Nature
January 1, 2021
Lindsay P Cameron, Robert J Tombari, Ju Lu et al.
468 citations
Ibogaine, a psychedelic alkaloid, shows anti-addictive effects in humans and animals but has safety issues including toxicity and heart arrhythmias. Researchers engineered tabernanthalog, a water-soluble, non-hallucinogenic, non-toxic analogue made in a single step. In rodents, tabernanthalog promoted structural neural plasticity, reduced alcohol- and heroin-seeking behavior, and produced antidepressant-like effects. This demonstrates that careful chemical design can create safer, non-hallucinogenic variants of psychedelic compounds with therapeutic potential.
Journal of Neuroscience
January 19, 2005
Dao‐yao He, Nancy N. H. Mcgough, Ajay Ravindranathan et al.
181 citations
Ibogaine, a natural alkaloid with side effects that prevent clinical use, reduces alcohol consumption in rats. In two-bottle choice and operant self-administration tests, ibogaine decreased ethanol intake and also reduced relapse-like drinking. The effect is mediated by glial cell line-derived neurotrophic factor (GDNF) in the ventral tegmental area (VTA): ibogaine microinjected into the VTA reduced self-administration, systemic ibogaine increased GDNF expression in the midbrain, and in dopaminergic SHSY5Y cells ibogaine activated the GDNF pathway (phosphorylation of Ret and ERK1). Intra-VTA GDNF mimicked ibogaine's effect, while anti-GDNF antibodies blocked it. GDNF in the VTA therefore mediates ibogaine's action on ethanol consumption, suggesting GDNF as a target for alcoholism medications that could avoid ibogaine's side effects.
Proceedings of the National Academy of Sciences of the United States of America
June 10, 2008
Sebastien Carnicella, Viktor Kharazia, Jerome Jeanblanc et al.
132 citations
Infusing GDNF directly into the ventral tegmental area (VTA) of rats rapidly and dose-dependently reduces their operant self-administration of alcohol, but not sucrose. This effect is specific to the VTA, as infusion into the neighboring substantia nigra does not alter alcohol responding. GDNF activates the MAPK signaling pathway in the VTA, and blocking this pathway prevents the reduction in alcohol self-administration. GDNF also blocks the reacquisition of alcohol self-administration after extinction, indicating it reduces relapse-like behavior. The findings suggest GDNF, via MAPK activation, acts as a fast-acting and selective agent to diminish alcohol consumption and seeking.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
November 1, 2006
Dao‐yao He, Dorit Ron, Dao‐yao He et al.
67 citations
A single dose of Ibogaine, a putative anti-addiction drug, triggers a sustained increase in glial cell line-derived neurotrophic factor (GDNF) in midbrain cells. Using cultured dopaminergic-like SHSY5Y cells, short-term Ibogaine exposure initiated a self-sustaining positive feedback loop: GDNF mRNA rose, protein was expressed, and the GDNF signaling pathway activated, which further increased GDNF mRNA. This autoregulatory cycle explains Ibogaine's long-lasting reduction of drug craving in humans and alcohol and drug intake in rodents. The discovery of this GDNF-mediated feedback loop suggests potential for GDNF-based treatments for addiction and neurodegenerative diseases.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
November 1, 2006
Dao‐yao He, Dorit Ron, Dao‐yao He et al.
67 citations
A single dose of Ibogaine, a putative anti-addiction drug, triggers a sustained increase in glial cell line-derived neurotrophic factor (GDNF) in midbrain cells. Using cultured dopaminergic-like SHSY5Y cells, short-term Ibogaine exposure initiated a self-sustaining positive feedback loop: GDNF mRNA rose, protein was expressed, and the GDNF signaling pathway activated, which further increased GDNF mRNA. This autoregulatory cycle explains Ibogaine's long-lasting reduction of drug craving in humans and alcohol and drug intake in rodents. The discovery of this GDNF-mediated feedback loop suggests potential for GDNF-based treatments for addiction and neurodegenerative diseases.
Addiction biology
October 1, 2010
Sebastien Carnicella, Dao-Yao He, Quinn V Yowell et al.
49 citations
Noribogaine, a metabolite of ibogaine, increases GDNF expression in cell cultures and reduces alcohol self-administration when infused into the ventral tegmental area (VTA) of rats, whereas 18-MC, a synthetic ibogaine derivative, does not affect GDNF expression or alcohol responding in the VTA. These findings indicate that noribogaine and 18-MC act through different mechanisms and brain sites to reduce alcohol consumption, and that noribogaine may share ibogaine's anti-addictive properties without some of its side effects.