Login Register Cart 0
Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Systematic Review Article

Ibogaine/Noribogaine in the Treatment of Substance Use Disorders: A Systematic Review of the Current Literature

Author(s): Alessio Mosca*, Stefania Chiappini, Andrea Miuli, Gianluca Mancusi, Maria Chiara Santovito, Francesco Di Carlo, Mauro Pettorruso, John M. Corkery, Carlos Canessa, Giovanni Martinotti and Massimo Di Giannantonio

Volume 21, Issue 11, 2023

Published on: 07 February, 2023

Page: [2178 - 2194] Pages: 17

DOI: 10.2174/1570159X21666221017085612

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Ibogaine and noribogaine are psychedelic substances with dissociative properties naturally occurring in plants of the Apocynaceae family. Research has shown their efficacy in treating substance use disorders (SUD), particularly in opiate detoxification, but their efficacy and toxicity are still unclear.

Objective: This review aims to assess the anti-addictive role of ibogaine and evaluate its side effects.

Methods: A systematic literature review was conducted on the 29th of November 2021 using PubMed, Scopus and Web of Science databases through the following search strategy: ("Ibogaine" OR "Noribogaine") AND ("SUD" OR "substance use disorder" OR "craving" OR "abstinence" OR "withdrawal" OR "addiction" OR "detoxification") NOT animal NOT review NOT "vitro." The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed for data gathering purposes. Research methods were registered on PROSPERO (CRD42021287034).

Results: Thirty-one articles were selected for the systematic revision, and two were considered for analysis. The results were organised according to the type of study: case reports/case series, randomised- controlled trials (RCTs), open-label, survey and observational studies. The main outcomes were related to the anti-addictive effect of ibogaine and its cardiac toxicity. A meta-analysis of side effects was conducted using RevMan 5.4 software, showing a significant risk of developing headaches after ibogaine/noribogaine treatment.

Conclusion: The results show some efficacy of ibogaine in the treatment of SUDs, but its cardiotoxicity and mortality are worrying. Further studies are needed to assess its therapeutic efficacy and actual safety.

Keywords: Ibogaine, noribogaine, substance use disorder, addiction, psychedelics, withdrawal symptoms.

