v 1.0 - April 1995
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- A Brief History
- Ibogaine, Psychotherapy, and the Treatment of Substance-Related Disorders
- Brief Ibogaine Bibliography
Ibogaine is not a substitute for narcotics or stimulants, is not addicting and is given in a single administration modality (SAM). It is a chemical dependence interrupter. Retreatment may occasionally be needed until the person being treated with Ibogaine is able to extinguish certain conditioned responses related to drugs they abuse. Early data suggests that a period of approximately two years of intermittent treatments may be required to attain the goal of long-term abstinence from narcotics and stimulants for many patients. The majority of patients treated with Ibogaine remain free from chemical dependence for a period of three to six months after a single dose. Approximately ten percent of patients treated with Ibogaine remain free of chemical dependence for two or more years from a single treatment and an equal percentage return to drug use within two weeks after treatment. Multiple administrations of Ibogaine over a period of time are generally more effective in extending periods of abstinence.
A BRIEF HISTORY
Ibogaine, a naturally occurring alkaloid found in Tabernanthe iboga and other plant species of Central West Africa, was first reported to be effective in interrupting opiate narcotic dependence disorders in U.S. patent 4,499,096 (Lotsof, 1985); cocaine dependence disorders in U.S. patent 4.587,243 (Lotsof, 1986) and poly-drug dependence disorders in U.S. patent 5,152,994 (Lotsof, 1992). The initial studies demonstrating Ibogaine's effects on cocaine and heroin dependence were accomplished in a series of focus group experiments by H. S. Lotsof in 1962 and 1963. Additional data on the clinical aspects of Ibogaine in the treatment of chemical dependence were reported by Kaplan (1993), Sisko (1993), Sanchez-Ramos & Mash (1994), and Sheppard (1994).
Prior to Ibogaine's evaluation for the interruption of various chemical dependencies, the use of Ibogaine was reported in psychotherapy by Naranjo (1969, 1973) and at the First International Ibogaine Conference held in Paris (Zeff, 1987). The use of Ibogaine-containing plants has been reported for centuries in West Africa in both religious practice and in traditional medicine (Fernandez, 1982; Gollnhofer & Sillans 1983, 1985) An overview of the history of Ibogaine research and use was published by Goutarel et al. (1993).
Claims of efficacy in treating dependencies to opiates, cocaine, and alcohol in human subjects were supported in preclinical studies by researchers in the United States, the Netherlands and Canada. Dzoljic et al. (1988) were the first researchers to publish Ibogaine's ability to attenuate narcotic withdrawal. Stanley D. Glick et al. (1992) at Albany Medical College published original research and a review of the field concerning the attenuation of narcotic withdrawal. Maisonneuve et al. (1991) determined the pharmacological interactions between Ibogaine and morphine, and Glick et al. (1992) reported Ibogaine's ability to reduce or interrupt morphine self-administration in the rat. Woods et al. (1990) found that Ibogaine did not act as an opiate, and Aceto et al. (1991) established that Ibogaine did not precipitate withdrawal signs or cause dependence.
Cappendijk and Dzoljic (1993) published Ibogaine's effect in reducing cocaine self-administration in the rat. Broderick et al. (1992) first published Ibogaine's ability to reverse cocaine-induced dopamine increases and later, on Ibogaine's reduction of cocaine-induced motor activity and other effects (1994). Broderick et al.'s research supported the findings of Sershen et al. (1992), that Ibogaine reduced cocaine-induced motor stimulation in the mouse. Sershen (1993) also demonstrated that Ibogaine reduced the consumption of cocaine in mice. Glick (1992) and Cappendijk (1993) discovered in the animal model that multiple administrations of Ibogaine over time were more effective than a single dose in interrupting or attenuating the self-administration of morphine and cocaine, supporting Lotsof's findings in human subjects (1985).
Popik et al. (1994) determined Ibogaine to be a competitive inhibitor of MK-801 binding to the NMDA receptor complex. MK-801 has been shown to attenuate tolerance to opiates (Trujillo & Akil 1991) and alcohol (Khanna et al. 1993). MK-801 has also shown a blockade of "reverse tolerance" of stimulants (Karler et al. 1989). Ibogaine's effects on dopamine, a substance hypothesized to be responsible for reinforcing pleasurable effects of drugs of abuse, and the dopamine system were found by Maisonneuve et al. (1991), Broderick et al. (1992) and Sershen et al. (1992). Ibogaine binding to the kappa opiate receptor was reported by Deecher et al. (1992). Thus we begin to see a broad spectrum of mechanisms by which Ibogaine may moderate use of substances so diverse as opiate narcotics, stimulants and alcohol.
