78 replies to this topic

[crusader]

you would think something that elevates NGF, BDNF, and GDNF, would be deserving of more praise, i dont understand the hesitance to recommend and/or self medicate with this substance?



i would understand the rejection if someone came on here as an 18 year old and declared that they were going to go on an indefinite trial of selegiline until they were 65, however, cant it not be used as a short term clutch to induce all of the above mentioned growth factors?

is there something I am not understanding ?

[formergenius]

I don't like it for the Amphetamine metabolites. The mere idea of having that stuff in my system makes me anxious as hell.
Aside from that, I don't see the problem, aside from MAOI acitivy.

[crusader]

I don't like it for the Amphetamine metabolites. The mere idea of having that stuff in my system makes me anxious as hell.
Aside from that, I don't see the problem, aside from MAOI acitivy.

i remember reading a post from a member of this forum describing that those amphetamine metabolites are the equivalent of "1/1000th" of a 10mg adderal pill

Edited by crusader, 21 February 2013 - 11:54 PM.

[anagram]

Its really not as bad as people try to frame it.
As someone who has been prescribed Nardil, Vyvanse, and Ritalin, I can vouch for Selegiline's positive effects, it is possibly the best medication I have ever gotten.
The reason why so many people say Selegiline is terrible is possibly because a lot of people on longecity don't actually have Depression that bad and don't achive selegiline's full effect, most people here are very successful without drugs and are simply looking for something to give them a moderate edge over others, not anything that is primarily a mood enhancer. Remember that Selegiline inhibits MAO_B primarily, which does not cause "effects" in normal people unless your dopamine levels are very low.

Many people here are actually taking dopamine antagonists and Serotonin antagonists because some of those drugs increase NGF, GDNF, BDNF more than Selegiline. Selegiline's positive effect on growth factors is from its Dopamine antagonism which unfortunately Selegiline is a relatively weak dopamine antagonist, it lacks the strength of many newer medications that have enormous effects on NGF, BDNF, GDNF.


Unless you have very low dopamine Selegiline will also definitely give you mood swings, and there is a bit of a withdraw for the people taking the tablets(the EMSAM patches they are much much safer and generate less methamphetamine).
People have died from getting addicted to Selegiline, its an honest drug, please look into more modern solutions(dopamine/serotonin antagonists) if you are interested in a sharp cognitive boast.

Edited by anagram, 22 February 2013 - 02:52 AM.

[spermidine]

selegiline is frowned upon because its outdated and semi-toxic compared to the newer version of rasagiline.
so anagram why dont you switch to rasagiline and report results later as either better or worse ?

[jadamgo]

Taking selegiline the usual way (swallowing the pills) is frowned upon because most of the selegiline is converted to amphetamine metabolites, which aren't particularly toxic, but also aren't particularly helpful for the sorts of problems people want to use selegiline for.

Taking it sublingually or via the EMSAM patch is not frowned upon by most people who seriously understand the differences between sublingual/dermal selegiline and oral selegiline.

As for rasagiline, it is incapable of treating depression by itself. It's an okay treatment for Parkinson's disease, and perhaps general life extension, and likely has some mild nootropic effects. If you can afford the higher price of rasagiline over selegiline and just want a general life-extender/nootropic, then by all means, get rasagiline! It's far more convenient because you don't have to spend 10 minutes letting it dissolve under your tongue to use it safely. For those people wanting mood boosts, or who can't afford rasagiline, taking selegiline under the tongue is fine.

[anagram]

Just get the EMSAM, seriously! $25 dollers for 30 x 6mg patches with insurance, its fucking re-diculous man! The tablet form Selegiline raises blood amphetamine to such high levels that the effect is no longer caused by MAO-I, but rather the amphetamine metabolites themselves. In addition, EMSAM raises actual blood Selegiline to levels far higher that the tablets, it is no comparison. You can either get yourself addicted to expensive speed or get the "true" benefit of Selegiline.
- I should mention that someone began taking <100mg tablets a day because they got addicted, insanity.

[spermidine]

anagram i asked you about why you wont try the upgraded version of selegiline which is rasagiline and you didnt aknowledge it.

[Major Legend]

I think its just the forums tend to bring the newer meds to the front page, selegeline was discussed a lot a while back.

What are the good effects of a sublingual dose on a normal person with slight ADD? The last time I tried it it gave me severe brain fog/retardation for a week, and I was high on the first da, but that was via oral administration, transdermal or sublingual was not discussed much.

[RS3RS]

I don't like it for the Amphetamine metabolites. The mere idea of having that stuff in my system makes me anxious as hell.
Aside from that, I don't see the problem, aside from MAOI acitivy.

A lot of people seem to spout this idea, and I'm quite sure they are acting on irrational fears that (as have been pointed out already in this thread) are very unfounded.

