What factors contribute to tolerance?

[staples]

SWIM has found that 10mg of adderall is a decent amount, he prefers 15mg for studying, and 20mg makes his teeth chatter. His little sister went from being prescribed 5mg up to 30mg over the course of a year.

My question is with regard to a friend of mine who took adderall for the first time recently. He weighs about the same as SWIM (I think he said 157lb? that wouldn't be far off), he's very healthy and very fit. He did not feel the effects of 10 or 20mg, and 30mg was okay, but only lasted for 4 hoursish (SWIM tells me that even 10mg, feeling weak for him, still lasts closer to 6!).

I can understand increased tolerance over time, such as the case with SWIM's sister, but what could cause such little effect from an amount that would have SWIM grinding his teeth, to someone who's similar in weight/height, doesn't use any other drugs (no interactions), and furthermore has never used adderall before and could not have built a tolerance that way?

[staples]

::bump::

I have a little more information as well as questions... no one can offer any ideas?

My friend ingested baking soda, waited a bit (~15-20 minutes?), took 40mg Adderall XR, and ~45-65 minutes later he had an energy shot (one of those overpriced "5-hour energy!" shots).

This seems to affect him about as much as 15mg adderall with no baking soda or energy drink affects SWIM!

The next day my friend tried to duplicate his procedure to achieve the same effect but didn't notice it as much.

I have confirmed his body weight is 167 lbs. He also has 10% body fat percentage, if that matters.

Is there any more information that would be helpful? heart rate/blood pressure?

Is it just how some people are?

Thanks

[coldkate]

it can be just psychological. everybody's body reacts differently to everything, sometimes noticeably distinct differences. that's the only thing i can really think of. besides that, adderall affects dopamine levels or something.... maybe that other guy has already higher levels of dopamine naturally or something. either way it seems like a psychological issue. i'm a psychology major but i'm totally just guessing on this one and i'm probably wrong, lol. sorry didn't really help. it's a med that affects the way you FEEL... feeling more energy, feeling loss of appetite.... all psychological.

[MJDW]

SWIM has an answer for SWIY's question about the 5-Hour Energy thing. This is something SWIM quoted from their site:

5-Hour Energy contains large amounts of Vitamin C and many B Vitamins.

Vitamin C (ascorbic acid) prevents the absorption of amphetamines. Google it for more information.

[staples]

ok so apparently he was joking when he said 157 lbs (apparently that's heavy).. he's only 137 lbs.

As for vitamin C being the culprit -- he's also tried it without the energy shot, and I cannot see how that little (compared to adderall dosage) vitamin C could have that huge of an effect, but then I'm not a doctor. At any rate, those energy shots have only increased the effect of adderall for SWIM, shouldn't the other ingrediants out-weigh the counter-effects of vitamin C? Nonetheless, shouldn't the baking soda have significantly countered vitamin C's effects??

I'm thinking it must be psychological, but THEN, why no side effects? no teeth-grinding?

A mildly effective dose for my friend seems to be 45 mg! Correct me if I'm wrong, but isn't 40 mg the limit (the highest dose prescribeable? in the US, at least)?

What also puzzles me but does point more towards psychological tolerance is that my friend reports trouble sleeping. Even on "low" doses that he barely or does not feel.

How can a drug keep you up but you can't "feel" it??

Slightly off-topic: Would it be advisable for my friend to take his effective dose (45mg) and then a benzo such as ativan, or a sleep aid like ambien to help with sleep? I hear doctors often prescribe benzo's alongside adderall but not necessarily sleeping-aids... My main concern for him is becoming dependant on ativan/ambien just for the sake of having a successful study session...

[jazzmetalguitar]

Vitamin C certainly can have a powerful effect on the effectiveness of amphetamines in your body (though from my understanding it doesn't prevent absorption, rather creates a more acidic enviroment that expels it more quickly). However, in your friend's case the vitamin C shouldn't have been an issue because he also dosed himself with baking soda (and you said he's tried it without the energy shot).

