[h2]IBOGAINE IN THE TREATMENT OF CHEMICAL DEPENDENCE DISORDERS: CLINICAL PERSPECTIVES[/h2] [h3](A Preliminary Review)[/h3] [h4]H.S. LOTSOF[/h4] © 1994 Dedicated to the work J. Bastiaans and N.F.P. Adriaans
in memory of N. Kribus
[h3]INTRODUCTION[/h3] The primary purpose of this paper is to provide general information to the clinician who will be using the Lotsof Proceduresm (Goutarel, 1993) developed by NDA International, Inc. in which Ibogaine
is administered to treat chemical dependence disorders. This is a preliminary report. The patient base upon which my conclusions have been made totals thirty-five treatment episodes. All clinical observations conducted after 1963 have been made on patients treated outside of the United States.
Ibogaine is not a substitute for narcotics
, 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. It is noteworthy that twenty-nine of the thirty-five patients successfully treated with Ibogaine had numerous unsuccessful experiences with other treatment modalities.
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 (1994) 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.
The effects of Ibogaine treatment are viewed in three categories: acute, intermediate and long-term. The acute and intermediate effects have sometimes been referred to as the effects and aftereffects. The two major effects of Ibogaine are A) the ability to interrupt narcotic and stimulant withdrawal and B) the attenuation or elimination of the craving to continue to seek and use opiates, stimulants and alcohol (Lotsof 1985, 1986, 1989). Knowledge concerning the use of Ibogaine in treating alcohol dependence is limited to: 1) a single alcohol-only dependent patient and 2) the attenuation and, in some cases, cessation of alcohol use in persons treated for poly-drug dependence disorders. Ibogaine's ability to treat nicotine
dependence (Lotsof, 1991) has been seen in poly-drug dependent subjects treated primarily for opiate and/or cocaine use .
First, there are some general considerations. The primary obligations of the treatment team are four-fold: 1 ) to earn the trust of the patient, 2) to maintain the comfort of the patient, 3) to assist the patients in interrupting their chemical dependence 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. This is a process the Dutch treatment community refers to as normalization.
In the Lotsof Proceduresm, for which a manual is now being prepared, the sense of conflict seen in most treatment modalities between the doctor and patient over the immediate ceasing of drug use does not exist. The patients have been allowed, if narcotic-dependent, to continue their use of narcotics until a certain time prior to treatment with Ibogaine. There is no conflict over opiate use before treatment as our position has been that Ibogaine will either work to interrupt chemical dependence or it will not. Patients dependent on stimulants are not maintained on stimulants and this has not created a problem for the patients or the medical staff.
Prior to our conducting Ibogaine treatments in hospitals, addicted patients were allowed to use their personal supply of narcotics until the evening before treatment. However, during hospital-administered Ibogaine sessions, the narcotic-dependent patient is maintained on medications prescribed by the principal investigator during the three to five day intake process preceding their treatment with Ibogaine. Even under these circumstances, patient distrust of the medical establishment and their extreme fear of going into withdrawal has resulted in the smuggling of narcotics into hospital environments. In order to protect the patient from possible overdose due to narcotics, stimulants or other drugs, a thorough physical examination is performed on all patients upon their admission to hospital environments. The examination and a search of the patient's possessions prior to treatment with Ibogaine serve two important functions. The first, is to limit the possibility of accidental overdose from secreted drugs. The second, is to provide a complete understanding of the patient's physical health, since many of the people seeking treatment for chemical dependence have masked various and often numerous medical problems for years or even decades by self-medicating with illicit drugs.
The acute effects of Ibogaine are dramatic. The initial reaction is usually noted within forty-five minutes after the oral dose and full effects are generally evident within two to two and a half hours. The earliest subjective indication by patients of Ibogaine's effects is the report of a pervasive oscillating sound. The patient tends to lie down and, if asked to stand or walk, shows signs of ataxia
The protocol for the Lotsof Proceduresm stipulates that the patient remain in bed with as little movement as possible from the time of Ibogaine administration, as nausea associated with Ibogaine use has proven to be motion-related or, in later stages (those longer than four hours after administration), possibly to be a psychosomatic reaction to previously repressed traumatic experiences. In addition to keeping the patient as still as possible, we use a non-phenothiazine anti-nauseant, as phenothiazines may interfere with the psychoactive
properties of Ibogaine. If the patient vomits in less than two and a half hours after the administration of Ibogaine, an examination of the regurgitated material should be made to determine how much Ibogaine may have already been absorbed by the patient. A rectal infusion of Ibogaine to supplement the lost portion of the dose may be provided if it is not possible for this dose to be administered orally. The rectal administration should occur only if the patient has previously consented to this mode of dosing.
One of Ibogaine's principal effects during its first phase of action is to produce a state which emulates dreaming, aside from the fact that the subject is fully awake and has the ability to respond to the treatment staff's questions. In most cases, people under the influence of a therapeutic dose of Ibogaine do not wish to speak. They prefer instead to pay close attention to the visual presentation of memories or phenomena they are experiencing, that have been noted to have both Freudian and Jungian connotations.