I might be cautious of using high doses for non-nootropic purposes, but let's look at a typical nootropic dose -- 1.5 (one and one half) mg sublingual every other day. If you're concerned about amphetamine metabolites, let's look at some facts:

1. Sublingual administration, bypassing first-pass metabolism (these metabolites are created in the liver through oral administration), significantly reduces the formation of amphetamine-based metabolites. Don't have the source saved now, and can't remember the exact percent, (you can look it up if you're interested as it's fairly common knowledge on this forum), but sublingual administration reduces amphetamine metabolites by some 80+% according to Pubmed research.

2. Concentration of amphetamine metabolites cannot exceed the original dosage of selegiline. If you intake 0.75 mg per day (1.5 mg every other day), even assuming this process was somehow 100% efficient, you're raising concern over 3/4ths mg of levoamphetamine metabolites (including levomethamphetamine, which is (vice-versa from the dextro variety) less stimulating than regular ampheta) per day. That just seems pretty silly, considering even low doses of Adderall is highly debated as to significant effects on neurotoxicity -- and those are substantially more than we're talking about here.

Also, I'm assuming 100% conversion just for arguement's sake... If we assume oral Selegiline is 100% converted into amphetamine (which I assure you it is not), and take into account data that suggests sublingual administration reduces formation of those metabolites by 80%, we're now only looking at 0.15% of a mg of very weak amphetamine metabolites per day. Come on!!

3. Selegiline protects against damage caused by larger doses of amphetamine-based drugs that are hundreds of times more powerful than levo-isomer metabolites, and are administered in doses thousands of times larger than any of these relatively inactive metabolites. Check this out if you need proof:

http://www.ncbi.nlm..../pubmed/7542394


With all of that in mind (and please correct me if anything is wrong!), I really wouldn't worry about the effects of these metabolites in the slightest. I'm going to continue low-dose selegiline until I see research suggesting I should stop.

[spermidine]

thats great RS3RS but how come selegiline is mentioned to be slightly toxic ? originally i assume people thought its because of the amphetamine metabolites but im not sure now.

[anagram]

Selegiline has other chemical products made during its manufacture, toxic ones. People with Parkinsons actually became much worse off and many died during the first few trials. TEVA did a good job of covering this up, however they have not entirely eliminated these dangerous chemical byproducts. The tablets are typically manufactured in India which supplies chems as Bulk, not specifically for pharmaceutical purposes... you get my point. It is dangerous for people to take Selegiline on a day to day basis because of these toxic by products. If you take a much higher dose, one used for Parkinsons, you will actually be somewhat protected from these toxins, but in low doses they're effects become apparent. Selegiline tablets are as risky as getting Piracetam or some RC from china, just get a legit prescription seriously!
Higher dose = more protection = unwanted side effects
lower dose = toxic by products but better for longevity.

Rasagiline is fairly expensive however it is much much much safer than Selegiline, it has less toxic chemicals associated with it. Rasagiline is also 10x better than Selegiline in terms of mental boast. I have never tried it however I have asked others on the internet and a few responded with amazing claims. I would get some except its cost is really high. Perhaps one day If I save enough, I will get some from longevity-systems.com . One of the things about Rasagiline which makes it 10x better is the fact that it releases much more GDNF than Selegiline. Rasagiline also protects human cells against hypoxia while Selegiline failed to do this in a consistent manner. Rasagiline may be the first drug ever on the market to be specifically designed for increasing human maximum life span. If you have the money to get Rasagiline, people on Longecity will envy you to bits.

http://www.ncbi.nlm....pubmed/11795516

Edited by anagram, 23 February 2013 - 06:25 PM.

[crusader]

being what some would describe as a "novice" regarding nootropics, i admit that im relegated to trusting the knowledge of others and making an informed decision that would benefit me most. However, it is difficult to do such a thing when there is so much conflicting information regarding nootropics on this forum.


for instance, jadamgo sais how rasagiline would yield "mild" nootropic results, while anagram sais rasgailine is 10x better than selegiline in terms of mental boost.


i mean something is either wrong or it is right, so, who is misinformed here? how can i make a decision when people are giving myself and non members reading this topic conflicting information?

[csrpj]

Taking selegiline the usual way (swallowing the pills) is frowned upon because most of the selegiline is converted to amphetamine metabolites, which aren't particularly toxic, but also aren't particularly helpful for the sorts of problems people want to use selegiline for.

Taking it sublingually or via the EMSAM patch is not frowned upon by most people who seriously understand the differences between sublingual/dermal selegiline and oral selegiline.

