Annals of the New York Academy of Sciences
June 1, 2002
Emmanuel S Onaivi, Syed F Ali, Sanika S Chirwa et al.
23 citations
Mapping the human genetic code may help identify genes involved in addictions. Microarray technologies have linked specific genes to diseases. Pharmacological treatments for addiction have been largely disappointing, prompting interest in the controversial natural alkaloid ibogaine. Research on gene expression and signaling molecules in rat brain models shows that psychostimulants like methamphetamine and cocaine alter long-term potentiation in the hippocampus, possibly creating a threshold beyond which excessive brain stimulation occludes LTP. Ibogaine broadly regulates these signal transduction pathways and influences immediate early genes, suggesting it may signal addiction-related gene products, though further evaluation is needed.
Annals of the New York Academy of Sciences
May 1, 1998
Yossef Itzhak, Syed F Ali
20 citations
Ibogaine, a hallucinogenic alkaloid, may help treat opioid and cocaine addiction. Its neurochemical mechanisms are unclear. In rat cortex and cerebellum membrane preparations, ibogaine bound to high- and low-affinity phencyclidine (PCP) sites in the cortex (Ki(H) = 0.01-0.05 μM; Ki(L) = 2-4 μM) and only low-affinity sites in the cerebellum (Ki = 2-4 μM). It showed no affinity for NMDA receptor binding sites at concentrations >100 μM. Affinity for sigma-1 and sigma-2 sites ranged from 1.5-3 μM. Binding to PCP sites may contribute to ibogaine's potential anti-addiction properties, while sigma site interactions may cause adverse effects.
Annals of the New York Academy of Sciences
May 1, 1998
Zbigniew Binienda, Michael A Beaudoin, Brett T Thorn et al.
13 citations
Ibogaine, a psychoactive alkaloid with antiaddictive properties, can cause neurotoxicity. In anesthetized rats, a single 50 mg/kg dose of ibogaine produced an immediate decrease in heart rate and reduced EEG power across delta, theta, alpha, and beta frequency bands during the first 30 minutes, with recovery within 15 minutes. In the caudate nucleus, dopamine levels fell while dopamine turnover increased; serotonin levels rose in the frontal cortex. These physiological changes likely stem from ibogaine's interactions with multiple neurotransmitter systems.
Annals of the New York Academy of Sciences
May 1, 1998
Emmanuel S Onaivi, Syed F Ali, Amitabha Chakrabarti
13 citations
Ibogaine, a substance with potential antiaddiction effects against alcohol, psychostimulants, and opiates, was studied in mice and cell cultures to explore its mechanism. In mice, acute ibogaine doses reduced aversion to open arms in a plus-maze test, while subacute administration caused fluctuating aversive and antiaversive behavior over 14 days. Ibogaine reversed withdrawal aversions in mice abruptly withdrawn from cocaine. In PC 12 cells, cocaine disrupted signal transduction by altering protein kinase C isoform expression and activity and calcium levels. The findings suggest ibogaine's antiaddictive property may involve modifying central nervous system neurotransmission related to anxiety, but whether PKC signaling is important remains unknown.