Tiletamine‑zolazepam (commercially Zoletil 50) is a veterinary anesthetic combination that has been increasingly reported as a substance of recreational abuse. The chronic neurotoxic and multisystem consequences of human exposure are incompletely characterized, and routine toxicology panels do not detect this compound. This study reports clinical, laboratory, and neuroimaging findings and tracks outcomes over a two‑year prospective follow‑up period after initial retrospective case identification.
The aim was to characterize neurological and systemic injury after recreational inhalation of tiletamine‑zolazepam (Zoletil 50), with particular attention to relapse behavior and persistent deficits during a two‑year observation period.
The investigators conducted a retrospective case series of patients who presented to their institution with toxicity attributed to inhalation of Zoletil 50. They reviewed clinical features, laboratory results, and neuroimaging findings where available. Long‑term outcomes and relapse rates were assessed during a prospective two‑year follow‑up of discharged patients. Ethical approval for the study was obtained from the local ethics committee; as a retrospective study, individual informed consent was not required by the committee.
Thirty‑six subjects were included. The most consistent neurological sign was postural tremor, observed in all 36 patients (100%). Early after admission, 22 patients (61.1%) exhibited sustained, high‑amplitude tremor. Cerebellar ataxia was common, reported in 30 patients (83%), and visual disturbance was present in 20 patients (56%). Hallucinatory perceptual disturbance occurred in 16 patients (44%). A minority (four patients, 11%) developed bradykinesia and rigidity consistent with parkinsonian features.
These findings indicate a broad spectrum of central nervous system involvement after Zoletil 50 inhalation, with prominent movement disorder signs (tremor and ataxia) and perceptual phenomena.
Biochemical abnormalities were frequently observed. Elevated transaminases occurred in 53% of patients, and hypokalemia was present in 44%. The abstract notes that neuroimaging findings were analyzed, but specific imaging results are not detailed in the source abstract. Therefore, image‑based observations were part of the study data set but are not reported here in the source text.
Two patients died during the initial hospitalization due to cardiorespiratory failure. The remaining 34 patients were discharged from the hospital and entered the follow‑up cohort.
Relapse after discharge was common: 20 of 34 discharged patients (59%) experienced at least one relapse. Relapse occurred early in most cases: 17 of those 20 relapsed within the first month after discharge. Repeated relapse was associated with further morbidity; a third death occurred during follow‑up after a fifth relapse.
These data highlight that relapse after recreational Zoletil 50 use is both frequent and tends to occur early, underlining the need for early intervention and follow‑up after hospitalization.
At two years, outcome assessment was available for 33 survivors. Persistent neurological deficits were present in 11 of these 33 patients (one patient’s status at two years is not described in the abstract). Reported persistent problems included subjective memory decline in seven patients, visual impairment in six patients, and ongoing bradykinesia in two patients that required levodopa treatment.
Thus approximately one‑third of long‑term survivors continued to experience neurological deficits two years after initial exposure.
Recreational inhalation of tiletamine‑zolazepam (Zoletil 50) is associated with a wide spectrum of neurological and systemic toxicity. The most consistent clinical features observed in this series were tremor, ataxia, and visual disturbance, often accompanied by hallucinations. Systemic effects such as transaminase elevation and hypokalemia were common, and cardiorespiratory collapse was fatal in a subset of patients. Relapse after discharge is frequent and typically occurs early; recurrent exposure was linked to additional morbidity and death in at least one case during follow‑up.
Clinicians evaluating young patients with new, unexplained tremor, ataxia, or perceptual disturbances should consider exposure to tiletamine‑zolazepam, particularly because standard toxicology screens may not detect this drug combination. Close post‑discharge monitoring and interventions to reduce relapse risk are implied by the high early relapse rate.
This report is a retrospective case series from a single institution, and as such cannot establish causation definitively. Neuroimaging and other data were collected but specific imaging results are not reported in the abstract. The authors recommend prospective controlled studies to confirm causation, define the full spectrum of toxicity, and better characterize mechanisms and optimal management strategies for both acute and chronic sequelae.
Overall, the study documents significant acute and chronic harms associated with recreational Zoletil 50 inhalation and highlights the need for clinician awareness and further research.