practice at start, because you likely won't notice anything profound. It will take usually about 2 weeks of solid meditation practice to notice anything drastic or profound. What will typically occur is an incredible state of calmness and clarity, that will last for literally hours after you're finished meditating. It may last all day. But, it is a drastic and extraordinary change in your state of consciousness that will put you into a much healthier mental state than you were prior.  You will be happy. That happiness will last. But the benefits of meditation really only occur after long-term practice. That said, I said you have to work for your repair. You are not one of these lucky people who didn't damage their brain through extensive MDMA use.  You did, and now you have to pay the price, by working to recover. Meditative practice is not easy at first. It might even be frustrating, as you won't notice anything after your initial practice. But keep at it. Eventually, it will hit you like a ton of happy, fluffy bricks, and you'll realize what you're really experiencing. When you get into a solid meditative practice, on top of keeping up with exercise and a healthy diet, you will notice changes and you will notice them quickly. Far, far far far far quicker than you ever would through supplementation alone, or even anything else minus meditation. Meditation is the cornerstone to the mental work you are required to do.  It is imperative for a strong, much quicker recovery.  Your life will become meditation. You will learn to love it, and you will appreciate it. But you must do it. 

 

Good brain games/mental work.  

 

Read books, read books that require mental work and focus. They will be hard at first, and get easier with time. You will find your reading speed quickening, especially when combined with the other good practices outlined above. You will see your vocabulary increase, you will see your thinking speed increase in fluidity.

 

Use the dual-n-back game you may have heard about. Use it daily. This will increase your working memory, aka your ability to hold multiple working thoughts at once and be able to manipulate them.

 

Other good stuff. Insert good mental work stuff here.  Basically anything hard on you mentally.

 

 

THE SINGLE MOST IMPORTANT THING TO REMEMBER WHILE YOU ENGAGE IN THESE ACTIVITIES:

 

This recovery will TAKE TIME. It will not be instantaneous, nor will it even be quick. It will be difficult (mostly at first), and it will certainly be frustrating. You may not see any benefits after 2 weeks of constant work. You might not even see them very much after a month. But 2 months? 3 months? 6 months?  If you kept up these healthy practices and proper supplement use for a full year, I bet you would quite literally be back as strong a mental state as you held before. It won't be the same mental state as who you were prior to your MDMA use. You will absolutely be a different person, but you will be happy, and you will be mentally strong (and likely physically ) The longer you keep up practice of these healthy practices, the greater benefits you will reap. If you keep these practices up consistently and for long enough, it is almost certain that you will be in a stronger, better mental state than you were even PRIOR to MDMA use. You will be smarter than many others, wiser as well. As you've been through the ringer, and you've recovered. You will understand the mind to a much greater extent than most others, as you've seen its lower depths of anguish, as well as its higher branches of beauty.  But, most importantly: RECOVERY WILL TAKE WORK. I CANNOT emphasize this enough. You will need to work, and you'll need to push yourself consistently. It will be hard in the beginning, but easier with time and practice.  If you do not work, you will likely never recover fully until genetic engineering or other major drug inventions come out...and even then, you will ABSOLUTELY, POSITIVELY not benefit in the same way that you would by engaging in the work necessary.

 

 

FINALLY, A PERSONAL ANECDOTE ON MY OWN LIFE AND WHY I EVEN BEGAN STUDYING NEUROSCIENCE: You may draw a couple parallels to your story, albeit differently.

 

I have endured about 6 concussions over the course of my life. I have lost about 80-90% of my sense of smell, my vision isn't what it used to be (one concussion literally swelled my occipital lobe and made me completely, 100% blind for 3-4 hours) my shortterm memory is/was shit, my long-term memory isn't/wasn't great either, and my cleverness is nearly half what it used to be.  My word recall is fairly shot in comparison to what it used to be, my general ability express myself on the whole isn't phenomenal in comparison to who I used to be. These concussions occurred in my teenage to late teenage years, allthewhile I was constantly smoking weed (I don't have anything against adults using weed, but after learning quite a lot, I believe it is extremely irresponsible for adolescents to habitually use weed. This weed smoking certainly didn't help my concussive recovery.)  

 

Essentially, I turned myself into a fragmented version of who I once was. I'm sure you obviously relate. This loss of myself is what encouraged me to study neuroscience. It is the constant desire to improve, to regain what I have lost. And I have. I have regained much of what I've lost, through constant work. I am still not quite at 100% where I used to be, but I am excelling in other ways. My motivation is stronger. My willpower is stronger. My knowledge is much stronger.  It's all about working, and understanding that there's beauty in the process.  Though my concussions have taken much away from me...they've inspired my fascination and dedication to neuroscience, and have given me the purpose of self-improvement in my life.  I have improved my condition dramatically, and I know you can too with dedication and work.

 

You've got a long, long road ahead of you, but I welcome you to the beginning of that path.

 

If you have any other questions, please let me know.

 

I started this post with literally just the intentions of correcting misinformation...but figured I might as well continued onward. I hope it has helped, and I hope you give it a chance to read through all of this.

 

 

Edit: After a couple edits I've realized my writing is shit when I'm tired. So I apologize for any grammatical errors or what have you, I'm exhausted after moving apartments all day.

1. single receptors do down regulate.

 

2. densities of receptors do return to its previous state in absence of stimulation. hence NMDA antagonists are good as well as Tianeptine

 

3.  receptors compensate in the presence of low serotonin, receptors upregulate (sometimes bringing side effects until other regulatory mechanisms catch up)

 

4. there is no conclusive evidence for Magnesium L-Threonate to be any different in pharmacology then to Magnesium Citrate, for example.

 

5. doses to cause damage via exotoxicity is far greater then what can be achieved. most mouse models are intravenous. the peak of action is more detrimental to overall action. even in mouse studies, injections were mostly done straight in to the brain, which bipases CYP conversion to MDA, which in it self can cause neurotoxicity, but not MDMA it self.

 

6. it is good to take Curcumin for example, for its actions on NK-kB inhibition, which can attenuate the downstream oxidative pathways

Edited by Advanc3d, 15 August 2014 - 03:57 AM.

