Reinforcing and subjective effects of methylphenidate in adults with and without attention deficit hyperactivity disorder (ADHD)

“Comorbidity in adult ADHD is common and among non-ADHD individuals, those with no psychiatric history may be least likely to misuse MPH (Kessler et al. 2006).”

“Dependent measures—subject-rated effects The Adjective Rating Scale (Oliveto et al. 1992), the Addiction Research Center Inventory (Martin et al. 1971), the Drug-Effect Questionnaire (Rush et al. 2001; Stoops et al. 2004), and a Side Effects Questionnaire (SEQ; Rapoport et al. 1980) were used to assess subjective effe…”

“Epidemiological surveys suggest that illicit use of prescription stimulants like MPH is more likely to occur in individuals with more extensive drug use history ( McCabe et al. 2005 ).”

“…use of MPH in both the USA and other countries have led to significant controversy regarding the abuse, misuse, and diversion of MPH (Berbatis et al. 2002; Fogelman and Kahan 2001; Ivis and Adlaf 1999; Lin et al. 2005; Robison et al. 1999; Romano et al. 2002; Safer et al. 1996; Zito et al. 2000).”

“This hypothesis is supported by studies showing differences in dopamine transporter (DAT) density in relevant striatal areas in ADHD patients compared to controls (Cheon et al. 2003; Dougherty et al. 1999; Dresel et al. 2000; Krause et al. 2000, 2002, 2003; Larisch et al. 2006; Spencer et al. 2005; Volkow et al. 2007).”

“This hypothesis is supported by studies showing differences in dopamine transporter (DAT) density in relevant striatal areas in ADHD patients compared to controls (Cheon et al. 2003; Dougherty et al. 1999; Dresel et al. 2000; Krause et al. 2000, 2002, 2003; Larisch et al. 2006; Spencer et al. 2005; Volkow et al. 2007).”

“Dependent measures—subject-rated effects The Adjective Rating Scale (Oliveto et al. 1992), the Addiction Research Center Inventory (Martin et al. 1971), the Drug-Effect Questionnaire (Rush et al. 2001; Stoops et al. 2004), and a Side Effects Questionnaire (SEQ; Rapoport et al. 1980) were used to assess subjective effe…”

“Methylphenidate (MPH) is commonly prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), with hundreds of trials demonstrating efficacy in managing the disorder in children and adults (Elia et al. 1999; Goldman et al. 1998).”

“…use of MPH in both the USA and other countries have led to significant controversy regarding the abuse, misuse, and diversion of MPH (Berbatis et al. 2002; Fogelman and Kahan 2001; Ivis and Adlaf 1999; Lin et al. 2005; Robison et al. 1999; Romano et al. 2002; Safer et al. 1996; Zito et al. 2000).”

“…Department of Psychiatry, Duke University Medical Center, Durham, NC, USA S. H. Kollins (*) Duke ADHD Program, 718 Rutherford Street, Durham, NC 27701, USA e-mail: Kolli001@mc.duke.edu profile similar to other drugs of abuse, such as amphetamine and cocaine (Kollins 2003; Kollins et al. 2001).”

“…by studies showing differences in dopamine transporter (DAT) density in relevant striatal areas in ADHD patients compared to controls (Cheon et al. 2003; Dougherty et al. 1999; Dresel et al. 2000; Krause et al. 2000, 2002, 2003; Larisch et al. 2006; Spencer et al. 2005; Volkow et al. 2007).”

“This hypothesis is supported by studies showing differences in dopamine transporter (DAT) density in relevant striatal areas in ADHD patients compared to controls (Cheon et al. 2003; Dougherty et al. 1999; Dresel et al. 2000; Krause et al. 2000, 2002, 2003; Larisch et al. 2006; Spencer et al. 2005; Volkow et al. 2007).”

