Medication Development of Ibogaine as a Pharmacotherapy for Drug Dependence a

@article{Mash1998MedicationDO,
  title={Medication Development of Ibogaine as a Pharmacotherapy for Drug Dependence a},
  author={Deborah C. Mash and Craig A. Kovera and Billy E. Buck and M D Norenberg and Paul Shapshak and William Lee Hearn and Juan R. Sanchez-Ramos},
  journal={Annals of the New York Academy of Sciences},
  year={1998},
  volume={844}
}
ABSTRACT: The potential for deriving new psychotherapeutic medications from natural sources has led to renewed interest in rain forest plants as a source of lead compounds for the development of antiaddiction medications. Ibogaine is an indole alkaloid found in the roots of Tabernanthe iboga (Apocynaceae family), a rain forest shrub that is native to equatorial Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and in higher doses as a sacrament in religious… Expand
Ibogaine as a treatment for substance misuse: Potential benefits and practical dangers.
TLDR
There is a need to develop better opiate detoxification treatment against a background of increasing opioid-related fatalities, and a congener of ibogaine, 18-MC, appears to be safer and is to undergo clinical trials. Expand
Ibogaine for treating drug dependence. What is a safe dose?
TLDR
To consider an appropriate and safe initial dose for humans, necessary safety factors need to be applied to the animal data; these would include factors such as intra- and inter-species variability and for susceptible people in a population (such as drug users). Expand
Mechanisms of action of ibogaine: relevance to putative therapeutic effects and development of a safer iboga alkaloid congener.
TLDR
In this study, animal models have been used to study ibogaine's interactions with drugs of abuse, to investigate its mechanisms of action, and to help develop an iboga derivative that will have an improved safety profile. Expand
Safety of ibogaine administration in detoxification of opioid dependent individuals: a descriptive open-label observational study.
TLDR
An open-label observation study found that ibogaine treatment of patients with opioid use disorder can induce a clinically relevant but reversible QTc prolongation, bradycardia, and severe ataxia. Expand
Combating Substance Abuse with Ibogaine: Pre- and Posttreatment Recommendations and an Example of Successive Model Fitting Analyses
TLDR
A number of theory-driven, pretreatment and posttreatment recommendations that have good potential for enhancing ibogaine's effectiveness are suggested and a minimum set of patient- and treatment-related variables be included in all ibogane publications involving human participants. Expand
Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes
TLDR
It is reported here that ibogaine therapy administered in a safe dose range diminishes opioid withdrawal symptoms and reduces drug cravings and product development of single oral dose administration of Ibogaine for the treatment of opioid withdrawal during medically supervised detoxification to transition drug dependent individuals to abstinence is supported. Expand
Ibogaine offers an alternative approach for treating opiate addiction
TLDR
Ibogaine is a naturally occurring indole alkaloid that may be an effective alternative form of treatment for individuals struggling with opiate addiction and/or withdrawal and is found that iboga alkaloids such as ibogaine are effective at reducing morphine self-administration in rats. Expand
hERG Blockade by Iboga Alkaloids
TLDR
Results may relate to observations of persistent QT prolongation and cardiac arrhythmia at delayed intervals of days following ibogaine ingestion, and suggest that the iboga alkaloids might provide an informative paradigm for investigation of the structural biology of the hERG channel. Expand
Comparative neuropharmacology of ibogaine and its O-desmethyl metabolite, noribogaine.
TLDR
Ibogaine and noribogaine are equipotent in their ability to evoke a transient stimulation of dopamine metabolism that is characterized by profound depletion of tissue DA in mesolimbic, mesocortical, and mesostriatal terminal projection areas. Expand
Noribogaine (12‐Hydroxyibogamine): A Biologically Active Metabolite of the Antiaddictive Drug Ibogaine
TLDR
The present data demonstrate that NORIBO is biologically active and undoubtedly contributes to the in vivo pharmacological profile of IBO in rats, and appears less likely to produce the adverse effects associated with IBO (i.e., tremors and stress‐axis activation), suggesting that the metabolite may be a safer alternative for medication development. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 62 REFERENCES
A preliminary investigation of ibogaine: case reports and recommendations for further study.
TLDR
Ibogaine, an alkaloid with psychotropic effects at doses of 200-300 mg and above, was taken by seven individuals who were addicted to opiates and may serve as a model for the development of improved agents for the treatment of substance abuse in the future. Expand
Comparison of the behavioral effects of ibogaine from three sources: mediation of discriminative activity.
TLDR
The results indicate that ibogaine is readily discriminable from its vehicle and that ib Bogaine from each of the three supplies produced statistically similar discrimination with ED50 values ranging from 2.5 to 3.4 mg/kg, which should allow for pre-clinical work using any of these research samples to be comparable. Expand
Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin.
TLDR
It is reported here that 12-hydroxyibogamine, a primary metabolite of ibogaine, displays high affinity for the 5-HT transporter and elevates extracellular 5- HT and may heighten mood and attenuate drug craving. Expand
Ibogaine neurotoxicity: a re-evaluation
TLDR
Re-examined cerebellar responses to the high doses of ibogaine used by O'Hearn and Molliver and sought to determine whether a lower dose, one effective in reducing morphine and cocaine self-administration, produced similar responses, to suggest the degenerative and "anti-addictive' properties of Ibogaine reflect different actions of the drug. Expand
Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum
TLDR
In some rats, there were persistent decreases in morphine or cocaine intake for several days after a single injection or after two or three weekly injections of one or another of these alkaloids; R-ibogamine produced such effects more consistently than any of the other alkaloid effects. Expand
Effects and aftereffects of ibogaine on morphine self-administration in rats.
TLDR
In some rats, there was a persistent decrease in morphine intake for several days or weeks after a single injection of ibogaine; other rats began to show such persistent changes only after two or three weekly injections whereas a few rats were apparently resistant to prolonged aftereffects. Expand
Effects of ibogaine and noribogaine on the antinociceptive action of μ-, δ- and κ-opioid receptor agonists in mice
Ibogaine, an alkaloid isolated from the bark of the African shrub, Tabernanthe iboga, has been claimed to decrease the self-administration of drugs of abuse like morphine, cocaine and alcohol. ToExpand
Effects of ibogaine on acute signs of morphine withdrawal in rats: Independence from tremor
Because of the claim that ibogaine suppresses the symptoms of "narcotic withdrawal" in humans, the effect of ibogaine on naltrexone-precipitated withdrawal signs in morphine-dependent rats wasExpand
High affinity ibogaine binding to a mu opioid agonist site.
  • E. Codd
  • Chemistry, Medicine
  • Life sciences
  • 1995
TLDR
Ibogaine is an agonist at the mu opioid receptor with a Ki value of about 130 nM, potentially explaining ibogaine's antinociceptive effects as well as its reported reduction of opioid withdrawal symptoms and attenuation of drug seeking behavior. Expand
Inhibitory effects of ibogaine on cocaine self-administration in rats.
TLDR
The results indicate that ibogaine or its metabolite(s) is a long-lasting interruptor of cocaine dependence, which supports similar observations from uncontrolled clinical studies. Expand
...
1
2
3
4
5
...