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Selegiline and curving tolerance

selegiline deprenyl tolerance withdrawal downregulate receptors nmda cdp-choline dopamine magnesium

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#1 **DEACTIVATED**

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Posted 22 March 2013 - 07:24 PM


Hi,

I'd like to discuss a safe and reliable method to use Selegiline long term without developing tolerance or withdrawal. I'm just going to dive right in in hopes of attracting other experienced Selegiline users and/or knowledgeable persons about the drug. Much of the Selegiline discussions on this board tend to end with no conclusions about the specific issue of tolerance.

First off, Selegiline raises dopamine levels in the brain. Most of us know this. Most of us also know that when levels are raised the receptors are then down regulated. Let me just stop for one second because I want to take this moment to briefly clarify that I am not as experienced or knowledgeable about how the brain works compared to many others on this message board. Far too many times have I been overwhelmed by the information many possess and I will not pretend to know what I'm talking about, but I know a little. Some of the tolerance from Selegiline is obviously from the down regulation of the receptors, so I'll start with that.

How can you avoid down regulating the receptors? Well, there are supplements that can help to upregulate them and that's probably pretty close to what you'd want. CDP-Choline is a big one along with Inositol. I'm sure there are others and maybe someone can shed more light on them. Anyway, if these supplements can upregulate the receptors, can't one just supplement with them occasionally to boost receptor densities?

Now, what about keeping receptors from down regulating faster? In the "great porn experiment" by Gary Wilson he discusses how porn can down regulate D2 receptors through visual stimulation paired with masturbation. This is already kind of controversial so I'd like to steer away from it. But really, we can achieve natural hits of dopamine from our own body through food, sex, and other activities that are rewarding. These must down regulate receptors as well, but probably not much. Even so, maybe it's possible to slow the down regulation of receptors by excluding anything else that might release high amounts of dopamine through supplementation or natural in-house activities. Off the top of my head that could include limiting caffeine, l-tyrosine, dlpa, porn, amphetamines, and maybe high calorie foods. This method I admit seems a little on the irrelevant side of things, but it's not hard to implement.

Now onto more complicated out-of-my league areas. Apparently there's this rumor that has been proven anecdotally 100's of times that NMDA receptor antagonists can slow down the tolerance build up to amphetamines. Selegiline isn't exactly an amphetamine, but it's been stated multiple times that it may as well be a very low dose of one. The mechanisms must at least be similar enough that NMDA receptor antagonists can still slow the tolerance build up. Memantine is the biggest one next to DXM for achieving this. Magnesium is also supposed to help but some say it's not nearly as useful as the others.

Ok so there's options to lengthening the time between re-cycling Selegiline and I hope I haven't totally turned the subject up on it's head with misinformation.

Please now allow me to share my methods and goals with this drug. I intend to use Selegiline at 5mg/weekly at 1mg/daily on weekdays with weekends off. I'll be dosing it in the evening sublingually after some fatty food for better absorption. I will then be using CDP-Choline at 250mg EOD indefinitely or until I become depressed. I might increase the dose after weeks of evaluation with no depression. I will also be supplementing with 500mg of Magnesium Citrate and 144mg of Magnesium Threonate daily.

Continuing.. I am a 23 year old male that exercises intensely 3-4 times a week. I eat well with many vegetables, fruits, and high quality protein. I get good sleep and I keep stress at bay. I also supplement with superfoods, vitamins, and minerals all from natural sources. I think I've built a good foundation for a normal healthy life. But now I want to take it a bit further with Selegiline.

I've reacted very well to this drug. It makes me more calm, more focused, less stressed, more joyful, more social, more motivated, less anxiety, better motor control... it's just been wonderful. I am hoping that at low doses and with the right accommodating supplements and lifestyle I can keep using it for 3-4 months with full benefits meaning no withdrawal or tolerance. Take a month off and then return for another 3-4 month cycle.

....

So what do ya'll think? I'm more or less just trying to ensure that I am on a practical track with this drug. On another note, I have some unopened memantine that I kind of wanted to add but I'm not so sure anymore. Is it worthwhile? Or is magnesium good enough?