Ibogaine is currently under review by the National Institute on Drug Abuse. On March 8, 1995 an Ibogaine Review meeting was held to determine if the Medications Development Division of NIDA would proceed to multi-site clinical studies. That decision is now being awaited.
The FDA has already approved one human Ibogaine research project and is considering changes that may allow the research to move more quickly. Additionally the National Institute on Drug Abuse may proceed to multi-site human studies to determine if Ibogaine is effective in treating cocaine dependency. The ministry of Health in the Republic of Panama has approved experimental Ibogaine treatments at therapeuic doses which puts it about two years head of the United States. Researchers in Israel and Turkey are also considering human trials for opiates and alcoholism.
Ibogaine is not an LSD-like drug and appears according to early reports to be effective in the treatment of various forms of chemical dependence including opiates, stimulants, alcohol, nicotine or combinations of the above. The real surprise seemed to come when prelimiary treatment of methadone dependent persons also appeared to be effective in the same two to four day Lotsof procedure for the treatment of addiction. The substance has a psycho/pharmacological effects including both Freudian and Jungian perceptions in addition to its ability to diminish narcotic withdrawal.
Ibogaine's actions breaks down into three component parts. The first is a four to six hour period emulating dreaming in which either visual presentations or thoughts dealing with past events are experienced. The second is a cognitive or intellectual period in which those experiences are evaluated and the third is a period of residual stimulation eventually resulting in sleep. It is after the patient awakes that the effects are principally noticed in a lack of a desire in the majority of patients to seek or use the drugs they were abusing. However, it should be noted that the responses to the drug are very individual just as the patient has individual characteristics.
IBOGAINE, PSYCHOTHERAPY, AND THE TREATMENT OF SUBSTANCE-RELATED DISORDERS
Barbara E. Judd, CSW
Presented at The Eighth International Conference on Drug Related Harm
November 19, 1994
I have been working with chemically dependent patients, some having dual diagnoses, for twelve years in outpatient settings. My observations have been that the earliest phase of recovery, the first ninety days, is the most difficult for the therapist and the patient. I would like to compare and contrast certain issues seen as obstacles by patients, some of whom were treated with the Lotsof method and some treated in traditional outpatient settings.
My observations are based on a small sample of patients seen in the U.S. and overseas. These observations are inconclusive and my work is ongoing.
My involvement with Ibogaine began in June 1993, when I was approached by the International Coalition for Addict Self-Help (ICASH) and requested to provide aftercare for five patients who were treated with Ibogaine and were eager to share their experience and struggles. Four of the group were white males ranging in age from early thirties to mid forties. One was a female in her thirties. Their dependencies were to heroin, Methadone and/or cocaine. Additional substance use included marijuana, alcohol and psychedelics. This group met once a week for the duration of one year.
Concurrent treatment was provided to one member of this group on an individual basis. This patient, who we will refer to as "M" is still presently under my care. "M" is thirty-three years old and formally heroin/methadone/cocaine dependent. He has been using drugs since the age of fourteen.
My most recent involvement with Ibogaine has been with NDA International, Inc. when I participated in the treatment of three patients using the Lotsof method in Panama. All three patients were white males in the thirty to forty age range. Two of the patient's major drug of choice was cocaine which was taken, orally, nasally or by IV injection by one patient; the other by oral or nasal administration only. The third patient was heroin/cocaine dependent and occasionally used methadone in attempts to curb his habit. All patients had used drugs from six to sixteen years.
One of the most difficult aspects of treatment is getting the patient to enter treatment. The three major obstacles are the fear of detoxification, lack of insight, and the inability of patients to control their urges to use drugs. These are the areas where I have observed the benefits of Ibogaine treatment versus traditional methods.
Fear of Detoxification
Across the board, addicts who enter outpatient treatment programs report that their fear of detoxing from drugs has prevented them from attending treatment. Although withdrawal from cocaine is not as severe or obvious as that from opiate narcotics, there is a fear of the psychological pain of never being able to use again. There is also a dread that once drug free, feelings that have been blocked by self-medicating will surface and be too overwhelming for the patient to handle.
Most heroin addicts are petrified of withdrawal symptoms and are afraid of hospital detoxification. Outpatient clients have stated to me that they have delayed treatment to avoid this anticipated discomfort.
My observations with Ibogaine treated patients have been that patients are eager to be treated when they know that Ibogaine promises to eliminate painful withdrawal, takes one administration with up to seventy-two hours of supervised care, and promises to interrupt their urges to use drugs.
