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  1. #1
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    I've been taking 1mg/day Rasagiline along with DLPA for about a month and a half. Recently stopped the DLPA as it made me ravenously hungry and pizza faced... WOAH low cortisol sucks, took me an entire day of laying in bed under 5 covers shivering, coughing up boogers to make my way to CVS and get some Pseudoephedrine. Pseudoephedrine should hold me up for the 40 days it takes for the cortisol lowering effects to disappear.



    Since I've started this treatment, I've noticed a complete inability to handle the sun. Couldn't find any sun sensitivity warnings on either Selegiline or Rasagiline. I looked further into how exactly Selegiline lowers cortisol, and it turns out it does so by directly inhibiting ACTH secretion.



    Since ACTH is the precursor to A-MSH, would this be what was most likely responsible for the sun sensitivity?

  2. #2
    Senior Member Ex Dubio's Avatar
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    Quote Originally Posted by dudinator View Post
    I've been taking 5mg/day Rasagiline along with DLPA for about a month and a half. Recently stopped the DLPA as it made me ravenously hungry and pizza faced... WOAH low cortisol sucks, took me an entire day of laying in bed under 5 covers shivering, coughing up boogers to make my way to CVS and get some Pseudoephedrine. Pseudoephedrine should hold me up for the 40 days it takes for the cortisol lowering effects to disappear.



    Since I've started this treatment, I've noticed a complete inability to handle the sun. Couldn't find any sun sensitivity warnings on either Selegiline or Rasagiline. I looked further into how exactly Selegiline lowers cortisol, and it turns out it does so by directly inhibiting ACTH secretion.



    Since ACTH is the precursor to A-MSH, would this be what was most likely responsible for the sun sensitivity?


    Not sure what you're suggesting altered cortisol levels. IIRC, DLPA supposedly converts to PEA in the brain and of course MAO-B inhibitors halt the break-down of PEA. Thus what you were getting from the combination was amphetamine-like effects. Doesn't explain the hunger, but it does explain your withdrawal symptoms, which were more likely akin to amphetamine withdrawal than the result of low cortisol. (Although mildly reduced cortisol is typical in amphetamine withdrawal.) This is also why pseudoephedrine was effective, because you were experiencing withdrawal-induced low levels of NE.



    Selegiline doesn't directly lower cortisol according to most studies I've seen, though it may have adverse effects on MR/GR expression and immune system function.



    Now when you say you can't handle the sun, what treatment are you referring to (pseudoephedrine and selegiline?), and what effects do you get in the sun? Do you mean photophobia, i.e. everything seems painfully bright, or are you getting rashes and/or an allergic reaction?



    This is almost certainly unrelated to ACTH and alpha-MSH.

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    Quote Originally Posted by Ex Dubio View Post
    Not sure what you're suggesting altered cortisol levels. IIRC, DLPA supposedly converts to PEA in the brain and of course MAO-B inhibitors halt the break-down of PEA. Thus what you were getting from the combination was amphetamine-like effects. Doesn't explain the hunger, but it does explain your withdrawal symptoms, which were more likely akin to amphetamine withdrawal than the result of low cortisol. (Although mildly reduced cortisol is typical in amphetamine withdrawal.) This is also why pseudoephedrine was effective, because you were experiencing withdrawal-induced low levels of NE.



    Selegiline doesn't directly lower cortisol according to most studies I've seen, though it may have adverse effects on MR/GR expression and immune system function.



    Now when you say you can't handle the sun, what treatment are you referring to (pseudoephedrine and selegiline?), and what effects do you get in the sun? Do you mean photophobia, i.e. everything seems painfully bright, or are you getting rashes and/or an allergic reaction?



    This is almost certainly unrelated to ACTH and alpha-MSH.


    Why are a third of the threads on M&M about Selegiline related to the fatigue it induces in some people? Before I started the DLPA I was on Rasagiline for a week and about half way through that week I had the midday crashes that so many people report with MAO-B inhibitors.



    The effects of DLPA and Amph with me are quite different unfortunately. Amph suppresses appetite while the other does the opposite. Both were prosocial but with a different feel to it. DLPA was more like wanting to be the life of the party and longing to be around people, whereas Amph gave me a sort of dominant social feeling.



    I've been through Amph withdrawal and yes, many of the symptoms were similar. However, this time I had increased mucus production like non I've ever had before, and random rashes/itchiness for a couple days. The mucus could be due to an infection I'd been staving off symptoms of for a week due to the drug, but I don't know what the deal with the rashes are.



    I guess I shouldn't have used the clinical term "sun sensitivity". Mainly I just burnt much easier than I normally do, and I'm very observant of how my skin reacts to the sun being of Irish/Swedish heritage.



    What do you mean by adverse effects on the immune system? An increase in auto-immune incidence? PMID:9564633 - suggests a stimulatory role of Selegiline on immune markers, unless it has a suppressive effect in other areas I'm not aware of?



    I know dogs and humans aren't the same, but how does Selegiline lower Cortisol in Cushings treated dogs?

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    Senior Member Ex Dubio's Avatar
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    Quote Originally Posted by dudinator View Post
    Why are a third of the threads on M&M about Selegiline related to the fatigue it induces in some people? Before I started the DLPA I was on Rasagiline for a week and about half way through that week I had the midday crashes that so many people report with MAO-B inhibitors.


