Preliminary examination of orexin receptor antagonism with suvorexant in individuals with Methamphetamine use disorder: a case series study

<b>Background:</b> No FDA-approved medications for methamphetamine (MA) use disorder (MUD) are available. Suvorexant (SUVO), a dual orexin receptor antagonist that is FDA approved for insomnia treatment, reduces MA self-administration and MA-induced reinstatement responding in preclinical studies. SUVO may also reduce MA use by targeting substance use risk factors, including insomnia, stress, cue reactivity, and craving. This case series study assessed the (1) feasibility and safety of administering suvorexant in a sample of individuals with MUD; and (2) preliminary effects of suvorexant on objective and subjective measures of sleep, stress, and cue reactivity/craving. <b>Method:</b> Participants (<i>n</i> = 3) were randomized to receive 1 week of SUVO or placebo using a within-subject, crossover design with a 1-week washout period between doses. Participants completed self-report (sleep quality, stress), behavioral (cold pressor task), and physiological measures (heart rate, electroencephalogram) during all three weeks. Participants wore a Fitbit to monitor sleep throughout the study. <b>Results:</b> Participants completed all study visits and tasks. One report of severe drowsiness and of severe headache were made; no other severe side effects were associated with SUVO. SUVO improved total sleep time and resulted in lower resting-state alpha power, but was mixed for subjective sleep quality. SUVO administration was associated with increased overall brain reactivity to cues that was not specific to MA cues and also reduced stress, though self-reported stress demonstrated mixed results. <b>Conclusion:</b> Suvorexant was safe and tolerable in a MUD sample. Future research may benefit from investigating SUVO in a well-controlled study with a larger sample.