“…use of MPH in both the USA and other countries have led to significant controversy regarding the abuse, misuse, and diversion of MPH (Berbatis et al. 2002; Fogelman and Kahan 2001; Ivis and Adlaf 1999; Lin et al. 2005; Robison et al. 1999; Romano et al. 2002; Safer et al. 1996; Zito et al. 2000).”

“Other studies have shown that a substantial minority of young people report lifetime and past year use of prescription stimulants and that diversion is a common problem (Johnston et al. 2006; Kroutil et al. 2006).”

“At least two studies have shown that longeracting formulations produce lower magnitude subjective effects in non-ADHD individuals, and future work should clarify whether similar formulation differences are observed for reinforcing measures (Kollins et al. 1998; Spencer et al. 2006).”

“…is supported by studies showing differences in dopamine transporter (DAT) density in relevant striatal areas in ADHD patients compared to controls (Cheon et al. 2003; Dougherty et al. 1999; Dresel et al. 2000; Krause et al. 2000, 2002, 2003; Larisch et al. 2006; Spencer et al. 2005; Volkow et al.…”

“This hypothesis is supported by studies showing differences in dopamine transporter (DAT) density in relevant striatal areas in ADHD patients compared to controls (Cheon et al. 2003; Dougherty et al. 1999; Dresel et al. 2000; Krause et al. 2000, 2002, 2003; Larisch et al. 2006; Spencer et al. 2005; Volkow et al. 2007).”

“This hypothesis is supported by studies showing differences in dopamine transporter (DAT) density in relevant striatal areas in ADHD patients compared to controls (Cheon et al. 2003; Dougherty et al. 1999; Dresel et al. 2000; Krause et al. 2000, 2002, 2003; Larisch et al. 2006; Spencer et al. 2005; Volkow et al. 2007).”

“At least two studies have shown that longeracting formulations produce lower magnitude subjective effects in non-ADHD individuals, and future work should clarify whether similar formulation differences are observed for reinforcing measures (Kollins et al. 1998; Spencer et al. 2006).”

“The PR session lasted 60 min and was administered via computer (Rush et al. 2001; Stoops et al. 2003, 2004).”

“Dependent measures—subject-rated effects The Adjective Rating Scale (Oliveto et al. 1992), the Addiction Research Center Inventory (Martin et al. 1971), the Drug-Effect Questionnaire (Rush et al. 2001; Stoops et al. 2004), and a Side Effects Questionnaire (SEQ; Rapoport et al. 1980) were used to assess subjective effe…”

“This hypothesis is supported by studies showing differences in dopamine transporter (DAT) density in relevant striatal areas in ADHD patients compared to controls (Cheon et al. 2003; Dougherty et al. 1999; Dresel et al. 2000; Krause et al. 2000, 2002, 2003; Larisch et al. 2006; Spencer et al. 2005; Volkow et al. 2007).”

“For example, several studies have shown that the personality trait of sensation seeking is positively associated with the reinforcing effects of amphetamine (Kelly et al. 2006; Stoops et al. 2007).”

“Consequent increases in use of MPH in both the USA and other countries have led to significant controversy regarding the abuse, misuse, and diversion of MPH (Berbatis et al. 2002; Fogelman and Kahan 2001; Ivis and Adlaf 1999; Lin et al. 2005; Robison et al. 1999; Romano et al. 2002; Safer et al. 1996; Zito et al. 2000…”

“The PR session lasted 60 min and was administered via computer (Rush et al. 2001; Stoops et al. 2003, 2004).”

“…reinforcing effects in non-ADHD adults when administered under routine laboratory conditions, although when environmental conditions are manipulated (i.e., sleep deprivation, high demand tasks), MPH exhibits more robust reinforcing effects (Chait 1994; Roehrs et al. 1999; Stoops et al. 2005).”

“A number of single-case studies describe inappropriate intranasal or intravenous use of orally prescribed MPH (Garland 1998; Levine et al. 1986; Massello and Carpenter 1999).”

