15 replies to this topic

[zos]

I began taking 1.25mg of deprenyl on Monday. Stepped up to 2.5mg yesterday, which I plan to continue for a bit. So far, so good. I did notice tiredness after my first dose, but 2.5mg of dex-amphetamine seems to neutralize it. My goal is to increase motivation and relieve anhedonia.

A bit of my psych history:

Severe lack of motivation since early childhood. Difficulty focusing on things except for the rare occasion I would become "hyper-focused" on something that really interested me. Classic ADD, no H.

OCD since early childhood, mainly in the form nail biting.

Dysthymia, anhedonia, and anxiety(especially severe with public speaking) since mid teens. Experimented with alcohol, cannabis and psilocybe mushrooms during this time. Symptoms amplified in late teens.

In my early 20's I moved out on my own, and sought treatment from a psychiatrist. Diagnosed with depression/anxiety and prescribed paroxetine, 20mg. Helped alot with general low mood and anxiety. But I began to notice more and more blunting of emotions, anhedonia and daytime tiredness. After about 4 years, I tried to taper down and discontinue use. All went well for a few months until one night the depression came surging back. Decided to go back on paroxetine 20mg after a few weeks of no improvement. Seems to not be quite as effective the second time around. Stayed on for another 3-4 years. Within the last 6 months I have switched to sertraline 100mg's, and also have gotten a script for dex-amphetamine 20mg a day. Tiredness is alot better, focus is helped with the dex(however i get no euphoria from dex as many other people report and no real motivation boost). Anhedonia is still very much present.

Current situation:

Despite everything, I have held down a constant job for the last 7 years and am moderately successful.

My current plan is to taper down and possibly discontinue sertraline while increasing deprenyl up to 5mg/day to work on my suspected dopamine deficiencies rather than focusing on serotonin.

Other chemical intake:

10+ year daily cannabis user, I have stopped completely, 3 weeks ago.
1-2 drinks on weeknights, more on weekends
1 gram EPA/DHA omega3 oils daily (last 4 years)
5000 IU's vitamin D3 daily (last 5 years)
500MG DLPA daily (last 3 months)
20mg dex-amp daily (down to 5mg since starting deprenyl)
100mg sertraline daily (down to 75mg since starting deprenyl, plan to goto 50mg or less depending on progress)

*** Occasional opiate user(usually morphine a couple times a month). Nothing gives me motivation like opiates, I get so much work done! (Amphetamines dont even compare as they really just help me focus but dont give me any motivational drive) Also, they completely eliminate my anhedonia. But I know opiates are not a sustainable treatment so Im seeking out other long term options(considering trying LDN as well, I have some naltrexone on hand). ***


Sorry if this is all over the place, trying to pack as much information in as coherently as possible.

Any advice on my plan/actions thus far would be greatly appreciated - especially from people with similar symptoms who have tried deprenyl or other treatments. I have read through most of the deprenyl threads on this forum so far. Thanks!

Edited by zos, 29 September 2010 - 07:19 PM.

[jadamgo]

How did this go for you? Sorry nobody responded before now.

Hopefully you've been able to push that sertraline dose down significantly before considering an increase in selegiline dosage.

You should be getting a clearly noticeable effect from the DLPA together with selegiline. If you aren't, then you either need to increase the dose, or perhaps you just don't respond to DLPA. It just doesn't work for some people. If you don't respond to DLPA, I'd suggest starting supplementation with tyrosine and LOW-DOSE phenethylamine. (If you've gotten up to 5mg selegiline or more, then an effective daily dose of phenethylamine would very likely be somewhere between 10mg and 50mg.)

Whether you stick with DLPA or switch to tyrosine and possibly PEA, you will know if it's working. You'll probably know within hours. Of course, it can take a month or two for full effects to kick in, but you should be able to identify some effect within no more than 3 days of starting that combo.

