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			{{short description|Psychoactive substance found in plants in the family Apocynaceae}}
	{{drugbox
			{{Use dmy dates|date=June 2017 }}
			{{cs1 config|name-list-style=vanc|display-authors=6}}
			{{Infobox drug
	| Watchedfields = changed		| Watchedfields = changed
	| verifiedrevid = 408566906		| verifiedrevid = 443866754
			| IUPAC_name = (1R,15R,17S,18S)-17-ethyl-7-methoxy-3,13-diazapentacyclononadeca-2(10),4(9),5,7-tetraene
	| IUPAC_name =
	| image = Ibogaine.svg		| image = Ibogaine.svg
			| image_class = skin-invert-image
	| image2 = Ibogaine-3d-sticks.png
	| width = 180		| width =
			| image2 = Ibogaine-from-xtal-Mercury-3D-bs.png
	| InChI = 1/C20H26N2O/c1-3-13-8-12-9-17-19-15(6-7-22(11-12)20(13)17)16-10-14(23-2)4-5-18(16)21-19/h4-5,10,12-13,17,20-21H,3,6-9,11H2,1-2H3/t12-,13+,17+,20+/m1/s1
			| image_class2 = bg-transparent
	| InChIKey = HSIBGVUMFOSJPD-CFDPKNGZBI
			| width2 =
			<!--Clinical data-->
			| tradename = Lambarène, Iperton<ref name="Mash2023" /><ref name="MaciulaitisKontrimaviciuteBressolle2008" />
			| pregnancy_AU =
			| pregnancy_US =
			| pregnancy_category =
			| routes_of_administration = Oral
			| class = ]; ]; ]; ]; ]
			<!--Legal status-->
			| legal_AU = S4
			| legal_CA = Prescription only
			| legal_CA_comment = <ref name="hc-sc.gc.ca">{{cite web| work = Health Canada | publisher = Government of Canada, Health|title=Notice - Prescription Drug List (PDL): Multiple additions|url=http://www.hc-sc.gc.ca/dhp-mps/prodpharma/pdl-ord/pdl-ldo-noa-ad-2017-05-16-eng.php |language=en|date=12 May 2017}}</ref>
			| legal_NZ = Prescription only
			| legal_NZ_comment = <ref name="Galea_2011">{{cite journal | vauthors = Galea S, Lorusso M, Newcombe D, Walters C, Williman J, Wheeler A | title = Ibogaine--be informed before you promote or prescribe | journal = Journal of Primary Health Care | volume = 3 | issue = 1 | pages = 86–7 | date = March 2011 | pmid = 21359272 | url = https://www.rnzcgp.org.nz/assets/documents/Publications/JPHC/March-2011/JPHCMarch11CompleteIssue.pdf#page=86 | access-date = 4 December 2015 | veditors = Goodyear-Smith F }}</ref>
			| legal_UK = PSA
			| legal_UN = Unscheduled
			| legal_US = Schedule I
			<!--Pharmacokinetic data-->
			| bioavailability =
			| protein_bound =
			| metabolism =
			| elimination_half-life =
			| excretion =
			<!--Identifiers-->
			| CAS_number_Ref = {{cascite|correct|??}}
			| CAS_number = 83-74-9
			| ATC_prefix = None
			| PubChem = 197060
			| DrugBank =
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| ChemSpiderID = 170667
			| UNII_Ref = {{fdacite|correct|FDA}}
			| UNII = 3S814I130U
			| ChEBI = 5852
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 1215855		| ChEMBL = 1215855
			| synonyms = 12-Methoxyibogamine
			<!--Chemical data-->
			| C=20 | H=26 | N=2 | O=1
			| SMILES = CC1C2C3c4c5ccc(OC)cc5c4CC(C2)13
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C20H26N2O/c1-3-13-8-12-9-17-19-15(6-7-22(11-12)20(13)17)16-10-14(23-2)4-5-18(16)21-19/h4-5,10,12-13,17,20-21H,3,6-9,11H2,1-2H3/t12-,13+,17+,20+/m1/s1		| StdInChI = 1S/C20H26N2O/c1-3-13-8-12-9-17-19-15(6-7-22(11-12)20(13)17)16-10-14(23-2)4-5-18(16)21-19/h4-5,10,12-13,17,20-21H,3,6-9,11H2,1-2H3/t12-,13+,17+,20+/m1/s1
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = HSIBGVUMFOSJPD-CFDPKNGZSA-N		| StdInChIKey = HSIBGVUMFOSJPD-CFDPKNGZSA-N
	| CAS_number = 83-74-9
			<!-- Physical data -->
	| ATC_prefix = none
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 170667
	| UNII = 3S814I130U
	| PubChem = 197060
	| C=20 | H=26 | N=2 | O=1
	| molecular_weight = 310.433 g/mol
	| smiles = O(c1ccc2c(c1)c3c(n2)5C4C(5N(CC3)C4)CC)C
	| melting_point = 152		| melting_point = 152
	| melting_high = 153		| melting_high = 153
	| bioavailability =
	| protein_bound =
	| metabolism =
	| elimination_half-life = 2 hours
	| excretion =
	| pregnancy_AU =
	| pregnancy_US =
	| pregnancy_category =
	| legal_AU =
	| legal_CA =
	| legal_UK =
	| legal_US = Schedule I
	| routes_of_administration = oral
	}}		}}
			'''Ibogaine''' is a ] ] obtained either by extraction from plants in the family ] such as '']'', '']'', and '']'' or by ] from the precursor compound ], another plant alkaloid.<ref name="Mash2023">{{cite journal | vauthors = Mash DC | title = IUPHAR - invited review - Ibogaine - A legacy within the current renaissance of psychedelic therapy | journal = Pharmacol Res | volume = 190 | issue = | pages = 106620 | date = April 2023 | pmid = 36907284 | doi = 10.1016/j.phrs.2022.106620 | url = | doi-access = free }}</ref><ref name="MaciulaitisKontrimaviciuteBressolle2008">{{cite journal | vauthors = Maciulaitis R, Kontrimaviciute V, Bressolle FM, Briedis V | title = Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review | journal = Hum Exp Toxicol | volume = 27 | issue = 3 | pages = 181–194 | date = March 2008 | pmid = 18650249 | doi = 10.1177/0960327107087802 | bibcode = 2008HETox..27..181M | url = }}</ref> The ] of ibogaine was described in 1956.<ref>{{cite patent| country = US| number = 2813873| status = patent| title = Derivatives of the ibogaine alkaloids| fdate = 9 October 1956| gdate = 19 November 1957| invent1 = Morrice-Marie Janot|invent2=Robert Goutarel| assign1 = Les Laboratoires Gobey}}</ref> Structural elucidation by ] was completed in 1960.<ref>{{ cite journal | vauthors = Soriano-García M | title = Structure of ibogaine | journal = ] | year = 1992 | volume = 48 | issue = 11 | pages = 2055–2057 | doi = 10.1107/S0108270192002786 | bibcode = 1992AcCrC..48.2055S }}</ref><ref>{{Cite journal | vauthors = Soriano-García M, Walls F, Rodríguez A, Celis IL | title = Crystal and molecular structure of ibogamine: An alkaloid from ''Stemmadenia galeottiana'' | doi = 10.1007/BF01181911 | journal = Journal of Crystallographic and Spectroscopic Research | volume = 18 | issue = 2 | pages = 197–206 | year = 1988 | bibcode = 1988JCCry..18..197S | s2cid = 97519993 }}</ref><ref>{{Cite journal | vauthors = Arai G, Coppola J, Jeffrey GA | doi = 10.1107/S0365110X60001369 | title = The structure of ibogaine | journal = Acta Crystallographica | volume = 13 | issue = 7 | pages = 553–564 | year = 1960 | bibcode = 1960AcCry..13..553A }}</ref>
	'''Ibogaine''' is a naturally occurring ] substance found in a number of plants, principally in a member of the ] family known as iboga ('']'').
			The psychoactivity of the root bark of the iboga tree'', Tabernanthe iboga'', one of the plants from which ibogaine is ]ed, was first discovered by the ] tribes of Central Africa, who passed the knowledge to the ] tribe of ]. French explorers in turn learned of it from the Bwiti tribe and brought ibogaine back to Europe in 1899–1900, where it was subsequently marketed in France as a stimulant under the trade name ''Lambarène'' until the 1960s.<ref name="Mash2023" /><ref name="MaciulaitisKontrimaviciuteBressolle2008" /> It was also marketed as Iperton.<ref name="MaciulaitisKontrimaviciuteBressolle2008" /> Although ibogaine's ] properties were first widely promoted in 1962 by ], its Western medical use predates that by at least a century.
	A ], the substance is banned in some countries; in other countries it is being used to treat ] to ]s, ] and other drugs. Derivatives of ibogaine that lack the substance's hallucinogen properties are under development.<ref>{{cite news|url=http://www.villagevoice.com/2010-11-17/news/ibogaine-hallucingen-heroin/|title=Ibogaine: Can it Cure Addiction Without the Hallucinogenic Trip?|author=Keegan Hamilton|date=17 Nov 2010|newspaper=Village Voice}}</ref>
			During an eighteen-year timeline, a total of 19 fatalities temporally associated with the ingestion of ibogaine were reported, from which six subjects died of acute heart failure or cardiopulmonary arrest. Its ] in many countries has slowed scientific research.<ref name="The Ibo subculture">{{cite journal |vauthors= Alper KR, Lotsof HS, Kaplan CD |title= The ibogaine medical subculture |journal= Journal of Ethnopharmacology |volume= 115 |issue= 1 |pages= 9–24 |date= January 2008 |pmid= 18029124 |doi= 10.1016/j.jep.2007.08.034 |url= http://www.ibogaine.org/subculture.html |archive-url= https://web.archive.org/web/20080206110946/http://www.ibogaine.org/subculture.html |url-status= dead |archive-date = 6 February 2008}}</ref> Various derivatives of ibogaine designed to lack psychedelic properties, such as ], are under preliminary research.
	==Descriptive summary==
	Ibogaine-containing preparations are used in medicinal and ritual purposes within ]n spiritual traditions of the ], who claim to have learned it from the ]. Although it was first commonly advertised as having ] properties in 1962 by ], its western use predates that by at least a century. In France it was marketed as ''Lambarene'', a medical drug used for dieting. Additionally, ] documents released in the 1980s show that the U.S. ] studied the effects of ibogaine in the 1950s.<ref name="http://www.ibogamind.com/ibogainetimeline">http://www.ibogamind.com/ibogainetimeline</ref>
			{{TOC limit|3}}
	Ibogaine is an ] that is obtained either by extraction from the iboga plant or by semi-synthesis from the precursor compound ], another plant alkaloid. A full organic synthesis of ibogaine has been achieved. The synthesis process is too expensive and challenging to be used to produce a commercially significant yield, primarily due to the need to conduct the synthesis in an ] environment.{{Citation needed|date=October 2010}}
			== Psychoactive effects ==
	In the early 1960s, anecdotal reports appeared concerning ibogaine's effects.<ref name="K.R. Alper, H.S. Lotsof, G.M. Frenken , D.J. Luciano , J. Bastiaans 1999 234–42">{{cite journal |author=K.R. Alper, H.S. Lotsof, G.M. Frenken , D.J. Luciano , J. Bastiaans |year=1999 |title=Treatment of Acute Opioid Withdrawal with Ibogaine |journal=The American Journal on Addictions |volume=8 |issue=3 |pages=234–42 |url=http://www.ibogaine.desk.nl/p234_s.pdf | accessdate = 2009-06-16 |pmid=10506904 |doi=10.1080/105504999305848}}</ref> Since that time, it has been the subject of investigation into its abilities to interrupt addictions to ], ], ], and ]. It is thought that ibogaine may have potential to facilitate introspection, helping to elucidate the psychological issues and behavior patterns that drive addictions or other problems. However, ibogaine therapy for drug addiction is the subject of some controversy. For myriad reasons it has been placed in the strictest drug prohibition schedules in the United States and a handful of other countries. Canada and Mexico both allow ibogaine therapy facilities to operate and openly contribute to further understanding of the detoxification and therapeutic process that ibogaine has the potential to facilitate.
