18 replies to this topic

[Rags847]

I've often wondered about this in regards to Piracetam and a Choline source (and in regards to Nootropics in general).

1] Do brain benefits just accrue: increased thinking and corpus colusom activity leading to increased neuronal connectivity (neuroplasticity)?

Or

2] Does the brain always balance itself out and down-regulate: create less synapse receptors and neurochemicals in response to the influx from the outside source (the pills)?

Any information and theories on this would be welcome.

By the way, I love Piracetam. Tried many things, but Piracetam has surpassed my expectations!

[keatah]

I've often wondered about this in regards to Piracetam and a Choline source (and in regards to Nootropics in general).

1] Do brain benefits just accrue: increased thinking and corpus colusom activity leading to increased neuronal connectivity (neuroplasticity)?

Or

2] Does the brain always balance itself out and down-regulate: create less synapse receptors and neurochemicals in response to the influx from the outside source (the pills)?

Any information and theories on this would be welcome.

By the way, I love Piracetam. Tried many things, but Piracetam has surpassed my expectations!

Downregulation is very common. It just creeps up on you, that's all.

[Rags847]

Downregulation is very common. It just creeps up on you, that's all.

What have been your experiences with down regulation, keatah?
Do you feel extra slow off of nootropics?
Do you cycle?
Think their use is worth it?

[pezzonovante]

Great thread, I would appreciate it if the more knowledgeable posters shared their views on this.

[dopamine]

Down-regulation of receptors occurs as a compensatory response to the increased presence of a particular neurotransmitter at specific receptor sites. Such a phenomenon can be a good thing, for example in the treatment of depression down-regulation of beta-adrenergic receptors is considered to be a therapeutic and desirable effect throughout the course of treatment. In the present context, I presume most are concerned about the down-regulation of acetylcholine (ACh) receptors from the use of substances that either inhibit metabolic breakdown (e.g. ACh esterase inhibitors) or increase ACh release. Such concerns are legitimate, particularly for healthy people taking cholinergic substances, as receptor downregulaion is a prerequisite to the treatment of certain mental conditions (not an enhancement of already existing cognitive capacity). However, upon discontinuation, I presume the brain would re-compensate for the decreased presence of certain neurotransmitter molecules by up-regulating the affected receptor sites. Permanent, irreversible down-regulation can occur under certain extreme conditions, but the brain is incredibly elastic, and as long as a healthy dose of moderation is used, I don't think it is something to worry excessively about.

[Rags847]

Permanent, irreversible down-regulation can occur under certain extreme conditions, but the brain is incredibly elastic, and as long as a healthy dose of moderation is used, I don't think it is something to worry excessively about.

Thanks, dopamine. Good to see you back and posting more.
What is your recommendation regarding cycling nootropics (# of days on/off)?

[dopamine]

Permanent, irreversible down-regulation can occur under certain extreme conditions, but the brain is incredibly elastic, and as long as a healthy dose of moderation is used, I don't think it is something to worry excessively about.

Thanks, dopamine. Good to see you back and posting more.
What is your recommendation regarding cycling nootropics (# of days on/off)?

Very hard to speculate on that, as it really depends on which substance you are cycling. Something like huperzine I would cycle every 3-4 weeks or so (with about a week off), as the effects on ACh are very direct. Nootropics like piracetam, aniracetam, oxiracetam, etc. are much more difficult to speculate on, as they have no central mechanism of action that is well-understood. In the latter case, I tend to simply finish the supply I have, and let the natural grace period between running out and re-stocking to act as the "off" period.

[rabagley]

I think if you're going to take a nootropic it should be taken only as needed.

How do you define "needed"? Is that as in "needed to treat a diagnosed medical condition"? Or perhaps as in "needed to perform at my personal best"? Or some other meaning of the term? "needed" is far too vague to have meaning without further explanation.

I'm in favor of a long-term goal of "used for potential maximizing", BTW. And I do think that supplementation of nootropics can do that. It just takes more time and patience than most are willing to put in to find a stack and schedule (vacations) that actually produces long-term maximization of potential. YMMV.

Edited by shepard, 29 December 2007 - 05:06 AM.

[Rags847]

I think if you're going to take a nootropic it should be taken only as needed.

I'm thinking of doing this with nootropics.
Taking them on days off, on heavy studying and reading days.
I feel piracetam and citicoline kick in a half hour to an hour after taking them on an empty stomach.
This way down-regulation, and always being speed up with a more electric brain through daily use, would be less of a concern.

[johnny K]

What do you guys recommend for someone who has taken ecstasy 8 yrs back and is now seeing a severe lack of short and long term memory?

[bgwithadd]

There's a little bit of both invovled. I don't think cyclyinh them makes much sense, but it depends what they are. You will have some downregulation over time but it will not be so much as to negate it entirely so long term use is generally fine.

For drugs like adderall, use sparingly because it just develops tolerance over time and it is insidious about sneaking up and addicting you. Any time you take a large dose you also pump up your tolerance a ton. So, it's worth it to cyclem stimulants if you have ADD and take breaks regularly.

Johnnyk - mdma agonist, gabapenin, huperzine A, lithoum orotate, ashwaghanda, bacopa, ALCAR arginate, idebenone, taurine, , pine bark extract, thiamine, and possibly a nicotine patch for a limited time as it grows receptor sites in the brein.

[kikai93]

I've often wondered about this in regards to Piracetam and a Choline source (and in regards to Nootropics in general).

1] Do brain benefits just accrue: increased thinking and corpus colusom activity leading to increased neuronal connectivity (neuroplasticity)?

