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Ibogain Faktatråd.

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Fru-Lindgren
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Joined: 12 May 2006
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PostPosted: Fri 19 May, 2006 15:50    Post subject: Ibogain Faktatråd. Reply with quote

Ibogain, Iboga.

Innehåll

• Generell information
• Växter som innehåller Ibogain
• Effekter
• Neuropsykofarmakologi
• Kemi
• Externa länkar


Generell information
Ibogain är en ganska okänt ämne med antiaddiktiva och hallucinogena effekter som återfinns i några växtarter som växer i Afrika.

Ibogain har visat sig vara ett mycket effektivt medel för att avsluta ett missbruk av opiater (heroin, morfin) men har även givit goda resultat i botandet av alkohol, kokain och nikotinberoende vid djurstudier. Efter en ibogainbehandling så är suget efter heroin borta, men man bör ta en behandling till, efter någon/några veckor för att effekten ska bli permanentare.

Läkemedelsbolagen verkar inte vara alltför intresserade av en substans som bara är tänkt att säljas för konsumtion vid 1-3 tillfällen per person och liv som maximum. Sedan verkar ju Ibogain i vissa aspekter dessutom vara ett *läkemedel* och inte någon symptomlindrare som de flesta läkemedel i dag faktiskt är. Dessutom kanske andra luckrativa marknader försvinner, tex subutex & metadon marknaden. Patenteringsbarheten och det kortsiktiga vinstintresset verkar ju vara en större drivkraft för vissa individer och företag än medmänsklighet!

Är Ibogain ett narkotikum av typ I?
Quote:

Klassningen av preparat görs av Läkemedelsverket som upprättar och kungör förteckningar över narkotika. Den senaste heter "LVFS (1997:12), ändrad och omtryckt 2000:7, ändrad 2001:4 och 2002:4, om förteckningar över narkotika". Klassningen bestäms till stor del av internationella överenskommelser, men därutöver finns det i Narkotikastrafflagen (1968:64) ett antal kriterier som Läkemedelsverket ska grunda sin bedömning på. För att klassas som narkotika ska ett ämne anses vara hälsofarligt, beroendeframkallande eller euforiserande. I den officiella klassningen finns det fem undergrupper.

Förteckning I: Droger som i Sverige anses sakna medicinskt värde, t.ex. heroin, kokain, cannabis och hallucinogener. Dessa är förbjudna att tillverka, importera eller sälja.


Ibogain är narkotikaklassad i USA, Belgien, Sverige, Schweiz och Danmark. Narkotikaklassningen av ibogain i såsom typ I narkotikum förefaller inte ha någon större grad av logisk relevans, då typ I narkotika per definition ska sakna värde såsom medicinsk humanläkemedel, vilket man inte kan säga att ibogain gör, ivarjefall inte om man tittar på de vetenskapliga resultaten. Ibogainmissbruk verkar vara okänt av vetenskapen, det hjälper dock till mot vissa typer av missbruk.


Växter som innehåller Ibogain
Tabernanthe iboga
Voacanga africana (innehåller inte Ibogain, men väldigt närbesläktade ämnen)
Fler arter inom Tabernanthe och Voacanga är också aktiva.
Släktet Tabernaemontana (Små mängder Ibogain)


Effekter
Ibogains effekter på beroenden av opiattyp verkar ganska klara, de flesta upplever ett klart minskat sug efter opiater samt att den större delen av abstinenssymptomen verkar försvinna. Djurförsök indikerar också att Ibogain skulle kunna vara verksamt vid andra typer av beroenden, alkohol, amfetamin kokain och nikotin är några av de ämnen som nämnts när det gäller kemiskt beroende.

I små doser stimulerande, i högre doser hallucinogen. Effekten av Ibogain är intensiv och håller i sig från 24 timmar till flera dygn. Det är av flera skäl inte rekomendabelt att ta ibogain utanför sjukhusmiljö eller liknande.

(with 200 mg, orally) "Subjectively, the most unpleasant symptoms were the anxiety, the extreme apprehension, and the unfamiliar mood associated with visual and bodily hallucinations. The visual hallucinations appeared only in the dark and consisted of blue disks dancing up and down the walls. Dysesthesia of the extremities. a feeling of light-weightedness, and hyperacusis were other symptoms noted. Autonomic signs, such as dryness of the mouth, increased perspiration, slight pupillary dilation, and increase in pulse rate, as well as extrapyramidal syndromes (fine tremors, slight ataxia, enhanced tendon reflexes and clonus) were also present. The peak effect was reached at about 2 hours after swallowing the drug; it subsided gradually, leaving as a residue complete insomnia. No undesirable after-effects, such as exhaustion or depression occurred." - Alexander Shulgin

För avgiftning av heroinister används doser på 1-2g Ibogain. Vilket är en extremt hög dos!!


Neuropsykofarmakologi
Antiaddiktion: Ibogainets effekt på missbruk av alkoholtyp verkar främst vara medierad via ökningar av GDNF* i VTA (ventral tegmental area) som förser bland annat nucleus accumbens med dopamin & dopaminstödjande celler) Det ligger nära tillhand att spekulera i att Ibogainets effekter på andra typer av missbruk även medieras via denna funktion. GDNF (*Glia derived neurotropic factor), är som namnet antyder en nervtillväxtfaktor. tillförsel i hjärnan av denna tillväxtfaktor i VTA området ger en liknande effekt på försökdjurs missbruksvanor som Ibogain.

Hallucinogenitetens farmakologi: För dess verkningar är det svårt att dra någon definitiv slutsats, eftersom det engagerar de flesta transmittosystemen direkt eller indirekt. Se länken nedan om Ibogains farmakologi

Övrigt: Många användare rapporterar att de ”ser” liknande fenomen, som instruktiva repriser av livshändelser vilken ledde dem in på nuvarande spår, medans andra rapporterar en terapeutisk shamansk vision som hjälper dem att övervinna rädsla och negativa känslor som driver på missbruket.
De som behandlats med Ibogain brukar ofta berätta om ett omedelbart slut på de potentiellt livshotande abstinenssymptomen!

Biverkningar
Biverkningsprofilen är att anse som ofullständig, då flera orsakssamband är oklara. Dödliga fall med hjärtarrytmier har rapporterats under Ibogainterapi, andra studier föreslår att det finns en risk för hjärnskada vid extremt höga doser. Purkinjeceller verkar vara extra känsliga för denna effekt.

Dödsfall:Det har antagits att man löper över 1% risk att dö vid doser över 15 mg/per kilo kroppsvikt vid bruk utanför sjukhusmiljö. De flesta dödsfallen som finns dokumenterade verkar ha inträffat vid höga doser till missbrukare. De dokumenterade dödsfallen är på sannolika grunder bara en liten del av den verkliga siffran, då man kan anta att en känd heroinmissbrukare inte röner någon större förvåning då fallet bordläggs hos obducenten. Och vem letar i detta fall efter Ibogain eller relaterade alkaloider? Man gör verkligen klokt i att rena sitt hela system innan bruk så att inga andra aktiva droger finns i systemet. För heroinisten föreslås absolut minst 24 timmars uppehåll från drogen, för metadon absolut minst 48 timmars avhållsamhet, längre är givetvis säkrare och bättre. Dödsfall har inträffat till följd av kvävning av egna spyor 40 timmar efter intag av Ibogain. Ingen verkar riktigt veta varför vissa personer dör. – Men en sak börjar klarna – Ibogain anses idag inte lika ofarlig som det gjordes för 5 -6 år sedan. Förhoppningsvis vet man mycket mer om 5 år än nu (maj 2006) Det finns all anledning att vara mycket försiktig med en substans som kan generera så mycket åt båda hållen.

Ataxi vilket karakteriseras av skakiga, osäkra rörelser samt dålig balans. Tremor skakningar. Kväljningar, det vänder sig i magen, illamående, lätta kramper. Fall av cirkulationspåverkan har noterats.

Det är sålunda ingen drog som smickrar in sig sött hos missbrukaren, utan snarare en ganska skakig resa som inte uppskattas av narkomanerna. Kanske är det just därför som ibogainmissbruk inte är känt av vetenskapen.

Man ska också hålla i minnet att Ibogain är en experimentell och kraftfull drog så att det är på många sätt vist att läsa igenom Manual for Ibogaine Therapy av Howard S. Lotsof & Boaz Wachtel samt att läkarundersöka sig innan, som absolut minsta försiktighetsåtgärd.

Pga av Ibogainets biverkningsprofil har blickarna riktats mot den kemiska kusinen 18-methoxycoronaridine, vilken saknar Ibogainets biverkningar. ingen forskning av större omfattning verkar dock pågå kring denna substans.

Länkar
Manual for Ibogaine Therapy av Howard S. Lotsof & Boaz Wachtel
http://www.ibogaine.org/manual.html

TiHKAL #25 IBOGAINE
http://www.erowid.org/library/books_online/tihkal/tihkal25.shtml

Erowid Ibogaine Vault
http://www.erowid.org/chemicals/ibogaine/ibogaine.shtml

Ibogain & GDNF
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids==15659598

Ten years of therapy in one night
http://books.guardian.co.uk/departments/healthmindandbody/story/0,,1045038,00.html

Pharmacology of Ibogaine and Ibogaine-Related Alkaloids
http://www.ibogaine.org/alkaloids.html

18-methoxycoronaridine
http://www.ibogaine.org/18_mc.ppt

Life after Ibogaine: An exploratory study of the long-term effects of ibogaine treatment on drug addicts http://www.ibogaine.org/ibogaine_udi_bastiaans.pdf

Mer om ibogainbehandling
http://www.ibeginagain.org


Last edited by Fru-Lindgren on Sun 21 May, 2006 19:50; edited 2 times in total
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Masque
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Joined: 14 May 2006
Posts: 467
Topics: 67

PostPosted: Fri 19 May, 2006 21:43    Post subject: Reply with quote

Fler länkar (jag klistrar denna tråden också)


The Ibogaine Story: Report on the STATEN ISLAND PROJECT
http://www.cures-not-wars.org/ibogaine/iboga.html

Om Ibogain på engelska wikipedia:
http://en.wikipedia.org/wiki/Ibogaine
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BellaDonna



Joined: 15 May 2006
Posts: 4
Topics: 1

PostPosted: Tue 23 May, 2006 16:18    Post subject: Reply with quote

Denna forskningsrapport är tagen ur tidskriften NEXUS , årg. 1 nr. 2 1998


IBOGAIN
BOTAR NARKOMANI

sammanställt och redigerat ur olika källor, däribland Howard S. Lotsofs
internethemsida om ibogain: www.ibogaine.org/index.html

En alkaloid som utvinns ur växtriket och som kallas ibogamin eller mer allmänt ibogain (engelska: ibogaine) har visat sig kunna bryta den onda cirkeln av narkotikaberoendet och visat sig vara särskilt effektivt i att bekämpa beroende av opium och dess derivat heroin, liksom kokain, andra narkotika och även alkohol.