			Ibogaine is derived from the root of '']'', a plant known to exhibit ] effects in its users.<ref name = "Alper_2001b">{{cite journal | vauthors = Alper KR, Beal D, Kaplan CD | title = A contemporary history of ibogaine in the United States and Europe | journal = The Alkaloids. Chemistry and Biology | volume = 56 | pages = 249–81 | year = 2001 | pmid = 11705112 | url = http://www.ibogaine.desk.nl/ch14.pdf | publisher = Academic Press | doi = 10.1016/S0099-9598(01)56018-6 | access-date = 21 September 2013 | archive-url = https://web.archive.org/web/20160304031149/http://www.ibogaine.desk.nl/ch14.pdf | archive-date = 4 March 2016 | url-status = dead |isbn=978-0-12-469556-6 |oclc=119074996 }}</ref> The experience of ibogaine occurs in two phases, termed the visionary phase and the introspection phase. The visionary phase has been described as ]ic, referring to the dreamlike nature of its ] effects, and lasts for 4 to 6 hours. The second phase, the introspection phase, is responsible for the psychotherapeutic effects.{{Citation needed|reason=This is a psychopharmacological claim about the compound's mechanism of action. It should be supported by research.|date=February 2023}} It can allow people to conquer their fears and ]s.{{Citation needed|reason=This can be taken as a claim about the compound's clinical efficacy. Should rephrase or add source.|date=February 2023}} Ibogaine catalyzes an ] reminiscent of dreaming while fully conscious and aware so that memories, life experiences, and issues of trauma can be processed.<ref name="clinicalmanagement">{{Cite book|title=Practical Skills and Clinical Management of Alcoholism & Drug Addiction | vauthors = Obembe SB |page=88 |url=http://www.sciencedirect.com/science/book/9780123985187 |isbn=9780123985187 |year=2012 |publisher=Elsevier |oclc=802345585 }}</ref>
			== Uses ==
	While ibogaine's ] in the U.S. has slowed scientific research into its anti-addictive properties, the use of ibogaine for drug treatment has grown in the form of a large worldwide medical ].<ref>{{cite journal |author=K.R. Alper, H.S. Lotsof, C.D. Kaplan |year=2008 |title=The Ibogaine Medical Subculture |journal=J. Ethnopharmacology |volume=115 |issue=1 |pmid=18029124 |pages=9–24 |url=http://www.ibogaine.org/subculture.html | accessdate = 2008-02-22 |doi=10.1016/j.jep.2007.08.034}}</ref> Ibogaine is now used by treatment clinics in 12 countries on six continents to facilitate detoxification and relief of chemical dependence to substances such as methadone, heroin, alcohol, powder cocaine, crack cocaine, and ], and to facilitate ] and spiritual exploration.
			]
			===Medical===
	== Psychoactive effects ==
			Clinical studies of ibogaine to treat drug addiction began in the early 1990s, but concerns about ] terminated those studies.<ref name="Brown_2013">{{cite journal | vauthors = Brown TK | title = Ibogaine in the treatment of substance dependence | journal = Current Drug Abuse Reviews | volume = 6 | issue = 1 | pages = 3–16 | date = March 2013 | pmid = 23627782 | doi = 10.2174/15672050113109990001 }}</ref> A 2022 review indicated that severe ]s, including deaths, have impeded progress toward clinical adoption of ibogaine for use in opioid abstinence.<ref name="Köck_2022">{{cite journal |vauthors=Köck P, Froelich K, Walter M, Lang U, Dürsteler KM |title=A systematic literature review of clinical trials and therapeutic applications of ibogaine |journal=Journal of Substance Abuse Treatment |volume=138 |issue= |pages=108717 |date=July 2022 |pmid=35012793 |doi=10.1016/j.jsat.2021.108717 |url=https://www.jsatjournal.com/article/S0740-5472(21)00443-8/fulltext}}</ref> There is insufficient evidence to determine whether ibogaine is useful for treating addiction.<ref name="Köck_2022"/><ref name="Vastag_2005">{{cite journal | vauthors = Vastag B | title = Addiction research. Ibogaine therapy: a 'vast, uncontrolled experiment' | journal = Science | volume = 308 | issue = 5720 | pages = 345–6 | date = April 2005 | pmid = 15831735 | doi = 10.1126/science.308.5720.345 | s2cid = 70642078 }}</ref>
			== Adverse effects ==
	At doses of around 1-2 mg/kg of body weight, ibogaine has a mild stimulant effect. Doses of 4 mg/kg or greater can cause a “dream-like” visual phase followed by an introspective phase.<ref name="http://www.ibogamind.com/ibogainepsychoactiveeffects">http://www.ibogamind.com/ibogainepsychoactiveeffects</ref> Therapeutic doses are typically 10 mg/kg and upwards for psychotherapy use, and 15 mg/kg and upwards for interruption of addiction.
			Immediate adverse effects of ibogaine ingestion may include nausea, tremors leading to ], headaches, and mental confusion.<ref name=drugs/> In long-term use, ] may last for several days, possibly including ], irritability, emotional instability, ]s, aggressive behavior, and thoughts of ].<ref name=drugs/> In the heart, ibogaine causes ] at higher doses, apparently by blocking ] ]s and slowing the ].<ref name="Alper_2016">{{cite journal | vauthors = Alper K, Bai R, Liu N, Fowler SJ, Huang XP, Priori SG, Ruan Y | title = hERG Blockade by Iboga Alkaloids | journal = Cardiovascular Toxicology | volume = 16 | issue = 1 | pages = 14–22 | date = January 2016 | pmid = 25636206 | doi = 10.1007/s12012-015-9311-5 | s2cid = 16071274 | url = https://cdr.lib.unc.edu/downloads/qr46r634b }}</ref><ref name="Koenig_2015" /> Ibogaine should not be used during pregnancy or breastfeeding.<ref name=drugs/>
			Ibogaine has potential for adverse ] with other psychedelic agents and ]s.<ref name=drugs/><ref name="Koenig_2015" />
	The visual phase is characterized by open-eye visuals, closed-eye visuals, and dreamlike sequences. Objects may be seen as distorted, projecting tracers, or having moving colors or textures. When the eyes are closed, extremely detailed and vivid geometric and fractal visions may be seen. Subjective reports often include a movie-like recollection of earlier life experiences as well as dreamlike sequences with symbolism of one's present or anticipated future. Other effects in the visual phase may include laughing, sensations of euphoria or fear, and temporary short-term memory impairment. The visual phase usually ends after one to four hours, after which the introspective phase begins.<ref name="ibogaworld-effects">http://www.ibogaworld.com/712/ibogaine-psychoactive-effects</ref>
			Death may occur with the use of ibogaine,<ref name="Koenig_2015">{{cite journal |vauthors=Koenig X, Hilber K |title=The anti-addiction drug ibogaine and the heart: a delicate relation |journal=Molecules|volume=20 |issue=2 |pages=2208–28 |date=January 2015 |pmid=25642835 |pmc=4382526 |doi=10.3390/molecules20022208|doi-access=free}}</ref> especially if consumed with opioids or in people with existing ]ities, such as ] or ]s.<ref name=drugs/>
	Ibogaine is not a hallucinogen. It is an oneirophrenic or "remogen" referring to the REM or Rapid Eye Movement normally occurring for brief periods of time during the sleep/dream state. Ibogaine catalyses this state of REM for hours while fully conscious and aware so that memories; life experiences; and issues of trauma can be processed in a subjective manner.<ref name="ibogafoundation-addictioninteruption">http://www.ibogafoundation.com/4/39/Addiction+Interruption</ref>
			===Neurotoxicity===
	The introspective phase is typically reported to bring elevated mood, a sense of calm and euphoria, and a distinct intellectual and emotional clarity. Subjects often report being able to accomplish deep emotional and intellectual introspection into psychological and emotional concerns. It is also during this period that opioid addicts first notice the absence of withdrawal symptoms or cravings. The duration of the introspective phase is highly variable, usually lasting hours but sometimes lasting days.<ref name="ibogaworld-effects"/>
			Laboratory studies in rats indicate that high-dose ibogaine may cause degeneration of ] ].<ref>{{cite journal | vauthors = O'Hearn E, Molliver ME | title = Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline | journal = Neuroscience | volume = 55 | issue = 2 | pages = 303–10 | date = July 1993 | pmid = 8377927 | doi = 10.1016/0306-4522(93)90500-f | s2cid = 25273690 }}</ref> However, subsequent research found no evidence of ] in a primate.<ref name="Mash_1998">{{cite journal | vauthors = Mash DC, Kovera CA, Buck BE, Norenberg MD, Shapshak P, Hearn WL, Sanchez-Ramos J | title = Medication development of ibogaine as a pharmacotherapy for drug dependence | journal = Annals of the New York Academy of Sciences | volume = 844 | issue = 1 | pages = 274–92 | date = May 1998 | pmid = 9668685 | doi = 10.1111/j.1749-6632.1998.tb08242.x | bibcode = 1998NYASA.844..274M | s2cid = 22068338 }}</ref>
			In limited human research, ] revealed no evidence of neuronal degenerative changes in a woman who had received four separate doses of ibogaine ranging between 10 and 30&nbsp;mg⁄ kg over a 15-month interval.<ref name="Mash_1998" /> A published series of fatalities associated with ibogaine ingestion found no evidence for consistent neurotoxicity.<ref name="Alper_2012">{{cite journal | vauthors = Alper KR, Stajić M, Gill JR | title = Fatalities temporally associated with the ingestion of ibogaine | journal = Journal of Forensic Sciences | volume = 57 | issue = 2 | pages = 398–412 | date = March 2012 | pmid = 22268458 | doi = 10.1111/j.1556-4029.2011.02008.x | s2cid = 6670557 }}</ref>
	== Side effects and safety ==
	One of the first noticeable effects of large-dose ibogaine ingestion is ], a difficulty in coordinating muscle motion which makes standing and walking difficult without assistance. ] (dry mouth), ], and vomiting may follow. These symptoms may be long in duration, ranging from 4 to 24 hours in some cases. Ibogaine is sometimes administered by enema to help the subject avoid vomiting up the dose. Psychiatric medications are strongly contraindicated in ibogaine therapy due to adverse interactions. Some studies also suggest the possibility of adverse interaction with heart conditions. In one study of canine subjects, ibogaine was observed to increase ] (the normal change in heart rate during respiration).<ref>http://www.puzzlepiece.org/ibogaine/literature/gershon1962.pdf</ref> Ventricular ] has been observed in a minority of patients during ibogaine therapy.<ref></ref> It has been proposed that there is a risk of QT-interval prolongation following ibogaine administration.<ref>{{cite journal |author=Maas U, Strubelt S |title=Fatalities after taking ibogaine in addiction treatment could be related to sudden cardiac death caused by autonomic dysfunction |journal=Med. Hypotheses |volume=67 |issue=4 |pages=960–4 |year=2006 |pmid=16698188 |doi=10.1016/j.mehy.2006.02.050 |url=http://linkinghub.elsevier.com/retrieve/pii/S0306-9877(06)00209-X}}</ref> This risk was further demonstrated by a case reported in the ] documenting ] and ] after initial use.<ref>{{cite journal |author=Hoelen DW, Spiering W, Valk GD |title=Long-QT syndrome induced by the antiaddiction drug ibogaine |journal=N. Engl. J. Med. |volume=360 |issue=3 |pages=308–9 |year=2009 |month=January |pmid=19144953 |doi=10.1056/NEJMc0804248 }}</ref>
			== Pharmacology ==
	There are 12 documented fatalities that have been loosely associated with ibogaine ingestion.<ref></ref> Exact determinations of the cause of death have proven elusive due to the quasi-legal status of ibogaine and the unfamiliarity of medical professionals with this relatively rare substance. No autopsy to date has implicated ibogaine as the sole cause of death. Causes given range from significant pre-existing medical problems to the co-consumption of drugs such as opiates which are potentiated by ibogaine. Also, because ibogaine is one of the many drugs that are partly metabolized by the ] complex, caution must be exercised to avoid ] or drugs that inhibit CP450, in particular foodstuffs containing ] or ], common ones being grapefruit juice<ref>http://www.mayoclinic.com/health/food-and-nutrition/AN00413</ref> and ].