    The situation with selegiline is a bit odd. There are anecdotal reports all over the internet of selegiline-induced chronic fatigue that occasionally doesn't even go away with drug cessation. There are, in contrast, no such reports in the literature and no obvious mechanism, as selegiline does not directly affect cortisol levels.



    As a result, we can only speculate about what may induce the fatigue state. I mostly think it comes down to an imbalance between DAergic and NEergic transmission in the hypothalamus and surrounding structures (hippocampus, BNST, etc.). Chronic increases in DA transmission without corresponding enhancements of NE transmission seem to result in peculiar changes in GR/MR receptor density that may be related to the chronic fatigue, but honestly it's pretty damn hard to say. Other theories involve augmentation of immune response (at dendritic cells, IIRC) directly by DA; NE, in contrast, normally opposes this effect.



    My point is that there's no good evidence it's directly cortisol-related, but it's likely related either to immune activation or the HPA.




    The effects of DLPA and Amph with me are quite different unfortunately. Amph suppresses appetite while the other does the opposite. Both were prosocial but with a different feel to it. DLPA was more like wanting to be the life of the party and longing to be around people, whereas Amph gave me a sort of dominant social feeling.


    Fair enough. DLPA in general, and specifically this combination, is very poorly researched. I was simply trying to relate its effects to a combination with more research on it.




    I've been through Amph withdrawal and yes, many of the symptoms were similar. However, this time I had increased mucus production like non I've ever had before, and random rashes/itchiness for a couple days. The mucus could be due to an infection I'd been staving off symptoms of for a week due to the drug, but I don't know what the deal with the rashes are.


    Gotcha. Sounds like something screw with the immune system, whether an infection or mild autoimmunity.




    I guess I shouldn't have used the clinical term "sun sensitivity". Mainly I just burnt much easier than I normally do, and I'm very observant of how my skin reacts to the sun being of Irish/Swedish heritage.


    Interesting. Again, maybe immune related. I just can't imagine alpha-MSH is involved here, but I honestly can't rule it out I suppose.




    What do you mean by adverse effects on the immune system? An increase in auto-immune incidence? PMID:9564633 - suggests a stimulatory role of Selegiline on immune markers, unless it has a suppressive effect in other areas I'm not aware of?



    I know dogs and humans aren't the same, but how does Selegiline lower Cortisol in Cushings treated dogs?


    I mean an enhancement of immune activity, possibly manifesting as autoimmunity. I haven't read up on the interactions between DA and the immune system, but someone like ATB could give you a really good explanation. So yeah, we're talking about immune stimulation.



    And yes, I'm familiar with the study you're talking about, namely (PMID: 10449218). However, a more recent study found selegiline ineffective in canines with Cushing's (PMID: 15181926). Moreover, a number of studies have found DA agonists not to have any effect on cortisol levels. As D2 is the only putative DA receptor subtype for HPA suppression, the same could be assumed for selegiline.



    It's also worth noting that dog physiology is really different than human. Remember, we're much more closely evolutionarily related to rats and mice than we are to dogs. Primates do, after all, share a much more recent ancestor with rats than we do with canines.

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    Interesting, I've only allowed the fatigue to manifest for three days at the most at a time without using something NErgic. Hopefully I'm in the clear there. I've read enough of these boards to never want to experience chronic fatigue.



    The difference in effects of the DLPA and AMP is very interesting and could have something to do with the enkephalinase inhibition by the DLPA. I'm finished with that combo though, it's effects are superior do AMP from day 2-3 after which tolerance sets in, even with Memantine, since it stays in your body for so long. The effects then change from being AMP-like to the effects I described; hungry, horny, and long to be around people - helping them. To put it in a freudian way, exaggerated Id, and Superego without any of the Ego that AMP provides for me. For some reason though, day 1 of DLPA is extremely dysphoric, any drugs I take while on day 1 seem to have no effect on the pleasure centers in my brain. It's literally impossible to feel good except for a strange libido boost similar to what I get with a Salvia trip.



    The illness, besides the lingering mucus cough in the morning and lost voice is for the most part gone, so I'm wagering that the Rasagiline is merely giving me an exaggerated immune response. As I understand, an exaggerated immune response could easily go hand in hand with increased sun burn sensitivity. I'm not well read on cellular repair mechanisms but I'm guessing the bodies response to cell damage via pathogen vs. radiation is at least somewhat similar.



    I usually thought of the immune system through diurnal rhythm. High-Night Low-Day. I figured if DA increases towards the evening this would warrant an increase in immune response. Now that I've read through the Canine studies a bit better, it reads that ACTH increases were attenuated rather than decreased. IMO this might have more to do with the immune stimulating properties of the Selegiline possibly slowing/preventing further growth of the tumor causing Cushings.

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    the equivalent parkinson's doses are selegiline 5mg 2x/day, while rasagiline is taken 1mg once a day, so its possible you may have just been taking a shitload of rasagiline.

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    Quote Originally Posted by ridley View Post
    the equivalent parkinson's doses are selegiline 5mg 2x/day, while rasagiline is taken 1mg once a day, so its possible you may have just been taking a shitload of rasagiline.


    Oops, I took the Rasagiline equivalency to Selegiline and accidentally typed it out as such. Meant to say 1mg Rasagiline a day, the equivalent to 5mg of Selegiline.



    2mg of Rasagiline a day inhibits the majority of MAO-B like 10mg of Selegiline would, after which they begin to suicidally inhibit MAO-A. If I were to do this I most likely would have ran into many troubles based on my weekend activities.

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