[medicineman]

There are several things you should consider....

Receptor down regulation does not = receptor damage. who ever said that is a idiot.

MDMA it self has no toxicity at normal doses, but what is toxic is its MDA metabolite due to metabolism. therefore it has the potential to cause oxidative stress.

What you can do is take Agomelatine routinely, and Noopept. Tianeptine also restores post synaptic receptor sensitivity; and Agmatine or memantine can restore receptor sensitivity and density

if repair is what you are concerned about then dont waste your money on all these exotic supplements. Take good antioxidants, like Vitamin C, Gamma-tocopherol, Alpha-Lipoic Acid (these 3 time release), BioPQQ, Ubiquinol......
You can also potentially undertake a Ketogenic diet. ketones are extremely neuroprotectant. under ketosis your brain uses ketones as a substrate for energy, glycolysis is significantly reduced. therefore significant decreases in oxidation due to glucose metabolism. ketosis also increases endogenous glutathione production. remember the brain uses 20% of the bodies entire metabolism, therefore it is always in oxidative damage/repair. we need to get 'damage' out of that and the only way is through a ketogenic diet.

take these steps and you'll be back to normal

Hi Advanc3d,

I have emailed several professors on the topic and they said that what I am suffering with can no longer be because of receptor downregulation - due to the length of time it has been.
They said the receptors would have been downregulated - but they would have upregulated themselves over weeks or months. I have been like this 6 years. I was hoping and praying it was downregulation - but it appears it can't be and it is actual damage. :(

I have been told my an expert on MDMA that it is the 5-htp nerve endings (presynaptic) that are damaged - not the receptors.

Ketogenic diets are awesome - I already try to follow the 'Bulletproof Diet' by Dave Asprey. Thank you for your comment though - I was not aware of how it benefited then brain in this way.

There is no "damage", you are being misinformed. and if there was, the body contains an infinite mechanisms of counter regulatory measures, whether it be pre-synaptic or post synaptic, they can self regulate and increase or decrease output to compensate considering every neurotransmitter sets have autoreceptors and inhibitory and excitatory roles. also take note that users of heavy methampethamine usage got 90-98% regeneration of nerve conductivity (either from higher output due to compensation or from more being produced via growth factors) after 18months of abstinence.

there is no 'evidence' of 5-htp nerve ending damage from MDMA in humans (but rather from its metabolite MDA, which can be reduced by taking enzyme inhibitors). possibly with rats and monkeys but they use doses surpassing possible doses used in humans to prove a concept. rats have metabolites of MDMA that do not exist in humans. most of the rat studies are MDMA injection in to the brain as well.

other scenario is, you have had bad batches of proposed MDMA that contained highly neurotoxic byproducts that weren't washed out when it was made.

we might not have brain samples, but we know MDMA/ecstasy users (retrospectively of course) consistently score worse on certain measures of cognition.

those studies are full of limitations..

Serotonergic system is partly responsible for cognition and it influences other systems such as dopaminergic and adrenergic systems as well as endorphins and vasopressin and a whole lot of others. imflamatory markers change in different areas of the brain, etc.. i can explain to you every part of it, but it is irrelevant... once abstinence is provided, these effects on learning are reversed.

a lot of the MDMA users are not single drug users either, so it cannot be conclusive.

Worst cognition problems occur once someone comes off SSRI's for example...

the ssri comment is completely unsubstantiated. there is no evidence aside from yellow card schemes that ssris are cognitively harmful. and then you have ssri withdrawal. on the other hand, I can dish out a large number of articles showing how ssris are actually highly neuroprotective, with established mechanisms. do people develop cognitive dulling, etc with ssris? of course it's bound to happen once you tamper with such an integral part of the cns. but I don't really feel your analogy with MDMA and ssris. are you implying that ssris are more damaging? if so, then I'm sorry, that's just extremely wishful thinking. Wagner et al, performed a prospective study, which is much better than the old retrospective ones, and once again, after controlling for all factors, guess what?

the tests on ecstasy users have repeatedly shown deficits in cognition. not one, or two. most. that includes controlling for many factors. the bottom line is, MDMA does leave long lasting changes. I was a former MDMA user, and I prefer not to indulge in fantasies. facing up to the facts and trying to learn from them is preferable than to pretend everything is fine.

Edited by medicineman, 15 August 2014 - 07:14 AM.

[Advanc3d]

 

 

 

 

 

There are several things you should consider....

Receptor down regulation does not = receptor damage. who ever said that is a idiot.

MDMA it self has no toxicity at normal doses, but what is toxic is its MDA metabolite due to metabolism. therefore it has the potential to cause oxidative stress.

What you can do is take Agomelatine routinely, and Noopept. Tianeptine also restores post synaptic receptor sensitivity; and Agmatine or memantine can restore receptor sensitivity and density

if repair is what you are concerned about then dont waste your money on all these exotic supplements. Take good antioxidants, like Vitamin C, Gamma-tocopherol, Alpha-Lipoic Acid (these 3 time release), BioPQQ, Ubiquinol......
You can also potentially undertake a Ketogenic diet. ketones are extremely neuroprotectant. under ketosis your brain uses ketones as a substrate for energy, glycolysis is significantly reduced. therefore significant decreases in oxidation due to glucose metabolism. ketosis also increases endogenous glutathione production. remember the brain uses 20% of the bodies entire metabolism, therefore it is always in oxidative damage/repair. we need to get 'damage' out of that and the only way is through a ketogenic diet.

take these steps and you'll be back to normal

Hi Advanc3d,

I have emailed several professors on the topic and they said that what I am suffering with can no longer be because of receptor downregulation - due to the length of time it has been.
They said the receptors would have been downregulated - but they would have upregulated themselves over weeks or months. I have been like this 6 years. I was hoping and praying it was downregulation - but it appears it can't be and it is actual damage. :(

I have been told my an expert on MDMA that it is the 5-htp nerve endings (presynaptic) that are damaged - not the receptors.