			=== Pharmacodynamics ===
			{| class="wikitable floatright"
			|+ Ibogaine (and metabolite)<ref name="pmid11705115">{{Cite journal |vauthors=Glick SD, Maisonneuve IM, Szumlinski KK |title=Mechanisms of action of ibogaine: Relevance to putative therapeutic effects and development of a safer iboga alkaloid congener |pmid=11705115 |url=http://www.ibogaine.desk.nl/ch02.pdf |year=2001 |volume=56 |pages=39–53 |doi=10.1016/S0099-9598(01)56006-X |journal=The Alkaloids: Chemistry and Biology |issn=1099-4831 |isbn=978-0-12-469556-6 |oclc=119074996 |url-status=dead |archive-url=https://web.archive.org/web/20140405054248/http://www.ibogaine.desk.nl/ch02.pdf |archive-date=5 April 2014}}</ref><ref name="pmid26807959">{{cite journal |vauthors= Litjens RP, Brunt TM |title= How toxic is ibogaine? |journal= Clinical Toxicology |volume= 54 |issue= 4 |pages= 297–302 |year= 2016 |pmid= 26807959 |doi= 10.3109/15563650.2016.1138226 |issn=1556-3650 |oclc=6027439727 |s2cid= 7026570 }}</ref>
			! scope="col" | Site || Ibogaine || ]
			|-
			! scope="row" | {{abbrlink|MOR|μ-Opioid receptor}}
			| 2,000–100,000 || 700–3,000
			|-
			! scope="row" | {{abbrlink|DOR|δ-Opioid receptor}}
			| >100,000 || 5,000–25,000
			|-
			! scope="row" | {{abbrlink|KOR|κ-Opioid receptor}}
			| 2,000–4,000 || 600–1,000
			|-
			! scope="row" | ]
			| 16,000 || >100,000
			|-
			! scope="row" | ]
			| >10,000 || >10,000
			|-
			! scope="row" | ]
			| 2,600 || >100,000
			|-
			! scope="row" | ]
			| 2,500–9,000 || 11,000–15,000
			|-
			! scope="row" | ]
			| 90–400 || 5,000–19,000
			|-
			! scope="row" | {{abbrlink|NMDA|N-Methyl-D-aspartate receptor}}
			| 1,000–3,000 || 6,000–15,000
			|-
			! scope="row" | {{abbrlink|nACh|Nicotinic acetylcholine receptor}}
			| 20 || 1,500
			|-
			! scope="row" | {{abbrlink|SERT|Serotonin transporter}}
			| 500 || 40
			|-
			! scope="row" | {{abbrlink|DAT|Dopamine transporter}}
			| 2,000 || 2,000
			|- class="sortbottom"
			| colspan="3" | Values are K<sub>i</sub> (nM). The smaller the value, the<br />more strongly the drug binds to the site.
			|}
			Ibogaine affects many different ] systems simultaneously.<ref name="Popik & Skolnick 1999">{{cite journal <!-- Citation bot bypass--> | vauthors = Popik P, Skolnick P |title=Pharmacology of Ibogaine and Ibogaine-Related Alkaloids |journal=The Alkaloids: Chemistry and Biology |publisher=Academic Press |volume=52 |date=1999 |isbn=978-0-12-469552-8 |doi=10.1016/s0099-9598(08)60027-9 |pages=197–231 |issn=1099-4831 |oclc=505140539 |url=http://www.ibogaine.desk.nl/alkaloids.html |url-status=dead |archive-url=https://archive.today/20120526225220/http://www.ibogaine.desk.nl/alkaloids.html |archive-date=26 May 2012}}</ref><ref name="Alper_2001">{{cite journal | vauthors = Alper KR | veditors = Alper KR, Glick SD |journal= The Alkaloids: Chemistry and Biology |publisher=Academic |location=San Diego |year=2001 |pages=1–38 |isbn=978-0-12-469556-6 |issn=1099-4831 |oclc=119074989 |volume=56 |title=Ibogaine: A Review | doi = 10.1016/S0099-9598(01)56005-8 | pmid = 11705103 |url=http://ibogaine.org/ch01.pdf |url-status=dead |archive-url=https://web.archive.org/web/20070927225940/http://ibogaine.org/ch01.pdf |archive-date=27 September 2007}}</ref>
	== Therapeutic uses ==
	=== Treatment for opiate addiction ===
			Noribogaine is most potent as a ]. It acts as a moderate ] agonist<ref name="pmid26302653">{{cite journal | vauthors = Maillet EL, Milon N, Heghinian MD, Fishback J, Schürer SC, Garamszegi N, Mash DC | title = Noribogaine is a G-protein biased κ-opioid receptor agonist | journal = Neuropharmacology | volume = 99 | issue = December 2015 | pages = 675–88 | date = December 2015 | pmid = 26302653 | doi = 10.1016/j.neuropharm.2015.08.032 | doi-access = free |issn=0028-3908 |oclc=5921346571}}</ref> and weak ] agonist<ref name="pmid26302653"/> or weak partial agonist.<ref name="pmid24204784">{{cite journal | vauthors = Antonio T, Childers SR, Rothman RB, Dersch CM, King C, Kuehne M, Bornmann WG, Eshleman AJ, Janowsky A, Simon ER, Reith ME, Alper K | title = Effect of Iboga alkaloids on µ-opioid receptor-coupled G protein activation | journal = PLOS ONE | volume = 8 | issue = 10 | pages = e77262 | year = 2013 | pmid = 24204784 | pmc = 3818563 | doi = 10.1371/journal.pone.0077262 | bibcode = 2013PLoSO...877262A | doi-access = free |issn=1932-6203 |oclc=5534534188}}</ref> It is possible that the action of ibogaine at the kappa opioid receptor may indeed contribute significantly to the psychoactive effects attributed to ibogaine ingestion; '']'', another plant recognized for its strong hallucinogenic properties, contains the chemical ], which is a highly selective kappa opioid agonist. Noribogaine is more potent than ibogaine in rat drug discrimination assays when tested for the subjective effects of ibogaine.<ref name="pmid10379526">{{cite journal | vauthors = Zubaran C, Shoaib M, Stolerman IP, Pablo J, Mash DC | title = Noribogaine generalization to the ibogaine stimulus: correlation with noribogaine concentration in rat brain | journal = Neuropsychopharmacology | volume = 21 | issue = 1 | pages = 119–26 | date = July 1999 | pmid = 10379526 | doi = 10.1016/S0893-133X(99)00003-2 | doi-access = free |issn=1740-634X |oclc=9523107895}}</ref>
	The most-studied therapeutic effect of ibogaine is the reduction or elimination of ] to ]s<ref name="K.R. Alper, H.S. Lotsof, G.M. Frenken , D.J. Luciano , J. Bastiaans 1999 234–42"/>, with success rates of 80% or more <ref></ref>. An integral effect is the alleviation of symptoms of opioid ]. Research also suggests that ibogaine may be useful in treating dependence on other substances such as ], ], and ] and may affect compulsive behavioral patterns not involving substance abuse or chemical dependence.<ref name="K.R. Alper, H.S. Lotsof, G.M. Frenken , D.J. Luciano , J. Bastiaans 1999 234–42"/>
			=== Pharmacokinetics ===
	Proponents of ibogaine treatment for drug addiction have established formal and informal clinics or self-help groups in ], ], the ], ], the ], ], ], the ], ], ], the ] and ], where ibogaine is administered as an experimental compound. Many users of ibogaine report experiencing visual phenomena during a waking dream state, such as instructive replays of life events that led to their addiction, while others report therapeutic ]ic visions that help them conquer the fears and negative emotions that might drive their addiction. It is proposed that intensive counseling, therapy and aftercare during the interruption period following treatment is of significant value. Some individuals require a second or third treatment session with ibogaine over the course of the next 12 to 18 months. A minority of individuals relapse completely into opiate addiction within days or weeks. A comprehensive article (Lotsof 1995) on the subject of ibogaine therapy detailing the procedure, effects and aftereffects is found in "Ibogaine in the Treatment of Chemical Dependence Disorders: Clinical Perspectives".<ref>H.S. Lotsof (1995). (Originally published in MAPS Bulletin (1995) V(3):19-26)</ref> Ibogaine has also been reported in multiple small-study cohorts to reduce cravings for methamphetamine.<ref>{{cite book |author=Giannini, A. James |title=Drugs of Abuse |publisher=Practice Management Information Corporation |year=1997 |isbn=1-57066-053-0 |edition=2nd}}</ref>
			Ibogaine is metabolized in the human body by cytochrome P450 2D6 (]) into ] (more correctly, O-desmethylibogaine or 12-hydroxyibogamine). Both ibogaine and noribogaine have a ] of around two hours in rats,<ref>{{cite journal | vauthors = Baumann MH, Rothman RB, Pablo JP, Mash DC | title = In vivo neurobiological effects of ibogaine and its O-desmethyl metabolite, 12-hydroxyibogamine (noribogaine), in rats | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 297 | issue = 2 | pages = 531–9 | date = May 2001 | pmid = 11303040 | url = http://jpet.aspetjournals.org/cgi/content/full/297/2/531 |issn=0022-3565 |oclc=118935157}}</ref> although the half-life of noribogaine is slightly longer than that of the parent compound. It is proposed that ibogaine is deposited in fat and metabolized into noribogaine as it is released.<ref>{{cite journal | vauthors = Hough LB, Bagal AA, Glick SD | title = Pharmacokinetic characterization of the indole alkaloid ibogaine in rats | journal = Methods and Findings in Experimental and Clinical Pharmacology | volume = 22 | issue = 2 | pages = 77–81 | date = March 2000 | pmid = 10849889 | doi = 10.1358/mf.2000.22.2.796066 | url = http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=6&p_RefId=796066 |issn=0379-0355 |oclc=118905358}}</ref> After ibogaine ingestion in humans, noribogaine shows higher plasma levels than ibogaine and is detected for a longer period of time than ibogaine.<ref>{{cite journal | vauthors = Mash DC, Kovera CA, Pablo J, Tyndale RF, Ervin FD, Williams IC, Singleton EG, Mayor M | title = Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures | journal = Annals of the New York Academy of Sciences | volume = 914 | issue = 1 | pages = 394–401 | date = September 2000 | pmid = 11085338 | doi = 10.1111/j.1749-6632.2000.tb05213.x | citeseerx = 10.1.1.598.8242 | bibcode = 2000NYASA.914..394M | s2cid = 33436971 |issn=0077-8923 |oclc=117596065}}</ref>
			==Chemistry==
	There is also evidence that this type of treatment works with ]<ref>A. Ludwig, J. Levine, L. Stark, R. Lazar (1969). (Originally published in The American Journal of Psychiatry (1969) )</ref> which has been shown to have therapeutic effect on alcoholism as far back as the 1960s. Both ibogaine and LSD appear affective at encouraging introspection and giving the user occasion to reflect on where their addiction came from while also occasioning an intense, transformative experience that can put established patterns of behaviour into perspective, but ibogaine has the added benefit of preventing withdrawal effects.
