Is Methylphenidate Like Cocaine?: Studies on Their Pharmacokinetics and Distribution in the Human Brain
Abstract
BACKGROUND: The purposes of this study were to investigate the pharmacokinetics of methylphenidate hydrochloride (Ritalin) in the human brain, to compare them with those of cocaine, and to evaluate whether cocaine and methylphenidate compete for the same binding sites. METHODS: We used positron emission tomography to measure the temporal and spatial distribution of carbon 11 (11C)-labeled methylphenidate. These results were compared with those obtained previously for [11C]cocaine. Eight healthy male subjects, 20 to 51 years of age, were scanned with [11C]methylphenidate. Three were tested twice to assess test-retest variability, four were tested at baseline and after administration of methylphenidate, and one was tested with [11C]methylphenidate and [11C]cocaine. Two baboons were scanned to evaluate whether there was competition between cocaine and methylphenidate for the same binding sites in the brain. RESULTS: The uptake of [11C]methylphenidate in the brain was high (mean +/- SD, 7.5% +/- 1.5%), and the maximal concentration occurred in striatum. Pretreatment with methylphenidate decreased binding only in striatum (40%). Although the regional distribution of [11C]methylphenidate, was identical to that of [11C]cocaine and they competed with each other for the same binding sites, these two drugs differed markedly in their pharmacokinetics. Clearance of [11C]methylphenidate from striatum (90 minutes) was significantly slower than that of [11C]cocaine (20 minutes). For both drugs, their fast uptake in striatum paralleled the experience of the "high." For methylphenidate, the high decreased very rapidly despite significant binding of the drug in the brain. In contrast, for cocaine, the decline in the high paralleled its fast rate of clearance from the brain. CONCLUSION: We speculate that because the experience of the high is associated with the fast uptake of cocaine and methylphenidate in the brain, the slow clearance of methylphenidate from the brain may serve as a limiting factor in promoting its frequent self-administration.
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The contribution of the speed at which dopamine increases occur in the brain is influenced by the route of administration.
“The contribu tion of the speed at which dopamine increases occur in the brain is also influenced by the route of administration 38 .”
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Methylphenidate and amphetamines are given the same drug classification by health authorities and perform similarly in traditional assays of abuse.
“Health authorities have given methylphenidate the same drug classification as amphetamines and they both perform similar to each other in traditional assays of abuse [280,281].”
From European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD (2010) · cites this paper as [281]
PET studies confirmed that stimulants increase synaptic DA, first with intravenous MP and later with oral clinical doses.
“PET study confirmed this hypothesis, first with intravenous doses of MP (Volkow et al, 1995(Volkow et al, , 1999a) ) and then with oral clinical doses of MP (Swanson et al, 1999;Volkow et al, 1999bVolkow et al, , 2002)).”
From Understanding the Effects of Stimulant Medications on Cognition in Individuals with Attention-Deficit Hyperactivity Disorder: A Decade of Progress (2011) · cites this paper as Volkow et al, 1995
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- Authors
- Volkow, N. D.
- Affiliations
- Brookhaven National Laboratory (US)
- Corresponding author
- Volkow, Nora D.
- ORCID
- Volkow, Nora D.
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 1995-06-01
- Volume
- 52
- Issue
- 6
- Pages
- 456
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2116795024
- Cited by
- 575
- References
- 47
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 9 · 2023: 12 · 2022: 8 · 2021: 14 · 2020: 13 · 2019: 10 · 2018: 9 · 2017: 9 · 2016: 16 · 2015: 20 · 2014: 21 · 2013: 22 · 2012: 33
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ns015638-15)
- National Institute on Drug Abuse (5RO1-DA06891, R01DA006891)
- National Institute of Neurological Disorders and Stroke (NS15638)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- methylphenidate, cocaine, brain pharmacokinetics, striatum, binding site competition, drug clearance, self-administration, positron emission tomography
- MeSH terms
- Adult, Animals, Brain, Carbon Radioisotopes, Cerebellum, Cocaine, Corpus Striatum, Half-Life, Humans, Male, Methylphenidate, Middle Aged, Papio, Self Medication, Time Factors, Tissue Distribution, Tomography, Emission-Computed, Substance-Related Disorders
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