Ketogenic diets are awesome - I already try to follow the 'Bulletproof Diet' by Dave Asprey. Thank you for your comment though - I was not aware of how it benefited then brain in this way.

There is no "damage", you are being misinformed. and if there was, the body contains an infinite mechanisms of counter regulatory measures, whether it be pre-synaptic or post synaptic, they can self regulate and increase or decrease output to compensate considering every neurotransmitter sets have autoreceptors and inhibitory and excitatory roles. also take note that users of heavy methampethamine usage got 90-98% regeneration of nerve conductivity (either from higher output due to compensation or from more being produced via growth factors) after 18months of abstinence.

there is no 'evidence' of 5-htp nerve ending damage from MDMA in humans (but rather from its metabolite MDA, which can be reduced by taking enzyme inhibitors). possibly with rats and monkeys but they use doses surpassing possible doses used in humans to prove a concept. rats have metabolites of MDMA that do not exist in humans. most of the rat studies are MDMA injection in to the brain as well.

other scenario is, you have had bad batches of proposed MDMA that contained highly neurotoxic byproducts that weren't washed out when it was made.

we might not have brain samples, but we know MDMA/ecstasy users (retrospectively of course) consistently score worse on certain measures of cognition.

those studies are full of limitations..

Serotonergic system is partly responsible for cognition and it influences other systems such as dopaminergic and adrenergic systems as well as endorphins and vasopressin and a whole lot of others. imflamatory markers change in different areas of the brain, etc.. i can explain to you every part of it, but it is irrelevant... once abstinence is provided, these effects on learning are reversed.

a lot of the MDMA users are not single drug users either, so it cannot be conclusive.

Worst cognition problems occur once someone comes off SSRI's for example...

the ssri comment is completely unsubstantiated. there is no evidence aside from yellow card schemes that ssris are cognitively harmful. and then you have ssri withdrawal. on the other hand, I can dish out a large number of articles showing how ssris are actually highly neuroprotective, with established mechanisms. do people develop cognitive dulling, etc with ssris? of course it's bound to happen once you tamper with such an integral part of the cns. but I don't really feel your analogy with MDMA and ssris. are you implying that ssris are more damaging? if so, then I'm sorry, that's just extremely wishful thinking. Wagner et al, performed a prospective study, which is much better than the old retrospective ones, and once again, after controlling for all factors, guess what?

the tests on ecstasy users have repeatedly shown deficits in cognition. not one, or two. most. that includes controlling for many factors. the bottom line is, MDMA does leave long lasting changes. I was a former MDMA user, and I prefer not to indulge in fantasies. facing up to the facts and trying to learn from them is preferable than to pretend everything is fine.

 

 

 

We are not talking about 'damage'.

 

I have studied SSRI's in and out and it has a lot of potential problems

Semi-permanent alteration of the HPA axis

Semi-permanent alteration of gene expression on the SERT and as well as responding receptors and their altered modulation of adjacent neurotransmitters (DA, NE), (partly the reason of long lasting sexual issues)

Semi-permanent alterations of antidiuretic hormone 

 

I rather not discuss how a rise in serotonin downstream lowers DA/NE which are then not subjected to counterregulatory systems like direct regulatory effects of SSRIs has on serotonin

 

The degree of permanency and when it actually becomes long-lasting is under debate but a lot of anecdotes have been shown that there are semi-permanent changes to how the body regulates energy expenditure and metabolism (HPA) upto1 year post chronic use. Other studies show how cortisol secretion does not return back to pre-treatment, and lasts upto 1 year (possibly greater, but studies didnt go longer)

 

Do i really want to flop out studies and shows all of this out of my archive of studies? no, you can look google it your self

 

unfortunately when people take SSRIs, its usually chronic and not acute like MDMA administration. 

Edited by Advanc3d, 18 August 2014 - 12:21 AM.

[Michael Rian]

I apologize if this is off topic or has no interest, but would the anti-depressant Agomelatine have any potential instead of an SSRI?  I was on SSRis for about 5 years and being off of them for about 2 years now, I never want to go back.  I also made the mistake of abusing MDMA and a handful of other substances, while on medications such as SSRI and benzos.  Since being clean off of everything, I have maintained a rigorous exercise routine, very healthy diet, proper sleep, and a healthy social life for about 2 years now, but I still deal with all the repercussions of my past behavior and addictions.  I feel like I have reached a plateau in my recovery and I want to try medications again, this time around being sober from the other drugs.  I have an appointment with a psychiatrist in September and I would greatly appreciate any advice or opinons on which medications to bring up in our conversation.  I hope this post is taken as a contribution to the thread and not as a personal cry for help, as I think there may be others in my position wondering the same thing.  Anyways, Thank you to the OP and everyone in this thread for all the excellent information and discussions! Very much appreciated indeed.  

[VERITAS INCORRUPTUS]

Well, a lot of bandying about about this and that, when it is largely seen to be determined as due to axonal loss

 

Prescription:  axonogenics

 

To note, Advanc3d is largely on target within that which he has addressed.

 

Notable as well,  'clean living', some good exercise, a healthy diet, and a well-rounded 'core' pro-health supplement program  as prior recommended can never hurt either - can't hurt to hammer in the obvious, right?

 

More antioxidants is not always better, as to that seeming recommendation as above, though with proper usage they certainly can be part of a strong core supplement program

 

Damage of this nature however will not see much benefit from antioxidants.  Responsible incorporation of antioxidants will simply largely counter potential damage that can occurs from normal body processes/stress/oxidative stress, especially if one engages that which fosters higher levels of such.  Within damaged states this can indeed be higher, in particular ones that create a direct imposition of higher oxidative stress, but not within such that will really bear relevance within significantly playing a factor as to remedying the damage we are primarily discussing.

 

Anyway, if you need any more help, always happy to...