			]
			Ibogaine is a ]. It has two separate ] centers, meaning that there are four different stereoisomers of ibogaine. These four isomers are difficult to ].<ref name="Shulgin & Shulgin 1997">{{Cite book |vauthors = Shulgin A, Shulgin A |chapter=IBOGAINE; 12-METHOXYIBOGAMINE |chapter-url=https://archive.org/details/tihkalcontinuati0000shul/page/486/mode/2up |chapter-url-access=registration | title=Tihkal: the continuation |url=https://search.worldcat.org/title/1360062118 |url-access=registration |via=Internet Archive |publisher=Transform Press |publication-place=Berkeley, CA |year=1997 |isbn=978-0-9630096-9-2 |oclc=1360062118 |pages=487–490}}</ref>
	=== Chronic pain management ===
			=== Synthesis ===
	In 1957, Jurg Schneider, a pharmacologist at ], found that ibogaine potentiates ] ].<ref>Jurg Schneider (assignee: Ciba Pharmaceuticals), Tabernanthine, Ibogaine Containing Analgesic Compositions. (pdf)</ref> Further research was abandoned, and no additional data was ever published by Ciba researchers on ibogaine–opioid interactions. Almost 50 years later, ] and ] released the first treatment protocol for concomitant administration of ibogaine with ] in human subjects, indicating ibogaine reduced tolerance to opioid drugs.<ref>Patrick K. Kroupa, Hattie Wells (2005): (pdf)</ref> Kroupa ''et al.'' published their research in the ''] Journal'' demonstrating that administration of low-"maintenance" doses of ibogaine HCl with ] decreases ]. It should be noted however, that the potentiation action of ibogaine may make this a very risky procedure.
			One recent total synthesis<ref>{{Cite journal | vauthors = Jana GK, Sinha S | doi = 10.1016/j.tet.2012.06.027 | title = Total synthesis of ibogaine, epiibogaine and their analogues | journal = Tetrahedron | volume = 68 | issue = 35 | pages = 7155–7165 | year = 2012 |issn=0040-4020 |oclc=5901603422}}</ref> of ibogaine and related drugs starts with 2-iodo-4-methoxyaniline which is reacted with triethyl((4-(triethylsilyl)but-3-yn-1-yl)oxy)silane using ] in ] to form 2-(triethylsilyl)-3-(2-((triethylsilyl)oxy)ethyl)-1H-indole. This is converted using N-iodosuccinamide and then ] to form 2-(2-iodo-1H-indol-3-yl)ethanol. This is treated with ], ], and ] to form 2-iodo-3-(2-iodoethyl)-1H-indole. Then, using 7-ethyl-2-azabicyclooct-5-ene and ] ] in ], the ibogaine precursor 7-ethyl-2-(2-(2-iodo-1H-indol-3-yl)ethyl)-2-azabicyclooct-5-ene is obtained. Using palladium acetate in DMF, the ibogaine is obtained. If the exo ethyl group on the 2-azabicyclooctane system in ibogaine is replaced with an endo ethyl, then epiibogaine is formed.
			Crystalline ibogaine hydrochloride is typically produced by semi-synthesis from ] in commercial laboratories.<ref name="pmid11942686">{{cite journal | vauthors = Jenks CW | title = Extraction studies of Tabernanthe iboga and Voacanga africana | journal = Natural Product Letters | volume = 16 | issue = 1 | pages = 71–6 | date = February 2002 | pmid = 11942686 | doi = 10.1080/1057563029001/4881 | s2cid = 23390825 |issn=1057-5634 |oclc=4803437833}}</ref><ref>{{Cite web|title = Voacanga Extraction Manual: Phase 4: Production and Purification of Ibogaine|url = http://puzzlepiece.org/ibogaine/literature/voacanga_extraction_manual_phase_4.pdf|website = www.puzzlepiece.org|access-date = 4 December 2015}}</ref> It can be prepared from voacangine through one-step demethoxycarbonylation process too.<ref name="pmid31095891">{{cite journal |vauthors=Krengel F, Mijangos MV, Reyes-Lezama M, Reyes-Chilpa R |title=Extraction and Conversion Studies of the Antiaddictive Alkaloids Coronaridine, Ibogamine, Voacangine, and Ibogaine from Two Mexican Tabernaemontana Species (Apocynaceae) |journal=Chemistry & Biodiversity |volume=16 |issue=7 |pages=e1900175 |date=July 2019 |pmid=31095891 |doi=10.1002/cbdv.201900175 |s2cid=157058497 |issn=1612-1872 |oclc=8185274820}}</ref>
	=== Psychotherapy ===
			===Derivatives===
	Ibogaine has been used as an adjunct to ] by ], documented in his book ''The Healing Journey''.<ref>{{cite book |author=Naranjo, Claudio |title=The healing journey: new approaches to consciousness |publisher=Pantheon Books |location=New York |year=1973 |isbn=0-394-48826-1 |url=http://www.ibogaine.desk.nl/naranjo.html |chapter=V, Ibogaine: Fantasy and Reality |pages=197–231}}</ref>
			A synthetic derivative of ibogaine, ] (18-MC), is a selective α3β4 antagonist that was developed collaboratively by the neurologist Stanley D. Glick (Albany) and the chemist Martin E. Kuehne (Vermont).<ref>{{cite journal | vauthors = Pace CJ, Glick SD, Maisonneuve IM, He LW, Jokiel PA, Kuehne ME, Fleck MW | title = Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration | journal = European Journal of Pharmacology | volume = 492 | issue = 2–3 | pages = 159–67 | date = May 2004 | pmid = 15178360 | doi = 10.1016/j.ejphar.2004.03.062 |issn=0014-2999 |oclc=110898054}}</ref> This discovery was stimulated by earlier studies on other naturally occurring analogues of ibogaine, such as ] and ], that showed these compounds to have anti-addictive properties.<ref>{{cite journal | vauthors = Glick SD, Kuehne ME, Raucci J, Wilson TE, Larson D, Keller RW, Carlson JN | title = 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 | journal = Brain Research | volume = 657 | issue = 1–2 | pages = 14–22 | date = September 1994 | pmid = 7820611 | doi = 10.1016/0006-8993(94)90948-2 | s2cid = 1940631 |issn=0006-8993 |oclc=4923262393}}</ref><ref>{{cite journal |url=http://www.shvoong.com/medicine-and-health/1611478-antiaddictive-indole-alkaloids-ervatamia-yunnanensis/ |vauthors=Hua T |title=Antiaddictive indole alkaloids in Ervatamia yunnanensis and their bioactivity |journal=Academic Journal of Second Military Medical University |date=28 January 2006 |access-date=15 August 2012 |archive-date=13 February 2012 |archive-url=https://web.archive.org/web/20120213104620/http://www.shvoong.com/medicine-and-health/1611478-antiaddictive-indole-alkaloids-ervatamia-yunnanensis/ |url-status=dead }}</ref> More recently, non- and less-hallucinogenic analogs, ] and ibogainalog, were engineered by scientists attempting to produce non-cardiotoxic ibogaine derivatives by removing the ] isoquinuclidine ring. In animal models, both molecules failed to produce ]s, and tabernanthalog failed to produce any head twitch response, suggesting psychedelic effects were absent.<ref>{{cite journal | vauthors = Cameron LP, Tombari RJ, Lu J, Pell AJ, Hurley ZQ, Ehinger Y, Vargas MV, McCarroll MN, Taylor JC, Myers-Turnbull D, Liu T, Yaghoobi B, Laskowski LJ, Anderson EI, Zhang G, Viswanathan J, Brown BM, Tjia M, Dunlap LE, Rabow ZT, Fiehn O, Wulff H, McCorvy JD, Lein PJ, Kokel D, Ron D, Peters J, Zuo Y, Olson DE | title = A non-hallucinogenic psychedelic analogue with therapeutic potential | journal = Nature | volume = 589 | issue = 7842 | pages = 474–479 | date = January 2021 | pmid = 33299186 | pmc = 7874389 | doi = 10.1038/s41586-020-3008-z | bibcode = 2021Natur.589..474C |issn=0028-0836 |oclc=8816084004}}</ref><ref>{{cite news| vauthors = Hamilton J |date=2020-12-09|title=Progress Toward A Safer Psychedelic Drug To Treat Depression And Addiction |url= https://www.npr.org/sections/health-shots/2020/12/09/944572325/progress-toward-a-safer-psychedelic-drug-to-treat-depression-and-addiction|access-date=2020-12-12|website=NPR.org}}</ref>
			== Biosynthesis ==
			]
			Ibogaine biosynthesis begins with tryptophan undergoing enzymatic decarboxylation by tryptophan decarboxylase (TDC) to form a tryptamine. Secologanin, an iridoid synthesized from isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), is reacted with tryptamine to make strictosidine. A glycosidic bond cleavage of strictosidine by strictosidine β-deglucosidase (SGD) produces a lactol. The lactol opens and produces an aldehyde, then condenses to form an iminium. Through isomerization and reduction by geissoschizine synthase 1 (GS1), 19E-geissoschizine is yielded. The indole is oxidized and the molecule undergoes intramolecular Mannich reaction and Grob fragmentation to form preakuammicine. Preakuammicine is highly unstable and therefore reduced to stemmadenine by oxidation-reduction reactions (REDOX 1 and REDOX 2). Stemmadine is acylated by stemmadine Ο-acetyltransferase (SAT) to yield stemmadine acetate. Through oxidation by precondylocarpine acetate synthase (PAS) and reduction by dihydroprecondylocarpine acetate synthase (DPAS), an enamine intermediate is formed. The intermediate undergoes fragmentation to produce an iminium that tautomerizes to yield dehydrosecodine. Coronaridine synthase (CorS) catalyzes the isomerization of dehydrosecodine and an unusual cycloaddition is completed. The iminium is reduced by DPAS and NADPH to form (-)-coronaridine.{{citation needed |date=August 2024}}
			There are two pathways (-)-coronaridine can take to become (-)-ibogaine. The first pathway begins with a P450 enzyme, ibogamine-10-hydroxylase (I10H), and methylation of noribogaine-10-Ο-methyltransferase (N10OMT) to produce (-)-voacangine. Polyneudridine aldehyde esterase-like 1 (PNAE1) and a spontaneous decarboxylation can convert (-)-voacangine to (-)-ibogaine. The second pathway consists of PNAE1 and the spontaneous decarboxylation occurring first to yield (-)-ibogamine, then the reaction of I10H-mediated hydroxylation and N10OMT-catalyzed O-methylation to produce (-)-ibogaine.<ref>{{cite journal | vauthors = Iyer RN, Favela D, Zhang G, Olson DE | title = The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs | journal = Natural Product Reports | volume = 38 | issue = 2 | pages = 307–329 | date = March 2021 | pmid = 32794540 | pmc = 7882011 | doi = 10.1039/D0NP00033G |issn=0265-0568 |oclc=8646253022}}</ref>
			== Natural occurrence ==
			Ibogaine occurs naturally in iboga root bark. Ibogaine is also available in a total alkaloid extract of the ''Tabernanthe iboga'' plant, which also contains all the other iboga alkaloids and thus has only about half the potency by weight of standardized ibogaine hydrochloride.<ref name="pmid11942686"/>
	== History ==		== History ==
