A postmortem study found no statistically significant difference in morphine concentrations between heroin users with pregabalin detected and a gabapentinoid-negative comparison group. That result did not establish that pregabalin reduced heroin intake, that doses were identical, or that the combination had no toxicological interaction.
Two comparisons addressed different questions
Nahar and colleagues screened femoral-vein blood from 3,750 coronial cases. The methods describe a two-year period, January 2016 through December 2017, although the abstract states a one-year end date. Of 354 people classified as heroin users, 69 were pregabalin-positive and 264 were negative for both pregabalin and gabapentin. These were distinct study groups rather than a complete two-way split of all 354.
The first comparison examined morphine concentrations between those 69 pregabalin-positive cases and 264 controls. A second analysis examined the relationship between pregabalin and morphine within 67 pregabalin-positive heroin cases after excluding two suspected intentional overdoses.
How heroin exposure was classified
Morphine had to be present in blood or urine. In addition, another heroin-related compound had to be detected, or the circumstances had to strongly support heroin use. Examples included 6-acetylmorphine or relevant scene evidence. Morphine detection alone was not treated as universally specific for heroin.
Nine pregabalin-positive heroin cases had no morphine detected in blood but had morphine and heroin-related compounds in urine. This matters when reading a blood concentration range beginning at zero: a zero blood entry did not mean the person failed the study’s exposure criteria.
Quantitative methods and the null findings
Pregabalin was measured by LC–MS/MS following protein precipitation, with a reported linear range of 0.5–50 µg/mL and positivity threshold of 0.5 µg/mL. Morphine-positive specimens underwent duplicate quantification by a validated solid-phase extraction and GC–MS procedure. The morphine assay was linear over 0.01–1.00 µg/mL; detection and quantification limits were both 0.01 µg/mL, and reported intra-day and inter-day imprecision were below 5%.
Reported morphine concentrations in the 69 pregabalin-positive heroin cases ranged from 0.00 to 1.46 µg/mL, with a median of 0.15 µg/mL. In the 264 controls, the range was 0.00–20.00 µg/mL and the median 0.13 µg/mL. The Mann–Whitney comparison gave p = 0.98, providing no significant distribution difference.
Within the restricted 67-case group, the results section reports no significant pregabalin–morphine association, with p = 0.95. The discussion gives a different nonsignificant value, p = 0.69. That inconsistency prevents presenting a single unqualified correlation p value; neither value supports a demonstrated association.
Why this did not measure an individual’s heroin dose
Unknown dosing times, staggered consumption and different elimination rates could separate the two measured concentrations. A postmortem blood value was not an administered-dose record. The study also lacked a uniform postmortem interval and individual paired antemortem results.
The absence of a significant concentration difference did not establish equivalent doses or equal toxicity. These comparisons were not designed as equivalence tests. They also did not directly measure respiratory depression or quantify a pregabalin–opioid interaction.
Co-detections remained relevant
Compared with controls, pregabalin-positive heroin cases more often had antidepressants, benzodiazepines, methadone, other opioids and antipsychotics detected; the reported comparisons were significant at p ≤ 0.001. Those associations complicated single-drug attribution, but did not identify which combination caused an individual death.
The defensible interpretation retains the null morphine findings alongside the broader co-detection pattern. For related exposure-classification limits, see negative autopsy drug screens and medication histories.
Primary source
Nahar LK, Murphy K, Paterson S. Toxicological Relevance of Pregabalin in Heroin Users: A Two-Year Postmortem Population Study. Journal of Analytical Toxicology. 2022;46:471–478. doi:10.1093/jat/bkab070.
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