Toxicological relevance of pregabalin in heroin users: a two-year post-mortem population study

Pregabalin (PGL) is a gabapentinoid used to treat epilepsy, neuropathic pain and generalized anxiety disorder. PGL is also misused by heroin users as it enhances the effects of heroin. While it is thought those who misuse PGL take it in amounts greater than the recommended therapeutic dose, it is unknown whether there is a significant difference between the amounts of PGL used by heroin users compared to non-heroin users. This study hypothesized that the PGL concentrations in post-mortem (PM) samples taken from heroin users positive for PGL would be higher than those in non-heroin users. Between 1 January 2016 and 31 December 2016, a routine drug screen and a specific screen for PGL were carried out on femoral-vein bloods from 3,750 PM Coroners’ cases. Of the cases screened, 354 were heroin users, of which 264 cases were negative for gabapentinoids and therefore used as the control-heroin-user group. PGL was positive in 229 cases, of which 69 were heroin users and 160 were non-heroin users. On comparing the PGL concentrations, statistically higher concentrations were observed in the heroin users compared to non-heroin users (P = 0.002). There was no correlation between the concentrations of PGL and morphine (from heroin) in the heroin users (P = 0.95), and the amount of heroin (morphine) consumed was not dependant on whether PGL was consumed or not (P = 0.98). The prevalence of anti-depressants, benzodiazepines, methadone and non-heroin-related opioids was seen to be significantly higher in heroin users that were positive for PGL than the control-heroin users (P = < 0.001 for all drugs). This study suggests that heroin users are using greater amounts of PGL compared to non-heroin users; however, the magnitude of the difference in use may not be sufficient to conclude that heroin users are at substantially greater risk of PGL toxicity compared to non-heroin users. Results indicate that heroin users who take PGL are more likely to use multiple depressant drugs, hence increasing the risk of multi-drug toxicity and death in this population