16 replies to this topic

[fall]

I successfully used Selegiline (high dose) to treat depression and to some extent ADHD for many years. I recently switched to another MAOI but I would like to continue low-dose selegiline for its many positive effects on drive, creativity, neuroprotection, reversal of brain damage from abuse, and longevity. Thing is I bought a lot of pharma-grade Selegiline, only to later get it prescribed, this led to quite the overstock... none of it has expired so with my current dose it will last me well beyond 10 years, more like 20+. Does Selegiline retain its potency for this long in sealed bottles and boxes?

Also, ideally I wish I could trade some with any ADHD stimulant as my current MAOI does little for my ADHD. It seems, however, that this is not technically legally feasible? Are there any small nootropic/longevity groups/communities based in Sweden or the EU where I could check with people? Even if I keep everything for myself it is still not very practical when it comes to travel..

Edited by fall, 26 December 2024 - 10:51 AM.

[gamesguru]

The lowest bond dissociation energy occurs between the nitrogen atom and propargyl group (at the C-N bond, approximately 52 kJ/mol). The molecule likely deprotonates, hydrolyzes, or undergoes oxidative deamination/cleavage. Decomposition would result in a deacetylenated L-methamphetamine complex (such as benzylmethylamine) under prolonged exposure to normal atmospheric conditions (21% oxygen and 1.5% water vapor).
 
Exposure to UV light may further catalyze decomposition through photolytic pathways.
 
Even if stored ideally (under an inert gas and away from light, heat, or moisture), it will slowly decompose. I wouldn't expect more than 50% potency after 10 years and perhaps 35% after 20 years.

[fall]

The lowest bond dissociation energy occurs between the nitrogen atom and propargyl group (at the C-N bond, approximately 52 kJ/mol). The molecule likely deprotonates, hydrolyzes, or undergoes oxidative deamination/cleavage. Decomposition would result in a deacetylenated L-methamphetamine complex (such as benzylmethylamine) under prolonged exposure to normal atmospheric conditions (21% oxygen and 1.5% water vapor).

Exposure to UV light may further catalyze decomposition through photolytic pathways.

Even if stored ideally (under an inert gas and away from light, heat, or moisture), it will slowly decompose. I wouldn't expect more than 50% potency after 10 years and perhaps 35% after 20 years.

Many thanks!
I appreciate your detailed response and direct answer. Interesting stuff albeit beyond my basic understanding of chemistry.
Now, you made me curious and left me with more questions ha! But the main one I had was answered so feel free to respond per convenience if you can!
Would it be correct to say that the decomposition the substance undergoes results in a different substance with potentially other physiological effects, or would it be more correct to say it is a lesser effective of the same substance? Perhaps difficult to answer and I wouldn't be surprised if the nature of the decomposition process varies. I guess the most relevant question would be, is it possible for a non-toxic substance such as selegiline to become toxic in a decomposed form.- in one way or the other through the processes described ("molecule likely deprotonates, hydrolyzes, or undergoes oxidative deamination/cleavage")?

[fall]

I keep my medication away from heat and light, and to my knowledge under quite dry conditions. The bulk of it is also sealed so atmospheric conditions ought to be quite stable and mostly limited to either tightly factory packed blisters or sealed pharma pill bottles(?). I guess I am comfortable using it for upwards 10 years so long as it is harmless. The neuroprotection/nootropic/longecity effects from selegiline appears to work even in small concentrations.
I would honestly use a daily large dose like used to if it wasn't for the potent MAOI, since I already take a MAOI...
I'll keep taking low-dose for now and see if perhaps I can find someone in need!

Edited by fall, 30 December 2024 - 11:12 PM.

[gamesguru]

the decomposition the substance undergoes results in a different substance with potentially other physiological effects, or would it be more correct to say it is a lesser effective of the same substance?

 

If stored in foil packs, Selegiline should stay fresh for a while. It will lose potency over the years (hard to say how much, anywhere from 5 to 50%), but it's unlikely to decompose into toxic constituents.

