iboga fruit
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Ann. N.Y. Acad. Sci. 965: 28-46 (2002). © 2002 New York Academy of Sciences. ONAIVI et al.: IBOGAINE PHARMACOGENETICS Ibogaine Signals Addiction Genes and Methamphetamine Alteration of Long-Term PotentiationEMMANUEL S. ONAIVI,a,b SYED F. ALI,c SANIKA S. CHIRWA,d JEAN ZWILLER,e NATHALIE THIRIET,f B. EMMANUEL AKINSHOLA,g AND HIROKI ISHIGUROb aDepartment of Biology, William Paterson University, Wayne, New Jersey 07470, USA bMolecular Neurobiology Branch, IRP, NIDA-NIH, Baltimore, Maryland 21224, USA cNeurochemistry Laboratory, Division of Neurotoxicology Research, National Center forToxicological Research/FDA, Jefferson, Arizona 72079, USA dDepartment of Anatomy and Physiology, Meharry Medical College,Nashville, Tennessee 37308,USA eINSERM U338, Center de Neurochemimie, Strasbourg, France fMolecular Neuropsychiatry, NIDA-NIH, Baltimore, Maryland 21224, USA gDepartment of Pharmacology, Howard University College of Medicine,Washington D.C. 20059, USA ABSTRACTThe 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 ÒthresholdÓ 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. KEYWORDS: KEYWORDS: ibogaine; pharmacogenomics; pharmacotherapy: psychostimulant; gene chip; addiction; methamphetamine; haplotypes; SNPs; signal transduction; animal model INTRODUCTIONAnn. N.Y. Acad. Sci. 965: 28-46 (2002). © 2002 New York Academy of Sciences. ONAIVI et al.: IBOGAINE PHARMACOGENETICS The compulsive use of addictive substances despite adverse consequences continues to affect society, and the science underlying these addictions in general remains poorly understood. This is because the pharmacological treatment of drug and alcohol addiction has largely been disappointing. The good news is that the mapping of the human genetic code will enable us to identify potential gene products involved in human addictions and other diseases that have hereditary components. Indeed the compulsive use of addictive substances leading to neuroadaptation activates signal transduction pathways that regulate changes in gene expression. Thus, genetic vulnerability and environmental factors are important determinants in transitions from casual drug use to compulsive use of addictive substances. Addiction is therefore a polygenic disorder that affects the brain and peripheral tissues and does not follow simple Mendelian monogenic inheritance. While our knowledge of the pharmacogenomics and pharmacogenetics of addiction has yet to produce therapeutic targets to treat drug addicts, few findings of positive allelic association rarely withstand replication. A genome-wide, parallel search to determine at-risk genes and programs of gene expression patterns using quantitative trait loci (QTLs) mapping of rodent strains and DNA microarray analysis reveals at best genetic heterogeneity and complexity of addictions. Much effort recently has been focused on pharmacogenomics and addiction to opiates, alcoholism and substance abuse, genetic influences on smoking, and candidate genes. Others have focused on the application of DNA microarrays to study human alcoholism, or changes in non-human primate nucleus accumbens gene expression after chronic cocaine treatment, and large-scale analysis of gene expression changes during acute and chronic exposure to D9-THC in rats. Addiction is therefore a biological process and a brain disease that is not caused by one single gene, but rather involves multiple vulnerable genes, with significant contribution from environmental factors, including the trigger by the availability of abused substance(s). Thus, as the usefulness of 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 ibogaine and psychostimulants such as amphetamines in in vivo and in vitro models. Our work and that of others reveal that complex but defined signal transduction pathways are associated with the compulsive use of addictive substances and that the putative regulation of these signals by ibogaine may be linked to its broad spectrum of action on numerous biological systems.
Address for correspondence: Emmanuel S. Onaivi, Department of Biology, William Paterson
University, 300 Pompton Road, Wayne, NJ 07470. Voice: 973-720-3453; fax: 973-720-3730.
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© 1999The Ibogaine Dossier