Abstract
Rationale
There has been controversy over the abuse potential of methylphenidate (MPH) in the context of treatment for attention deficit hyperactivity disorder (ADHD).
Objective
The objective of this study was to compare the reinforcing and subjective effects of oral MPH in adults with and without ADHD.
Materials and methods
Following screening, 33 adults (n = 16 with ADHD; n = 17 free from psychiatric diagnoses) completed four pairs of experimental sessions, each of which included a sampling session and a self-administration session. During sampling sessions, subjects received in randomized order 0 (placebo), 20, 40, and 60 mg MPH. During self-administration sessions, subjects completed a progressive ratio (PR) task to earn portions of the dose received on the corresponding sampling session. Subjective effects were recorded throughout all sessions. The main outcome measure for the study was the number of ratios completed on the PR task. Secondary measures included peak subjective effects and area-under-the-curve values for subjective effects.
Results
Compared to the control group, the ADHD group completed more ratios on the PR task. Both groups showed robust effects of methylphenidate on subjective endpoints. Main effects of group were noted on subjective effects involving concentration and arousal.
Conclusions
Compared to placebo, MPH produced reinforcing effects only for the ADHD group and not for the control group. Increases in stimulant-related subjective effects in non-ADHD subjects were not associated with drug reinforcement.
Similar content being viewed by others
Notes
The trapezoid method sums post drug administration values according to the following formula: [1/2 × (time 1 value) + sum (time 2 value + time 3 value + …time n − 1 value) + 1/2 × (time n value)]. This method has been used previously to describe time course effects of drugs in laboratory studies (Kollins and Rush 1999).
References
Abreu ME, Griffiths RR (1996) Drug tasting may confound human drug discrimination studies. Psychopharmacology (Berl) 125:255–257
Berbatis CG, Sunderland VB, Bulsara M (2002) Licit psychostimulant consumption in Australia, 1984–2000: international and jurisdictional comparison. Med J Aust 177:539–543
Brady J (1988) The reinforcing functions of drugs and assessment of abuse liability. NIDA Res Monogr 81:440–456
Chait LD (1994) Reinforcing and subjective effects of methylphenidate in humans. Behav Pharmacol 5:281–288
Cheon KA, Ryu YH, Kim YK, Namkoong K, Kim CH, Lee JD (2003) Dopamine transporter density in the basal ganglia assessed with [123I]IPT SPET in children with attention deficit hyperactivity disorder. Eur J Nucl Med Mol Imaging 30:306–311
Conners CK, Erhardt D, Sparrow EP (1998) Conners Adult ADHD Rating Scale. Multi-Health Systems, Inc., Multi-Health Systems, Inc.
Dougherty DD, Bonab AA, Spencer TJ, Rauch SL, Madras BK, Fischman AJ (1999) Dopamine transporter density in patients with attention deficit hyperactivity disorder. Lancet 354:2132–2133
Dresel S, Krause J, Krause KH, LaFougere C, Brinkbaumer K, Kung HF, Hahn K, Tatsch K (2000) Attention deficit hyperactivity disorder: binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment. Eur J Nucl Med 27:1518–1524
Elia J, Ambrosini PJ, Rapoport JL (1999) Treatment of attention-deficit-hyperactivity disorder. N Engl J Med 340:780–788
Epstein JN, Johnston DE, Conners CK (2000) Conners Adult ADHD Interview for DSM-IV. Multi-Health Systems, Multi-Health Systems
First MB, Gibbon M, Spitzer RL, Williams JBW (1996) User’s guide for the Structured Clinical Interview for DSM-IV Axis I Disorders—Research Version. Biometrics Research Department, Biometrics Research Department
Fogelman Y, Kahan E (2001) Methylphenidate use for attention deficit hyperactivity disorder in northern Israel–a controversial issue. Isr Med Assoc J 3:925–927
Fredericks EM, Kollins SH (2004) Assessing methylphenidate preference in ADHD patients using a choice procedure. Psychopharmacology (Berl) 175:391–398
