Deprenyl (Selegiline) and MDMA

[Advanc3d]

yeah 1 mg/day oral is well within competitive maoi-b. you'd have to be on probably 15/day oral to get mao-a inhibition in 1 week, and even then it's a stretch. i've taken 10/ every other day for weeks with no mao-a inhibition (didn't have reaction to tyramine). though when i ate chocolate it got me every so slightly buzzed =) (the pea). i think it's a great alternative to just increasing doses of stimulants. deprenyl has been proven to be neuroprotective for mdma use. you're not going to run the risk of serotonin syndrome because of the deprenyl's mao inhibition. if you take a dose low enough to be competitive mao-b (to be safe <10mg), what can happen is the dopaminergic aspect of mdma is potentiated and you go into hypertensive crisis because of that. serotonin syndrome would be independently based on your mdma dose and your tolerance. if you really want to be safe, you should start at even lower than 50% of your average mdma dose; 25% would be good, and take between 1 and 2.5 mg deprenyl. just make sure you don't keep redosing with deprenyl over the period of a roll. that will make hypertensive crisis much more likely.

i really have to reiterate. i only have experience with deprenyl + d-amp/ methylphenidate, not mdma or other psychedelics.

i guess if things go badly, you could just down a lot of fruit juice or something acidic to speed up the mdma metabolism.

don't take any sedatives on the downer though (that is if there is one: the reason you're taking the deprenyl is to avoid it). benzo's, barbiturates, opiods, can and probably will react unpredictably with deprenyl.

thanks for your reply, everything makes sense now
i was thinking i would just take a large dose of l-theanine (500mg) if i need to relax from it

 

[shamus]

Any neuroprotection offered by the selegeline might be offset by increased hypertermia.

Hyperthermia?


I thought temperature regulation is 5HT mediated.

 

[Ell]

Hyperthermia?


I thought temperature regulation is 5HT mediated.

Yes, but 5-HT synthesis isn't affected by deprenyl much, if at all.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6SYT-4KD583C-2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=34ce0d582c86392b301c07dccd682048

There is no one decisive cause of MDMA neurotoxicity. Obviously it's caused by overdose, but one theory that explains why deprenyl is neuroprotective is that when MDMA is taken in high doses, much of the brain's serotonin is released into the synaptic cleft via reverse pump action, and much dopamine is released as well; so, when the dopamine is ready to be reabsorbed, it will go to the closest open terminal, in this case, often a serotonin terminal because so many are empty. Then MAO-B will deaminate the excess DA into free radicals, which will clot in the serotonergic terminals, and peroxidize (damage) their lipid membranes. Hence nervous damage.

If MAO-B inhibition is underway, the dopamine won't have the chance to be pumped into the serotonergic terminals. Hence neuroprotection.

And let me reiterate, you will NOT go into hypertensive crisis when mao-a is not being inhibited, unless purely from MDMA overdose. All the deprenyl will do in that case is reduce that damage by holding the dopamine back from serotonin terminals. Neuroprotection.

The key is to not be using MDMA in large quantities in the FIRST place. So many people use ridiculous quantities to induce profound effects. If you can just be satisfied with a lower dose, you will go a long way to preserving your brain's neurotransmitters.

 

[Advanc3d]

Yes, but 5-HT synthesis isn't affected by deprenyl much, if at all.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6SYT-4KD583C-2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=34ce0d582c86392b301c07dccd682048

There is no one decisive cause of MDMA neurotoxicity. Obviously it's caused by overdose, but one theory that explains why deprenyl is neuroprotective is that when MDMA is taken in high doses, much of the brain's serotonin is released into the synaptic cleft via reverse pump action, and much dopamine is released as well; so, when the dopamine is ready to be reabsorbed, it will go to the closest open terminal, in this case, often a serotonin terminal because so many are empty. Then MAO-B will deaminate the excess DA into free radicals, which will clot in the serotonergic terminals, and peroxidize (damage) their lipid membranes. Hence nervous damage.

If MAO-B inhibition is underway, the dopamine won't have the chance to be pumped into the serotonergic terminals. Hence neuroprotection.

And let me reiterate, you will NOT go into hypertensive crisis when mao-a is not being inhibited, unless purely from MDMA overdose. All the deprenyl will do in that case is reduce that damage by holding the dopamine back from serotonin terminals. Neuroprotection.