			The use of iboga in African spiritual ceremonies was first reported by French and Belgian explorers in the 19th century, beginning with the work of French naval physician and ] of ] ].<ref name="GRIFFON du BELLAY">{{cite web |title=Marie Théophile GRIFFON du BELLAY (1829–1908) |website=ecole.nav.traditions.free.fr |date=2023-02-05 |url=https://ecole.nav.traditions.free.fr/officiers_griffon_theophile.htm |archive-url=https://web.archive.org/web/20230306023457/https://ecole.nav.traditions.free.fr/officiers_griffon_theophile.htm |archive-date=2023-03-06 |url-status=dead}}</ref> The first botanical description of the ''Tabernanthe iboga'' plant was made in 1889. Ibogaine was first isolated from ''T. ]'' in 1901 by Dybowski and Landrin<ref>{{cite journal |vauthors=Dybowski J, Landrin E |year=1901 |title=PLANT CHEMISTRY. Concerning Iboga, its excitement-producing properties, its composition, and the new alkaloid it contains, ibogaine |journal=C. R. Acad. Sci. |volume=133 |page=748 |url=http://www.ibogaine.desk.nl/dybowski.html |access-date=20 May 2013 |archive-url=https://web.archive.org/web/20130710095016/http://www.ibogaine.desk.nl/dybowski.html |archive-date=10 July 2013 |url-status=dead }}</ref> and independently by Haller and Heckel in the same year using ''T. iboga'' samples from ]. Complete synthesis of ibogaine was accomplished by G. Büchi in 1966.<ref>{{cite journal | vauthors = Büchi G, Coffen DL, Kocsis K, Sonnet PE, Ziegler FE |year=1966 |title=The Total Synthesis of Iboga Alkaloids |journal=J. Am. Chem. Soc. |volume=88 |issue=13 |pages=3099–3109 |doi=10.1021/ja00965a039|bibcode=1966JAChS..88.3099B }}</ref> Since then, several other synthesis methods have been developed.<ref>{{Cite thesis|year=1999 |url=http://e-collection.ethbib.ethz.ch/ecol-pool/diss/fulltext/eth13329.pdf |archive-url=https://web.archive.org/web/20120729170535/http://e-collection.library.ethz.ch/view/eth:23217 |archive-date=29 July 2012 | vauthors = Frauenfelder C |title= Ph.D. |page=24 |url-status=dead }}</ref>
			From the 1930s to 1960s, ibogaine was sold in France in the form of Lambarène, an extract of the '']'' plant, and promoted as a mental and physical stimulant.<ref name="Mash2023" /> It was formulated at doses of 200{{nbsp}}mg extract containing low doses of 4 to 8{{nbsp}}mg ibogaine per tablet.<ref name="MaciulaitisKontrimaviciuteBressolle2008" /><ref name="Mash2023" /> The drug enjoyed some popularity among post-World War II athletes. Lambarène was withdrawn from the market in 1966 when the sale of ibogaine-containing products became illegal in France.<ref name="Freedlander 2003">{{cite journal | vauthors = Freedlander J |title=Ibogaine: a Comprehensive Literature Review |url=https://ibogaine.mindvox.com/articles/ibogaine-novel-anti-addictive-compound-comprehensive-literature-review/ |volume=1 |year=2003 |journal=Journal of Drug Addiction, Education, and Eradication |publisher=Nova Science Publishers |oclc=609715451 |issn=1546-6965 |pages=79–98 |access-date=2024-07-23 |via=ibogaine.mindvox.com}}</ref><ref name="Mash2023" /> Another formulation was Iperton, which contained '']'' extract 40{{nbsp}}mg per dose unit.<ref name="MaciulaitisKontrimaviciuteBressolle2008" />
	It is uncertain exactly how long iboga has been used in African spiritual practice, but its activity was first observed by French and Belgian explorers in the 19th century. The first botanical description of the ''Tabernanthe iboga'' plant was made in 1889. Ibogaine was first isolated from ''T. ]'' in 1901 by Dybowski and Landrin<ref>{{cite journal |author=J. Dybowski, E. Landrin |year=1901 |title=PLANT CHEMISTRY. Concerning Iboga, its excitement-producing properties, its composition, and the new alkaloid it contains, ibogaine |journal=C. R. Acad. Sci. |volume=133 |pages=748 |url=http://ibogaine.desk.nl/dybowski.html | accessdate = 2006-06-23}}</ref> and independently by Haller and Heckel in the same year using ''T. iboga'' samples from ]. In the 1930s, ibogaine was sold in France in 8&nbsp;mg tablets under the name "Lambarene". The total synthesis of ibogaine was accomplished by G. Büchi in 1966.<ref>{{cite journal |author=G. Büchi, D.L. Coffen, Karoly Kocsis, P.E. Sonnet, and Frederick E. Ziegler |year=1966 |title=The Total Synthesis of Iboga Alkaloids |journal=J. Am. Chem. Soc. |volume=88 |issue=13 |pages=3099–3109 |url=http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/1966/88/i13/f-pdf/f_ja00965a039.pdf | format = pdf | accessdate = 2006-06-23 |doi=10.1021/ja00965a039}} {{Dead link|date=October 2010|bot=H3llBot}}</ref> Since then, several further totally synthetic routes have been developed.<ref>C. Frauenfelder (1999) (pdf)</ref> The use of ibogaine in treating substance use disorders in human subjects was first observed by ] in 1962, for which he was later awarded {{US patent|4499096}} in 1985. In 1969, Claudio Naranjo was granted a French patent for the use of ibogaine in psychotherapy.
			In 2008, Mačiulaitis and colleagues stated that in the late 1960s, the ] classified ibogaine as a "substance likely to cause dependency or endanger human health". The ] also assigned it to a ], and the ] banned it as a potential doping agent.<ref name="MaciulaitisKontrimaviciuteBressolle2008" />
	Ibogaine was placed in US Schedule 1 in 1967 as part of the US government's strong response to the upswing in popularity of psychedelic substances, though iboga itself was scarcely known at the time. Ibogaine's ability to attenuate opioid ] confirmed in the rat was first published by Dzoljic ''et al.'' (1988).<ref>{{cite journal |author=Dzoljic ED, Kaplan CD, Dzoljic MR |title=Effect of ibogaine on naloxone-precipitated withdrawal syndrome in chronic morphine-dependent rats |journal=Arch Int Pharmacodyn Ther |volume=294 |issue= |pages=64–70 |year=1988 |pmid=3233054 }}</ref> Ibogaine's use in diminishing ] self-administration in preclinical studies was shown by Glick ''et al.'' (1991)<ref>{{cite journal |author=Glick SD, Rossman K, Steindorf S, Maisonneuve IM, Carlson JN |year=1991 |title=Effects and aftereffects of ibogaine on morphine self-administration in rats |journal=Eur. J. Pharmacol |volume=195 |issue=3 |pages=341–345 | accessdate = 2006-06-24 |doi=10.1016/0014-2999(91)90474-5 |pmid=1868880}}</ref> and ibogaine's capacity to reduce ] self-administration in the rat was shown by Cappendijk ''et al.'' (1993).<ref>{{cite journal |author=Cappendijk SLT, Dzoljic MR |year=1993 |title=Inhibitory effects of ibogaine on cocaine self-administration in rats |journal=European Journal of Pharmacology |volume=241 |pages=261–265 |pmid=8243561 |doi=10.1016/0014-2999(93)90212-Z |issue=2-3}}</ref> Animal model support for ibogaine claims to treat ] were established by Rezvani (1995).<ref>{{cite journal |author=Rezvani A, Overstreet D, Lee Y |year=1995 |title=Attenuation of alcohol intake by ibogaine in three strains of alcohol preferring rats. |journal=Pharmacology, Biochemistry, and Behaviour |volume=52 |pages=615–20 |pmid=8545483 |doi=10.1016/0091-3057(95)00152-M |issue=3}}</ref>
			Anecdotal reports concerning ibogaine's effects appeared in the early 1960s.<ref name="Alper">{{cite journal | vauthors = Alper KR, Lotsof HS, Frenken GM, Luciano DJ, Bastiaans J | title = Treatment of acute opioid withdrawal with ibogaine | journal = The American Journal on Addictions | volume = 8 | issue = 3 | pages = 234–42 | year = 1999 | pmid = 10506904 | doi = 10.1080/105504999305848 | url = http://www.ibogaine.desk.nl/p234_s.pdf | url-status = dead | archive-url = https://web.archive.org/web/20020126202626/http://www.ibogaine.desk.nl/p234_s.pdf | archive-date = 26 January 2002 |issn=1055-0496 |oclc=122057314}}</ref> Its anti-addictive properties were discovered accidentally by ] in 1962, at the age of 19, when he and five friends—all heroin addicts—noted subjective reduction of their craving and ] symptoms while taking it.<ref>{{Cite news|title = Howard Lotsof Dies at 66; Saw Drug Cure in a Plant|url = https://www.nytimes.com/2010/02/17/us/17lotsof.html|newspaper = The New York Times|date = 17 February 2010|access-date = 11 June 2015|issn = 0362-4331| vauthors = Hevesi D }}</ref> Further anecdotal observation convinced Lotsof of its potential usefulness in treating substance addictions. He contracted with a Belgian company to produce ibogaine in tablet form for clinical trials in the Netherlands, and was awarded a United States patent for the product in 1985. The first objective, placebo-controlled evidence of ibogaine's ability to attenuate opioid withdrawal in rats was published by Dzoljic ''et al.'' in 1988.<ref>{{cite journal | vauthors = Dzoljic ED, Kaplan CD, Dzoljic MR | title = Effect of ibogaine on naloxone-precipitated withdrawal syndrome in chronic morphine-dependent rats | journal = Archives Internationales de Pharmacodynamie et de Therapie | volume = 294 | pages = 64–70 | year = 1988 | pmid = 3233054 |issn=0003-9780 |oclc=115924585}}</ref> Diminution of ] self-administration was reported in preclinical studies by Glick ''et al.'' in 1991.<ref>{{cite journal | vauthors = Glick SD, Rossman K, Steindorf S, Maisonneuve IM, Carlson JN | title = Effects and aftereffects of ibogaine on morphine self-administration in rats | journal = European Journal of Pharmacology | volume = 195 | issue = 3 | pages = 341–5 | date = April 1991 | pmid = 1868880 | doi = 10.1016/0014-2999(91)90474-5 |issn=0014-2999 |oclc=121337019}}</ref> Cappendijk ''et al.'' demonstrated reduction in ] self-administration in rats in 1993,<ref>{{cite journal | vauthors = Cappendijk SL, Dzoljic MR | title = Inhibitory effects of ibogaine on cocaine self-administration in rats | journal = European Journal of Pharmacology | volume = 241 | issue = 2–3 | pages = 261–5 | date = September 1993 | pmid = 8243561 | doi = 10.1016/0014-2999(93)90212-Z |issn=0014-2999 |oclc=121698805}}</ref> and Rezvani reported reduced ] in three strains of "alcohol-preferring" rats in 1995.<ref>{{cite journal | vauthors = Rezvani AH, Overstreet DH, Lee YW | title = Attenuation of alcohol intake by ibogaine in three strains of alcohol-preferring rats | journal = Pharmacology, Biochemistry, and Behavior | volume = 52 | issue = 3 | pages = 615–20 | date = November 1995 | pmid = 8545483 | doi = 10.1016/0091-3057(95)00152-M | s2cid = 38567079 |issn=0091-3057 |oclc=121166985}}</ref>
	The name "Indra extract", in strict terms, refers to 44&nbsp;kg of an iboga extract manufactured by an unnamed European industrial manufacturer in 1981. This stock was later purchased by Carl Waltenburg, who distributed it under the name "Indra extract". Waltenburg used this extract to treat heroin addicts in ], Denmark, a ] village where heroin addiction was widespread in 1982.<ref></ref> Indra extract was offered for sale over the Internet until 2006, when the Indra web presence disappeared. It is unclear whether the extracts currently sold as "Indra extract" are actually from Waltenburg's original stock, or whether any of that stock is even viable or in existence. Ibogaine and related ] compounds are susceptible to ] when exposed to oxygen<ref>a)Taylor WI (1965): "The Iboga and Voacanga Alkaloids" (Journal?), Pages 203, 207 and 208. Oxidation products: ]s; indolenine, iboquine and iboluteine. </ref>
	,<ref name=Kontrim06>{{cite journal |author=Kontrimaviciūte V, Mathieu O, Mathieu-Daudé JC, ''et al.'' |title=Distribution of ibogaine and noribogaine in a man following a poisoning involving root bark of the ''Tabernanthe iboga'' shrub |journal=J Anal Toxicol |volume=30 |issue=7 |pages=434–40 |year=2006 |month=September |pmid=16959135 |url=http://openurl.ingenta.com/content/nlm?genre=article&issn=0146-4760&volume=30&issue=7&spage=434&aulast=Kontrimavici&#x16B;te}}</ref> as opposed to their salt form, which is stable. The exact methods and quality of the original Indra extraction was never documented, so the real composition of the product remains uncertain.
