Cross tolerance?

[razorwiredildo]

back in the day swim used to get high off of ritalins and concertas quite a bit.
eventually, he got a tolerance, the high started to suck and he stopped.

about a year later, swim tried adderall. he is a 135 lb male. he snorted about 20-25 mg of generic adderall instant realease. he got high but not as high as he though he should. it felt like maybe a moderate ritalin buzz.
other people that swim was with did similar amounts and got tweaked the hell out.

swim wants to know if he just didn't do enough or if maybe his methylphenidate use caused some kind of tolerace to adderall.
this seems possible because swim thinks that ritalin and adderall work in similar ways.

[angela20377]

swiy is probably right about the cross tolerance but it seems a little odd that after a year of not using stimulants, swiy still has a significant tolerance to adderall. everyone's body is different though, so i guess it makes sense, but it still sucks. swim also experiences this problem among stimulants including cocaine and propylhexedrine. swim suggests trying the adderall XR rather than IR if swiy gets the chance. (shes found that it works better for her)

EDIT:candy kids right, the binders on the XR are pretty nasty for one's nose

[candy_kid]

^^ thought I'd point out that if the op's friend is snorting adderall, then xr should be avoided. The binders that make it slow release are very bad for anyone's nose and will likely prevent a portion from getting absorbed too

@op: as for how high someone goes, swim finds adderall gives him massive stimulation and almost no dopaminergic "buzz", he actually feels mildly depressed, he's constantly hungry and nothing is fun... D-amphetamine on the other hand is quite euphoric for swim, he can only assume that the l-amphetamine in adderall is releasing too much of something (epinephrine?), which ends up blocking him from experiencing all his other favourite neurotransmitters being released by the d-amp in adderall, or even naturally... maybe your friend has something to a lesser extent of this going on and should try d-amphetamine on its own?

Amphetamine tolerance btw is mostly the body's recognition of the drug, which wouldn't be affected by methylphenidate. The other part, due to dopamine receptor desensitization caused by the methylphenidate could have been involved, but should have reversed at the very worst in much less than a year, unless actual damage was done to the receptors. Does your friend still feel any negative long term effects from the ritalin? That would suggest your dopamine system is still feeling the methylphenidate, if not I'd have to assume this is just your friend's own personal reaction to adderall, just like swim has his-- like angela said, everyones different right

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[jazzmetalguitar]

Ok. To my knowledge all ADHD meds are stimulants which target the brain's levels of catecholamines (dopamine, serotonin, and norepinephrine). Dextro-amphetamines and dextro-methylphenidates bind to dopamine transporters to prevent reuptake of dopamine. Levo-amphetamines and levo-methylphenidates bind to norepinephrine to prevent reuptake of norepinephrine. Both dextro-'s and levo-'s are attracted to transporters which are serotonergic, however binding to such transporters is quite rare. Thus, the effects of ADHD drugs are mostly dopaminergic and norepinephrinergic. These two varities of salts(in the case of Adderall only)/compounds typically act independently of each other. It is important also to understand that the amphetamines and the methylphenidates are virtually analogous.

Now when the amps. or methyls. block reuptake of dopamine and norepinephrine it is theorized that serotonin is thus neglected by carriers and thus is not sufficiently released. Thus a case like this where swiy has been off the methylphenidate for a year, we can no longer attribute this tolerance to recognition of the compound by the body (likely!). And so we theoretically are left with three options in my mind: desensitization of dopamine receptors, desensitization of norepinephrine receptors, or ultrasensitive serotonin receptors (i feel this unlikely and without a cause but since experts believe the body's treatment of serotonin while on these amps. and methyls. may also be causing things we must list it as a possibility). I don't view receptor damage as completely unlikely. The brain is a sensitive thing and it doesn't like to repair itself. A fourth possibility that occurs to me (remember that the brain is a lot more complex than we can even begin to understand, it adapts habits and methods of its own and not one persons works exactly the same; hence people can train their bodies to hit REM sleep in about 10 minutes with the Übermensch sleep methods), it is a possibility that you brain and the targeted regions are more inclined towards methylphenidate (in a sort of reverse tolerance but more like: you are more comfortable talking to someone you know) and thus the amphetamine which is foreign, unique, and new can not give its full kick, because your body A) isn't expecting these things to happen for they are chemically altered but also B) when this does occur your brain is used to methylphenidate causing it and thus the amphetamines are not as well recieved. SWIM has this happen when he tried methylphenidate for the first time after being fairly used to using Adderall (the methylphenidate just didn't give me the drive I was used to; note: the methylphenidate began to do better after a few uses).