“This hypothesis is supported by studies showing differences in dopamine transporter (DAT) density in relevant striatal areas in ADHD patients compared to controls (Cheon et al. 2003; Dougherty et al. 1999; Dresel et al. 2000; Krause et al. 2000, 2002, 2003; Larisch et al. 2006; Spencer et al. 2005; Volkow et al. 2007).”

“A number of single-case studies describe inappropriate intranasal or intravenous use of orally prescribed MPH (Garland 1998; Levine et al. 1986; Massello and Carpenter 1999).”

“The PR session lasted 60 min and was administered via computer (Rush et al. 2001; Stoops et al. 2003, 2004).”

“, sleep deprivation, high demand tasks), MPH exhibits more robust reinforcing effects (Chait 1994; Roehrs et al. 1999; Stoops et al. 2005).”

“, sleep deprivation, high demand tasks), MPH exhibits more robust reinforcing effects (Chait 1994; Roehrs et al. 1999; Stoops et al. 2005).”

“…previous studies of drug reinforcement have conducted “responder analyses” by examining subjects who worked for drug administration versus those who did not to help identify those individual difference and drug factors that are most strongly associated with reinforcement (Perkins et al. 1997).”

“Drug administration procedures were designed to ensure that participants swallow the capsules and did not open them in their mouths and taste the contents (Abreu and Griffiths 1996).”

“…use of MPH in both the USA and other countries have led to significant controversy regarding the abuse, misuse, and diversion of MPH (Berbatis et al. 2002; Fogelman and Kahan 2001; Ivis and Adlaf 1999; Lin et al. 2005; Robison et al. 1999; Romano et al. 2002; Safer et al. 1996; Zito et al. 2000).”

“These findings are consistent with previous work that showed children and young adults with ADHD reliably chose MPH over placebo, with a lack of significant effects for subjective effects (Fredericks and Kollins 2004; MacDonald Fredericks and Kollins 2005).”

“This method has been used previously to describe time course effects of drugs in laboratory studies (Kollins and Rush 1999).”

“…use of MPH in both the USA and other countries have led to significant controversy regarding the abuse, misuse, and diversion of MPH (Berbatis et al. 2002; Fogelman and Kahan 2001; Ivis and Adlaf 1999; Lin et al. 2005; Robison et al. 1999; Romano et al. 2002; Safer et al. 1996; Zito et al. 2000).”

“phenidate to function as a reinforcer, but only in the ADHD group [54].”

“…with ADHD also have more difficulty learning to adaptively allocate behavior in order to maximize reinforcement and there is evidence that stimulant drugs improve learning under these conditions (Kollins et al., 1997; Luman et al., 2009a, 2009b; Murray and Kollins, 2000; Tripp and Alsop, 1999).”

“Previous research has found that the likeability of psychostimulants in individuals with ADHD is associated more with therapeutic effect than with euphoric effects (Fredericks and Kollins 2004 2005; Kollins et al. 2009).”

“…right medial dorsal nucleus Right thalamus 18, −20, 16 0.035 Left thalamus −8, −16, 10 0.036 Psychopharmacology dosing and, to lesser degree, after therapeutic oral doses (Kollins et al. 2009; Volkow et al. 1999), depending on rate of drug clearance in the striatum (Parasrampuria et al. 2007;…”

“of substance dependence, but not those of “drug liking”, “euphoria”, or “high”.(94,99,100) Other studies, in contrast,”

“…15, 30, 60, 150 mg/70 kg, sc N/A ✓ ✓ ✓ Martin et al. (1971) Normal volunteers 20 and 40 mg, po N/A ✓ ✓ ✓ Kollins et al. (1998) ADHD subjects 20 and 40 mg, po N/Ay ✓ ✓ Not stated Kollins et al. (2009) Normal volunteers 20 and 40 mg, po D-amphetamine 10 and 20 mg po ✓ ✓ Not stated Rush et al.…”

“While methylphenidate and amphetamines may be self-administered by laboratory animals and have shown subjective and reinforcing effects in humans [Kollins et al. 2009], nonstimulant medications approved for the treatment of ADHD, including, atomoxetine, guanfacine or clonidine, lack any reinforcing effects and consequ…”

“Methylphenidate is an intermediatepotency DA transporter inhibitor and is known to produce euphoria at higher doses [29,30] and to have a relevant abuse potential [31,32].”