 

There's not much data on Selegiline's shelf life or decomposition products. You can, however, read about some potential byproducts with the related compound, amphetamine, albeit under high temperature, pyrolytic conditions. The phenolic 6-carbon ring is stable, so it's not surprising to see byproducts like benzylethyltrimethylammonium (BEMA) and trans-beta-methylstyrene. We'd likely see similar byproducts with Selegiline stored over a long period. There could also be some acetylenic amine byproducts (from the other end of the molecule) and potentially some H+, CO, or CO2 gas. The thing to remember is Selegiline's potency — it's active at a few milligrams per week! Any decomposition byproducts would likely be less potent and exceedingly unlikely to affect anything at that level of exposure.
 

Analysis of pyrolysis products of methamphetamine - PubMed

https://pubmed.ncbi....h.gov/15538957/

 

 

For what it's worth, amphetamine-related chemicals tend to be remarkably stable. I've heard it argued that amphetamine would be viable if left next to a mummified Pharaoh in the Great Pyramids 4,500 years ago (but that may be a slight exaggeration).

Stability over 32 months for amphetamine is only slightly outside the error bounds for measurements. Selegiline is likely less stable, but it's unclear to what degree.

 

Stability of seized amphetamine during 32 months of storage - ScienceDirect
https://www.scienced...66591072030044X

 

It was observed a loss of purity during the storage time of 1,59 % at 12 months, 2,34 % at 24th months, and 6,43 % at 32 months. The percentual change found at 12 months and 24 months cannot be said to be a significant result since it is within the error rate associated, according to the Horwitz equation (2%), and the estimated error of the technique (5%).

 

 

You might also encounter some trace impurities from the synthesis, which you can read about here for amphetamine. Researchers have studied many of these without cause for alarm. Production impurities in Selegiline would differ slightly, but (again) it's doubtful they would pose any significant human risk, especially at the levels seen.

 

Impurities in illicit amphetamine: a review | UNODC - Bulletin on Narcotics - 1981 Issue 3 - 004

https://www.unodc.or..._3_page005.html

 

Edited by gamesguru, 31 December 2024 - 06:38 AM.

[fall]

If stored in foil packs, Selegiline should stay fresh for a while. It will lose potency over the years (hard to say how much, anywhere from 5 to 50%), but it's unlikely to decompose into toxic constituents.

There's not much data on Selegiline's shelf life or decomposition products. You can, however, read about some potential byproducts with the related compound, amphetamine, albeit under high temperature, pyrolytic conditions. The phenolic 6-carbon ring is stable, so it's not surprising to see byproducts like benzylethyltrimethylammonium (BEMA) and trans-beta-methylstyrene. We'd likely see similar byproducts with Selegiline stored over a long period. There could also be some acetylenic amine byproducts (from the other end of the molecule) and potentially some H+, CO, or CO2 gas. The thing to remember is Selegiline's potency — it's active at a few milligrams per week! Any decomposition byproducts would likely be less potent and exceedingly unlikely to affect anything at that level of exposure.



For what it's worth, amphetamine-related chemicals tend to be remarkably stable. I've heard it argued that amphetamine would be viable if left next to a mummified Pharaoh in the Great Pyramids 4,500 years ago (but that may be a slight exaggeration).

Stability over 32 months for amphetamine is only slightly outside the error bounds for measurements. Selegiline is likely less stable, but it's unclear to what degree.



You might also encounter some trace impurities from the synthesis, which you can read about here for amphetamine. Researchers have studied many of these without cause for alarm. Production impurities in Selegiline would differ slightly, but (again) it's doubtful they would pose any significant human risk, especially at the levels seen.

Very well then, I feel like I can continue using my current stock for quite some time then. As you mentioned, selegiline's efficacy even at a few mg per week (for my intended use i.e., longecity, neuroprotection etc.) will likely mean that any loss of potency will be insignficant.

Interestingly, (anecdotally) daily dosing of 10 mg was quite effective for some years as an antidepressant, doses between 15mg - 35mg did not appear to provide any additional benefit. In order to get a significant anti-depressant effect one might want to consider the transdermal solution or possibly 10 mg oral alone or along with very low (<1.3mg) sublingual dose.

Amphetamine is such an interesting substance.

Thanks for taking the time to provide sources I shall give them a read.

[Danniel]

@gamesguru  would it be okay to dissolve the Selegiline in water (or San Pelegrino) for an easier dosage? I am currently dissolving a 5mg pill in a bottle of 200ml water to take a 50ml solution / 1mg Selegiline every other day.

