Although expanding the availability of buprenorphine—a first-line pharmacotherapy for opioid-use disorder (OUD)—has increased the capacity of healthcare systems to offer treatment, starting this medication is fraught with significant barriers. Standard induction regimens require persons with OUD to taper and discontinue full opioid agonists and experience opioid withdrawal prior to the first dose of buprenorphine. Further, emerging evidence indicates that precipitated withdrawal during induction may impact long-term treatment outcomes. Microinduction is a novel approach that, by harnessing buprenorphine’s unique pharmacological profile, may allow circumventing the needed for prolonged opioid tapers, and reduce the risk of precipitated withdrawal—holding promise to enhance treatment access. In this review, we examine the pharmacological basis for microinduction and appraise the evidence of this approach to improve clinical outcomes among persons with OUD. First, we highlight the potential dose-dependent effects of buprenorphine on two key neuroadaptations at the mu-opioid receptor (MOR)—resensitization and upregulation. We then focus on how microinduction may reverse these chronic MOR neuroadaptations, allowing the maintenance of an adequate opioid tone, and thereby potentially circumventing opioid withdrawal. Second, we describe the clinical evidence available, derived from observational reports and open-label studies, examining the potential efficacy of microinduction. Despite significant heterogeneity—exemplified by variable buprenorphine formulations, daily doses, and schedules of administration—these data provide preliminary support for the feasibility of microinduction. Finally, we provide new mechanistic, methodological, and clinical insights to guide future translational research, as well as randomized, placebo-controlled clinical trials in this compelling agenda of pharmacotherapy development.

Objectives: Alternative transition protocols from methadone to buprenorphine in the treatment of opioid use disorder (OUD) are needed to reduce the risk of precipitated withdrawal and opioid use during induction. Methods: Case report (n = 1). Results: One patient with OUD underwent a rapid microinduction outpatient protocol that did not cause precipitated withdrawal or require preceding taper before cessation of methadone. The induction was carried out safely in the outpatient setting. Conclusions: This report provides a patient-centered approach demonstrating feasibility and cost-effectiveness of rapid transition to buprenorphine in the US outpatient psychiatry setting. Barriers to adherence to opioid agonist therapy may be reduced using this protocol.

With rising rates of cannabis use in the general population and an increasing number of US states legalizing both recreational and medical cannabis use, it is important to be informed about the adverse consequences of cannabinoids. This Commentary provides an overview of the psychiatric effects of plant-based and synthetic cannabinoids, differentiating acute effects from effects associated with persistent use. Cannabinoids produce multiphasic and dose-dependent effects on anxiety, mood, and perception, in addition to impairing cognition and psychomotor function. Generally, in healthy individuals, the acute negative psychiatric effects of cannabinoids are rated as milder in severity compared with those in individuals with pre-existing psychiatric disorders. With chronic exposure to cannabinoids, the probability of developing tolerance and dependence can increase. A problematic pattern of cannabis use can lead to clinically significant impairment and distress. Cessation of cannabis use in individuals who are tolerant and dependent can lead to a withdrawal syndrome. Studies report long-term cannabis exposure has been linked to psychiatric disorders, such as anxiety, psychotic and mood disorders. Limitations to the existing evidence notwithstanding, the plausibility of a causal relationship between cannabinoid exposure and persistent negative psychiatric outcomes, and the potential for long-term brain changes by regular exposure, especially for adolescents, are sufficient to warrant discussions with clinicians and the public. Implications for clinicians who certify, prescribe, or care for patients receiving cannabinoids are discussed, and a case is made for further research to better understand the impact of legalization on public mental health.