(16) Self-Reported Effects Associated With Xylazine/Medetomidine in Drug Checking Samples

Background & Introduction: The illicit opioid supply in the US is dominated by fentanyl. Adulteration or contamination of the illicit drug supply is well known. In particular, two alpha-2 adrenergic agonists (xylazine and medetomidine) have been noted to appear in the drug supply. The purpose of adulteration is unclear but may include enhancement of drug effect or duration of effects. In 2023, Hamilton County (Cincinnati, OH’s county seat) Public Health (HCPH) partnered with the Centers for Disease Control and Prevention (CDC), the University of North Carolina (UNC) Street Drug Analysis Lab, and community-based organizations to pilot a drug checking program. The purpose of this study was to use data from the drug checking program to determine whether the presence of alpha-2 adrenergic agonists was associated with any additional subjective effects noted by the user.

Methods: Participants could voluntarily submit drug samples at three different community sites. This study included samples collected from 1/24 - 8/25. Samples included drug residues, powder, or used paraphernalia. All samples were submitted anonymously but included a questionnaire. Participants identified what they thought the substance was and participants could also note any “unusual effects” that they perceived following use of the drug. These were limited to a drop down menu of 15 different options which did include “other” where free text could be entered. Multiple effects could be noted by the participant. The samples were then sent to the UNC Drug Analysis lab that performed gas chromatography/mass spectrometry for drug identification. Drugs were noted to be either present as “trace amounts” or as a “primary substance” (which could be multiple substances). Odds Ratios (OR) were calculated by bivariate analysis and multivariate logistic regression. Effects were only analyzed if the drug was a primary substance. A composite outcome of “sedating", “stronger”, "more down”, or “longer” was used to identify the possibility of enhanced effects with fentanyl. The composite outcome was selected a priori to capture user-perceived enhancement of opioid effects.

Results: 144 samples were submitted. 6 samples did not have enough drug to be identified. Of the 138 samples remaining, 48 had xylazine detected as a primary substance. “Sedating” was noted by participants in 31 samples and was associated with the presence of xylazine with an OR of 2.98 (95% CI 1.30-6.84). “Stronger” was noted in 17 samples and was associated with the presence of xylazine with an OR of 3.12 (95% CI 1.10-8.86)). “Longer” was noted in 5 samples and only in samples with xylazine present. No other effects were statistically significant. “More down” was noted in 10 samples with an OR of 1.98 (95% CI 0.55 - 7.12). “Unusual taste” was noted in 5 samples. 4 of these contained xylazine and the 5th contained xylazine in trace amounts. Xylazine detection was associated with increased odds of the composite outcome (OR 2.27, 95% CI 1.08–4.78). When stratified by the presence of fentanyl, the OR dropped to 1.44 (95% CI 0.64 - 3.24). Medetomidine was noted in 25 samples as a primary substance. Medetomidine was associated with “hallucinations” with an OR of 14.9 (95% CI 1.48 - 149.6), but there were only 4 mentions of “hallucinations”. Of note, medetomidine was present in 3/4 and the 1 sample that did not contain medetomidine contained methamphetamine which could possibly result in psychotic effects. No other effects were statistically significant although stronger and more down trended toward significance. The composite outcome with medetomidine had an OR of 1.25 (95% CI 0.51 - 3.11).

Conclusion & Discussion: The presence of xylazine in drug samples was associated with increased odds of self-reported effects, particularly sedation. Although the association was attenuated after controlling for fentanyl, the findings suggest that xylazine may contribute to meaningful effects in the unregulated drug supply. Medetomidine was not associated with statistically significant effects (other than hallucinations) although that may have been limited by a small sample size. A possible association with hallucinations was observed, though estimates were unstable due to low event counts. However, hallucinogenic effects have previously been noted to be associated with medetomidine. Key study limitations include: drug identifications are largely qualitative with no way to attribute effects to actual drug presence or amount. Drug effects were subjective impressions and voluntarily submitted although participants were unaware of drug composition before submitting effects. In addition, the participants were submitting effects in comparison with previous drug use and we have no way of knowing what was contained in previous drug usage. Ultimately, this study may provide some insight as to the purpose of adulteration and whether the commonly hypothesized purpose of synergistic effect has true effects. This may aid in overdose prevention as drug users are more fully aware of drug composition and effects.

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