Ibogaine Signals Addiction Genes

HSLotsof at aol.com HSLotsof at aol.com
Thu Jul 11 13:46:37 EDT 2002

 Ann N Y Acad Sci 2002 Jun;965:28-46     


Ibogaine Signals Addiction Genes and Methamphetamine Alteration of Long-Term 


Onaivi ES, Ali SF, Chirwa SS, Zwiller J, Thiriet N, Akinshola BE, Ishiguro H.

Department of Biology, William Paterson University, Wayne, New Jersey 07470, 


The mapping of the human genetic code will enable us to identify potential 

gene products involved in human addictions and diseases that have hereditary 

components. Thus, large-scale, parallel gene-expression studies, made 

possible by advances in microarray technologies, have shown insights into the 

connection between specific genes, or sets of genes, and human diseases. The 

compulsive use of addictive substances despite adverse consequences continues 

to affect society, and the science underlying these addictions in general is 

intensively studied. Pharmacological treatment of drug and alcohol addiction 

has largely been disappointing, and new therapeutic targets and hypotheses 

are needed. As the usefulness of the pharmacotherapy of addiction has been 

limited, an emerging potential, yet controversial, therapeutic agent is the 

natural alkaloid ibogaine. We have continued to investigate programs of gene 

expression and the putative signaling molecules used by psychostimulants such 

as amphetamine in in vivo and in vitro models. Our work and that of others 

reveal that complex but defined signal transduction pathways are associated 

with psychostimulant administration and that there is broad-spectrum 

regulation of these signals by ibogaine. We report that the actions of 

methamphetamine were similar to those of cocaine, including the propensity to 

alter long-term potentiation (LTP) in the hippocampus of the rat brain. This 

action suggests that there may be a "threshold" beyond which the excessive 

brain stimulation that probably occurs with compulsive psychostimulant use 

results in the occlusion of LTP. The influence of ibogaine on immediate early 

genes (IEGs) and other candidate genes possibly regulated by psychostimulants 

and other abused substances requires further evaluation in compulsive use, 

reward, relapse, tolerance, craving and withdrawal reactions. It is therefore 

tempting to suggest that ibogaine signals addiction gene products.

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