Almost everyone's opinion on using speed/amphetamine/meth is that the best highs were the first two (or three). That is also the case with me.
When I first tried speed I've used very small amount (I'd say it was around 50 mg) of rather pure amphetamine and damn, it was the best day of my life :] I remember that I was euphoric for around 12 hours, I couldn't stop talking, the music sounded extremely well, I was full of motivation and never felt better in my whole life. Afterwards I had no comedown.
My second attempt wasn't as fantastic, but also wonderful. Since then I've never achieved that extremely euphoric sensation with my head tingling from pleasure and my insides screaming "DAMN I FEEL FUCKING AWESOME!!!". After a year of my speed usage and trying doses even four times as high as the 1st amount I tried - I never came close to that feeling. Sure, I can be motivated, energetic, have a great time during the tweak, be very sociable, but it is still not like during the first two times. I'm aware that amphetamine tolerance develops very quickly and stays at that level for a long period of time (even when taking breaks), so lately I've been doing some online reading on that subject.
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.
So basically we have following NDMA antagonists:
1. Memantine (Akatinol/Axura)
2. Acamprosate (Campral)
3. Amantadine (Symmetrel/Amantix)
4. Magnesium (supplement)
(funny that 5,6,7 are recreational drugs)
Two of them have minimal (or none) side effects and have been identified (and verified by one anecdotal person, which has been taking amphetamine-type stimulants and NDMA antagonist with same beneficial effects for a period of 2 years) as preventing amphetamine tolerance: 1) Memantine and 2) Acamprosate.
1) Memantine is a partial NMDA antagonist that effectively puts an upper limit on Ca++ influx without compromising healthy levels of Ca++ influx. Memantine is not available in the US at this time. It is in stage 3 trials for Alzheimer’s disease. US approval may come within the next 2 years. Memantine is now approved in the European Union for the treatment of Alzheimer’s. It has been marketed in Germany since 1978 for the treatment of dementia and other cognitive disorders. It comes in 10mg tablets. One or two tablets/day are sufficient to prevent amphetamine tolerance, overactivity of the NMDA receptor and consequent free radical stress inside the neuron. The most expensive option though.
2) Acamprosate (n-acetyl-homo-taurine) analogue of the amino acid taurine. Alternatively, it may be termed as a carrier molecule for taurine, that allows taurine to readily cross the blood brain barrier, unlike taurine itself. Taurine is a NMDA receptor antagonist. Acamprosate is an investigational drug in the US, undergoing stage 2 (?) trials for the treatment of alcoholics. It is available in most European countries as a treatment for alcoholism, with great efficiacy. Cheaper than memantine, however efficiacy should be the same.
3) Amantadine, originally used in the treatment and prophylaxis of influenza infection and drug-induced Parkinsonism, also blocks NMDA receptors. Besides it is beneficial in traumatic head injury, dementia, multiple sclerosis,cocaine withdrawal and depression. Amantadine appears to act through several pharmacological mechanisms, none of which have been identified as the one chief mode of action. It is a dopaminergic, noradrenergic and serotonergic substance, blocks monoaminoxidase A and NMDA receptors, and seems to raise beta-endorphin/beta-lipotropin levels. I couldn't find what amount of the drug should be used to block NDMA. Cheaper than Acamprosate. No one has tested it yet, but I think it would be a good choice.
4) Magnesium is also 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.
5) DXM - definitely the cheapest option of all NDMA antagonists, but I'd rather use Memantine or Acamprosate. Although, I've heard anecdotes that doses as low as 70 mg/day are enough to block NDMA - I couldn't find those amounts in abstracts/studies.
6) and 7) I wouldn't use as an amphetamine tolerance prevention. Ketamine for its known effects (you wouldn't want to be in a K-hole during the tweak just for the sake of prevention tolerance)
PCP - this one doesn't need explanation. It has nasty side-effects and I've mentioned it just because it is a NDMA antagonist. I wouldn't touch it even if it was dirt cheap.
So basically combination of partial NDMA antagonist and amphetamines should prevent tolerance. But I'm curious whether NDMA antagonists are able to *reduce* amphetamine tolerance. If yes then my goal would be to reduce it as far as to the point of first speed experience :] Right now, I have high amphetamine tolerance (too much tweaking during short time in the summer) so I will be using Acamprosate to try and reduce my tolerance. I'll post my results here.
And sorry for the length of the post - but I just wanted to write down everything I researched during last few days (I skipped PubMed abstracts).