Den är oerhört löftesrik, eftersom den behandlar missbrukets både fysiologiska och psykologiska problem, ty den både påskyndar frigörelseprocessen och hjälper missbrukare att inse den grundläggande orsaken till missbruket och så återta kontrollen över det egna livet.
Ibogain utvinns i första hand ur den tropiska växten Tabernanthe iboga, som är inhemsk i Västafrika nära ekvatorn, men det har också isolerats ur Tabernanthe manii, Ervatamia yunnanensis och Ervatamia orientalis, buskar som alla är medlemmar av familjen Apocynacae. Ervatamia orientalis växer främst i Gordon Vale i nordligaste Queensland i Australien, ett kustområde i monsunbältet kännetecknat av klängväxtbuskage. Analys av bladen av just denna art har visat betydande halter av ibogain och en allmän alkaloidprofil som speglar tabernantheväxten, Tabernanthe iboga.
Tabernanthe är en växt som av hävd nyttjats av stammar i Kongo- och Gabonregionerna i Västafrika, där man sätter värde på den för dess många medicinska egenskaper liksom dess rusgivande, sexuellt stimulerande och hallucinationsframkallande egenskaper, som yttrar sig när delar av växten intas i stora doser för ceremoniella ändamål. Inom bwitistammen tuggar man tabernantheroten under de långa jaktexpeditionerna för att minska trötthet och sömnbehov. Stammarna mitsogo-bwiti och fang-bwiti i Gabon uppges nyttja växten i sina invigningsritualer för båda könen. I förberedelserna inför ceremonin krävs av deltagarna att de intar en större dos genom att länge tugga tabernantheblad och -rotbark. De följande upplevelserna har liknats vid de stadier som iakttagits i en studie av 150 människor, som berättat om s.k. nära-döden-upplevelser (NDU) i tillstånd av klinisk död.
Tabernantheroten fördes ut ur Gabon första gången år 1864 men beskrevs först år 1889 av Naturhistoriska museet i Paris. En kristalliserad alkaloid isolerades först av Dybrowsky och Landrin år 1901 och kallades ibogain. Åren 1901-05 gjorde många franska farmakologer studier av roten, varvid de fastställde ibogainets kliniska effektivitet som hjärtstimulerande medel och som ett medel mot neurasteni och allmän svaghet. Det var emellertid först år 1939 som man återupptog det seriösa studiet av den farmakodynamiska och terapeutiska potential denna alkaloid har. Och på grund av dess hallucinogena egenskaper fann tabernantheroten vägen in i 60-talets drogkultur och klassades till sist, 1972, som hallucinogent ämne.
År 1962 prövade heroinisten Howard Lotsof ibogain som ett nytt sätt att bli "hög". Efter en hallucinatorisk upplevelse, som varade i ett och ett halvt dygn, kände han inte längre behov av heroin. Det mest anmärkningsvärda var att han inte heller led av några av de abstinensbesvär som normalt förknippas med heroin. Lotsof berättade om ibogain för sex andra missbrukare, som prövade drogen. Fem av dem förlorade sitt begär efter heroin. Dessa häpnadsväckande resultat drev Lotsof till att forska vidare om ibogainets verkan. Från mitten av 80-talet till början av 90-talet sökte och erhöll Lotsof flera patent på användningen av ibogain i behandlingen av narkotika- och alkoholmissbruk.
I Nederländerna har man sedan 1990 behandlat 40 missbrukare under kontrollerade förhållanden. USAs federala läkemedelsstyrelse Food and Drug Administration (FDA) har dock inte godkänt ibogainet för användning i landet, och drogen är i USA olaglig.

MEDICINSK BEHANDLING AV KEMISKT DROGBEROENDE

Ibogain är inget surrogat för narkotika eller stimulantia, och den ges till patienten vid ett enstaka tillfälle, s.k. single administration modality (SAM). Det är ett medel som avbryter det kemiska beroendet. I vissa fall kan man behöva upprepa behandlingen, tills den ibogainbehandlade patienten förmår lämna vissa betingade reaktioner, som hänger samman med den drog han eller hon missbrukar. Tidigt framkomna data utvisar att många patienter kan behöva återkommande behandling under cirka två års tid för att nå sitt mål att långsiktigt avstå från narkotika och stimulantia. Majoriteten av dem som behandlats med ibogain förblir fria från kemiskt beroende under en tid av tre till sex månader efter en enda dos. Cirka 10 procent av dem som behandlats med ibogain förblir fria från kemiskt beroende i två eller fler år efter en enda behandling, och lika många återfaller i missbruk inom två veckor efter behandlingen. Flerfaldig användning av ibogain under en viss tid är i allmänhet mer verksam, om man vill förlänga tiden av avhållsamhet.
Den första uppgiften om att ibogain har verkan att bryta opiatberoende lämnades i US Patent No. 4,499,096 (Lotsof, 1985), att bryta kokainberoende i US Patent No. 4,587,243 (Lotsof, 198G) och flerdrogberoende i US Patent No. 5,124,994 (Lotsof, 1992).
De första studier, där ibogainets inverkan på kokain- och heroinberoende visades, utförde Howard S. Lotsof 1962 och 1963 i en rad experiment med utvalda grupper.
Ytterligare uppgifter om de kliniska aspekterna av ibogain i behandling mot kemiskt beroende lämnades av Kaplan (1993), Sisko (1993), Sanchez-Ramos och Mash (1994) och Sheppard (1994).
Före dessa utvärderingar av ibogainets förmåga att bryta olika slag av kemiskt beroende hade Naranjo (1969, 1973) och den första internationella ibogainkonferensen i Paris (Zeff, 1987) rapporterat om användningen av drogen i psykoterapi. Fernandez (1982), liksom Gollnhofer och Sillans (1983, 1985) har skrivit om hur ibogainhaltiga växter nyttjats under hundratals år i såväl religiösa riter som folkmedicinen.
En översikt över ibogainanvändningens och -forskningens historia utgavs av Goutarel med flera (1993).
Påståenden om att drogen var verksam i behandling mot människors opiat-, kokain- och alkoholberoende fick stöd i prekliniska studier utförda av forskare i Förenta staterna, Nederländerna och Kanada. Dzoljic med flera (1988) var de första forskare som skrev om ibogainets förmåga att mildra symptomen vid abstinens från narkotika. Stanley D. Glick med flera (1992) vid Albang Medical College publicerade ursprunglig forskning och en översikt över fältet beträffande mildring av symptomen vid abstinens från narkotika. Maisonneuve med flera (1991) bestämde den farmakologiska växelverkan mellan ibogain och morfin, och Glick med flera (1992) skrev om ibogainets förmåga att minska eller bryta råttors självdosering av morfin. Woods med flera (1990) fann att ibogainet inte fungerade som ett opiat, och Aceto med flera (1991) fastställde att ibogainet inte framkallade abstinenssymptom eller beroende.
Cappendijk och Dzoljic (1993) skrev om ibogainets verkan i att minska råttors självdosering av kokain. Broderick med flera (1992) var de första som skrev om ibogainets förmåga att kasta om dopaminökningar som framkallats av kokain och skrev senare (1994) om hur ibogain minskar motorisk aktivitet och andra effekter som framkallats av kokain. Forskning som Broderick med flera utfört stöder Sershens med fleras rön (1992) att ibogain minskar kokainframkallad motorisk stimulans hos möss. Sershen visade också (1993) att ibogain minskade kokainkonsumtion hos möss.
Glick (1992) och Cappendijk (1993) fann i djurförsök att flerfaldiga ibogaindoseringar under en längre tid var verksammare än enstaka doser för att bryta eller minska självdosering av morfin och kokain, vilket stödde Lotsofs rön beträffande människor (1985).
Popik med flera (1994) bestämde att ibogainet är en konkurrenskraftig hämmare av MK-801-bindning till NMD-Areceptorkomplexet. MK-801 har visats minska toleransen för opiater (Trujillo och Akil, 1991) och även för alkohol (Khanna med flera, 1993). MK-801 har också visats blockera "omvänd tolerans" för stimulantia (Kader med flera, 1989). Ibogainets effekter på dopamin (ett ämne som antas förstärka de behagliga effekterna av narkotika) och dopaminsystemet upptäcktes av Maisonneuve med flera (1991), Broderick med flera (1992) och Sershen med flera (1992). Deecher med flera (1992) skrev om ibogainets bindning till kappaopiatreceptorn.
Det framträder alltså ett brett fält av mekanismer, varmed ibogainet kan minska missbruket av så olika ämnen som opiat- narkotika, stimulantia och alkohol.

"Ibogain var en mental process för mig, ett slags andlig rening och ett sanningsserum."

HUR EFFEKTERNA FORTSKRIDER

Man har funnit att ibogainets verkan fortskrider i tre stadier:
(1) Ett fyra till sex timmar långt skede som liknar drömmande, där patienten upplever intensiva ljud, ljus, ser bilder och tänker på eller återupplever händelser i sitt tidigare liv.
(2) Ett kognitivt eller intellektuellt skede, där upplevelser från det första skedet ingår i en intensiv utvärderingsprocess och sedan byggs in i en ny jaguppfattning.
(3) Ett skede av kvarstående stimulans, som efter hand medför sömn. Lotsof beskriver detta skede såsom innefattande sömnperioder om tre till fyra timmar under loppet av 24 till 40 timmar. Patienten vaknar därefter i utmärkt form och med en ny självtillit.
Som jämförelse kan nämnas att den amerikanske hjärtspecialisten Michael Sabom i en studie av 150 människor som "räddats ur döden" noterade att nära-döden-upplevelsen (NDU), allteftersom den fortskred, allmänt kännetecknades av följande skeden:
(1) Autoskopiska (autoskopi = att skåda sig själv) skedet: subjektiv känsla av att vara död, frid och välbefinnande, avsaknad av kropp, visioner av materiella föremål och händelser;
(2) Transcendentala skedet: tunnel eller mörkt område, utvärdering av det tidigare livet, ljus, inträde i en transcendental värld (inträde i ljuset), möten med andra varelser, återvändande till livet.
Intressant är att många av dessa människor genomgick en anmärkningsvärd förvandling under sin NDU. Många av dem, som uppgav sig ha sett hela livet blixtra förbi, miste sin rädsla för döden, kände sig starkare, lugnare och mer optimistiska, och de kunde sedan se mer positivt på livet.
Vid ibogainbehandling är det efter att patienten har vaknat som effekterna främst märks, ty majoriteten patienter känner då inte längre något begär efter de droger de missbrukat. Det bör emellertid noteras att responserna på ibogain är mycket individuella och varierar lika mycket som individerna själva är olika.
Enligt Lotsof har patienter uppgivit att de känt ett minskat sömnbehov under en tid upp till fyra månader, ibland ända till sex månader, efter att de fått ibogainbehandlingen.
En ung holländska har skrivit detta om sina erfarenheter av ibogainbehandling:
"Jag tappade intresset för droger i allmänhet, för ibogainets effekt går långt utöver deras effekt, fast inte nödvändigtvis på något behagligt sätt. Upp till fyra månader efter behandlingen upplevde jag färger och ljus mycket intensivt.
"Ibogain var en mental process för mig, ett slags andlig rening och ett sanningsserum, som jag skulle få erfara resultaten av med tiden. Det är först nu, efter sex månader, som jag kan säga att jag inte längre är missbrukare. Det tar tid att erkänna att det inte finns någon återvändo. Ibogainet är inte i sig en lösning, även om det tar bort abstinensen fullständigt. "
Ibogainet tillhandahåller redskapet för att övervinna beroendet, men patienten måste själv ha viljan att förändras. Ibogainet hjälper individen inse att all kunskap som krävs för att bota honom finns att tillgå, om detta verkligen är vad han vill.