Garland EJ (1998) Intranasal abuse of prescribed methylphenidate [letter]. J Am Acad Child Adolesc Psych 37:1242–1243
Goldman LS, Genel M, Bezman RJ, Slanetz PJ (1998) Diagnosis and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Council on Scientific Affairs, American Medical Association. JAMA 279:1100–1107
Grace AA (2001) Psychostimulant actions on dopamine and limbic system function: Relevance to the pathophysiology and treatment of ADHD. In: Solanto MV, Arnsten AFT, Castellanos FX (eds) Stimulant Drugs & ADHD: Basic and Clinical Neuroscience. Oxford University Press, Oxford, pp 134–157
Ivis FJ, Adlaf EM (1999) Prevalence of methylphenidate use among adolescents in Ontario. Can J Public Health 90:309–312
Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE (2006) Monitoring the Future national survey results on drug use, 1975-2005. Volume I: Secondary school students (NIH Publication No. 06-5883). National Institute on Drug Abuse, Bethesda, MD
Kelly TH, Robbins G, Martin CA, Fillmore MT, Lane SD, Harrington NG, Rush CR (2006) Individual differences in drug abuse vulnerability: d-amphetamine and sensation-seeking status. Psychopharmacology (Berl) 189:17–25
Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, Faraone SV, Greenhill LL, Howes MJ, Secnik K, Spencer T, Ustun TB, Walters EE, Zaslavsky AM (2006) The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 163:716–723
Kollins SH (2003) Comparing the abuse potential of methylphenidate versus other stimulants: a review of available evidence and relevance to the ADHD patient. J Clin Psychiatry 64(Suppl 11):14–18
Kollins SH, Rush CR (1999) Effects of training dose on the relationship between discriminative-stimulus and self-reported drug effects of d-amphetamine in humans. Pharmacol Biochem Behav 64:319–329
Kollins SH, Rush CR, Pazzaglia PJ, Ali JA (1998) Comparison of acute behavioral effects of sustained-release and immediate-release methylphenidate. Exp Clin Psychopharmacol 6:367–374
Kollins SH, MacDonald EK, Rush CR (2001) Assessing the abuse potential of methylphenidate in nonhuman and human subjects: a review. Pharmacol Biochem Behav 68:611–627
Krause KH, Dresel SH, Krause J, Kung HF, Tatsch K (2000) Increased striatal dopamine transporter in adult patients with attention deficit hyperactivity disorder: effects of methylphenidate as measured by single photon emission computed tomography. Neurosci Lett 285:107–110
Krause KH, Dresel SH, Krause J, Kung HF, Tatsch K, Ackenheil M (2002) Stimulant-like action of nicotine on striatal dopamine transporter in the brain of adults with attention deficit hyperactivity disorder. Int J Neuropsychopharmacol 5:111–113
Krause KH, Dresel SH, Krause J, la Fougere C, Ackenheil M (2003) The dopamine transporter and neuroimaging in attention deficit hyperactivity disorder. Neurosci Biobehav Rev 27:605–613
Kroutil LA, Van Brunt DL, Herman-Stahl MA, Heller DC, Bray RM, Penne MA (2006) Nonmedical use of prescription stimulants in the United States. Drug Alcohol Depend 84:135–143
Larisch R, Sitte W, Antke C, Nikolaus S, Franz M, Tress W, Muller HW (2006) Striatal dopamine transporter density in drug naive patients with attention-deficit/hyperactivity disorder. Nucl Med Commun 27:267–270
Levine B, Caplan YH, Kauffman G (1986) Fatality resulting from methylphenidate overdose. J Anal Toxicol 10:209–210
Lin SJ, Crawford SY, Lurvey PL (2005) Trend and area variation in amphetamine prescription usage among children and adolescents in Michigan. Soc Sci Med 60:617–626
MacDonald Fredericks E, Kollins SH (2005) A pilot study of methylphenidate preference assessment in children diagnosed with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 15:729–741
Martin WR, Sloan JW, Sapira JD, Jasinski DR (1971) Physiologic, subjective and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther 12(2):245–258
Massello W 3rd, Carpenter DA (1999) A fatality due to the intranasal abuse of methylphenidate (Ritalin). J Forensic Sci 44:220–221
