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Opioids Methadone Tolerance

M

Mass08

Bluelighter
Joined
Feb 22, 2012
Messages
775
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Cloud 9
Hey everyone,

So I just replied to the post in here about NMDA antagonists and their effects on tolerance to drugs and this got me to thinking. There is some data out there that states that NMDA antagonists prevent tolerance increases for different substances. I know that there is still a lot of research to be done on the subject and we don't have all of the information currently, but if this is the case why do people on methadone need ever increasing doses? I believe I read somewhere that the racemic methadone that is dispensed at U.S. methadone clinics acts as a NMDA antagonist, shouldn't that prevent tolerance? Is it because it isn't a very strong NMDA antagonist?

Cheers,
Jason
 
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Usually they don't need ever increasing dosages. Most people will find a dose that will comfortably hold them for twenty four hours, but still up their dose to chase a high. I'm currently on a dose far too low, but I will say, if I don't take methadone, I do not feel opiates nearly as much, and the euphoria from amphetamines is greatly diminished. The one weird thing I've noticed though is that combining benzo's with methadone is actually less euphoric for me than suboxone and benzo's were, and my benzo tolerance seems to skyrocket way faster now. But that could just have to do with the fact that I've been taking benzo's at varying dosages for about three years straight, and at some point tolerance just starts to kick ones ass, and that nice serenity starts to fade into something more mundane.
 
Znegative said:
Usually they don't need ever increasing dosages.
Click to expand...
They do need ever-increasing dosages if they want to feel euphoria and analgesia. After a while a stabile dose simply alleviates withdrawal symptoms and nothing more. Isn't that the same for all opioids? It's not like you need ever-increasing doses of any opioid in order to merely alleviate withdrawal, correct?

Most, if not all (?) the studies on NMDA antagonists preventing or reversing tolerance to opioids have been done on animals. It's clear that the same rules don't apply to humans because there is a study saying giving rats magnesium completely reversed objective tolerance to morphine and obviously taking magnesium doesn't magically reset your tolerance to morphine for a human.

The idea is that NMDA must at least have some kind of complex role in tolerance and dependence to drugs, and that perhaps NMDA antagonists in the right dose can potentially slow the rise of tolerance in humans. Tolerance is a very complicated and poorly understood thing and has a number of different mechanisms and methadone is only a weak NMDA antagonist. It's possible that tolerance to methadone might build less slowly than tolerance to other opioids, but that is even debatable in my opinion (although I'm sure it depends on the person because there are those rare people who say they still felt high from their methadone after being on it for 6 months).
 
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