 

I was worried that in the solution (with sparkling water) the properties of Selegiline might change. Would appreciate your expert opinion.

[gamesguru]

Very well then, I feel like I can continue using my current stock for quite some time then. As you mentioned, selegiline's efficacy even at a few mg per week (for my intended use i.e., longecity, neuroprotection etc.) will likely mean that any loss of potency will be insignficant.

Interestingly, (anecdotally) daily dosing of 10 mg was quite effective for some years as an antidepressant, doses between 15mg - 35mg did not appear to provide any additional benefit. In order to get a significant anti-depressant effect one might want to consider the transdermal solution or possibly 10 mg oral alone or along with very low (<1.3mg) sublingual dose.

Amphetamine is such an interesting substance.

Thanks for taking the time to provide sources I shall give them a read.

 

I, too, tried larger doses, but in the sublingual form. I tried taking 6-7 mg sublingually throughout the day, but I found the high degree of dopamine signaling too unpleasant to maintain.

I take it every five or so days now, around 2-4 mg each time. It gives some benefits that way and complements my other stimulants well .

I found that Saffron and Tropoflavin (or Eutropoflavin) had equally powerful, if not better, antidepressant effects. Supposedly, there is some concern about skin cancers or adrenal diseases surrounding long-term, high-dose Selegiline therapy. Vets prescribe Selegiline for pituitary Cushing's disease in dogs; perhaps it's not surprising that it can have powerful (and sometimes nefarious) activity on the adrenal system.

 

 

@gamesguru  would it be okay to dissolve the Selegiline in water (or San Pelegrino) for an easier dosage? I am currently dissolving a 5mg pill in a bottle of 200ml water to take a 50ml solution / 1mg Selegiline every other day.

 

I was worried that in the solution (with sparkling water) the properties of Selegiline might change. Would appreciate your expert opinion.

 

I tried dissolving 65 mg of Selegiline HCl in a 3 mL eyedropper of water (or ethanol). For me, it was not even sparingly soluble at room temperature.

I'm truthfully not sure about the interactions between Selegiline and mineral water. I know, for example, that LSD is sensitive to chlorinated solvents, especially when the solvent is basic, but I don't know what it decomposes into or what the biological effects might be. I reckon loads of people drink tap water with their Adderall, and there hasn't been any investigation into harmful byproducts produced by the chlorine. Long-term storage next to other things in mineral water (low concentrations of calcium and magnesium ions and other dissolved metals) should similarly be safe; I can't see anything toxic forming that way. But to be safe, I wouldn't store it that way for long. Try to consume it within a few days after dissolving. Try to keep it refrigerated and away from light. Consider using distilled water as a precaution.

 

If you're getting 5 mg tablets, splitting them in half is easy. Splitting them into quarters is a little trickier, but it's okay if the pieces are uneven — it doesn't have to be an exact science .

[gamesguru]

I also forgot (in my original analysis) that Selegiline is practically always sold as the hydrochloride salt Selegiline HCl.

 

Here are some simulated decay times for other substances. This study is from 1991, but it lists Amphetamine as stable for 18 years (at 5 °C).

 

Determination of Product Shelf Life and Activation Energy for Five Drugs of Abuse | Wayback Machine
https://web.archive..../3/398.full.pdf
(page 401)

 Screenshot from 2025-01-11 22-03-59.png   59.13KB   0 downloads

 

 

Regarding the adrenal glands, I found that it's contraindicated for certain adrenal tumors and hyperthyroidism.

 

Selegiline - Oral | HealthLink BC
https://www.healthli...selegiline-oral

PRECAUTIONS

Before using this medication, tell your doctor or pharmacist your medical history, especially of:

- a certain kind of adrenal gland tumor (pheochromocytoma)
- overactive thyroid (hyperthyroidism)

[fall]

I also forgot (in my original analysis) that Selegiline is practically always sold as the hydrochloride salt Selegiline HCl.

Here are some simulated decay times for other substances. This study is from 1991, but it lists Amphetamine as stable for 18 years (at 5 °C).



Regarding the adrenal glands, I found that it's contraindicated for certain adrenal tumors and hyperthyroidism.