Back to deprenyl -- once you've stopped the sertraline, you can start bumping its dose up more. Are you swallowing the deprenyl, or letting it absorb sublingually? 2.5mg swallowed is not likely to be a very effective dose for what you're trying to do. Work your way up to 10 or 15mg swallowed daily. If that still hasn't helped you out after a few weeks, you may need to try an even higher dose. Some people take 20-30mg daily for depressive symptoms.

You probably already know that for the larger swallowed doses, it's helpful to take half with breakfast and half with lunch. You need to eat it with a meal so it can absorb properly.

If you are already taking the 2.5mg sublingually, I wouldn't advise titrating it much higher than 12.5 mg daily. At that dose, you would already have to start watching out for tyramine reactions.

Important: as you titrate deprenyl UP, you need to titrate dextroamphetamine DOWN. If you can discontinue dextroamphetamine, that could be very helpful. Consider replacing it with methylphenidate if you need a stimulant together with the deprenyl. Be warned: stimulants + deprenyl can start getting euphoric, which is addictive. If you use a stimulant together with deprenyl, please take holidays off the stimulant! Try and get 2 days a week without taking any dex or methylphenidate at all. Weekends are a great time to take stimulant holidays. (You don't need deprenyl holidays.)

[FunkOdyssey]

Automatic message


This topic has been moved from "Bioscience, Health & Nutrition -> Bioscience -> Medicine & Diseases" to "Bioscience, Health & Nutrition -> Supplements -> Nootropics".

[FunkOdyssey]

Why haven't you ever tried bupropion for anhedonia and motivation?

J Affect Disord. 2004 Mar;78(3):235-41.
Assessing the effects of bupropion SR on mood dimensions of depression.

Tomarken AJ, Dichter GS, Freid C, Addington S, Shelton RC.

Department of Psychology, College of Arts and Sciences, Vanderbilt University, Nashville, TN 37203, USA. andrew.j.tomarken@vanderbilt.edu
Abstract

BACKGROUND: We assessed the therapeutic effects of bupropion SR and placebo on mood and anxiety symptoms derived from the tripartite model of mood. Based on evidence indicating linkages between dopaminergic activity and the emotional dimension of positive affect/anhedonia, we hypothesized that the dopaminergic effects of bupropion SR would yield particularly pronounced effects on symptoms of anhedonia, relative to anxiety.

METHODS: Nineteen depressed outpatients were randomly assigned to treatment with either bupropion SR 300 mg/day or placebo during a 6-week initial treatment phase. This was followed by a second open-label phase in which patients previously treated with bupropion SR had their dose increased to 400 mg/day, and the placebo group was initiated on bupropion SR 300 mg/day.

RESULTS: Random regression analyses revealed that during the initial double-blind phase, bupropion SR elicited greater declines than placebo on all measures except those that assessed anxiety. By contrast, the weakest placebo effects were evident on anhedonia. Items assessing the low positive affect pole of the anhedonia dimension were more sensitive to earlier/lower dose bupropion SR treatment, whereas items assessing the high positive affect pole were more sensitive to later/higher dose bupropion SR treatment.

LIMITATIONS: Replication and extension using a larger sample size are mandated.

CONCLUSIONS: This study suggests that the catecholaminergic effects of bupropion SR tended to produce more robust effects on anhedonia/positive affect than placebo.

[kassem23]

A couple of suggestions:

- Memantine + d-amphetamine (thereby getting the pro-social and motivational aspects from d-amphetamine back from up-regulation of D1/D2), some people report good results for this.
- Tianeptine, for some people it simply "fixes them" -- worth a shot.
- Buproprion, as FunkOdyssey already mentioned is also a valid choice, also a very hit-or-miss kind of drug.


And, you may want to try another SSRI -- since sertraline has peculiar interactions with d-amphetamine due to it's DRI properties -- or completely cut it off... IIRC, SSRIs reduces hedonic drive, due to a decrease in mPFC activity, so you may want to try something else.

[jadamgo]

Ahh, why didn't I recommend that too?

