Reinforcing, subject-rated, performance and physiological effects of methylphenidate and d-amphetamine in stimulant abusing humans

Abstract

Methylphenidate has potential for abuse because it produces behavioural effects similar to those observed with other abused stimulants, such as d-amphetamine and cocaine. The aim of this study was to further characterize the abuse potential of oral methylphenidate relative to oral d-amphetamine. Ten drug-abusing volunteers were recruited to participate in this study, which consisted of seven dose conditions: methylphenidate (16, 32 and 48 mg), d-amphetamine (8, 16 and 24 mg) and placebo. The reinforcing effects of these drugs were assessed during a self-administration session (preceded by a sampling session for each condition) with a modified progressive-ratio procedure. Subject-rated, performance and physiological effects were assessed concurrently during both the sampling and self-administration sessions. The intermediate dose of methylphenidate and d-amphetamine increased responding significantly above placebo levels. Both methylphenidate and d-amphetamine produced dose-dependent increases in stimulant-like subject ratings (e.g. Active, Alert, or Energetic and High), but the effects of these drugs were not isomorphic. These findings are consistent with epidemiological data and previous findings from laboratory studies that suggest methylphenidate has at least some abuse potential.

Characterization of methylphenidate self-administration and reinstatement in the rat

“…In agreement with two previous studies (Collins et al 1984;Nielsen et al 1984), rats readily learned to selfadminister methylphenidate on a FR1 schedule. We extended this finding to show that rats, like humans Stoops et al 2004) and non-human primates (Lile et al 2003), will work to self-administer methylphenidate on a PR schedule of reinforcement. A role for dopamine in mediating the reinforcing effects of methylphenidate was shown by the demonstration that self-administration of methylphenidate was altered by treatment with either the D1 dopamine receptor antagonist SCH23390 or the D2 dopamine receptor antagonist eticlopride.…”

Reinforcing effects of methylphenidate: influence of dose and behavioral demands following drug administration

“…The modified progressive-ratio procedure has been used previously and is a reliable measure of drug reinforcement in humans (Comer et al 1997(Comer et al , 1998Rush et al 2001;Stoops et al 2004). During each self-administration session, volunteers were given eight opportunities to respond on a standard Apple keyboard to earn all, or some, of the capsules that were administered during the sampling sessions.…”

“…We have previously characterized the reinforcing effects of oral methylphenidate using a modified progressive-ratio schedule Stoops et al 2004). In each of those studies, methylphenidate functioned as a reinforcer and increased prototypical, stimulant-like, subject-rated effects.…”

Subjective and physiological effects of acute intranasal methamphetamine during d-amphetamine maintenance

“…In the earlier trial, amphetamine-dependent patients who injected drug were randomly assigned to receive 54 mg/day slow-release methylphenidate (N=17) or placebo (N=19) for 20 weeks (Tiihonen et al 2007). Methylphenidate, a piperidine derivative, inhibits dopamine reuptake and produces a constellation of stimulant-like behavioral effects that are similar to those of amphetamine (Ritz et al 1987;Rush et al 1998Rush et al , 2001Sevak et al 2009;Stoops et al 2004Stoops et al , 2005. Methylphenidate-treated patients had significantly fewer amphetamine-positive urine specimens than placebotreated patients.…”