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Need advice/guidance on deprenyl (selegiline)

dopamine deprenyl selegiline p-f-deprenyl pf-deprenyl

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#1 effinrich

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Posted 21 September 2020 - 02:24 AM


Hello,

This is my first post, so I only have 4 left today, but I'm happy to be a part of the community and look forward to engaging with like-minded folks.  I should state the following is going to be a thought dump of sorts as  I haven't found a consistent nor thorough source of information on any of this, so I'm looking for help and guidance.

 

I'm in need of guidance on deprenyl dosage, initial effects as well as comparison with p-f-deprenyl.  I've currently been on deprenyl (first p-f-deprenyl then just deprenyl after dosing issues with the powder) for 11 days, which is not very long at all.  I've seen so many conflicting dosages and administrations and not sure if what I'm doing is correct.

 

Overview:

  • Age: 44
  • Current deprenyl dosage: 1.25mg sublingual from 5mg tablet
  • Duration: 11 days
  • Diet: Somewhere between paleo and keto, but as a rule just eat clean and make my own food
  • Fitness:  Work out between 3-5 days a week for the last 8 years regardless of other things going on including severe depression, etc.  It's my mainstay.
  • What I know about deprenyl:  I know the MOA of deprenyl, that men over 40 should take relatively higher doses, that MAO-A inhibition starts at higher doses around 10mg, the half-life is 2 weeks.

Background:
As of 11 days ago I was on anywhere between 30-60mg prescribed adderall a day, depending on workload, which barely made a dent in my wandering disinterest.  This was my second go with adderall and only over the past year or so.  Prior to this I made due with bromantane, tianeptine sulphate, caffeine/l-theanine and various racetams.  This period lasted around 2 years and was just effective enough to keep me propped up.  The 5 (ish) years prior to this were very low dose adderall with a litany of nootropics.  Anyway, bromantane is fantastic, but also highly variable for me.  The inconsistent spouts of exhaustion, which always felt very much like serotonin activity despite it's low affinity for those receptors, were eventually intolerable.  Upon trialing deprenyl I dropped to tiny 5mg doses as needed. 

 

My reason for trialing deprenyl is my severe, ongoing treatment resistant anhedonia despite adderall and a slew of other compounds/supplements used for motivation/cognitive issues.  I did, however, eliminate my other most bothersome depression/add issues, but of course not the one symptom that has plagued me since birth.  That anhedonia combined with lack of drive, general enjoyment of life and lack of confidence led to me getting to the point of just staring at my computer doing zero work for weeks (software developer) and I was headed toward losing my job.  After thoroughly researching deprenyl and, as much as was possible, p-f-deprenyl and their associated positive and negative anecdotes I ordered both compounds.  P-f-deprenyl was the fastest available and the deprenyl 5mg tablets were supposed to take several weeks to arrive, but came in less than 2.  I should also state that I had little hope for this compound because why would I?  I had no expectations, kinda assumed it would make me feel like garbage and act like a tranquilizer or something despite it's MOA.  Also, nothing has really done much over 8 years of this journey, but mostly because the better the anecdotes, the greater the chance of it doing nothing for me.  

 

So 11 days ago I received the p-f-deprenyl and started immediately with what I roughly believe to be 2mg sublingual.  I say roughly because digital scales, unless very expensive, are useless for anything under 5mg and suspect even at that number.  The next 2 days dosing the same, but was completely exhausted.  i had expected this as I'd seen several comments suggesting this possibility.  On day 3, and 4 days before a huge deadline, everything changed.  Like i came back to life, but not in a sweaty manic way, just in the perfect amount.  I was able to knock out enough work to cover the deadline for this demo I had.  This was achievable with the same 2mg dose of p-f-deprenyl and little to no adderall or caffeine.  I used a tiny bit of noopept as well.  More importantly I had the motivation, real motivation, to do a lot of things that had been rotting on the vine.  The point is it looked promising.  However the dosing was a huge issue and I had no idea how much I was taking.  

 

At this point I decided to make a solution of vodka and the p-f-deprenyl so I could dose accurately with a dropper.  That seemed ok, but I was wary of that combination.  I have no idea if the p-f degrades in vodka, but I also had so few resources on p-f-deprenyl to find anything useful in terms of moving forward, but the tablet deprenyl arrived around this time, so I jumped to that option for the easier pill cutting dosage.  I've been cutting the 5mg pills into 1.25mg quarters and dosing sublingually since the 16th, so only 4 days, but I have a lot of questions.