KLINISKT FÖRFARANDE

Effekterna av ibogainbehandling kan indelas i tre grupper: effekter på kort, medellång och lång sikt. Effekterna på kort och medellång sikt har ibland kallats verkningar och efterverkningar. Ibogainets två viktigaste effekter är: (1) förmågan att häva abstinensbesvär av narkotika eller stimulantia och att (2) minska eller häva begäret efter fortsatt bruk av opiater, stimulantia och alkohol (Lotsof, 1985, 1986, 1989).
Kunskapen om användningen av ibogain i behandling mot alkoholmissbruk är begränsad till: (1) en enda patient som missbrukat alkohol enbart och (2) flera patienter som behandlats för flerfaldigt missbruk och därvid minskat och i vissa fall helt upphört med sitt missbruk av alkohol.
Att ibogain har effekt mot nikotinberoende (Lotsof, 1991) har visat sig hos patienter, som behandlats främst för sitt missbruk av opiater och/eller kokain.
Några allmänna beaktanden ifråga om förhållningssätt vid behandlingen:
Den behandlande personalen har fyra huvudsakliga åligganden: (1) Att vinna patientens tillit; (2) att bibehålla patientens välbefinnande; (3) att bistå patienten i att häva dennes kemiska beroende; och (4) att tillföra det nätverk av psykosocialt stöd som de flesta av patienterna behöver för att kunna växa i en känsla av personlig framgång och förmåga att fungera som en produktiv samhällsmedlem. Detta är en process, som det holländska behandlingsgruppen kallar "normalisering".
Inom Lotsof-proceduren (en handbok för denna håller på att utarbetas) uteblir den konfliktstämning som i de flesta behandlingsmetoder märks mellan läkaren och patienten i frågan om att omedelbart bryta drogmissbruket. Om patienten är narkotikaberoende, får han eller hon fortsätta att använda narkotika intill en viss tid före ibogainkuren. Det råder ingen konflikt om bruket av opiat före kuren, ty som Lotsof hävdar har ibogainet den verkan att det antingen häver det kemiska beroendet eller inte. I proceduren ingår att en patient, som är beroende av stimulantia inte ges sådana, och detta förfarande har inte vållat vare sig patienter eller personal några problem.
Innan Lotsof-proceduren började genomföras på sjukhus under försöksvillkor, fick missbrukarna använda sitt personliga förråd av narkotika fram till kvällen före ibogainbehandlingen.

Det verkar vara denna insikt som får patienten att upphöra med sitt missbruk

När ibogainbehandling numera ges på sjukhus, får den narkotikaberoende patienten en medicinering, som förskrivits av huvudutredaren, under de tre till fem dygns behandling som föregår själva ibogainkuren.
Även under sådana betingelser har det förekommit att patienters misstro mot sjukvården och starka rädsla för abstinensbesvär medfört att narkotika smugglats in i sjukhusmiljön. Såsom en skyddande åtgärd måste alla patienter, som ska få ibogainbehandling på sjukhus, vid ankomsten till sjukhuset genomgå en grundlig läkarundersökning och därefter medge att deras medhavda tillhörigheter genomsöks. Detta tjänar två viktiga syften. För det första begränsar det risken för oönskad inblandning av narkotika eller andra stimulantia. För det andra ger det en mer heltäckande kunskap om patientens kroppsliga hälsa, viktigt eftersom många av dem som söker behandling för kemiskt beroende ofta har många andra hälsoproblem som de maskerat, i åratal eller t.o.m. årtionden, genom att själva medicinera med olagliga, beroendeframkallande medel.

FÖRFARANDE OMEDELBART EFTER DOSERING

De kortsiktiga effekterna av ibogain är dramatiska. Den första reaktionen hos patienten kan vanligen märkas inom 45 minuter efter doseringen, som görs genom munnen. De fulla effekterna är allmänt påtagliga inom två till två och en halv timmar. Den första subjektiva indikation på ibogainets verkan som patienten själv ger beskriver ett genomträngande vibrerande ljud. Patienten tenderar att lägga sig ner. Om patienten ombeds att stå eller gå omkring, visar han eller hon tecken på ataxi (sjuklig fumlighet).
Protokollet för Lotsof-proceduren föreskriver att patienten ska ligga till sängs och röra sig så litet som möjligt alltifrån ibogainbehandlingen börjar. Det illamående som förknippas med användningen av ibogain har nämligen bevisats vara relaterat till rörelse eller, i senare skeden (mer än fyra timmar efter medicineringen), möjligen en psykosomatisk reaktion på tidigare förträngda traumatiska upplevelser.
Förutom att patienten hålls så stilla som möjligt föreslår protokollet något medel mot illamående som inte bygger på fenotiasiner, då dessa ämnen kan inverka menligt på ibogainets psykoaktiva egenskaper. Om patienten får uppkastning mindre än två och en halv timmar efter medicineringen, bör man analysera det uppkastade materialet för att fastställa hur mycket ibogain patienten hunnit uppta. Om det inte visar sig möjligt att sedan tillföra den kompletterande dosen oralt, kan denna ges genom rektal infusion, men endast om patienten tidigare lämnat sitt medgivande till detta doseringssätt.

AUTONOMA RESPONSER

Under den första till och med den femte timmen av ibogainbehandling stiger patientens blodtryck måttligt, 10-15 procent, och i vissa fall åtföljs detta av en minskning av pulsen. De mest markanta autonoma förändringarna inträffar mellan en och en halv och två och en halv timmar efter den terapeutiska doseringen av ibogainet.
I många fall förhöjs patientens puls på grund av oro han eller hon känner före ibogainbehandlingen.

VISUALISERINGSSKEDET

En av ibogainets huvudsakliga effekter under det första skedet av verkan är att medlet inger ett tillstånd som liknar dröm, fastän patienten är fullt vaken och förmögen att besvara den behandlande personalens frågor.
De som står under påverkan av en terapeutisk dos ibogain vill i de flesta fall inte tala. De föredrar att i stället rikta uppmärksamheten på de visuella minnesbilder eller fenomen de upplever - visuella bilder om man vilka man noterat att de har både freudianska och jungianska anknytningar.
Upplevelsen av det visuella materialet sker snabbt. Några patienter har beskrivit det som en snabbspolad film, andra som en visning av diapositiv där varje diabild innehåller en rörlig bild av en bestämd händelse eller omständighet i skådarens liv. I båda fallen framställs det visuella materialet så komprimerat och snabbt att om patienten distraheras om så bara för ett ögonblick, kan det menligt inverka på avreageringsprocessen. Därför bör sjukvårdspersonalens intrång vara minimalt under ibogainbehandlingens första skede.

KOGNITIV UTVÄRDERING

Efter visualiseringsskedet kommer i Lotsof-proceduren ett andra skede av ibogainpåverkan. Under detta utvärderar patienten intellektuellt tidigare erfarenheter och beslut. Visualiseringsskedet har då upphört, vanligen abrubt, efter en period av tre till fem timmar. Inom procedurens parametrar är det emellertid regel snarare än undantag att reaktionerna varierar individuellt.
Ifråga om patientens egen utvärderingsprocess ska följande noteras. När patienten tidigare fattat beslut, föreföll dessa att vara de enda möjliga vid tillfällena ifråga. Ibogainet har emellertid den inverkan att livsföring, handlande och beteende kan omvärderas, så att patienten ser alternativ till en gång fattade beslut, alternativ som stod till buds vid tillfällena i fråga. Denna insikt verkar sätta patienten i stånd att förändra sitt nuvarande beteende och upphöra med sitt missbruk.

ORÖRLIGT BETEENDE UNDER BEHANDLING

Under visualiseringsskedet och in i det kognitiva utvärderingsskedet uppvisar patienter orörlighet i beteendet (Depoortere, 1987). Under denna tid företer patienten rytmisk, långsam hjärnvågsaktivitet i frekvensbandet 4-6 Hz, mönster som förknippas med dröm och sömn men klart kan skiljas från dessa tillstånd. Dessa EEG-mönster förknippas med ett tillstånd som kännetecknas av orörlighet.
Några tidiga iakttagare av Lotsof-proceduren (Kaplan, 1990) trodde i början att tillståndet var ett slags förlamning, men när patienter ombads resa sig och röra sig, kunde de göra detta, om än med viss svårighet.

Det dröjer vanligen två till tre dygn innan patienten märker att begäret upphört

HÄVANDE AV BEGÄR

Det akuta hävandet av begäret efter droger är unikt för Lotsof-proceduren i egenskap av behandling mot kemiskt beroende. Patienten själv märker vanligen inte effekten, förrän ibogainets huvudsakliga verkningar (visualisering, kognitiv utvärdering, orörlighet i beteendet och markant kvarvarande stimulans) inte längre framträder och patienten fått tillfälle att sova.
Det dröjer vanligen två till tre dygn, innan patienten märker att begäret upphört. I ett mindre antal behandlingar känner sig patienten återställd till hälsa och fri från beroendet efter endast ett dygn. Däremot brukar sjukvårdspersonalen märka att begäret upphört hos patienten 45 minuter till en och en halv timme efter behandlingens början.
Enligt NDA International (det företag för medicinsk utveckling som Howard Lotsof startat för att ge handledning till experimentell terapi enligt Lotsof-proceduren) har den erfarenhet man på senare år vunnit vid behandling av 20 personer utanför USA visat att majoriteten patienter kan behöva en serie behandlingar för att häva sina betingade responser på en lång tids kemiskt beroende. Tre av dessa patienter behövde dock bara en enda behandling för att häva sitt kemiska beroende som varat i minst två år.
En fördel med ibogain är att det ger patienten tidsperioder som är fria från begär. Det är under dessa som psykiatern, socialarbetaren, terapeuten, vårdaren och patienten ofta bildar ett sammansvetsat arbetslag som kan förverkliga en långsiktig frihet frän missbruk.

MINSKNING AV SÖMNBEHOVET

I alla behandlade fall minskar ibogainet patientens sömnbehov till så litet som tre eller fyra timmar per natt. Denna effekt kan vara en månad eller längre, varvid behovet gradvis återgår till det normala.
Två teorier om denna effekt har framlagts. Den ena teorin handlar om att ibogainet eller någon av dess metaboliter har en långvarig biologisk tillgänglighet. Detta stämmer överens med farmakokinetiska studier som gjorts vid University of Miami (Mash, 1995). Den andra teorin föreslår att orsaken ligger i minskningen av de psykologiska sömnbehov som hänger samman med behovet av att drömma. Det som talar för denna teori är att ibogain i det första behandlingsskedet framkallar ett intensivt drömlikt tillstånd som varar i flera timmar.
Minskningen av sömnbehovet ses av majoriteten patienter som en olägenhet, eftersom de varit vana vid att använda droger och sömner som flyktmekanismer. Dessa patienter kan behöva något mildare lugnande medel de första dagarna efter ibogainbehandlingen.
Normala försiktighetsmått bör vidtas när personer med missbrukarbakgrund får lugnande medel. En minoritet av patienterna har dragit fördel av den längre vakenheten till att hinna mera i sitt arbetsliv.

PSYKOSOCIALT STÖD

Alla aspekter på behandling för kemiskt beroende, som förekommer i andra behandlingsformer förekommer också i ibogainbehandlingen.
Patientens kännetecken - såsom psykopatologi, beteende, sociala färdigheter, liksom behandlingsgruppens kompetens - har stor betydelse för behandlingsresultatet.
I de fall, där patienten redan har de yrkes- och utbildningsmässiga färdigheter han eller hon behöver för att lyckas i samhället, kan uppgiften bli något lättare.
I de fall, där patienten inte har dessa färdigheter eller behöver få vård för andra besvär än det kemiska beroendet, måste vård och träning ges genom strukturer för psykosocialt stöd.
Trauma, som patienten upplevat i barndomen, förefaller spela en betydelsefull roll i det krav på att bli älskade och den rädsla för att bli övergivna som kännetecknar många av de behandlade (Bastiaans, 1991).
Många av de vedertagna parametrarna för distans mellan terapeut och patient är inte effektiva vid ibogainbehandling. Patienterna kräver en närmare och intensivare ledning och är i allmänhet öppnare för den. De kräver snabbare ingripande för att lära sig sådant de måste kunna för att fungera i samhället liksom för att övervinna och sakligt förstå de olika trauman de upplevat i livet.
Ibogain är därför inte en behandlingsform för kliniker, som föredrar att bara medicinera för att sedan dra sig undan från patienten.