Although I belive that selegiline in low-moderate dose will have beneficial effects in the majority of the healthy aging population, whenever cancer is present or at risk - a high level of precaution might be in place. If there is a cause for concern, such as a tumor present or very high genetic predisposition for cancer, one may want to consider the many mechanisms of action the drug exerts, unless there is a high benefit over risk ratio it might be better to avoid selegiline. Conversely, a high benefit over risk would be someone at risk of developing a neurodegenerative disease e.g., parkinson or alzheimer. Adrenal- -cancers or -dysfunction does indeed appear to be a potential contraindication. I speculate that the apoptotic and antiapoptotic properties as well as the catecholaminergic enhancing effect is partially why. There are case reports of selegline (more often in combination with other drugs) causing transient pseudopheochromocytoma. With that said, given the widespread and well-documented use of selegiline, with its use being especially high in older individuals and persons with serious neurodegenerative conditions, the lack of case reports showing any serious adverse events that one can directly attribute to the drug is refreshing and makes it stand out at the forefront of drugs capable of making us healthier. I think it is important to understand (as you mentioned earlier) that the drug is rather effective at very low dose. Indeed, some studies suggest 100-1000 times smaller than a commonly used dose still help slow neuronal degeneration among other benefits while likely avoiding any potential adverse effect. I will add some sources later.

[fall]

I also forgot (in my original analysis) that Selegiline is practically always sold as the hydrochloride salt Selegiline HCl.

Here are some simulated decay times for other substances. This study is from 1991, but it lists Amphetamine as stable for 18 years (at 5 °C).



Regarding the adrenal glands, I found that it's contraindicated for certain adrenal tumors and hyperthyroidism.

Interesting to see how vastly different the projected stability is among different substances. 18 years is likely a good indicator. I'd be happy if I can make my stock last x2 that time so next re-stock happens in time for my retirement. The decay time study is actually a good indication that most medicines can likely be stocked with emergency kits/pantry and be expected to still work in case of disaster. THC the master of all of course dwarfs everything else. It would be interesting to see a stability comparison in different cannabinoids. I am guessing most of them would be quite stable for long periods of time (in isolated form away from plant material). In the plant itself, one specific cannabinoid level(CBN) actually increases in aging cannabis plant material. I wonder why they decided to measure cocaine's inactive metabolite benzoylecgonine and not cocaine.



Here are some studies relating to my previous post:

Pseudophaeochromocytoma in parkinsonian patient treated with fluoxetine plus selegiline
https://pubmed.ncbi....ih.gov/8094789/

Pseudopheochromocytoma in a parkinsonian patient treated with selegiline
https://pubmed.ncbi....ih.gov/7740240/

R(-)-deprenyl potentiates dopamine-induced cytotoxicity toward catecholaminergic neuroblastoma SH-SY5Y cells

"The results show that both dopamine and L-DOPA are quite cytotoxic toward SH-SY5Y cells. R(-)-deprenyl rather than reducing this dopamine-induced toxicity actually enhances it."

https://www.scienced...980114?via=ihub

(-)-Deprenyl, a selective MAO-B inhibitor, with apoptotic and anti-apoptotic properties
"Our findings support the view that 100, or even 1000 times lower dose of (-)-deprenyl can be offered in human therapy to protect, or slow down neuronal degeneration, than it is presently used. With low dose of the drug the dopaminergic adverse events could be avoided, while anti-apoptotic activity might be preserved."
https://www.scienced...001025?via=ihub

Edited by fall, 18 January 2025 - 10:22 PM.

[gamesguru]

Yep. I'm unsure if it's smoke and mirrors or reliable science, but other studies report benefits from a "super low dose."

 

(−)Deprenyl and (−)1-phenyl-2-propylaminopentane, [(−) PPAP] act primarily as potent stimulants of action potential — transmitter release coupling in the catecholaminergic neurons - ScienceDirect
https://www.scienced...024320596000148

 

The activity of the catecholaminergic neurons in the rat brain is enhanced significantly 30 min after the subcutaneous injection of very small doses of (−)deprenyl (threshold doses: 0.01 mg/kg for noradrenergic neurons and 0.025 mg/kg for dopaminergjc neurons). As a catecholaminergic activity enhancer (CAE) substance (−)deprenyl is about ten times more potent than its parent compound, (−)methamphetamine. While the (+)methamphetamine is 3–5 times more potent than (−)methamphetamine in releasing catecholamines, the (−)methamphetamine is the more potent CAE substance.