			As the use of ibogaine spread, its administration varied widely; some groups administered it systematically using well-developed methods and medical personnel, while others employed haphazard and possibly dangerous methodology. Lotsof and his colleagues, committed to the traditional administration of ibogaine, developed treatment regimens themselves. In 1992, Eric Taub brought ibogaine to an offshore location close to the United States, where he began providing treatments and popularizing its use.<ref>{{Cite web | vauthors = Ditton MC |title = A Home for Ibogaine in Barcelona|url = http://www.huffingtonpost.com/mary-clare-ditton/a-home-for-ibogaine-in-ba_b_56563.html|website = The Huffington Post|access-date = 11 June 2015|date = 17 July 2007}}</ref> In ], Lex Kogan, another leading proponent, joined Taub in systematizing its administration. The two men established medically monitored treatment clinics in several countries.<ref name="treatmentmag">{{cite web |title= Costa Rican Center a Leader in Alternative Ibogaine Therapy |website=Treatment Magazine |date= 11 September 2012 |url= http://www.treatmentmagazine.com/newswires/307-costa-rican-center-a-leader-in-alernative-ibogaine-therapy.html |access-date= 11 June 2015|archive-url=https://web.archive.org/web/20131203074414/http://www.treatmentmagazine.com/newswires/307-costa-rican-center-a-leader-in-alernative-ibogaine-therapy.html|archive-date=December 3, 2013 |url-status=dead}}</ref>
	Data demonstrating ibogaine's efficacy in attenuating opioid withdrawal in drug-dependent human subjects was published by Alper ''et al.'' (1999)<ref>{{cite journal |author=Alper KR, Lotsof HS, Frenken GM, Luciano DJ, Bastiaans J |title=Treatment of acute opioid withdrawal with ibogaine |journal=Am J Addict |volume=8 |issue=3 |pages=234–42 |year=1999 |pmid=10506904 |url=http://www.ibogaine.desk.nl/p234_s.pdf |format=PDF |doi=10.1080/105504999305848}}</ref> and Mash ''et al.'' (2000).<ref>{{cite journal |doi=10.1111/j.1749-6632.2000.tb05213.x |author=Mash DC, Kovera CA, Pablo J, ''et al.'' |title=Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures |journal=Ann. N. Y. Acad. Sci. |volume=914 |issue= |pages=394–401 |year=2000 |month=September |pmid=11085338 |url=http://ibogaine.mindvox.com/Articles/Mash-01.pdf}}</ref>
			In 1981, an unnamed European manufacturer produced 44&nbsp;kg of iboga extract. The entire stock was purchased by Carl Waltenburg, who distributed it under the name "Indra extract" and used it in 1982 to treat heroin addicts in the community of ].<ref name = "Alper_2001b" /> Indra extract was available for sale over the Internet until 2006, when the Indra web presence disappeared. Various products are currently sold in a number of countries as "Indra extract", but it is unclear if any of them are derived from Waltenburg's original stock. Ibogaine and related ] compounds are susceptible to ] over time.<ref name="Kontrim06">{{cite journal | vauthors = Kontrimaviciūte V, Mathieu O, Mathieu-Daudé JC, Vainauskas P, Casper T, Baccino E, Bressolle FM | title = Distribution of ibogaine and noribogaine in a man following a poisoning involving root bark of the ''Tabernanthe iboga'' shrub | journal = Journal of Analytical Toxicology | volume = 30 | issue = 7 | pages = 434–40 | date = September 2006 | pmid = 16959135 | doi = 10.1093/jat/30.7.434 | doi-access = free |issn=0146-4760 |oclc=5113088519}}</ref><ref name="Taylor 1965">{{cite book | vauthors = Taylor WI |title=The Alkaloids: Chemistry and Physiology |chapter=Chapter 9 The Iboga and Voacanga Alkaloids |publisher=Elsevier |volume=8 |date=1965 |isbn=978-0-12-469508-5 |doi=10.1016/s1876-0813(08)60048-2 |pages=203–235 |oclc=4922128763 |chapter-url=http://www.puzzlepiece.org/ibogaine/literature/taylor1965.pdf |via=Puzzle Piece}}</ref>
	== Formulations ==
			The ] (NIDA) began funding clinical studies of ibogaine in the United States in the early 1990s, but terminated the project in 1995.<ref>{{cite web |url=http://www.ibogaine.desk.nl/ibogaineresearch.ppt |format=PPT |date=2003-05-12 | vauthors = Doblin R |title=A Non-Profit Approach to Developing Ibogaine into an FDA-Approved Medication |url-status=dead |archive-url=https://web.archive.org/web/20121030115002/http://www.ibogaine.desk.nl/ibogaineresearch.ppt |archive-date=30 October 2012}}</ref> Data demonstrating ibogaine's efficacy in attenuating opioid withdrawal in drug-dependent human subjects was published by Alper ''et al.'' in 1999.<ref name="Alper_1999">{{cite journal <!-- Citation bot bypass--> |vauthors = Alper KR, Lotsof HS, Frenken GM, Luciano DJ, Bastiaans J |title=Treatment of Acute Opioid Withdrawal with Ibogaine |journal=The American Journal on Addictions |volume=8 |issue=3 |year=1999 |pmid=10506904 |doi=10.1080/105504999305848 |pages=234–242 |url=http://www.ibogaine.desk.nl/p234_s.pdf |url-status=dead |archive-url=https://web.archive.org/web/20020126202626/http://www.ibogaine.desk.nl/p234_s.pdf |archive-date=2002-01-26 |issn=1055-0496 |oclc=122057314}}</ref> A cohort of 33 patients were treated with 6 to 29&nbsp;mg/kg of ibogaine; 25 displayed resolution of the signs of opioid withdrawal from 24 hours to 72 hours post-treatment, but one 24-year-old female, who received the highest dosage, died. Mash ''et al.'' (2000), using lower oral doses (10–12&nbsp;mg/kg) in 27 patients, demonstrated significantly lower objective opiate withdrawal scores in heroin addicts 36 hours after treatment, with self-reports of decreased cocaine and opiate craving and alleviated depression symptoms. Many of these effects appeared sustainable over a one-month post-discharge follow-up.<ref>{{cite journal | vauthors = Mash DC, Kovera CA, Pablo J, Tyndale RF, Ervin FD, Williams IC, Singleton EG, Mayor M | title =Ibogaine: Complex Pharmacokinetics, Concerns for Safety, and Preliminary Efficacy Measures | journal = Annals of the New York Academy of Sciences | volume = 914 | issue = 1 | pages = 394–401 | date = September 2000 | pmid = 11085338 | doi = 10.1111/j.1749-6632.2000.tb05213.x | url = http://ibogaine.mindvox.com/Articles/Mash-01.pdf | citeseerx = 10.1.1.598.8242 | bibcode = 2000NYASA.914..394M | s2cid = 33436971 | access-date = 6 July 2006 | archive-url = https://web.archive.org/web/20070303181654/http://ibogaine.mindvox.com/Articles/Mash-01.pdf | archive-date = 3 March 2007 | url-status = dead |issn=0077-8923 |oclc=117596065}}</ref>
	In Bwiti religious ceremonies, the rootbark is pulverized and swallowed in large amounts to produce intense psychoactive effects. In Africa, iboga rootbark is sometimes chewed, which releases small amounts of ibogaine to produce a stimulant effect. Ibogaine is also available in a total alkaloid extract of the ''Tabernanthe iboga'' plant, which also contains all the other iboga alkaloids and thus has only about one-fifth the potency by weight as standardized ibogaine hydrochloride.<ref></ref>
			==Society and culture==
	Currently, pure crystalline ibogaine hydrochloride is the most standardized formulation. It is typically produced by the semi-synthesis from ] in commercial laboratories. Ibogaine has two separate ] centers which means that there are four different stereoisomers of ibogaine. These four isomers are difficult to ].<ref>Shulgin & Shulgin (1997), ], p. 487.</ref>
			=== Legal status ===
			{{Further|Legal status of ibogaine by country}}
	A synthetic derivative of ibogaine, ] (18-MC), is a selective α3β4 antagonist that was developed collaboratively by the neurologist Stanley D. Glick (Albany) and the chemist Martin E. Kuehne (Vermont).<ref>{{cite journal |author=Pace CJ, Glick SD, Maisonneuve IM, ''et al.'' |title=Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration |journal=Eur. J. Pharmacol. |volume=492 |issue=2-3 |pages=159–67 |year=2004 |month=May |pmid=15178360 |doi=10.1016/j.ejphar.2004.03.062 |url=http://linkinghub.elsevier.com/retrieve/pii/S0014299904003723}}</ref> This discovery was stimulated by earlier studies on other naturally occurring analogues of ibogaine such as ] and ] that showed these compounds also have anti-addictive properties.<ref>{{cite journal |author=Glick SD, Kuehne ME, Raucci J, ''et al.'' |title=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 |journal=Brain Res. |volume=657 |issue=1-2 |pages=14–22 |year=1994 |month=September |pmid=7820611 |url=http://linkinghub.elsevier.com/retrieve/pii/0006-8993(94)90948-2 |doi=10.1016/0006-8993(94)90948-2}}</ref><ref></ref>
			{{As of|2024}}, the legal status of ibogaine varies widely among countries, as it may be illegal to possess or use, may be legalized, may be ], or is under consideration for future legislation.<ref name="bbc">{{cite news |author1=Chesak J| title=What psychedelics legalisation and decriminalisation looks like around the world|url=https://www.bbc.com/future/article/20240320-legal-status-of-psychedelics-around-the-world |access-date=22 March 2024 |work=BBC |date=22 March 2024}}</ref>
			In the United States, although some cities and states have decriminalized psychedelic chemicals, plants and ]s, ibogaine has had minimal legislation, and remains illegal under federal law, as of 2023.<ref name=bbc/><ref name="siegel">{{cite journal |vauthors=Siegel JS, Daily JE, Perry DA, Nicol GE |title=Psychedelic Drug Legislative Reform and Legalization in the United States |journal=JAMA Psychiatry |volume=80 |issue=1 |pages=77–83 |date=January 2023 |pmid=36477830 |pmc=10069558 |doi=10.1001/jamapsychiatry.2022.4101 |issn=2168-622X |oclc=9705254062}}</ref> The US ] enforces ibogaine as a ] under the ].<ref name="drugs">{{cite web |title=Iboga (ibogaine)|publisher=Drugs.com |url=https://www.drugs.com/npp/iboga.html |access-date=22 March 2024 |date=21 April 2023}}</ref>
	==Pharmacology==
			===Treatment clinics===
	The pharmacology of ibogaine is quite complex, affecting many different ] systems simultaneously.<ref>P. Popik, P. Skolnick (1998). Pharmacology of Ibogaine and
			Ibogaine treatment clinics have emerged in ], ], ], the ], ], and ], all operating in what has been described as a "legal gray area".<ref name = "BBC">{{cite web | vauthors = Hegarty S | title=Can a hallucinogen from Africa cure addiction? | website=BBC News | date=2012-04-10 | url=https://www.bbc.com/news/magazine-17666589 | access-date=2024-07-24}}</ref><ref name = "maps">{{cite web | title=Ibogaine Therapy | website=Multidisciplinary Association for Psychedelic Studies - MAPS | date=1979-04-19 | url=https://maps.org/1979/04/18/ibogaine-therapy-t/ | access-date=2024-07-24}}</ref> ] also has treatment centers.<ref name=treatmentmag/> Covert, illegal neighborhood clinics are known to exist in the United States, despite active ] surveillance.<ref name="Hunter 2005">{{cite web | vauthors = Hunter A | title=Busted for Iboga | website=The Village Voice | date=2005-12-13 | url=https://www.villagevoice.com/busted-for-iboga/ | access-date=2024-07-24}}</ref> While clinical guidelines for ibogaine-assisted detoxification were released by the Global Ibogaine Therapy Alliance in 2015,<ref name="Clinical Guidelines">>{{cite web | title=Clinical Guidelines for Ibogaine-Assisted Detoxification | website=IBOGAINE SAFETY GUIDELINES | date=2020-10-28 | url=https://ibogaineguidelines.com/ | access-date=2024-07-24}}</ref><ref>{{Cite web|url=https://www.ibogainealliance.org/|title=The Global Ibogaine Therapy Alliance (GITA)|website=The Global Ibogaine Therapy Alliance|access-date=14 January 2016|archive-date=25 January 2016|archive-url=https://web.archive.org/web/20160125093313/http://www.ibogainealliance.org/|url-status=dead}}</ref> addiction specialists warn that the treatment of drug dependence with ibogaine in non-medical settings, without expert supervision and unaccompanied by appropriate psychosocial care, can be dangerous — and, in approximately one case in 300, potentially fatal.<ref name = "maps"/>
	Ibogaine-Related Alkaloids. </ref><ref>{{cite book |author=Kenneth R. Alper; Glick, Stanley D. |title=The alkaloids: chemistry and biology |publisher=Academic |location=San Diego |year=2001 |pages=1–38 |isbn=0-12-469556-6 |volume=56 |chapter=Ibogaine: A Review |url=http://ibogaine.org/ch01.pdf |format=PDF}}</ref>
