94 replies to this topic

[thedevinroy]

I've been experimenting with a few things around the house, plus a few other things...

Ashwagandha
Surprisingly good synergy. Notice a warmth, full body. Notice an increase in perception of strength. It has a good and stable energy, not a hyper energy. Increases hunger, which is good, since I usually get less hungry with Selegiline. Increases sex drive, but in a more interesting way... females are more fascinating to me, and I generally use day dreams 50% more frequent towards structuring future social interactions (jokes, lines, etc.). Low interaction with serotonergic effects.

Green Tea
Awesome focus. Lasts a few hours before I need a re-up. Green tea was never this effective for focus before. I believe it has to do with the poly-catechols in green tea, primarily EGCG, a potent inhibitor of COMT, which is apparently a pretty prevalent enzyme in the PFC. Green tea also increases hunger for me in sort of a strange way. Tea catechins have affinity for cannabinoid receptors. Which is an added benefit.

Black Tea
Good focus. Good energy. It's a bit like green tea, but not as great for focus. Instead, there is a better energy boost.

Coffee
Holy crap, does coffee make you high. Silly, light-headed, and out of line. Not a good synergy in higher doses, but it definitely brightens mood easily and effectively with just a few sips.

Huperzine A
Theoretically, and actually, there should be a synergy between Selegiline and the NMDA Antagonist / AcetylCholinEsterase Inhibitor, Huperzine A. Selegiline actually increases acetylcholinesterase activity ([1] [2]), while Huperzine inhibits it. NMDA antagonism is also very important to sustain the effects of release agents such as phenethylamine (broken down by MAO-B) and L-amphetamine (some ADHD patients are prescribed Memantine for this reason). I notice a less frantic, more organized mental state when taking Huperzine A with Selegiline. In addition, I do not get depressed with Huperzine A, like I would normally taking it straight (AChE frees up choline for methylation).

Anyone else have any synergies with Selegiline?

Edited by devinthayer, 10 November 2011 - 10:36 PM.

[X_Danny_X]

Doesnt Huperzine A make your depression worse? for people who are suffering from depression that is.

[thedevinroy]

Doesnt Huperzine A make your depression worse? for people who are suffering from depression that is.

Exactly my point. Taking Huperzine A with Selegiline negates the side effects from each. They cancel each other's side effects out, providing a potentially amazing synergy. Selegiline is a very powerful antidepressant, so I didn't get depressed when taking Huperzine A.

Edited by devinthayer, 11 November 2011 - 02:19 PM.

[Metabolic]

Coffee is definitely synergistic with selegiline as well for me. Before selegiline, it was coffee and cigarettes (also a MAO-B inhibitor). I don't know if it's the catecholaminergic or enkephalinergic (endorphins) effect of DLPA and tianeptine, but selegiline seems to potentiate those too.

I guess my impression is that selegiline is a general intensifier of the rush feelings: the adrenaline rush, the dopamine rush, and the endorphin rush.

[thedevinroy]

Coffee is definitely synergistic with selegiline as well for me. Before selegiline, it was coffee and cigarettes (also a MAO-B inhibitor). I don't know if it's the catecholaminergic or enkephalinergic (endorphins) effect of DLPA and tianeptine, but selegiline seems to potentiate those too.

I guess my impression is that selegiline is a general intensifier of the rush feelings: the adrenaline rush, the dopamine rush, and the endorphin rush.

This reminds me. Playing guitar for 15 minutes gives me such a rush. I get in such a creative mood, things just flow out. Guitar and Selegiline have a good synergy.

Haven't tried DLPA with Selegiline. What can you tell me about the synergy?

[Metabolic]

The synergy for me is very mild euphoria, like some chocholate ice cream without the taste and cold textures (obviously).

People generally seem more interested in the PEA + Selegiline combo.
Some mention DLPA + S as a mild form of PEA + S because L-phenylalanine is a precursor to PEA.
Others mention that DLPA + S lifts mood because L-phenylalanine is a precursor to tyrosine (which is a precursor to norepinephrine and dopamine) and S's MAO-B inhibition prolongs the party.