 

 

 

the widespread and well-documented use of selegiline, with its use being especially high in older individuals and persons with serious neurodegenerative conditions, the lack of case reports showing any serious adverse events that one can directly attribute to the drug is refreshing

 

The only issue with this is that most patients taking a larger dose are Parkinson's patients who will likely (sadly) be dead in 10 years and not contribute much to the long-term/longitudinal safety analysis.

The FDA approved Selegiline for depression in 2006, and its use here remains relatively uncommon. As of now, it's not clear how safe it is in the long run.

 

 

[fall]

Yep. I'm unsure if it's smoke and mirrors or reliable science, but other studies report benefits from a "super low dose."





The only issue with this is that most patients taking a larger dose are Parkinson's patients who will likely (sadly) be dead in 10 years and not contribute much to the long-term/longitudinal safety analysis.

The FDA approved Selegiline for depression in 2006, and its use here remains relatively uncommon. As of now, it's not clear how safe it is in the long run.

Thanks for adding that study.

I agree that evaluating long-term effects in that specific pool is problematic. Selegiline has been used in various contexts for a relatively long time though, FDA approved it for parkinson in 1989, several European countries were many years earlier. There was also a small fraction of people who believed in various purported pro-sexual and nootropic effects, which is quite notable imo since many studies now support these claims. Joseph Knoll, one of the early developers of selegline, BPAP, and PPAP.. is thought to have used selegiline in his last 28 years. I am sure there are a number of case reports indicating long-term safety. My first few years of use was coincidentally a pretty wild period of my life, I feel as though selegiline might have shielded some of the potential harm and aging that could have come from that time, just a crazy personal theory ha! Surely, what saved me most was regular exercise and being fit.

[gamesguru]

Thanks for adding that study.

I agree that evaluating long-term effects in that specific pool is problematic. Selegiline has been used in various contexts for a relatively long time though, FDA approved it for parkinson in 1989, several European countries were many years earlier. There was also a small fraction of people who believed in various purported pro-sexual and nootropic effects, which is quite notable imo since many studies now support these claims. Joseph Knoll, one of the early developers of selegline, BPAP, and PPAP.. is thought to have used selegiline in his last 28 years. I am sure there are a number of case reports indicating long-term safety. My first few years of use was coincidentally a pretty wild period of my life, I feel as though selegiline might have shielded some of the potential harm and aging that could have come from that time, just a crazy personal theory ha! Surely, what saved me most was regular exercise and being fit.

 

You're welcome. Please note that interspecies differences in biochemistry can profoundly affect drug responses. For example, rodents have markedly less MAO-B in their brains and metabolize the drug faster, which results in a need for larger doses. It's possible that ultra-low dose Selegiline activates different systems (unrelated to MAO-B) and that these systems are more sensitive in rodents. In that case, humans wouldn't necessarily see the same benefits. We don't know.

 

The pro-sexual effects are relatively well-established, but I don't view them as a necessarily good thing. There's a moderate association between Selegiline use and impulse control disorders (hypersexuality, compulsive shopping, and pathological gambling). The weird thing is that Selegiline can have unpredictable effects here — sometimes it can improve self-control, other times it diminishes it. At least for me, the nootropic, motivating, and energy-boosting effects diminished after the honeymoon phase.

 

The sub-milligram doses used for life extension and nootropic purposes are likely safe. The uncertainty lies more so in the doses used for Parkinsonism and Depression, which is ~10 mg daily. More contemporary researchers have cast doubt on the veracity and significance of the early studies on life extension, with some studies failing to replicate the benefits — and we don't know if these benefits translate to humans in a significant way.

 

It's possible that Selegiline diminished stress and promoted energy for you during that phase in your life. There are many potential ways it can help.

[fall]

I am aware of the link between selegiline use and impulse control disorders. I believe this is true but perhaps selegiline's role in this is more of a case of facilitating a trigger in certain individuals. Perhaps a person is more prone to this if bipolar or schizophrenic. The pro-sexual effects I referred to was benefits such as improved sexual performance, increased arousal, and perhaps most importantly a slowing down in the decline of sexual activity. 

