Medetomidine, a potent central acting α2 agonist, has emerged as a fentanyl adulterant in the non-medical opioid supply. Its use has been linked to a novel withdrawal syndrome that is often resistant to conventional treatment protocols. Four cases are presented exemplifying extreme, but increasingly common forms of this withdrawal syndrome. A literature review is provided demonstrating both the paucity of available literature as well as potential avenues for treatment and future research. As adulterants continue to proliferate in the illicit drug supply, clinicians should anticipate atypical withdrawal phenotypes and consider early intervention.

Background: Mitragynine pseudoindoxyl (MP) is a semi-synthetic kratom metabolite increasingly sold online and over-the-counter, marketed misleadingly as “kratom” or “7-OH,” despite lacking FDA approval and safety data in humans. Methods: This case report describes a 44-year-old male with polysubstance use history who developed opioid withdrawal symptoms after regular MP use (400 mg daily for pain management following neck injury). Vital signs, alcohol and opioid withdrawal scores and clinical outcomes were recorded. Results: The patient presented exhibiting symptoms of moderate opioid withdrawal in the absence of other opioid use. A buprenorphine macro-induction protocol was initiated. Following pre-treatment using chlorpromazine as an anti-emetic and diazepam to treat concomitant alcohol withdrawal, 32 mg buprenorphine were provided (16 mg × 2) on day one, with subsequent maintenance dosing and adjunctive medications. The patient demonstrated significant symptomatic improvement with decreased COWS scores and expressed interest in long-acting injectable buprenorphine maintenance therapy. Discussion: This represents the first documented case of suspected MP withdrawal successfully managed with buprenorphine macro-induction, demonstrating the potential efficacy of this approach for novel semi-synthetic kratom metabolites when standard withdrawal management protocols are insufficient. Further studies should evaluate long term outcomes and validate findings.

Objectives: Medetomidine, a veterinary alpha-2-adrenergic agonist, has emerged as a dominant adulterant in the Philadelphia illicit opioid supply, producing a severe withdrawal syndrome requiring significant inpatient support. We developed an intravenous dexmedetomidine protocol for intermediate care units (IMCU) and describe the safety and feasibility of delivering this care outside the intensive care unit (ICU). Methods: A retrospective descriptive analysis of patients who received dexmedetomidine under an IMCU orderset for alpha-2 withdrawal was conducted at two urban medical centers in Philadelphia, PA, from April 2024 to February 2026. Encounters were classified as protocol-concordant or protocol-discordant by dosing and level of support; the concordant cohort was primary. Variables included demographics and addiction consult status. Outcomes included length of stay (hospital and IMCU), ICU admission, rapid response team activation, intubation, and discharge disposition. Results: Of 487 encounters, 449 (92.2%) were protocol-concordant and 38 (7.8%) protocol-discordant. All subsequent results describe the protocol-concordant cohort (n=449) unless otherwise noted. The cohort was predominantly male (58.1%) with a mean age of 41.8 years. Median hospital stay was 6.0 days and median IMCU stay was 2.2 days. ICU admission was not required in 50.1% of encounters. Rapid response team activation occurred in 38 encounters (8.5%), the majority for escalating withdrawal management. Patient-directed discharge occurred in 41.4% of encounters. Conclusions: An IMCU dexmedetomidine protocol deployed across seven monitored units at 2 hospitals offers a replicable framework for managing medetomidine withdrawal while potentially mitigating critical care capacity challenges. Identified opportunities include modification of titration and dosing strategies and further investment in addiction consult infrastructure.

Background: Mitragynine pseudoindoxyl (MP) is a semi-synthetic kratom metabolite increasingly sold online and over-the-counter, marketed misleadingly as "kratom" or "7-OH," despite lacking FDA approval and safety data in humans. Methods: This case report describes a 44-year-old male with polysubstance use history who developed opioid withdrawal after regular MP use (400 mg daily for pain management following neck injury). Vital signs, alcohol and opioid withdrawal scores and clinical outcomes were recorded. Results: The patient presented exhibiting symptoms of moderate opioid withdrawal. A buprenorphine macro-induction protocol was initiated. Following pre-treatment using chlorpromazine as an anti-emetic and diazepam to treat concomitant alcohol withdrawal, 32 mg buprenorphine were provided (16 mg x 2) on day one, with subsequent maintenance dosing and adjunctive medications. The patient demonstrated significant symptomatic improvement with decreased COWS scores and expressed interest in long-acting injectable buprenorphine maintenance therapy. Discussion: This represents the first documented case of MP withdrawal successfully managed with buprenorphine macro-induction, demonstrating the potential efficacy of this approach for novel semi-synthetic kratom metabolites when standard withdrawal management protocols are insufficient. Further studies should evaluate long term outcomes and validate findings.

Medetomidine, a potent central acting α2 agonist, has emerged as a fentanyl adulterant in the non-medical opioid supply. Its use has been linked to a novel withdrawal syndrome that is often resistant to conventional treatment protocols. Four cases are presented exemplifying extreme, but increasingly common forms of this withdrawal syndrome. A literature review is provided demonstrating both the paucity of available literature as well as potential avenues for treatment and future research. As adulterants continue to proliferate in the illicit drug supply, clinicians should anticipate atypical withdrawal phenotypes and consider early intervention.