Ibogaine, alkaloid of plant origin, is not yet an officially prescribed drug but many experts consider it a perspective agent in drug dependency cure. The assumption is based on a couple of past open trials and virtually accidental uses of single doses of Ibogaine or short-term Ibogaine therapies resulting in long-term drug abstention for several months, and often ongoing. The above-mentioned incredibly promising effect of Ibogaine, as well as its sometimes questioned safety of application in pharmacotherapy, are currently being tested in experimental and clinical trials. The results are interesting and encouraging.
Ibogaine is an alkaloid discovered in the roots of Tabernathe Iboga shrub (of Apocynacae family, Contonae order) as well as in some other species growing in the rain forests of Central and Western Africa around the equator. The aborigines traditionally chewed the roots for treatment of fatigue, hunger and thirst. Higher doses, especially in extracts, changed the state of mind and were used for religious ritual purposes (best-known is the application in the “Bwiti” religion).
The main active agent – the indole alkaloid called Ibogaine – was first extracted from the root of Iboga in 1901. Its exact structure, however, has only been known since 1957 (the first complete synthesis of Ibogaine from nicotine-amide was performed in 1975). Early 20th century psychotherapists recommended Ibogaine as a stimulating agent in treatment of and recovery from neurasthenia. In the 1930’s extracts containing Ibogaine were sold under the names of Lambarene (France) or Alperton, as stimulating agents and muscle tonics without substantial establishment in medicinal practice. When, in 1906, reports of hallucinogenic effects of Ibogaine began to increase in number its application was prohibited in a number of countries (including the U.S.A. in 1970).
A new revival of pharmaceutical interest in Ibogaine was initiated by the incredible news of its effect in treatment of drug dependency. In 1962-1963 H. S. Lotsof, still in the United States, first opened clinical sessions with heroin and cocaine dependent patients, including himself. He reported that a single dose caused long-term disappearance of desire for the drug craving in some of the dependent patients, inhibiting abstention symptoms in heroin-dependent patients.
About twenty years later Lotsof returned to Ibogaine (continuing his research in the Netherlands), trying to introduce it to the pharmaceutical market under the name of Endabus. Lotsof’s Ibogaine-based therapies were patented in stages (1985 – 1992) for treatment of opiate, cocaine, alcohol, nicotine and multiple dependency – U.S. patent, Lotsof – opiates (1985), cocaine (1986), alcohol (1989), nicotine (1991) and multiple dependency (1992).
Application of Ibogaine in controlled studies performed in the Netherlands was supported by NDA International from 1985. The results of the Dutch studies were very promising: Application of a single dose of Ibogaine (20-25 mg/kg of body weight) led to six-month abstention of minimum two-thirds of the patients (out of the total number of 35 heroine and cocaine dependent), two-year or longer abstention of 10% of the patients, and return to the drug after 14 days of only 10% of the patients. Lotsof also reported improved prognoses after repeated Ibogaine sessions (1).
Unfortunately, in the course of one of the studies a young heroine-dependent female patient died by an unlucky coincidence. The legal action against Lotsof discovered no neglect on the part of the therapist, and the applied dose of Ibogaine was also low and usual (the Ibogaine level in the blood of the deceased patient was 0.75 mg/l). It is maintained that the death might have been caused by simultaneous application of Ibogaine and the drug (the patient probably secretly smoked heroin in the course of the session).
This case, however, pointed out lack of scientific and pharmacological knowledge of Ibogaine – mechanisms of its effect, pharmacokinetics etc. Clinical studies in the Netherlands were discontinued and the focus of the research was moved to experimental pre-clinical level.
Preclinical studies confirmed the effect of Ibogaine in inhibition of symptoms of abstention from opiates and inhibition of “autoapplication” of inhibiting and stimulating drugs, including alcohol and nicotine. A number of details increasing accuracy of pharmacokinetic and toxicological information were acquired, including significant contribution of long-term effectiveness of the active metabolite of noribogaine to the effect of ibogaine. Other related metabolites and derivatives of Ibogaine were tested, including 18-MK substance (18-metoxykoronaridine) with minimum toxicity even in high doses etc. Ibogaine was discovered to influence a number of neuromediating and other regulation systems.
At present clinical tests of Ibogaine are continued, for example in cooperation with the Miami University, U.S.A. (Professor D. C. Mash) or the Panama University. Results of clinical study phase 1 – safety and kinetics – have been published, together with results of phase 2 of research – in first patients, and appear promising.
On the basis of current knowledge a preliminary conclusion can be drawn; about the safety of application of Ibogaine and its active metabolite of Noribogaine in drug dependent subjects, its inhibition of opiate withdrawal symptoms after a single dose and inhibition of craving for heroine and cocaine after a single dose, noting the long-term effect in some patients, or extension of the effect by repeated sessions.
Regarding the multiple effect of the substance on various neuromediators and potential effect on different types of dependencies (in animal experiments blocking autoapplication of opiates, amphetamine, cocaine, alcohol, nicotine) Ibogaine may be considered the beginning of a new trend in research into pharmacotherapy of drug dependence. Ibogaine and its derivatives might be applied in treatment of many more dependencies, including the frequent poly-drug dependencies so difficult to deal with. Of course further research will be necessary.
A number of dose-dependent central psychotropic effects of Ibogaine have been reported in humans. Effects of extract from the root of Tabernathe Iboga are more complex and can differ from the effects of Ibogaine itself. The root extract in sufficient doses evokes fantastic visual images, feelings of excitement, drunkenness, mental confusion to hallucination.
The extract from Iboga root is certainly a CNS stimulating agent, high doses being likely to cause spasms, paralysis and eventually apnea. High doses may also cause hearing, visual and taste synaesthesia and moods ranging from deep sorrow to rejoicing euphoria.
Oral application of Ibogaine or root extract may generate subjective effects lasting for about 6 hours. About 50% of Ibogaine treated individuals described confusion, gesture dis-coordination, nausea, vomiting.
Typical symptoms include sleepiness, with the subject unwilling to move, open its eyes, and communicate (even though being able to communicate). Many subjects react with increased sensitivity to light and preference for darkness. Noise and sounds are very irritating. The resulting condition resembles sleep, although the person is conscious.
The subjects have described fantastic images in quick succession, like a quickly projected film or quickly changing slides. The contents of the images have differed, often including typical archetypal contents, personal experience, problems, past decisions and relationships, including images of animals and other people. Although the fantasies can be manipulated by both the subject and the psychotherapist, the quick succession of images is easy to break. That is why the activity of psychotherapist focuses on the period immediately following the session itself. Higher doses of Ibogaine may cause visual and other hallucinations, often combined with fear and evil apprehensions.
Preliminary results of clinical trials phase 2 (39 patients, application of a single dose, 1 month follow up) have so far demonstrated effect of Ibogaine in the course of detoxification of opiate-dependent patients and in short-term stabilization of drug-dependent subjects before or in early stages of therapy. Ibogaine has significantly reduced craving for cocaine and heroine during detoxification. Depressive symptoms in patients (self-assessment) have also been reduced, the improvement as a rule being preserved until the end of the therapeutic program (30 days).
Iboga regarding serotonin and neurotransmitter