One interesting note -- I saw a study where individuals without any mental pathology were given bupropion, to see what its effects were on the non-depressed patient. People who took 150mg/day had improvements in mood, working memory span, voluntary attention control, energy, and motivation. People who took 300mg/day only had improvements in energy, if I recall correctly. I would post a link to the study here, but I can't seem to find it. Disclaimer: the study only lasted about 2 weeks, so it might not accurately reflect how bupropion works in the long term.

The moral is: you may want to try low-dose bupropion and see if it helps.

[kassem23]

Ahh, why didn't I recommend that too?

One interesting note -- I saw a study where individuals without any mental pathology were given bupropion, to see what its effects were on the non-depressed patient. People who took 150mg/day had improvements in mood, working memory span, voluntary attention control, energy, and motivation. People who took 300mg/day only had improvements in energy, if I recall correctly. I would post a link to the study here, but I can't seem to find it. Disclaimer: the study only lasted about 2 weeks, so it might not accurately reflect how bupropion works in the long term.

The moral is: you may want to try low-dose bupropion and see if it helps.

Interesting study, if you find it please link.. I would be happy to look over it, I'm especially interested in the number of participants, since from what I've heard, buproprion is mostly hit-or-miss, and some people experience a lethargic, brain-fog, memory-loss whereas others experience better mood etc..

[FunkOdyssey]

J Psychopharmacol. 2007 Jul;21(5):461-71. Epub 2006 Oct 18.
The other face of depression, reduced positive affect: the role of catecholamines in causation and cure.

Nutt D, Demyttenaere K, Janka Z, Aarre T, Bourin M, Canonico PL, Carrasco JL, Stahl S.

University of Bristol Psychopharmacology Unit, Bristol, UK. david.j.nutt@bristol.ac.uk
Abstract

Despite significant advances in pharmacologic therapy of depression over the past two decades, a substantial proportion of patients fail to respond or experience only partial response to serotonin re-uptake inhibitor antidepressants, resulting in chronic functional impairment. There appears to be a pattern of symptoms that are inadequately addressed by serotonergic antidepressants - loss of pleasure, loss of interest, fatigue and loss of energy. These symptoms are key to the maintenance of drive and motivation. Although these symptoms are variously defined, they are consistent with the concept of ;decreased positive affect'. Positive affect subsumes a broad range of positive mood states, including feelings of happiness (joy), interest, energy, enthusiasm, alertness and self-confidence. Although preliminary, there is evidence to suggest that antidepressants that enhance noradrenergic and dopaminergic activity may afford a therapeutic advantage over serotonergic antidepressants in the treatment of symptoms associated with a reduction in positive affect. Dopaminergic and noradrenergic agents, including the dual acting norepinephrine and dopamine re-uptake inhibitors, have demonstrated antidepressant activity in the absence of serotonergic function, showing similar efficacy to both tricyclic and serotonin re-uptake inhibitor antidepressants. Moreover, the norepinephrine and dopamine re-uptake inhibitor bupropion has been shown to significantly improve symptoms of energy, pleasure and interest in patients with depression with predominant baseline symptoms of decreased pleasure, interest and energy. Focusing treatment on the predominant or driving symptomatology for an individual patient with major depression could potentially improve rates of response and remission.

PMID: 17050654

I found the study you guys are talking about but I don't think it's relevant to real-life as they only followed the subjects for 7 days and bupropion doesn't show its true colors for a good 4-6 weeks (in common with nearly all antidepressants).

J Clin Psychopharmacol. 2003 Jun;23(3):233-9.
Neurochemical and psychotropic effects of bupropion in healthy male subjects.

Gobbi G, Slater S, Boucher N, Debonnel G, Blier P.

Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montréal, Quebec, Canada.
Abstract

Bupropion is a weak inhibitor of noradrenaline (NE) and dopamine (DA) reuptake and has no direct action on serotonin (5-HT) neuronal elements. In the rat brain, bupropion suppresses NE neuron firing activity via the activation of alpha(2)-adrenoceptors and increases that of 5-HT neurons through an indirect action on NE neurons. Twenty-five healthy young male volunteers, with no previous history of psychiatric disorders, were randomized to one of four 7-day regimens: placebo, bupropion (150 mg) once daily, bupropion (150 mg) twice a day, and methylphenidate SR (20 mg daily). To assess the activity of the NE reuptake process, the blood pressure response to intravenous tyramine was determined. A decrease in the systolic pressure response to tyramine was considered evidence of NE reuptake inhibition. Effects on 5-HT reuptake were assessed by measuring whole blood 5-HT concentration, with a decrease serving as an index of 5-HT reuptake blockade. The Profile of Mood States (POMS) scale was used to assess behavioral and psychological changes. Neither bupropion nor methylphenidate altered the tyramine pressor response, in contrast to previous data that demonstrated decreases were obtained with NE reuptake inhibitors. Neither drug modified 5-HT concentrations. However, POMS scores revealed that bupropion at a dosage of 150 mg/day increased composedness, agreeability, and energy, whereas 300 mg/day improved only attention. In contrast, methylphenidate improved only energy. These data provide no evidence that bupropion acts as an inhibitor of NE or 5-HT reuptake in healthy humans. Presumably it enhances synaptic availability of NE by increasing release. Yet, because its behavioral profile is different from that of methylphenidate, it may not share all the biochemical properties of psychostimulants.

PMID: 12826985

Edited by FunkOdyssey, 26 October 2010 - 03:26 PM.

[zos]

Thanks for the response. So far, so good with the selegiline. I have been keeping a daily log, but currently Ive weaned myself completely off the sertraline and Im up to 5mg Selegiline per day. I noticed a fairly significant improvement in mood/energy with the 2.5mg of selegiline initially and have since been keeping things pretty stable while titrating down on the sertraline and up on the selegiline. I stopped Sertraline completely about 5 days ago so Im thinking of upping my selegiline to 7.5mg daily next week(kind of feel like I should let my body fully adjust to being sertraline deprived for a bit longer to get to some sort of baseline). And to answer your question about selegiline ingestion, I usually let it dissolve a bit sub-lingually (2-3 minutes) and then swallow the rest.

Effects from DLPA have been questionable but I do seem to feel a bit more energetic(ive taken up to 1G in the morning daily but usually just do 500mg). I cant rule out placebo effect though. Ill have to look into tyrosine.

I got some PEA a couple weeks ago to play with(500mg caps). WOW. Interesting stuff. I started out with ~50-100mg +1h, no real noticeable effect. Another 200mg +1h, didnt notice much. Ended up taking a full 500mg cap and blasted off - talkative, a bit euphoric, increased urge to smoke cigarettes. All in all, a very similar effect to what I get with morphine. It lasted about 1-1.5 hours. The comedown really sucked and I felt very heavy bodied and hollow chested if that makes sense. Seems that 250mg or below doesnt do much if anything, but usually 500mg with cause pretty noticeable effects. Also, sometimes I will get extremely flushed in the face with very warm sensations. Dont really like the stuff all that much so far, as its effects and dosages are unpredictable for me and the comedown just makes me feel completely drained.

As far as the dexamphetamine, I dont really take it much anymore, Ill go 5-6 days between doses often. Ive found that the selegiline seems to give me most of the same benefits. When I do take dexamp occasionally (to help stay up late, or counter the effects of not enough sleep the night before) I will usually do 2.5-5mg. Seems the selegiline may potentiate it a bit, but dexamphetamine has never had a very pronounced effect on me even at highish (40-50mg) doses. It just takes away the tiredness and allows me to zone out on menial tasks more easily.

Some other things Ive tried since the last post...Ive played around with 2-4mg a night of Naltrexone, no real noticeable effects - i plan to do more of a continuous study of LDN once I feel the sertraline is completely out of my system. Also got some 5-HTP and take 50mg a night since I stopped sertraline completely. I was feeling anxious the day after I stopped sertraline completely, which has gone away since I started the 5-HTP (coincidence maybe?).

How did this go for you? Sorry nobody responded before now.

Hopefully you've been able to push that sertraline dose down significantly before considering an increase in selegiline dosage.

