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A question regarding tolerance

H

Harry Redknapp

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Jan 10, 2000
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A statement I read on another board:
It is only possible to have a tolerance against fat-soluble drugs because they are the only ones that stay in the body.
Surely this is not true?
No smart arsed answers or flames please. Just a simple true/false and an explanation would do nicely.
Thank you for your help :)
Click to expand...
 
no explination but sounds like bollocks to me. The fact that it takes me 5x as many pills as it used to, to get high dosn't mean I have any MDMA or metabolites in my body. This is why we can pass drug tests after a few days. The way I should think most tolerances ocur is partly mental, you get used to the effects of the drug and so learn how to operate on it rather than getting f'ed and not being able to function. Secondly like with nicotine our body becomes used to it and so the levels of whatever drug need to be maintained in the body for it to function correctly. I'm sure someone with actual ;) knowlage will come and correct me but thats my guess.
[ 03 January 2002: Message edited by: Johny Boy ]
 
The techie explanation offered up for tollerance is all about receptor down-regulation due to molecules of the drugs being in the brain still (or some such mumbo jumbo)
But like you say - it takes a helluva lot of MDMA to get me buzzing these days. Likewise with amphetamine. Christ - even beer has a tollerance. But the only drug I know of that is fat soluble is THC. (and to be honest with you I haven't noticed so much of a tollerance to it - one spliff still gets me stoned)
But I would like someone to gimme a decent explanation before I go rip the poor cunts head off ;)
 
It's total bullshit... if that was the case I would still be getting off on 10mg of oxycodone and a 100ug/hr fentanyl patch would bring me close to death .. you can become tollerant to most any drug - fat soulable or not ...
Another reason to not visit other drug message boards..
 
The explanation for amphetamine tolerance is easy. It indirectly stimulates the CNS by releasing endogenous catecholamines (norepinephrine, dopamine). MAO eventually destroys most of the released dopamine (the rest is reabsorbed into neurons). So after using for a certain period of time, the catecholamine stores of the brain become depleted. But the stores are replenished fairly quickly with a break from using (sleep is important in synthesizing new pools of dopamine). Most of this is true for cocaine and MDMA also.
Some drugs like alcohol (which is water soluble) have more than one method of inducing tolerance. First the CNS eventually adapts its activity to accomodate the presence of depressants (if used often enough). The CNS increases its activity to offset the depressant effects and maintain a normal state of arousal. So when an alky stops drinking, the CNS continues as you were still drinking. And you're not so the activity is great enough to cause seizures, shakes, etc. Also the liver gets better at breaking down alcohol (enzyme induction) so it is metabolized quicker.
Is this what you were asking for?
 
whether it is water soluable or not is inconsequential....
amphetamine is an amine releaser, thus DIRECTLY stimulates the CNS via enhancing synaptic norepinephrine.
Tolerance can either be metabolic or pharmacodynamic or most likely a combination. Metabolic tolerance involves an increased synthesis of the drug by specific liver enzymes leading to an increase in the amount of substance/drug needed to achieve the original effect or "high."
Neurons are involved in Pharmacodynamic tolerance Due to the drug being consistantly present, receptors either increase, or reduce their sensitivity through down-regulation.
 
Psychology 103/ Techniques in Physiological Psychology
Amphetamine and Behavior
"Amphetamine is an indirect catecholamine agonist that does not bind to catecholamine
receptors directly but serves to increase the amount of catecholamines in the synapse by
promoting presynaptic release, preventing presynaptic reuptake, and inhibiting MAO activity."
From another document:
"Indirect agonists are associated with tachyphylaxis [tolerance] due to the ever-decreasing supply of endogenous neurotransmitter than can be displaced from the nerve ending."
[The brackets are mine]
One more:
"Drugs such as cocaine and amphetamine produce their effects by changing the flow of neurotransmitters. These drugs are defined as indirect acting because they depend on the activity of neurons. In contrast, some drugs bypass neurotransmitters altogether and act directly on receptors. Such drugs are direct acting."
In short, amphetamine itself does not make you high/more alert/etc. It is the dopamine/norepinephrine that it displaces from neurons that causes its effects.
 
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