KVINNLIGA PATIENTERS SÄKERHET

En 24-årig kvinnlig patient, som i Nederländerna behandlades med ibogain för kemiskt beroende, avled av icke diagnosticerade orsaker. Obduktionen klargjorde visserligen inte dödsorsaken, men en ibogainhalt av 0,75 mg/1 påvisades i blodet. Denna halt har inte befunnits vara toxisk i djurförsök eller i tidigare studier av människor som gjorts av NDA International.
Efter detta dödsfall (och ett tidigare anmält dödsfall av en schweiziska, som fick ibogain under psykoterapibehandling, som inte hade något som helst samband med NDAs forskningsprogram) uteslöt FDA kvinnor ur de kliniska försök som för närvarande pågår vid University of Miami.
FDAs beslut strider emellertid emot de riktlinjer beträffande kön de nationella sjukvårdsinstituten dragit upp. Dessa riktlinjer förordar att man medtar kvinnor på de kliniska försökens tidigaste stadier för att kunna bäst bestämma säker beten för kvinnor.
NDA International uppger att 30 procent av dess patienter varit kvinnor och att de inte uppvisat några negativa effekter av ibogainet vare sig under eller efter behandlingen. Med tanke på alla omständigheter bör emellertid Lotsof-proceduren genomföras endast på sjukhus eller klinik där patienten står under oavbruten bevakning av personal och elektronisk utrustning.
Ett pågående internationellt forskningsprogram samlar material för att kunna uppställa en hypotes om den nederländska kvinnans död. Dessutom söker NDA International samarbete med schweiziska myndigheter för undersökning av den schweiziska kvinnans död.

ARRANGEMANG I SAMBAND
MED IBOGAINBEHANDLING

NDA International, Inc. har fått många förfrågningar om ibogainbehandling för drogberoende.
De enda behandlingar, som för närvarande är godkända av något lands sjukvårdsmyndigheter, är sådana som pågår på sjukhus i Mellanamerika inom ramen för ett försöksprogram.
På grund av de stora kostnaderna för sjukhusvistelsen och övriga arrangemang i samband med detta program är grundkostnaden per person 15 500 US$ för behandling i grupp om tre. Kostnaden för individuell behandling är betydligt större. Dessa kostnader innefattar inte de föregående läkarundersökningarna, resa till och kostnader i New York för den erforderliga medicinska för- och efterbehandlingen.

Hänvisningar

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16. Kaplan, C. D., personlig kontakt med Howard Lotsof, 1990.
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PostPosted: Wed 14 Jun, 2006 19:02    Post subject: Reply with quote

Ibogaine: A Novel Anti-Addictive Compound
A Comprehensive Literature Review

By,
Jonathan Freedlander
Advisor: Carlo DiClemente, Ph.D.
University of Maryland, Baltimore County



Introduction and History:

Ibogaine is a naturally occurring indole alkaloid, found in a variety of African shrubs of the Tabernanthe genus (Obach, Pablo, and Mash, 1998). The root of the Tabernanthe iboga plant (also known as eboga) is the most frequently cited source of ibogaine, and this plant contains 11 other known psychoactive constituents (Popik, and Skolnick, 1999). Chemically, ibogaine is classified as a tryptamine, being a rigid analog of melatonin, and is structurally similar to harmaline, another natural alkaloid and psychedelic (Xu et al, 2000). Ibogaine was first extracted from the Tabernanthe iboga root in 1901 by Dybowsky and Landrin (Goutarel, Gollnhofer, and Sillans, 1993). It can also be synthesized from nicotinamide by way of a 13 or 14 step process, although extraction from the iboga root is a simpler method for obtaining the compound (Shulgin and Shulgin, 1977).

At low doses, ibogaine exerts primarily a stimulant effect, increasing alertness and reducing fatigue, hunger, and thirst (Rezavani, Overstreet, and Lee, 1995), though not in the manner of stereotypical CNS stimulants, such as amphetamine or cocaine (Da Costa, Sulklaper, and Naquet, 1908). At higher doses (typically above 3 mg/kg), ibogaine’s primary psychological effects include the retrieval of repressed memories, closed eye visual imagery (CEVs), and a state characterized as “waking dreaming” (Popik and Glick, 1996). From anecdotal reports, it appears that memories are relived in a sense, primarily in a visual modality, but without the emotional weight they carried when the events occurred, allowing the individual to view them with greater insight (Naranjo, 1974; Alper et al, 1999). Subjectively, these effects have been described as fantasies, “as a movie run at high speed, or a slide show” (Lotsof, 1995). These fantasies are easy to manipulate by both the subjects and the clinician, and therefore this phenomenon has been sighted as a potentially valuable tool in psychotherapy (Naranjo, 1967, 1974). The imagery experienced under the effects of ibogaine is often largely Jungian in content, involving archetypes seemingly common across cultures; frequently animals, birth and rebirth sequences, and/or the subject with or without individuals (Popik and Glick, 1996). While ibogaine does share features common with many compounds labelled as hallucinogenic, it does not cause thought disturbances, alterations in reality testing, nor is it psychomimetic (Luciano, 1998; Goutarel, Gollnhofer, and Sillans 1993; Popik and Glick, 1996). Rather than classify ibogaine as a hallucinogen, it is suggested that the compound be termed oneirogenic, due to the “waking dream” state it induces, from the Greek, meaning “dream creator” (Naranjo, 1974; Goutarel, Gollnhofer, and Sillans, 1993).

In addition to ibogaine’s psychological effects, it elicits a number of physical effects, which include tremor, light sensitivity, nausea and vomiting, ataxia, and dystonia (Lotsof, 1994; Glick, Maisonneuve, and Szumlinski, 2000). All of these effects, psychological and physical, manifest in a dose-dependent fashion (Schechter and Gordon, 1993). In light of these properties, and that the sum effects of ibogaine can last up to 24 – 36 hours, ibogaine is not considered to have a high potential for abuse (Popik and Glick, 1996). Indeed, those who have experienced ibogaine, typically characterize its effects as a “rough trip;” one that is not suitable for recreational use (Shulgin and Shulgin, 1977).

Accordingly, when ibogaine was introduced to the United States’ black market in the 1960’s, it showed little popularity, and subsequently has infrequently been seen sold illicitly (Goutarel, Gollnhofer, and Sillans, 1993). The U. S. Drug Enforcement Agency reports having encountered only a few illicit samples in their interdiction efforts (Cooper, 1988). According to Dharir (1971), ibogaine first appeared on the illegal drug market in 1967, and was reported in a handful of cases by the police of Suffolk County, NY and San Francisco, CA. Shortly thereafter, however, ibogaine suddenly disappeared from the black market, perhaps due to a lack of profit motive for drug dealers, resulting from ibogaine’s putative anti-addictive effects (which will be discussed later in this paper) (Goutarel, Gollnhofer, and Sillans, 1993).

Various preparations of plants containing ibogaine have been used for centuries in traditional African medicine, as first reported by French and Belgian explorers in the 19th century (Popik and Skolnick, 1999). The iboga root may be eaten whole, or crushed and ground and mixed with other ingredients, sometimes including other psychoactive compounds (Fernandez, 1982). These preparations, in varying quantities, have been used as a stimulant to battle hunger, thirst, and fatigue during hunting, as an aphrodisiac, and as a catalyst for spiritual discovery involved in the initiation rites of the Bouti (Stafford, 1983). The Bouti (also Bwiti) is a religious society found among the indigenous peoples of the Gabon and Cameroon nations of western Africa, and initiation into this society, involving the use of ibogaine containing substances, is central to their cultures (Fernandez, 1982; Goutarel, Gollnhofer, and Sillans, 1993).

Literally, Bouti means “those of the chapel”. The primary purpose of these initiation rites, as described by the initiates, is to travel through the land of the tribal ancestors, and emerge in the “pristine uterine condition” (Fernandez, 1982). This ritual is referred to by its participants as “cracking the skull” (Sheppard, 1994). The initiate, in the ibogaine-induced state, makes contact with the ancestral spirits, under the guidance of those already initiated. After the ceremony, the initiate is reborn as an adult in the tribe, having previous transgressions and illnesses removed in the initiation process (Fernandez, 1982).

Ibogaine was first introduced as a pharmaceutical product to Western medicine in the form of Lamberene, an extract of the Tabernanthe manii plant (Popik and Skolnick, 1999). Advertised as a mental and physical stimulant, it contained about 8 mg of ibogaine and was “…indicated in cases of depression, asthenia, in convalescence, infectious disease, [and] greater than normal physical or mental efforts by healthy individuals” (Goutarel, Gollnhofer, and Sillans, 1993). The drug enjoyed some popularity among post World War II athletes, but was eventually removed from the market, when the sale of ibogaine-containing products was prohibited in 1966.

Dr. Claudio Naranjo, a Chilean psychiatrist, was the first to study ibogaine’s potential psychotherapeutic effects. In the early 1960’s, Naranjo conducted a series of case studies (approximately 40 studies, with 30 patients) using doses of 4 – 5 mg/kg, in which he found that ibogaine had the ability to facilitate closure of unresolved emotional conflicts (Popik and Glick, 1996). This closure was mediated by ibogaine’s aforementioned ability to enhance retrieval of repressed memories. Naranjo found that ibogaine allowed his patients to view their past experiences in an objective manner, which enabled them to confront personal issues that were previously unapproachable (Naranjo 1974).

Around the same time that Dr. Naranjo was conducting his case studies, ibogaine’s anti-addictive effects were serendipitously discovered. In 1962, Howard Lotsof, addicted to heroin at the time, took a dose of ibogaine (estimated to be about 500 mg) that a chemist friend had given him, tantalized by the promise of a 32 hour trip (Goutarel, Gollnhofer, and Sillans, 1993, De Rienzo, Beal, et al, 1997). He woke up the next morning with the startling revelation that he no longer desired heroin; in fact he remained free of the drug for years to follow (Lotsof, 1990). Though Lotsof was not a doctor, nor a scientist, his personal experience with ibogaine led him to investigate the drug further.

Over the course of the next year, Lotsof led a series of non-clinical focus groups under the auspices of S & L Laboratories, which he set up “to procure drugs and administer them to interested persons” (Lotsof, Della Sera, and Kaplan, 1995, Alper, Beal, and Kaplan, 2001). At that time, psychedelics were not scheduled drugs, and were effectively available to anyone who started their own chemical “company”, needing little more than an official looking letterhead (De Rienzo, Beal, et al, 1997). Between 1962 and 1963, Lotsof administered ibogaine to 20 individuals at a variety of doses, up to 19 mg/kg (Alper, Beal, and Kaplan, 2001). Of these 20 subjects, 7 were heroin dependent, and noted the alleviation of withdrawal symptoms and drug craving after ingesting ibogaine. Additionally, 5 of these 7 individuals were able to maintain abstinence from heroin for 6 months or longer.

Shortly thereafter in 1963, the Food and Drug Administration (FDA) noticed the large amount of psychedelics Lotsof was ordering, and tracked a shipment of 100 g of mescaline to the laboratory he had set up (De Rienzo, Beal, et al, 1997). Though psychedelics were not illegal at that time, unauthorized use of mescaline on humans was punishable by a six month sentence. The FDA’s search of his premises discovered no mescaline, but did find 2 g of ibogaine, which the FDA agents forced Lotsof to sell to them. Subsequently, the FDA cut off his access to controlled substances, despite the fact that they found nothing with which they could charge him.

