I read a post on another forum, The New Bluelight, that taking extra magnesium in a chelated form helps a great deal toward controlling tolerance to stimulants. I'm investigating this. My psychiatrist never heard of this, but MDs are often out of the loop on benefits of higher than normal doses of nutrients. Just wondering if anyone else has heard that. When I get more info substantiating or debunking this I'll post it. The dose of magnesium to take if you're taking any of the stimulants is around 1000 mg. and works best in a chelated formulation. Allegedly.

Update: Found the info and it is a little technical for the "lay" person but makes the point that anyone taking amphetamine or Ritalin probably should take extra magnesium. Here it is.

[borrowed from The Blue Light forum]

Amphetamine tolerance is caused by excess Ca++ influx through the NMDA receptor gated calcium channels on the outer membranes of the dopamine cells bodies in the ventral tegental area, one of two areas in the brain with concentrations of dopamine producing neurons.
As alluded to above, taking an appropriate NMDA* (partial) antagonist will prevent the development of a tolerance for the effects of an amphetamine or amphetamine-like stimulant. Also, by preventing excess Ca++ influx into the neuron, an NMDA antagonist will prevent associated brain alterations and damage (excitotoxicity).

Studies have indicated that amphetamine tolerance is prevented by exogenous or endogenous agents that are able to inhibit excess Ca++ influx into the neuron through the gated calcium channels on the neuronal membrane that have NMDA subtype glutamate receptors.Glutamate , the body’s major excitatory neurotransmitter, opens the gated calcium ion channels upon attaching to the NMDA receptor. A number of other receptors are also expressed on these calcium channels, which, when stimulated, either facilitate or inhibit glutamate’s action.

It is also important that agents that inhibit calcium channel activity not also cause deficient Ca++ influx. For example, ketamine is a full NMDA receptor antagonist, that prevents excess Ca++ influx and amphetamine tolerance. But being a full NMDA antagonist, ketamine in excessive doses results in deficient Ca++ influx. This could be one of the reasons it leaves K-user in a state of disassociation.

Magnesium is an NMDA antagonist. Most people are deficient in magnesium, and stress reduces magnesium levels. Whether or not one takes amphetamines, magnesium supplementation is very important for mood, general well-being and keeping stress levels under control. It is also important to take magnesium in efficient form, with adequate bioavailability. The best type is magnesium glycinate (chelated) with bioavailability at around 80%. Second best is magnesium carbonate with (I don't remember exactly) bioavailability at little above 30%. Supplemented magnesium should be at 500 mg/day level. Also there is a study which shows that children who use amphetamine-type stimulants have bad magnesium/calcium balance. Calcium levels stay the same with amphetamine usage, but magnesium levels drop.


* The NMDA receptor is a receptor for the neurotransmitter glutamate, which is the most important excitatory transmitter in the brain. It is not only a receptor, but also a channel (it is thus a ligand-gated ionic channel). N-methyl-D-aspartate is the famous agonist of the NMDA receptor, the latter being named after it. It is a very complex and fascinating ligand-gated channel that seems to be involved in the toxic effects of excessive glutamate, and in many other processes like synaptic plasticity and target recognition.

Hmmm... Mrs. Clam sells supplements of all kinds and is pretty knowledgeable about them. I'm going to bring this to her attention and report her reaction to it.

I know that acidifying agents such as citric acid and ascorbic acid etc. lower the absorption of
(meth)amphetamines and that this can play an antogonizing role towrds tolerance. And on the flipside of this is that alkalinizing agents like sodium bicarbonate increase the absorption of (meth)amphetamines, and increase the blood levels of said substances so as to potentiate their effects.



This that you've shared about the possible benefits about magnesium is most certainly an interesting subject to explore! Personally, I don't see why the paper that was published and posted here would be invalidated seeing as how the history of such papers is only produced after painstakingly made research using the scientific process.

While continuous dosing with amphetamine causes tolerance, intermittent dosing produces "reverse tolerance" or sensitization to its psychological effects. As a result, regular users commonly experience a quick decrease of unwanted side effects, without an equivalent loss of its stimulant properties.

i know this might sound like a druggie question but is it possible to reverse your amphetamine tolerance? i read the part about ketamine but ketamine is an animal tranquilizer when given to animals and a very potent hallucenogen when given to humans, but what all is there to reverse tolerance as i only felt like i could concentrate the most when i first started taking it (when i felt the euphoria) i know thats not too good but thats when it was the most effective (and its not very effective at 10 mg's a day but doc is uneasy with raising dose...

i doubt they have any effect in avoiding amphetamine tolerance, they work for morphine tolerance tough

Amphetamine use of 3 weeks + causes higher than normal plasma levels of magnesium to begin with so this may not be the hottest idea.

Don't you think that ingesting metals on the basis of a speculative benefit is a bit risky ?

ME :D

This is the first that I have heard that NMDA receptors play any rols in amphetamine's pharmacology. If I remember correctly, amphetamine doesn't even work via ion-channels, but through a protein-kinase enzyme that phosphorylates an intracellular portion of the dopamine transport protein, inducing reverse uptake.

Now, I suppose that the author may be referring to the action that dopamine has on the postsynaptic neuron, but blocking the NMDA receptor is not going to fix that, because this would reduce activity in that neuron, which is the opposite of what you're trying to do by using amphetamines.

Also, I do not know if magnesium is an NMDA antagonist in high doses, but NMDA antagonists produce some very noticeable effects...NMDA antagonism is responsible for the effects of the dissociative anaesthetics: ketamine, PCP, and dextromethorphan. Dissociative anaesthesia is a fairly intense form of hallucination in which the subject feels as though his mind has been dissociated from his body, similar to an out of body experience.

One interesting side-note, though, is that NMDA antagonists appear to help with Alzheimer's disease, although I'm not sure how. They are sometimes prescribed along with cholinesterase inhibitors (which slow the breakdown of acetylcholine, a chemical involved in memory) to slow the progression of the disease.

I was recently prescribed Riluzole, a partial NMDA antagonist in addition to Adderall. I never heard until now of any effects on tolerance. I did notice a definite increase in stimulation since I started the drug, like when first started Adderall, which I thought was odd since drowsiness is listed as a principle side effect, not stimulation. Hmm. It might be that the Riluzole is making the Adderall more potent. (tolerance reversal).

There seems to be very little published information on this since Riluzole is normally only prescribed for Lou Gehrig's Disease or "Stephen Hawking's Disease" or whatever you want to call it. Not depression or ADD. So its interaction with other psychoactives is pretty much unknown.

Maybe I can cut back on the Adderall now.

:soapbox: One more thing: as far as I know, NMDA receptors do play a role in dopamine (and dopamine agonist) pharmacology.link (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15079860&dopt=Abstract)

Not that I'm able to make much sense of medical journals.