	Because of its fairly low potency at any of its target sites, ibogaine is used in doses anywhere from 5&nbsp;mg/kg of body weight for a minor effect to 30&nbsp;mg/kg in the cases of strong polysubstance addiction. It is unknown whether doses greater than 30&nbsp;mg/kg in humans produce effects that are therapeutically beneficial, medically risky, or simply prolonged in duration. In animal neurotoxicity studies, there was no observable neurotoxicity of ibogaine at 25&nbsp;mg/kg, but at 50&nbsp;mg/kg, one-third of the rats had developed patches of neurodegeneration, and at doses of 75&nbsp;mg/kg or above, all rats showed a characteristic pattern of degeneration of ], mainly in the ].<ref>{{cite journal |author=Xu Z, Chang LW, Slikker W, Ali SF, Rountree RL, Scallet AC |title=A dose-response study of ibogaine-induced neuropathology in the rat cerebellum |journal=Toxicol. Sci. |volume=57 |issue=1 |pages=95–101 |year=2000 |month=September |pmid=10966515 |url=http://toxsci.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=10966515 |doi=10.1093/toxsci/57.1.95}}</ref> While caution should be exercised when extrapolating animal studies to humans, these results suggest that neurotoxicity of ibogaine is likely to be minimal when ibogaine is used in the 10–20&nbsp;mg/kg range typical of drug addiction interruption treatment regimes, and indeed death from the other pharmacological actions of the alkaloids is likely to occur by the time the dose is high enough to produce consistent neurotoxic changes.<ref name=Kontrim06/><ref>{{cite journal |author=Maciulaitis R, Kontrimaviciute V, Bressolle FM, Briedis V |title=Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review |journal=Hum Exp Toxicol |volume=27 |issue=3 |pages=181–94 |year=2008 |month=March |pmid=18650249 |doi=10.1177/0960327107087802 |url=http://het.sagepub.com/cgi/pmidlookup?view=long&pmid=18650249}}</ref>
	=== Metabolites ===		=== Media ===
			==== Documentary films ====
			* {{ill|Detox or Die|wd=Q123678894|italic=yes|short=yes}} (2004). Directed by David Graham Scott. Scott begins videotaping his heroin-addicted friends. Before long, he himself is addicted to the drug. He eventually turns the camera on himself and his family. After 12 years of debilitating, painful dependence on methadone, Scott turns to ibogaine. Filmed in Scotland and England, and broadcast on ] as the third installment in the documentary series ''One Life''.<ref name="Detox or Die">{{cite web | title=Detox or Die |series=One Life | website=BFI | date=2004-06-08 | url=https://collections-search.bfi.org.uk/web/Details/ChoiceFilmWorks/150690331 | access-date=2024-07-24}}</ref>
			* {{ill|Ibogaine: Rite of Passage|wd=Q123678902|italic=yes|short=yes}} (2004). Directed by Ben Deloenen. Cy, a 34-year-old heroin addict, undergoes ibogaine treatment with Dr. Martin Polanco at the Ibogaine Association, a clinic in Rosarito, Mexico. Deloenen interviews people formerly addicted to heroin, cocaine, and methamphetamine, who share their perspectives about ibogaine treatment. In Gabon, a ] woman receives iboga root for her depressive malaise. Deloenen visually contrasts this Western, clinical use of ibogaine with the Bwiti use of iboga root, but emphasizes the Western context.<ref name="IFFR EN">{{cite web |title=Ibogaine: Rite of Passage |website=IFFR EN |date=January–February 2005 |url=https://iffr.com/en/iffr/2006/films/ibogaine-rite-of-passage |access-date=2024-09-02}}</ref>
			* {{ill|Facing the Habit|wd=Q123678903|italic=yes|short=yes}} (2007). Directed by Magnolia Martin. Martin's subject is a former millionaire and stockbroker who travels to Mexico for ibogaine treatment for heroin addiction.<ref name="SFFFF 2007">{{cite web |title=The 2007 FFF Winners |website=San Francisco Frozen Film Festival (SFFFF) |date=2007-07-13 |url=https://www.frozenfilmfestival.com/2007 |access-date=2024-09-02 |at=Facing the Habit (WORLD PREMIERE)}}</ref>
			* ''Tripping in Amsterdam'' (2008). In this short film directed by Jan Bednarz, Simon "Swany" Wan visits Sara Glatt's iboga treatment center in Amsterdam.<ref>{{cite web |url=http://current.com/green/89043771_tripping-in-amsterdam.htm |title=Tripping in Amsterdam |author=<!--Staff writer(s) no by-line.--> |date=23 June 2008 |publisher=Current.com |access-date=7 April 2013 |archive-url=https://web.archive.org/web/20121011061542/http://current.com/green/89043771_tripping-in-amsterdam.htm |archive-date=11 October 2012 |url-status=dead }}</ref> ] broadcast the documentary in 2008 as part of their "Quarter-life Crisis" programming roster.
			* {{ill|I'm Dangerous with Love|wd=Q123678904|italic=yes|short=yes}} (2009). Directed by Michel Negroponte. Negroponte examines ]'s long, clandestine career of treating heroin addicts with ibogaine.<ref name="Lanthier 2011">{{cite web |last=Lanthier |first=Joseph Jon |title=Review: I'm Dangerous with Love |website=Slant Magazine |date=2011-01-10 |url=https://www.slantmagazine.com/film/im-dangerous-with-love/ |access-date=2024-09-02}}</ref>
			* One of the five segments of "Hallucinogens DMT" (2012), ], Episode 4 of '']'' on ], a former heroin user treats addicts with ibogaine in Canada. He himself used ibogaine to stop his abuse of narcotics.{{citation needed|date=September 2024}}
			* The "Underground Heroin Clinic" segment of "Addiction" (2013). ], episode 7 of the ] documentary series '']'' examines the use of ibogaine to interrupt heroin addiction.<ref name="VICE 2013-05-17">{{cite web |title=A New Episode of Our TV Show Is Airing Tonight |website=VICE |date=2013-05-17 |url=https://www.vice.com/en/article/a-new-episode-of-our-tv-show-is-airing-tonight/ |access-date=2024-09-09}}{{primary source inline|date=September 2024}}</ref><ref>{{YouTube|id=mkkMhKEfOqw|title=Tobaccoland & Underground Heroin Clinic {{!}} VICE on HBO (Season 1, Episode 7)}}</ref>
			* ''The Ibogaine Safari'' (2014). A documentary by filmmaker Pierre le Roux which investigates the claims of painless withdrawal from opiates such as ]/heroin in South Africa by taking several addicts on an adventure "safari" while taking ibogaine. The documentary won the award for 'Best Documentary Short' at the 2014 ].<ref name="Ibogaine Media">{{cite web |title=Ibogaine Media |website=ibogaworld.com |date=2019-11-13 |url=https://www.ibogaworld.com/ibogaine-media/ |access-date=2024-09-09}}{{better source needed|date=September 2024|reason=ibogaworld.com is an ibogaine advocate}}</ref><ref>{{YouTube |id=vRTDpX3Aek4 |title=The Ibogaine Safari}}</ref>
			* {{ill|Iboga Nights|wd=Q130237268|short=yes|italic=yes}} (2014). Directed by David Graham Scott.<ref name="Iboga Nights 2015-07-31">{{cite web |title=Iboga Nights |website=Top Documentary Films |date=2015-07-31 |url=https://topdocumentaryfilms.com/iboga-nights/ |access-date=2024-09-04}}</ref>
			* {{ill|Dosed (2019 film)|lt=Dosed|wd=Q130243329|italic=yes|short=yes}} (2019). A documentary by Tyler Chandler and Nicholas Meyers. Synopsis- After years of no success with prescription drugs, a suicidal Adrianne seeks help from underground healers with her depression, anxiety, and opioid addiction by utilizing illegal psychedelics like magic mushrooms and iboga.<ref name="Kenigsberg 2020">{{cite web |last=Kenigsberg |first=Ben |title='Dosed' Review: The Case for Plant-Based Recovery |website=The New York Times |date=2020-03-19 |url=https://www.nytimes.com/2020/03/19/movies/dosed-review.html |access-date=2024-09-06}}</ref>
			* "Synthetic Ibogaine - Natural Tramadol" (2021). This episode of the documentary series '']'' on ], follows a struggling local addict to an ibogaine ritual.<ref name="Phelps 2021">{{cite web |last=Phelps |first=Hollis |title=Hulu's 'Hamilton's Pharmacopeia' Shows That We Can No Longer Ignore Connections Between Religion and Drugs |website=Religion Dispatches |date=2021-06-21 |url=https://religiondispatches.org/hulus-hamiltons-pharmacopeia-shows-that-we-can-no-longer-ignore-connections-between-religion-and-drugs/ |access-date=2024-09-08}}</ref>
			* {{ill|Lamar Odom Reborn|wd=Q130267969|short=yes|italic=yes}} (2022). A documentary by ], in which famous ] athlete (and former '']'' star) ] seeks out ibogaine and other therapies to heal PTSD, anxiety, and addiction.<ref name="Hernandez 2021">{{cite web |last=Hernandez |first=Victoria |title=Lamar Odom prepares to fight Aaron Carter, but first he fought PTSD |website=Los Angeles Times |date=2021-06-10 |url=https://www.latimes.com/sports/lakers/story/2021-06-10/lamar-odom-fight-aaron-carter-ptsd-ketamine-ibogaine-documentary |access-date=2024-09-09}}</ref>
			==== Print media ====
	Ibogaine is ] in the human body by ] 2D6, and the major metabolite is ] (12-hydroxyibogamine). Noribogaine is most potent as a ] and acts as a moderate κ- and weak µ-] full agonist and therefore, also has an aspect of an ] similar to compounds like ]. It is possible that this action of noribogaine at the kappa opioid receptor may indeed contribute significantly to the psychoactive effects attributed to ibogaine ingestion; ], another plant recognized for its strong hallucinogenic properties, contains the chemical ] which is a highly selective kappa opioid agonist. Both ibogaine and noribogaine have a ] of around two hours in the rat,<ref>{{cite journal |author=Baumann MH, Rothman RB, Pablo JP, Mash DC |title=In vivo neurobiological effects of ibogaine and its O-desmethyl metabolite, 12-hydroxyibogamine (noribogaine), in rats |journal=J. Pharmacol. Exp. Ther. |volume=297 |issue=2 |pages=531–9 |date=1 May 2001|pmid=11303040 |url=http://jpet.aspetjournals.org/cgi/content/full/297/2/531 }}</ref> although the half-life of noribogaine is slightly longer than the parent compound. It is proposed that ibogaine is deposited in fat and metabolized into noribogaine as it is released.<ref>{{cite journal |author=Hough LB, Bagal AA, Glick SD |title=Pharmacokinetic characterization of the indole alkaloid ibogaine in rats |journal=Methods Find Exp Clin Pharmacol |volume=22 |issue=2 |pages=77–81 |year=2000 |month=March |pmid=10849889 |url=http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=6&p_RefId=796066 |doi=10.1358/mf.2000.22.2.796066}}
			While in Wisconsin covering the primary campaign for the ], ] ] submitted a satirical article to '']'' accusing ] candidate ] of being addicted to ibogaine. Many readers, and even other journalists, did not realize that the ''Rolling Stone'' piece was facetious. The ibogaine assertion, which was completely unfounded, did significant damage to Muskie's reputation, and was cited as a factor in his loss of the nomination to ].<ref name="Remembering Ed Muskie">{{cite web | title=Online NewsHour: Remembering Ed Muskie | website=pbs.org | date=1999-02-03 | url=http://www.pbs.org/newshour/bb/remember/muskie_3-26.html | archive-url=https://web.archive.org/web/19990427124548/http://www.pbs.org/newshour/bb/remember/muskie_3-26.html | archive-date=27 April 1999 | url-status=dead | access-date=17 January 2023 }}</ref> Thompson later said he was surprised that anyone believed it.<ref>{{cite AV media | vauthors = Gibney A |author-link= Alex Gibney |year=2008 |title=] |medium= Motion picture |oclc=259718859}}</ref> The article is included in Thompson's post-election anthology, '']'' (1973).<ref>{{Cite book |year=1973 |title=Fear and Loathing on the Campaign Trail '72 |isbn=978-0-87932-053-9 |oclc=636410 |pages= |publisher=Straight Arrow Books |url=https://archive.org/details/fearloathingonth00thom/page/150 }}</ref>
	</ref> Noribogaine shows higher plasma levels than ibogaine and may therefore be detected for longer periods of time than ibogaine. Noribogaine is also more potent than ibogaine in rat ]s when tested for the subjective effects of ibogaine.<ref>{{cite journal |author=Zubaran C, Shoaib M, Stolerman IP, Pablo J, Mash DC |title=Noribogaine generalization to the ibogaine stimulus: correlation with noribogaine concentration in rat brain |journal=Neuropsychopharmacology |volume=21 |issue=1 |pages=119–26 |year=1999 |month=July |pmid=10379526 |doi=10.1016/S0893-133X(99)00003-2 |url=http://www.nature.com/npp/journal/v21/n1/abs/1395327a.html}}</ref> Noribogaine differs from ibogaine in that it contains a ] instead of a ] ] at the 12 position.