However, in 1966, LSD, mescaline, and psilocybin were categorized by the U.S. federal government as Schedule I narcotics; drugs with no medicinal value and a high potential for abuse. Shortly thereafter, Assistant U.S. Attorney Robert Morenthau had Lotsof arrested on drug conspiracy charges. When Lotsof spoke about ibogaine’s anti-addictive effects in court, the judge had his testimony stricken from the record. Lotsof was found guilty on 4 misdemeanours, and sentenced to 14 months in prison. Upon release in 1968, Lotsof was “shattered”. He travelled to Nepal, where, for the first time in five years, he ate opium, and became re-addicted. In 1969, he tried to locate some ibogaine with the hopes of breaking his addiction again, but discovered that it had been added to the list of Schedule I drugs, and was unable to find any.

Upon returning to New York, Lotsof entered a methadone maintenance program, which he considered life saving. However, “the system of administering methadone was becoming more restrictive to patient life styles,” and so with the knowledge he had gained from his experiences with ibogaine, Lotsof endeavored to wean himself off methadone (Lotsof, 2002). In December of 1973, just as he was coming off of methadone, Lotsof met Dana Beal, the then new leader of the Yippie movement. Beal and Lotsof “hit it off from the start”, and over the next six years, collaborated on a variety of projects, including three films, a series of Rock Against Racism concerts, and further investigation of ibogaine.

In 1981, a Yippie subcommittee named Citizens Against Heroin began to fund Lotsof’s ibogaine research. He used the bulk of this funding to execute an exhaustive literature search in the New York University library (where he had previously been a film student). By late 1983, Lotsof believed he had enough information to back his claims of ibogaine’s anti-addictive effects, and initiated a series of patents for Endabuse (NIH 10567), an oral preparation of ibogaine hydrochloride in capsule form. These patents indicated Endabuse for the “rapid interruption” of opiate dependence disorders (U.S. Patent 4,99,096, 1985), cocaine dependence disorders (U.S. Patent 4,587,243, 1986), nicotine dependence disorders (U.S. Patent 5,026,697, 1991) and poly-substance abuse disorders (U.S. Patent 5,152,994 1992) (Lotsof, Della Sera, and Kaplan, 1995).

Lotsof first made contact with the conventional scientific community in 1986, when he contracted with a professor at McGill University in Montreal to study ibogaine’s effects on alcohol dependence. However, the professor turned the project over to a graduate student and never published the results. (Fortunately, the contract for the experiment specified that Lotsof owned the data, and in 1988 he discovered that the results showed a significant reduction in alcohol intake by rats after administration of ibogaine.) Also in 1986, Lotsof founded a New York based organisation, NDA International, Inc., with the dual mission of furthering the humanitarian applications of ibogaine and marketing the proprietary preparation, Endabuse (Goutarel, Gollnhofer, and Sillans, 1993).

After that, Lotsof sent a sample of ibogaine to researchers in the Pharmacology Department at Erasmus University in Rotterdam, where the investigators published the first paper indicating the effectiveness of ibogaine in the reduction of opiate self-administration in an animal model (Alper, Beal, and Kaplan, 2001). The team at Erasmus also furthered the development of a method of injecting it into the ventricles of rat brains, which was originally conceived by Konig and Klippel in 1963. This reduced the amount of ibogaine needed to produce the effects of regular intravenous or intraperitoneal administration (De Rienzo, Beal, et al, 1997).

In 1989, Lotsof contracted with Dr. Stanley Glick, head of the Department of Pharmacology and Toxicology at Albany College of Medicine. This was perhaps the most pivotal of Lotsof’s contacts with the scientific community. After examining ibogaine’s long lasting effects on morphine self administration in rats, Dr. Glick became keenly interested in furthering ibogaine research. Although Lotsof had run out of funding at the time, having to break his contract with Glick, Glick continued with his own research, and over the years produced a significant body of work on ibogaine and related compounds (De Rienzo, Beal, et al, 1997).

Lotsof and colleagues developed a specific procedure (aptly named the Lotsof ProcedureTM) for the use of Endabuse, which involves comprehensive short and long term medical, psychological, and social care of the patient. Lotsof describes the procedure a single administration modality (SAM), and summarises the primary obligations of the treatment team as:

“four-fold: 1) to earn the trust of the patient, 2) to maintain the comfort of the patient, 3) to assist the patient in interrupting their chemical dependency, and 4) to supply the psychosocial support network needed by the majority of patients to enable them to develop a sense of personal accomplishment and the ability to function as productive members of society” (Lotsof, 1994).

One of the differences between the Lotsof Procedure and conventional addiction treatment that it stresses most is the level and nature of the rapport between the clinicians and the patient. As Lotsof describes (1994), “… the sense of conflict seen in most treatment modalities between the doctor and patient over the immediate ceasing of drug use does not exist”. Treatment is approached with a “pro-choice attitude” by the caregivers, where abstinence is not demanded (Frenken, 1998). Rather, the patient is allowed to continue using drugs until a certain time before the procedure, based on the amount of time needed for the given drug to clear the body. The position of the treatment team is “that ibogaine will either work to interrupt chemical dependence or it will not” (Lotsof, 1994).

Another noteworthy difference of the Lotsof Procedure is the rapidity with which psychosocial support needs to be provided to the patient. “Ibogaine presents a symptom-free window of opportunity which the patient and therapist must take advantage of” (Lotsof, 1994). Because ibogaine (putatively) allows for an immediate interruption in the patient’s addiction, the patient is generally found to be in a receptive psychological state earlier in the course of therapy. Therefore “they will require faster intervention to learn societal skills and to overcome and objectively understand various traumas experienced during their lives” (Lotsof, 1994). Additionally, Lotsof asserts that many of the accepted boundaries between the therapist and patient can hinder ibogaine treatment, that patients will require a closer and more intensive guidance.

As word of Lotsof’s discovery gradually spread across the world, an unofficial global network of ibogaine therapy providers developed (Alper et al, 1999). This network was largely supported by the efforts of the New York based International Coalition for Addict Self-Help (ICASH), founded by Robert Sisko. ICASH is described “as having a self-help orientation in the tradition of European user self-help organizations, such as the Junkiebond in the Netherlands” (Alper, Beal, and Kaplan, 2001). This is not surprising, as ICASH often acted in partnership with the Dutch Addict Self Help group (DASH, now known as International Addict Self-Help, or INTASH). Together, these groups are estimated to have treated 40 to 45 individuals between 1989 and 1993. Though not officially sanctioned, the results of these treatments were reported in publications from Erasmus University. Self-help groups for the use of ibogaine also developed in the U. K., Slovenia, Italy, the Czech Republic, and France.

Professionals from various disciplines also became interested in examining ibogaine’s potential. Deborah Mash, professor of neurology at the University of Miami, became interested in ibogaine research after hearing a presentation on it at a conference in 1991 (Alper, Beal, and Kaplan, 2001). In 1992, NDA International and the University of Miami collaborated to organize a clinical trial of ibogaine. The following year, Mash received approval for an Investigational New Drug Application from the FDA. The study was not completed, however, due to lack of funds, and NDA International and the University of Miami commenced litigation of intellectual property rights. Since 1996, Mash has operated an ibogaine treatment centre on the Caribbean island of St. Kitts.

Therapist Eric Taub also relocated from Florida to the Caribbean in order to establish an ibogaine therapy program. Since 1992, Taub has treated approximately 310 patients, 130 of which sought treatment for chemical dependency (Alper, Beal, and Kaplan, 2001). Through ibogaine therapy, Taub aides the patient in changing patterns of “reactive” or subconsciously determined behaviour, including, but not limited to substance addiction. Ibogaine’s role in this psychotherapy is to facilitate a reduction of “pathologically acquired or learned” associations of cues or internal representations with corresponding motivational states and behaviour. In accord with Lotsof’s methods, Taub stresses the rapidity and intensity with which support must be provided following the administration of ibogaine for successful treatment.

Dr. Jan Bastiaans was the president of the Psychoanalytic Institute in Amsterdam from 1954 to 1961, professor of psychiatry at the State University of Leiden from 1963 to 1985, and a major figure in the history of the psychotherapeutic use of psychedelics (Grof, 2001). Bastiaans work with psychedelics was sparked by his interest in the use of pharmacological methods in the treatment of war related trauma in the wake of World War II. In particular, his work focused on the treatment of concentration camp survivors, often using LSD or psilocybin to facilitate therapy (Snelders, 1998). Over time, Bastiaans began to develop the methods he used in therapy with war survivors to treat survivors of other traumas. In 1992, Bastiaans collaborated with NDA international, adapting his methods to treat those with substance addictions (Alper, Beal, and Kaplan, 2001). However in 1993, one of the few known ibogaine related fatalities occurred under his supervision. Although the official Dutch inquiry found no evidence to suggest wrongdoing on the part of Bastiaans, he was forced to give up his practice by the Medische Tuchtraad, the Dutch medical supervisory board. In his last years, Bastiaans became bitter over the lack of recognition for his contributions to psychotherapy and died in 1997.




Pharmacology:

The principle method of ibogaine metabolism is O-demethylation by the liver, which yields O-desmethylibogaine (also known as 12-hydroxyibogaimine or, most commonly, noribogaine) and perhaps other, as of yet undetected, metabolites (Popik and Skolnik, 1999; Mash et al, 2000). Obach et al (1998) found that, of ibogaine consumed, 75 – 80 % was accounted for as noribogaine. Hough et al (1996) reported that ibogaine, when administered intraperitoneally in rats, is subject to a significant “first pass” effect; that is its pharmacological actions begin before it is metabolized. They also found that ibogaine has a high propensity to be deposited in adipose tissue, showing high levels in fat for at least 12 hours after administration. It is hypothesized that this quality may enable a single dose of ibogaine to provide a long acting “depot-like time course of action” (Popik and Glick, 1996).

Additionally, noribogaine has a longer half-life than ibogaine, and is also psychoactive; therefore it is possible that this metabolite may play a role in ibogaine’s long-term effects (Mash et al, 2000). Pearl et al. (1997) detected presence of noribogaine in rodent brains up to 19 hours after an intraperitoneal administration of 40 mg/kg of ibogaine, while the half-life of ibogaine has been established to be 60 minutes (Dhahir, 1971; Zetler, Singbarth, and Schlosser, 1972). Oral administration of ibogaine in rabbits (10 mg/kg) yielded peak urine concentrations at a maximum of 4 – 5 hours, rapidly decreasing thereafter, until complete absence at 6 hours (Dhahir, 1971; Cartoni and Giarusso, 1972). In addition to urine, both ibogaine and noribogaine are detectable in many other bodily materials, including blood, liver, and brain (Cartoni and Giarusso, 1972; Bertol, Mari, and Froldi, 1976).

The O-demethylation of ibogaine in the liver is catalysed by the P4502d6 cytochrome, which has important clinical implications (Obach, Pablo, and Mash, 1998). Approximately 5 – 10 % of Caucasians lack the gene needed to produce this enzyme, and are therefore more prone to adverse reactions from drugs metabolised by it (Gonzalez and Meyer, 1991). In addition, this cytochrome is involved in the metabolism of a number of pharmacological compounds, including neuroleptics, beta-blockers, tricyclic antidepressants, and opioids, raising possible issues of adverse interactions with ibogaine (Eichelbaum and Gross, 1990; Fromm, Kroemer, and Eichelbaum, 1997). Furthermore, individuals lacking this gene are less likely to benefit from the therapeutic effects of drugs metabolised by P4502d6 (Obach, Pablo, and Mash, 1998).