« Previous Next »
Graphical Abstract

[1]
Fernandez, J.W. Bwiti: An Ethnography of the Religious Imagination in Africa; Princeton University Press: Princeton, 1982. Available from: https://books.google.it/books?id=vbGpQgAACAAJ
[2]
Pope, H.G. Tabernanthe iboga: An African narcotic plant of social importance. Econ. Bot., 1969, 23(2), 174-184.
[http://dx.doi.org/10.1007/BF02860623]
[3]
Landrin, A. Iboga and ibogaine. Kessinger Publishing: Whitefish, Montana, 1905.
[4]
Wilson, C.; Millar, T.; Matieschyn, Z. Novel treatment of opioid use disorder using ibogaine and iboga in two adults. J. Psychedelic Stud., 2020, 4(3), 149-155.
[http://dx.doi.org/10.1556/2054.2020.00133]
[5]
Mash, D.C.; Kovera, C.A.; Pablo, J.; Tyndale, R.; Ervin, F.R.; Kamlet, J.D.; Lee Hearn, W. Ibogaine in the treatment of heroin withdrawal. Alkaloids Chem. Biol., 2001, 56, 155-171.
[http://dx.doi.org/10.1016/S0099-9598(01)56012-5] [PMID: 11705106]
[6]
Mash, D.C.; Kovera, C.A.; Pablo, J.; Tyndale, R.F.; Ervin, F.D.; Williams, I.C.; Singleton, E.G.; Mayor, M. Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures. Ann. N. Y. Acad. Sci., 2000, 914(1), 394-401.
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb05213.x] [PMID: 11085338]
[7]
Glue, P.; Lockhart, M.; Lam, F.; Hung, N.; Hung, C.T.; Friedhoff, L. Ascending-dose study of noribogaine in healthy volunteers: Pharmacokinetics, pharmacodynamics, safety, and tolerability. J. Clin. Pharmacol., 2015, 55(2), 189-194.
[http://dx.doi.org/10.1002/jcph.404] [PMID: 25279818]
[8]
Corkery, J.M. Ibogaine as a treatment for substance misuse: Potential benefits and practical dangers. Prog. Brain Res., 2018, 242, 217-257.
[http://dx.doi.org/10.1016/bs.pbr.2018.08.005] [PMID: 30471681]
[9]
Barber, M.; Gardner, J.; Savic, M.; Carter, A. Ibogaine therapy for addiction: Consumer views from online fora. Int. J. Drug Policy, 2020, 83, 102857.
[http://dx.doi.org/10.1016/j.drugpo.2020.102857] [PMID: 32693321]
[10]
Jacobs, M.T.; Zhang, Y.W.; Campbell, S.D.; Rudnick, G. Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter. J. Biol. Chem., 2007, 282(40), 29441-29447.
[http://dx.doi.org/10.1074/jbc.M704456200] [PMID: 17698848]
[11]
Wells, G.B.; Lopez, M.C.; Tanaka, J.C. The effects of ibogaine on dopamine and serotonin transport in rat brain synaptosomes. Brain Res. Bull., 1999, 48(6), 641-647.
[http://dx.doi.org/10.1016/S0361-9230(99)00053-2] [PMID: 10386845]
[12]
Alper, K.R.; Lotsof, H.S.; Kaplan, C.D. The ibogaine medical subculture. J. Ethnopharmacol., 2008, 115(1), 9-24.
[http://dx.doi.org/10.1016/j.jep.2007.08.034] [PMID: 18029124]
[13]
Pearl, S.M.; Herrick-Davis, K.; Teitler, M.; Glick, S.D. Radioligand-binding study of noribogaine, a likely metabolite of ibogaine. Brain, Res; , 1995, 675, pp. 342-344.
[14]
Pablo, J.P.; Mash, D.C. Noribogaine stimulates naloxone-sensitive [35S]GTPγS binding. Neuroreport, 1998, 9(1), 109-114.
[http://dx.doi.org/10.1097/00001756-199801050-00022] [PMID: 9592058]
[15]
Antonio, T.; Childers, S.R.; Rothman, R.B.; Dersch, C.M.; King, C.; Kuehne, M.; Bornmann, W.G.; Eshleman, A.J.; Janowsky, A.; Simon, E.R.; Reith, M.E.A.; Alper, K. Effect of Iboga alkaloids on µ-opioid receptor-coupled G protein activation. PLoS One, 2013, 8(10), e77262.
[http://dx.doi.org/10.1371/journal.pone.0077262] [PMID: 24204784]
[16]
Glick, S.D.; Maisonneuve, I.M. Development of novel medications for drug addiction. The legacy of an African shrub. Ann. N. Y. Acad. Sci., 2000, 909(1), 88-103.
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb06677.x] [PMID: 10911925]
[17]
Helsley, S.; Dlugos, C.A.; Pentney, R.J.; Rabin, R.A.; Winter, J.C. Effects of chronic ibogaine treatment on cerebellar Purkinje cells in the rat. Brain Res., 1997, 759(2), 306-308.
