Ibogaína: un psicodélico atípico con potencial antiadictivo / Ibogaine: an atypical psychedelic with anti-addictive potential

El trastorno por uso de sustancias es una enfermedad crónica de graves consecuencias. Actualmente, los tratamientos farmacológicos no apuntan a corregir los cambios neurobiológicos generados en el cerebro por el uso crónico de sustancias de abuso, sino que se enfocan principalmente en la atenuación de algunos de los síntomas que padece el consumidor. La ibogaína es un psicodélico atípico que, tanto en estudios observacionales como en ensayos clínicos abiertos, ha mostrado una propiedad antiadictiva que perdura en el tiempo. Sin embargo, su delicado perfil de toxicidad cardíaca, así como su uso en entornos sin adecuadas medidas de seguridad, han limitado su progresión en las investigaciones clínicas. Los efectos antiadictivos de ibogaína han disparado diversas líneas de investigación básica, preclínica y clínica, que buscan confirmar su efectividad, entender sus mecanismos de acción y delimitar su perfil de seguridad. Dada la poca información disponible para los profesionales de salud sobre esta sustancia, esta revisión busca aportar información acerca de su potencial terapéutico, posibles mecanismos de acción y riesgos asociados a su administración.

Substance use disorder is a chronic disease with severe consequences. Currently, pharmacological treatments do not aim to correct the neurobiological changes generated in the brain by the chronic use of substances of abuse, but rather focus mainly on attenuating some of the user's symptoms. Ibogaine is an atypical psychedelic that has shown long-lasting and interesting antiaddictive properties in both observational studies and open-label clinical trials. However, its delicate profile of cardiac toxicity, as well as its use in settings without adequate safety measures, have limited its progression in clinical research. The anti-addictive effects of ibogaine have triggered diverse scientific research in basic, preclinical, and clinical areas, which seek efficacy confirmation and to fully understand ibogaine´s underlying mechanisms of action and its safety profile. Given that there is little information available to health professionals about ibogaine and its antiaddictive properties, this review aims to provide published data about its therapeutic potential in drug addiction, its mechanisms of action, and risks associated with its administration.

Treating drug dependence with the aid of ibogaine: a retrospective study.

Ibogaine is an alkaloid purported to be an effective drug dependence treatment. However, its efficacy has been hard to evaluate, partly because it is illegal in some countries. In such places, treatments are conducted in underground settings where fatalities have occurred. In Brazil ibogaine is unregulated and a combined approach of psychotherapy and ibogaine is being practiced to treat addiction. To evaluate the safety and efficacy of ibogaine, we conducted a retrospective analysis of data from 75 previous alcohol, cannabis, cocaine and crack users (72% poly-drug users). We observed no serious adverse reactions or fatalities, and found 61% of participants abstinent. Participants treated with ibogaine only once reported abstinence for a median of 5.5 months and those treated multiple times for a median of 8.4 months. This increase was statistically significant (p < 0.001), and both single or multiple treatments led to longer abstinence periods than before the first ibogaine session (p < 0.001). These results suggest that the use of ibogaine supervised by a physician and accompanied by psychotherapy can facilitate prolonged periods of abstinence, without the occurrence of fatalities or complications. These results suggest that ibogaine can be a safe and effective treatment for dependence on stimulant and other non-opiate drugs.

Anti-HIV-1 activity of the Iboga alkaloid congener 18-methoxycoronaridine.

The Iboga alkaloid congener 18-methoxycoronaridine (18-MC) exhibits in vitro leishmanicidal and in vivo anti-addiction properties. In this paper, we describe that 18-MC inhibits HIV-1 infection in human peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages. We found that 18-MC inhibits the replication of primary isolates of HIV-1 in a dose-dependent manner, regardless of the preferential chemokine receptor usage of the isolates, at non-cell-toxic concentrations. The antiretroviral activity of 18-MC resulted in EC (50) values of 22.5 +/- 4.7 microM and 23 +/- 4.5 microM for R5 and X4 isolates, respectively, in PBMCs, and a therapeutic index (TI) of 14.5. Similar findings were observed for inhibition of HIV-1 replication in macrophages: EC (50) equal to 12.8 +/- 5 microM and 9.5 +/- 3 microM for an R5 virus after 14 and 21 days of infection, respectively, with TI equal to 25.6 and 34.5. 18-MC moderately inhibits the HIV-1 enzyme reverse transcriptase (IC (50) = 69.4 microM), which at least partially explains its antiretroviral activity.

Ibogaine attenuation of morphine withdrawal in mice: role of glutamate N-methyl-D-aspartate receptors.

Ibogaine (IBO) is an alkaloid with putative antiaddictive properties, alleviating opiates dependence and withdrawal. The glutamate N-methyl-D-aspartate (NMDA) receptors have been implicated in the physiological basis of drug addiction; accordingly, IBO acts as a noncompetitive NMDA antagonist. The purpose of this study was to evaluate the effects of IBO on naloxone-induced withdrawal syndrome in morphine-dependent mice, focusing on the role of NMDA receptors. Jumping, a major behavioral expression of such withdrawal, was significantly (P<.01) inhibited by IBO (40 and 80 mg/kg, 64.2% and 96.9% inhibition, respectively) and MK-801 (0.15 and 0.30 mg/kg, 67.3% and 97.7%, respectively) given prior to naloxone. Coadministration of the lower doses of IBO (40 mg/kg) and MK-801 (0.15 mg/kg) results in 94.7% inhibition of jumping, comparable to the effects of higher doses of either IBO or MK-801. IBO and MK-801 also significantly inhibited NMDA-induced (99.0% and 71.0%, respectively) jumping when given 30 min (but not 24 h) prior to NMDA in nonaddictive mice. There were no significant differences in [3H]MK-801 binding to cortical membranes from naive animals, morphine-dependent animals, or morphine-dependent animals treated with IBO or MK-801. This study provides further evidence that IBO does have an inhibitory effect on opiate withdrawal symptoms and suggests that the complex process resulting in morphine withdrawal includes an IBO-sensitive functional and transitory alteration of NMDA receptor.