But according to my expert wikipedia sleuthing, I think there is definitely something going on with the fact that the other component, D-phenylalanine, blocks enkephalin (endorphin) degradation by the enzyme carboxypeptidase A. If that doesn't pique interest, note that the inhibition of endorphin breakdown also leads to an inhibition of GABA release in the ventral tegmental neurons in the midbrain, which results in greater dopamine release. This can be seen as a complementary to selegiline as there is evidence (PMID: 8278449) to suggest that selegiline facilitates the nigrostriatal dopamine (DA)-ergic system but fails to facilitate mesolimbic dopaminergic activity (which explains why I find tianeptine to be complementary to selegiline as well). IOW, selegiline facilitates dopamine in the nigrostriatal DA system and DLPA indirectly takes care of the dopamine in the midbrain through endorphin and GABA modulation of VTA efferent fiber projections through the midbrain. It's a bit convoluted, but convolution seems inevitable when it comes to laying down the carpet for maximal dopaminergic coverage.

Edited by Metabolic, 12 November 2011 - 03:18 AM.

[thedevinroy]

The synergy for me is very mild euphoria, like some chocholate ice cream without the taste and cold textures (obviously).

People generally seem more interested in the PEA + Selegiline combo.
Some mention DLPA + S as a mild form of PEA + S because L-phenylalanine is a precursor to PEA.
Others mention that DLPA + S lifts mood because L-phenylalanine is a precursor to tyrosine (which is a precursor to norepinephrine and dopamine) and S's MAO-B inhibition prolongs the party.

But according to my expert wikipedia sleuthing, I think there is definitely something going on with the fact that the other component, D-phenylalanine, blocks enkephalin (endorphin) degradation by the enzyme carboxypeptidase A. If that doesn't pique interest, note that the inhibition of endorphin breakdown also leads to an inhibition of GABA release in the ventral tegmental neurons in the midbrain, which results in greater dopamine release. This can be seen as a complementary to selegiline as there is evidence (PMID: 8278449) to suggest that selegiline facilitates the nigrostriatal dopamine (DA)-ergic system but fails to facilitate mesolimbic dopaminergic activity (which explains why I find tianeptine to be complementary to selegiline as well). IOW, selegiline facilitates dopamine in the nigrostriatal DA system and DLPA indirectly takes care of the dopamine in the midbrain through endorphin and GABA modulation of VTA efferent fiber projections through the midbrain. It's a bit convoluted, but convolution seems inevitable when it comes to laying down the carpet for maximal dopaminergic coverage.

You just gave me a mental boner. I never got heavy into studying the regions of the brain. Looks like i might need some DLPA. That might be my magical synergy.

[zodiac]

Devin, DLPA in combination with Selegiline definitely do promote a slow-release of 'natural' PEA... generally more preferable than taking exogenous PEA every 1-2 hrs or something. It does take a bit of time to build up properly -- DLPA bid for a few days to two weeks (with maybe something like B-6 or "B-100" complex at night w/ a gabaergic to sleep), and it isn't a high like a lot of people try to foolishly chase with PEA -- but hey, gotta stop chasing our own tail one day, eh? ;D

[thedevinroy]

Devin, DLPA in combination with Selegiline definitely do promote a slow-release of 'natural' PEA... generally more preferable than taking exogenous PEA every 1-2 hrs or something. It does take a bit of time to build up properly -- DLPA bid for a few days to two weeks (with maybe something like B-6 or "B-100" complex at night w/ a gabaergic to sleep), and it isn't a high like a lot of people try to foolishly chase with PEA -- but hey, gotta stop chasing our own tail one day, eh? ;D

Awesome. Will have to give it a shot next upcoming paycheck.

[thedevinroy]

Tried the herbal combo: Ashwagandha (6mg-9mg Withanolides), Ginkgo Biloba (120mg of 24/6), and Gotu Kola (450mg whole). It treated the hyperactivity beautifully, but it left me slow. I added some Zinc (25mg) to the mix, and it cured the slowness until the hyperness of the Selegiline wore off about 8 hours later. Turns out Zinc is an NMDA antagonist and GABA antagonist at the benzodiazepene binding site as well as an improtant co-factor in converting serotonin to melatonin via activating vitamin B6.

[computeTHIS]

SAM-e can be taken with Selegiline, despite contraindications. I take 400mg tablets as-needed. It takes about 5 hours for SAM-e to reach peak blood-serum levels. Sometimes it can cause an elevated heart rate, or symptoms of mania (being overactive isn't always a bad thing tho), in my experience - which is why I take it as-needed.

