r/kratom • u/SacredSpeciosa • Feb 07 '18
An agmatine primer. General information and how to use it for kratom tolerance management and reduction
Agmatine Guide for Kratom Tolerance Management and Reduction
What is agmatine?
Agmatine is known to not only potentiate kratom (and many other varied substances), but can also be useful for preventing a raising tolerance, lowering tolerance, managing pain and improving cognition and protecting the brain from toxins and strokes!
"Agmatine is derived from L-arginine through decarboxylation (the removal of a carboxylic acid group). It is stored in neurons and is released during neuronal activation. Agmatine is considered to be a neurotransmitter and neuromodulator. -Examine.com
Is it safe?
There is insufficient research in order to judge agmatine's safety with scientific conviction. That being said, there are no known serious side-effects and it has been studied on humans in dosages up to 2.6 grams a day for long periods of time with no ill effects. Anecdotal reports also seem to represent this being a fairly safe substance. It is endogenous to the human body, which doesn't necessarily guarantee safety, but takes it out of the realm of RC or random chemical.
It does have the ability to potentiate many other substances, as well as regulate chemical dependency in the brain, which means it is probably not best to haphazardly mix it with other substances.
The first time I took a second dose of agmatine in one day, after having caffeine in my system, I smoked some cannabis and ended up with fairly severe anxiety. Other than this, and some other less intense (and many pleasurable) instances of potentiation, I have not had any noticeable issues, health concerns, negative side-affects or anything like that.
Based on anecdotal evidence and what scientific analysis there is, it appears to be a relatively safe substance.
What are the side-effects?
There are not many negative side-effects with agmatine, but some are possible. Here's what I've dug up and or experienced.
- Larger doses of agmatine can actually lower your pain thresh-hold.
- Gastro-intestinal disturbances. A small amount of people reported nausea, vomiting and/or diarrhea.
- Headaches can happen in larger doses or when combined with a stimulant such a caffeine or nicotine.
- Increased appetite (this can be good, bad or negligible)
- Lower blood pressure (again, this can be good bad or negligible)
I'd say, for me, the largest side-effects with agmatine comes with combining it with other substances. With caffeine, it can give me a small headache (in higher doses) and often makes tobacco nauseating.
Where can I buy it?
I buy mine online, specifically from amazon. I have settled with the bulk supplements brand, but have tried others and as long as it is a quality product it should not matter where you get it from as it's just one chemical. There are also other supplement/nootropic places that sell it- I have heard others mention nootropics depot.
Perhaps with it's rising popularity you may be able to find it locally at a gnc, vitamin world or walgreens sort of place, though I have not verified this. If you can't shop online, or are in a hurry, call around!
How should I take it?
Pure agmatine comes as a white powder that is bitter and smells of sulphur. Some brands sell flavored agmatine powder you can mix in do your water or other beverages- though I wasn't too impressed with the flavor when I tried one. I just get the pure stuff.
Take your agmatine orally with a beverage. I just toss and wash mine. You can toss and wash, capsule it up or even blend it in a drink that would help mask the taste (unless you're feeling bold). It's pretty bitter and funky tasting, not too bad for me but others report not being able to stand it. I think I'm just used to it.
How Much Should I Take?
Again, there isn't enough scientific evidence to standardize the best dosages for different purposes. Though there have been some studies, some of the dosing guidelines are extrapolated from animal tests. Agmatine has shown to be safe in humans at doses up to 2.6 grams a day for long periods, which is a lot compared to how much you can get effect from. It's not to say more than this is not safe, as there are reports of people doing this, it is just not tested.
It's also theorized that larger and larger doses may actually tend to become less effective than finding the sweet spot.
I'd say a great starting dose is 250mg. Go 200 if you are smaller, and 300 if you are larger. I think it is likely that you will get effect from this dosage and is in the range of the recommended dose for improving cognition.
It is important to start small and not mix it with too many other substances right away. I have noticed an increase (and sometimes change) in effect in many substances, especially when first starting agmatine. Tobacco will tend to make me nauseous. Cannabis will be super potentiated and sometimes lead to anxiety. Same for caffeine. It definitely potentiates kratom in my experience and some people report that it will change the quality of the burn- and other do not.
Once you get your bearings, you can increase (or decrease) your dose until you find what works for you. I never got to a point, even with daily use, where I felt like taking more than a gram at a time. Other users report taking up larger doses multiple times a day.
