AChE-I Research

[muscleupcrohn]

A while ago I made a post on huperzine and galantamine, pretty much the two more common AChE inhibitors used in supplements. The study referenced compared 100-200mcg huperzine to 4-8mg galantamine, and also 2.5-5mg donepezil. Info on that study can be found here:

https://anabolicminds.com/community/index.php?threads/Huperzine-and-Galantamine.279501/

So we see that they’re both similarly effective acute AChE-Is in healthy subjects, but that they may only be conditionally beneficial in improving cognition, perhaps during sleep deprivation and/or particularly difficult or challenging tasks.

That said, I’ll now add on to my last post with more info on AChE-Is:

The half-life of huperzine is often mentioned as being particularly long, which then lead to the recommendation of frequent cycling.

We often hear huperzine is touted to have a half-life of ~12 hours, likely coming from this study:

https://www.ncbi.nlm.nih.gov/m/pubmed/18348466/

Which noted a 716 minute (~12 hour) half-life, but this was with a 400mcg dose. As well see later, this is a rather high (and I’ll say unnecessary) dose, so let’s put that aside for a moment.

If you’ll excuse the poor quality of this PDF, notice that a 100mcg dose seems to have a half-life just under 5 hours:

http://www.chinaphar.com/article/download/7054/7702

As we’ll soon see, 100mcg is a more reasonable, yet still useful, dose of huperzine.

Here, 100mcg was used 2x daily in adolescent students:

http://www.chinaphar.com/article/download/7802/8893

I’m not certain how much they weighed, but a cursory search seems to put junior middle schoolers at ~51.5kg or so, give or take:

https://www.sciencedirect.com/science/article/pii/S2095254617301175

so that comes out to ~3.88mcg/kg/day, or ~272mg/day for a 70kg person, split into 2 ~136mg doses.

Also, there has been documented tolerance buildup to the AChE-I effects of donepezil in humans, while rodent research seems to suggest this may not be the case with huperzine, and the human studies have shown superior acute effects as well:

https://www.ncbi.nlm.nih.gov/m/pubmed/16923332/

Not to mention that, in humans, huperzine may also be superior to donepezil and galantamine to pair with memantine for treating AD (100mcg 2x daily huperzine vs 2-6mg galantamine 2x daily vs 5-10mg donepezil 1x daily):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402907/

In summary, huperzine’s frequently touted 12 hour half life seems to be with a high 400mcg dose. A 100mcg dose seems to be closer to 5 hours. Given that 100-200mcg is an effective dose as an AChE-I, probably just stick to 200mcg/day, and frequent cycling likely isn’t as pressing of a concern as it is often claimed to be based on the 400mcg half-life. Anyway, it seems to be no more pressing of a concern than that of galantamine, which seems to poses similar AChE-I activity at 4-8mg as 100-200mcg huperzine, while itself having a half-life of 7.6 hours at 4mg and 7.2 hours at 8mg, yet I rarely see anyone mention the necessity of cycling galantamine, while it’s almost always mentioned with huperzine.

https://www.ncbi.nlm.nih.gov/m/pubmed/20156150/

TL;DR:

-The ~12 hour half-life so often claimed for huperzine seems to be based on a (high) 400mcg dose

-The half-life with 100mcg seems to be closer to 5 hours

-100-200mcg huperzine seems to possess similar acute AChE-I activity as 4-8mg galantamine in healthy subjects

-4-8mg galantamine seems to have a half-life of 7-8 hours, longer than that of 100mcg huperzine

-Both huperzine and galantamine may only be conditionally beneficial for improving cognition

-Huperzine may not be subject to the same tolerance buildup that donepezil is, based on rodent research anyway

-Huperzine may be better than galantamine and donepezil when paired with memantine god treating AD

 

[HIT4ME]

Interesting - and I didn't understand that half life can change with dosing so I looked into it more.

And what I found actually makes me wonder if you have actually dug up information that SUPPORTS the need to cycle huperzine.

One of the possible reasons a higher dose of a drug can have a longer half life is that it "self inhibits" it's own breakdown.

Basically you only have so much availability of certain enzymes needed to metabolize a drug, so a higher dose can out place the availability if these enzymes and thus prevent it's own metabolism by depleting these enzymes.

So with a 400 mg dose this appears to happen acutely, but that doesn't necessarily mean a lower dose with a shorter half life is safe.

You may not deplete the enzymes acutely with the smaller dose, but over time you could see a depletion of enzymes with chronic use, and the half life would get longer and longer.