The key is to not be using MDMA in large quantities in the FIRST place. So many people use ridiculous quantities to induce profound effects. If you can just be satisfied with a lower dose, you will go a long way to preserving your brain's neurotransmitters.

hold on,
if theres no MAO-B to metabolise the dopamine, wouldnt that cause an overflow of dopamine floating around when MDMA releases them. thus depending on the dose of deprenyl and how much % the MAO-B is inhibited, it will increase the duration and intensity of the peak in a non-serotonergic way untill the dopamine is stored back?

would this be incorrect then?

but then again what we get from pills aren't always pure mdma, nearly all the time in australia its laced with amphetamine of some kind, and from what i gathered, speed + mdma = super neurotoxic

 

[grue]

And let me reiterate, you will NOT go into hypertensive crisis when mao-a is not being inhibited, unless purely from MDMA overdose. All the deprenyl will do in that case is reduce that damage by holding the dopamine back from serotonin terminals. Neuroprotection.

Well, inhibiting MAO-B is going to slow down the metabolism (and increase concentration) of any substituted phenethylamine, right?

The problem is that this adds a real unpredictable element. Less dose control, not that you know how much is really in that pill anyway.

 

[shamus]

I'm not sure if I follow Ell, why would more dopamine equate with less 'having the chance' to interact with the SERT?

I was under the impression the neuroprotective qualities of deprenyl rest in the reduced amount of dopamine that ends up oxidised, & I thought this held true for MDMA + dep too.

 

[Advanc3d]

With food its written that bioavailability is increased by threefolds.

is it a good idea to take a low dose (1.5mg) with food or without for the desired effects of topic subject

 

[Coolio]

http://www.jneurosci.org/cgi/content/full/27/38/10203

Monoamine Oxidase-B Mediates Ecstasy-Induced Neurotoxic Effects to Adolescent Rat Brain Mitochondria

Ema Alves,1,3 Teresa Summavielle,1,5 Cecília Juliana Alves,1 Joana Gomes-da-Silva,1,6 José Custódio Barata,7 Eduarda Fernandes,2 Maria de Lourdes Bastos,3 Maria Amélia Tavares,1,4 and Félix Carvalho3

1Neurobehaviour Unit, Instituto de Biologia Molecular e Celular, 2Physical-Chemistry Department and 3Toxicology Department, Faculty of Pharmacy, REQUIMTE, 4Institute of Anatomy, Medical School of Porto, University of Porto, 4099-002 Porto, Portugal, 5Departamento de Ciências Biomédicas, Escola Superior de Tecnologia da Saúde, Instituto Politécnico do Porto, 4000-294 Porto, Portugal, 6Escola de Saúde, University of Aveiro, 3180-193 Aveiro, Portugal, and 7Biochemistry Department, Faculty of Pharmacy, University of Coimbra, 3000-295 Coimbra, Portugal


Abstract
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References

3,4-Methylenedioxymethamphetamine (MDMA)-induced neurotoxicity and the protective role of monoamine oxidase-B (MAO-B) inhibition were evaluated at the mitochondrial level in various regions of the adolescent rat brain. Four groups of adolescent male Wistar rats were used: (1) saline control, (2) exposed to MDMA (4 x 10 mg/kg, i.p.; two hourly), (3) treated with selegiline (2 mg/kg, i.p.) 30 min before the same dosing of MDMA, and (4) treated with selegiline (2 mg/kg, i.p.). Body temperatures were monitored throughout the whole experiment. Animals were killed 2 weeks later, and mitochondria were isolated from several brain regions. Our results showed that "binge" MDMA administration causes, along with sustained hyperthermia, long-term alterations in brain mitochondria as evidenced by increased levels of lipid peroxides and protein carbonyls. Additionally, analysis of mitochondrial DNA (mtDNA) revealed that NDI nicotinamide adenine dinucleotide phosphate dehydrogenase subunit I and NDII (nicotinamide adenine dinucleotide phosphate dehydrogenase subunit II) subunits of mitochondrial complex I and cytochrome c oxidase subunit I of complex IV suffered deletions in MDMA-exposed animals. Inhibition of MAO-B by selegiline did not reduce hyperthermia but reversed MDMA-induced effects in the oxidative stress markers, mtDNA, and related protein expression. These results indicate that monoamine oxidation by MAO-B with subsequent mitochondrial damage may be an important contributing factor for MDMA-induced neurotoxicity.

 

[Advanc3d]

If selegiline were to be combined with Base Amphetamine , how much amphetamine will be dangerous in the combination considering the dopamine issue?

note, selegiline dose <2mg per day (with food, orally)

 

[Advanc3d]

I been taking 1.5mg/day selegiline hcl orally with food for a week.


lastnight i consumed what i suspected to be a average quality of base amphetamine in capsule which i measured out my self to be approx 150mg
results: no potentiation experienced, average amphetamine high.

i took half a good quality MDMA pill after 5 hours of the above consumption.
results: the best high ive had in the past year.


note: i been taking pills for 2 years on a monthly basis so i have a reasonably good tolerance

 

[Advanc3d]

can a moderator fix the spelling of selegiline in the title please?

