“I am 100 percent in favor of the intelligent use of drugs, and 1,000 percent against the thoughtless use of them, whether caffeine or LSD.” (Timothy Leary, in Chaos and Cyber Culture)
We’re going “back to the future” with recent research into the therapeutic benefits of hallucinogens for treating alcoholism and mood disorders. (See additional stories here and here; and a previous blog, “As Harmless as Aspirin?”) Classical hallucinogens such as LSD, mescaline or psilocybin, and dissociative anesthetics such as ketamine and PCP might be “useful” in the treatment of major depression, anxiety disorders and OCD. A recent study concluded: “There was evidence for a beneficial effect of LSD on alcohol misuse.” A single dose of LSD was found to be associated with a decrease in alcohol misuse. Another longitudinal study suggested that: “hallucinogens may promote alcohol and drug abstinence and prosocial behavior in a population with high rates of recidivism [with individuals on probation or parole].”
An issue of Current Drug Abuse Reviews (volume 6, number 1, 2013) was devoted to the investigation of psychedelics and their potential as therapeutic agents in the treatment of addiction. Several different articles suggested the therapeutic benefits of a variety of psychoactive substances—some classics and some newer ones.
Rick Doblin, in “Psychedelic-Assisted Psychotherapy for the Treatment of Addiction,” said: “There are multiple frameworks for understanding how psychedelic therapy can alleviate substance abuse.” He noted that the idea that psychedelics can be helpful in combating drug abuse conflicts with “the notion that psychedelic drug use is inherently wrong.”
Michael Bogenschutz of the University of New Mexico Health Sciences Center suggested that sacramental use of classic hallucinogens, like the Native American Church’s use of peyote, “is strongly associated with decreased alcohol and drug use.”
Lisa Jerome and others lobbied for studies that tested MDMA-assisted psychotherapy in people with an active substance use disorder. “It appears that MDMA, like classic psychedelics, may have a place in addressing substance abuse or dependence, which could be linked to its pharmacology or its psychological effects.”
Ayahuasca, a psychotropic brew prepared from an Amazonian vine and bush, may be associated with reduced substance use and “improvements in several cognitive and behavioral states.”
Thomas Kingsley Brown reported that ibogaine, a psychoactive alkaloid found in a rainforest shrub of West Central Africa, helps with withdrawal symptoms and reduces drug cravings.
A study of ayahuasca-assisted treatment for substance use problems by Gerald Thomas and others suggested that it was associated with significant improvements in several factors related to problematic substance use. While this particular study occurred in Canada, ayahuasca has been used as a remedy to help overcome drug addictions in Peru and Brazil. “Although these programs claim improved health outcomes for patients who complete them, neither has been evaluated with sufficient scientific rigor to provide definitive evidence of the success of their approaches.”
Ibogaine is not used in the US to treat addiction because of its severe side effects, which include hallucinations, bradycardia (slow heart rate), whole-body tremors and ataxia (lack of muscle control during voluntary movements). It also had cerebellar toxicity with high doses in rats. Nevertheless, it is a growing form of treatment outside the US. A subculture of ibogaine clinics has sprung up in Mexico. Read about a trip to one here.
A synthetic derivative of ibogaine, 18-MC, has been developed and is said to show promise. It resulted in “a long-lasting decrease in ethanol, morphine, cocaine, methamphetamine and nicotine self-administration [in rats], and attenuation [decrease] of opioid withdrawal symptoms.” Significantly, it is not expected to have hallucinogenic effects and does not have the negative side effects noted above with ibogaine.
In 2012 Savant HWP, a privately-owned pharmaceutical company in California, received a three-year grant from the National Institute on Drug Abuse (NIDA) for the pre-clinical development of 18-MC. Stanley Glick, the scientific founder of Savant and a long time researcher with ibogaine, said: “18-MC is likely to be the first of a new generation of agents effective against a broad spectrum of addictions—from hard drugs such as heroin and cocaine, to alcohol, nicotine and even sugary, high-fat foods, possibly reducing obesity rates.” On September 23rd of 2014 Savant announced they had begun human safety clinical trials on 18-MC. “Savant HWP plans to develop 18-MC as a treatment for many forms of addiction and compulsive behavior, with an initial focus on cocaine and opiate dependencies.”
The so-called “psychedelic treatment” approach, based on the original work of Humpry Osmond, uses pre and post therapeutic sessions and one large dose of your hallucinogen-of-choice (LSD, ayahuasca, psilocybin, mescaline). The spiritual, therapeutic goal is captured here by Aldous Huxley’s description of his experience with mescaline in The Doors of Perception:
The man who comes back through the Door in the Wall will never be quite the same as the man who went out. He will be wiser but less cocksure, happier but less self-satisfied, humbler in acknowledging his ignorance yet better equipped to understand the relationship of words to things, of systematic reasoning to the unfathomable Mystery which it tries, forever vainly, to comprehend.