Three patients: Panama
- Patient "1" had used approximately $100 each per day of heroin and cocaine by IV administration for twenty of the thirty days prior to Ibogaine treatment.
- Patient "2", prior to treatment was using $80 per day of cocaine and alcohol.
- Patient "3" was using $50 of cocaine on a daily basis via IV injection and smoking. He had previously been heroin dependent.
For these patients to have had little discomfort during withdrawal, speaks to the importance of the use of Ibogaine in the beginning of the recovery process. As patient "M" had stated, "Ibogaine is a much more humane and dignified approach to detox".
Obstacles Within Traditional Treatment
Returning to the obstacles of treatment, the second being the patients' lack of insight. Insight is necessary for patients to be able to focus and develop goals while in recovery.
Patients in traditional outpatient groups who have less than ninety days clean, spend more time struggling with their urges to use and dealing with their defenses, specifically denial. They do develop insight into their problems, however, it takes at least one year of group treatment meetings one or two times a week on a regular basis.
In contrast, my involvement with providing aftercare for the Ibogaine treated group showed these patients as having tremendous insight into their own issues, their feelings, and what might have caused them to use in the first place.
After their Ibogaine treatment, patients began to see their drug use as destructive. This realization, coupled with psychotherapy, has allowed these patients to work on how to stay clean and to focus on what they must do to maintain a less destructive lifestyle.
The reason for this insight developed by these patients appears to be the release of repressed material during the visualization stage of Ibogaine treatment. This material includes both images and racing thoughts, which somehow get processed to allow patients to have a better understanding of their emotional histories.
The urge to use drugs again, is the highest cause for people to drop out of traditional treatment. Relapse, I think, is clearly inherent in the definition of substance-related disorders. In working with people treated with or without Ibogaine, my observations have been that relapse at some point is certain.
However, according to members in the Ibogaine group, Ibogaine had reduced their urges to use, anywhere from two months to more than one year. This advantage allowed these patients to get a head start in their recovery, whereas clients in traditional outpatient treatment have a great deal of confusion around how to control their urges. Consequently, those patients have to learn very basic and concrete ways to stay clean as taught by self-help meetings, and emphasized in psychotherapy. The Ibogaine aftercare group did not appear to need self-help type assistance to reduce their urges, but seemed to benefit well from psychotherapy.
In conclusion, there is difficulty treating the drug addicted patient, particularly in the early stages of recovery, because of their fear of detox, their lack of insight, and their urges to relapse.
Thus far, there is no opportunity for Ibogaine treatment within the United States. It is my recommendation that there be future research done with Ibogaine, so that some of the above mentioned observations are supported by more conclusive data.
The prospects for a painless withdrawal method makes Ibogaine an attractive alternative to traditional treatment methods. Because Ibogaine interrupts substance related disorders, it gives patients a head start in their recovery. It also increases the patients' receptiveness to psychotherapy, which is a necessary component to the recovery process.
Brief Ibogaine Bibliography
- Aceto MD, Bowman E, Harris LS
Dependence studies of new compounds in the rhesus monkey, rat and mouse,
NIDA Research Monograph, 95:578,607, 1990.
- Broderick PA, Phelan FT, Berger SP,
Ibogaine alters cocaine induced biogenic amine and psychostimulant dysfunction but not [3H] GBR-12935 binding to the dopamine transporter protein,
NIDA Research Monograph, 119:285, 1992.
- Broderick PA, Phelan FT, Eng F, Wechsler RT,
Ibogaine Modulates Cocaine Responses Which Are Altered Due to Environmental Habituation: In Vivo Microvoltammetric and Behavioral Studies,
Pharmacology Biochemistry and Behavior, 49(3):711-728, 1994.
- Cappendijk SLT, Dzoljic MR,
Inhibitory effects of ibogaine on cocaine self-administration in rats,
European Journal of Pharmacology, 241:261-265, 1993.
- Cappendijk, SLT, Fekkes D, Dzoljic MR,
The inhibitory effects of norharman on morphine withdrawal syndrome in rats: comparison with ibogaine,
Behavioural Brain Research, 65:117-119, 1994.
- Deecher DC, Teitler M, Soderland DM, Bornmann WG, Kuehne MR, Glick SD,
Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies,
Brain Research, 571:242-247, 1992.
- Depoortere H,
Neocortical Rhythmic Slow Activity during Wakefulness and Paradoxical Sleep in Rats,
Neuropsychobiology, 18:160-168, 1987.
