We’ve been taking 1.25mg Selegiline every morning for close to 2 years now.
Since I’m nearly perfect anyways, it’s hard to tell if it’s made a difference LoL!
But our youngest son (40y/o) who has pretty high ADHD takes 2.5mg every day and after about 6 months offered his unsolicited opinion, “it’s working! and I find better focus and more clarity of thought”
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LukeMV
#82
You split the 5mg tabs into quarters I imagine? That’s what I do as well.
Although, I’ve seen some say it’s better to take sublingual. I’m not sure how accurate that is.
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adssx
#83
Sublingual is way more potent. 1.25 mg sublingual is like 5 mg orally from what I remember.
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Yep, sort of, 1/2 for the son and 1/4 each for the Boss and I 
so 1 tab per day.
adssx
#85
When you (or your son) don’t take selegiline (intentionally or because you forgot), did you notice any withdrawal/rebound symptoms?
2 Likes
At the 1.25mg dose I don’t notice anything taking it nor if I miss a dose or 2.
Our son at 2.5mg does notice the effect and if he misses a dose.
A number of our interventions are “brain” focused
Occasionally, maybe a couple times a month I take 2.5mg but I don’t notice anything at that dose either. Since I don’t have a “condition” that this drug would technically benefit I never expected to notice much but was looking for “something” but nothing.
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adssx
#87
Thanks.
So you take it only for its purported longevity properties?
What are your other brain focused interventions?
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I’ve tried a couple nootropics but never noticed much.
Besides sleep, exercise and a decent diet we do a few things;
- a variety of basic supplements
- tVNS
- creatine
- selegiline
- caffeine
- microdose golden teacher 'shrooms a couple times a year
- low dose THC (oral)
- GLP1-R’s
- growth hormone secretagogues
- DHEA
- melatonin
Will be trying a few peptides in the New Year
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I’ve been taking it orally most days since I was in my fifties (late 60s now). Started off with 1/4 of a 5 mg tablet, gone up to 1/2 2.5mg after age 60. Don’t feel any different but am taking it on the evidence we have so far.
Just had a list of the normal NHS blood tests. Doc phoned up to give me the results, seemed slightly incredulous that everything was in normal range, except for too much testosterone.
5 Likes
adssx
#90
A novel neuroprotective mechanism of selegiline by suppressing the pro-apoptotic activity of protein disulfide isomerase 2025
Beyond its role in MAO-B inhibition, selegiline exhibits neuroprotective effects, potentially through anti-apoptotic mechanisms. Recent studies have shown that selegiline can prevent mitochondria-dependent apoptosis [1], whereas the specific molecular targets for such effect remain elusive.
In summary, we leveraged selegiline’s unique N-propargylamine moiety for ABPP and identified PDI as a key target in our study. Selegiline covalently binds to PDI at residues S32, C56, and K207, notably within the catalytic CGHC motif at C56, thereby inhibiting PDI’s enzymatic activity. Typically, PDI plays a protective role in the unfolded protein response (UPR), but it can also exhibit pro-apoptotic functions in neurodegenerative diseases, leading to mitochondrial outer membrane permeabilization (MOMP) and cell death. Our findings reveal that selegiline-mediated inhibition of PDI prevents MOMP in isolated mitochondria and rescues ER stress-induced apoptosis in MN9D cells, thereby unveiling a novel aspect of its neuroprotective mechanism.
5 Likes
Neo
#91
@adssx So perhaps on and off cycles of some short - would not want it to stop good apoptosis?
adssx
#92
I don’t know enough about this.
What I know is that selegiline 1.25 mg (1/4 of a pill) lifted my mild depression and apathy after a few weeks. I stopped after a month, and 2 months later my mental health is still great. (Why did I stop? It increased my blood pressure and I’m not sure about its long-term use. I also wanted to see if I could do without it and the test was successful.) So given its longevity + neuroprotection potential, low-dose selegiline might be the best antidepressant at least for mild symptoms? If my depression comes back I’ll try again selegiline (effectively cycling it as needed).
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