“For each consequence, the first ratio required 75 responses, and each successive ratio required 1.75 times the previous ratio such that the response requirements for each reinforcer were 75,131, 229, 401, 702, 1,229, 2,151, 3,764, and so on (Kollins et al. 2009).”

“Given that some studies have shown differential patterns of stimulant drug effects in ADHD versus non-ADHD samples (Kollins et al., 2009), future work should evaluate whether co-administration of stimulants and THC results in similar effects in individuals with and without ADHD.”

“ADHD and substance abuse has been known to have high comorbidity, but the effects of non ADHD chronic MP treatment on substance abuse vulnerability is less well understood [14,15].”

“6 which is considered a schedule II drug by the Drug Enforcement Agency in the United States, can inhibit the uptake of dopamine and noradrenaline, and has several stimulant-like effects that are accompanied by abuse potential in humans (Kollins et al., 2009).”

“To address this issue, we designed an exploration/habituation/spatial change paradigm, the familiar arena-novel alcove (FA-NA) task, based on the observation that the restlessness, fidgeting, and generally unnecessary gross body movements associated with ADHD tend to be less pronounced in novel environments than in fa…”

“MPH has been found to be a reinforcer in humans with ADHD, and humans with and without ADHD have reported ‘liking’ the effects of MPH and would take it again (Kollins et al., 2009).”

“Further, drug self-administration has been shown to vary as a function of sensation-seeking status, inattention status, drinking status, and sex (Stoops et al., 2007a; Kollins et al., 2009; Vansickel et al., 2010; Stanley et al., 2011).”

“Indeed, laboratory studies have shown that methylphenidate and amphetamines are self-administered by laboratory animals,(117) and in humans there is evidence of the subjective and reinforcing effects of these psychostimulants.(118) The abuse potential of psychostimulants is mediated by a series of factors, including t…”

“Using horizontal line scales with “0” labeled “not at all” and “100” labeled “extremely,” a vertical mark was made to indicate the intensity of the following drug effects: (1) Do you feel any drug effect? (2) How high are you? (3) Do the drugs have any good effects? (4) Do the drugs have any bad effects? (5) Do you li…”

“Kollins et al. (2009) found that ADHD individuals consistently preferred MPH to placebos, whereas no significant preference emerged for controls.”

“However, an experimental study on the acute effects of ADHD medications in people with ADHD showed limited support for differences in feeling the stimulant effects between patients and controls (Kollins et al., 2009).”

“In humans, MPH produces positive subjective effects (Kollins et al., 2001, 2009; Heil et al., 2002; Stoops et al., 2005a; Patrick et al., 2007), which may serve as discriminative stimuli.”

“For each consequence, the first ratio required 75 responses and each successive ratio required 1.75 times the previous ratio such that the ratio requirements for each reinforcer were 75 responses, 131 responses, 229 responses, and so on (Kollins et al., 2009; Kollins, English, Roley, et al., 2012).”

“Consistent with these findings, a laboratory study revealed that methylphenidate, an abused stimulant, produced greater reinforcing effects and more variable subjective effects in adults diagnosed with ADHD, relative to controls (6).”

“The positive subjective effects of MPH reported by adult humans (Heil et al., 2002; Stoops et al., 2005; Patrick et al., 2007; Kollins et al., 2009) likely serve as discriminative stimuli.”

“Alternatively, healthy individuals may choose to use this drug because of its subjective effect on perception of self confidence, [11] sense of concentration, [15] alertness and vigor, fatigue [6, 8], mood [6] and well being [9, 16, 17].”