Edited by CrackaLackN, 22 March 2013 - 07:29 PM.


#2 peakplasma

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Posted 22 March 2013 - 08:46 PM

I'm the guy from the other thread.

What do you mean tolerance? Why do you think this?

I'm at >5 years so I think I've been using Selegiline longer than most people and haven't experienced tolerance.

Inventor Dr. Joseph Knoll described it as a Catecholaminergic Activity Enhancer (CAE) which means it makes your natural stimulants (like a runner's high) more intense and lasting.

The loss of MAO selectivity is actually reverse tolerance! - since it becomes more powerful the longer you use and it since it starts spilling into MAO-A which can be dangerous. I would cycle it only if you have BP or psychiatric (can cause a bit of mania) issues.

Also, MAO activity increases as you age, so simply getting older will counteract any loss of sensitivity.

Also, I think adding Memantine to Selegiline might be a bit dangerous.

Edited by peakplasma, 22 March 2013 - 08:52 PM.

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#3 Healthy Tony

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Posted 22 March 2013 - 09:13 PM

I'm the guy from the other thread.

What do you mean tolerance? Why do you think this?

I'm at >5 years so I think I've been using Selegiline longer than most people and haven't experienced tolerance.

Inventor Dr. Joseph Knoll described it as a Catecholaminergic Activity Enhancer (CAE) which means it makes your natural stimulants (like a runner's high) more intense and lasting.

The loss of MAO selectivity is actually reverse tolerance! - since it becomes more powerful the longer you use and it since it starts spilling into MAO-A which can be dangerous. I would cycle it only if you have BP or psychiatric (can cause a bit of mania) issues.

Also, MAO activity increases as you age, so simply getting older will counteract any loss of sensitivity.

Also, I think adding Memantine to Selegiline might be a bit dangerous.

Why would mixing Memantine to Selegiline be dangerous? I was actually going to recommend to the OP that he try Memantine, because using NMDA antagonists for tolerance reduction is more than anecdotal, it is actually quite a well understood mechanism. I'll try and find some info on this later. And I was thinking you should probably take the memantine before bed, when your selegiline levels are at their lowest.

Edit: Wait how much selegiline are you taking per day?

Edited by TheRockst4r, 22 March 2013 - 09:14 PM.


#4 **DEACTIVATED**

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Posted 22 March 2013 - 09:14 PM

Hey peakplasma,

Well, tolerance might not be the best word but there must be down regulation of dopamine receptors, no? You've just said that you haven't experienced any tolerance. That relieves me greatly and I've read other users state the same thing. Also that after discontinuing they felt fine too. It just sounds too good to be true is all.

I don't even want to ask why Memantine would be dangerous, haha. I'm simply not that interested in it except for enhancing selegiline.

Do you mind me asking your age and dosage of selegiline? I think 5mg/week is good for me with some cycling. I am theorizing that my MAO activity is very active because of how well I react to inhibitors.

Edited by CrackaLackN, 22 March 2013 - 09:15 PM.


#5 peakplasma

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Posted 22 March 2013 - 09:40 PM

I'm 28 and I work closely with my MD to cycle and fine tune my dosage so it varies - but over the last year, I have averaged roughly 4mg-7mg a week.

You should do some reading on the functions of the Dopaminergic Synapse to understand this better. MAO inactivates dopamine before it is packaged into synaptic vesicles; so an MAO inhibitor does not increase dopamine in the synapse by reversing or altering transport like cocaine, amphetamines and other stimulants.

Memantine is a D2 agonist and combined with an MAO inhibitor it has the potential to cause psychiatric problems (see side effects of Parkinson's medications aka gay sex addiction).

memantine potencies at NMDA receptors and dopamine D2(High) receptors are of a similar order of magnitude, it is likely that the clinical features of memantine can be attributed to its action at both types of receptors.


If you are serious about Selegiline find an MD that knows a bit about it. They have access to tons of resources and it makes some of the stuff on the internet (like combining memantine and selegiline) seem ridiculous.

Edited by peakplasma, 22 March 2013 - 09:51 PM.

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#6 **DEACTIVATED**

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Posted 22 March 2013 - 11:17 PM

You're right, I should read more.

So you're saying that selegiline won't down regulate dopamine receptors? I feel like a broken record asking that. If so then this thread doesn't even serve its original purpose.

#7 peakplasma

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Posted 22 March 2013 - 11:46 PM

No, Selegiline shouldn't downregulate dopamine receptors (but it does enhance dopamine release so if you combine it with a dopamine releaser like amphetamine or do something excessive like benders with hookers and blow it might mess with your reward system a bit)

With that in mind, it's great if you're an athlete gives you a great runner's high and keeps you focused.

#8 jadamgo

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Posted 23 March 2013 - 01:55 AM

MAOIs don't cause the same desensitization problems that you get with illegal drugs. As you gradually reach a steady state of MAO inhibition, the dopamine receptors' quantity and sensitivity reach a new equilibrium. Same with serotonin and norepinephrine.

Don't cycle MAOIs -- the name of the game is "steady state". Try splitting your dose into a morning and afternoon dose, instead of taking it all in the morning. Take the same dose every day unless you're intentionally retitrating your dosage to a higher or lower level.
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#9 **DEACTIVATED**

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Posted 23 March 2013 - 03:29 PM

I'd really dislike to turn this thread into something else now, but you guys are hella knowledgeable.

Do you think I could get away with increasing my dose to 10mg/week? Perhaps 1mg in the morning and 1mg in the afternoon (like jadamgo recommends) and only on weekdays. Is there anything I should do besides be healthy while continuing Selegiline? I'm not sure how else to word that mainly because I don't really know what I'm asking. I just want to hear about the risks.

Also, can anyone recommend anything that goes very well with Selegiline? Or at least point me to some options that I can read further on. I was thinking about throwing Bacopa in the mix maybe 3x/week to enhance serotonin slightly. Maybe Ashwagandha a couple times a week to cover stress and possibly more testosterone production. Can't go wrong there, right?

Although, I don't want to just be randomly throwing regimens together. Opinions?

#10 peakplasma

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Posted 23 March 2013 - 03:48 PM

10mg/week should be fine.

It mixes well with almost everything in my opinion but its dangerous with stimulants (Craze, Jack3D, PEA, Adderal) and other antidepressants (MAOis,SSRIs,SNRIs).

Edited by peakplasma, 23 March 2013 - 04:01 PM.

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#11 **DEACTIVATED**

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Posted 23 March 2013 - 07:37 PM

Yes,

Selegiline is actually very calming for me but is just.. unpleasant with even caffeine or just stims like you mentioned. Nothing wrong with cutting those out! Or at least sparingly.

Thanks for your time and I hope you don't mind some PMs here and there. I'm going to do some reading hopefully.

Edited by CrackaLackN, 23 March 2013 - 07:38 PM.


#12 Mr. Pink

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Posted 23 March 2013 - 11:36 PM

curbing*
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#13 peakplasma

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Posted 24 March 2013 - 04:06 AM

Yes,

Selegiline is actually very calming for me but is just.. unpleasant with even caffeine or just stims like you mentioned. Nothing wrong with cutting those out! Or at least sparingly.

Thanks for your time and I hope you don't mind some PMs here and there. I'm going to do some reading hopefully.

Yeah no prob.

#14 renfr

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Posted 24 March 2013 - 04:10 PM

What factor causes increase of MAO in aging people?

#15 peakplasma

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Posted 24 March 2013 - 07:15 PM

What factor causes increase of MAO in aging people?


The observation is empirical. I don't think they have figured out the exact cause but there are a few theories.

Several' class='bbc_url' title='External link' rel='nofollow external'>http://www.sciencedirect.com/science/article/pii/S0197458097000377']Several studies of human brain postmortem report that monoamine oxidase B (MAO B) increases with age and it has been proposed that this increase reflects age-associated increases in glial cells.

→ source (external link)

Edited by peakplasma, 24 March 2013 - 07:16 PM.

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#16 KoolK3n

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Posted 11 April 2013 - 10:28 PM

I still don't see why Deprenyl can't be combined with Memantine.

#17 owtsgmi

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Posted 18 April 2013 - 11:27 PM

I still don't see why Deprenyl can't be combined with Memantine.


Me neither. I've been taking rasagiline interspersed with memantine for a couple years now. Memantine definitely resets the rasagiline for me.

Oh, and rasagiline is a MUCH better selegiline, IMO. Cleaner and no amp residue. I've tried both.

#18 KoolK3n

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Posted 19 April 2013 - 12:00 AM

Me neither. I've been taking rasagiline interspersed with memantine for a couple years now. Memantine definitely resets the rasagiline for me.

Oh, and rasagiline is a MUCH better selegiline, IMO. Cleaner and no amp residue. I've tried both.


Exactly!

I made a new thread exploring different methods to eliminate tolerance with selegiline, check it out:
http://www.longecity...tions-toxicity/

Edited by KoolK3n, 19 April 2013 - 12:07 AM.

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#19 peakplasma

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Posted 19 April 2013 - 01:55 AM

Memantine is a D2 agonist.

#20 KoolK3n

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Posted 19 April 2013 - 02:39 AM

Memantine is a D2 agonist.


Really? (Sarcasm)

Anyways, http://www.ncbi.nlm....ubmed/10486178/

#21 peakplasma

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Posted 19 April 2013 - 02:53 AM

I don't think you fully appreciate the risks of the combination.

Secondly, do you have the full study? There is little information in that abstract not to mention that it appears to be an in-vitro.

Edited by peakplasma, 19 April 2013 - 02:55 AM.


#22 KoolK3n

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Posted 19 April 2013 - 03:05 AM

I don't think you fully appreciate the risks of the combination.

Secondly, do you have the full study? There is little information in that abstract not to mention that it appears to be an in-vitro.

Seriously, I don't see the harm in combining the two. The only reason why your against it was something about gay sex addiction (lol) in one of your previous posts. And no I don't have the $31.50 for the full study.

Edited by KoolK3n, 19 April 2013 - 03:06 AM.


#23 peakplasma

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Posted 19 April 2013 - 03:55 AM

I'm not sure how to respond.. may I recommend read up on pharma theory? Or consult with someone with a background in pharma or medicine?

Besides the vast number of potential theoretical risks, I haven't seen much research on the combination so the biggest risk might be a contraindication based on some yet to be elucidated mechanism.

#24 KoolK3n

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Posted 19 April 2013 - 11:24 AM

I'm not sure how to respond.. may I recommend read up on pharma theory? Or consult with someone with a background in pharma or medicine?


Look at post #5 of this thread. You did say "look at Parkinson's side effects aka gay sex addiction" ehh what?

Besides the vast number of potential theoretical risks,


I'll ask again, what theoretical risks? I'm asking you to explain why and/or provide evidence.

Edited by KoolK3n, 19 April 2013 - 11:26 AM.


#25 peakplasma

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Posted 19 April 2013 - 04:08 PM

Seriously, I'm not sure you fully appreciate the risks of what you're doing to yourself. Go ask your MD to explain these risks to you because its obvious you won't listen to me.

Otherwise, look up dopamine dysregulation syndrome.

EDIT: Here is an interesting example.

Reversible Transvestic Fetishism in a Man With Parkinson's Disease Treated With Selegiline

Abstract


Dopaminergic therapy in patients with Parkinson's disease may change the quality as well as the quantity of sexual interest and behavior. This 72-year-old man had a 37-year history of Parkinson's disease treated with a right thalamotomy and was later treated with levodopa for more than 20 years. Selegiline (5 mg twice daily) was added for motor fluctuations. He developed a frequent impulse to wear women's clothing but did not act on this impulse until his wife died over a year later. He then began to dress in women's clothing an average of once per week. He stated he had never thought of cross-dressing previously. The selegiline was stopped, and his urge to wear women's clothing ceased. Paraphilias are a rare behavioral complication of Parkinson's disease treatment. Other paraphilias have been attributed to dopamine agonists, suggesting that the action of the monoamine oxidase inhibitor responsible for the patient's transvestism in this case was dopamine potentiation. Drug-induced paraphilias and hypersexuality may represent a reversal of the putative premorbid Parkinson's disease personality traits of introversion, cautious behavior, and lack of novelty-seeking. A biologic basis for transvestism, and paraphilias in general, is not known. Rare clues emerge from cases similar to this one.

Edited by peakplasma, 19 April 2013 - 04:17 PM.

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#26 KoolK3n

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Posted 19 April 2013 - 04:55 PM

Seriously, I'm not sure you fully appreciate the risks of what you're doing to yourself.


You keep saying that but don't care to explain them. I'm all ears.

#27 KoolK3n

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Posted 19 April 2013 - 05:02 PM

Dopaminergic therapy in patients with Parkinson's disease may change the quality as well as the quantity of sexual interest and behavior. This 72-year-old man had a 37-year history of Parkinson's disease treated with a right thalamotomy and was later treated with levodopa for more than 20 years. Selegiline (5 mg twice daily) was added for motor fluctuations. He developed a frequent impulse to wear women's clothing but did not act on this impulse until his wife died over a year later. He then began to dress in women's clothing an average of once per week. He stated he had never thought of cross-dressing previously. The selegiline was stopped, and his urge to wear women's clothing ceased. Paraphilias are a rare behavioral complication of Parkinson's disease treatment. Other paraphilias have been attributed to dopamine agonists, suggesting that the action of the monoamine oxidase inhibitor responsible for the patient's transvestism in this case was dopamine potentiation. Drug-induced paraphilias and hypersexuality may represent a reversal of the putative premorbid Parkinson's disease personality traits of introversion, cautious behavior, and lack of novelty-seeking. A biologic basis for transvestism, and paraphilias in general, is not known. Rare clues emerge from cases similar to this one.


Hmmm a 72 year old whose had Parkinson's for 37 years and has been treated with L-Dopa for over 20 years. Geee I wonder.
1. It's a case study and there are millions taking that combo so the occurrence of this works out to be 1:several million.
2. Weren't we talking about Memantine?

Edited by KoolK3n, 19 April 2013 - 05:07 PM.


#28 peakplasma

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Posted 19 April 2013 - 05:09 PM

Why don't you talk to your MD about this? It's clear you don't have a good understanding of the risks of dopaminergic therapy. Do some reading for yourself.

I'm just trying to be helpful so I'm not sure why you are being so rude and sarcastic. Given that aggression is a classic symptom of dopamine dysregulation perhaps you have already caused some damage.

EDIT:

Hmmm a 72 year old whose had Parkinson's for 37 years and has been treated with L-Dopa for over 20 years. Geee I wonder.
1. It's a case study and there are millions taking that combo so the occurrence of this works out to be 1:several million.
2. Weren't we talking about Memantine?


We are talking about dopaminergic therapy. Drugs that affect dopaminergic pathways (especially agonists) should not be underestimated since adverse effects can be debilitating.

You are saying there are no risks just because there is a paucity of research on the combination - this is critically flawed.

Edited by peakplasma, 19 April 2013 - 05:25 PM.

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#29 KoolK3n

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Posted 20 April 2013 - 12:32 AM

Why don't you talk to your MD about this? It's clear you don't have a good understanding of the risks of dopaminergic therapy. Do some reading for yourself.


Quite the opposite, it's become clear that you don't have a good understanding of neuroscience. I've asked you over and over and over again to explain why Memantine and Selegiline combo might be dangerous. You fail to answer my question and redirecting me to an MD isn't adding to the discussion.
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#30 KoolK3n

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Posted 20 April 2013 - 12:39 AM

Given that aggression is a classic symptom of dopamine dysregulation perhaps you have already caused some damage.


Yup, when someone challenges your viewpoint, they are deemed to have DDS.

You are saying there are no risks just because there is a paucity of research on the combination - this is critically flawed.


I never not warned of possible risks. I mentioned the estimation of an ideal dose of around 10mg/d or lower. The latter preferably.

Edited by KoolK3n, 20 April 2013 - 12:44 AM.






Also tagged with one or more of these keywords: selegiline, deprenyl, tolerance, withdrawal, downregulate, receptors, nmda, cdp-choline, dopamine, magnesium

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