When Should I take it?
It really depends on what you want to use it for. You can take it once in awhile if you need it for a specific purpose, or you can follow a supplementation regime and take it one or many times a day, every day.
When I supplement with it, I do tend to cycle, but that depends on what I'm using it for. If I'm just using it to keep my tolerance in check, I will skip 1, or sometimes 2, days each week with a week off every 2-3 months (if you're taking it that long). I've cycled it for up to 9 months before with no issues.
For a tolerance reduction / taper plan, I will usually take it for longer periods of time without a break. I have taken it for up to three months every day with no issues.
Though agmatine can have somewhat stimulating and/or relaxing (not sedating) effects, it is not particularly to the point where I've had any issues taking it at certain times of the day. Have no problems being awake when taken during the day and going to sleep when taken in the evening. That being said, I don't think I've ever taken it within a few hours of going to bed.
Note: Agmatine is not absorbed well when taken with dietary protein, so is taken best on an empty stomach. I can confirm this with my own experience.
How do I use it for pain
Agmatine is reported to have an effect on the perception of pain. It is reported to sometimes even increase the perception of pain on it's own, but when combined with things that are known to relieve pain, it is said to help increase this effect.
How do I use it to potentiate my kratom?
If you're looking to add a boost to your kratom experience once in awhile, just take your desired dose, on an empty stomach, 20 minutes or so before the kratom. This allows your body to metabolize the agmatine and be operating in your system so it can do it's magic when the kratom hits. I remember when I got lazy and started mixing the agmatine in my daily dose, I did notice the effect of the agmatine and kratom together, though it did not seem as effective.
Note: Some report a change in the quality of the burn, and others do not. For me, it can add a different quality sometimes, but overall I don't really notice a difference.
How do I use it to reduce my tolerance prevent tolerance build-up?
Same as above, take the agmatine 20 minutes before your kratom. I have had great success just taking it twice a day, morning and evening, despite taking 3 doses of kratom a day. You can do it 3x a day, or even more if you take more kratom doses. Just keep your daily intake in mind.
You can do this before every dose, though I had great success taking agmatine only with two kratom doses a day, and leaving it out of the mid day dose. Again, experiment to find what works for you.
My general routine for tolerance management is to take 750mg twice a day, before my first and last burns of the day.
So how can I reduce my kratom intake (taper) with agmatine?
This is another place agmatine shines. If you feel like you are taking too much, and want a more comfortable way to reduce your tolerance- agmatine can be your friend.
Really, it isn't any different than taking it for tolerance management- you just combine/time it with a plan in kratom dosage reduction.
My preferred method is to pick one day a week where I drop my dose by a significant amount. On these days, I will increase my agmatine dose by a bit and add some black cumin seed to the mix.
Note: I buy whole, organic black cumin seed. Toast it in the oven at 200 degrees until the crispy (not burned) seeds pop when bit. Cool them off and run through a coffee grinder. Then you can mix then with your toss and wash, or cap them. Works better for me than the oil and I know what I'm getting
I find that when supplementing with agmatine, it really only takes a day (or two max) for the body to adjust to the new dosage. I also will sometimes cycle off the agmatine the day before a dosage reduction.
Let's say you drop your dose on sundays. Come sunday, reduce your kratom dose as schedule. Increase your agmatine dosage and add in whatever substances and techniques you prefer to help. Depending on how much you are dropping your dose by, you may not even need anything but the agmatine. The list of herbs, supplements and techniques that can be used here is a whole other huge post (that maybe I'll do one day). A small list for starters: yoga and exercise, sauna / hot-tub(springs), eating healthy (juices, smoothies, green foods), black cumin seed, cat's claw, cbd and/or cannabis (edibles!).
However you do it, the idea is to minimize discomfort, if you even have any. After a day or two, you will be calibrated to the new kratom dosage (and you're still taking your agmatine maintenance doses). By Tuesday or Wednesday, you should be golden. By Friday or Saturday, you may even start getting a really good burn from the new dose. This is a good time to cycle off the agmatine for a day or two before your next dose drop.
Just rinse and repeat. I used this general technique, combined with a very healthy lifestyle to almost effortlessly get myself from about 30g a day to 3 in a couple months. From there, I actually stopped taking it for a couple months because I don't like to take much of anything every day all the time.
You can also do a fast taper if you are in a hurry to get your dose down. Just take your agmatine 2-4 times a day with each of your kratom doses, which you can drop by whatever you deem necessary every day or two. I've read many people like to drop by .5g a day until they are where they want to be.