Like many tryptamines (e.g. serotonin, melatonin, d-lysergic acid diethylamide or LSD, psilocybin, N,N-dimethyltryptamine or DMT), the pharmacodynamics of ibogaine are particularly complex, involving multiple sites of action. Ibogaine affects, both directly and indirectly, dopaminergic, glutamatergic, serotonergic, opioid, nicotinic, sigma, gamma-aminobutrylic acidergic (GABA), nicotinic, cholingeric, and muscarinic pathways, as well as calcium regulation and voltage-dependent sodium channels (Popik and Glick, 1996; Glick and Maisonneuve, 1998; Alper et al, 1999; Popik and Skolnik, 1999). It is therefore thought that ibogaine’s effects are a product of a combination of its interactions with these systems. However, there have been a number of discrepancies reported with regard to the specific manners in which ibogaine exerts its pharmacological actions (Popik and Skolnick, 1999). Additionally, noribogaine affects many of the same neural components as ibogaine, which further complicates the study of its pharmacological profile (Mash et al, 2000).

A great deal of attention has been paid to ibogaine’s effects on the dopaminergic system, as dopamine is theorized to play a primary role in the sensitization, reinforcing, and motivational properties of drugs of abuse (Fibiger and Phillips, 1986; Berrige and Robinson, 1998). Robinson and Berrige (1993) proposed that the incentive salience of drug-taking behaviors is related to neurotransmission in mesotelencephalic dopamine pathways, in which the repeated administration of addictive drugs sensitizes the incentive salience of drug related cues. Compared to drug-naïve individuals, drug addicts have increased sensitivity to both the positive (Grant et al 1996; Ligouri, Hughes, Goldberg, and Callas, 1997) and negative (Ellinwood 1968; Angrist, 1983) reinforcing effects of drugs of abuse. These reinforcements are apparently mediated through enhanced brain activity in brain regions innervated by the mesolimbic dopamine system, including the frontal cortex (Alper et al, 1999) and the amygdala (Childress et al, 1999). According to this theory, if activity in sensitized dopamine pathways is decreased, it should alleviate addictive drug craving (Blackburn and Szumlinski, 1997).

Though ibogaine does not appear to affect binding at dopamine receptors or transporters (Broderick, Phelan, and Berger, 1992), it has been found to reduce extracellular levels of dopamine in the nucleus accumbens (Glick and Maisonneuve, 1998; Glick et al, 1999). Ibogaine effects on dopamine metabolites appear to be inconsistent. When measurements are taken shortly after administration (within 2 hours), or when high concentrations are used (greater than 100 μM), increases in dihydroxyphenyl-acetic acid (DOPAC) and homovanilic acid (HVA) are seen (Maisonneuve, Keller, and Glick, 1991; Maisonneuve, Rossman, Keller and Glick, 1992; Sershen, Hashim, Harsing, and Lajtha, 1992). However, when lower concentrations are used (e.g. 10 μM) or measurements are taken after a longer period of time (up to a week), dopamine brain concentrations remain unchanged, and metabolite concentrations decrease (Maisonneuve, Keller, and Glick, 1991; Shershen, Hashim, Harsing, and Lajtha, 1992).

Sershen et al (1994) reported that ibogaine’s effects on dopaminergic function are largely regulated by its interactions with serotonin receptors. This was inferred from their finding that ibogaine inhibited the ability of the 5-HT1b agonist CGS-12066A to increase stimulation induced dopamine release in rat and mouse striatal slices. It has also been demonstrated that ibogaine increased the ability of the 5-HT3 agonist phenylbiguanide to produce stimulation evoked dopamine release in mouse striatal slices (Sershen, Hashim, and Lajtha, 1995). Taken together, these findings support the notion that ibogaine’s effects on serotonin have a role in determining its dopaminergic effects, but the specific nature of this role has yet to be determined.

Ibogaine has been found to increase 5-HT concentrations in both the nucleus accumbens and striatum of the rat (Broderick, Phelan, Eng, and Wechsler, 1994; Ali et al, 1996). However, Benwell et al (1996) found that ibogaine reduced serotonin levels in the medial prefrontal cortex. Furthermore, studies of ibogaine’s specific actions at serotonin receptors have been inconclusive. Deecher et al (1992) found that ibogaine did not displace ligands acting at 5-HT1a, 5-HT1b, 5-HT1c, 5-HT1d, 5-HT2, or 5-HT3 receptors, while Repke et al (1994) found that it did inhibit binding of 5-HT1a, 5-HT2a, and 5-HT3 ligands with low affinity (>100, 12.5, and >100 μM). Additionally, Sweetnam et al showed that ibogaine inhibits radioligand binding to both 5-HT2 and 5-HT3 receptors, with considerably higher affinity (approximately 4 μM), while Helsley et al (1998) found that ibogaine bound to 5-HT2 receptors with low affinity in vitro ( > 40 μM), but occupied this receptor in vivo following systemic administration.

It is postulated that ibogaine may act as a reversible inhibitor of serotonin transporters, as concluded from the observation that it inhibited transporters in the isolated kidney cells of pigs (Popik and Skolnick, 1999). Sershen et al (1994) found that, at doses of 40-50 mg/kg, ibogaine decreased levels of 5-hydroxyindoleacetic acid [5-HIAA] in the frontal cortex, hippocampus and olfactory tubercle of the mouse. Ibogaine was also found to decrease 5-HIAA levels in the nucleus accumbens and striatum of the rat, but to increase 5-HIAA levels in the medial prefrontal cortex (Benwell, Holtom, Moran, and Balfour, 1996; Ali et al, 1996). The differing effects of ibogaine on serotonergic function in different areas of the brain have yet to be explained. Indeed, this is the case with most psychedelic compounds, making a strong case for the further scientific study of these substances.

Like dopamine systems, the glutamatergic pathway has often been implicated in drug abuse and addiction, specifically N-methyl D-aspartate (NDMA) channel receptors. Preclinical data have consistently indicated that NMDA antagonists interfere with sensitization, tolerance, and dependence related to stimulant, alcohol, benzodiazepine, barbiturate, and opiate use (Trujillo and Akil, 1991; Wolf and Khansa, 1991; Khanna, Kalant, Shah, and Chau, 1993; File and Fernandez, 1994; Popik and Skolnik, 1996). Furthermore, blockers of NDMA receptors have been show to reduce nalaxone-induced jumping in morphine-dependent mice (Layer et al, 1996; Popik and Skolnick, 1996). NMDA antagonists act by occupying a binding site within a calcium channel, which is normally gated by glutamate, the brain’s principle excitatory neurotransmitter (Helsley, Rabin, and Winter, 2001).

Ibogaine has been found to act as a non-competitive antagonist at NDMA receptor channels (Popik et al, 1995), which is supported by the finding that ibogaine has a high affinity for NDMA site binding (Glick and Maisonneuve, 1998; Helsey, Rabin, and Winter, 2001). Popik et al (1994) showed that ibogaine substituted for MK-801 (dizocilipine, a known NMDA antagonist) at a rate of approximately 70% in drug discrimination studies in mice. In addition, ibogaine has been shown to inhibit binding of both MK-801 (an NDMA antagonist) and PCP at NDMA receptors (Layer et al, 1996; Helsley et al, 1998). Ibogaine, at 80 mg/kg, also blocked NMDA-induced convulsions in mice for up to 72 hours after administration (Leal, de Souza, and Elisabetsky, 2000).

It has been demonstrated that certain sigma ligands may be effective in the treatment of drug abuse, due to their ability to block the behavioral effects of cocaine and amphetamine in non-human subjects (Helsley et al, 1998). Of all binding sites that have been studied thus far, ibogaine shows the greatest affinity for σ2 receptors, with reported K1 values ranging from 90 – 201 nM (Bowen et al, 1995; Mach, Smith, and Childers, 1995). Because of its high affinity for σ2 receptors, ibogaine has been proposed to act as a σ2 agonist (Bowen, Vilner, Bandarage, and Keuhne, 1996). Studies have also shown that ibogaine also binds to σ1 receptors with an affinity of less than 10 μM (Mach, Smith, and Childers, 1995). In support of this finding, ibogaine was shown to inhibit [3H]pentazocine (a σ1 receptor ligand) binding to high and low affinity sites in the mouse cerebellum (Popik and Skolnick, 1999).

Bowen et al (1995) hypothesized that ibogaine’s interaction with sigma receptors, particularly σ2 receptors, may be responsible for its effects on the regulation of calcium release from intracellular stores. They found that ibogaine produced a concentration dependent increase of 13 – 45 % in intracellular calcium levels. Additionally, ibogaine was shown to non-competitively antagonize calcium-induced contraction of the aorta and mesenteric artery in the rat (Hajo-Tello et al, 1985). The practical implications, however, of ibogaine’s effects on calcium regulation are not yet clear.

Of particular interest with regards to its putative role in interrupting opiate dependence are ibogaine’s effects on the opioid system. Ibogaine does not appear to be a conventional opioid agonist or antagonist (Alper et al, 1999). Bhargava et al (1997) found that ibogaine bound to μ-, δ-, and κ-opioid receptors low affinity, 11.0, > 100, and 3.77 μM, respectively. However, they did find that noribogaine had considerably higher affinities for these receptors; 2.66 μM for μ-, 24.72 μM for δ-, and 0.96 μM for κ-opioid receptors. These findings have been supported by results showing even higher affinities for noribogaine binding, with affinities of up to 160 nM at the μ-opioid receptor (Pablo and Mash, 1998). It is therefore hypothesized that noribogaine may play a significant role in ibogaine’s effects on opiate dependency (Bhargava, Cao, Zhao, 1997; Mash et al, 2000).

While ibogaine does not show high affinity for opioid receptor binding, it has been shown to exert some less direct effects on the opioid system. Ibogaine inhibits the binding of [3h]U-69593 to κ-opioid receptors, with a Ki value of 2 – 4 μM (Repke, Artis, Nelson, and Wong, 1994). However this inhibition is reversible, and therefore is not likely to contribute to ibogaine’s long-term effects (Popick and Skolnick, 1999). Additionally, it has been shown, through a two-site model, that ibogaine inhibits naloxone binding at μ-opioid receptors in the forebrain of mice with a Ki value of 130 nM (Codd, 1995). This suggests that ibogaine may act as μ-opioid agonist of a novel type (Bhargava, Cao, and Zhao, 1997).

Ibogaine, at concentrations < 10 μM, has been shown to selectively inhibit nicotinic receptor mediated catecholamine release in the mesolimbic system (Mah et al, 1998). This inhibition was reversible at low doses (10 μM), but persisted for at least 19 hours with washout at higher doses. Like NDMA and dopaminergic systems, the mesolimbic catecholamine system is implicated in the addictive process. It is considered to be a part of the reward pathway that mediates positive reinforcement in drug addiction (Di Chiara and Imperato, 1988).

A recent study by Glick, Maisonneuve, Kitchen, and Fleck (2002) asserts that, although ibogaine and noribogaine exhibit low to moderate binding affinities at many sites, the most critical site of action for the modulation of drug self-administration may be the α3β4 nicotinic receptor. They found that both ibogaine and its synthetic analog 18-methoxycoronaridine exhibit a more potent antagonism at this site than at α4β2 nicotinic receptors, or at NMDA or 5-HT3 receptors. Additionally, co-administration of either ibogaine or 18-methoxycoronaridine at sub-therapeutic doses with another α3β4 antagonist (either mecamyline or dextromethorphan) produced a significant therapeutic response. Because α3β4 receptors are mainly located in the medial habenula and the interpeduncular nucleus, and exist in the dopaminergic nuclei of the ventral tegmental area in only low densities, these researchers suggest that the dopaminergic mesolimbic pathway may not be directly involved in mediating ibogaine’s anti-addictive effects. It is hoped that further study will reveal these mechanisms in more detail.


