Hippocampal and cognitive changes following non-fatal opioid overdose
Abstract
Background: Despite the ongoing opioid-related public health emergency in North America, the influences of non-fatal opioid overdose on brain structure remain unclear, largely due to a paucity of pre-overdose brain images. Hippocampal atrophy, potentially with corollary cognitive deficits, associated with hypoxic insult is a possible consequence of non-fatal opioid overdose.
Research objectives: Investigate overdose-associated changes in hippocampal volume.
Methods: Linear mixed effect modelling indexed hippocampal volume changes captured in repeat brain MRI from before and after self-reported opioid overdose in 22 individuals. Data from 66 propensity-matched non-overdosing participants are the reference for unrelated changes (mean 1.7 years between scans). Participants were from a naturalistic cohort study of health of vulnerably housed people in Vancouver, Canada (N = 515, 2008–2023). Follow-up paired tests of cognitive data from assessments completed close to the time of MRIs explore possible overdose-associated changes in memory and processing speed (operationalized as composite scores respectively derived from the Hopkins Verbal Learning and Stroop tests).
Results: Participants who overdosed between MRIs had more hippocampal volume loss compared to reference participants (97 mm3 versus 25 mm3 mean loss of bilateral hippocampal volume, respectively; χ² group-time = 4.8, p = .029, B = -47.1; χ² time = 1.6, p = .211, B = -13.6). Irrespective of overdose, memory performance was unchanged around this time (overdose between assessments: V= 89.00, p = .825, rrb = -.06; reference group: V=898.50, p =.738, rrb = -.05). There was a trend towards decreasing processing speed for those who overdosed (t(18)=2.11, p =.049, Hedge’s g =0.46; means before and after overdose: 0.08 and -0.30), without changes in the reference group (t(61)=-1.10, p=.275, g =-0.14).
Conclusions: Loss of hippocampal volume and potentially processing speed may be associated with non-fatal opioid overdose.
Key messages: • In this retrospective matched cohort analysis, 22 individuals with self-reported opioid overdose between brain MRIs, matched to 66 similar participants, had greater decreases in hippocampal volume.
• Participants showed a trend towards decreased processing speed, without changes in memory, between cognitive assessments before and after self-reported opioid overdose.
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BibTeX
@article{saint2026hippocampal,
title = {{Hippocampal and cognitive changes following non-fatal opioid overdose}},
author = {S A Saint and L N Farah and B K Nelson and A E Thornton and D J Lang and K M Gicas and A T Vertinsky and W Su and W G Honer and W J Panenka},
journal = {The European Journal of Public Health},
year = {2026},
month = oct,
doi = {10.1093/eurpub/ckag169.1097},
url = {https://doi.org/10.1093/eurpub/ckag169.1097},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Hippocampal and cognitive changes following non-fatal opioid overdose
AU - S A Saint
AU - L N Farah
AU - B K Nelson
AU - A E Thornton
AU - D J Lang
AU - K M Gicas
AU - A T Vertinsky
AU - W Su
AU - W G Honer
AU - W J Panenka
PY - 2026
DA - 2026/10/01
JO - The European Journal of Public Health
DO - 10.1093/eurpub/ckag169.1097
UR - https://doi.org/10.1093/eurpub/ckag169.1097
AB - Background: Despite the ongoing opioid-related public health emergency in North America, the influences of non-fatal opioid overdose on brain structure remain unclear, largely due to a paucity of pre-overdose brain images. Hippocampal atrophy, potentially with corollary cognitive deficits, associated with hypoxic insult is a possible consequence of non-fatal opioid overdose. Research objectives: Investigate overdose-associated changes in hippocampal volume. Methods: Linear mixed effect modelling indexed hippocampal volume changes captured in repeat brain MRI from before and after self-reported opioid overdose in 22 individuals. Data from 66 propensity-matched non-overdosing participants are the reference for unrelated changes (mean 1.7 years between scans). Participants were from a naturalistic cohort study of health of vulnerably housed people in Vancouver, Canada (N = 515, 2008–2023). Follow-up paired tests of cognitive data from assessments completed close to the time of MRIs explore possible overdose-associated changes in memory and processing speed (operationalized as composite scores respectively derived from the Hopkins Verbal Learning and Stroop tests). Results: Participants who overdosed between MRIs had more hippocampal volume loss compared to reference participants (97 mm3 versus 25 mm3 mean loss of bilateral hippocampal volume, respectively; χ² group-time = 4.8, p = .029, B = -47.1; χ² time = 1.6, p = .211, B = -13.6). Irrespective of overdose, memory performance was unchanged around this time (overdose between assessments: V= 89.00, p = .825, rrb = -.06; reference group: V=898.50, p =.738, rrb = -.05). There was a trend towards decreasing processing speed for those who overdosed (t(18)=2.11, p =.049, Hedge’s g =0.46; means before and after overdose: 0.08 and -0.30), without changes in the reference group (t(61)=-1.10, p=.275, g =-0.14). Conclusions: Loss of hippocampal volume and potentially processing speed may be associated with non-fatal opioid overdose. Key messages: • In this retrospective matched cohort analysis, 22 individuals with self-reported opioid overdose between brain MRIs, matched to 66 similar participants, had greater decreases in hippocampal volume. • Participants showed a trend towards decreased processing speed, without changes in memory, between cognitive assessments before and after self-reported opioid overdose.
SN - 1101-1262
SN - 1464-360X
ER -