As for rasagiline, it is incapable of treating depression by itself. It's an okay treatment for Parkinson's disease, and perhaps general life extension, and likely has some mild nootropic effects. If you can afford the higher price of rasagiline over selegiline and just want a general life-extender/nootropic, then by all means, get rasagiline! It's far more convenient because you don't have to spend 10 minutes letting it dissolve under your tongue to use it safely. For those people wanting mood boosts, or who can't afford rasagiline, taking selegiline under the tongue is fine.

so rasagiline is better in every way than selegeine except for its effect on mood?

[anagram]

I don't believe that jadamgo truly knows if Rasagiline is worse for mood, "it likely does not have nootropic effects".
Rasagiline is much better for neuroprotection than Selegiline.
http://www.ncbi.nlm....pubmed/21224199
http://www.ncbi.nlm....pubmed/23196982

-Rasagiline is probably much better for mood than Selegiline is.
Rasagiline reversed Resprine induced depression without changing the levels of brain monoamines. This suggests that Rasagiline could be used as a specific mood enhancer. Feeling depressed? Rasagiline could offer a alternative to common stimulates, it is devoid of aggressive monoamine level fluctuation that is associated with amphetamine use, however appears to be a wonder drug of sorts due to selective mood enhancement.
http://www.ncbi.nlm....pubmed/12504917

Rasagiline looks amazing!

[spermidine]

anagram, i googled site you mentioned longevity-systems.com and i cannot find any website as such. can you tell me the actual site ?

[medievil]

Because at the doses used here its been shown to increase mortality in parkinson patients indicating this dose may be on the wrong side of the biphasic curve, on that side it shorten the lifespan of rodents and increases mortality, wich sounds quite simular to increased mortality in parkinson patients.

Even tough logically it will improve the symptions.

[spermidine]

^ and there was so much talk about how it extends life. do you have a good article of the mortality related to it ?

[Spectre]

I had some great experiences with Selegiline, definitely helped my brain in numerous ways. I wouldn't worry about the amphetamine metabolites, people are exaggerating the effects. Selegiline has actually been studied and shown to reverse the neurotoxic effects of methamphetamine.

[brainslugged]

Because at the doses used here its been shown to increase mortality in parkinson patients indicating this dose may be on the wrong side of the biphasic curve, on that side it shorten the lifespan of rodents and increases mortality, wich sounds quite simular to increased mortality in parkinson patients.

Even tough logically it will improve the symptions.

So, what dose do you think we should be taking? Most people are already taking small doses of 1-2mg on a less than every day basis. That already seems quite low, lower than the parkinson study which was 5-10mg daily IIRC.Also, does anyone have the meth study? If it was conducted using humans, I would assume that we are, in fact using the correct dosage, since it protects against aging through the same mechanism, right?Perhaps the parkinson's patients died from accumulation of MAO-A inhibition and the subsequent increased blood pressure and thus bodily stress/deterioriation to an already frail system. Does anyone know what they died of? If a significant amount was stroke or heart attack, this would be my bet.

[medievil]

Just google deprenyl increased mortality parkinson guys, the dose used was 5mg.

I was thinking of trying it myself too, was betting at 2mg a day, the lower the more chance its on the good side.

Rats die of too much deprenyl too, biphasic curve its called they say, so be on the right side or die soon buddy.

The metabolites is the good thing about deprenyl, should augment dex if they are in high enough doses, dont see the problem must come from the amp kills my brain hype.

[leftside]

I'm currently taking 2mg Mon, Weds and Fri mornings. I like it and will continue with this regime for another 6 months at least.

[medievil]

It has been shown to potentiate stimulants while preventing the negative cardiovascular effects, atleast with methamphetamine wich makes me interested, also i beleived the increased da should help anticepatory anhedonia wich phenibut helped but id like to avoid that stuff for now also because its way to expensive and im also getting my stim doses under control, eventually the addition of reboxetine could aid motivational issues or anything if response to stims is negative due to balance shifted from be to da, might make some ppl less motivated and more inclined to do addictive kinda stuff, but that depends on their brain wiring.

[leftside]

It has been shown to potentiate stimulants while preventing the negative cardiovascular effects,

It does. I rotate a number stimulants mid-week (yerba mate, green tea, modafinil, kola nut, cacao and phenylpiracetam). It definitely makes the caffeine based stimulants (yerba mate, green tea and kola nut) stronger.I don't drink coffee as it gives me too many negative side-effects. The only time I've had a "good" cup of coffee was at a coffee farm in Colombia. Very nice smooth stimulation with no side-effects.

As a side note I do take Phenibut once every two weeks. I take 1.5g at 6pm and then have a great nights sleep. It doesn't make me drowsy or tired in any way, but the sleep is good.

[medievil]

How does it modulate phenibut as it should modulate da release, not that da causes euphoria but it should change the addictive property's maybe a bit?

