Discriminative Stimulus Effects of Tramadol in Humans

Abstract

Tramadol is an unscheduled atypical analgesic that acts as an agonist at -opioid receptors and inhibits monoamine reuptake. Tramadol can suppress opioid withdrawal, and chronic administration can produce opioid physical dependence; however, diversion and abuse of tramadol is low. The present study further characterized tramadol in a three-choice discrimination procedure. Nondependent volunteers with active stimulant and opioid use (n ϭ 8) participated in this residential laboratory study. Subjects were trained to discriminate between placebo, hydromorphone (8 mg), and methylphenidate (60 mg), and tests of acquisition confirmed that all volunteers could discriminate between the training drugs. The following drug conditions were then tested during discrimination test sessions: placebo, hydromorphone (4 and 8 mg), methylphenidate (30 and 60 mg), and tramadol (50, 100, 200, and 400 mg). In addition to discrimination measures, which included discrete choice, point distribution, and operant responding, subjective and physiological effects were measured for each test condition. Both doses of hydromorphone and methylphenidate were identified as hydromorphone-and methylphenidate-like, respectively. Lower doses of tramadol were generally identified as placebo, with higher doses (200 and 400 mg) identified as hydromorphone, or opioid-like. The highest dose of tramadol increased ratings on the stimulant scale, but was not significantly identified as methylphenidate-like. Tramadol did not significantly increase subjective ratings associated with reinforcement. Taken together, these results extend previous work with tramadol as a potential medication for the treatment of opioid dependence and withdrawal, showing acute doses of tramadol exhibit a profile of effects similar to opioid agonists and may have abuse liability in certain populations.

Topical Review on the Abuse and Misuse Potential of Tramadol and Tilidine in Germany

“…This was confirmed in recent studies with human volunteers that confirmed opioid-like discrimination and dose-related physical dependence after chronic administration (23,24). Mild withdrawal symptoms have been reported following discontinuation or dose reductions in animals as well as in humans (25).…”

Tramadol Abuse in a Binge Pattern in a Young Depressed Woman

“…In clinical trials, the effects of tramadol vary widely depending on the subjects [18]. In a study that characterized tramadol in a discrimination procedure in 8 subjects with active opioid and stimulant use, who were trained to discriminate among placebo, 8 mg hydromorphone, and 60 mg methylphenidate, an oral dose of tramadol 400 mg had stimulant-like effects and increased ratings on the stimulant scale [19]. In another double-blind double-dummy randomized study, 1 out of 10 opioid addicts in abstinence identified the oral dose of 200 mg as an antidepressant and 3 subjects identified it as an opioid antagonist.…”

Influence of sensitization on the discriminative stimulus effects of methylphenidate in mice

“…Direct evidence that MPH produces a discriminative stimulus comes from several drug discrimination studies in humans (Duke et al , 2011; Lile et al , 2006; Stoops et al , 2005b), rats (Overton and Shen, 1988; Perkins et al , 1991) and mice (Griffin et al , 2012a; McGovern et al , 2011). A number of reports also describe the ability of MPH to at least partially substitute for other psychostimulants such as cocaine (Bondareva et al , 2002; Li et al , 2006; Rush et al , 2002; Schweri et al , 2002), amphetamine (Bondareva et al , 2002; Czoty et al , 2004) and methamphetamine (Desai et al , 2010; Sevak et al , 2009).…”