			Author and ] ] co-wrote the 1997 book ''The Ibogaine Story''.<ref>{{cite book | vauthors = Beal D, De Rienzo P | title = The Ibogaine Story: Report on the Staten Island Project | publisher = Autonomedia | date = 1997 | isbn = 1570270295 }}</ref>
	== Research ==
			American author ] wrote about his own experience of ibogaine in his book '']'' (2002),<ref>{{Cite book | vauthors = Pinchbeck D |author-link= Daniel Pinchbeck |title= Breaking Open the Head: A Psychedelic Journey into the Heart of Contemporary Shamanism |publisher=Broadway Books |year=2002 |isbn=9780767907422 |oclc=50601753}}</ref> and in a 2003 article for '']'' titled "Ten years of therapy in one night".<ref>{{cite news | vauthors = Pinchbeck D |author-link= Daniel Pinchbeck |date= 19 September 2003 |title= Ten years of therapy in one night |url= https://www.theguardian.com/books/2003/sep/20/booksonhealth.lifeandhealth |newspaper= ] |location= London |access-date=15 December 2013}}</ref>
	An ibogaine research project was funded by the US ] in the early 1990s. The National Institute on Drug Abuse (NIDA) abandoned efforts to continue this project into clinical studies in 1995, citing other reports that suggested a risk of brain damage with extremely high doses and fatal heart arrhythmia in patients having a history of health problems<!-- What is the basis for this claim? Is there a reference to confirm this? -->,{{Citation needed|date=November 2009}} as well as inadequate funding for ibogaine development within their budget. However, NIDA funding for ibogaine research continues in indirect grants often cited in peer-reviewed ibogaine publications.
			Author and musician ] based his debut novel '']'' on his real-life experiences with heroin addiction and an ibogaine clinic in Mexico.<ref>{{cite book| vauthors = Rickly G |author-link= Geoff Rickly |title= Someone Who Isn't Me |url= https://www.rosebooks.co/someone-who-isnt-me}}</ref>
	In addition, after years of work and a number of significant changes to the original protocol, on August 17, 2006, a ]-sponsored research team received "unconditional approval" from a Canadian Institutional Review Board (IRB) to proceed with a long-term observational case study that will examine changes in substance use in 20 consecutive people seeking ibogaine-based therapy for opiate dependence at the Iboga Therapy House in British Columbia, Canada.
	== Legal status ==		==== Television drama ====
			Ibogaine factors into the stories of these episodes from television drama series:
	Ibogaine and its ] were regulated by the U.S. ] in 1967 pursuant to its enhanced authority to regulate ], ], and ] granted by the 1965 Drug Abuse Control Amendments (DACA) to the ]. In 1970, with the passage of the ], it was classified as a ]-controlled substance in the United States, along with other psychedelics such as ] and ]. Since that time, several other countries, including Sweden, Denmark, Belgium, and Switzerland, have also banned the sale and possession of ibogaine. Although illegal in these countries, ibogaine has been used by hundreds of drug dependents in the United States and abroad. ], a pioneer in bringing awareness to ibogaine's success in helping long-time drug dependents to quit their addiction, and others have been offering willing persons the treatment. In the Czech Republic and Slovenia, taking advantage of less prohibitive legal systems, ibogaine has been applied to people coming from the U.S. and other countries seeking a safe haven.
			* {{Cite episode |title=Patent Pending |series=FBI: Most Wanted |series-link=FBI: Most Wanted |network=] |date=15 November 2022 |season=4 |number=6 }}
	Ibogaine is not the subject of any regulation in Canada.<ref>Johnson, Gail straight.com (January 2, 2003) </ref><ref>, Canadian Department of Justice website. Accessed 5 November 2009.</ref> In Sweden, a non-profit foundation was formed in early 2006 to address the issue of providing ibogaine for addiction interruption within established drug treatment care.<ref></ref>
			* {{Cite episode |title=Via Negativa |episode-link=Via Negativa (The X-Files) |series=The X-Files |series-link=The X-Files |network=] |date=17 December 2000 |season=8 |number=7 }}
			* {{Cite episode |title=Getting Off |series=CSI: Crime Scene Investigation |series-link=CSI: Crime Scene Investigation |network=] |date=26 February 2004 |season=4 |number=16 }}
			* {{Cite episode |title=Users |series=Law & Order: Special Victims Unit |series-link=Law & Order: Special Victims Unit |network=] |date=4 November 2009 |season=11 |number=7 }}
			* {{Cite episode |title=Echoes |series=Nikita |series-link=Nikita (TV series) |network=] |date=24 February 2011 |season=1 |number=16 }}
			* {{Cite episode |title=One Last Time |episode-link=One Last Time (Homeland) |series=Homeland (TV series) |series-link=Homeland (TV series) |network=]|date=24 November 2013 |season=3 |number=9}}
			* {{Cite episode |title=Bon Voyage |series=Graceland (TV series) |series-link=Graceland (TV series) |network=] |date=6 August 2015 |season=3 |number= 7 }}
	==Hunter S Thompson==		==== Radio ====
			* {{Cite episode |title=Sink or Swim. Act Two. I'm Not a Doctor But I Play One at the Holiday Inn. |series=This American Life |series-link=This American Life |date=1 December 2006 |number=321 }} — A former heroin addict realizes that he wants to help other addicts kick their habits. The problem is, he wants to do this using a hallucinogenic drug - ibogaine - that is completely illegal, and which requires medical expertise he doesn't have.<ref>{{Cite episode |title=Sink or Swim. Act Two. I'm Not A Doctor But I Play One At The Holiday Inn. |url=https://www.thisamericanlife.org/321/sink-or-swim |access-date=17 August 2015 |series=This American Life |series-link=This American Life | vauthors = Olkowski L, Kay T |date=1 December 2006 |number=321 |minutes=16 }}</ref>
	In 1972, journalist ] accused democratic candidate ] of being addicted to ibogaine in a satirical piece while covering the Wisconsin primaries of the ] for '']'' magazine. Many readers, and even other journalists, did not realize that Thompson was being facetious. The claim, of course, was completely unfounded, and Thompson himself is documented in the movie '']'' discussing the self-fabricated joke of Muskie's alleged ibogaine use and his surprise that anyone actually believed the claim.<ref>The original article was republished as ''Fear and Loathing on the Campaign Trail '72'' (New York: Popular Library, 1973), pp. 150-154</ref>
			==Research==
	==I'm Dangerous With Love==
			=== Addiction treatment ===
			The most-studied therapeutic effect of ibogaine is the possible reduction or elimination of ] to ]s. Research suggests that ibogaine may be useful in treating dependence on other substances such as ], ], and ], and may affect compulsive behavioral patterns not involving substance abuse or chemical dependence.{{medical citation needed|date=March 2024}} Researchers note that there remains a "need for systematic investigation in a conventional clinical research setting."<ref name=Alper/>
			Many users of ibogaine report experiencing visual phenomena during a waking dream state, such as instructive replays of life events that led to their addiction, while others report therapeutic ]ic visions that help them conquer the fears and ]s that might drive their addiction. It is proposed that intensive counseling, therapy, and aftercare during the interruption period following treatment is of significant value. Some individuals require a second or third treatment session with ibogaine over the course of 12 to 18 months. A minority of individuals relapse completely into opiate addiction within days or weeks.<ref>{{Cite journal | vauthors = Lotsof HS |year=1995 |url=http://ibogaine.desk.nl/clin-perspectives.html |title=Ibogaine in the Treatment of Chemical Dependence Disorders: Clinical Perspectives |journal=MAPS Bulletin |volume=3 |pages=19–26 |url-status=dead |archive-url=https://web.archive.org/web/19970122031859/http://www.ibogaine.desk.nl/clin-perspectives.html |archive-date=22 January 1997|df=dmy-all}}</ref>
	A 2009 feature documentary, ''I'm Dangerous with Love'' by filmmaker ], covered the work of ] and his long-running underground ibogaine treatment for heroin addiction.<ref> (official site). .</ref><ref>Scheck, Frank. , ], January 12, 2011. .</ref>
			=== Psychotherapy ===
			Ibogaine was used as an adjunct to ] by ], documented in his book ''The Healing Journey''.<ref>{{cite book | vauthors = Naranjo C |title=The healing journey: new approaches to consciousness |publisher=Pantheon Books |location=New York |year=1973 |isbn=978-0-394-48826-4 |chapter-url=http://www.ibogaine.desk.nl/naranjo.html |chapter=V, Ibogaine: Fantasy and Reality |pages= |access-date=15 August 2012 |url=https://archive.org/details/healingjourneyne00nara/page/197 }}</ref> He was awarded patent {{patent|CA|939266}} in 1974.
	== See also ==		== See also ==
	* ]		* ]
			* ]
			* ]
			* ]
			* ]
			* ]
	== References ==		== References ==
	{{Reflist|2}}		{{Reflist|30em}}
	=== Further reading ===
	* ] writes of his own experience with ibogaine (among other psychoactives) in '']''.
	* is a documentary film about the use of ibogaine in Bwiti tradition and addiction medicine.
	== External links ==		== External links ==
			* {{cite web |title=News on ibogaine |website=National Center for Biotechnical Information |date=2020-03-19 |url=https://www.ncbi.nlm.nih.gov/search/research-news/8973/ |access-date=2024-09-06}}
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