Toxicology:

The LD50 of ibogaine seems to vary depending on the animal, and the route of administration. When administered intraperitoneally in the guinea pig, the LD50 was shown to be 82 mg/kg (Dhahir, 1971). In the rat, the LD50 was shown to be 145 mg/kg when administered intraperitoneally, but 327 mg/kg when administered intragastrically (Popick and Skolnik, 1999). Thus, ibogaine does not seem to have a great liability for lethality.

There have been, however, three recorded human deaths related to the intake of ibogaine, reported by Lotsof et al (2002). The first, in 1989, was a 40 year old woman, administered 8 mg/kg for the purpose of psychotherapy. This is the lowest dose known to precipitate an ibogaine related death. Four hours into the session, she suffered cardiac arrest, and an autopsy showed significant blockage of the main arteries to the heart. Thus, should ibogaine prove to be a viable therapy, contraindications for patients with cardiovascular problems would most likely be necessary.

The second fatality (the fatality that led to Dr. Jan Bastiaans dismissal) occurred in 1993, a 24 year old Dutch woman being treated for heroin dependency. She received 29 mg/kg in a split dose of 23 mg/kg followed by an additional dose of 6 mg/kg 3 hours later. The patient died 16 hours later of unknown causes; an autopsy did not reveal any specific pathology. However, a sheet of charred tinfoil was found in her personal affects, indicating the possibility that she had consumed heroin during the course of her ibogaine treatment. (A popular method of heroin administration among Dutch addicts is to heat the heroin on a sheet of tinfoil and inhale the vapors, sometimes known as “chasing the dragon”). It is conceivable then, that a heroin-ibogaine interaction may have been the cause of death, as ibogaine has been shown to increase the effects and toxicity of opiates (Popick and Glick, 1996).

The third recorded fatality occurred in 2000, in the U.K. The patient was a 38 year old male, and suffered from hepatitis C. He was administered a total of approximately 5 grams of a total iboga extract standardised to 15% ibogaine. This was a most peculiar case, as the fatality did not occur until after the effects of ibogaine had subsided, 38 hours after initial administration. Police toxicologist Dr. John Taylor told testified that the level of ibogaine in the dead man's blood was “well below the normal toxic dose” (Kerr, 2001). According to writer Nick Sandberg (2002), the official inquest named the primary cause of death as asphyxiation due to vomit clogging airways, with liver failure as a secondary cause.

Of more importance to the general population than these isolated incidents, are recent reports of ibogaine neurotoxicity. There are, however, some discrepancies among these reports. Dhahir (1971) found no pathological changes in the liver, kidney, heart or brain of the rat following chronic intraperitoneal ibogaine administration (10 mg/kg for 30 days, and 40 mg/kg for 12 days.) Likewise, Sanchez-Ramos and Mash (1994) found no evidence of gross pathology in African green monkeys given ibogaine in oral doses of 5 – 25 mg/kg for four consecutive days.

In higher doses, though, ibogaine has been shown to cause definitive neurotoxic effects. At a single intraperitoneal dose of 100 mg/kg, ibogaine was shown to cause marked degeneration of Purkinje cells and activation of microglia in discrete radial bands of the rat cerebellar cortex (O’Hearn and Molliver, 1997). In support of these findings, Xu et al (2000) found that degeneration of Purkinje cells was visible at intraperitoneal doses beginning at 75 mg/kg, showing increasing damage at 100 mg/kg. This study revealed that the neurotoxicity of ibogaine is dose-dependent, a finding also supported by other investigations (Molinari, Maisonneuve, and Glick, 1996).

O’Hearn and Molliver (1997) propose that ibogaine is not directly toxic to Purkinje cells, but rather causes Purkinje cell degeneration through sustained activation of the olivocerebellar projection. Scallet et al (1996) reported that activation of serotonin receptors in the forebrain is the initial site of ibogaine neurotoxicity. Cortifugal axons could then stimulate the inferior olive and its excitotoxic climbiner-fiber pathway to the cerebellum (Xu et al, 2000). This lends support to O’Hearn and Molliver’s theory of trans-synaptic excitoxicity mediated by the olivocerebllar projection.

In light of these findings, a number of researchers have recently been studying the effects of a synthetic congener of ibogaine, 18-methoxycoronaradine, more commonly known as 18-MC. Similar to ibogaine, 18-MC decreases levels of extracellular dopamine in the nucleus accumbens (Szumlinksi, Maisonneuve, and Glick, 2000). Likewise, 18-MC has similar effects to ibogaine on the attenuation of morphine and cocaine self-administration (Glick et al, 1996) and alcohol intake (Rezvani et al, 1997). However, unlike ibogaine, 18-MC is non-tremorigenic, does not induce brachycardia, nor does it cause damage to Purkinje cells, or the brain in general (Glick et al, 1996; Molinari, Maisonneuve, and Glick, 1996; Glick, Maisonneuve, and Szumlinski, 2000). FDA protocol studies of human toxicity had been approved and were underway at the University of Miami, under the direction of neurologist Deborah Mash, but the trials were discontinued due to lack of funding. However, should future studies deem ibogaine too hazardous for clinical use, 18-MC could represent a viable alternative.

Use as an Anti-Addictive:
Currently pharmalogical treatments for substance addiction disorders can be broadly defined as falling two categories; replacement therapy and aversion therapy (Barber and O’Brien, 1999). 1) Replacement therapy includes treatments such as methadone maintenance and non-tobacco nicotine drugs. These therapies replace the drug of abuse with a theoretically safer drug. 2) Aversion therapy includes drugs such as naltrexone and antabuse, which interact with the drug of abuse, causing unpleasant effects such as physical pain, nausea, and vomiting. The hope is that while on these drugs, the patient will avoid use of the drug of abuse, out of desire to avoid the painful side effects.

Ibogaine has distinct advantages over both these models of treatments. Both replacement and aversion therapies are long-term treatments, requiring frequent visits to the clinician over an extended period of time. Contra wise, ibogaine therapy, as described previously, involves more intensive intervention over a shorter time frame (Lotsof, 1994). Unlike the drugs used in replacement therapies, ibogaine itself does not appear to be addictive. Repeated administration of ibogaine, at doses of 10 and 40 mg/kg, did not result in dependence in rats as measured by the Primary Physical Dependence test (Aceto, Bowman, and Harris, 1990). A large concern with methadone treatment is its potential for illicit use; it is not uncommon for patients to sell their supply of methadone on the black market, and revert to heroin use (Barber and O’Brien, 1999). As noted earlier, ibogaine is considered to have a low potential for abuse. Aversion therapies, due to their unpleasant nature, often show high incidences of patient-non-compliance, and subsequent relapse (Barber and O’Brien, 1999). This is generally not an issue with ibogaine therapy; patients treated with ibogaine tend to be more receptive to intervention (Lotsof, 1994).

There is a significant body of evidence supporting ibogaine’s efficacy in the treatment of substance addition disorders. Case studies and anecdotal reports of humans have sighted ibogaine’s ability to interrupt opiate and cocaine addictions for 6 months or longer (Goutarel, Gollnhofer, and Sillans, 1993; Judd, 1994; Sheppard, 1994; Luciano, 1998; Alper et al, 1999). Clinical trials with non-human subjects have substantiated these results. A single intraperitoneal dose of 40 mg/kg reduced self-administration of cocaine for up to 5 days in cocaine-preferring rats (Cappenijk and Dzoljic, 1994). In support of this finding, intraperitoneal doses of ibogaine at 20 – 40 mg/kg reduced cocaine-induced hypermotility (Sershen, Hashim, Harsing, and Lajtha, 1992; Broderick, Phelan, Eng, and Wechsler, 1994; Maisonneuve et al, 1997). Some studies, however, have shown increased locomotor activity induced by ibogaine in non-human cocaine and amphetamine dependent subjects (Maisonneuve, Keller, and Glick, 1992; Maisonneuve and Glick, 1992). Maisonneuve et al (1997) propose that these differences are a result of the time interval between the injections of ibogaine and the given stimulant. Furthermore, ibogaine’s effects on stimulant-induced locomotion, as well as on reduction of cocaine self-administration, appear to be dose-dependent (Glick et al, 1994).

Ibogaine has also been shown to reduce morphine self-administration in clinical trials using non-human subjects. In rats, ibogaine dose dependently reduced intravenous morphine self-administration both immediately after injection and the next day, at doses of 2.5 – 40 mg/kg (Glick et al, 1991). Dworkin et al (1995) found that intraperitoneal doses of ibogaine at 40 and 80 mg/kg reduced heroin self-administration in rats, but only on the day it was administered. The reason for this discrepancy is not yet clear. In human users of heroin (with a daily average use of 0.64 g), oral ibogaine doses of 6 – 29 mg/kg eliminated heroin seeking behaviour for at least 72 hours in 76% of patients treated (Alper et al, 1999).

In addition to reducing opiate self-administration, ibogaine has been shown to reduce symptoms of opiate withdrawal. In rats, intraperitoneal doses of 40 and 80 mg/kg dose-dependently reduced naloxone-induced withdrawal symptoms; including rearing, head hiding, chewing, teeth chattering, writhing, and penile licking (Glick et al, 1992, Parker et al, 2002). In morphine dependent rhesus monkeys, subcutaneous injections of ibogaine (2 and 8 mg/kg) partially suppressed the total number of withdrawal signs (Aceto, Bowman, and Harris, 1990). Alper et al (1999) found that, out of 33 human patients treated with ibogaine, 25 reported no subjective complaints of withdrawal symptoms at 24 and 48 hours post-treatment.

Ibogaine has also been shown to interfere with both alcohol and nicotine dependency. When administered intraperitoneally or intragastrically, but not subcutaneously, ibogaine dose-dependently reduced alcohol intake in rats, without altering blood alcohol levels or food intake (Rezvani, Overstreet, and Lee, 1995). The difference in effects of route of administration may reflect a role of noribogaine in mediating ibogaine’s reduction of alcohol intake. Glick et al (1998) found that intraperitoneal ibogaine pretreatment (19 hours beforehand) of 40 mg/kg significantly decreased oral nicotine self-administration in rats for at least 24 hours. Additionally, this ibogaine pre-treatment significantly attenuated nicotine-induced dopamine release in the nucleus accumbens (Benwell, Holtom, Moran, and Balfour, 1996).



Conclusion and Commentary:
Ibogaine could represent a truly novel approach to addiction treatment. Very loosely, ibogaine seems to “reset” the neural pathways and behavioural phenomena that comprise substance addiction, directly addressing the etiology of the disorder. Though the specific pharmacological actions of ibogaine are not yet clear, the evidence thus far seems to suggest such a hypothesis, at least in its broadest sense, and clearly warrants further investigation. This notion is also reflected in the theme of rebirth seen in the religious use of the iboga root by the indigenous peoples of western Africa.