You should be getting a clearly noticeable effect from the DLPA together with selegiline. If you aren't, then you either need to increase the dose, or perhaps you just don't respond to DLPA. It just doesn't work for some people. If you don't respond to DLPA, I'd suggest starting supplementation with tyrosine and LOW-DOSE phenethylamine. (If you've gotten up to 5mg selegiline or more, then an effective daily dose of phenethylamine would very likely be somewhere between 10mg and 50mg.)

Whether you stick with DLPA or switch to tyrosine and possibly PEA, you will know if it's working. You'll probably know within hours. Of course, it can take a month or two for full effects to kick in, but you should be able to identify some effect within no more than 3 days of starting that combo.

Back to deprenyl -- once you've stopped the sertraline, you can start bumping its dose up more. Are you swallowing the deprenyl, or letting it absorb sublingually? 2.5mg swallowed is not likely to be a very effective dose for what you're trying to do. Work your way up to 10 or 15mg swallowed daily. If that still hasn't helped you out after a few weeks, you may need to try an even higher dose. Some people take 20-30mg daily for depressive symptoms.

You probably already know that for the larger swallowed doses, it's helpful to take half with breakfast and half with lunch. You need to eat it with a meal so it can absorb properly.

If you are already taking the 2.5mg sublingually, I wouldn't advise titrating it much higher than 12.5 mg daily. At that dose, you would already have to start watching out for tyramine reactions.

Important: as you titrate deprenyl UP, you need to titrate dextroamphetamine DOWN. If you can discontinue dextroamphetamine, that could be very helpful. Consider replacing it with methylphenidate if you need a stimulant together with the deprenyl. Be warned: stimulants + deprenyl can start getting euphoric, which is addictive. If you use a stimulant together with deprenyl, please take holidays off the stimulant! Try and get 2 days a week without taking any dex or methylphenidate at all. Weekends are a great time to take stimulant holidays. (You don't need deprenyl holidays.)

Edited by zos, 26 October 2010 - 04:33 PM.

[zos]

Bupropion is on my list to try and I probably will if I dont get the stable long term effects Im looking for from the selegiline. I am a bit hesitant to try it though because its an SNRI like Strattera. When I tried strattera it was horrible for me. Couldnt sleep, constant night sweats, and it completely broke my dick. I would be interested to hear from anyone whos tried both strattera and bupropion and how they differed. Also, bupropion is kind of expensive and selegiline is dirt cheap from ADC.

Why haven't you ever tried bupropion for anhedonia and motivation?

J Affect Disord. 2004 Mar;78(3):235-41.
Assessing the effects of bupropion SR on mood dimensions of depression.

Tomarken AJ, Dichter GS, Freid C, Addington S, Shelton RC.

Department of Psychology, College of Arts and Sciences, Vanderbilt University, Nashville, TN 37203, USA. andrew.j.tomarken@vanderbilt.edu
Abstract

BACKGROUND: We assessed the therapeutic effects of bupropion SR and placebo on mood and anxiety symptoms derived from the tripartite model of mood. Based on evidence indicating linkages between dopaminergic activity and the emotional dimension of positive affect/anhedonia, we hypothesized that the dopaminergic effects of bupropion SR would yield particularly pronounced effects on symptoms of anhedonia, relative to anxiety.

METHODS: Nineteen depressed outpatients were randomly assigned to treatment with either bupropion SR 300 mg/day or placebo during a 6-week initial treatment phase. This was followed by a second open-label phase in which patients previously treated with bupropion SR had their dose increased to 400 mg/day, and the placebo group was initiated on bupropion SR 300 mg/day.

RESULTS: Random regression analyses revealed that during the initial double-blind phase, bupropion SR elicited greater declines than placebo on all measures except those that assessed anxiety. By contrast, the weakest placebo effects were evident on anhedonia. Items assessing the low positive affect pole of the anhedonia dimension were more sensitive to earlier/lower dose bupropion SR treatment, whereas items assessing the high positive affect pole were more sensitive to later/higher dose bupropion SR treatment.