[http://dx.doi.org/10.1016/S0006-8993(97)00365-X] [PMID: 9221953]
[18]
Maillet, E.L.; Milon, N.; Heghinian, M.D.; Fishback, J.; Schürer, S.C.; Garamszegi, N.; Mash, D.C. Noribogaine is a G-protein biased κ-opioid receptor agonist. Neuropharmacology, 2015, 99, 675-688.
[http://dx.doi.org/10.1016/j.neuropharm.2015.08.032] [PMID: 26302653]
[19]
Zubaran, C.; Shoaib, M.; Stolerman, I.P.; Pablo, J.; Mash, D.C. Noribogaine generalization to the ibogaine stimulus: Correlation with noribogaine concentration in rat brain. Neuropsychopharmacology, 1999, 21(1), 119-126.
[http://dx.doi.org/10.1016/S0893-133X(99)00003-2] [PMID: 10379526]
[20]
Llansola, M.; Sanchez-Perez, A.; Cauli, O.; Felipo, V. Modulation of NMDA receptors in the cerebellum. 1. Properties of the NMDA receptor that modulate its function. Cerebellum, 2005, 4(3), 154-161.
[http://dx.doi.org/10.1080/14734220510007996] [PMID: 16147947]
[21]
Skolnick, P. Ibogaine as a glutamate antagonist: Relevance to its putative antiaddictive properties. Alkaloids Chem. Biol., 2001, 56, 55-62.
[http://dx.doi.org/10.1016/S0099-9598(01)56007-1] [PMID: 11705116]
[22]
Glick, S.D.; Maisonneuve, I.M.; Kitchen, B.A.; Fleck, M.W. Antagonism of α3β4 nicotinic receptors as a strategy to reduce opioid and stimulant self-administration. Eur. J. Pharmacol., 2002, 438(1-2), 99-105.
[http://dx.doi.org/10.1016/S0014-2999(02)01284-0] [PMID: 11906717]
[23]
He, D.Y.; McGough, N.N.H.; Ravindranathan, A.; Jeanblanc, J.; Logrip, M.L.; Phamluong, K.; Janak, P.H.; Ron, D. Glial cell line-derived neurotrophic factor mediates the desirable actions of the anti-addiction drug ibogaine against alcohol consumption. J. Neurosci., 2005, 25(3), 619-628.
[http://dx.doi.org/10.1523/JNEUROSCI.3959-04.2005] [PMID: 15659598]
[24]
Autry, A.E.; Monteggia, L.M. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol. Rev., 2012, 64(2), 238-258.
[http://dx.doi.org/10.1124/pr.111.005108] [PMID: 22407616]
[25]
Brackenridge, P. Ibogaine therapy in the treatment of opiate dependency. Drugs Alcohol Today, 2010, 10(4), 20-25.
[http://dx.doi.org/10.5042/daat.2010.0724]
[26]
Lotsof, H.S.; Alexander, N.E. Case studies of ibogaine treatment: Implications for patient management strategies. Alkaloids Chem. Biol., 2001, 56, 293-313.
[http://dx.doi.org/10.1016/S0099-9598(01)56020-4] [PMID: 11705114]
[27]
Glick, S.D.; Rossman, K.; Rao, N.C.; Maisonneuve, I.M.; Carlson, J.N. Effects of ibogaine on acute signs of morphine withdrawal in rats: Independence from tremor. Neuropharmacology, 1992, 31(5), 497-500.
[http://dx.doi.org/10.1016/0028-3908(92)90089-8] [PMID: 1528400]
[28]
Glick, S.D.; Rossman, K.; Steindorf, S.; Maisonneuve, I.M.; Carlson, J.N. Effects and aftereffects of ibogaine on morphine self-administration in rats. Eur. J. Pharmacol., 1991, 195(3), 341-345.
[http://dx.doi.org/10.1016/0014-2999(91)90474-5] [PMID: 1868880]
[29]
Glick, S.D.; Kuehne, M.E.; Raucci, J.; Wilson, T.E.; Larson, D.; Keller, R.W., Jr; Carlson, J.N. 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. Brain Res., 1994, 657(1-2), 14-22.
[http://dx.doi.org/10.1016/0006-8993(94)90948-2] [PMID: 7820611]
[30]
Drug Enforcement Administration. Code of federal regulations: Food and drugs, 2012. Available from: https://www.govinfo.gov/content/pkg/CFR-2012-title21-vol3/pdf/CFR-2012-title21-vol3.pdf.
[31]
Rebera, A. The Poisons Standard, 2018. Available from: https://www.legislation.gov.au/Details/F2019L00032
[32]
Ministero della Giustizia. Gazzetta Ufficiale anno 157 numero 187 Roma, 2016. Available from: https://www.anci.it/gazzetta-ufficiale-anno-157-n-187-pdf/
[33]
Alper, K.R.; Lotsof, H.S.; Frenken, G.M.; Luciano, D.J.; Bastiaans, J. Treatment of acute opioid withdrawal with ibogaine. Am. J. Addict., 1999, 8(3), 234-242.