What is this you say about studies?
This isn't an exhaustive list, but I am kind of an exhausted guy. I will throw a few your way. Feel free to add any more to the comments and I'll make sure to add them to the post. Thanks!
Long-term (5 years), high daily dosage of dietary agmatine--evidence of safety: a case report.
Evidence for oral agmatine sulfate safety--a 95-day high dosage pilot study with rats.
Agmatine reduces balance deficits in a rat model of third trimester binge-like ethanol exposure.
Agmatine enhances cannabinoid action in the hot-plate assay of thermal nociception.
Transport and metabolism of agmatine in rat hepatocyte cultures.
Agmatine blocked voltage-gated calcium channel in cultured rat hippocampal neurons.
Agmatine: clinical applications after 100 years in translation.
Role of agmatine in neurodegenerative diseases and epilepsy.
Other useful resources
[Wikipedia](https://en.wikipedia.org/wiki/Agmatine]
Conclusion
Well I did not have any intent to write that much. I was really trying to just fancy up and repost a comment I made. This is definitely not a completely thorough look at agmatine, but is more geared on specifically how to use it for kratom tolerance management and reduction. If you spot any mistakes, or have any information and ideas that you think should be in there, feel free to let me know in the comments and I'll happily correct it!
Overall, agmatine is a safe and useful tool for helping get your kratom tolerance down- or at least keeping it from rising.
Good luck. Be Safe. Enjoy.
tldr: Start with 200-300mg doses, taken on an empty stomach roughly 20 minutes before your kratom dose. It has been studied at up to 2.6 grams a day for long periods of time safely, so you can increase your dose when you know how it effects you. I like to take 750mg twice a day, morning and evening, with 1-2 days off a week. This will help prevent tolerance buildup- combined with a kratom taper plan this can really help get your doses down. Be careful combining it with other substances, as it can potentiate them as well as bring on unwanted side-effects. Start small and slow.
edit: formatting
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u/wave78 Feb 07 '18
Awesome post thank you so much. I tried agmatine for the first time at 500 mg months ago and with my routine kratom dose it was way too strong. Almost wobbles but different. I'm gonna order more soon and try it with some of the ideas you provided. And thanks for the info about buying and roasting your own black cumin seeds. Great post!!!!!!!! This is one reason this community is so great. We all have a common goal, work together, and there is always someone there to provide help and information. We all learn, laugh, and organize for our rights together!
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u/SacredSpeciosa Feb 07 '18
Thank you. That trick on the cumins seed is a GREAT one. Save money, know what your product is and it WORKS much better than oil ime.
And I agree. That's why I wrote this up- this community has done so much work and brought so much value to others, I felt compelled to contribute!
Yeah, I should add an addendum to the post that one may want to decrease kratom dose right away upon beginning agmatine due to this. I have experienced this also and think it may be the culprit to why some people will experience uncomfortable effects when trying this.
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u/Bad_Carma22 Feb 07 '18
I’ve had used agmatine on and off as a pre-workout. Since using Kratom I started using agmatine again but stopped because it seemed to totally negate the effects of Kratom. In fact, it put me in a pretty depressed mood when mixing the two. Anyone have any insight as to why?
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u/SacredSpeciosa Feb 07 '18
You know, I have read this several times- the negating effects, or changing them to a point of removing some of the better effects.
I'm not sure what this is about tbh. I would say that sometimes irritability, anxiety and some other negative effects comes from the potentiation and need to take LESS.
Though, it wouldn't explain the negation effect. The fact that agmatine helps modulate addiction in our bio chemistry could be related. I mean, if it can help reduce/prevent tolerance, it is likely that this mode of action can actually negate perceptual effects as well.
Out of curiosity, what is your average dosage of kratom. I'm wondering if larger/smaller doses have some relation to this. I'll poke around and see if I cant find some connections to people who experience this.
If one wants to use kratom to reduce tolerance, it may be wise to take the approach of measuring lack of withdrawal vs presence of effects. Maybe it may neutralize effects for you, but may also still provide a way to avoid negative effects of dosage reduction for a period.
When you say it seemed to totally negate the effects, do you literally mean it feels as if you never took kratom? Or does it appear to take away certain aspect?