[Advanc3d]

I apologize if this is off topic or has no interest, but would the anti-depressant Agomelatine have any potential instead of an SSRI?  I was on SSRis for about 5 years and being off of them for about 2 years now, I never want to go back.  I also made the mistake of abusing MDMA and a handful of other substances, while on medications such as SSRI and benzos.  Since being clean off of everything, I have maintained a rigorous exercise routine, very healthy diet, proper sleep, and a healthy social life for about 2 years now, but I still deal with all the repercussions of my past behavior and addictions.  I feel like I have reached a plateau in my recovery and I want to try medications again, this time around being sober from the other drugs.  I have an appointment with a psychiatrist in September and I would greatly appreciate any advice or opinons on which medications to bring up in our conversation.  I hope this post is taken as a contribution to the thread and not as a personal cry for help, as I think there may be others in my position wondering the same thing.  Anyways, Thank you to the OP and everyone in this thread for all the excellent information and discussions! Very much appreciated indeed.  

 

Agomelatine has very poor bioavailability. Sublingual 2mg = 50mg to give a comparison.

its affinity on 5-HT2c is extremely low and its effects are not contributed from it. So what it actually is doing is regulating sleep, increasing time spent in slow-wave sleep, and etc. which init self alliviates depression.

Agomelatine also increases BDNF in the frontal cortex. so its 'effects' are subjective and you would have to try it for your self. i dont recommend SSRI's to anyone unless they are literally suicidal, even then there are better alternatives.

 

Well, a lot of bandying about about this and that, when it is largely seen to be determined as due to axonal loss

 

Prescription:  axonogenics

 

To note, Advanc3d is largely on target within that which he has addressed.

 

Notable as well,  'clean living', some good exercise, a healthy diet, and a well-rounded 'core' pro-health supplement program  as prior recommended can never hurt either - can't hurt to hammer in the obvious, right?

 

More antioxidants is not always better, as to that seeming recommendation as above, though with proper usage they certainly can be part of a strong core supplement program

 

Damage of this nature however will not see much benefit from antioxidants.  Responsible incorporation of antioxidants will simply largely counter potential damage that can occurs from normal body processes/stress/oxidative stress, especially if one engages that which fosters higher levels of such.  Within damaged states this can indeed be higher, in particular ones that create a direct imposition of higher oxidative stress, but not within such that will really bear relevance within significantly playing a factor as to remedying the damage we are primarily discussing.

 

Anyway, if you need any more help, always happy to...

 

The issue is that the body is always in damage-repair and lack of autophagy. and usually due to our life style the equilibrium is towards damage. Oxidative stress overwhelms most of the time, hence why we have so many ailments in health these days.

 

Caloric Restriction, Intermittent fasting, and Keto diet, rank from least effective to most effective in terms of its effects on switching this equilibrium around.

Ketosis is extremely potent in terms of repair and neuro protection, it significantly increases BDNF, GDNF\. being in sustained ketosis of averaging at 3mmol/l is suffice to negate the most prevalent oxidative stress in the brain, and that is from glycolysis. once this is taken under control, endogenous antioxidants become more potent in doing their action and other things... and the brain can actually repair it self, as well as the body.

 

Ketogenic diet is the only proven concept in rat models to reverse diabetic complications, which is significant considering 'doctors' dont believe it is possible

 

http://www.ncbi.nlm....les/PMC2649682/

[VERITAS INCORRUPTUS]

 

 

Well, a lot of bandying about about this and that, when it is largely seen to be determined as due to axonal loss

 

Prescription:  axonogenics

 

To note, Advanc3d is largely on target within that which he has addressed.

 

Notable as well,  'clean living', some good exercise, a healthy diet, and a well-rounded 'core' pro-health supplement program  as prior recommended can never hurt either - can't hurt to hammer in the obvious, right?

 

More antioxidants is not always better, as to that seeming recommendation as above, though with proper usage they certainly can be part of a strong core supplement program

 

Damage of this nature however will not see much benefit from antioxidants.  Responsible incorporation of antioxidants will simply largely counter potential damage that can occurs from normal body processes/stress/oxidative stress, especially if one engages that which fosters higher levels of such.  Within damaged states this can indeed be higher, in particular ones that create a direct imposition of higher oxidative stress, but not within such that will really bear relevance within significantly playing a factor as to remedying the damage we are primarily discussing.

 

Anyway, if you need any more help, always happy to...

 

The issue is that the body is always in damage-repair and lack of autophagy. and usually due to our life style the equilibrium is towards damage. Oxidative stress overwhelms most of the time, hence why we have so many ailments in health these days.

 

Caloric Restriction, Intermittent fasting, and Keto diet, rank from least effective to most effective in terms of its effects on switching this equilibrium around.

Ketosis is extremely potent in terms of repair and neuro protection, it significantly increases BDNF, GDNF\. being in sustained ketosis of averaging at 3mmol/l is suffice to negate the most prevalent oxidative stress in the brain, and that is from glycolysis. once this is taken under control, endogenous antioxidants become more potent in doing their action and other things... and the brain can actually repair it self, as well as the body.

 

Ketogenic diet is the only proven concept in rat models to reverse diabetic complications, which is significant considering 'doctors' dont believe it is possible

 

http://www.ncbi.nlm....les/PMC2649682/

 

 

Hence my recommendation and long-standing contention that supplemental antioxidants are integral for any 'core' supplement program, and should accommodate the degree of stress one is engendering within their lifestyle, as well as genetic dispositions to handle such.

 

Most doctors know less than most well-informed health conscious people, and grasp onto dogmas so firmly as to lose any real degree of open-minded consideration for most anything outside such.  So what they in general believe and espouse certainly should always be taken within understanding such.

 

Diabetic complications can be alleviated and even remedied by many sound programs, that encompass proper diet, exercise, and supplementation.  Indeed ketogenic oriented diets will be the standard as to diet, being it is the means to foster the necessary insulin-dependent modulations.  Here we come back to the area of upregulation, sensitivity, tolerance and all that  

 

Within that, it would seem this thread has been answered more than sufficiently for an EOD, at least, unless anyone sees some real missing piece of the puzzle

[serp777]

Like others in this thread have said, it sounds like you got a batch that had other neurotoxic components. The mdma itself was very unlikely to do that much damage in a one time event, unless you're genetically susceptible/extremely unlucky. 

 

I'm almost wondering if seratonin is even your problem here. It could have been a chemically induced brain injury instead, which depression is often associated with. 

