(28) Quetiapine, A Novel Additive to the Illicit Heroin Supply in Los Angeles

Background & Introduction: The rise of the “fourth wave” of the US overdose crisis has been characterized by the polysubstance use of illicit opioids combined with other drug classes, such as stimulants, benzodiazepines, xylazine, and other substances. The community-based drug checking movement is also increasingly shedding light on diverse psychoactive substances used to augment illicit opioids. Here we share findings from a drug checking program in Los Angeles CA, highlighting quetiapine—a commonly-used atypical antipsychotic—as a novel additive in heroin samples.

Quetiapine and its metabolites exert dosage-dependent antipsychotic, antidepressant, and sedative effects due to its complex receptor interactions including D2, 5HT2A, 5HT2C and Alpha2 antagonism, 5HT1A agonism, and norepinephrine reuptake inhibition. Previous literature has described the “street value” of quetiapine in carceral and other settings and noted that some individuals intentionally crush and snort, smoke, or inject it, to magnify the sedative effects, and employ it as part of polysubstance mixtures, especially with cocaine[1], [2]. To our knowledge, no study has previously documented unintentional quetiapine use as an additive to illicit opioids. The side effects of quetiapine are also dose-dependent, and include sedation, weight gain and metabolic impacts, dizziness, and akathisia, as well as a lower, but non-zero, risk of movement disorders.

Methods: This study leveraged data from a community-based drug checking program in Los Angeles, California operated at several sites. The program offered free services to clients who provided a trace quantity of drug product for immediate testing via a series of immunoassay-based testing strips, as well as Fourier Transform Infrared Spectroscopy. These results were provided immediately to the client. Additionally, subsequent testing was performed whereby the substance and/or related paraphernalia were swabbed with a cotton-tipped applicator, assigned an anonymized unique identifier, and submitted to the National Institute of Standards and Technology (NIST) for analysis with direct analysis in real time mass spectrometry (DART-MS). Resulting spectra were compared to a library of over 1,300 compounds including psychoactive substances and cutting/bulking agents. Clients also completed a survey containing questions about sociodemographic information and expected drug contents. More details about the methodological approach have been previously described[3]. Data were visualized in R version 4.4.1 and chi-squared tests were used to assess differences in heroin samples containing vs. not containing quetiapine. This study was deemed as exempt from review by the UCLA IRB given its funding by CDC OD2A:LOCAL, rendering it a public health surveillance activity.

Results: Of n=562 samples with complete data assessed at community drug checking sites in Los Angeles between February 2023 and February 2024, n=178 contained heroin and/or fentanyl according to analysis by DART-MS. Of these, a total of n=52 contained heroin, and n=157 contained fentanyl. Of the n=52 samples containing heroin, n=13 (25.0%) contained quetiapine. No heroin-negative samples contained quetiapine; therefore, this exploratory analysis focused on heroin-positive samples.

Quetiapine-positive heroin samples tended to be less likely to contain fentanyl, xylazine, and methamphetamine compared to quetiapine-negative heroin samples. Among quetiapine-positive heroin samples, n=4 (30.8%) contained fentanyl, compared to n=27 (69.2%) of quetiapine-negative heroin samples (p=0.05). Xylazine-positivity was detected in n=5 (12.8%) of quetiapine-negative heroin samples, compared to n=0 quetiapine-positive heroin samples (p=0.39). Methamphetamine-positivity was detected in n=7 (17.9%) of quetiapine-negative heroin samples, compared to n=1 (7.7%) of quetiapine-positive heroin samples (p=.217).

All quetiapine-positive samples were identified by clients as expected to contain black tar heroin, and samples were described by staff with consistent terms such as “sticky paste”, “black in color”, and “vinegary odor”. No clients reported expecting their samples to contain quetiapine. Participants did not identify any consistent unexpected effects of quetiapine-positive samples. However, one participant noted that their samples produced a “pins and needles” sensation which they found unusual (which is possibly a description of akathisia).

The sociodemographic characteristics of clients presenting with quetiapine-positive and quetiapine-negative samples were similar (and with no significant differences) with respect to gender, age group, and race/ethnicity.

Conclusion & Discussion: This paper provides the first drug-checking-based evidence in the academic literature—to our knowledge—of quetiapine as an additive to the illicit heroin supply. Limited previous studies have described intentional misuse of quetiapine, especially together with illicit stimulants[1], [2]. In contrast to those studies, we find quetiapine added to black tar heroin, unbeknownst to the end consumer. Notably, the presence of quetiapine was associated with fewer other adulterants, including less fentanyl, xylazine, and methamphetamine presence in heroin samples. This may indicate that heroin augmentation with quetiapine represents an alternative strategy—and likely a less risky one—compared to augmentation with fentanyl. Nevertheless, unintentional quetiapine ingestion represents possible risks including sedation, weight gain, or akathisia. Regular consumption of high-dose quetiapine could also cause a more complex withdrawal syndrome than heroin alone[4]. There is no evidence in the literature to suggest quetiapine increases opioid overdose risk[5].

This analysis is exploratory in nature, leveraging a small sample size, and only representative a select set of drug checking sites. It is further limited by lacking quantitative information about quetiapine concentration/dosing. Nevertheless, it does highlight how drug checking approaches can shed light on novel polysubstance patterns that can be subsequently verified in larger studies.

References: [1] S. Kim, G. Lee, E. Kim, H. Jung, and J. Chang, “Quetiapine misuse and abuse: Is it an atypical paradigm of drug seeking behavior?,” J Res Pharm Pract, vol. 6, no. 1, p. 12, 2017, doi: 10.4103/2279-042X.200987.
[2] O. V. Tcheremissine, “Is quetiapine a drug of abuse? Reexamining the issue of addiction,” Expert Opinion on Drug Safety, vol. 7, no. 6, pp. 739–748, Nov. 2008, doi: 10.1517/14740330802496883.
[3] C. L. Shover et al., “Rapid emergence of UV stabilizer Bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate (BTMPS) in the illicit fentanyl supply across the United States in July-August 2024: Results from drug and drug paraphernalia testing,” Sep. 16, 2024, medRxiv. doi: 10.1101/2024.09.13.24313643.
[4] W. J. Cubała and J. Springer, “Quetiapine abuse and dependence in psychiatric patients: a systematic review of 25 case reports in the literature,” Journal of Substance Use, vol. 19, no. 5, pp. 388–393, Oct. 2014, doi: 10.3109/14659891.2013.810309.
[5] F. D. Andersen et al., “Combined effects of quetiapine and opioids: A study of autopsy cases, drug users and sedation in rats,” Addiction Biology, vol. 27, no. 5, p. e13214, Sep. 2022, doi: 10.1111/adb.13214.