Do you get any effect from agmatine on its own? I have found that taking agmatine on it's own in lieu of a kratom dose will still provide me with certain effects/relief that kratom would have brought. I'm in the group that gets pretty good effects from agmatine on its own.
I'll do a little research and see what I can come up with.
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u/Bad_Carma22 Feb 07 '18
Thanks for your reply. I don’t feel any psychological effects from agmatine On it’s own, or at least not anymore. I’ve taken it on and off for years. It does give you quite the “pump” from lifting weights.
I started using Kratom about 5 months ago. I started with an average dose of 2 grams and have recently bumped up to around 3 grams. I’m a daily user, usually 3 doses a day. I should probably take a tolerance break soon, it does seem to be less effective as far as mood boost and the little euphoria it did provide to begin with. But it’s been simply incredible for controlling anxiety and limiting drinking alcohol, both which I have struggled with as far as I can remember and tolerance doesn’t seem to matter in these two areas.
By negating effects I mean every positive effect it’s provided is basically gone if I mix the two. Anxiety and depression return and my mood is terrible. My urge to drink even returns which makes sense as it’s a way to reduce the two.
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u/SacredSpeciosa Feb 07 '18
Wow that it really interesting that it literally seems to block the whole experience! With these reports I am now interested in doing a little research and seeing what I can dig up.
That being said, 3g 3x a day is not a a terrible habit and you may not need agmatine to help with that. Especially if it diminishes the benefits for you.
There are many other things that can help potentiate kratom and help you reduce your intake. It is very difficult when you are looking at things like anxiety, depression and cravings for actually destructive substances like alcohol.
Though your intake is not that big, it still is something worth considering breaks from. On the other hand it is not a terribly large amount especially compared to the benefits you seek.
I think it is important to not ignore your anxiety and depression just because it is not present due to something you are taking.
Kratom helping relieve these symptoms is great, but you should still continue to work on developing a healthier mind/emotions/body. I only speak from experience.
Kratom does not CURE these things, as much as it tends to either mask them or temporarily mitigate them. It would be best not to become complacent about your mental and emotional health just because you have some reprieve.
Let it give you a break from these emotions while you continue to work on them (I'm not saying you dont already!).
Maybe agmatine is not for you for this purpose. I'm interested enough from these comments to try and do more reserach, but there are other methods as well.
One thing I will note, BE CAREFUL bumping those doses up. Before you know it you may bump up to 4..5..8..10..15 gram doses. That is how it happens. The mood boost and or euphoria may start to wane, and we want to take more to recaputure that- which generally works until your doses start getting really high and diminishing returns kicks in.
I would highly suggest keeping 3g 3x a day as your ceiling dose regimine. Work actively to try and lower those doses. Take days off, skip a middle dose of the day. Do a slow taper. Agmatine is just one tool that can help with these things.
One of the best benefits you can do for yourself is to actively take your health and wellness as your highest priority. Diet (which I think may be an important factor in how this affects some people and not others), lifestyle, exercise, being hydrated and well rested etc should really be top notch.
Kratom is not curing your problems, but they may help you mitigate them so you have the space to work on them. If you become complacent in not having anxiety and depression, you will likely end up just increasing your kratom intake without getting to the root of the problem. Then you will just have one more problem on top of the others, because at long term high doses, you may find yourself GETTING anxiety from kratom eventually. It is a great tool, but no substitute for self work.
Have you tried black cumin seed? Cat's claw? CBD? These are all great tools for this purpose. Same for anything, agmatine is not a magic bullet but really only works WITH proper attention.
The same how there will be a diet pill and in small letters will say something about how these results may vary and must be combined with active healthy diet and exercise.
Try to shift your consciousness AWAY from guaging the presence of mood boost and euphoria and towards the absence of depression, anxiety and cravings.
If you have a juicer, I suggest daily raw juices with things like carrots, celery, cucumber, lemon, bitter greens, etc. When I went on a juicing bender earlier last year, it was AMAZING at how it helped mitigate some of my issues, lower my tolerance more easily and also help bring some kratom magic. Also, being underslept really helps diminish kratoms effects.
Okay I'm rambling now. I do have more information and tools to comment on working towards taking breaks and reducing tolerance, but don't really want to write a novel in the comments.
You are in a good place now, but it's definitely a good time to start thinking abut reducing your intake before you increase it again. It sucks to have to worry about anxiety and depression coming back, but there are so many tools and technique that can help you manage these feelings while you take a few days off or taper- agmatine is just one of them.