McCabe SE, Knight JR, Teter CJ, Wechsler H (2005) Non-medical use of prescription stimulants among US college students: prevalence and correlates from a national survey. Addiction 100:96–106
Oliveto AH, Bickel WK, Hughes JR, Shea PJ, Higgins ST, Fenwick JW (1992) Caffeine drug discrimination in humans: acquisition, specificity and correlation with self-reports. J Pharmacol Exp Ther 261:885–894
Perkins KA, Grobe JE, Caggiula A, Wilson AS, Stiller RL (1997) Acute reinforcing effects of low-dose nicotine nasal spray in humans. Pharmacol Biochem Behav 56:235–241
Rapoport JL, Buchsbaum MS, Weingartner H, Zahn TP, Ludlow C, Mikkelsen EJ (1980) Dextroamphetamine. Its cognitive and behavioral effects in normal and hyperactive boys and normal men. Arch Gen Psychiatry 37:933–943
Robison LM, Sclar DA, Skaer TL, Galin RS (1999) National trends in the prevalence of attention-deficit/hyperactivity disorder and the prescribing of methylphenidate among school-age children: 1990-1995. Clin Pediatr (Phila) 38:209–217
Roehrs T, Papineau K, Rosenthal L, Roth T (1999) Sleepiness and the reinforcing and subjective effects of methylphenidate. Exp Clin Psychopharmacol 7:145–150
Romano E, Baillargeon RH, Wu HX, Robaey P, Tremblay RE (2002) Prevalence of methylphenidate use and change over a two-year period: a nationwide study of 2- to 11-year-old Canadian children. J Pediatr 141:71–75
Rush CR, Essman WD, Simpson CA, Baker RW (2001) Reinforcing and subject-rated effects of methylphenidate and d-amphetamine in non-drug-abusing humans. J Clin Psychopharmacol 21:273–286
Safer DJ, Zito JM, Fine EM (1996) Increased methylphenidate usage for attention deficit disorder in the 1990s. Pediatrics 98:1084–1088
Solanto MV (2002) Dopamine dysfunction in AD/HD: integrating clinical and basic neuroscience research. Behav Brain Res 130:65–71
Spencer TJ, Biederman J, Madras BK, Faraone SV, Dougherty DD, Bonab AA, Fischman AJ (2005) In vivo neuroreceptor imaging in attention-deficit/hyperactivity disorder: a focus on the dopamine transporter. Biol Psychiatry 57:1293–1300
Spencer TJ, Biederman J, Ciccone PE, Madras BK, Dougherty DD, Bonab AA, Livni E, Parasrampuria DA, Fischman AJ (2006) PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short- and long-acting oral methylphenidate. Am J Psychiatry 163:387–395
Stoops WW, Glaser PE, Rush CR (2003) Reinforcing, subject-rated, and physiological effects of intranasal methylphenidate in humans: a dose–response analysis. Drug Alcohol Depend 71:179–186
Stoops WW, Glaser PE, Fillmore MT, Rush CR (2004) Reinforcing, subject-rated, performance and physiological effects of methylphenidate and d-amphetamine in stimulant abusing humans. J Psychopharmacol 18:534–543
Stoops WW, Lile JA, Fillmore MT, Glaser PE, Rush CR (2005) Reinforcing effects of methylphenidate: influence of dose and behavioral demands following drug administration. Psychopharmacology (Berl) 177:349–355
Stoops WW, Lile JA, Robbins CG, Martin CA, Rush CR, Kelly TH (2007) The reinforcing, subject-rated, performance, and cardiovascular effects of d-amphetamine: influence of sensation-seeking status. Addict Behav 32:1177–1188
Volkow ND, Wang GJ, Newcorn J, Fowler JS, Telang F, Solanto MV, Logan J, Wong C, Ma Y, Swanson JM, Schulz K, Pradhan K (2007) Brain dopamine transporter levels in treatment and drug naive adults with ADHD. Neuroimage 34:1182–1190
Zito JM, Safer DJ, dosReis S, Gardner JF, Boles M, Lynch F (2000) Trends in the prescribing of psychotropic medications to preschoolers. JAMA 283:1025–1030
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was funded by grant R01DA017196 from the National Institute on Drug Abuse (SHK).
Rights and permissions
About this article
Cite this article
Kollins, S.H., English, J., Robinson, R. et al. Reinforcing and subjective effects of methylphenidate in adults with and without attention deficit hyperactivity disorder (ADHD). Psychopharmacology 204, 73–83 (2009). https://doi.org/10.1007/s00213-008-1439-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-008-1439-6