Acute buspirone dosing enhances abuse-related subjective effects of oral methamphetamine

Abstract

There is not an approved pharmacotherapy for treating methamphetamine use disorder. This study sought to determine the effects of acute buspirone treatment on the subjective and cardiovascular effects of oral methamphetamine in order to provide an initial assessment of the utility, safety, and tolerability of buspirone for managing methamphetamine use disorder. We predicted that acute buspirone administration would reduce the subjective effects of methamphetamine. We also predicted that the combination of buspirone and methamphetamine would be safe and well tolerated. Ten subjects completed the protocol, which tested three methamphetamine doses (0, 15, and 30 mg) in combination with two buspirone doses (0 and 30 mg) across 6 experimental sessions. Subjective effects and physiological measures were collected at regular intervals prior to and after dose administration. Methamphetamine produced prototypical subjective and cardiovascular effects. Acute buspirone administration increased some of the abuse-related subjective effects of methamphetamine and also attenuated some cardiovascular effects. The combination of oral methamphetamine and buspirone was safe and well tolerated. Acute buspirone administration may increase the abuse liability of oral methamphetamine. Chronic buspirone dosing studies remain to be conducted, but given preclinical findings and the outcomes of this work, the utility of buspirone for treating methamphetamine use disorder appears limited.

Buspirone maintenance does not alter the reinforcing, subjective, and cardiovascular effects of intranasal methamphetamine

“…No subjects withdrew from the study due to study medications and no serious adverse events occurred. These data are consistent with prior reports showing that the combination of buspirone with methamphetamine (Pike et al, 2016; Paterson et al, 2014) and cocaine (Bolin et al, 2016) is safe and tolerable. These findings are also concordant with a past study demonstrating that buspirone alone does not engender subjective effects (Strickland et al, 2017).…”

“…Methamphetamine also produced a constellation of prototypical stimulant-like subjective effects indicative of abuse potential (e.g., Good Effects and Like Drug) and elevated systolic and diastolic blood pressure. These effects are consistent with the type and magnitude of effects typically observed following methamphetamine administration by various routes (e.g., Hart et al, 2001; Kirkpatrick et al, 2012; Marks et al, 2016; Pike et al, 2016; Stoops et al, 2015), but was not impacted by buspirone maintenance.…”

“…By contrast, buspirone attenuated locomotor effects (Jackson et al, 1994), cue-induced reinstatement (Shelton et al, 2013), and the discriminative-stimulus effects (Nader and Woolverton, 1994) of methamphetamine in other preclinical studies. In the human laboratory, acute buspirone administration enhanced some of the subjective effects of low doses of oral methamphetamine (e.g., Good Effects and Like Drug) (Pike et al, 2016). Mixed results have also been observed in behavioral studies that examined interactions between buspirone and cocaine (Bergman et al, 2013; Czoty and Nader, 2015; Gold and Balster, 1992; John et al, 2015, Mello et al, 2013).…”

“…In rhesus monkeys, buspirone attenuated the discriminative-stimulus effects of methamphetamine (Nader and Woolverton, 1994) but not methamphetamine self-administration (John et al, 2015). In the human laboratory, buspirone pretreatment enhanced some subjective effects of oral methamphetamine (e.g., Good Effects and Like Drug), but attenuated the cardiovascular effects (Pike et al, 2016). Those studies employed acute buspirone dosing, which does not reflect how buspirone would be used in the clinic.…”

Update on methamphetamine: an old problem that we have recently encountered

“…Short-term effects of methamphetamine include euphoria, alertness, wakefulness, increased confidence, hyperactivity, and loss of appetite (33,34). Dopamine release is responsible for the euphoric effects of methamphetamine, but long-term use of methamphetamine causes molecular changes in the dopamine system, contributing to nerve terminal damage in the brain and leading to impaired motor skills, rapid cognitive decline, increased anxiety, psychotic disorders, violent behavior, hallucination, delusions and depression (35).…”