 

Perhaps you could try noopept, which is powerful cholinergenic. There's also the option of a low dose lithium supplement; people who drink water that has natural lithium are generally less depressed.  

[Plasticperson]

when people don't take high doses of antioxidants with MDMA  ... i know people who roll with once a month and they say they don't receive any prolonged effects with strong antioxidants taken with the MDMA...MDMA also has trace amount of mercury. Its used in the manufacturing. As far as u helping you out goes try some Rhodiola it really helped my one friend with HPPD

[Advanc3d]

when people don't take high doses of antioxidants with MDMA  ... i know people who roll with once a month and they say they don't receive any prolonged effects with strong antioxidants taken with the MDMA...MDMA also has trace amount of mercury. Its used in the manufacturing. As far as u helping you out goes try some Rhodiola it really helped my one friend with HPPD

err

 

Mercury?

the synthesis route to MDMA using mercury compounds as a potential catalyst/intermediate isnt performed and if it is, it accounts for 1% of production as there are 50 other synthesis routes which are 'simpler' to perform by the average chemist.

 

Mercury is extremely poorly absorbed, unless it is organic. in this instance it is elemental, which is lower bioavailability then inorganic mercury which is pretty low to begin with

Edited by Advanc3d, 19 August 2014 - 11:11 PM.

[Plasticperson]

 

when people don't take high doses of antioxidants with MDMA  ... i know people who roll with once a month and they say they don't receive any prolonged effects with strong antioxidants taken with the MDMA...MDMA also has trace amount of mercury. Its used in the manufacturing. As far as u helping you out goes try some Rhodiola it really helped my one friend with HPPD

err

 

Mercury?

the synthesis route to MDMA using mercury compounds as a potential catalyst/intermediate isnt performed and if it is, it accounts for 1% of production as there are 50 other synthesis routes which are 'simpler' to perform by the average chemist.

 

Mercury is extremely poorly absorbed, unless it is organic. in this instance it is elemental, which is lower bioavailability then inorganic mercury which is pretty low to begin with

 

 

Err

 

your wrong?

a couples grams of mercury salt is needed for the amalgamation of MDP2P to MDMA which is the simplest most prevalent way of making MDMA.... now its up to the discretion of the chemist to distill and then wash the final product with acetone which removes mercury and other byproducts but also reduces the valuable weight of the final product. 

[heal and help :)]

BUMP

sorry to revive this old thread out of the blue, but I thought it would be a good opportunity to catch up on any potential progress the past 2 years?

 

(also, just to note - after publicising my year long strugglle from an MDMA binge, in an attempt to reach out and give harm reduction advice, many friends have since described to me their experiences, and they all got better though taking drasitcially different amounts of time, and I have already seen dramatic improvements in multiple areas, so i do want to say please dont lose hope it will get better and there is something out there which is right for you as an individual in terms of healing, ims rue, we just have to continue our search to find the one that fits us)

[Autumn Knight]

BUMP

sorry to revive this old thread out of the blue, but I thought it would be a good opportunity to catch up on any potential progress the past 2 years?

 

(also, just to note - after publicising my year long strugglle from an MDMA binge, in an attempt to reach out and give harm reduction advice, many friends have since described to me their experiences, and they all got better though taking drasitcially different amounts of time, and I have already seen dramatic improvements in multiple areas, so i do want to say please dont lose hope it will get better and there is something out there which is right for you as an individual in terms of healing, ims rue, we just have to continue our search to find the one that fits us)

 

What have you done that specifically helped?

 

It has been almost 9 years since my binge, and my deficits are still crippling.

[gamesguru]

I can definitely vouch for the bacopa, magnesium, exercise, and meditation.  When I was deciding on my stack, serotonin repair was a major concern.  So without further adieu, here's what else I've found.  Lots of other things influence serotonin (zinc, lithium, schizandra, etc.) so I included the most practical results, which are the ones that made it into my stack.

Identification of antidepressant-like ingredients in ginseng root (Panax ginseng C.A. Meyer) using a menopausal depressive-like state in female mice: participation of 5-HT2A receptors.
Yamada N1, Araki H, Yoshimura H. (2011)

RATIONALE: After reports of adverse effects with hormone replacement therapy, such as reproductive and breast cancer and coronary heart disease, much attention has been given to the development of new remedies to alleviate menopausal depression in women, but methods for their preclinical evaluation have not been clarified. We previously developed a procedure to predict the drug effect on the menopausal depressive-like state in female mice.
OBJECTIVES: We attempted to identify psychoactive components from ginseng root, one of the earliest known materials for menopausal disorder, and to clarify the possible mechanism involved.
METHODS: As an index of a depressive-like state, we used the prolongation of immobility time induced by an ovariectomy during the forced swimming test. Chronic treatment with the candidate substance began the day after ovariectomy and continued for 14 days. To examine whether the 5-HT(2A) receptor antagonist ritanserin antagonized the antidepressant-like effect of ginsenoside Rb(1), ritanserin was given as pretreatment 15 min before the daily administration of ginsenoside Rb(1) and the antagonistic effect was compared with ginsenoside Rb(1) alone.
RESULTS: Ginsenoside Rb(1) and compound K were active ingredients that dose-dependently prevented the prolongation of immobility time induced by ovariectomy. Co-administration of ritanserin, a 5-HT(2A)-receptor antagonist, antagonized the effect of ginsenoside Rb(1).
CONCLUSIONS: We suggest that ginsenoside Rb(1) and its metabolite, compound K, are antidepressant-like components of the ginseng root, and that 5-HT(2A) receptors may play an important role in mediating the antidepressant-like effect of ginsenoside Rb(1).