[http://dx.doi.org/10.1080/105504999305848] [PMID: 10506904]
[34]
Belgers, M.; Leenaars, M.; Homberg, J.R.; Ritskes-Hoitinga, M.; Schellekens, A F A.; Hooijmans, C.R. Ibogaine and addiction in the animal model, a systematic review and meta-analysis. Transl. Psychiatry, 2016, 6(5), e826.
[http://dx.doi.org/10.1038/tp.2016.71] [PMID: 27244235]
[35]
C Mash, D. Breaking the cycle of opioid use disorder with Ibogaine. Am. J. Drug Alcohol Abuse, 2018, 44(1), 1-3.
[http://dx.doi.org/10.1080/00952990.2017.1357184] [PMID: 29215917]
[36]
Litjens, R.P.W.; Brunt, T.M. How toxic is ibogaine? Clin. Toxicol. (Phila.), 2016, 54(4), 297-302.
[http://dx.doi.org/10.3109/15563650.2016.1138226] [PMID: 26807959]
[37]
Vastag, B. Addiction research. Ibogaine therapy: A “vast, uncontrolled experiment. Science, 2005, 308, 345-346.
[38]
Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; Chou, R.; Glanville, J.; Grimshaw, J.M.; Hróbjartsson, A.; Lalu, M.M.; Li, T.; Loder, E.W.; Mayo-Wilson, E.; McDonald, S.; McGuinness, L.A.; Stewart, L.A.; Thomas, J.; Tricco, A.C.; Welch, V.A.; Whiting, P.; Moher, D. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ, 2021, 372(71), n71.
[http://dx.doi.org/10.1136/bmj.n71] [PMID: 33782057]
[39]
Bernardo, W.M. PRISMA statement and PROSPERO. Int. Braz. J. Urol., 2017, 43(3), 383-384.
[http://dx.doi.org/10.1590/S1677-5538.IBJU.2017.03.02] [PMID: 28520335]
[40]
Sterne, J.A.C.; Savović, J.; Page, M.J.; Elbers, R.G.; Blencowe, N.S.; Boutron, I.; Cates, C.J.; Cheng, H.Y.; Corbett, M.S.; Eldridge, S.M.; Emberson, J.R.; Hernán, M.A.; Hopewell, S.; Hróbjartsson, A.; Junqueira, D.R.; Jüni, P.; Kirkham, J.J.; Lasserson, T.; Li, T.; McAleenan, A.; Reeves, B.C.; Shepperd, S.; Shrier, I.; Stewart, L.A.; Tilling, K.; White, I.R.; Whiting, P.F.H; iggins, J.P.T. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ, 2019, 366, l4898.
[http://dx.doi.org/10.1136/bmj.l4898] [PMID: 31462531]
[41]
RevMan User guide. Welcome to RevMan 5.4. 2020. Available from: https://training.cochrane.org/system/files/uploads/protected_file/RevMan5.4_user_guide.pdf
[42]
Messori, A.; Maratea, D.; Fadda, V.; Trippoli, S. Using risk difference as opposed to odds-ratio in meta-analysis. Int. J. Cardiol., 2013, 164(1), 127.
[http://dx.doi.org/10.1016/j.ijcard.2012.06.078] [PMID: 22795708]
[43]
Walter, S.D. Choice of effect measure for epidemiological data. J. Clin. Epidemiol., 2000, 53(9), 931-939.
[http://dx.doi.org/10.1016/S0895-4356(00)00210-9] [PMID: 11004419]
[44]
Higgins, J.P.T.; Thomas, J.; Chandler, J.; Cumpston, M.; Li, T.; Page, M.J.; Welch, V.A. (editors). Cochrane Handbook for Systematic Reviews of Interventions, 2nd Edition; John Wiley & Sons: Chichester, UK, 2019.
[45]
Aćimović, T.; Atanasijević, T.; Denić, K.; Lukić, V.; Popović, V.; Bogdanović, M. Death due to consumption of ibogaine: Case report. Forensic Sci. Med. Pathol., 2021, 17(1), 126-129.
[http://dx.doi.org/10.1007/s12024-020-00342-0] [PMID: 33433774]
[46]
Grogan, J.; Gerona, R.; Snow, J.W.; Kao, L. Ibogaine consumption with seizure-like episodes, QTc-prolongation, and captured cardiac dysrhythmias. J. Emerg. Med., 2019, 57(4), e99-e104.
[http://dx.doi.org/10.1016/j.jemermed.2019.06.052] [PMID: 31630892]
[47]
Knuijver, T.; Belgers, M.; Markus, W.; Verkes, R-.J.; van Oosteren, T.; Schellekens, A. Hallucinogen persisting perception disorder after ibogaine treatment for opioid dependence. J. Clin. Psychopharmacol., 2018, 38(6), 646-648.
[http://dx.doi.org/10.1097/JCP.0000000000000966] [PMID: 30300292]
[48]
Barsuglia, J.P.; Polanco, M.; Palmer, R.; Malcolm, B.J.; Kelmendi, B.; Calvey, T. A case report SPECT study and theoretical rationale for the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder. Prog. Brain Res., 2018, 242, 121-15.