Should further study replicate the results found thus far, and find ibogaine safe for use in clinical practice, this would be a major step forward in addiction treatment. Current methods of therapy, particularly in the United States, are often ineffectual; typically it takes an addict 4 to 7 times through conventional rehabilitation before abstinence is achieved (Anderson, 1996; Finney, Moos, and Timko, 1999). Ibogaine therapy represents a possibility to significantly reduce the length of time needed to break the addictive cycle

In addition to the amount of effort and time needed, current rehabilitation programs are often degrading to the individual, perpetuating the stigma that addicts are somehow “bad people” (Luciano, 1998). As one patient stated, “ibogaine is a much more humane and dignified approach to detox [sic]” (Judd, 1994). Ibogaine treatment involves a more intimate relationship between the patient and the clinician (or, more appropriately, the team of clinicians), involving a greater level of trust and compassion than is generally seen in typical addiction counselling (Lotsof, 1995). Judd (1994) observed that ibogaine has significant advantages over traditional treatment methods with respect to what she considers the three major obstacles in addiction treatment; fear of detoxification, lack of insight, and the inability of addicts to control their urges to use drugs. The potential benefits of this compound necessitate a greater amount of clinical research. Should further studies suggest that the risks of ibogaine are too great for general use, research on the compound’s effects may nevertheless elucidate unknown aspects of the psychophysiological basis of substance addiction.

While it is fortuitous that serious scientific inquiry into ibogaine’s potential has begun, it is unfortunate that it took such a length of time from the initial discovery of its therapeutic properties. It is unfortunate that politics continue to impede the progress of science. There is a great need for a return of objectivity to science, as far too often today biases and self-serving interests are the driving forces behind scientific exploration. Researchers interested in studying ibogaine’s effects and uses often find themselves fighting an uphill battle to attain the approval and funding necessary to proceed with research. Because of ibogaine’s status as a Schedule I controlled substance, researchers face a great amount of bureaucracy that can often prevent an effective study to be performed. Though it is both logical and practical that dangerous chemicals be controlled as to their permitted uses, often these controls are over extended to the point of prohibiting scientific advancement.

But despite these obstacles, word about ibogaine’s potential uses is slowly spreading. Non-profit organizations are still functioning to inform the public about the therapy, such as Dana Beal’s Cures Not Wars (http://www.cures-not-wars.org) and Howard Lotsof’s Dora Weiner Foundation (http://www.doraweiner.org). New organizations are being formed (outside the United States) to provide ibogaine treatment, such as Vancouver Mayoral candidate Marc Emery’s Iboga Therapy House (which provides treatment at no cost). And Dr. Mash now runs a government licensed ibogaine treatment center, Healing Visions, on the Carribean Island of St. Kitts.

But as promising as these developments are, ibogaine therapy is still beyond the reach of the majority of people who might benefit from it most. We are also still far from truly understanding ibogaine’s complex actions, and indeed, we are still far from understanding the neurological mechanisms of addiction in general. That isn’t to minimize the progress that has been made in both of those areas, as much of it has been quite inspirational. But it will take a good deal of perseverance to ensure that this progress continues, and comes to the fruition that could contribute to the alleviation of one of our most pressing, but often overlooked, issues in mental health; chemical dependency.

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Operator



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PostPosted: Thu 10 Aug, 2006 13:49    Post subject: Reply with quote

Ibogain terapi. Behandlings manualen, läs gärna igenom och kommentera.

http://www.ibogaine.desk.nl/manual.html

OM några år har vi förhoppningsvis en bättre sådan fast på det lilla minortitetsspråket svenska.

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Thaumiel



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PostPosted: Sun 04 Feb, 2007 02:14    Post subject: Reply with quote

Hej.

Vart engagerad för länge sedan av Micke att syssla med verifiering av artiklar och liknande. Har haft häcken full ganska länge men kan nu engagera mig ordentligt.

Första frågan: har vi en svensk översättning av terapi-manualen länkad precis ovan, och om inte, vill vi ha det? Jag är beredd att ge mig på att översätta den som del av mina tjänster.

MVH
Mathias
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Masque
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PostPosted: Sun 04 Feb, 2007 09:31    Post subject: Reply with quote

Terapimanualen är ganska ointressant (just nu) att översätta, den riktar ju sig i första han till de som behandlar, inte de som behandlas. Möjligen att man kan översätta utvalda delar av den... men i mina ögon så har det låg prioritet.

Den text Operator klippt in ovan; "Ibogaine: A Novel Anti-Addictive Compound. A Comprehensive Literature Revie" är intressantare, eftersom vi i nuläget på hemsidan saknar en bra sammanställning av ibogainets farmakologiska egenskaper.

Den får du väldigt gärna översätta!

finns som pdf här: http://www.v72.org/PDF/ibogaine_freelander.pdf
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PostPosted: Fri 13 Apr, 2007 12:45    Post subject: Reply with quote

Glial Cell Line-Derived Neurotrophic Factor Mediates the
Desirable Actions of the Anti-Addiction Drug Ibogaine against
Alcohol Consumption

Hela artikeln som pdf fil

http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&blobtype=pdf&artid=1193648

Quote:
Ibogaine treatment does not result in cell death
To confirm that the effects of ibogaine are not attributable to a neurotoxic effect of the drug,
we examined the brains of mice (n = 2) injected with 40 mg/kg ibogaine and compared them
with uninjected control mice (n =2) using the Fluoro-Jade technique, a technique that has been
used to identify ibogaine-induced cerebellar toxicity (Schmued and Hopkins, 2000). We
scanned serial coronal sections from anterior forebrain to hindbrain of ibogaine-treated and
control brains for brightly fluorescing (dying) neurons. Although myelin, ependymal cells, and
choroid plexus were lightly stained, we observed no brightly fluorescing dying neurons in
either control or ibogaine-treated brains (data not shown). Particular attention was paid to the
midbrain, the region in which we found the increase in GDNF mRNA after ibogaine, and to
the cerebellum, because cell death has been reported in the cerebellum after administration of
high doses of ibogaine (O’Hearn and Molliver, 1993, 1997). The lack of staining that we
observed is in concordance with previous data (Molinari et al., 1996; Schmued and Hopkins,To assay cell death in vitro, SHSY5Y cells were treated with 10 μM ibogaine for 24 hr. Parallel
cultures were treated with 4 μM Wortmannin (PI3 kinase inhibitor) or 2 μM Latrunculin B (actin
polymerization inhibitor) for 90 min. After treatment, cells were fixed in 4% paraformaldehyde
for 3 min and placed in 100% ethanol for 1 min, followed by a 1 min distilled water
wash. The cells were then treated in KMnO4 for 3 min followed by 5 min incubation in a
0.001% acetylated Fluoro-Jade solution. After three washes in distilled water, the cells were
cleared in xylene for 1 min, coverslipped with DPX, and visualized using a Leica fluorescent
microscope with a FITC filter and 10× and 20× objectives.

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PostPosted: Sun 15 Apr, 2007 18:13    Post subject: Reply with quote

Mer belägg kommer in om att att låga nivåer av tillväxtfaktorn GDNF ökar sårbarheten/benägenheten för missbruk. Det är ju just GDNF uttrycken som medicineringen ibogain tenderar att öka, vilket ju kan förklara en del av de goda effekterna man har sett på både djur och människor.


från:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17356005

Quote:
1: FASEB J. 2007 Mar 13; [Epub ahead of print] Links
Enduring vulnerability to reinstatement of methamphetamine-seeking behavior in glial cell line-derived neurotrophic factor mutant mice.Yan Y, Yamada K, Niwa M, Nagai T, Nitta A, Nabeshima T.
*Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan; andLaboratory of Neuropsychopharmacology, Kanazawa University Graduate School of Natural Science & Technology, Kanazawa, Japan.

Genetic factors are considered to play an important role in drug dependence/addiction including the development of drug dependence and relapse. With the use of a model of drug self-administration in mutant mice, several specific genes and proteins have been identified as potentially important in the development of drug dependence. In contrast, little is known about the role of specific genes in enduring vulnerability to relapse, a clinical hallmark of drug addiction. Using a mouse model of reinstatement, which models relapse of drug-seeking behavior in addicts, we provide evidence that a partial reduction in the expression of the glial cell line-derived neurotrophic factor (GDNF) potentiates methamphetamine (METH) self-administration, enhances motivation to take METH, increases vulnerability to drug-primed reinstatement, and prolongs cue-induced reinstatement of extinguished METH-seeking behavior. In contrast, there was no significant difference in novelty responses, METH-stimulated hyperlocomotion and locomotor sensitization, food-reinforced operant behavior and motivation, or reinstatement of food-seeking behavior between GDNF heterozygous knockout mice and wild-type littermates. These findings suggest that GDNF may be associated with enduring vulnerability to reinstatement of METH-seeking behavior and a potential target in the development of therapies to control relapse.--Yan, Y., Yamada, K., Niwa, M., Nagai, T., Nitta, A., Nabeshima, T. Enduring vulnerability to reinstatement of methamphetamine-seeking behavior in glial cell line-derived neurotrophic factor mutant mice.

PMID: 17356005 [PubMed - as supplied by publisher]


GDNF är ju en potent tillväxtfaktor för hjärnan vilket det inte torde råda någon tvekan om, att ibogain ökar nivåerna av den råder det heller ingen tvekan om.

Quote:
GDNF and addiction.Ron D, Janak PH.
Ernest Gallo Research Center, Department of Neurology, University of California, San Francisco, Emeryville, USA. dorit@itsa.ucsf.edu

Biochemical adaptations to drugs of abuse and alcohol are especially profound in midbrain dopaminergic neurons. Long-lasting molecular and structural changes in mesolimbic dopaminergic neurons that result from chronic exposure to drugs of abuse and alcohol are thought to underlie adverse behaviors such as compulsive drug seeking and relapse. Recent studies suggest that a subset of these changes is prevented/reversed by activation of the glial cell line-derived neurotrophic factor (GDNF) signaling pathway. Behavioral effects of drugs of abuse such as cocaine and alcohol are also negatively regulated by GDNF: inhibition of the endogenous GDNF pathway enhances the activity of drugs of abuse, while administration of GDNF reduces the severity of the effects. In this review, we summarize the data implicating GDNF as a negative regulator of drug and alcohol addiction. We also provide evidence to suggest that therapies that activate GDNF signaling may be useful for the treatment of drug and alcohol addiction.

PMID: 16519005 [PubMed - indexed for MEDLINE]


Då får vi hoppas att vi får igång en forskning värd namnet om ämnen som kan höja tillgängligheten och funktionen av GDNF, antagligen kommer det att innebära en revolution i behandlingen av vissa typer degenerativa hjärnsjukdomar att få en höjning av GDNF-nivåerna.

se: http://www.unr.nevada.edu/~hqt/
Bilderna talar sitt tydliga språk. GDNF ger en nettotillväxt i hjärnan av fungerande vävnad vid den degenerativa hjärnsjukdomen parkinson.

Quote:
Role for GDNF in biochemical and behavioral adaptations to drugs of abuse.

* Messer CJ,
* Eisch AJ,
* Carlezon WA Jr,
* Whisler K,
* Shen L,
* Wolf DH,
* Westphal H,
* Collins F,
* Russell DS,
* Nestler EJ.

Laboratory of Molecular Psychiatry and Yale Center for Genes and Behavior, Yale University School of Medicine and Connecticut Mental Health Center, New Haven 06508, USA.

The present study examined a role for GDNF in adaptations to drugs of abuse. Infusion of GDNF into the ventral tegmental area (VTA), a dopaminergic brain region important for addiction, blocks certain biochemical adaptations to chronic cocaine or morphine as well as the rewarding effects of cocaine. Conversely, responses to cocaine are enhanced in rats by intra-VTA infusion of an anti-GDNF antibody and in mice heterozygous for a null mutation in the GDNF gene. Chronic morphine or cocaine exposure decreases levels of phosphoRet, the protein kinase that mediates GDNF signaling, in the VTA. Together, these results suggest a feedback loop, whereby drugs of abuse decrease signaling through endogenous GDNF pathways in the VTA, which then increases the behavioral sensitivity to subsequent drug exposure.

PMID: 10798408 [PubMed - indexed for MEDLINE]

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