Thus lower doses would be safer acutely, but the chronic use would still be an issue and this supports the need to cycle off.

I suppose this is probably more of the reason to cycle off than the half life...a 12 hour half life with 2x a day dosing isn't really all that crazy.

 

[muscleupcrohn]

Interesting - and I didn't understand that half life can change with dosing so I looked into it more.

And what I found actually makes me wonder if you have actually dug up information that SUPPORTS the need to cycle huperzine.

One of the possible reasons a higher dose of a drug can have a longer half life is that it "self inhibits" it's own breakdown.

Basically you only have so much availability of certain enzymes needed to metabolize a drug, so a higher dose can out place the availability if these enzymes and thus prevent it's own metabolism by depleting these enzymes.

So with a 400 mg dose this appears to happen acutely, but that doesn't necessarily mean a lower dose with a shorter half life is safe.

You may not deplete the enzymes acutely with the smaller dose, but over time you could see a depletion of enzymes with chronic use, and the half life would get longer and longer.

Thus lower doses would be safer acutely, but the chronic use would still be an issue and this supports the need to cycle off.

I suppose this is probably more of the reason to cycle off than the half life...a 12 hour half life with 2x a day dosing isn't really all that crazy.

You can 100% have dose-dependent half life’s. Here’s two random examples:

https://www.ncbi.nlm.nih.gov/m/pubmed/8212419/

https://www.ncbi.nlm.nih.gov/m/pubmed/7310640/

And, regarding that point, every time I read about the necessity of cycling Huperzine, the 12 hour half life was mentioned, with people claiming that galantamine is a better option for regular use due to a shorter half life. So if huperzine needs to be cycled MORE now that we know it has a shorter half-life than previously suspected, then galantamine would still also need to be cycled frequently, as it’s half life is still less than what we believed huperzine’s was. Yet there’s never calls for that, and incessant claims that it’s a better option for regular use.

There’s also the rodent study that seems to suggest that huperzine isn’t subject to the same tolerance buildup over time that something like donepezil is, so the need to cycle to prevent tolerance buildup also isn’t super likely IMO.

There’s actually MORE studies on huperzine, both in healthy humans and people with cognitive decline, that use 200-400mcg/day, with doses of 100-200mcg, than anything else, so single doses of 100-200mcg are the norm in what is considered “safe,” not bolus doses of 400mcg, which only a few studies have actually used for any period of time.

If you’re concerned with the safety of it, I wouldn’t worry much at all about using 100-200mcg/serving and per day for several weeks. Not at all. Plus it’s effective at that dose.

 

[muscleupcrohn]

Interesting - and I didn't understand that half life can change with dosing so I looked into it more.

And what I found actually makes me wonder if you have actually dug up information that SUPPORTS the need to cycle huperzine.

One of the possible reasons a higher dose of a drug can have a longer half life is that it "self inhibits" it's own breakdown.

Basically you only have so much availability of certain enzymes needed to metabolize a drug, so a higher dose can out place the availability if these enzymes and thus prevent it's own metabolism by depleting these enzymes.

So with a 400 mg dose this appears to happen acutely, but that doesn't necessarily mean a lower dose with a shorter half life is safe.

You may not deplete the enzymes acutely with the smaller dose, but over time you could see a depletion of enzymes with chronic use, and the half life would get longer and longer.

Thus lower doses would be safer acutely, but the chronic use would still be an issue and this supports the need to cycle off.

I suppose this is probably more of the reason to cycle off than the half life...a 12 hour half life with 2x a day dosing isn't really all that crazy.

You can 100% have dose-dependent half life’s. Here’s two random examples:

https://www.ncbi.nlm.nih.gov/m/pubmed/8212419/

https://www.ncbi.nlm.nih.gov/m/pubmed/7310640/

And, regarding that point, every time I read about the necessity of cycling Huperzine, the 12 hour half life was mentioned, with people claiming that galantamine is a better option for regular use due to a shorter half life. So if huperzine needs to be cycled MORE now that we know it has a shorter half-life than previously suspected, then galantamine would still also need to be cycled frequently, as it’s half life is still less than what we believed huperzine’s was. Yet there’s never calls for that, and incessant claims that it’s a better option for regular use.

There’s also the rodent study that seems to suggest that huperzine isn’t subject to the same tolerance buildup over time that something like donepezil is, so the need to cycle to prevent tolerance buildup also isn’t super likely IMO.