[leftside]

To be honest I don't know. I only started taking Phenibut recently. After I read the horror stories about it I said to myself "ok this is great stuff, but must limit it to once every 2 weeks". Even though I'll try almost anything (at least once) I don't consider myself to have an addictive personality.

[medievil]

I took it daily for ages but withdrew with diazepam wich is painless due to money issues, plan to stay off now, the withdrawal isnt a big issue if you got diazepam around, otherwise if you run out prepare for the fun, had it a few times and its fucked up, but nothing compared to benzo withdrawal wich is milder but there's like no end to it.

[jadamgo]

Taking selegiline the usual way (swallowing the pills) is frowned upon because most of the selegiline is converted to amphetamine metabolites, which aren't particularly toxic, but also aren't particularly helpful for the sorts of problems people want to use selegiline for.

Taking it sublingually or via the EMSAM patch is not frowned upon by most people who seriously understand the differences between sublingual/dermal selegiline and oral selegiline.

As for rasagiline, it is incapable of treating depression by itself. It's an okay treatment for Parkinson's disease, and perhaps general life extension, and likely has some mild nootropic effects. If you can afford the higher price of rasagiline over selegiline and just want a general life-extender/nootropic, then by all means, get rasagiline! It's far more convenient because you don't have to spend 10 minutes letting it dissolve under your tongue to use it safely. For those people wanting mood boosts, or who can't afford rasagiline, taking selegiline under the tongue is fine.

so rasagiline is better in every way than selegeine except for its effect on mood?

Almost -- rasagiline is better for nootropic effects and convenience, but it not only lacks strong antidepressant effects, it also costs more per dose. If you just want a nootropic, and have money to burn, rasagiline is the way to go. But not everyone has money to burn, or is looking for mere nootropic effects. Those people would be better off taking selegiline sublingually or, if they have health insurance, dermally.

[spermidine]

if rasagiline doesnt have as strong antidepressant effect as selegiline, isnt it good idea to combine them both same time ?

[brainslugged]

Here's a meta-analysis of selegiline treatment.

Conclusion: These results contrast with those of the PDRG-UK study and demonstrate no increase in mortality associated with selegiline treatment whether or not patients also received levodopa.

Still, this is a bit worrying

CONCLUSION—Therapy with selegiline and levodopa in combination may be associated with severe orthostatic hypotension not attributable to levodopa alone. Selegiline also has pronounced symptomatic motor effects in advanced Parkinson's disease. The possibilities that these cardiovascular and motor findings might be due either to non-selective inhibition of monoamine oxidase or to amphetamine and met-amphetamine are discussed.

Here is another study with no increased mortality from selegiline, even with other dopamine agonists. I think that L-dopa is the main killer, here. Actually, acording to this study, if I am reading it right, selegiline restored parkinson's patients to normal mortality rate.

Conclusions: Subjects with PD had twice the rate of mortality relative to age- and sex-matched comparators. However, those subjects who received selegiline at any time in combination with co-careldopa or co-beneldopa showed no significant difference in mortality compared with the comparators. Monotherapy with levodopa was associated with the highest mortality.

Also, check it out

Compared with the findings for an age-matched group not taking deprenyl, a higher risk of mortality in Parkinson's disease patients taking deprenyl has recently been reported. Since a biological basis for this observation was not apparent, an epidemiological explanation was sought. Expected mortality over a 6-year period in four hypothetical age-matched groups was determined. Although groups were age matched, ages of individuals within the groups varied. Variation of individual ages within each group, without affecting the age-match comparability, produced a marked variation in expected group mortality. Mortality comparisons between age-matched groups can be invalid. This epidemiological trap might account for the recent unexplained high mortality observed in a group of Parkinson's disease patients taking deprenyl.

A pretty neat page for favorable selegiline studies.


I found two studies showing increased mortality.

This one is the most worrying. Mostly because of the graph on this page, showing that mortality started to increase the most after the 2 year mark, which was the limit of at least one of the studies I read in favor.

Then here is the one by PDRG-UK that is referenced in the study which dismisses the increased mortality.

Increased mortality in patients on selegiline combined with l-dopa led to premature termination of this arm after 6 years.

I am thinking about using selegiline at moderately high doses(15-30), sublingually as a non-selective MAOI, since Parnate seems to be extremely effective in social anxiety (and I am hoping it will be effective for AvPD/SPD related symptoms as well, since those are really the root of my social problem right now). I just need to read up more on diet limitations just to be safe, and my selegiline needs to hurry up and get here. Maybe not though, considering the looks of the increased mortality with a high dosage. Parnate itself would probably be better for that purpose. AMPH or other stimulants would probably be ideal for the entirty of my problems, but I can't currently get my hands on any.

Edited by brainslug, 28 February 2013 - 11:32 PM.