The experiencing of visual material is rapid. Some patients have described it as a movie run at high speed; others as a slide show, each slide containing a motion picture of a specific event or circumstance in the viewer's life. In either case, the presentation of visual material is so compressed and fast moving that distracting the patient for even a moment may interfere with the process of abreaction. Therefore, in treatment, the intrusion of the medical staff should be kept to a minimum during Ibogaine's primary phase.
During the first through the fifth hour there is a moderate rise in blood pressure of ten to fifteen percent and, in some cases, an associated decline in the pulse rate. The most significant autonomic changes occur between one and a half and two and a half hours after administration of therapeutic doses of Ibogaine. In many cases the patients' pulse rates are elevated due to anxiety prior to the administration of Ibogaine.
On two occasions, persons with transient hypertension
were treated. In one of those instances the patient's blood pressure dropped to normal levels during the primary and secondary stages of treatment. The second hypertensive exhibited little change at a 23mg/kg therapeutic dose, but showed significant changes on two occasions when provided with only a 1.6mg/kg test dose. The two 1.6mg/kg doses were supplied due to our concern over the patient's hypertension. He had been previously treated with an 18mg/kg dose by Dutch Addict
Self-Help (DASH) with no apparent negative results. This alleviated somewhat our concern for the patient's safety. Variation in individual patient reactions should be anticipated.
FEMALE PATIENT SAFETY
One 24-year-old female patient treated with Ibogaine for chemical dependence died from undiagnosed causes in the Netherlands. Although her autopsy did not determine the cause of death, it reported Ibogaine levels of 0.75mg/liter in blood. This level has not been seen to be toxic in animal research or in our prior human studies. Subsequent to this death and to a previously reported death of a Swiss woman who received Ibogaine during a psychotherapy session in Europe, totally unrelated to NDA's research program, the FDA excluded women from the present clinical trials taking place at the University of Miami. However, the FDA decision is contrary to the gender guidelines of the National Institutes of Health. The guidelines with regard to women call for the inclusion of women at the earliest stages of clinical trials, as this would provide the greatest determination of safety for women. Thirty percent of NDA International's patients have been women who have shown no negative effects from taking Ibogaine either during or after treatment. However, considering all of the circumstances, the Procedure should be administered only in a hospital or clinic with the patient under continuous staff observation and electronic monitoring.
An ongoing international research program is developing evidence to determine a hypothesis for the cause of death of the woman in the Netherlands. We are additionally seeking Swiss government cooperation concerning the death of the Swiss woman. The results of this research may facilitate either an exclusion criteria or an antidote allowing Ibogaine safely to treat chemical dependence in women.
The second phase of Ibogaine's action during the Lotsof Proceduresm is one of the patients' intellectual evaluation of their previous experiences and decisions. This occurs after the visualization phase, which generally ends abruptly in three to five hours. However, individual reactions and variations are the norm and not the exception within the parameters of the Procedure.
Regarding this process of evaluation by the patient, in many cases, when various decisions were made by the patient in the past, those decisions appeared to be the only options available at the time. However, due to Ibogaine's ability to allow the reevaluation of one's life, actions and behavior , it is possible for the patient to understand that alternatives to their original decisions were available, and this knowledge appears to allow the patient to modify their current behavior and cease their drug dependence.
ATTENUATION OF NARCOTIC WITHDRAWAL
One of the major acute effects experienced with Ibogaine treatment is the attenuation or elimination of narcotic withdrawal in opiate-dependent patients. This is extremely important to the narcotic-dependent patients who live in fear of going into withdrawal.
The treatment team's experience in the field is of the utmost importance in dealing with this aspect of the Procedure as withdrawal symptoms are a combination of physical and, in many cases, psychosomatic manifestations that are anxiety-driven. Therefore, it is imperative for the medical and paramedical staff to have experience in identifying and distinguishing between these varieties of symptoms. Provided below are examples of psychosomatic withdrawal manifestations demonstrated by two of the patients treated outside the United States.
On one occasion I was called into the room by a colleague about twenty hours after Ibogaine had been administered to a twenty-five year old male heroin-dependent patient. The patient had been using approximately 1/4 gram of heroin a day, but soon increased his daily intake to two grams while in the Netherlands.
I was informed that the patient was complaining of muscle spasms; I asked the patient if this was true, and he concurred. I asked if I might see these spasms and the patient agreed, showing me the calf of his leg. The patient was exhibiting what appeared to be involuntary movements. I checked his pupils and observed that they were not dilated, nor was he exhibiting any other form or manifestation of withdrawal. When I turned to my colleague for discussion I noticed the patient's spasms had ceased. When I turned to the patient and once again examined his calf, the spasms returned. I turned away once again, but continued to watch him and the spasms ceased again. I informed the patient that I believed the spasms to be psychosomatic in origin. I placed a pillow under the patient's calf to give it support and covered the patient with a blanket. The spasms did not occur again.