There’s actually MORE studies on huperzine, both in healthy humans and people with cognitive decline, that use 200-400mcg/day, with doses of 100-200mcg, than anything else, so single doses of 100-200mcg are the norm in what is considered “safe,” not bolus doses of 400mcg, which only a few studies have actually used for any period of time.

If you’re concerned with the safety of it, I wouldn’t worry much at all about using 100-200mcg/serving and per day for several weeks. Not at all. Plus it’s effective at that dose.

 

[muscleupcrohn]

Interesting - and I didn't understand that half life can change with dosing so I looked into it more.

And what I found actually makes me wonder if you have actually dug up information that SUPPORTS the need to cycle huperzine.

One of the possible reasons a higher dose of a drug can have a longer half life is that it "self inhibits" it's own breakdown.

Basically you only have so much availability of certain enzymes needed to metabolize a drug, so a higher dose can out place the availability if these enzymes and thus prevent it's own metabolism by depleting these enzymes.

So with a 400 mg dose this appears to happen acutely, but that doesn't necessarily mean a lower dose with a shorter half life is safe.

You may not deplete the enzymes acutely with the smaller dose, but over time you could see a depletion of enzymes with chronic use, and the half life would get longer and longer.

Thus lower doses would be safer acutely, but the chronic use would still be an issue and this supports the need to cycle off.

I suppose this is probably more of the reason to cycle off than the half life...a 12 hour half life with 2x a day dosing isn't really all that crazy.

You can 100% have dose-dependent half life’s. Here’s two random examples:

https://www.ncbi.nlm.nih.gov/m/pubmed/8212419/

https://www.ncbi.nlm.nih.gov/m/pubmed/7310640/

And, regarding that point, every time I read about the necessity of cycling Huperzine, the 12 hour half life was mentioned, with people claiming that galantamine is a better option for regular use due to a shorter half life. So if huperzine needs to be cycled MORE now that we know it has a shorter half-life than previously suspected, then galantamine would still also need to be cycled frequently, as it’s half life is still less than what we believed huperzine’s was. Yet there’s never calls for that, and incessant claims that it’s a better option for regular use.

There’s also the rodent study that seems to suggest that huperzine isn’t subject to the same tolerance buildup over time that something like donepezil is, so the need to cycle to prevent tolerance buildup also isn’t super likely IMO.

There’s actually MORE studies on huperzine, both in healthy humans and people with cognitive decline, that use 200-400mcg/day, with doses of 100-200mcg, than anything else, so single doses of 100-200mcg are the norm in what is considered “safe,” not bolus doses of 400mcg, which only a few studies have actually used for any period of time.

https://www.hindawi.com/journals/ecam/2014/363985/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781107/

If you’re concerned with the safety of it, I wouldn’t worry much at all about using 100-200mcg/serving and per day for several weeks. Not at all. Plus it’s effective at that dose.

 

[muscleupcrohn]

Interesting - and I didn't understand that half life can change with dosing so I looked into it more.

And what I found actually makes me wonder if you have actually dug up information that SUPPORTS the need to cycle huperzine.

One of the possible reasons a higher dose of a drug can have a longer half life is that it "self inhibits" it's own breakdown.

Basically you only have so much availability of certain enzymes needed to metabolize a drug, so a higher dose can out place the availability if these enzymes and thus prevent it's own metabolism by depleting these enzymes.

So with a 400 mg dose this appears to happen acutely, but that doesn't necessarily mean a lower dose with a shorter half life is safe.

You may not deplete the enzymes acutely with the smaller dose, but over time you could see a depletion of enzymes with chronic use, and the half life would get longer and longer.

Thus lower doses would be safer acutely, but the chronic use would still be an issue and this supports the need to cycle off.

I suppose this is probably more of the reason to cycle off than the half life...a 12 hour half life with 2x a day dosing isn't really all that crazy.

You can 100% have dose-dependent half life’s. Here’s two random examples:

https://www.ncbi.nlm.nih.gov/m/pubmed/8212419/

https://www.ncbi.nlm.nih.gov/m/pubmed/7310640/

And, regarding that point, every time I read about the necessity of cycling Huperzine, the 12 hour half life was mentioned, with people claiming that galantamine is a better option for regular use due to a shorter half life. So if huperzine needs to be cycled MORE now that we know it has a shorter half-life than previously suspected, then galantamine would still also need to be cycled frequently, as it’s half life is still less than what we believed huperzine’s was. Yet there’s never calls for that, and incessant claims that it’s a better option for regular use.

