Background: Gabapentin is an anticonvulsant adjunct and a neuropathic pain analgesic that has become widely abused in Egypt in the last decade after scheduling its analogue pregabalin in 2012. Clonazepam is an antiepileptic drug approved for treatment of various types of seizures. Clonazepam has a high-recognized potential for abuse, as well as tolerance, physical dependence, and ultimately addiction.

The aim of this research is to study and evaluate the hepatotoxic and nephrotoxic effects of sub chronic misuse of gabapentin in relation to a well-known highly addictive drug like clonazepam.

Methods: Using a previously validated animal model, 30 healthy adult male albino rats were included, divided into three equal randomization groups: group I (normal saline), group II (clonazepam misuse), and group III (gabapentin misuse). Rats in each group received the respective drugs for 50 days. After this time, liver enzymes (AST, ALT and ALP) and renal biomarkers (urea, creatinine and uric acid) were measured and hepatic and renal histopathology was evaluated.

Results: Both gabapentin and clonazepam were associated with numerous biochemical and histopathological alterations relative to controls. Clonazepam was associated with higher elevation of (AST and ALT) as well as more histopathological changes to a greater degree than gabapentin.

Conclusions: The study underscores the importance of careful monitoring of protein markers of hepatocyte injury as well as renal biomarkers in patients receiving gabapentin for long-term duration, either as a misuse or in addict patients during withdrawal.