 

Yes you are right, indeed the study does make use of wistar rats. Although rats and humans will certainly have different outcomes, they do mention some effects that carry over:

 

"Very low doses of (-)deprenyl increase catecholtiergic activity in the brain (1). 

This catecholaminergic activity enhancer (0%) effect was assumed to be responsible for the 

peculiar consequences of long lasting treatment with (-)deprenyl (2,3,4), that is an aging rat performs better sexually and lives longer than its untreated control (5,6,7). Likewise, a (-)deprenyl 

treated Parkinsonian patient deteriorates slowly (8,9,10) and lives longer"

 

 

Also interesting:

"Why does, however, as shown in Fig.2, a small, 1 mg/kg dose of (-)PPAP make a tetrabenatie treated rat capable to escape successfully in the shuttle box? In the light of the preceding analysis, our assumption is that (-)PPAP stimulates coupling of action potential to 

transmitter release in the catecholaminergic neurons, thus, a higher number of vesicles leave the 

neurons in response to stimulation, suffient for successful performance in the shuttle box. Since 

action potential induced increase in cytosolic Ca*+ is required for the fusion of the transmitter 

vesicles with the plasma membrane, (-)deprenyl and (-)PPAP may increase cytosolic Ca*+ levels in 

response to stimulation"

 

 

 

"All in all, the results presented are substantially supporting the conchrsion that the peculiar 

CAE effect exerted by (-)deprenyl and (-)PPAP in the pharmacologically active lowest dose-range 

is realized via the stimulation of action potential-transmitter release coupling in the 

catecholaminergic neurons of the brain by increasing cytosolic Car+ levels to stimulation. The assumption is that, in very low doses, (-)deprenyl and (-)PPAP act either by mimicking the effect of or activate or mobilize hitherto undetected, highly potent endogenous 

CAE substances. The endogenous CAE substances, for which circumstantial evidence was presented previously (12,21), are thought to regulate the catechohtminergic activity of the brain. This is the direct on for future work."

 

Edited by fall, 25 January 2025 - 10:52 PM.

[gamesguru]

I am aware of the link between selegiline use and impulse control disorders. I believe this is true but perhaps selegiline's role in this is more of a case of facilitating a trigger in certain individuals. Perhaps a person is more prone to this if bipolar or schizophrenic. The pro-sexual effects I referred to was benefits such as improved sexual performance, increased arousal, and perhaps most importantly a slowing down in the decline of sexual activity. 

 

Yes you are right, indeed the study does make use of wistar rats. Although rats and humans will certainly have different outcomes, they do mention some effects that carry over:

 

"Very low doses of (-)deprenyl increase catecholtiergic activity in the brain (1). 

This catecholaminergic activity enhancer (0%) effect was assumed to be responsible for the 

peculiar consequences of long lasting treatment with (-)deprenyl (2,3,4), that is an aging rat performs better sexually and lives longer than its untreated control (5,6,7). Likewise, a (-)deprenyl 

treated Parkinsonian patient deteriorates slowly (8,9,10) and lives longer"

 

I agree. Selegiline only has a mild effect in causing/worsening impulse control disorders, but it's an effect nonetheless. My point was that "increased [sexual] arousal" is not always seen as a good thing, for example, if you're single or non-monogamous. If you have a wife and want to have sex with her more often, then sure, it's a good thing.

 

Parkinson's patients deteriorating more slowly is probably due to reduced dopamine auto-oxidation, which lessens the stress on dopamine neurons and improves the prognosis of Parkinson's patients. The study does not establish beyond a reasonable doubt that Selegiline's utility in treating Parkinson's disease is due to a CAE effect.

 

I'm skeptical that Selegiline has a strong CAE effect at doses below the threshold for MAO-B inhibition. I've microdosed it under 0.5 mg and haven't felt much. The CAE effect would only last 4-6 hours, correct (unlike the MAO-B inhibition, which lasts a week or more)?

[gamesguru]

Correction: The phenolic 6-carbon ring is not 100% stable. It is susceptible to hydroxylation at the 4-carbon position.