There’s also the rodent study that seems to suggest that huperzine isn’t subject to the same tolerance buildup over time that something like donepezil is, so the need to cycle to prevent tolerance buildup also isn’t super likely IMO.

There’s actually MORE studies on huperzine, both in healthy humans and people with cognitive decline, that use 200-400mcg/day, with doses of 100-200mcg, than anything else, so single doses of 100-200mcg are the norm in what is considered “safe,” not bolus doses of 400mcg, which only a few studies have actually used for any period of time.

https://www.hindawi.com/journals/ecam/2014/363985/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781107/

If you’re concerned with the safety of it, I wouldn’t worry much at all about using 100-200mcg/serving and per day for several weeks. Not at all. Plus it’s effective at that dose.

 

[muscleupcrohn]

Interesting - and I didn't understand that half life can change with dosing so I looked into it more.

And what I found actually makes me wonder if you have actually dug up information that SUPPORTS the need to cycle huperzine.

One of the possible reasons a higher dose of a drug can have a longer half life is that it "self inhibits" it's own breakdown.

Basically you only have so much availability of certain enzymes needed to metabolize a drug, so a higher dose can out place the availability if these enzymes and thus prevent it's own metabolism by depleting these enzymes.

So with a 400 mg dose this appears to happen acutely, but that doesn't necessarily mean a lower dose with a shorter half life is safe.

You may not deplete the enzymes acutely with the smaller dose, but over time you could see a depletion of enzymes with chronic use, and the half life would get longer and longer.

Thus lower doses would be safer acutely, but the chronic use would still be an issue and this supports the need to cycle off.

I suppose this is probably more of the reason to cycle off than the half life...a 12 hour half life with 2x a day dosing isn't really all that crazy.

You can 100% have dose-dependent half life’s. Here’s two random examples:

https://www.ncbi.nlm.nih.gov/m/pubmed/8212419/

https://www.ncbi.nlm.nih.gov/m/pubmed/7310640/

And, regarding that point, every time I read about the necessity of cycling Huperzine, the 12 hour half life was mentioned, with people claiming that galantamine is a better option for regular use due to a shorter half life. So if huperzine needs to be cycled MORE now that we know it has a shorter half-life than previously suspected, then galantamine would still also need to be cycled frequently, as it’s half life is still less than what we believed huperzine’s was. Yet there’s never calls for that, and incessant claims that it’s a better option for regular use.

There’s also the rodent study that seems to suggest that huperzine isn’t subject to the same tolerance buildup over time that something like donepezil is, so the need to cycle to prevent tolerance buildup also isn’t super likely IMO.

There’s actually MORE studies on huperzine, both in healthy humans and people with cognitive decline, that use 200-400mcg/day, with doses of 100-200mcg, than anything else, so single doses of 100-200mcg are the norm in what is considered “safe,” not bolus doses of 400mcg, which only a few studies have actually used for any period of time.

https://www.hindawi.com/journals/ecam/2014/363985/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781107/

If you’re concerned with the safety of it, I wouldn’t worry much at all about using 100-200mcg/serving and per day for several weeks. Not at all. Plus it’s effective at that dose.

 

[muscleupcrohn]

Interesting - and I didn't understand that half life can change with dosing so I looked into it more.

And what I found actually makes me wonder if you have actually dug up information that SUPPORTS the need to cycle huperzine.

One of the possible reasons a higher dose of a drug can have a longer half life is that it "self inhibits" it's own breakdown.

Basically you only have so much availability of certain enzymes needed to metabolize a drug, so a higher dose can out place the availability if these enzymes and thus prevent it's own metabolism by depleting these enzymes.

So with a 400 mg dose this appears to happen acutely, but that doesn't necessarily mean a lower dose with a shorter half life is safe.

You may not deplete the enzymes acutely with the smaller dose, but over time you could see a depletion of enzymes with chronic use, and the half life would get longer and longer.

Thus lower doses would be safer acutely, but the chronic use would still be an issue and this supports the need to cycle off.

I suppose this is probably more of the reason to cycle off than the half life...a 12 hour half life with 2x a day dosing isn't really all that crazy.