 

[nuke]

Merged thread (don't think we need another), consider posting your experience to TR

 

[TRPPNASS_DSCOMONKE]

so according to that article the MAOB offered true protection, wow.

 

[blend]

I'm curious as to why you threw amphetamine into the mix, what did you think of it? Any notes on body temp. or heart rate?

 

[spacefacethebassace]

I was just thinking about posting a related topic when I, fortunately, decided to UTFSE.

I think it's pretty well established that low doses of selegiline taken 30-45 minutes before a standard dose of MDMA reduces MDMA-induced neurotoxicity, and that one need not worry about side effects from the combo any more than one need worry about side effects from the MDMA.

However, I'm also interested in taking fluoxetine to reduce MDMA-induced neurotoxicity...selegiline and fluoxetine are contra-indicated...so I won't be taking them concurrently unless I can find some information that says that a single low dose combination is relatively benign.

My question is, and I'm open to pure speculation here: which might be more neuroprotective: fluoxetine+MDMA or selegiline+MDMA?

That is, especially for all of you pharmacologists and pharmacology hobbyists out there, if you had to pick one, which would you pick and why?

 

[nuke]

I think it's pretty well established that low doses of selegiline taken 30-45 minutes before a standard dose of MDMA reduces MDMA-induced neurotoxicity, and that one need not worry about side effects from the combo any more than one need worry about side effects from the MDMA.

I wouldn't exactly say that. Very few people have used this combination and so the safety is still in doubt.

However, I'm also interested in taking fluoxetine to reduce MDMA-induced neurotoxicity...selegiline and fluoxetine are contra-indicated...so I won't be taking them concurrently unless I can find some information that says that a single low dose combination is relatively benign.

My question is, and I'm open to pure speculation here: which might be more neuroprotective: fluoxetine+MDMA or selegiline+MDMA?

That is, especially for all of you pharmacologists and pharmacology hobbyists out there, if you had to pick one, which would you pick and why?

The selegiline and MDMA would probably be more neuroprotective, and fluoxetine tends to inhibit the effectiveness of MDMA by occupying SERT.

But you would probably be fine consuming a large dose of a strong antioxidant (ex. idebenone) a couple hours before MDMA.

If MAO-B inhibition is underway, the dopamine won't have the chance to be pumped into the serotonergic terminals. Hence neuroprotection.

...how?

I have difficultly finding evidence of crossneuronal uptake for dopamine into serotonergic neurons. Dopaminergic neurons will uptake serotonin, however.

 

[thelearner]

I been taking 1.5mg/day selegiline hcl orally with food for a week.


lastnight i consumed what i suspected to be a average quality of base amphetamine in capsule which i measured out my self to be approx 150mg
results: no potentiation experienced, average amphetamine high.

i took half a good quality MDMA pill after 5 hours of the above consumption.
results: the best high ive had in the past year.


note: i been taking pills for 2 years on a monthly basis so i have a reasonably good tolerance

Sorry to bring this back from the dead, but have been doing a lot of research / learning about reducing neurotoxicity and this is a combo which interests me greatly.

I am wondering if you have any additional experiences with this combination and if so, can you provide more commentary on duration, etc.? In particular, my MDMA usage tends to span a period of about 6 hours with consumption of about 3 pills (at a rave) and I would really like an option that provides neuroprotection and allows me to reduce dosage and experience a longer duration from that dosage.

Your experiences and input here would be AWESOME.

 

[SkyblueMolly]

Low doses of selegiline would inhibit only MAO-B. Higher doses of selegiline will inhibit both MAO-B and MAO-A.
MDMA and low doses of selegiline would be safe.
Memantine is neuroprotective.
MDMA plus memantine would be neuroprotective.
MDMA plus low doses of selegiline plus memantine would me even more neuroprotective. Maybe use a lower dose of MDMA.
Don't do MDMA often.
Bromantane can upregulate your receptors epigenetically and enhance your brain's ability to synthesize dopamine, norepinephrine, and serotonin.
Modafinil is good.
Modafinil plus memantine is also good.
Low dose modafinil and selegiline.
Low dose modafinil and selegiline and memantine.
Adderall plus memantine is safe.
There's also adderall plus selegiline plus memantine.
And also adderall plus selegiline plus memantine plus phenylpiracetam and choline.
There's also NSI-189, and 9-Methyl-Beta-Carboline.