Anti-Addiction Drug Ibogaine against Alcohol Consumption
Dao-Yao He,1 * Nancy N. H. McGough,1 * Ajay Ravindranathan,1 Jerome Jeanblanc,1 Marian L. Logrip,1,3 Khanhky Phamluong,1 Patricia H. Janak,1,2,3 and Dorit Ron1,2,3
1Ernest Gallo Research Center, 2Department of Neurology, 3Neuroscience Graduate Program, University of California, San Francisco, Emeryville, California 94608
Alcohol addiction manifests as uncontrolled drinking despite negative consequences. Few medications are available to treat the disorder. Anecdotal reports suggest that ibogaine, a natural alkaloid, reverses behaviors associated with addiction including alcoholism; however, because of side effects, ibogaine is not used clinically. In this study, we first characterized the actions of ibogaine on ethanol self-administration in rodents. Ibogaine decreased ethanol intake by rats in two-bottle choice and operant self-administration paradigms. Ibogaine also reduced operant self-administration of ethanol in a relapse model. Next, we identified a molecular mechanism that mediates the desirable activities of ibogaine on ethanol intake. Microinjection of ibogaine into the ventral tegmental area (VTA), but not the substantia nigra, reduced self-administration of ethanol, and systemic administration of ibogaine increased the expression of glial cell line-derived neurotrophic factor (GDNF) in a midbrain region that includes the VTA. In dopaminergic neuron-like SHSY5Y cells, ibogaine treatment upregulated the GDNF pathway as indicated by increases in phosphorylation of the GDNF receptor, Ret, and the downstream kinase, ERK1 (extracellular signal-regulated kinase 1). Finally, the ibogaine-mediated decrease in ethanol self-administration was mimicked by intra-VTA microinjection of GDNF and was reduced by intra-VTA delivery of anti-GDNF neutralizing antibodies. Together, these results suggest that GDNF in the VTA mediates the action of ibogaine on ethanol consumption. These findings highlight the importance of GDNF as a new target for drug development for alcoholism that may mimic the effect of ibogaine against alcohol consumption but avoid the negative side effects.
Skipper Bowles Center for Alcohol Studies, University of North Carolina School of Medicine at Chapel Hill, USA.
Alcohol-preferring (P), Fawn-Hooded (FH) and alcohol-accepting (AA) rats were injected intraperitoneally (IP) or subcutaneously (SC) with different doses (10, 30, and 60 mg/kg) of Ibogaine or vehicle. In a separate experiment, FH rats were administered intragastrically (IG) with either 60 mg/kg of Ibogaine or vehicle for 5 days. In addition, the effects of Ibogaine on blood alcohol concentrations were measured. Our data show that, contrary to the SC administration of Ibogaine, IP administration of the agent significantly and dose-dependently reduced alcohol intake in these rats. Subchronic IG administration of 60 mg/kg of Ibogaine into FH rats significantly reduced alcohol intake without the development of tolerance or a significant effect on food or water intake. A single IP injection of 60 mg/kg Ibogaine into FH rats did not affect the blood alcohol levels. These results show that Ibogaine when injected IP or IG, but not SC, can significantly reduce alcohol intake without an effect on blood alcohol concentrations or food intake. These findings may suggest the involvement of Ibogaine's metabolite(s) in reducing alcohol intake. Although the neuronal mechanism(s) of action of Ibogaine on the regulation of alcohol intake is not fully understood, it is speculated that Ibogaine or its metabolite(s) exerts its attenuating effect on alcohol intake by modulating neurotransmitters/neuromodulators proposed to be involved in regulation of alcohol consumption.
Verkar fungera för att minsta råttors alkoholsug ... men i dagsläget finns det mycket lite information om övrigt som jag ser det just nu. Alkohol är en skenbart O-komplex drog vars beroenden och missbruk orsaker samhället gigantiska skador. Tyvärr kan jag inte se att ibogain i dagsläget kan rekommenderas.
En annan tänkbarhet manande till försiktighet är ju att storkonsumenter av alkohol inte helt sällan också har en mycket ansträngd leverfunktion, vilket kan vara en direkt kontraindikation till ibogainbehandling. Så grundsvaret på din fråga är : vet inte, det finns anledning att avvakta tills man vet mera.
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