You can 100% have dose-dependent half life’s. Here’s two random examples:

https://www.ncbi.nlm.nih.gov/m/pubmed/8212419/

https://www.ncbi.nlm.nih.gov/m/pubmed/7310640/

And, regarding that point, every time I read about the necessity of cycling Huperzine, the 12 hour half life was mentioned, with people claiming that galantamine is a better option for regular use due to a shorter half life. So if huperzine needs to be cycled MORE now that we know it has a shorter half-life than previously suspected, then galantamine would still also need to be cycled frequently, as it’s half life is still less than what we believed huperzine’s was. Yet there’s never calls for that, and incessant claims that it’s a better option for regular use.

There’s also the rodent study that seems to suggest that huperzine isn’t subject to the same tolerance buildup over time that something like donepezil is, so the need to cycle to prevent tolerance buildup also isn’t super likely IMO.

There’s actually MORE studies on huperzine, both in healthy humans and people with cognitive decline, that use 200-400mcg/day, with doses of 100-200mcg, than anything else, so single doses of 100-200mcg are the norm in what is considered “safe,” not bolus doses of 400mcg, which only a few studies have actually used for any period of time.

https://www.hindawi.com/journals/ecam/2014/363985/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781107/

If you’re concerned with the safety of it, I wouldn’t worry much at all about using 100-200mcg/serving and per day for several weeks. Not at all. Plus it’s effective at that dose.

 

[muscleupcrohn]

Wow, that post posted way too many times.

Anyway, I made a mistake in reading one study. I can admit when I screw up.

The study that I thought used ~100mcg apparently actually used 10x ~100mcg. That’s a big difference, and I’m an idiot for not catching it; looking now at the Cmax they reported relative to the other doses that were supposedly higher, that should have been a red flag. Anyway, this study that noted the ~5 hour half life used 990mcg, not 90mcg:

http://www.chinaphar.com/article/download/7054/7702

Summary of Study:
Dose: 990mcg
Half-life: ~5 hours
Cmax: 8.40 ug/L
Tmax: ~80 min

Then we have a study with 400mcg:

https://www.ncbi.nlm.nih.gov/m/pubmed/18348466/

Summary of Study:
Dose: 400mcg
Half-life: ~12 hours
Cmax: 2.59 ug/L
Tmax: ~58 min

Then we have two studies with 200mcg:

https://www.ncbi.nlm.nih.gov/m/pubmed/29058298/

Summary of Study:
Dose: 200mcg
Half-life: ~12 hours
Cmax: 1.550 ng/mL
Tmax: ~43 minutes

https://www.ncbi.nlm.nih.gov/m/pubmed/17939152/

Summary of Study:
Dose: 200mcg
Half-life: ~6 hours
Cmax: 2.47 ng/mL
Tmax: ~78 minutes

So we now have no real info on the half-life of huperzine at 100mcg, two varying half-life reports at 200mcg, one report at 400mcg, and 1 report at 990mcg.

But we do know that 200mcg huperzine reached peak AChE inhibition faster than 100mcg in the study below (72% of pre-drug activity in 30 minutes vs 83% in 90 minutes), if that helps with anything.

https://www.academia.edu/29881293/Physiological_and_neurobehavioral_effects_of_cholinesterase_inhibition_in_healthy_adults

 

[HIT4ME]

Haha, website quirks rock.

I wasn't arguing the half life isn't dose defendant. I was pointing out that I was unaware until hou brought this up of such situations.

What I was trying to point out is that, regardless of internet dogma, a drug with a shorter half life at a smaller dose indicates that it is self-inhibiting it's own metabolism. This happens typically through enzyme exhaustion, which means that long-term use can exhaust the enzyme at a smaller dose, just like the enzyme becomes exhausted acutely with a larger dose.

And this self-inhibiting action is likely the REAL reason to cycle off, not the half life itself. Even if it had a 12-hour half life that wouldn't necessitate cycling off on own. You can dose 12 hour half life drugs 2x per day and you will still reach steady concentrations around 2x the dose you are taking (with 400 mg in your system you will burn 200 mg in 12 hours and dose again, bringing you back to 400).

And I agree, 100-200 mg likely has a good safety profile at least for a couple months, but I could be wrong without real data...which you are digging up what we have so kudos for that.

 

[muscleupcrohn]

Haha, website quirks rock.

I wasn't arguing the half life isn't dose defendant. I was pointing out that I was unaware until hou brought this up of such situations.

What I was trying to point out is that, regardless of internet dogma, a drug with a shorter half life at a smaller dose indicates that it is self-inhibiting it's own metabolism. This happens typically through enzyme exhaustion, which means that long-term use can exhaust the enzyme at a smaller dose, just like the enzyme becomes exhausted acutely with a larger dose.