So IMO, it is certainly psychological. Adderall effects your dopamine and norepinephrine levels (boosts them and then prevents them from leaving the synapse). Now, note that everyone's brain does not have the same number of neurotransmitter receptors (i.e. schizophrenics can have ultra-sensitive and abundant dopamine receptors [theoretical], and people with Parkinson's lack dopamine in the proper areas while people with essential tremor can have receptor problems). So, there is a right dose for everyone and it is not physiologically based but rather neurochemically (curiously SWIM has essential tremor and yet is very senstitive to amphetamines). That explains the effectivess of the drug in various people. To answer the title of the forum then, these dopamine receptors become desensitized after too much stimulation (and chronic stimulation) and therefore you don't just become tolerant to amps but also dopamine, something you naturally need. (In addition, binges have been shown in rats to not only wreck receptors but reduce dopamine and serotonin levels by 30-40%, in some cases for weeks.)

Now, why are certain effects such as the teeth-grinding and such aren't present? A forum friend has led me towards the fact that a few of these symptoms are likely more related to NMDA receptors (which accepts the excitotoxins NMDA and glutamate). So when you have 5 or so different neurotransmitters to be taken into account. It's going to effect everyone differently. Note, SWIM just mention 5 chems and has only mentioned 4 (well, SWIM mentioned it but didn't discuss it). Serotonin is naturally depleted after amps use. This is the most likely cause of inability to sleep even after the drug itself has worn off. Don't even consider the benzos before you try 5-HTP. It will stabilize your serotonin levels and should fix the sleeping prob.
(special thanks to candy_kid here)

[staples]

Thank you jazzmetalguitar, that was a very very helpful reply.

My questions now are with regard to 5-HTP.

I knew that amphetamines affect serotonin, but I never got the sense that it was nearly the magnitude that they affect dopamine? But it (for some people?) does so enough to warrant taking this 5-HTP supplement?

It seems logical, then, that, if one were to take an amphetamine, one would also want to take some supplement from which your body can create more dopamine? Or do you get more than enough from a normal diet?

I've just now tried a couple simple forum and google searches without finding quite the right information about: 1) How should 5-HTP be administered with adderall in order to address sleeplessness? and 2) "Concerta and Ritalin" is under the catagory of "Amphetamines", but I don't believe they affect serotonin... would 5-HTP also help someone who has trouble sleeping after taking methylphenidate to study? (this topic may have to shift over to the methylphenidate forum)

[jazzmetalguitar]

It is certainly true that amphetamines stimulate dopamine much more than they do serotonin. In fact, even more norepinephrine is produced than serotonin. People who prefer that serotonin high find it in MDMA or methamphetamine. Now, all the highs aside. When the dopamine levels in one's body sky rocket or boost serotonin seems to naturally have an opposite effect. When DA goes up 5-HT down and vice versa. So, right there it is suggested that 5-HT is depleted (or more technically just not a neurochemically active due to dopamine's activity). That aside, serotonin levels have already altered. In addition, studies on rats show that binge patterns can result in low dopamine AND serotonin levels for up to three weeks.

[staples]

Originally Posted by jazzmetalguitar

It is certainly true that amphetamines stimulate dopamine much more than they do serotonin. In fact, even more norepinephrine is produced than serotonin. People who prefer that serotonin high find it in MDMA or methamphetamine. Now, all the highs aside. When the dopamine levels in one's body sky rocket or boost serotonin seems to naturally have an opposite effect. When DA goes up 5-HT down and vice versa. So, right there it is suggested that 5-HT is depleted (or more technically just not a neurochemically active due to dopamine's activity). That aside, serotonin levels have already altered. In addition, studies on rats show that binge patterns can result in low dopamine AND serotonin levels for up to three weeks.

I've just come back to read this post and I'm a little confused now. If an amphetamines spikes dopamine which lowers 5-HT...
1) Shouldn't you then have an excess of 5-HTP becase your body is using it more slowly? and even if you didn't...
2) Why does supplying yourself with ample 5-HTP do much at all, if seratonin levels are being kept lower, in the first place?

Also, When should one take 5-HTP supplemtns? morning? before bed? When does it need to be bioavailable, and how long after ingestion is it bioavailable, and for how long?

Thanks,
Staples