- Dhahir HI,
A Comparative Study of the Toxicity of Ibogaine and Serotonin
(Doctoral Dissertation, Indiana University) University Microfilms International, 71-25-341, 1971.
- Dzoljic ED, Kaplan CD, Dzoljic MR,
Effects of Ibogaine on Naloxone-Precepitated Withdrawal Syndrome in Chronic Morphine-Dependent Rats,
Archive of International Pharmacodynamics, 294:64-70, 1988.
- Glick SD, Rossman K, Steindorf S, Maisonneuve IM, Carlson JN,
Effects and aftereffects of ibogaine on morphine self-administration in rats,
European Journal of Pharmacology, 195:341-345, 1991.
- Glick SD, Rossman K, Rao NC, Maisonneuve IM, Carlson JN,
Effects of Ibogaine on Acute Signs of Morphine Withdrawal in Rats: Independence from Tremor,
Neuropharmacology, 31(5):497-500, 1992.
- Glick SD, Gallagher CA, Hough LB, Rossman KL, Maisonneuve IM,
Differential effects of ibogaine pretreatment on brain levels of morphine and (+) - amphetamine,
Brain Research, 588:173-176, 1992.
- Glick SD, Kuehne ME, Raucci J, Wilson TE, Larson E, Keller, Jr. RW, Carlson JN,
Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorgenic effects and to effects on dopamine release in nucleus accumbens and striatum,
Brain Research, 657:14-22, 1994.
- Goutarel R, Gollnhofer O, Sillans R,
Pharmacodynamics and Therapeutic Applications of Iboga and Ibogaine,
Psychedelic Monographs and Essays, vol. 6, 1993.
- Goutarel R, Gollnhofer O, Sillans R,
L'IBOGA CONTRE LA DEPENDENCE AUX STUPEFIANTS. PHARMACODYNAMIE ET APPLICATIONS PSYCHOTHERAPEAUTIQUES,
Psychotropes, 3(3):63-86, 1993.
- Harsing LG, Sershen H, Lajtha A,
Evidence that ibogaine releases dopamine from the cytoplasmic pool in isolated mouse striatum,
Journal of Neural Transmission, 96:215-225, 1994.
- Jacobson AE,
Biological Evaluation of Compounds for Their Physical Dependence Potential and Abuse Liability. XIII. Drug Tersting Program of the Committee on Problems of Drug Dependence, Inc.,
NIDA Research Monograph, 95:563, 1990.
- Kaplan CD, Ketzer E, de Jong J, de Vries M,
Reaching a State of Wellness: Multistage Explorations in Social Neuroscience,
Social Neuroscience Bulletin, 6(1):6-7, 1993.
- Keefner SM, Glick SD,
Ibogaine Antagonism of Morphine-Induced Hyperactivity: Enhancement by Prior Morphine Exposure and Role of Kappa Opioid Receptors,
Society of Neuroscience Abstracts, 20:502.5, 1994.
- Lotsof HS, U.S. patent 4,499,096;
Rapid Method for Interrupting the Narcotic Addiction Syndrome, 1985.
- Lotsof HS, U.S. patent 4,587,243;
Rapid Method for Interrupting the Cocaine and Amphetamine Abuse Syndrome, 1986.
- Lotsof HS, U.S. patent 4,857,523;
Rapid Method for Attenuating The Alcohol Dependency Syndrome, 1989.
- Lotsof HS, U.S. Patent 5,026,697,
Rapid Method for Interrupting or Attenuating The Nicotine/Tobacco Dependency Syndrome., 1991.
- Lotsof HS, U.S. patent 5,124,994;
Rapid Method for Interrupting or Attenuating Poly-drug Dependency Syndromes, 1992.
- Lotsof HS,
Ibogaine in the Treatment of Chemical Dependence Disorders: Clinical Perspectives (A Preliminary Review),
Bull. MAPS, 5(3), 1995.
- Mash DC, Douyon R, Hearn WL, Sambol NC & Sanchez-Ramos J,
A Preliminary Report on the Safety and Pharmacokinetics of Ibogaine,
Biological Psychiatry, 1995 In Press.
- Maisonneuve IM, Keller RW, Glick SD,
Interactions between ibogaine, a potential anti- addictive agent and morphine: an in vivo microdialysis study,
European Journal of Pharmacology, 199:35-42, 1991.
- Maisonneuve IM, Glick SD,
Interactions between ibogaine and cocaine in rats: in vivo microdialysis and motor behavior,
European Journal of Pharmacology, 212:263- 266, 1992.