[http://dx.doi.org/10.1016/bs.pbr.2018.08.002] [PMID: 30471678]
[49]
Cloutier-Gill, L.; Wood, E.; Millar, T.; Ferris, C.; Eugenia Socias, M. Remission of severe opioid use disorder with Ibogaine: A case report. J. Psychoactive Drugs, 2016, 48(3), 214-217.
[http://dx.doi.org/10.1080/02791072.2016.1180467] [PMID: 27192438]
[50]
Steinberg, C.; Deyell, M.W. Cardiac arrest after ibogaine intoxication. J. Arrhythm., 2018, 34(4), 455-457.
[http://dx.doi.org/10.1002/joa3.12061] [PMID: 30167018]
[51]
Hildyard, C.; Macklin, P.; Prendergast, B.; Bashir, Y. A case of QT prolongation and torsades de pointes caused by ibogaine toxicity. J. Emerg. Med., 2016, 50(2), e83-e87.
[http://dx.doi.org/10.1016/j.jemermed.2015.06.051] [PMID: 26329675]
[52]
Meisner, J.A.; Wilcox, S.R.; Richards, J.B. Ibogaine-associated cardiac arrest and death: Case report and review of the literature. Ther. Adv. Psychopharmacol., 2016, 6(2), 95-98.
[http://dx.doi.org/10.1177/2045125315626073] [PMID: 27141291]
[53]
Marta, C.J.; Ryan, W.C.; Kopelowicz, A.; Koek, R.J. Mania following use of ibogaine: A case series. Am. J. Addict., 2015, 24(3), 203-205.
[http://dx.doi.org/10.1111/ajad.12209] [PMID: 25877487]
[54]
Jalal, S.; Daher, E.; Hilu, R. A case of death due to ibogaine use for heroin addiction: Case report. Am. J. Addict., 2013, 22(3), 302.
[http://dx.doi.org/10.1111/j.1521-0391.2012.00330.x] [PMID: 23617876]
[55]
Mazoyer, C.; Carlier, J.; Boucher, A.; Péoc’h, M.; Lemeur, C.; Gaillard, Y. Fatal case of a 27-year-old male after taking iboga in withdrawal treatment: GC-MS/MS determination of ibogaine and ibogamine in iboga roots and postmortem biological material. J. Forensic Sci., 2013, 58(6), 1666-1672.
[http://dx.doi.org/10.1111/1556-4029.12250] [PMID: 23919354]
[56]
O’Connell, C.W.; Gerona, R.R.; Friesen, M.W.; Ly, B.T. Internet-purchased ibogaine toxicity confirmed with serum, urine, and product content levels. Am. J. Emerg. Med., 2015, 33(7), 985.e5-985.e6.
[http://dx.doi.org/10.1016/j.ajem.2014.12.023] [PMID: 25687617]
[57]
Papadodima, S.A.; Dona, A.; Evaggelakos, C.I.; Goutas, N.; Athanaselis, S.A. Ibogaine related sudden death: A case report. J. Forensic Leg. Med., 2013, 20(7), 809-811.
[http://dx.doi.org/10.1016/j.jflm.2013.06.032] [PMID: 24112325]
[58]
Alper, K.R.; Stajić, M.; Gill, J.R. Fatalities temporally associated with the ingestion of ibogaine. J. Forensic Sci., 2012, 57(2), 398-412.
[http://dx.doi.org/10.1111/j.1556-4029.2011.02008.x] [PMID: 22268458]
[59]
Pleskovic, A.; Gorjup, V.; Brvar, M.; Kozelj, G. Ibogaine-associated ventricular tachyarrhythmias. Clin. Toxicol. (Phila.), 2012, 50(2), 157.
[http://dx.doi.org/10.3109/15563650.2011.647031] [PMID: 22304378]
[60]
Sheppard, S.G. A preliminary investigation of ibogaine: Case reports and recommendations for further study. J. Subst. Abuse Treat., 1994, 11(4), 379-385.
[http://dx.doi.org/10.1016/0740-5472(94)90049-3] [PMID: 7966509]
[61]
Glue, P.; Cape, G.; Tunnicliff, D.; Lockhart, M.; Lam, F.; Hung, N.; Hung, C.T.; Harland, S.; Devane, J.; Crockett, R.S.; Howes, J.; Darpo, B.; Zhou, M.; Weis, H.; Friedhoff, L. Ascending single-dose, double-blind, placebo-controlled safety study of noribogaine in opioid-dependent patients. Clin. Pharmacol. Drug Dev., 2016, 5(6), 460-468.
[http://dx.doi.org/10.1002/cpdd.254] [PMID: 27870477]
[62]
Prior, P.L.; Prior, S.L. Ibogaine effect on cocaine craving and use in controlled pilot study. J. Addict. Ther., 2014, 1(1), 1-6.
[63]
Heink, A.; Katsikas, S.; Lange-Altman, T. Examination of the phenomenology of the ibogaine treatment experience: Role of altered states of consciousness and psychedelic experiences. J. Psychoactive Drugs, 2017, 49(3), 201-208.
[http://dx.doi.org/10.1080/02791072.2017.1290855] [PMID: 28266890]