LIMITATIONS: Replication and extension using a larger sample size are mandated.

CONCLUSIONS: This study suggests that the catecholaminergic effects of bupropion SR tended to produce more robust effects on anhedonia/positive affect than placebo.

[FunkOdyssey]

Bupropion is on my list to try and I probably will if I dont get the stable long term effects Im looking for from the selegiline. I am a bit hesitant to try it though because its an SNRI like Strattera. When I tried strattera it was horrible for me. Couldnt sleep, constant night sweats, and it completely broke my dick. I would be interested to hear from anyone whos tried both strattera and bupropion and how they differed. Also, bupropion is kind of expensive and selegiline is dirt cheap from ADC.

Strattera is an NRI. Bupropion is a weak NDRI which mainly seems to act as an NE releaser. Strattera is not an antidepressant and has fun side effects like retrograde ejaculation. These drugs are not remotely similar.

[zos]

Thanks. I do have some memantine which is on the back burner for now since I dont want to try too much at once. What would be a good starting dose and are there any interactions with selegiline to worry about?

Tianeptine I have read about and looks very interesting. Couldnt find it on ADC, but I could probably get a script from my pdoc down the road to try. Im not quite clear how INCREASING the reuptake of serotonin can cause similiar antidepressant effects to opposite effect of inhibiting reuptake with an SSRI. Any theories on this?

EDIT: Actually this is not approved for use in the US. If anyone has a source please PM me.

I am completely off the SSRI's now but I actually switched from paroxetine to sertraline because of the DRI effect, hoping it might help. I havent noticed any change in dexamphetamine effects though from when I was on paroxetine. Nor any other noticeable difference between the two SSRI's really, though if I had to guess Id say the paroxetine might have worked a bit better.

Interested about SSRI's decreasing hedonic drive because of effects on the mPFC. DO you have any links that go into more depth?

A couple of suggestions:

- Memantine + d-amphetamine (thereby getting the pro-social and motivational aspects from d-amphetamine back from up-regulation of D1/D2), some people report good results for this.
- Tianeptine, for some people it simply "fixes them" -- worth a shot.
- Buproprion, as FunkOdyssey already mentioned is also a valid choice, also a very hit-or-miss kind of drug.


And, you may want to try another SSRI -- since sertraline has peculiar interactions with d-amphetamine due to it's DRI properties -- or completely cut it off... IIRC, SSRIs reduces hedonic drive, due to a decrease in mPFC activity, so you may want to try something else.

Edited by zos, 26 October 2010 - 05:29 PM.

[zos]

Ahh, good to know.

Bupropion is on my list to try and I probably will if I dont get the stable long term effects Im looking for from the selegiline. I am a bit hesitant to try it though because its an SNRI like Strattera. When I tried strattera it was horrible for me. Couldnt sleep, constant night sweats, and it completely broke my dick. I would be interested to hear from anyone whos tried both strattera and bupropion and how they differed. Also, bupropion is kind of expensive and selegiline is dirt cheap from ADC.

Strattera is an NRI. Bupropion is a weak NDRI which mainly seems to act as an NE releaser. Strattera is not an antidepressant and has fun side effects like retrograde ejaculation. These drugs are not remotely similar.

[NR2(x)]

The posts above are of good quality,
Just as a side note;
I am currently looking at the important antioxidant role of Tryosine. It is utterly amazing. Metabolites(methylated ;-) ) concentrate by thousands of fold in the Mitochondria,where they decrease super oxide damage by a significant degree. I am trying to synthesis a write up at present but am having significant difficulty due to the general lack of material on this. In fact I think that compounds that Mcdevil enjoys so much have an MOA as a super antioxidant. DLPA does not share this MOA, therefore competitive inhibition of tryosine by DLPA my counter act DLPA beneficals. Maybe there is a need to take both. Acetyltryosine does not act as a antioxidant.

[John Barleycorn]

EDIT: Actually this is not approved for use in the US. If anyone has a source please PM me.