- Maisonneuve IM, Rossman KL, Keller Jr. RW, Glick SD,
Acute and prolonged effects of ibogaine on brain dopamine metabolism and morphine-induced locomotor activity in rats,
Brain Research, 574:69-73, 1992.
- Maisonneuve IM, Keller Jr. RW, lick, SD,
Interactions of ibogaine and D-amphetamine: in vivo microdialysis and motor behavior in rats,
Brain Research, 579:87-92, 1992.
- Molinan HH, Maisonneuve IM, Glick SD,
Dose Dependence of Ibogaine Neurotoxicity,
Society for Neuroscience Abstracts, 20:504.4, 1994.
- Naranjo C,
Psychotherapeutic Possibilities New Fantasy Enhancing Drugs,
Clinical Toxicology, 2(2):209-224, 1969.
- Naranjo C,
The Healing Journey,
Pantheon Books, Div. Random House, NY, 174-228, 1973.
- O'Hearn E, Long DB, Molliver MR,
Ibogaine induces glial activation in parasagittal zones of the cerebellum,
Neuropharmacology and Neurotoxicology, NeuroReport 4:299- 302, 1993.
- O'Hearn E, Molliver ME,
Degeneration of Purkinje Cells in Parasagittal Zones of the Cerebellar Vermis After Treatment with Ibogaine or Harmaline,
Neuroscience, 55(2):303-310, 1993.
- Popik P, Layer RT, Skolnick P,
The Putative anti-addictive drug ibogaine is a competitive inhibitor of [3H]MK-801 binding to the NMDA receptor complex,
Psychopharmacology, 114:672-674, 1994.
- Sanchez-Ramos J, Mash DC,
Ibogaine Research Update: Phase I Human Study,
MAPS, IV(4):11, 1994.
- Schechter MD, Gordon TL,
Comparison of the behavioral effects of ibogaine from three sources: mediation of discrimintive activity,
European Journal of Pharmacology 249:70-84, 1993.
- Schneider JA, McArthur M,
Potentiation Action of Ibogaine (Bogadin TM) on Morphine Analgesia,
Experientia, XII(8):323-324, 1956.
- Schneider JA, Sigg EB,
Neuropharmacological Studies of Ibogaine, An Indole Alkaloid with Central Stimulant Properties,
Annals New York Academy of Sciences, 66:765-776, 1957.
- Schneider, JA, Rinehart RK,
Analysis of the Cardiovascular Action of Ibogaine Hydrochloride,
Archive of International Pharmacodynamics, CX(1):92-102, 1957.
- Sershen H, Hashim A, Harsing L, Lajtha A,
Ibogaine Antagonizes Cocaine Induced Locomotor Stimulation in Mice,
Life Sciences, 50:1079-1086, 1992.
- Sershen H, Harsing LG, Hashim A, Lajtha A,
Ibogaine Reduces Amphetamine-Induced Locomotor Stimulation C57L/6By Mice, but Stimulates Locomotor Activity in Rats,
Life Sciences, 51:10003-1011, 1992.
- Sershen H, Hashim A, Lajtha A,
Ibogaine Reduces Preference for Cocaine Consumption in C57BL/6By Mice,
Pharmacology Biochemistry and Behavior. 46:942-948, 1993.
- Sershen H, Hashim A, Lajtha A,
Effects of Ibogaine on Serotonergic and Dopaminergic Interactions in Striatum of Mice and Rats,
Neurochemical Research, 19(11):1463- 1465, 1994 In Press.
- Sershen H, Hashim A, Lajtha A,
The Effects of Kappa-Opioid and 5-HT3-Induced Changes in Stimulation-Evoked Dopamine Release in Vitro from Striatum of C57BL/By Mice,
Brain Research , 1994, In Press.
- Sharpe LG, Jaffe JH,
Ibogaine Fails to Reduce Naloxone-Precipitated Withdrawal in the Morphine-Dependent Rat,
Neuropharmacology and Neurotoxicology (NeuroReport), 1:17-19, 1990.
- Sheppard SG,
A Preliminary Investigation of Ibogaine: Case Reports and Recommendations for Further Study,
Journal of Substance Abuse Treatment, 11(4):379-385, 1994.
- Sisko B,
Interrupting Drug Dependency: A Summary of 4 Case Histories,
MAPS 4(2):15-23, 1994.
- Woods JH, Medzihdsky F, Smith CB, Winger GD, France CP,
1989 Annual Report, Evaluation of New Compounds for Opioid Activity,
NIDA Research Monographs, 95:655-656, 1990.