"Polysubstance use may increase the risk of opioid overdose [36, 37] but although studies have found associations between overdose and combined use of heroin with other sedatives [38], the literature on overdose risk from heroin-stimulant combinations is limited [19, 39]. Goofball use has been associated with larger networks of PWID [19], which while potentially protective against overdose, may increase the likelihood of sharing injection equipment and contribute to transmission of bloodborne infections. Additionally, participants reported using methamphetamine to alter their sleep schedules or that methamphetamine use kept them awake for days, and the impact of sleep disturbances on susceptibility to opioid overdose needs additional study.

"Consistent with other studies [20], several respondents strongly believed in the ability of methamphetamine to prevent and reverse opioid overdose. Set against this are statistical data that show greater frequency of overdose among individuals co-using methamphetamine and heroin compared to people solely using heroin [19, 40] and rising numbers of deaths involving combinations of fentanyl and methamphetamine [41]. Increased mortality from co-use of these substances could represent greater co-use of methamphetamine overall or escalating fentanyl saturation of the opioid market but does not explain the lay belief in the possible protective effects of methamphetamine against opioid overdose.

"A potential explanation arises from recent mouse-model data which shows a bi-directional effect of amphetamine on fentanyl-depressed respiration depending on amphetamine dosage. Lower amphetamine doses depressed respiration after fentanyl, increasing the likelihood of overdose but higher amphetamine doses elevated respiration [42]. If applicable to humans, this finding may help to explain the apparent contradiction of methamphetamine both increasing and reducing the risks of fatal overdose and could lead to the development of important harm reduction strategies. However, more specific research on this drug interaction in humans is needed to understand this causal pathway.

"The importance of dosage and drug sequence when using methamphetamine to mitigate adverse respiratory effects of opioids, fentanyl in particular, requires further study. Order of use may not be evident in post-mortem toxicology and the interaction of these drug mechanisms over time needs further exploration. Amidst rising amphetamine-related hospitalizations [43, 44], research should also consider other specific morbidity risks posed by co-use of opioids and methamphetamine, including how non-injection modes of use (i.e. smoking, snorting [45]) may impact morbidity and mortality (e.g. by reducing HIV/HCV or overdose risks)."


Ondocsin, J., Holm, N., Mars, S.G. et al. The motives and methods of methamphetamine and ‘heroin’ co-use in West Virginia. Harm Reduct J 20, 88 (2023). doi.org/10.1186/s12954-023-00816-8