[64]
Knuijver, T.; Schellekens, A.; Belgers, M.; Donders, R.; Oosteren, T.; Kramers, K.; Verkes, R. Safety of ibogaine administration in detoxification of opioid‐dependent individuals: A descriptive openlabel observational study. Addiction, 2022, 117(1), 118-128.
[http://dx.doi.org/10.1111/add.15448] [PMID: 33620733]
[65]
Brown, T.K.; Noller, G.E.; Denenberg, J.O. Ibogaine and subjective experience: Transformative states and psychopharmacotherapy in the treatment of opioid use disorder. J. Psychoactive Drugs, 2019, 51(2), 155-165.
[http://dx.doi.org/10.1080/02791072.2019.1598603] [PMID: 30967101]
[66]
Davis, A.K.; Renn, E.; Windham-Herman, A.M.; Polanco, M.; Barsuglia, J.P. A mixed-method analysis of persisting effects associated with positive outcomes following ibogaine detoxification. J. Psychoactive Drugs, 2018, 50(4), 287-297.
[http://dx.doi.org/10.1080/02791072.2018.1487607] [PMID: 30020025]
[67]
Malcolm, B.J.; Polanco, M.; Barsuglia, J.P. Changes in withdrawal and craving scores in participants undergoing opioid detoxification utilizing ibogaine. J. Psychoactive Drugs, 2018, 50(3), 256-265.
[http://dx.doi.org/10.1080/02791072.2018.1447175] [PMID: 29608409]
[68]
Brown, T.K.; Alper, K. Treatment of opioid use disorder with ibogaine: Detoxification and drug use outcomes. Am. J. Drug Alcohol Abuse, 2018, 44(1), 24-36.
[http://dx.doi.org/10.1080/00952990.2017.1320802] [PMID: 28541119]
[69]
Davis, A.K.; Barsuglia, J.P.; Windham-Herman, A.M.; Lynch, M.; Polanco, M. Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short- and long-term outcomes and current psychological functioning. J. Psychedelic Stud., 2017, 1(2), 65-73.
[http://dx.doi.org/10.1556/2054.01.2017.009] [PMID: 30272050]
[70]
Noller, G.E.; Frampton, C.M.; Yazar-Klosinski, B. Ibogaine treatment outcomes for opioid dependence from a twelve-month followup observational study. Am. J. Drug Alcohol Abuse, 2018, 44(1), 37-46.
[http://dx.doi.org/10.1080/00952990.2017.1310218] [PMID: 28402682]
[71]
Schenberg, E.E.; de Castro Comis, M.A.; Chaves, B.R.; da Silveira, D.X. Treating drug dependence with the aid of ibogaine: A retrospective study. J. Psychopharmacol., 2014, 28(11), 993-1000.
[http://dx.doi.org/10.1177/0269881114552713] [PMID: 25271214]
[72]
Alper, K.R.; Lotsof, H.S.; Frenken, G.M.N.; Luciano, D.J.; Bastiaans, J. Ibogaine in acute opioid withdrawal. An open label case series. Ann. N. Y. Acad. Sci., 2000, 909(1), 257-259.
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb06687.x] [PMID: 10911935]
[73]
Nichols, D.E. Hallucinogens. Pharmacol. Ther., 2004, 101(2), 131-181.
[http://dx.doi.org/10.1016/j.pharmthera.2003.11.002] [PMID: 14761703]
[74]
Rodger, J. Understanding the healing potential of ibogaine through a comparative and interpretive phenomenology of the visionary experience. Anthropol. Consciousness, 2018, 29(1), 77-119.
[http://dx.doi.org/10.1111/anoc.12088]
[75]
Argento, E.; Tupper, K.W.; Socias, M.E. The tripping point: The potential role of psychedelic-assisted therapy in the response to the opioid crisis. Int. J. Drug Policy, 2019, 66, 80-81.
[http://dx.doi.org/10.1016/j.drugpo.2018.11.006] [PMID: 30743091]
[76]
Bender, D.; Hellerstein, D.J. Assessing the risk-benefit profile of classical psychedelics: A clinical review of second-wave psychedelic research. Psychopharmacology (Berl)., 2022, 239(6), 1907-1932.
[http://dx.doi.org/10.1007/s00213-021-06049-6] [PMID: 35022823]
[77]
Sousa, T.R.; Rema, J.; Machado, S.; Novais, F. Psychedelics and hallucinogens in Psychiatry: Finding new pharmacological targets. Curr. Top. Med. Chem., 2022, 22(15), 1250-1260.
[http://dx.doi.org/10.2174/1568026621666211201145800] [PMID: 34852736]
[78]
