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Substrates of Human CYP2D6
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
CYP2D6 is largely responsible for the metabolism of ibogaine to its O-desmethyl active metabolite 12-hydroxyibogamine (noribogaine) (Figure 3.111) (Obach et al. 1998), a psychoactive alkaloid isolated from the root of Tabernanthe iboga, a rainforest shrub native to Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger, and thirst, and in higher doses as a sacrament in religious rituals. Ibogaine represents a potentially useful therapeutic agent in the treatment of opiate and psychostimulant addiction and opiate withdrawal (Alper et al. 1999, 2000; Frances et al. 1992; Glick et al. 1992; Popik et al. 1995). Ibogaine has shown preliminary efficacy for opiate detoxification and for short-term stabilization of drug-dependent persons as they prepare to enter substance abuse treatment (Mash et al. 2000). Ibogaine and noribogaine interacted with 5-HT transporters (SERT/SLC6A4) to inhibit 5-HT uptake (Baumann et al. 2001; Mash et al. 1995).
Nutraceutical Intervention for Treatment of Alcoholism and Drinking Problems
Published in Raj K. Keservani, Anil K. Sharma, Rajesh K. Kesharwani, Nutraceuticals and Dietary Supplements, 2020
Both T. iboga and Voacanga africana are perennial shrubs innate to Central Africa and belongs to family Apocynaceae. They are largely used in customary African medicine. The root bark of T. iboga comprises ibogaine as its major alkaloid, although Ibogaine is one of some naturally occurring alkaloids found in V. africana. The psychoactive indole alkaloid known as ibogaine is used to treat cravings of alcohol, cocaine, heroin, and methamphetamine. Ibogaine is present in the root bark of Tabernanthe iboga that acts on the serotonin, dopamine, and opioid receptors to decrease substance cravings. The stimulating, fatigue-, thirst-, and hunger-ameliorating effects of ibogaine are well known since times immemorial. The preclinical evidence indicates that ibogaine considerably affect morphine and cocaine after self-administration in rodents. Recently, ibogaine has been testified to markedly decrease voluntary liquor consumption in alcohol-preferring rats. The dropping effect of ibogaine on alcohol intake was detected only when ibogaine was injected intraperitoneally or intragastrically and not subcutaneously, suggesting that the bioactive principle of ibogaine could be a metabolite produced by the liver. It has been found that ibogaine can be toxic in high doses, so an ibogaine analog, known as 18-methoxycoronaridine, has been developed to produce the same antiaddiction effects as ibogaine but without the toxic side effects. Iboga acts on the neurotransmitters that control drinking behavior and helps to reduce cravings and subdue extreme drinking (Carai et al., 2000).
Missed Opportunities? Beneficial Uses of Illicit Drugs
Published in Ross Coomber, The Control of Drugs and Drug Users, 2020
Lester Grinspoon, James B. Bakalar
Ibogaine is a psychedelic substance derived from the roots of an African plant, Tabernanthe iboga. Apparently it allows the user to “play back” visual memories using the eyelids or any surface as a sort of movie screen. Ibogaine was briefly used to enhance psychotherapy in the 1960s (Naranjo, 1969), but is now receiving attention mainly because of the claim that it can interrupt chemical dependency, greatly diminishing withdrawal symptoms and drug craving in heroin and cocaine addicts, and allowing them an opportunity to free themselves from addiction at least for a time. The interest was generated by Howard Lotsof, a heroin addict who found that the ibogaine experience interrupted his addiction. A number of addicts have undergone this experience under the supervision of Dr. Hans Bastiaans in the Netherlands, where use of ibogaine is not illegal. Among this small group of highly motivated addicts, some have remained drug-free without craving for at least six months. For these patients, ibogaine compares favorably with other forms of addiction treatment. A larger number have had their addictions interrupted but need other support to remain drug-free (Lotsof, 1990). These results have generated interest, and other researchers are beginning to explore the therapeutic potential of ibogaine. It has been found to reduce withdrawal symptoms in morphine-dependent rats (Dzoljic et al., 1988) and monkeys (Aceto et al., 1990), and it causes rats to self-administer less morphine (Glick et al., 1991) and cocaine (Cappendijk & Dzoljic, 1993). Animal studies have paved the way for clinical research that may determine whether or not ibogaine has the potential suggested by the anecdotal evidence.