Or

2] Does the brain always balance itself out and down-regulate: create less synapse receptors and neurochemicals in response to the influx from the outside source (the pills)?

Any information and theories on this would be welcome.

By the way, I love Piracetam. Tried many things, but Piracetam has surpassed my expectations!

Different drugs behave differently. In the realm of pharmaceutical psychotropes for instance, we can compare many SSRI's to Adderall. Adderall's effects are immediate and powerful, but Adderall causes downregulation (among other nasty effects) sooner than later and whoomp, the monkey is on your back. For Adderall cycling or occasional (weekend study) use is best. SSRI's are the other end of the scale, where plasma concentrations take time to build to therapeutic levels so sporadic dosing makes the drug less effective. My advice is due diligence with any substance you plan to ingest, and trial running one substance at a time, starting slow and building dosage as needed to achieve the desired effect (and no more). I'd cycle anything that doesn't require a constant maintainance dose. I'd also cycle anything with a questionable health profile.

[punkideas]

My take, based on my knowledge of neurotransmitters and receptors, would be that nootropics that have an acute effect (e.g. Adderall) would be likely to cause downregulation with regular use. For most nootropics with a cumulative effect (e.g. bacopa, EPA/DHA), downregulation is unlikely since the direct effect isn't neurotransmitter increase or receptor agonism. For some of the nootropics with a broader accute effect (e.g. piracetam), occasional cycling couldn't hurt.

My personal approach is to cycle off non-cumulative nootropics when I don't need them (school breaks, etc), and use acute ones only as needed. For the ones that show benefits with extended use, I use year-round with the intent of lifelong benefit. I'm trying to avoid downregulation over time, so that when I do need a boost, I can get a big one easily. Also, only using some of the more expensive ones as needed is cheaper.

[smoothVTer]

My take, based on my knowledge of neurotransmitters and receptors, would be that nootropics that have an acute effect (e.g. Adderall) would be likely to cause downregulation with regular use. For most nootropics with a cumulative effect (e.g. bacopa, EPA/DHA), downregulation is unlikely since the direct effect isn't neurotransmitter increase or receptor agonism. For some of the nootropics with a broader accute effect (e.g. piracetam), occasional cycling couldn't hurt.

My personal approach is to cycle off non-cumulative nootropics when I don't need them (school breaks, etc), and use acute ones only as needed. For the ones that show benefits with extended use, I use year-round with the intent of lifelong benefit. I'm trying to avoid downregulation over time, so that when I do need a boost, I can get a big one easily. Also, only using some of the more expensive ones as needed is cheaper.

Interesting approach, punkideas.

This begs the question: what are the cumulative nootropics vs. non-cumulative nootropics? Anyone want to add to the list?

[Erstwhile]

Bump. I think the question of cycling is especially relevant to piracetam, to which it seems possible to develop a tolerance for after all. What kind of cycling schedule would be best for piracetam?

[chrono]

My take, based on my knowledge of neurotransmitters and receptors, would be that nootropics that have an acute effect (e.g. Adderall) would be likely to cause downregulation with regular use. For most nootropics with a cumulative effect (e.g. bacopa, EPA/DHA), downregulation is unlikely since the direct effect isn't neurotransmitter increase or receptor agonism. For some of the nootropics with a broader accute effect (e.g. piracetam), occasional cycling couldn't hurt.

My personal approach is to cycle off non-cumulative nootropics when I don't need them (school breaks, etc), and use acute ones only as needed. For the ones that show benefits with extended use, I use year-round with the intent of lifelong benefit. I'm trying to avoid downregulation over time, so that when I do need a boost, I can get a big one easily. Also, only using some of the more expensive ones as needed is cheaper.

This is the best response here, I think. It really depends on the substance in a huge way.

As for piracetam, I think it's necessary to cycle as well. I try to take at least a day or two off every week, and for longer periods when I don't need such intense concentration. Unfortunately, I also feel like efficacy is a lot more hit-or-miss, so maybe just longer breaks would work better. It helps to have other non-racetam options to use during breaks, if you really need nootropics to do what you want/need. There are probably some longer threads here wherein you can find more opinions, but unfortunately I don't think it's possible to get very specific about the best cycle schedule, and it depends a lot on how it works best with your individual factors.

Edited by chrono, 17 November 2011 - 06:26 AM.

[hippocampus]

Can one develop tolerance to vitamins and minerals? For example, if you regularly consume some mineral, your body adapts to this steady source and when you eat food with this mineral, body doesn't use it.
I think this can happen, I used magnesium few years ago and I slept better every time I took it and was more calm, but after a while I developed tolerance. Similar with lecithin. Is there any way to avoid this (besides irregular taking/cycling)?

[angela86]

Can one develop tolerance to vitamins and minerals? For example, if you regularly consume some mineral, your body adapts to this steady source and when you eat food with this mineral, body doesn't use it.
I think this can happen, I used magnesium few years ago and I slept better every time I took it and was more calm, but after a while I developed tolerance. Similar with lecithin. Is there any way to avoid this (besides irregular taking/cycling)?

Maybe it's because you had a deficiency in magnesium, so when you used it initially, the effects were more than subtle. This happened with me as well - literally, to enhance my focus and attention threefold some days, I'd take a shot of espresso with two pure magnesium pills. It was insane how in sync with everything my mind felt, I didn't realize that the mineral was lacking until I took it. But it definetely wore off - I don't think it was because my body was adapting to it - or lowering any sense of tolerance- but more because I was no longer deficient, so my body didn't react the way it did initially (out of necessity.)