Wellbutrin has been a popular anti-depressant for those who can’t tolerate SSRI’s, or for people wanting to quit smoking (trade name Zyban). For a lot of people though, Wellbutrin can make them edgy, agitated and anxious. Adding Agmatine Sulfate, a novel endogenous neurotransmitter, to your regimen may not only help quell that tension, but may also increase Bup’s beneficial effects on depression.
I’ve talked quite a bit about Agmatine Sulfate. Since then I’ve also experimented quite a bit with it. Aside from the occasional accident of taking too much at once (it can sometimes cause intestinal disturbance if taken in too high of a dose) I’ve always been pleased with the effects. There is a very strong increase in Nitric Oxide, and therefore the pumps associated with it. A lot of people tend to say that it inhibits NO, but what they fail to realize is that it inhibits iNOS (inducible NOS, also known as cytokine NOS or cNOS, which is in the immune system realm) and nNOS(neuronal NOS) while increasing eNOS (endothelial NOS, which in layman’s terms means the veins and vessels , which is where bodybuilders want it, at least if the pump is something they think is beneficial).
Agmatine does some other really awesome stuff too though. It is a calcium channel blocker, it is an alpha2 adrenergic agonist (well sort of… It seems that this is up for debate – read the abstract), is an endogenous ligand for the imidazoline receptor (well, there again… sort of… read the previous link to see that there is some debate about this) and even seems to have an effect on the 5ht1 and 5ht2 receptors, which have an anti-depressant like effect. It’s also a fairly strong NMDA antagonist.
One thing is for sure. It will definitely give you some wicked pumps. It will also drop blood pressure, and if your brain chemistry is anything like mine, you’ll find it calming. The effect is subtle, but noticeable. While we have discovered that Agmatine is a neurotransmitter, I think it’s important to point out that we know serotonin, dopamine and norepinephrine are all transmitters as well, but swallowing a bucket of any of these substances will have a limited effect. In other words, just because something is a neurotransmitter doesn’t mean that you can just swallow it and boom, you’re feeling its effects. Even L-dopa has to be taken with a decarboxylase inhibitor in order for it to have any effect, and even then it’s like a carpet bombing of the nervous system compared to the effects of a dopamine reuptake inhibitor like cocaine. You see, that is where I think things will get interesting – when we start discovering ways of affecting how our body handles, appropriates, utilizes, and even stores Agmatine. But I will say that taking a gram of this three or four times a day will have a noticable beneficial impact on your mood, blood pressure, heart rate and muscle fullness. It will also turn down your aches and pains just a wee bit.
Wellbutrin on the other hand, is a relative of cathinone. Well actually, it IS a cathinone. MethCathinone, otherwise known as Khat, is a stimulant similar to amphetamine. Bupropion is actually meta-
In other words, I do believe bupropion has an effect on dopamine, but that is far from its main effects. If it was really good at doing that, we would have a drug of choice on our hands, and it would be scheduled. It would get you really high, and it would be self-rewarding, leading to drug seeking. Most people agree, even though it can be useful for depression, it doesn’t come anywhere close to something like cocaine in terms of its dopaminergic effects.
In addition to its effects on NE (norepinephrine) and DA (dopamine), Bupropion also antagonizes the nicotinic acetylcholine receptor. This is where its benefits for smokers comes into play. Unfortunately, this is also what keeps it from being a more “fun” drug. What I mean to say is that it blocks nicotine, which for some people can be very good at releasing dopamine indirectly. So taking bupropion will kill your buzz if you like nicotine, and while it’s good at inhibiting the reuptake of dopamine, it might also indirectly prevent its release due to its effects on nicotinic receptors.
So now let me get to the point of all this. You mean, there’s a point? Yup.
I started taking Wellbutrin a while back after deciding to start up Lexapro. Any time I have tried an SSRI, I have felt pretty dulled out physically speaking. Taking Wellbutrin gives you enough Norepinephrine (think excitement) that it helps take the edge of excess Serotonin (think puddle of contentment). But as has happened in the past, I discovered that Wellbutrin makes me anxious. Well, let me go back just a bit. Bupropion makes me anxious. I have been using generic Sustained Release Bupropion for a while. After reading this report, and reading other anecdotal experiences, I think it’s safe to say using the brand name might be the best idea in terms of dispersion. The time-release properties of the name brand just can’t be beat. And with bupropion and anxiety, it is all about timing. Beyond that though, there are still some people who get a little edgy and anxious due to the NE effects of Bupropion.
As it turns out, a study was done recently showing that Agmatine increases the anti-depressant efficacy of Bupropion. Not only that, but it seems that blocking Agmatine production in the brain kept Bupropion from being as effective. So this not only tells us that Agmatine can be a good addition to a Wellbutrin regimen, but it may be that Bupropion actually has some intrinsic effects on how Agmatine does its job in the brain. Again, as I mentioned earlier, we are looking to find ways of manipulating the Agmatine system in the brain as much as we are interested in the fascinating versatile effects of the amino acid by itself.
Evidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim test.
Although bupropion has been widely used in the treatment of depression, the precise mechanism of its therapeutic actions is not fully understood. The present study investigated the role of agmatine in an antidepressant like effect of bupropion in mouse forced swim test. The antidepressant like effect of bupropion was potentiated by pretreatment with agmatine (10-20mg/kg, ip) and by the drugs known to increase endogenous agmatine levels in brain viz., l-arginine (40 μg/mouse, icv), an agmatine biosynthetic precursor, ornithine decarboxylase inhibitor, dl-α-difluoromethyl ornithine hydrochloride, DFMO (12.5 μg/mouse, icv), diamine oxidase inhibitor, aminoguanidine (6.5 μg/mouse, icv) and agmatinase inhibitor, arcaine (50 μg/mouse, icv) as well as imidazoline I1 receptor agonists, moxonidine (0.25mg/kg, ip) and clonidine (0.015 mg/kg, ip) and imidazoline I2 receptor agonist, 2-(2-benzofuranyl)-2-imidazoline hydrochloride, 2-BFI (5mg/kg, ip). Conversely, prior administration of I1 receptor antagonist, efaroxan (1mg/kg, ip) and I2 receptor antagonist, idazoxan (0.25mg/kg, ip) blocked the antidepressant like effect of bupropion and its synergistic combination with agmatine. These results demonstrate involvement of agmatine in the antidepressant like effect of bupropion and suggest agmatine and imidazoline receptors as a potential therapeutic target for the treatment of depressive disorders.
As I began my usual startup of Wellbutrin XL (150mg ED) I found I had a certain edginess as per usual. After reading this study I started taking Agmatine again, and in a more regimented way. 2 grams, three times a day. I think 500mg would be sufficient, but I got a kilo on the cheap so I figured I would take it up a notch. It has definitely quelled the inner tension that Wellbutrin normally brings about in me. I am going to continue using the two together to see what, if any, anti-depressant enhancement might ensue. For those wishing to add this to their diet, make sure you take it on an empty stomach, and don’t overdo the dose. Too much and you can disturb your gut, whereas taking it with a meal tends to reduce instestinal uptake because Arginine competes for the same transporter, so the protein in your meal is going to fight for dibs.