Rodrigues, L.S.; Rossi, G.N.; Rocha, J.M.L.; Osório, F.; Bouso, J.C.; Hallak, J.E.C. Effects of ayahuasca and its alkaloids on substance use disorders: An updated (2016-2020) systematic review of preclinical and human studies. Eur. Arch. Psychiatry Clin. Neurosci., 2022, 272(4), 541-556.
[http://dx.doi.org/10.1007/s00406-021-01267-7] [PMID: 33914164]
[79]
Pearson, C.; Siegel, J.; Gold, J.A. Psilocybin-assisted psychotherapy for depression: Emerging research on a psychedelic compound with a rich history. J. Neurol. Sci., 2022, 434, 120096.
[http://dx.doi.org/10.1016/j.jns.2021.120096] [PMID: 34942586]
[80]
Martinotti, G.; Chiappini, S.; Pettorruso, M.; Mosca, A.; Miuli, A.; Di Carlo, F.; D’Andrea, G.; Collevecchio, R.; Di Muzio, I.; Sensi, S.L.; Di Giannantonio, M. Therapeutic potentials of ketamine and esketamine in obsessive-compulsive disorder (OCD), substance use disorders (SUD) and eating disorders (ED): A review of the current literature. Brain Sci., 2021, 11(7), 856.
[http://dx.doi.org/10.3390/brainsci11070856] [PMID: 34199023]
[81]
Romeo, B.; Hermand, M.; Pétillion, A.; Karila, L.; Benyamina, A. Clinical and biological predictors of psychedelic response in the treatment of psychiatric and addictive disorders: A systematic review. J. Psychiatr. Res., 2021, 137, 273-282.
[http://dx.doi.org/10.1016/j.jpsychires.2021.03.002] [PMID: 33730602]
[82]
Welsch, L.; Bailly, J.; Darcq, E.; Kieffer, B.L. The negative affect of protracted opioid abstinence: Progress and perspectives from rodent models. Biol. Psychiatry, 2020, 87(1), 54-63.
[http://dx.doi.org/10.1016/j.biopsych.2019.07.027] [PMID: 31521334]
[83]
Marton, S.; González, B.; Rodríguez-Bottero, S.; Miquel, E.; Martínez-Palma, L.; Pazos, M.; Prieto, J.P.; Rodríguez, P.; Sames, D.; Seoane, G.; Scorza, C.; Cassina, P.; Carrera, I. Ibogaine administration modifies GDNF and BDNF expression in brain regions involved in mesocorticolimbic and nigral dopaminergic circuits. Front. Pharmacol., 2019, 10, 193.
[http://dx.doi.org/10.3389/fphar.2019.00193] [PMID: 30890941]
[84]
He, D.-Y.; Ron, D. Autoregulation of glial cell line-derived neurotrophic factor expression: Implications for the long-lasting actions of the anti-addiction drug, Ibogaine. FASEB J., 2006, 20(13), 2420-2422.
[http://dx.doi.org/10.1096/fj.06-6394fje] [PMID: 17023388]
[85]
Thurner, P.; Stary-Weinzinger, A.; Gafar, H.; Gawali, V.S.; Kudlacek, O.; Zezula, J.; Hilber, K.; Boehm, S.; Sandtner, W.; Koenig, X. Mechanism of hERG channel block by the psychoactive indole alkaloid ibogaine. J. Pharmacol. Exp. Ther., 2014, 348(2), 346-358.
[http://dx.doi.org/10.1124/jpet.113.209643] [PMID: 24307198]
[86]
Koenig, X.; Hilber, K. The anti-addiction drug ibogaine and the heart: a delicate relation. Molecules, 2015, 20(2), 2208-2228.
[http://dx.doi.org/10.3390/molecules20022208] [PMID: 25642835]
[87]
Kovar, M.; Koenig, X.; Mike, Á.; Cervenka, R.; Lukács, P.; Todt, H.; Sandtner, W.; Hilber, K. 17th scientific symposium of the Austrian pharmacological society (APHAR). Joint meeting with the hungarian society of experimental and clinical pharmacology (MFT) Innsbruck, Austria. 29-30 September 2011. Abstracts. BMC Pharmacol., 2011, 11(Suppl 2), 1-20.
[http://dx.doi.org/10.1186/1471-2210-11-s2-a1] [PMID: 21999824]
[88]
Bouso, J.C.; Fornís, I.; Vilamala, M.V.; Loenen, B.D.; Sainz-Cort, A.; Jiménez-Garrido, D.F.; Santos, R.G.D.; Hallak, J.C.; Alcázar-Córcoles, M.Á.; Jenks, C.W. An analytical study of iboga alkaloids contained in Tabernanthe iboga-derived products offered by ibogaine treatment providers. Arch. Clin. Psychiatry, 2020, 47(2), 51-54.
[http://dx.doi.org/10.1590/0101-60830000000231]
[89]
Luz, M.; Mash, D.C. Evaluating the toxicity and therapeutic potential of ibogaine in the treatment of chronic opioid abuse. Expert Opin Drug Metab Toxicol., 2021, 17(9), 1019-1022.