 

Guidance and reason for my post:

First, i apologize for the disjointed text wall above. I'm trying to be as thorough as possible, but realize that may read like a rambling mess.  So for this entire trial, with both compounds, the results are all over the map.  One day is very good and i'm highly motivated, the next i'm completely exhausted and kind of an asshole, however there are sporadic clearings throughout those days as well.  Today, for example, I was incredibly tired and not comfortable using any stimulant other than a little caffeine due to all of the warnings on mixing these things.  However the tiredness would suddenly vanish and i'd start living life, but only for a short time, then back to nodding my head.  Another thing is, regardless of how my day goes - motivated or exhausted - falling asleep is easy even if I feel fully alert.  That's very nice, however waking up is an absurdly laborious act.  I mean drunken exhaustion for 2-3 hours after waking.

 

My questions:

  • Are these variable effects normal or not unheard of this early in starting deprenyl?
  • Is my sublingual dose of 1.25mg deprenyl enough or should I be taking 5mg orally as I'm in my 40s?  For that matter should I be taking it daily at all?
  • Is the liquid citrate form more consistent and generally better as so many anecdotal reports have stated?  If so, is there a reliable source for liquid citrate? (if this is vorboten, I apologize, but I've seen the same on may other posts.)
  • Is p-f-deprenyl stable in my ridiculous vodka solution and is that a viable option?  If not, what solvent would you suggest?
  • What are your thoughts on p-f-deprenyl vs deprenyl and if you have an opinion on this, which would you suggest i move forward with?
  • Is there a dosing schedule, titration, etc?
  • Could my exhaustion and variable results be related to dropping adderall so drastically?  If so, have you any ideas on how to ameliorate that issue?  Taper while using deprenyl, take as needed or something else?

Ok, that's it and I know it's a lot.  i promise I'm not high, just really wanted to cover as many bases as possible as my posts are limited to 5 a day.  Ask any questions you'd like, I have no qualms about sensitive topics or personal history to the point of deeming the requisite "I hope you don't mind me asking" unnecessary.

 

Thanks 

 


Edited by effinrich, 21 September 2020 - 02:29 AM.

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#2 Dbs

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Posted 09 October 2020 - 02:53 AM

You are trying to put a patch on your mental health instead of fixing your problem from the root. I suspect your anhedonia to be stress induced.
When the stress response runs on overtime the bodies sensitivity to cortisol negative feedback loop increases and the brain basically shuts down in order to preserve energy. As cortisol output decreases, catecholamine output increases to compensate. One feels constantly tense and feelings as well as pleasure dissapeares. Your best bet is ( although you probably don't want to hear this) to completely change your lifestyle.

Diet: ditch low carb as for gluconeogenesis cortisol production increases what will leave you burned out in the long run. Try incorporating carbs slowly in your diet.

Training: stop training for some time, at least don't do high intensity stuff. As said before, you digged yourself a hole with doing everything to an extreme, what led you stressed out, anhedonic. Further stressing yourself with high intensity training 5 times a week will not help you.

Stimulants: get rid of every stimulant including deprenyl. In your state they won't help you and are probably the cause of your anhedonia (lifestyle).

Sry, if all this sounds a little harsh.
Good luck

Edited by Dbs, 09 October 2020 - 02:54 AM.

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#3 effinrich

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Posted 09 October 2020 - 07:00 AM

You are trying to put a patch on your mental health instead of fixing your problem from the root. I suspect your anhedonia to be stress induced.
When the stress response runs on overtime the bodies sensitivity to cortisol negative feedback loop increases and the brain basically shuts down in order to preserve energy. As cortisol output decreases, catecholamine output increases to compensate. One feels constantly tense and feelings as well as pleasure dissapeares. Your best bet is ( although you probably don't want to hear this) to completely change your lifestyle.

Diet: ditch low carb as for gluconeogenesis cortisol production increases what will leave you burned out in the long run. Try incorporating carbs slowly in your diet.

Training: stop training for some time, at least don't do high intensity stuff. As said before, you digged yourself a hole with doing everything to an extreme, what led you stressed out, anhedonic. Further stressing yourself with high intensity training 5 times a week will not help you.

Stimulants: get rid of every stimulant including deprenyl. In your state they won't help you and are probably the cause of your anhedonia (lifestyle).

Sry, if all this sounds a little harsh.
Good luck

 

Hi Dbs,

No worries, not harsh at all.  You provided solid advice and likely learned from experience, but it is advice better suited for someone just starting this journey.  I am on the other end of the journey after several years of research and playing body detective with the help of some really great doctors in various fields.  I want to be as concise and detailed as possible as I'm new to the community, no one knows me, my experiences or what i've learned.  I would like to share my history and experience with these sort of things anyway, so I'll just dump that here and I apologize for the word wall below.   

