[study] Harmine stimulates proliferation of human neural progenitors

[Madrus]

(Mods move to appropriate section)

Harmine stimulates proliferation of human neural progenitors

Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in...

peerj.com

From what I understood:
* neural proliferation cells = used by specific regions in the human adult brain to continuously generate neural cells from
* Antidepressants = more neuronal proliferation cells
* Harmine = more neural progenitor cells (likely by inhibiting the responsible regulating kinase)

our results suggest that harmine exert proliferative effects in human neural progenitors ... by inhibiting DYRK1A. These findings shed light on the possible mechanisms behind the antidepressant effects of Ayahuasca described in patients.

I'd like to know if it's safe in the long run to be messing with a normal person's natural levels of these cells. So many things in the brain. So many complex interactions.

 

[fathomlessness]

I'd like to know if it's safe in the long run to be messing with a normal person's natural levels of these cells. So many things in the brain. So many complex interactions.

Yes, I agree it doesn't sound very enticing to be regarded as a human guinea pig for testing out long term harmala safety but then again just look how stable shamans are? My nag is with the proliferation of mono-amines on psychological stress. They studied MAOI effects on monkeys and found it made them more fidgety and aggressive. All those excess catecholamines bumping around in my brain wrecks my sleeping patterns also, dopamine & epinephrine just doesn't work for sleep time lol. Nevertheless, I am interested in microdosing harmalas for this neurogenesis specifically, although I would need to give my brain a few days down time every now and again.

 

[dreamer042]

It appears melatonin has a similar effect. (1,2) I would expect pinoline, being incredibly close to harmine, both structurally and pharmacologically, and a metabolite of melatonin production, to have similar effects as well.

What I'm getting at here is that we are already producing these substances endogenously every single night when we go to bed. Based on that fact, I've taken on the guinea pig challenge. I've been dosing harmalas with melatonin before bed nearly every night for a few years now and it's be an amazing adjunct to my life.

Timing is everything with harmalas imo/ime. Dosing in the daytime when serotonin and catecholamine levels are high does seem to be associated with irritability, restlessness, anxiety, increased heart rate and blood pressure, etc. When taken at night when melatonin and beta carboline levels are high, it's basically just supercharging what's already happening endogenously. Dreams become moar vivid, sleep is deeper and moar restful, and the mood boosting and antidepressant effects carry over into daily living.

 

[digitalvygr]

It appears melatonin has a similar effect. (1,2) I would expect pinoline, being incredibly close to harmine, both structurally and pharmacologically, and a metabolite of melatonin production, to have similar effects as well.

What I'm getting at here is that we are already producing these substances endogenously every single night when we go to bed. Based on that fact, I've taken on the guinea pig challenge. I've been dosing harmalas with melatonin before bed nearly every night for a few years now and it's be an amazing adjunct to my life.

Timing is everything with harmalas imo/ime. Dosing in the daytime when serotonin and catecholamine levels are high does seem to be associated with irritability, restlessness, anxiety, increased heart rate and blood pressure, etc. When taken at night when melatonin and beta carboline levels are high, it's basically just supercharging what's already happening endogenously. Dreams become moar vivid, sleep is deeper and moar restful, and the mood boosting and antidepressant effects carry over into daily living.

Wow, that is interesting Dreamer042! How much melatonin and how much Harmala and in what form/ROA? And what time do you do it in relation to the time you go to bed?

 

[Felnik]

Timing is everything with harmalas imo/ime. Dosing in the daytime when serotonin and catecholamine levels are high does seem to be associated with irritability, restlessness, anxiety, increased heart rate and blood pressure, etc. When taken at night when melatonin and beta carboline levels are high, it's basically just supercharging what's already happening endogenously. Dreams become moar vivid, sleep is deeper and moar restful, and the mood boosting and antidepressant effects carry over into daily living.[/quote]


This is really great information, thank you

 

[dreamer042]

Wow, that is interesting Dreamer042! How much melatonin and how much Harmala and in what form/ROA? And what time do you do it in relation to the time you go to bed?

10-30 mg range for both the melatonin and the harmalas. Sublingually. Harmalas are full spectrum (no manske) extract of rue in freebase form. Melatonin is in pure bulk powder form. I should mention as a side note that I worked up to that dosage of melatonin and have been having very positive results with it. Many people are quite surprised to hear such a high dosage when compared to to the recommended 1-3 mg doses. I find it weird and fairly unpleasant at doses under 10 mg, but the melatonin stuff is really a whole other thread and I don't want to get this one too far off topic.

I usually dose around 15-30 mins before I lay down for bed. It hits very fast sublingually and has a pleasant stoning/sedating effect. Sleep comes very easily. I've tried staying up for a few hours on it to ride out the psychoactive effects, it's fairly hypnotic, but in that very tired, eyelids are closing, sleep is beckoning sort of way.

I've noticed all the same positive benefits reported from microdosing other psychedelics. The enhanced creativity, the increased focus, the expanded awareness. It may just boil down to the fact I sleep so much better when I take these and the positive benefits stem from that. In any case, it's been an amazing asset to my life and I'm definitely planning to be a long term case study.

 

[digitalvygr]

Fascinating, thanks for spelling out the ranges and the fact that you worked up to it. Copied to my notes for possible experimentation later. I do currently take trytophan first thing in the AM w b6, b12, D3 and sunlight/light box therapy in order to load it for conversion to melatonin later at night, and I tend to get sleepy at 10 PM as a result. Recovery from exercise and creativity are up as a result of better sleep, so thus far I also plan to stick with this supplementation.

I suppose adding an MAOI might be a next step in this particular practice. Though if I take too much tryptophan in the AM, and then load it again at night w carbs, I tend to wake with sleep paralysis type effects and intense dreams, so it is already pretty potent...