And this self-inhibiting action is likely the REAL reason to cycle off, not the half life itself. Even if it had a 12-hour half life that wouldn't necessitate cycling off on own. You can dose 12 hour half life drugs 2x per day and you will still reach steady concentrations around 2x the dose you are taking (with 400 mg in your system you will burn 200 mg in 12 hours and dose again, bringing you back to 400).

And I agree, 100-200 mg likely has a good safety profile at least for a couple months, but I could be wrong without real data...which you are digging up what we have so kudos for that.

I got ahead of myself and posted before I double checked everything. Really silly mistake on my part; I’m getting rusty now that I’m not in school anymore I guess haha.

Realistically, I’d probably cycle off all nootropics every few months anyway (8-12 weeks max for most things IMO), and huperzine is definitely one of the ones with a more well-established safety profile IMO.

Edit: after my error, it looks like the half-life with 200mcg is either 6 or 12 hours, while the half life with 400mcg is 12 hours, and the half life with 990mcg is 5 hours. Let me check if the rodent study that noted no tolerance buildup also tracked half-life and/or Cmax or Tmax or not. That could clear things up a little bit perhaps.

 

[HIT4ME]

Having a shorter half life with a bigger dosage is interesting...although if it is one study I wonder about either some other confounding factor or some error in the study....

 

[muscleupcrohn]

Having a shorter half life with a bigger dosage is interesting...although if it is one study I wonder about either some other confounding factor or some error in the study....

Yeah, it’s really hard to know. The Cmax was higher, which makes sense, but like you said, it’s not much to go on.

That said, I think it’s probably best to stick to 100-200mcg doses, which we know are effective at acutely inhibiting AChE in healthy young subjects. And given that AChE-I may only be conditionally beneficial, such as during sleep deprivation or particularly demanding tasks, I think the new takeaway may be that the presence of acute effects make it a good option to add to a stack when needed, while the apparent lack of tolerance buildup with huperzine makes it also not contraindicated for daily use for several weeks as part of a stack.

 

[HIT4ME]

A little off topic, but just came across this...

Nigella sativa L., Supplementary Plant with Anticholinesterase Effect for Cognition Problems: A Kinetic Study - PubMed

N. sativa is a good candidate for seeking the new anticholinesterase agent and could be considered as a good supplement for the health of the elderly.

www.ncbi.nlm.nih.gov

 

[muscleupcrohn]

A little off topic, but just came across this...

Nigella sativa L., Supplementary Plant with Anticholinesterase Effect for Cognition Problems: A Kinetic Study - PubMed

N. sativa is a good candidate for seeking the new anticholinesterase agent and could be considered as a good supplement for the health of the elderly.

www.ncbi.nlm.nih.gov

Nice! It’s good stuff. If we’re talking other AChE-Is, sage is probably on the top of my list though, with more promising research than huperzine or galantamine IMO:

The results showed that administration of S. lavandulaefolia resulted in a consistent improvement for both the 25- and 50-microl dose on the 'Speed of Memory' factor. There was also an improvement on the 'Secondary Memory' factor for the 25-microl dose. Mood was consistently enhanced, with increases in self-rated 'alertness', 'calmness' and 'contentedness' following the 50-microl dose and elevated 'calmness' following 25 microl. These results represent further evidence that Salvia is capable of acute modulation of mood and cognition in healthy young adults. The data also suggest that previous reports of memory enhancement by Salvia may be due to more efficient retrieval of target material.

https://www.ncbi.nlm.nih.gov/m/pubmed/15639154/

The primary outcome measures were immediate and delayed word recall. The 50 microl dose of Salvia essential oil significantly improved immediate word recall in both studies. These results represent the first systematic evidence that Salvia is capable of acute modulation of cognition in healthy young adults.

https://www.ncbi.nlm.nih.gov/m/pubmed/12895685/

The current study combined an in vitro investigation of the cholinesterase inhibitory properties and phytochemical constituents of a S. lavandulaefolia essential oil, with a double-blind, placebo-controlled, balanced crossover study assessing the effects of a single dose on cognitive performance and mood. In this latter investigation 36 healthy participants received capsules containing either 50 µL of the essential oil or placebo on separate occasions, 7 days apart. Cognitive function was assessed using a selection of computerized memory and attention tasks and the Cognitive Demand Battery before the treatment and 1-h and 4-h post-dose. The essential oil was a potent inhibitor of human acetylcholinesterase (AChE) and consisted almost exclusively of monoterpenoids. Oral consumption lead to improved performance of secondary memory and attention tasks, most notably at the 1-h post-dose testing session, and reduced mental fatigue and increased alertness which were more pronounced 4-h post-dose. These results extend previous observations of improved cognitive performance and mood following AChE inhibitory sage extracts and suggest that the ability of well-tolerated terpenoid-containing extracts to beneficially modulate cholinergic function and cognitive performance deserves further attention.