I look forward to trying some of these recommendations. It's still unclear to me how Bacopa is beneficial, with or without Selegiline.

Maybe someone else here mentioned it, but David Pearce - the author of biopsychiatry.com, finds Amineptine to work best with Selegiline. If the best synergies involve higher dopamine levels as Amineptine would suggest, it's reinforcing my notion that small quantities of orally ingested cannabis may be ideal. If I lived in California I would give it a shot.

[thedevinroy]

I wish I had Amineptine... too bad it's not available in the USA and is scheduled...

I hadn't considered SAM-e due to the cost. Some have luck with TMG + NAC combo. Sublingual Methyl B12 seems to be a kicker from what I hear as well. Activated B9 (methyl-THF) might give the same kick.

I didn't realize SAM-e had such a long half-life. Perhaps I will give it a shot.

[thedevinroy]

DL-Phenylalanine seems to kickstart the Selegiline effect I had in week two, including dilated pupils, hyperactivity, creativity, but a decrease in vertigo. The first two doses gave me a headache, but this has subsided. Sad to say, I have already built tolerance to it over just a few days of taking 500mg 2x/day, and today I had to take 500mg sublingual (which tastes like minty anus) to get that effect. Not very effective in adding "focus" but it does add an antidepressant effect.

[thedevinroy]

5mg Methylene Blue + 500mg Vitamin C now 30 days past start causes no interaction with Selegiline: just a mood lift and increased thought speed.

[thedevinroy]

I am now speculating pinebark extract, since black/green tea was such a success. I am also re-ordering Huperzine A.

Ashwagandha + Ginkgo + Gotu Kola + Zinc is a good combo to fight hyperactivity and vertigo. It may be a bit strong, and I am still getting used to the sedative effects. I've been playing with the supplements in combo and by themselves, but ultimately, the best combo is all four at the same time.

At first, Gotu Kola was very sedating, so I would take it at night. Last night, it had a reverse effect, and I was slightly stimulated. Herbs are weird... Anyhow, I still got to sleep on time.

At first, Ginkgo was sedating, but after a while, it started feeling like Fish Oil.

Ashwagandha still, as always, is the best one of the batch: consistently produces a warm pleasant mood and steers away the vertigo without causing tiredness or sedation. Always helps my tooth ache. Always helps my memory. Always helps my self confidence. Good stuff.

Zinc by itself is hard to determine effects... some clarity of mind, but in a very subtle way.

Edited by devinthayer, 23 November 2011 - 07:17 PM.

[computeTHIS]

DL-Phenylalanine seems to kickstart the Selegiline effect I had in week two, including dilated pupils, hyperactivity, creativity, but a decrease in vertigo. The first two doses gave me a headache, but this has subsided. Sad to say, I have already built tolerance to it over just a few days of taking 500mg 2x/day, and today I had to take 500mg sublingual (which tastes like minty anus) to get that effect. Not very effective in adding "focus" but it does add an antidepressant effect.

I'm currently unable to feel any effect from 500mg DLPA or from 450mg Ashwagandha. It would appear that one day of cessation from SAM-e is not enough, it's effects seem to be over-riding everything else. But then I have to ask myself, if I'm feeling this great then what else do I really need?

[thedevinroy]

DL-Phenylalanine seems to kickstart the Selegiline effect I had in week two, including dilated pupils, hyperactivity, creativity, but a decrease in vertigo. The first two doses gave me a headache, but this has subsided. Sad to say, I have already built tolerance to it over just a few days of taking 500mg 2x/day, and today I had to take 500mg sublingual (which tastes like minty anus) to get that effect. Not very effective in adding "focus" but it does add an antidepressant effect.

I'm currently unable to feel any effect from 500mg DLPA or from 450mg Ashwagandha. It would appear that one day of cessation from SAM-e is not enough, it's effects seem to be over-riding everything else. But then I have to ask myself, if I'm feeling this great then what else do I really need?

I was considering TMG supplementation. Good for the liver, too.

