Variables That Affect the Clinical Use and Abuse of Methylphenidate in the Treatment

[Gregster]

Variables That Affect the Clinical Use and Abuse of Methylphenidate in the Treatment of ADHD
Nora D. Volkow, M.D., and James M. Swanson, Ph.D.

OBJECTIVE: Methylphenidate, the most common treatment for attention deficit hyperactivity disorder (ADHD), increases extracellular dopamine in the brain, which is associated with its reinforcing as well as its therapeutic effects. The authors evaluated variables that distinguish these two properties.

METHOD: The brain imaging and clinical literatures were analyzed to identify variables that contribute to the abuse liability as well as to the clinical efficacy of methylphenidate.

RESULTS: Four variables were identified.

1) Doseage: there is a threshold for methylphenidate-induced dopamine increases to be perceived as reinforcing and to produce therapeutic effects.

2) Pharmacokinetics: the reinforcing effects of methylphenidate are associated with rapid changes in serum concentrations and presumably fast dopamine increases (as achieved with intravenous injection or insufflation), whereas the therapeutic effects are associated with slowly ascending serum concentrations and presumably smoothly rising dopamine levels (as achieved with oral administration).

3) Individual differences: sensitivity to methylphenidate varies across individuals and sets a threshold for blood and brain levels required for reinforcing effects (drug liking) and for therapeutic effects (symptom reduction).

4) Context: the effects of methylphenidate are modulated by different settings in abuse (rituals of self-administration and powerful conditioning) and in clinical use (external demands of low activity and focused attention).

CONCLUSIONS: Reinforcing effects occur when methylphenidate elicits large and fast dopamine increases that mimic those of phasic dopamine cell firing, whereas therapeutic effects occur when methylphenidate elicits slow, steady-state dopamine increases that mimic those of tonic firing. Thus, the characteristics of clinical use (low doses administered orally and titrated for therapeutic effects) constrain methylphenidate's abuse.

[Ace]

Cool. I find that, as the weeks pass, I am having a harder and harder time remembering to take my 5 mg pill twice a day. Don't know what that means, aside from the low "reinforcing effect I am experienceing," apparently. I think I experience theraputic effects WHEN I remember to take the methylphenidate.

Thanks for the report!

[Lexicon]

Originally posted by Ace
Cool. I find that, as the weeks pass, I am having a harder and harder time remembering to take my 5 mg pill twice a day. Don't know what that means, aside from the low "reinforcing effect I am experienceing," apparently.

Well, according to the study, all ya gotta do to fix that is snort the little buggers.

[Els]

Ay... I'm afraid this one's too difficult for me being a non-native speaker of English... (Didn't you notice my accent?) Can you please help me understand because I'm very interested in this subject.

Thanks!

[Andrew]

CONCLUSIONS: Reinforcing effects occur when methylphenidate elicits large and fast dopamine increases that mimic those of phasic dopamine cell firing, whereas therapeutic effects occur when methylphenidate elicits slow, steady-state dopamine increases that mimic those of tonic firing. Thus, the characteristics of clinical use (low doses administered orally and titrated for therapeutic effects) constrain methylphenidate's abuse.

Translation

Methylphenidate (i.e. Ritalin) is more effective (as a treatment for ADHD) when taken in several smaller, oral (by mouth) doses.

The same med, taken at higher doses (especially by non-ADDers), may lead to abuse.

[kimo]

Originally posted by Els
Ay... I'm afraid this one's too difficult for me being a non-native speaker of English... (Didn't you notice my accent?) Can you please help me understand because I'm very interested in this subject.

Thanks!

Heck - English is my native language and I didn't understand that either!

Thanks for the translation Big!

[Els]

LOL, so I was not the only one missing the point.

I am currently experiencing exactly this: I take more doses now than in the beginning of my Ritalin trial and I'm wondering wether i shouldn't take smaller doses at a time. Now it's 6 x 10 mg and 1 x 0.5 late in the evening, but I'm soooo speedy. The rebound effect is so strong that 4 doses a day just won't do, but maybe 7 x 0.5 would be very good for me. I'll discuss this with my doctor.

[Matt S.]

I became severely addicted to ritalin/concerta anything in that family father was a cocaine addict maybe... I never actually abused any of them but i developed a physical tolerance too fast for normal and was at 140 mg per day but I can function fine on an amphetamine (Adderall XR 20 mg a day 2 10 mg doses) and stay there for almost a year... it is odd because most doctors think that amphetamines are more addicting but i guess it is all who you are

[attention]

Apparently abusers cannot distinguish between IVing Methylphenidate and cocaine (which have a similar mode of action)-this being a VERY dangerous practice, binders, particles etc.

Some folks will abuse anything, and with Ritalin IR being very rapid up and down acting, i would argue it is more abuseable than XR adderall or dexedrine, which take longer to come on and to drop off.