https://www.ncbi.nlm.nih.gov/m/pubmed/20937617/

RATIONALE: Species of Salvia (sage) have a long-standing reputation in European medical herbalism, including for memory enhancement. In recent controlled trials, administration of sage extracts with established cholinergic properties improved cognitive function in young adults.

OBJECTIVES: This randomised, placebo-controlled, double-blind, balanced, five-period crossover study investigated the acute effects on cognitive performance of a standardised extract of Salvia officinalis in older adults.

MATERIALS AND METHODS: Twenty volunteers (>65 years of age, mean = 72.95) received four active doses of extract (167, 333, 666 and 1332 mg) and a placebo with a 7-day wash-out period between visits. Assessment involved completion of the Cognitive Drug Research computerised assessment battery. On study days, treatments were administered immediately following a baseline assessment with further assessment at 1, 2.5, 4 and 6 h post treatment.

RESULTS: Compared with the placebo condition (which exhibited the characteristic performance decline over the day), the 333-mg dose was associated with significant enhancement of secondary memory performance at all testing times. The same measure benefited to a lesser extent from other doses. There also were significant improvements to accuracy of attention following the 333-mg dose. In vitro analysis confirmed cholinesterase inhibiting properties for the extract.

CONCLUSIONS: The overall pattern of results is consistent with a dose-related benefit to processes involved in efficient stimulus processing and/or memory consolidation rather than retrieval or working memory efficiency. These findings extend those of the memory-enhancing effects of Salvia extracts in younger populations and warrant further investigation in larger series, in other populations and with different dosing regimes.

https://www.ncbi.nlm.nih.gov/m/pubmed/18350281/

Salvia officinalis (sage) has previously been shown both to possess in vitro cholinesterase inhibiting properties, and to enhance mnemonic performance and improve mood in healthy young participants. In this double-blind, placebo-controlled, crossover study, 30 healthy participants attended the laboratory on three separate days, 7 days apart, receiving a different treatment in counterbalanced order on each occasion (placebo, 300, 600 mg dried sage leaf). On each day mood was assessed predose and at 1 and 4 h postdose. Each mood assessment comprised completion of Bond–Lader mood scales and the State Trait Anxiety Inventory (STAI) before and after 20 min performance of the Defined Intensity Stress Simulator (DISS) computerized multitasking battery. In a concomitant investigation, an extract of the sage leaf exhibited dose-dependent, in vitro inhibition of acetylcholinesterase and, to a greater extent, butyrylcholinesterase. Both doses of sage led to improved ratings of mood in the absence of the stressor (that is, in pre-DISS mood scores) postdose, with the lower dose reducing anxiety and the higher dose increasing ‘alertness’, ‘calmness’ and ‘contentedness’ on the Bond–Lader mood scales. The reduced anxiety effect following the lower dose was, however, abolished by performing the DISS, with the same dose also being associated with a reduction of alertness during performance. Task performance on the DISS battery was improved for the higher dose at both postdose sessions, but reduced for the lower dose at the later testing session. The results confirm previous observations of the cholinesterase inhibiting properties of S. officinalis, and improved mood and cognitive performance following the administration of single doses to healthy young participants.

https://www.nature.com/articles/1300907

 

[drseuss6969]

A while ago I made a post on huperzine and galantamine, pretty much the two more common AChE inhibitors used in supplements. The study referenced compared 100-200mcg huperzine to 4-8mg galantamine, and also 2.5-5mg donepezil. Info on that study can be found here:

https://anabolicminds.com/community/index.php?threads/Huperzine-and-Galantamine.279501/

So we see that they’re both similarly effective acute AChE-Is in healthy subjects, but that they may only be conditionally beneficial in improving cognition, perhaps during sleep deprivation and/or particularly difficult or challenging tasks.

That said, I’ll now add on to my last post with more info on AChE-Is:

The half-life of huperzine is often mentioned as being particularly long, which then lead to the recommendation of frequent cycling.