Evidence for the involvement of the serotonergic 5-HT(1A) receptors in the antidepressant-like effect caused by hesperidin [GRAPEFRUIT] in mice.
Souza LC1, de Gomes MG, Goes AT, Del Fabbro L, Filho CB, Boeira SP, Jesse CR. (2013)

The present study investigated a possible antidepressant-like activity of hesperidin using two predictive tests for antidepressant effect in mice: the forced swimming test (FST) and the tail suspension test (TST). Results demonstrated that hesperidin (0.1, 0.3 and 1 mg/kg, intraperitoneal, i.p.) decreased the immobility time in the FST and TST without affecting the locomotor activity in the open field test. The antidepressant-like effect of hesperidin (0.3 mg/kg) on the TST was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (pCPA; 100 mg/kg, i.p., an inhibitor of serotonin synthesis) and WAY100635 (0.1 mg/kg, subcutaneous, s.c., a selective 5-HT(1A) receptor antagonist). Pretreatment of mice with prazosin (1 mg/kg, i.p., an α(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α(2)-adrenoceptor antagonist), propranolol (2 mg/kg, i.p., a β-adrenoceptor antagonist), AMPT (100 mg/kg, i.p., an inhibitor of tyrosine hydroxylase), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D(2) receptor antagonist), ketanserin (1mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist) or MDL72222 (1 mg/kg, i.p., a 5-HT(3) receptor antagonist) did not block the antidepressant-like effect of hesperidin (0.3 mg/kg, i.p.) in the TST. Administration of hesperidin (0.01 mg/kg, i.p.) and fluoxetine (1 mg/kg), at subeffective doses, produced an antidepressant-like effect in the TST. The antidepressant-like effect caused by hesperidin in mice in the TST was dependent on an interaction with the serotonergic 5-HT(1A) receptors. Taken together, these results suggest that hesperidin possesses antidepressant-like property and may be of interest source for therapeutic agent for the treatment of depressive disorders.

Stress-induced 5-HT1A receptor desensitization: protective effects of Ginkgo biloba extract (EGb 761).
Bolaños-Jiménez F1, Manhães de Castro R, Sarhan H, Prudhomme N, Drieu K, Fillion G. (2015)

The effects of sub-chronic cold stress on the functioning of hippocampal 5-HT1A receptors in old isolated rats and the possible protective effects of Ginkgo biloba extract (EGb 761) were investigated. Cold exposure during five days, produced a significant reduction of the inhibitory effect of 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) on forskolin-stimulated adenylyl cyclase activity. In contrast, neither the affinity nor the density of hippocampal [3H]8-OH-DPAT binding sites were affected indicating that the reduced sensitivity of 5-HT1A receptors induced by stress is probably due to a modification of their coupling mechanisms to adenylyl cyclase. The stress-induced desensitization of 5-HT1A receptors was prevented by the administration of EGb 761 (50 mg/kg per os/14 days). These results clearly indicate that 5-HT1A receptors are desensitized by stress and point out the reduced capacity of old rats to cope with the adverse effects of a chronic stressor. EGb 761 appears to restore the age-related decreased capacity to adapt to a chronic stressor.

Dietary modulation of uptake transporters. PhD thesis, University of Leeds.
Naccarati, Chiara (2014)

Transporters play a determinant role in creating and maintaining physiological balance within the cells. Though, not much information exists on the modulation of transporters, especially in terms of polyphenols and other dietary components. Initially, a comprehensive database was created, using the high-performance search engine Genevestigator. The database summarises the existing knowledge on selected transporters (OAT1, OAT3, OATP1A2, OATP1B1, OATP1B3, OATP4C1, MRP2, MRP3, BCRP, MCT1, MCT7 and SMCT1). The anatomical distribution of the latters was investigated in the human heart, kidney, liver and intestine. Transcriptional modulation was also assessed, in response to biological mediators, disease, chemicals and drugs. It was shown that while some transporters were modulated from a large number of conditions, others only responded to few. Interestingly, not many dietary compounds were tested, highlighting the limited knowledge existing in this area. Subsequently, expression of a transporter of interest, the organic anion transporter 3 (OAT3), was assessed in liver HepG2 cells. It was predicted, on the basis of the Ct value, that OAT3 was expressed in the cell line at low levels. Modulation of OAT3, in response to stressors (hydrogen peroxide, tert-butyl hydroperoxide and ethanol) at various concentrations and for different time lengths was assessed. It was shown that none of the stressors affected the transporter. In the same cell line, uptake of the metabolite kaempferol-3-O-glucuronide was assessed, to establish whether uptake occurred in a carrier-mediated manner or through passive diffusion mainly. Uptake resulted to be carrier-mediated, although the low Vmax of the transport, close to detection limit, did not make possible further studies to identify the transporter(s) involved in its uptake. Finally, intestine Caco-2 cells were used to assess modulation of the serotonin transporter from green tea and coffee. For the first time, it was reported that green tea and coffee acted as modulators of serotonin uptake. Whole extracts showed to act in a concentration-dependent way. Physiological concentrations of individual green tea components showed not to have a significant effect on the uptake, however significant effect was observed when using supplement concentrations (equivalent to 7 cups). Physiological concentrations of several coffee components showed to modulate serotonin uptake. Among them, ferulic acid and 5-feruloylquinic acid showed to act in a competitive manner.

[heal and help :)]

with a combination of different practises i have been feeling much better, and continue to improve. during the time that i took no action i did not improve as much, and went through periods where i gave up hope - please do not give up hope, as I will elaborate on the very state of giving up hope can in itself be counterproductive to the situation, as hard as staying driven to the end goal of healing may feel at times. There is a way out! it may at times feel hard, but i can feel the cumulative positive effects the different attempts have had.

 

so first up, i guess dont neglect the basics - i abstained from drugs and exercised a lot (ideally daily), and am now changing my diet and getting better sleep (sleep is where the healing takes place, diet is where you get the necessary building blocks, and exercise increases blood flow to the brain increasing neurogenesis and overall wellbeing) . do not underestimate the power of these approaches.

 

supplementing with the basic nutrients the brain needs (you can get multivitamins, and dietary shakes, though do try and get this through diet too. avoid taking 5-HTP, this is a short-term solution at the expense of a long-term one), helped i think, while keeping my brain active and training it (in combination with the other factors, this should encourage healing and improvements in the areas of the brain activated. hence the phrase 'practise makes perfect', we get better at things through practise and activation because those parts of the brain develop), but i plan on changing my diet to the ketogenic diet, as the more i research, the more i realise just how significant a diet change can be (ketogenic diet for example changes your primary energy source from glucose to ketones, which are a more effective fuel for the brain but also is the energy source used by newborn infants, at a time of their lives when brain development is so incredibly fast).

