A Narrative Review on the Biochemical Effects of Drugs of Abuse on Liver and Kidney

Abstract

Background: Chronic abuse of opioids, stimulants, and analgesic drugs is associated with significant biochemical, immunological, and oxidative stress–related alterations in liver and kidney function. Although the toxic effects of these substances have been widely documented, available evidence remains fragmented and largely substance-specific, with limited comparative analysis and insufficient focus on recovery following drug withdrawal. This review aimed to synthesize current evidence regarding chronic drug-induced organ toxicity and post-withdrawal biochemical recovery patterns.

Methods: This narrative review analyzed findings from twenty peer-reviewed studies, predominantly preclinical animal-based investigations, with limited inclusion of available human clinical data. The review evaluated the effects of chronic exposure to opioids (tramadol, morphine, heroin), stimulants (amphetamine, cocaine, ketamine), and analgesics (acetaminophen and Tramacet). Biochemical and immunological parameters assessed included hepatic enzymes (ALT, AST, LDH), renal biomarkers (BUN and creatinine), oxidative stress markers (GSH, SOD, CAT, MDA), and pro-inflammatory cytokines (IFN-γ and IL-1β).

Results: Acetaminophen exhibited the most severe hepatotoxic and nephrotoxic effects, primarily mediated through its reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI). Opioids and stimulants produced moderate but clinically significant hepatic and renal injury, mainly through reactive oxygen species (ROS) generation and mitochondrial dysfunction. Oxidative stress biomarkers demonstrated reduced antioxidant defense and increased lipid peroxidation across most studies. Post-withdrawal findings revealed only partial normalization of biochemical and inflammatory parameters, indicating persistent and drug-specific toxic effects despite cessation of exposure.

Conclusion: Chronic abuse of opioids, stimulants, and analgesics can cause significant liver and kidney damage through oxidative and inflammatory mechanisms. Persistent abnormalities after withdrawal highlight the need for long-term monitoring and targeted therapeutic interventions.