[longevitynow]

In my experience 500 mg of DLPA doesn't have much of an effect. Go higher. 1500 mg

[computeTHIS]

DL-Phenylalanine seems to kickstart the Selegiline effect I had in week two, including dilated pupils, hyperactivity, creativity, but a decrease in vertigo. The first two doses gave me a headache, but this has subsided. Sad to say, I have already built tolerance to it over just a few days of taking 500mg 2x/day, and today I had to take 500mg sublingual (which tastes like minty anus) to get that effect. Not very effective in adding "focus" but it does add an antidepressant effect.

I'm currently unable to feel any effect from 500mg DLPA or from 450mg Ashwagandha. It would appear that one day of cessation from SAM-e is not enough, it's effects seem to be over-riding everything else. But then I have to ask myself, if I'm feeling this great then what else do I really need?

I was considering TMG supplementation. Good for the liver, too.

TMG could indeed be beneficial, and possibly a cheaper alternative to SAM-e. I'd love to find literature showing TMG quantity-equivalents to SAM-e, since TMG supposedly increases SAM-e by remethylating homocysteine.

I was finally able to to feel the effects of 500mg DLPA after 3 days' cessation from SAM-e. DLPA by itself didn't generate particularly helpful effects other than a dopamine high. Adding Huperzine A enabled me to be productive. It's possible that DLPA combined with some other things could be a nootropic alternative to dextroamphetamine. There's a thread on that topic somewhere but I'm too lazy to dig it up at the moment. The negative (and possibly neural-damaging) effects I see with similar meds to dextro seem to pertain to their action on norepinephrine. If there's a way of safely increasing norephinephrine I'd like to hear about it. In the mean time, SAM-e is working wonderfully for me.

[medievil]

The most potent methylation increasing supplement appears to be l methylfolate or deplin, but its highly expensive.

[thedevinroy]

The most potent methylation increasing supplement appears to be l methylfolate or deplin, but its highly expensive.

TMG is the most potent supplement by weight. It's like 36% methyl donors [(117.146 - 75.07) / 117.146 = 0.359175729]. Each molecule has three methyl groups. However, I do have reason to believe that it has limitations on absorption in conjunction with other nootropics like ALCAR and Alpha-GPC.

Methylfolate is quite potent, but I'd be careful for B12 imblance. Deplin seems like a better balance.

[X_Danny_X]

Doesn't Phenethylamine (PEA) gets destroyed by your stomach if taken orally? Also when you guys are saying DPLA, you are talking about Phenylalanine??

[thedevinroy]

Doesn't Phenethylamine (PEA) gets destroyed by your stomach if taken orally? Also when you guys are saying DPLA, you are talking about Phenylalanine??

Yes and yes. The stomach acid tends to do a number on DLPA. Taken sublingually multiplies the effects by a factor of two or more. It tastes like minty ass, so I try not to take sublingually if I don't need to.

[Ampa-omega]

A synergy you may want to try is selegiline with aniracetam, selegiline supposedly lowers seretonin levels, while aniracetam is a 5ht agonist/modulator not sure which exactly, selegiline would remove some of the anxiolytic quality from aniracetam and balance it out, selegiline will increase levels of PEA, pea will act as an excitatory neurotransmitter and also modulates ampa receptors, so it should theoretically work well with aniracetam.

Edited by Ampa-omega, 30 November 2011 - 10:26 PM.

[X_Danny_X]

Doesn't Phenethylamine (PEA) gets destroyed by your stomach if taken orally? Also when you guys are saying DPLA, you are talking about Phenylalanine??

Yes and yes. The stomach acid tends to do a number on DLPA. Taken sublingually multiplies the effects by a factor of two or more. It tastes like minty ass, so I try not to take sublingually if I don't need to.

man i do my best to avoid anything that is best taken sublingually. tasting the true taste of these compounds is nastyyyyyyyyyyyyyyyy. Phenylalanine is a precursor to Tyrosine.

why not just take Tyrosine since it is responsible for the neurotransmitters dopamine, norepinephrine and epinephrine.

[thedevinroy]

Doesn't Phenethylamine (PEA) gets destroyed by your stomach if taken orally? Also when you guys are saying DPLA, you are talking about Phenylalanine??

Yes and yes. The stomach acid tends to do a number on DLPA. Taken sublingually multiplies the effects by a factor of two or more. It tastes like minty ass, so I try not to take sublingually if I don't need to.

man i do my best to avoid anything that is best taken sublingually. tasting the true taste of these compounds is nastyyyyyyyyyyyyyyyy. Phenylalanine is a precursor to Tyrosine.

why not just take Tyrosine since it is responsible for the neurotransmitters dopamine, norepinephrine and epinephrine.