 

also doing one's best to maintain a positive mental attitude. hold up! this is genuine! multiple studies have shown depression, a 'mental' illness, to cause physical shrinkages in different parts of the brain that, naturally, impact cognitive functioning, though fortunately these are reversible. do not underestimate the power of the mind! imagine what the opposite could do (eg. studies have found smiling by itself led to an increased feeling of happiness, and happiness and pleasure are the result of physical releases in neurotransmitters, in the same way depression is a lack of these)

 

along with exercise, there's meditation, such as mindfulness - again, studies have linked this to physical benefits to the brain (and even to DNA, by activating different genes and preventing the shortening of the telomere and more), as well as inducing that positive mental attitude i talked about, which in turn would lead to more physical benefits 

 

i had some similar but significantly less severe problems a while ago after playing around with ritalin (i was prescribed. i have now learned not to abuse drugs), but what got me out of the drug-induced shit was a shift in my attitude from obsessive negative rumination to a positive frame of mind, induced by a retreat-week of intense exercise and meditation including Qi Gong. this is something i have been thinking about more recently, which i should have been doing this last year though i have begun to restart this practise

 

have you looked into nootropics at all? they may help.

 

 

BUMP

sorry to revive this old thread out of the blue, but I thought it would be a good opportunity to catch up on any potential progress the past 2 years?

 

(also, just to note - after publicising my year long strugglle from an MDMA binge, in an attempt to reach out and give harm reduction advice, many friends have since described to me their experiences, and they all got better though taking drasitcially different amounts of time, and I have already seen dramatic improvements in multiple areas, so i do want to say please dont lose hope it will get better and there is something out there which is right for you as an individual in terms of healing, ims rue, we just have to continue our search to find the one that fits us)

 

What have you done that specifically helped?

 

It has been almost 9 years since my binge, and my deficits are still crippling.

 

 

[Finn]

/Tianeptine made me a lot worse so I discontinued, zoloft made me feel slightly better but when I stopped taking it (after 3 years) I went back to the way I was before - so it obviously only temporarily masked the problem and did not cause any noticeable up-regulation.

 

 

Often it is more doable to "mask", or more like to manage the issue, than it is to fix the damage. 

 

For example, temporal lobe epilepsy, which can have a number of causes such as head injury, stroke, brain infections, structural lesions in the brain, or brain tumors, or it can be idiopathic and have no apparent cause. 

 

None of the temporal lobe epilepsy treatments are based on fixing the damage in temporal lobes. The main treatments are managing it with anti-epileptics, or if they don't work, surgery, where some parts of the damaged temporal lobe are removed, then the opposite side temporal lobe and other brain areas take over it's tasks.

 

Plenty of chronically depressed people stay on antidepressants for the rest of their lives, plenty of bipolar patients stay on mood stabilizer or mood stabilizer + antidepressant combo for the rest of their lives. I personally plan to stay on combination of at least 3 different neuropsychiatric medications for the rest of my life.

 

Since your symptom is depression, and you had somewhat positive response to one antidepressant, it might be more doable to treat this as chronic depression, rather than trying to figure the exact mechanism of what  MDMA did and how to reverse that change or heal that damage. If Zoloft (sertraline) made you feel somewhat better, you could try Zoloft + Remeron (mirtazapine) combo, or Remeron + SNRI, like Cymbalta (duloxetine) or Effexor (venlafaxine). If you manage to find working antidepressant or antidepressant combo with manageable side effects, staying on it for the rest of your life is ok, plenty of people here are taking antidepressants or other neuropsychiatric medication for the rest of their lives.

 

 

Edited by Finn, 06 March 2017 - 08:53 PM.

[gamesguru]

The severity of side effects is not expected to diminish with age, while the disease itself (often) does.  Steve Nash took it less and less as he got older, only turning to it in extremely desperate times, and otherwise relying on his mind's natural resilience and harmonizing essence.  That's what happens when you turn to medicine every time some minor thing goes wrong, you come to depend on it.. you become a pussy.  Ahhhh, is that what you want?

 

In fact, the more decades you take medication ABC the more severely it affects your genes and morphs your brain structure.  FWIW marijuana is also classified as a medicine.  Hence an argument for getting off the stuff late in life.  Older antipsychotics are known to cause motor dysfunction (tardive dyskinesia), newer ones cause diabetes, and some of both classes can push dementia over the edge to death[1].  As the body weakens in age, the severity and breadth of side effects of common medicines is expected to increase... I regret there is nothing sustainable about this approach, and the patient is increasingly encouraged to go the route of common sense health.

[PMFWIW]

Hi, Im new to longecity and I have come to ask you for help. I am obsessed with the thought that I have damaged my brain by MDMA use and I really want to evaluate how bad it is. These thoughts keep me awake at night reading forums, research papers and etc, which is bad by itself since I am constantly anxious and every fail in my daily life I attribute to drug use.

So here is some statistics. In the scope of 2 years here is what I believe is somewhat accurate estimations of my drug usage:

MDMA: 5.5 grams

Amphetamine sulfate: around 1.2g

Cocaine: under 1 gram

Mephedrone: 1g

Most of it happened during the first year. Should be noted that I have never taken 2 drugs simultaneously. my average session with mdma was about 3 mg/kg separated in somewhat equal dosages. Highest being around 6 mg/kg. Also I have never binged on any drug after I get back from a night out.

What has changed since my drug use: 

- Concentration and attention span have very noticeably worsened.

- Short term memory decreased

- emotional swings and instability

- social anxiety worsened

 

 

Overall, Im living a quite active lifestyle, gym, football etc.

 

Anyhow, would you say the damage is severe? Do you think I will ever feel normal again? Obviously no one would be able to give a definite answer but I want to make peace with myself and accept what was done so I can move on.

Thank you so much in advance, means world to me right now.

