A transcriptomic analysis in mice following a single dose of ibogaine identifies new potential therapeutic targets

Abstract

Ibogaine (IBO) is an atypical psychedelic with a complex mechanism of action. To date, the mechanisms that may underlie its anti-addictive effects are still not defined. This study aims to identify changes in gene expression induced by a single oral dose of IBO in the cortex of mice by means of a transcriptomic analysis for the first time. Our results showed significant alterations in gene expression in mouse frontal cortex samples 4 h after a single oral dose of IBO. Specifically, genes involved in hormonal pathways and synaptogenesis exhibited upregulation, while genes associated with apoptotic processes and endosomal transports showed downregulation. The findings were further corroborated through quantitative polymerase chain reaction (qPCR) analysis. However, the validation of gene expression related to hormonal pathways did not entirely align with the transcriptomic analysis results, possibly due to the brain region from which tissue was collected. Sex differences were observed, with female mice displaying more pronounced alterations in gene expression after IBO treatment. High variability was observed across individual animals. However, this study represents a significant advancement in comprehending IBO’s molecular actions. The findings highlight the influence of IBO on gene expression, particularly on hormonal pathways, synaptogenesis, apoptotic processes, and endosomal transports. The identification of sex differences underscores the importance of considering sex as a potential factor influencing IBO’s effects. Further research to assess different time points after IBO exposure is warranted.

Ibogaine Induces Cardiotoxic Necrosis in Rats—The Role of Redox Processes

“…Furthermore, female sex is among the additional risk factors for drug-induced TdP arrhythmias that should be considered before the use of ibogaine [ 6 ]. Previous results have shown that the bioavailability of ibogaine and its principal in vivo metabolite, noribogaine, is two to three times higher in female rats than in male rats [ 9 , 10 ] and that ibogaine has sex-specific effects on the central nervous system [ 11 , 12 , 13 ], liver, and kidneys, with ibogaine-induced pathological changes being more pronounced in female rats [ 10 , 14 , 15 ].…”