Autoregulation of glial cell line-derived neurotrophic factor expression: implications for the long-lasting actions of the anti-addiction drug, Ibogaine.

Abstract

We recently showed that the up-regulation of the glial cell line-derived neurotrophic factor (GDNF) pathway in the midbrain, is the molecular mechanism by which the putative anti-addiction drug Ibogaine mediates its desirable action of reducing alcohol consumption. Human reports and studies in rodents have shown that a single administration of Ibogaine results in a long-lasting reduction of drug craving (humans) and drug and alcohol intake (rodents). Here we determine whether, and how, Ibogaine exerts its long-lasting actions on GDNF expression and signaling. Using the dopaminergic-like SHSY5Y cell line as a culture model, we observed that short-term Ibogaine exposure results in a sustained increase in GDNF expression that is mediated via the induction of a long-lasting autoregulatory cycle by which GDNF positively regulates its own expression. We show that the initial exposure of cells to Ibogaine or GDNF results in an increase in GDNF mRNA, leading to protein expression and to the corresponding activation of the GDNF signaling pathway. This, in turn, leads to a further increase in the mRNA level of the growth factor. The identification of a GDNF-mediated, autoregulatory long-lasting feedback loop could have important implications for GDNF's potential value as a treatment for addiction and neurodegenerative diseases.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

• State of the evidence: Ibogaine for addiction ↑Supports

  Short-term ibogaine exposure produced a sustained increase in GDNF expression via a long-lasting autoregulatory positive feedback loop, offering a mechanism for long-lasting anti-addiction effects.

  Synthesized September 21, 2026

Comparable studies

Other preclinical and animal studies on ibogaine for addiction, most cited first.