Ibogaine and Subjective Experience: Transformative States and Psychopharmacotherapy in the Treatment of Opioid Use Disorder
Published in Journal of Psychoactive Drugs, 2019
Thomas K. Brown, Geoff E. Noller, Julie O. Denenberg
With three recent publications, the scientific evidence of the efficacy of ibogaine treatment is growing. These include Schenberg et al. (2014), showing efficacy with increased periods of abstinence from problem substances, primarily cocaine, following detoxification. Two observational studies provided evidence that ibogaine is effective in treating opioid use disorder. Both Brown and Alper (2018) and Noller, Frampton, and Yazar-Klosinski (2018) found that ibogaine is useful in acute opioid detoxification, significantly reducing withdrawal symptoms as measured by the Subjective Opioid Withdrawal Scale (Handelman et al. 1987). Both also showed, using the Addiction Severity Index (ASI; McLellan et al. 1999), that Drug Use Severity scores were significantly reduced 12 months following treatment. One study, based at treatment sites in Mexico (Brown and Alper 2018), also found significant improvements in ASI Family and Social Status subscores at all follow-up time points from one to 12 months following treatment. The other study, based in New Zealand (Noller, Frampton, and Yazar-Klosinski 2018), showed that ibogaine treatment was associated with improvement in depression symptoms at one month and 12 months following treatment, as measured by the Beck Depression Inventory-II (BDI-II; Beck, Steer, and Brown 1996).
On Addiction, Complexity, and Freedom: Toward a Liberation-Focused Addiction Treatment
Published in Journal of Psychoactive Drugs, 2019
In recent years, there has been an increased interest in the use of ibogaine as a method for treating opiate and other addictions (Brown 2013). Derived from Tabernanthe iboga, a plant used in sacred ceremonies by practitioners of the Bwiti religion in West Central Africa, ibogaine is now understood to be an “addiction interrupter” (Lotsof 1995). Increasingly being used as a treatment for addictions, this healing plant also has the potential to increase the capacity for freedom among those who are successfully treated with it. Amanda, who built on her ibogaine experience to transform her life, reflected on her journey: I’ve been clean ever since, a year and a half now…. I’ve got a job that I love, an amazing new boyfriend, my relationships with my family are healed; my life is totally different than it was. I’m healthier and happier than I can ever remember being. I have no craving or desire for the drugs that used to control my life…. I’ve been given a chance to hit the reset button, to begin my life again. Ibogaine is not a miracle drug. You have to really want it, and you have to be willing to do the work, and it is some of the most challenging work I’ve ever done in my life.” (Heyes and Carlander 2014)
A Mixed-Method Analysis of Persisting Effects Associated with Positive Outcomes Following Ibogaine Detoxification
Published in Journal of Psychoactive Drugs, 2018
Alan K. Davis, Elise Renn, Austin-Marley Windham-Herman, Martin Polanco, Joseph P. Barsuglia
Item means of the persisting effects of ibogaine questionnaire in the total sample indicate that most participants believed that they had experienced positive changes in psychological, behavioral, and social functioning after ibogaine treatment (Table 2). For the sample overall, participants reported the greatest positive changes in psychosocial functioning, which included changes in their sense of gratitude, ability to be a more authentic person, sense of meaning in life, appreciation for life, sense of life being interconnected, quality of relationships, importance of spirituality in life, sense of values, and acceptance of others (highest endorsed items with M > 0.84). Further, statistically significant differences in positive effects were associated with ibogaine treatment. Specifically, compared to participants in the non-responder subgroup, those in the treatment responder subgroup had significantly greater positive changes in their sense of gratitude, ability to be a more authentic person, sense of meaning in life, appreciation for life, experience of inner peace, feelings of love and openheartedness, experience of joy or bliss, experience of sacredness in daily life, ability to tolerate difficult or painful feelings, and capacity for coping with stress, and they experienced a significant decrease in feelings of unhealthy anger (d > 0.80, p <.01).