[http://dx.doi.org/10.1080/17425255.2021.1944099] [PMID: 34139922]
[90]
Martinotti, G.; De Risio, L.; Vannini, C.; Schifano, F.; Pettorruso, M.; Di Giannantonio, M. Substance-related exogenous psychosis: a postmodern syndrome. CNS Spectr., 2021, 26(1), 84-91.
[http://dx.doi.org/10.1017/S1092852920001479] [PMID: 32580808]
[91]
Martinotti, G.; Santacroce, R.; Pettorruso, M.; Montemitro, C.; Spano, M.; Lorusso, M.; di Giannantonio, M.; Lerner, A. Hallucinogen persisting perception disorder: Etiology, clinical features, and therapeutic perspectives. Brain Sci., 2018, 8(3), 47.
[http://dx.doi.org/10.3390/brainsci8030047] [PMID: 29547576]
[92]
Schifano, F.; Chiappini, S.; Miuli, A.; Corkery, J.M.; Scherbaum, N.; Napoletano, F.; Arillotta, D.; Zangani, C.; Catalani, V.; Vento, A.; Pettorruso, M.; Martinotti, G.; Massimo, D.G.; Guirguis, A. New psychoactive substances (NPS) and serotonin syndrome onset: A systematic review. Exp. Neurol., 2021, 339, 113638.
[http://dx.doi.org/10.1016/j.expneurol.2021.113638] [PMID: 33571533]
[93]
Schindler, E.A.D.; Sewell, R.A.; Gottschalk, C.H.; Luddy, C.; Flynn, L.T.; Lindsey, H.; Pittman, B.P.; Cozzi, N.V.; D’Souza, D.C. Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin. Neurotherapeutics, 2021, 18(1), 534-543.
[http://dx.doi.org/10.1007/s13311-020-00962-y] [PMID: 33184743]
[94]
Castellanos, J.P.; Woolley, C.; Bruno, K.A.; Zeidan, F.; Halberstadt, A.; Furnish, T. Chronic pain and psychedelics: A review and proposed mechanism of action. Reg. Anesth. Pain Med., 2020, 45(7), 486-494.
[http://dx.doi.org/10.1136/rapm-2020-101273] [PMID: 32371500]
[95]
Lotsof, H.S.; Wachtel, B. Manual for ibogaine therapy screening; safety, monitoring & aftercare. The Ibogaine Dossier, 2003. Available from: https://www.ibogainedossier.com/Ibogaine.pdf.
[96]
Alper, K.R.; Beal, D.; Kaplan, C.D. A contemporary history of ibogaine in the United States and Europe. Alkaloids Chem. Biol., 2001, 56, 249-281.
[http://dx.doi.org/10.1016/S0099-9598(01)56018-6] [PMID: 11705112]
[97]
Mash, D.C.; Kovera, C.A.; Buck, B.; Norenberg, M.D.; Shapshak, P.; Hearn, W.L.; Sanchez-Ramos, J. Medication development of ibogaine as a pharmacotherapy for drug dependence. Ann. N. Y. Acad. Sci., 1998, 844(1), 274-292.
[http://dx.doi.org/10.1111/j.1749-6632.1998.tb08242.x] [PMID: 9668685]
[98]
Borras, T. Preliminary efficacy and safety of ibogaine in the treatment of methadone detoxification. NCT04003948, 2022.
[99]
Yamaoto, T. A study of oral ibogaine in opioid withdrawal. NCT05029401, 2022.
[100]
dos Santos, R. Ibogaine in the treatment of alcoholism: A randomized, double-blind, placebo-controlled, escalating dose, phase 2 trial. NCT03380728, 2022.
[101]
Parkins, K. DemeRx and Atai get MHRA nod to start trial of ibogaine for opioid use disorder. Available from: https://demerx.com/demerx-and-atai-get-mhra-nod-to-start-trial-of-ibogaine-for-opioid-use-disorder/
[102]
Cameron, L.P.; Tombari, R.J.; Lu, J.; Pell, A.J.; Hurley, Z.Q.; Ehinger, Y.; Vargas, M.V.; McCarroll, M.N.; Taylor, J.C.; Myers-Turnbull, D.; Liu, T.; Yaghoobi, B.; Laskowski, L.J.; Anderson, E.I.; Zhang, G.; Viswanathan, J.; Brown, B.M.; Tjia, M.; Dunlap, L.E.; Rabow, Z.T.; Fiehn, O.; Wulff, H.; McCorvy, J.D.; Lein, P.J.; Kokel, D.; Ron, D.; Peters, J.; Zuo, Y.; Olson, D.E. A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature, 2021, 589(7842), 474-479.
[http://dx.doi.org/10.1038/s41586-020-3008-z] [PMID: 33299186]
[103]
Peters, J.; Olson, D.E. Engineering safer psychedelics for treating addiction. Neuroscience Insights, 2021, 16.
[http://dx.doi.org/10.1177/26331055211033847] [PMID: 34350400]

Rights & Permissions Print Cite
Article Metrics
70
2
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy