Evaluating the toxicity and therapeutic potential of ibogaine in the treatment of chronic opioid abuse

(+)-Catharanthine and (-)-18-methoxycoronaridine induce antidepressant-like activity in mice by differently recruiting serotonergic and norepinephrinergic neurotransmission

“…Plant alkaloids such as (-)-ibogaine [and its main metabolite noribogaine (12-hydroxyibogamine)] and (+)-catharanthine, and the synthetic derivative 18-methoxycoronaridine (18-MC) are coronaridine congeners with very interesting behavioral profile, including anti-addictive (Carnicella et al, 2010;Glick et al, 1999;Glick et al, 1991;Luz,Mash, 2021;Maisonneuve,Glick, 2003), sedative (Arias et al, 2020a), and antinociceptive (Arias et al, 2020b) activities.…”

The next frontier of combating drug addiction in America

“…There has also been a resurgence of research on the psychedelic compound ibogaine. The National Institute on Drug Abuse stopped funding research on ibogaine for addiction treatment back in 1995, largely due to its dangerous and potentially deadly side-effects [26]. But recently, researchers in other countries, as well as private companies in the U.S., have launched new studies of ibogaine or related compounds that purportedly lack its dangerous side effects [27].…”

Drug Transporters ABCB1 (P-gp) and OATP, but not Drug-Metabolizing Enzyme CYP3A4, Affect the Pharmacokinetics of the Psychoactive Alkaloid Ibogaine and its Metabolites

“…Although controlled human clinical trials on the efficacy and safety of ibogaine are lacking, several studies, both in animals and in humans, report long-term drug abstinence from various substances, including opioids, alcohol, and psychostimulants, and sustained reductions in depressive symptoms after ibogaine administration (Mash et al, 2000;Schenberg et al, 2014;dos Santos et al, 2017;Brown and Alper, 2018;Mash, 2018;Mash et al, 2018Wasko et al, 2018. Consequently, ibogaine, despite not being licensed as a therapeutic drug, has been increasingly used in informal self-help networks and treatment centers worldwide, mainly for the treatment of substance use disorders and for the management of opioid withdrawal symptoms (Brown, 2013;Brown and Alper, 2018;Corkery, 2018;Luz and Mash, 2021).…”

“…A major concern is the occurrence of possible adverse events related to the use of ibogaine, which include cardiac arrhythmias, psychosis, mania, seizures, and even fatalities (Koenig and Hilber, 2015;Litjens and Brunt, 2016;Schep et al, 2016;dos Santos et al, 2017;Wasko et al, 2018;Aćimović et al, 2021;Luz and Mash, 2021;Ona et al, 2021). However, most of these morbidities and mortalities occurred in uncontrolled/non-medical settings, where unknown or extremely high doses and variable purity of ibogaine were used (Alper et al, 2008;dos Santos et al, 2017).…”

“…Due to ibogaine lipophilicity, this alkaloid can accumulate in adipose tissue (Hough et al, 1996), which allows a slow release of ibogaine and subsequent rapid metabolism to noribogaine over an extended time period (Zubaran, 2000;Alper, 2001). Noribogaine, which displays a slow pharmacokinetic clearance (half-life of plasma noribogaine is around 24-30 h versus ibogaine 2-6 h) (Luz and Mash, 2021), is responsible for many of the effects seen after ibogaine therapy (Zubaran, 2000) and seems to be safe and well-tolerated when directly administered itself in healthy volunteers (Glue et al, 2015a). Ibogaine and noribogaine are excreted via urine and feces (60-70% of the administered dose in 24 h in rats) (Mačiulaitis et al, 2008).…”