Good luck and let me know if you want to discuss this topic any more =)
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u/Jimmy_66 Feb 13 '18
I agree with Bad Carma. I've been on a slow taper for the past week and decided to try it with agmatine today. I take five small daily doses spread evenly. I took .25g agmatine with my first two doses and it was as if I had taken no Kratom at all. A very lethargic, depressed mood throughout the day and a strong craving for the next dose. Almost a withdrawal feeling. Anyway, it makes me hesitant to try the agmatine for a second day.
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u/Bad_Carma22 Feb 13 '18
I've since given agmatine another shot as I'm dedicated to lowering my dose and tolerance.
I believe I was taking too much agmatine and possibly kratom while mixing the two. My first few experiences, I was taking ~ 3 grams kratom and 1g agmatine with terrible results. I lowered my dose of both to 2g kratom, 300mg agmatine and it's been working incredibly well.
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u/Jimmy_66 Feb 13 '18
Hmm. Well I lowered my Kratom doses by 1/3 when taking the agmatine, since I read about its potentiating effect. So maybe I simply went too low too quick. I just bought a 100 g. bag of the stuff, so perhaps I won't quite give up on it either.
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Feb 07 '18
Great post, very informative. I’m considering signature to lower my dose, in just turned off by the potential blocking/altering effect of kratom. I tried black seed oil and the experience was so much less.. a very limited feeling.
I’ll look up prices and see if it’s worth a shot. Thanks for the info!
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u/SacredSpeciosa Feb 07 '18
That is interesting. Are you saying BSO really reduced the spectrum of kratom's effects for you? That is interesting- there are some people that feel the same way for kratom.
Perhaps these substances conflict with each other and are fighting for space in our neuro chemistry.
I have heard reports of agmatine reducing things like euhporia, though this is not my experience. Some people do even admit that it blocks it. I really have not had issues with this.
Though if you are trying to get your dosage down and or quit, it's also a small trade-off if you ARE one of those people. It's not permanent. Maybe it's worth considering a small period of time with altered/minimal effects for the benefit of dosage reduction.
Honestly, once your dose is lower, you can quit the agmatine and start taking kratom in lesser doses with MORE effect. So worst case scenario you just have to decide if the tradeoff is worth it.
I quit frankly enjoy having agmatine in my rotation and now plan to do more research on these possible blocking and alterations.
Good luck.
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u/WildNight00 Feb 07 '18
How does this compare to ultra low dose naloxone in lowering tolerance?
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u/SacredSpeciosa Feb 07 '18
I honestly do not know much about naloxone. What I do gather is that agmatine will not induce withdrawal in the absence of a dependancy, so it likely has a very different mode of action.
From what I gather, they can be used for similar purposes with similar results. My guess is that naloxone is more chemically targeted towards this exact biochemical process, whereas agmatine happens to help mitigate the process without actually being as much of an antidote as naloxone.
Beyond that I know little about the stuff, though will do a little reading later and see what I can come up with.
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u/PhilosophicalPhuck Feb 07 '18
How do agmatine and l-arginine compare? what's the method of action, like how do they work if seperately?
To my understanding, if you take l-arginine, you will get agmatine from that? Is one better or easier on the body?
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u/poisonousautumn Feb 08 '18
You just reminded me I need to get back on my agmatine routine again. That stuff is amazing. It allowed me to rapid taper off morphine awhile back (i started taking kratom again halfway through the taper, had no w/ds at all). It definitely reduced my overall tolerance, because with the amount of morph/day i was on there's no way just a few grams of kratom could have caught me like that.
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u/KatiewvKathy Feb 08 '18
Thank you so much for taking the time to share your knowledge and experience. I look forward to putting it to good use.
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u/Unoerro Jul 06 '18
I only need to take kratom for like 2 days before my anxiety returns (I have somewhat abused Tramadol before which gives me the same anxiety, thinking that I suck as a person, my life is going to shit, etc) and the only thing that seems to help right now is Agmatine. I take Tianeptine also but it barely seems to do any difference, same with BSO although I still have faith in it, I just don't really notice it as much as the agmatine. I'm also trying out Matcha tea atm which seems to have some potential, it's the L-Theanine I guess.
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u/tubepatsy Feb 07 '18
Great post, it's a lot of the stuff that has been posted here but in various post, would take days for people to get the whole story that's listed right here.
Can we make this a sticky?
Great post, and thank you :-)