And so, lets try to figure out which it is:

Weakened Dopamine Receptor symptoms:
(Figured out as best SWIM can from dopamine deficiency issues)
1) lack of creative drive
2) ADHD like symptoms
3) social anxiety and antisocial behavior
4) reduced motivation
5) reduced pleasure
6) tremors/balance issues

Weakened Norephinephrine Receptor symptoms:
(Derived as above)
1) Depressed feelings
2) Possibly: hypotension
3) Difficulty handling stress
4) Concentration issues

Ultrasensitivity to Serotonin:
(Derived as above)
1) Hypomania
2) Hallucinations and Delusions
3) Hypertension
4) Twitching/Tremor

Unless swiy has experienced any of these symptoms (in which case you should look further into the issue which presents there) it is likely that your body simply is getting accustomed to the amphetamines over the methylphenidates. It is also possible that you are naturally more tolerant to amps. rather than methyls., just as SWIM tends to be less sensitive to methylphenidates. SWIM isn't quite sure, he presented a lot of material there. Hopefully people will debate?

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[candy_kid]

^^ norepinephrine desensitization would theoretically reduce stimulation, but not so much euphoria which is what I believe the op's friend was missing. ultrasensitivity to serotonin would have given an extremely serotonergic "high" which the op's friend likely would have enjoyed due to dextroamphetamine's small action on serotonin. Weakened dopamine system is definitely a possibility due to dopamine's small toxicity on it's own system when combined with MAO and the op's previous abuse- the op will hopefully be able to tell us if their friend has problems with this based on your list of symptoms however, unless they already have ADD in which case they will likely have a bunch of those symptoms anyway

btw, the effects of methylphenidate and amphetamine are analogous, but keep in mind that the cause of the effects aren't quite so much- and also (what I can only assume you were getting at) tolerance to the amphetamine molecules themselves as far as I've read (feel free to contest, I haven't read everything!) would not be affected by tolerance caused to the methylphenidate molecules

anyway, that's all I wanted to contest (since you requested it), it was a good and well thought out post all in all though -- also, your post did make me think of something; (listen up op) is it possible that the op's friend has ADD? people with add typically find amphetamines to have a calming effect allowing them to get work done and such, while people without will become manic, excitable and talkative. If the op's friend has ADD, they would likely find ritalin and adderall to have similar focusing effects, but wont get anything near that of their friends as far as "tweaking"-- it could explain the reason for the abuse of methylphenidate mentioned previously also as typically people with ADD will take stimulants regularly without too much negative impact on their lives prior to being diagnosed

@op: any input?

[jazzmetalguitar]

candy kid,
I was agreeing with you completely about the fact that despite the similarities of methylphenidate and amphetamines that their tolerances would not be transferable. Thus in my mind you must look not at the actual reception of the two drugs but rather their mechanisms of action and what they cause chemically in the brain. I also agree that the serotonin receptor desensitization would be the most likely, I really don't know too much about these neurotransmitters (I simply have read alot alot alot due to countless nights on adderall where I run out of actual work to do ironic huh?).

Now, the last point you made may perhaps be the best yet. It would certainly explain the cause of a fairly high tolerance and dependence in someone trying to get a high off something that doesn't quite make their "ADD mind" do that. In addition, when you add in the adderall factor it makes even more sense. Certainly, insufflation of 20-25mg of Adderall should cause one who has not used amphetamines, or even analogous stimulants, in over a year to get quite a speed and high. However, if someone with ADD did the same thing, 20-25mg would still be a bit above average and may cause a bit of a high but not a sufficient one for someone who is looking for that (just as say 5mg would do for a non-ADD person). Very interesting theory and quite likely in many ways I think.

[mitch88]

A few studies SWIM has looked up suggest that varying degrees of cross-tolerance with amphetamine can also be found in nicotine, caffeine, and ephedrine.

However, it's proven quite difficult for science to discriminate between the actual pharmacological cross-tolerance and the psychological "expectation" variety of cross-tolerance. Even with lab animals.