NDMA antagonists and their effect on tolerance

The following is a selected summary of a much larger and very helpful post at longecity by midievil titled NMDA antagonists for drug tolerance, does it work? A collection of the evidence and anecdotal reports..

NDMAR and stimulant tolerance

• PMID: 2671566 Blockade of "reverse tolerance" to cocaine and amphetamine by MK-801

• PMID: 9560846 The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants

• PMID: 11915303 Alteration of neuronal activities following repeated administration of stimulants

NDMAR and dopamine

• PMID: 1382178 Chronic administration of NMDA antagonists induces D2 receptor synthesis in rat.

• • D2 binding studies carried out in MK-801 chronically treated (0.3 mg/kg/day per os, for 50 days) and control rats revealed an increased receptor density in treated animals without a significant change in receptor affinity.

• PMID: 7770607 Effects of the NMDA-antagonist, MK-801, on stress-induced alterations of dopamine dependent behavior.

• PMID: 10443547 Adaptations of NMDA and dopamine D2, but not of muscarinic receptors following 14 days administration of uncompetitive NMDA receptor antagonists.

• • The same treatment with amantadine did increase [3H]raclopride binding to dopamine D2 receptors by 13.5%.

• PMID: 10214758 Decreased striatal dopamine-receptor binding in sporadic ALS: glutamate hyperactivity?

• • In drug-naïve, sporadic ALS patients we demonstrated decreased striatal D2-receptor binding in vivo that could be partially reversed by the glutamatergic transmission blocker riluzole.

• PMID: 12832726 Effect of combined treatment with imipramine and amantadine on the central dopamine D2 and D3 receptors in rats.

• • We can conclude that repeated administration of AMA, given together with IMI, induces the up-regulation of dopamine D2 and D3 receptors in the rat brain.

• PMID: 10096038 Modulation of dopamine D2 receptor expression by an NMDA receptor antagonist in rat brain.

• • In the striatum, a significant increase in striatal dopamine D2 receptor mRNA levels was shown in animals treated with CPP.

• PMID: 14997010 Enhanced expression of dopamine D(1) and glutamate NMDA receptors in dopamine D(4) receptor knockout mice.

• • The findings suggest that D1, D4, and NMDA receptors might interact functionally and that developmental absence of D4 receptors might trigger compensatory mechanisms that enhance expression of D1 receptors in NAc and CPu, and NMDA receptors in NAc, CPu, and hippocampus. The findings also encourage cautious interpretation of results in knockout mice with targeted absence of specific genes, as complex adaptive changes not directly related to the missing gene might contribute to physiological and behavioral responses.

Anecdotal Reports: 3 Samples From Each Section

DXM

• I've been using Delsym (dextromethorphan polistirex, DXM, a sustained-release preparation of DXM) to prevent amphetamine-tolerance as long as I've been taking them. So that would be about 8-9 months of use without breaks, and the proof is in the pudding. :-) I haven't developed any tolerance whatsoever to any of the drug's effects. [Prozac 40mg, Robotussin 15mg/6hours, 60mg/day Adderall]

• i just wanted to follow up on the subject of DXM and amphetamines. it's been my XP that a recommended dose of cough syrup, the only active ingredient being DXM, taken with 90mg XR adderall are as follows: much smoother onset, more of a ramp than a rocket, more mentally stimulating and less physically stimulating, greatly reduced negative side effects(rapid pulse, rebound effect after dosage wears off) and condition of user less obvious to the outside world. anyway, overall i am very pleased with the results of the combination. i plan on adding calcium and magnesium to my regimine as well.

• Today I decided, just to see how it goes, to take 30mg, less than my full prescribed dose, along with a tablespoon of delsym and some magnesium. Not only did I get the euphoria and motivation, but I also got the focus and energy and I DIDN'T FOR ONCE end up with freezing cold fingers!!! and its lasted much longer than using 4 times as much has and im not crashing. (Strange as it will not usually reverse tolerance retroactively, personal comment)

Memantine

• On the 12th day of being on 10mg memantine, I took my usual 15mg dose of amph, and felt a powerful surge of euphoria, sociability, confidence, and was completely free of SA. It was just like taking amphetamine for the first time! Over the next 4 days, I took 15mg each morning but skipped one day. Each dose was just as powerful and efficacious, AND the duration was extended to ~7-8 hours! So this brings me to today, where I decided to reduce my amph dose to 10mg, and it's working even better than 15mg did before starting memantine.

• Memantine has truly saved my life, i do not exaggerate.I currently take 15 mg Memantine a day......5 and 10mg/day both significantly inhibited tolerance, however, only for a period of 2-4 weeks, I could take Amphetamine consistently (every day, 30mg) with its mood-elevating and anxiety-reducing and pro-social benefits, continuing to remain and be of use. When tolerance becomes a problem, i take short 2-5 day breaks from Amphetamine, and every time, my tolerance goes down significantly, and I am able to resume amphetamine, with its beneficial effects being much stronger again.

• Memantine is good stuff. I've been taking 5mg a day for several weeks now, and i'm just now starting to see its tolerance prevention ability. I took one 20mg adderall XR + 5mg memantine this morning after a 4 day break from adderall and it has worked great all day. I lost the magic there for awhile but today the addy is working like it did during the first few months and this is just from 20mg.