 

I was quite exhausted when I wrote the original post and should have cleaned it up later, but the anhedonia has been a life long constant with very little variation.  The depression, anxiety and other awfulness I sorted out some time ago and those only came about around 8 years ago, the last of which being depression that started in a big way 2 years ago.  These things along with a host of other strange, very unpleasant physical symptoms were largely due to HPA axis dysfunction.  During that time I became very well acquainted with the lovely feeling of intense cortisol spikes around 3pm everyday that left me in a rigid state with an extremely tight jaw until around 1am daily for roughly a year.  Some of the other litany of symptoms were exercise intolerance to the point of being bedridden for a day after only moderate exercise, constant shoulder and neck tension, derealization, vertigo, severe confusion, rapidly dropping testosterone, weight gain, hyper sensitive to almost everything from daily stressors to a variety of foods and supplements.  This bizarre collection of symptoms that seemed to rapidly develop left my standard docs completely baffled, so they started throwing Prozac at me, which is the usual go to for mystery illnesses that include any measure of mental symptoms.  Ironically, that doctor wasn't far off in what would help many of my symptoms, but not for the reasons he thought.

 

Anyway, fast forward a few years into my obsessive research on symptoms, hormones, cortisol, the works.  That research, not quacky nonsense research, but actual medical journal research helped me find a functional medicine doc and HRT doc with whom I worked out plans of action that worked very well in gradually pulling me back up.  This included a battery of tests for mineral/vitamin deficiencies, full thyroid, pupil dilation for adrenal issues, hormone panel, etc.  My methylation was off as indicated by some higher homocysteine values, which led to a long, uncomfortable period of adjusting to methylfolate supplementation.  I'll skip the nasty bits, but it ended up being a huge factor in recovery.  Hormone optimization thru my HRT provider was the other.  At this point I was doing pretty well save the "cortisol hell" as I called it.

 

As you likely know, working on cortisol is tricky and many doctors don't know what the hell is going on there.  Saliva tests showed troughs and spikes well below and above their respective ranges at exactly the times of day as I predicted to my doctor.  This was below range in the am and several points above range starting at 4pm that gradually fell to slightly above range at midnight.  Essentially what should've have been my morning cortisol was surging late afternoon.  I requested my AM serum cortisol tested as I suspected it would come back normal, which it did.  This result further confirmed my adrenals were fine, cortisol fine, but the signaling was malfunctioning so to speak, which explained my irregular diurnal cortisol pattern.  I was started on black licorice root extract, which prolongs the half-life of cortisol.  This was somewhat helpful, but because i was having such drastic spikes in the pm, it wasn't as beneficial for me as others with only low morning cortisol.  Eventually I found a guy on a men's health forum who mentioned some HPA issues he was having that his doctor treated and optimized with temporary, low dose lexapro.  I'd never heard of this as a treatment for HPA axis dysfunction, but after a bit of research found that most of the SSRI and similar drugs work in this way.  Although not listed as a primary effect or MOA, SSRIs have a modulating effect on the HPA axis effectively regulating and resetting it (I don't mean this literally and "resetting" is surely not a thing in this area, just humor me).  During this research I found some doctors who theorized this was possibly the longterm therapeutic effect of SSRIs "via normalization of dysregulated central corticotropin-releasing factor (CRF) circuits". 

 

At this point I wanted to give the SSRI idea a chance, so I tried low dose lexapro as the anonymous forum user stated.  On the second day the cortisol spikes were completely gone, just stopped.  I continued for 14 days, which was a serotonin flooded, fatigue laden, very dumb feeling 2 weeks.  That's my typical response to serotonergics, so no surprise there.  At any rate, the SSRI thing worked much to my surprise.  Was dealing with that cortisol hell for at least a year and an SSRI wiped it out in less than 2 weeks.  

 

Thru all of his the anhedonia was always present just as the previous 34 years, so that's why I'm hear now trying to find a bit of guidance regarding deprenyl or really any dopamine enhancement I haven't already tried that has real effects.   

 

P.S. The point of the protracted, detailed rundown was to provide my CV relative to the things discussed on Longecity, but also to possibly enlighten anyone who may be dealing with HPA axis issues.  They are by far some of the worst hormone related problems I've every experienced.   







Also tagged with one or more of these keywords: dopamine, deprenyl, selegiline, p-f-deprenyl, pf-deprenyl

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