 

[jaiho]

How much time between the MDMA doses?

Typically mdma abuse induces a severe depression. Treatment with SSRIs would be useful until everything settles.

[PMFWIW]

It's hard to tell for sure now. I think on average once a month for a year taking around 300 mg per night. After that drastically reduced the frequency and continued to use once every three months.

Thank you for the reply.

[MDMarcus]

I guess OP and most of you are gone by now, but for those who still check in after all this time, Hi!
I myself did this stupid act of taking MDMA. Not tested, no measurement and i'd say very irresponsibly taken as i was probably malnurished, in pretty bad shape and continously high on weed for god knows how long. I only did mdma 5 times, 4 of which have been withing the last 180 days. I very much appreciate all the replies in this thread, as they to large degree are edeucated or well researched answers. With my basic knowledge of neurobiology and neurochemistry i'll be unable to provide much further insight. I will however try to add to the conversation.

First, my main concerns are not with my mood, but rather my focus and memory. I've been much more abesnt-minded as of late, short term memory is worse and i suspect my long term memories have somewhat faded. Nothing is for sure though, as it's hard to compare with something that no longer exist, if that explains it well enough. It's harder to remember faces of people i just met, and my life-story becomes less detailed. Also i remember more in words or the famous "schemas" that arise from cognitive psychology, and compared to my earlier memory which was almost exclusively in images and sound, is a lot less efficient. 

 

I've read countless of articles and forums, and the let me just say that all of this is very much speculation. Most drug related research is done on animals, and extrapolation to people is difficult. Some things are proven as i'm well aware of, but as we can see from reading the responses in this thread evidence is highly contradictory in many cases and very confusing. I'm not sure if we can properly controll for individual differences, and they might be a vital factor. The thread provides insight and information i've yet to come across, but a lot of it i've read as well. 

None of us can really know any of this for sure, and to a desperate person just like me it's quite frustrating. However, after reading the response from Rior i've been able to calm down about the matter. As he points out there is a lot you can do to improve your brain's capasity and funtionality, as neuroplasticity is a beautiful phenomenon. Sure a lot of us have damaged our potential, but suffering this minor setback a lot of us start wanting to improve, which otherwise we wouldn't feel the need to. Who knows, we might even go even further due to this. Therefore there is nothing really to worry about in terms of memory and intelligence. With my BASIC knowledge i reccommend the exact same as Rior, in terms of exercises or mental workouts, as this have proven to be very effective at even restoring major parts of your brain after damage. Healthy regions adapt the functions of the damaged ones. Due to double shifts it's not as good though, but considering none of us have had strokes or severe brain damages, (except Rior) it's not inconcievable that the damage is to large degree reversable. The natural mechanics of your brain is designed to do this kind of work. With this said i'll say my piece on supplements and healthy living. You probably can't add a lot of magic potions and pills to solve anything, as your body doesn't generally use the components that are excess, and i the cases everything is being used there is something called "too much" I'd focus on the mental workouts with a normal healthy lifestyle, where sufficient vitamin, protein and carbs are consumed only to provide your body with sufficient building blocks to do the work itself. With regards to antidepressants and serotonin supplements, they might both have an opposite effect, making your body "lazy" and reduce production of necessary neurotransmitters and hormones as they frequently come from the outside. Don't overdo it with supplements. 

To try to help out OP:
Have you gone to therapy? I'd strongly reccommend it if you find a good one. Some are terrible, so beware. However there is a chance that your depression is imagined pr caused by other very meaningfull factors that are easy to overlook. I do not know the case though. If your problem is on a neurological level then you seem to indeed have a form of chronic depression that will be hard to work with. Behavioural activation is a treatment designed from the functional analysis of depression, and directly counteract the mechanisms that induce or maintain depression. However if you do have a neurological or physiological problem this might not be sufficcient by itself.I need to say that i have faith in therapy either way. Nobody in the field of psychology really knows what's going on either, due to the complexity of our organism and hence the differend branches we work in, but there have been a lot of studies that find evidence that therapy can and will change you on a physiological and neurological level, so i'd reccommend giving it a go. If you combine good therapy with the advices presented to you in this thread i'm sure you'll see improvement. I highly agree with Rior, but i also reccommend to take it easy on the supplements. If something REALLY worked we'd know it, because the pharma companies would be all over it by now. Emotional imbalance or more specifically depression is a pain in the ass, but human nature allows us to readapt and change. 

I feel there is much more to say, but that might be because i left out all the science parts and ended on a more opinion based note. I can provide a lot of interesting reads, but i'm sure you are able to find them just as well. Let me know if anyone is interested in citations or further elaboration, i'd be happy to endulge you. Please let me know OP, how you are doing now and if you found anything that helped. Also i apolgise for the lack of structure and organization of my post.

[MDMarcus]

It's hard to tell for sure now. I think on average once a month for a year taking around 300 mg per night. After that drastically reduced the frequency and continued to use once every three months.

Thank you for the reply.

For the love of yourself stop taking the drug. 
(i'm not allowed to post links as i'm new to the forum)
This is a year long study that tried to determine the extent of the damage.

According to webmd which got an interview with the researcher Zarkanis, the patients who used MDMA on an average of 2.4 times a month for one year only scored half of what they did at the start of the study. This does not take into account the quality of the drug, says nothing about other drugs or how much they used before the study, so it has a lot of limitations, but is (Link)

 

You most likely have done some damage to yourself, but there is some consolidation
(link)
I didn't real it thouroghly, but the DEA speculates the damage potential. From what i can tell from rushing through the text and looking at the graphs the damage is reversible, but i would stop right now if i was you. Also start living a healthier lifestyle to aid the efforts of recovery. Better to stop now and revisit it in a year than continuing and causing yourself some severe and maybe permanent damage.

If you see this let me know, and i'll give you the links. If not i'll try to edit in the links when the limitation is lifted. the reads are quite good, especialy the DEA one. Zarkanis MDMA in google and you get the abstract, add webmd and you get the interview part and the title of the DEA read is Can MDMA (Molly, ecstasy) damage your brain?