The D-isomer inhibits the break down of endorphins, which causes a dopamine increase in the midbrain (according to WIki). It is not considered a precursor to Tyrosine. The L-isomer is converted into Tyrosine and is considered a "time-relase" dopamine precursor. Thus, DL-Phenylalanine tends to be the preferred choice over Tyrosine.

[thedevinroy]

A synergy you may want to try is selegiline with aniracetam, selegiline supposedly lowers seretonin levels, while aniracetam is a 5ht agonist/modulator not sure which exactly, selegiline would remove some of the anxiolytic quality from aniracetam and balance it out, selegiline will increase levels of PEA, pea will act as an excitatory neurotransmitter and also modulates ampa receptors, so it should theoretically work well with aniracetam.

Well PEA is like the body's amphetamine, which is known to increase dopamine/norepinephrine release and inhibit its re-uptake. The "focusing" effect from stimulants is said to be a decrease in NMDA receptors and increase in AMPA receptors in the PFC. I have yet to round up a study on PEA and AMPA interaction (I did look).

Are you sure Selegiline lowers serotonin and doesn't raise it? I feel pretty darn sedated from coffee and carbs.

[X_Danny_X]

Doesn't Phenethylamine (PEA) gets destroyed by your stomach if taken orally? Also when you guys are saying DPLA, you are talking about Phenylalanine??

Yes and yes. The stomach acid tends to do a number on DLPA. Taken sublingually multiplies the effects by a factor of two or more. It tastes like minty ass, so I try not to take sublingually if I don't need to.

man i do my best to avoid anything that is best taken sublingually. tasting the true taste of these compounds is nastyyyyyyyyyyyyyyyy. Phenylalanine is a precursor to Tyrosine.

why not just take Tyrosine since it is responsible for the neurotransmitters dopamine, norepinephrine and epinephrine.

The D-isomer inhibits the break down of endorphins, which causes a dopamine increase in the midbrain (according to WIki). It is not considered a precursor to Tyrosine. The L-isomer is converted into Tyrosine and is considered a "time-relase" dopamine precursor. Thus, DL-Phenylalanine tends to be the preferred choice over Tyrosine.

what is equivalent then to DPLA in terms of being just effective? I really dont want to put another substance under my tongue. Getting used to the taste of Noopept was hard enough. The way it sounds, DPLA is ten times worse.

so far there was mention of TMG and a couple of others. if the goal is to increase Selegiline's effects, isn't Hordenine a good candidate a well?

[Ampa-omega]

here

A synergy you may want to try is selegiline with aniracetam, selegiline supposedly lowers seretonin levels, while aniracetam is a 5ht agonist/modulator not sure which exactly, selegiline would remove some of the anxiolytic quality from aniracetam and balance it out, selegiline will increase levels of PEA, pea will act as an excitatory neurotransmitter and also modulates ampa receptors, so it should theoretically work well with aniracetam.

Well PEA is like the body's amphetamine, which is known to increase dopamine/norepinephrine release and inhibit its re-uptake. The "focusing" effect from stimulants is said to be a decrease in NMDA receptors and increase in AMPA receptors in the PFC. I have yet to round up a study on PEA and AMPA interaction (I did look).

Are you sure Selegiline lowers serotonin and doesn't raise it? I feel pretty darn sedated from coffee and carbs.

while i was searching on whether deprenyl increases serotonin a few weeks back, i stumbled upon somewhere where it was mentioned that it lowers serotonin levels, it may be dose dependent though, as some sites mention increases of serotonin at higher doses, i will try and find where i read about it lowering serotonin, cant remember exactly where it was mentioned.

here is a mention
http://www.selegilin.../serotonin.html

Edited by Ampa-omega, 01 December 2011 - 03:32 AM.

[nupi]

I would be surprised if it did not increase Serotonin, at the very least once you go into the dosage range where it loses MAO-B specificity...

It would open up interesting options though as you could stack it with SSRI which is usually a big nono with any MAOI

I wonder if you could stack it with Bupropion though - it is not entirely clear to me whether that one is serotonergic or not

Edited by nupi, 01 December 2011 - 04:15 AM.