I don't believe there's any problem with disclosing sources here. Take a look at magicpharma's prices. Or, alternatively, mine (the first pill was the only one that worked)

BTW, selegiline potentiates lots of stuff, primarily in the duration aspect. You might want to bear that in mind next time you're getting motivated.

And if you haven't done so already, try some decent chelated magnesium and zinc supplements at night. It's a no brainer. For the right individual, these supps can beat drugs and can give memantine a run for its money in the anti-tolerance department. You may well not be that individual, but you've got nothing to lose.

[jadamgo]

I have to caution you against taking high doses of phenethylamine with deprenyl -- though you already seem not to like it. The studies I've seen on its antidepressant efficacy and safety showed results at doses between 10mg and 60mg per day, without evidence of tolerance or toxicity. I don't know of any evidence for safety or antidepressant effects in the 100mg+ range. Though there are reports of people taking it for the euphoria, and occasionally getting addicted to it.

Anyway, the philosophy behind low dose phenethylamine supplementation for antidepressant effects is different from the use of high dose phenethylamine to get high. I'm not trying to knock anyone for getting high off something, but phenethylamine + deprenyl is a poor choice, like most other choices people make for things to get high on. In contrast, PEA is used in low doses as an antidepressant because depressed people presumably have low levels of PEA. That's why the PEA + deprenyl combination is sometimes called "PEA replacement therapy."

We don't currently have a way to measure PEA in the human brain, but we can measure its metabolites. Depressed populations show significant decreases in measurements of those metabolites. The main one they study is phenylacetate, aka phenylacetic acid. PAA levels are actually a good marker for depression -- it approaches normal levels in patients who are successfully treated with antidepressants of any type, or with psychotherapy, or when the depression resolves without medical/psychological treatment. Patients who are unsuccessfully treated for depression do not show the normalization of PAA levels. Again, that result applies to multiple types of antidepressants, and to psychotherapy.

(Random thought: It would be really interesting to watch PAA variation across the seasons in people with seasonal affective disorder, and to track how the PAA levels vary with the use of bright light therapy, and with the individual's response to the light therapy.)

The reason I just rambled about all that is to say this: of course the 500mg caps didn't work well for you. You were taking way too much phenethylamine, and not enough selegiline. It caused a brief high that had the typical prosociality, drive, and euphoria of phenethylamine. Then you got a nasty comedown because you didn't have enough MAO-B inhibition to keep the levels from dropping sharply after an hour or two.

What you're supposed to do is swallow 10mg of selegiline a day, split into a morning dose and an afternoon dose. Each dose of selegiline should be taken WITH FOOD so that it's bioavailable enough. The food should contain some fat, not just carbs and protein. You should also take somewhere between 10mg and 60mg per day of phenethylamine, split into a morning dose and an afternoon dose. You could also split the PEA into a morning, late afternoon, and nighttime dose if the nighttime dose doesn't cause insomnia for you.

If you can feel comedowns between doses of PEA, you aren't taking enough selegiline. You need enough MAO-B inhibition that a single PEA dose lasts for a large chunk of the day, perhaps all day. Some people only need one dose in the morning to be non-depressed all day. If you feel significant euphoria from the PEA, I'd suggest cutting the dose. It's just supposed to get rid of depression, not make you high. Getting high from PEA probably means that you're getting too much monoamine release, and you're going to have to start dealing with neurotransmitter depletion eventually. But the appropriate dose doesn't result in any noticeable depletion even in people who don't have supplements or a healthy diet.

If you don't feel anything at all from 60mg/day PEA replacement even with 10mg/day of selegiline, you could try 12.5 or 15mg of selegiline per day. But 15mg/day is already getting into MAO-A inhibition territory, so you'll have to watch out for the (very unlikely) risk of cheese reactions.

Now, all of what I just said will be for nought if you go up to 10mg selegiline a day and find that the depression goes away before you even try the low dose phenethylamine =P

Edited by jadamgo, 29 October 2010 - 09:50 PM.