We often hear huperzine is touted to have a half-life of ~12 hours, likely coming from this study:

https://www.ncbi.nlm.nih.gov/m/pubmed/18348466/

Which noted a 716 minute (~12 hour) half-life, but this was with a 400mcg dose. As well see later, this is a rather high (and I’ll say unnecessary) dose, so let’s put that aside for a moment.

If you’ll excuse the poor quality of this PDF, notice that a 100mcg dose seems to have a half-life just under 5 hours:

http://www.chinaphar.com/article/download/7054/7702

As we’ll soon see, 100mcg is a more reasonable, yet still useful, dose of huperzine.

Here, 100mcg was used 2x daily in adolescent students:

http://www.chinaphar.com/article/download/7802/8893

I’m not certain how much they weighed, but a cursory search seems to put junior middle schoolers at ~51.5kg or so, give or take:

https://www.sciencedirect.com/science/article/pii/S2095254617301175

so that comes out to ~3.88mcg/kg/day, or ~272mg/day for a 70kg person, split into 2 ~136mg doses.

Also, there has been documented tolerance buildup to the AChE-I effects of donepezil in humans, while rodent research seems to suggest this may not be the case with huperzine, and the human studies have shown superior acute effects as well:

https://www.ncbi.nlm.nih.gov/m/pubmed/16923332/

Not to mention that, in humans, huperzine may also be superior to donepezil and galantamine to pair with memantine for treating AD (100mcg 2x daily huperzine vs 2-6mg galantamine 2x daily vs 5-10mg donepezil 1x daily):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402907/

In summary, huperzine’s frequently touted 12 hour half life seems to be with a high 400mcg dose. A 100mcg dose seems to be closer to 5 hours. Given that 100-200mcg is an effective dose as an AChE-I, probably just stick to 200mcg/day, and frequent cycling likely isn’t as pressing of a concern as it is often claimed to be based on the 400mcg half-life. Anyway, it seems to be no more pressing of a concern than that of galantamine, which seems to poses similar AChE-I activity at 4-8mg as 100-200mcg huperzine, while itself having a half-life of 7.6 hours at 4mg and 7.2 hours at 8mg, yet I rarely see anyone mention the necessity of cycling galantamine, while it’s almost always mentioned with huperzine.

https://www.ncbi.nlm.nih.gov/m/pubmed/20156150/

TL;DR:

-The ~12 hour half-life so often claimed for huperzine seems to be based on a (high) 400mcg dose

-The half-life with 100mcg seems to be closer to 5 hours

-100-200mcg huperzine seems to possess similar acute AChE-I activity as 4-8mg galantamine in healthy subjects

-4-8mg galantamine seems to have a half-life of 7-8 hours, longer than that of 100mcg huperzine

-Both huperzine and galantamine may only be conditionally beneficial for improving cognition

-Huperzine may not be subject to the same tolerance buildup that donepezil is, based on rodent research anyway

-Huperzine may be better than galantamine and donepezil when paired with memantine god treating AD

This is great. I would love more of this.

 

[drseuss6969]

Are there any products selling this particular product?

 

[muscleupcrohn]

Are there any products selling this particular product?

Huperzine? You can get it in caps/pills everywhere. Galantamine is a little harder to find and a fair bit more expensive though, and sage (salvia officinalis) can be bought as a powder from places like Herbco and Starwest Botanicals for very cheap per serving.

 

[muscleupcrohn]

Are there any products selling this particular product?

Huperzine? You can get it in caps/pills everywhere. Galantamine is a little harder to find and a fair bit more expensive though, and sage (salvia officinalis) can be bought as a powder from places like Herbco and Starwest Botanicals for very cheap per serving.

 

[drseuss6969]

Huperzine? You can get it in caps/pills everywhere. Galantamine is a little harder to find and a fair bit more expensive though, and sage (salvia officinalis) can be bought as a powder from places like Herbco and Starwest Botanicals for very cheap per serving.

Thanks! I was talking about sage. I want to give it a shot

 

[muscleupcrohn]

Thanks! I was talking about sage. I want to give it a shot

No problem. Using powder, based on the two studies, id probably start with 600mg of the powder (the dose found to work well in one study), and if needed, increase the dose up to perhaps 1.25g, or 2.5g at the most (the equivalent of the 167-333mg of a 7.5:1 extract that was found to work well in another study). But don’t go higher than that, as the higher doses of the extract seemed to have little or no effects, suggesting an “inverted U” dose curve.