On another occasion I received a call from a person involved with Dutch Addict Self-Help (DASH) groups who had been observing a number of treatments. She informed me that a Yugoslavian woman in her mid to late twenties had been complaining of narcotic withdrawal during Ibogaine treatment, but the DASH observer did not believe this to be the case as there were no observable signs of withdrawal..
When I arrived, the patient was sitting on a couch. I checked her pupils and observed they were not dilated and asked her if she were in withdrawal. The patient said, she was.
"How are you in withdrawal? What are its manifestations?" I asked.
"I'm sick," she said.
I asked her if her eyes were tearing.
"Yes," she said, but her eyes were not tearing.
"Is your nose running?"
"Yes," she said, but her nose was dry.
"Do you have goose bumps?" I asked.
"Yes," she said, but I pointed out to her that she did not have goose bumps, and finally I said, "Do you have diarrhea?"
"Yes," she said, but I had no way to determine the validity of her statement.
The patient requested that I provide her with funds to return home, and I told her I did not think it wise for her to leave at this time, but would give her carfare in the morning. The following day the DASH observer informed me the patient left about four hours after I did, informing the observer as she left that she had not been sick, but had only said she was. This example should further demonstrate the importance of hospital administered treatments with a full medical staff of psychiatrists, neurologists, internists, therapists, nurses, peer counselors and patient advocates capable of evaluating and responding to any aspects of the patient's condition at all times.
The complaint of experiencing narcotic withdrawal after leaving the treatment environment has been reported in three cases. We have provided additional treatments six months to a year after the initial treatment to patients who were re-addicted and stated they had experienced some form of withdrawal within a week of their first Ibogaine treatment. Our working group decided to keep patients making such complaints under observation for periods equal to the number of post treatment days during which the patients stated they previously experienced withdrawal symptoms.
Our findings have been that, under the above conditions of monitoring, the reported withdrawal signs are usually symptoms of anxiety or anxiety related conditions that the patients characterized as withdrawal, i.e., nausea, diarrhea or increases in blood pressure in one hypertensive patient.
There have been two incidents which did not appear anxiety related, in which diarrhea occurred five to seven days after treatment in patients using one gram of heroin a day. These episodes were easily controlled with a single administration of an appropriate medication and did not occur again.
INTERRUPTION OF CRAVING
The acute interruption of craving to seek and use drugs of abuse is unique to the Lotsof Proceduresm as a treatment modality for chemical dependence disorders. This effect is generally not noticed by the patient until the principal actions of Ibogaine (visualization, cognitive evaluation, behavioral immobility and significant residual stimulation) are no longer evident and the patient has had the opportunity to sleep. The initial recognition of lack of craving is usually noticed forty-eight to seventy-two hours after Ibogaine administration. In a minority of treatments, recovery and the absence of craving may be evident to the person being treated in as little as twenty-four hours. The medical staff, on the other hand, usually notes the absence of craving in the patient in forty-five minutes to one and a half hours after Ibogaine administration.
Our experience gained in recent years through the treatment of twenty persons outside the United States has shown that the majority of patients may need a series of treatments before the conditioned responses (craving) to a long history of chemical dependence can be extinguished. However, for three of these patients a single treatment interrupted chemical dependence for a minimum of two years. The advantage of Ibogaine is that it begins to allow patients time periods free of craving during which the psychiatrist, social worker, therapist, paraclinician and the patient often bond into a cohesive working group to accomplish a state of long-term non-dependence by the patient to the drug(s) of abuse for which the patient is under treatment.
All aspects of treatment for chemical dependence disorders common to other treatment modalities are common to the use of Ibogaine. The patient's characteristics in terms of psychopathology, behavior, societal accomplishments, as well as the skills of the treatment team are significant to treatment outcomes.
In rare cases, when the patient already has the occupational, educational and skills needed to succeed in society, the task may be somewhat easier. In cases where the patient does not have those societal skills, or lacks medical care for disorders other than chemical dependence, care and training must be provided through psychosocial support structures.
Trauma suffered by the patient during childhood appears to play an important part in the drive for love and the fear of abandonment that is common to many of the patients we have treated (Bastiaans, 1991).
All psychosocial support paradigms should be available for the patient after the completion of an Ibogaine treatment. Their use should be contingent upon the evaluation of the patient's needs and progress.
One of the primary differences that social workers, counselors or therapists offering psychosocial support notice in post-Ibogaine treated patients, as compared to untreated subjects, is the rapidity with which the support can and must be provided to aid the patient in accomplishing goals and making decisions. Ibogaine presents a symptom-free window of opportunity which the patient and therapist must take advantage of. One patient put it this way: "Ibogaine and 12-Step (groups) both help you to get in touch with your soul. Ibogaine is like rocket fuel for that process." (Village Beat, 1990) It is imperative that ground control remain in contact with the patient, and this means moving quickly and dramatically to assist the patient to establish goals while the patient has the ability and desire to do so.
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