But we should also remember the warnings of Albert Hofmann, the inventor of LSD, who cautioned not to underestimate the potential negative consequences of a deliberate provocation of mystical experiences with hallucinogens like LSD. “Wrong and inappropriate use has caused LSD to become my problem child.” In the “LSD state” the boundaries between the self and the outer world effectively disappear. “A portion of the self overflows into the outer world. . . . This can be perceived as a bless[ing], or as a demonic transformation imbued with terror.”
In a March 6, 2019 interview with The New York Times, Gwyneth Paltrow was asked what the next big thing Goop would be plugging, and she responded: “I think how psychedelics affect health and mental health and addiction will come more into the mainstream.” At the time, she confessed she had never used psychedelics and was terrified at the process. And yet, she acknowledged there seemed to be a link between a psychedelic state and being connected to “some other universal cosmic something.” She then mentioned ibogaine, a hallucinogen being promoted as a treatment for addictions. The interviewer asked if ibogaine would be the next big thing she would read about on Goop, and Gwyneth back-pedaled, saying she didn’t know. Then “The Healing Trip,” appeared as the first episode for the Netflix series, The Goop Lab, where several Goop employees went to Jamaica to ingest magic mushrooms.
The New York Timesreferred to this as “Goop-ification,” when Gwyneth Paltrow’s health and beauty company, Goop, regularly wrote articles on the health benefits of hallucinogens. The Times article highlighted three authors. Michael Pollan, who wrote the best selling How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression and Transcendence, chronicled the history of psychedelic drugs, including his own personal use of psychedelics. There was a memoir, A Really Good Day, written by Aylet Waldman, and a novel about Timothy Leary, Outside Looking In, by T.C. Boyle.
Psychedelics have entered into mainstream conversations, with psychedelics being touted for wellness, lifehacking, therapy and self-care. The Milken Conference, a business event, had a panel called “Psychedelics: Mind-Enhancing Methods to Well-Being.” Silicon Valley entrepreneurs are using Ecstasy, LSD, and magic mushrooms. “A booming—and unregulated—shaman market has emerged.” Ironically, Pollan and Waldman, who published books on the benefits of psychedelics “worry about the ayahuasca retreat gentrification even as they usher more people in the door.” The promises made for what psychedelics can do for you harken back to the days of patent medicines.
But Pollan cautioned against legalizing psychedelics: “Psilocybin has a lot of potential as medicine, but we don’t know enough about it yet to legalize it.” Someone, he feared, could commit suicide while they were coming off of SSRIs in conjunction to their hallucinogenic therapy. “I do think we could have another backlash.” Goop urged caution as well:
If we’ve learned anything from interviewing psychiatrists and psychedelic researchers over the past few years, it’s two things: 1) Psychedelics have incredible potential as therapeutic agents, and 2) they are not something you should approach lightly—they require a great deal of care and expertise and support to have those desired therapeutic effects. They can leave you vulnerable and have the potential for serious (and in rare cases fatal) harm. If you’re considering any experimental healing experience, you should consult your own medical team and understand the risks before proceeding. And for anything involving psychedelics, verify the legal status, as psychedelics are illegal in many countries and unregulated in others.
This psychedelic “renaissance” was explored by Michael Pollan in his 2018 book, How to Change Your Mind. Pollan noted how Western science and modern drug testing depended on the ability to isolate one single variable. Yet it is not clear how the effects of a psychedelic drug can ever be isolated as a single variable from the context in which it is administered—the presence of the therapists involved, or the expectations of the person ingesting the psychedelic. “Any of these factors can muddy the waters of causality.” He then asked how was Western medicine to evaluate a psychiatric drug that appears to work by administering a certain kind of experience in the minds of the person, and not strictly by means of any pharmacological effect?
This is why it is important to understand that “psychedelic therapy” is not simply treatment with a psychedelic drug but rather a form of “psychedelic-assisted therapy,” as many of the researchers take pains to emphasize.
One of those researchers is Dr. Kenneth Alper, who has coauthored multiple papers with Howard Lotsof (See Part 1 for more about Howard Lotsof) and is the first editor of an English language text on ibogaine. In “Ibogaine: A review,” an article in The Alkaloids Chemistry and Biology, February 2001, he said there were “stages” or phases to the subjective experience of ibogaine. He said ibogaine was typically given in a nonhospital setting as a single dose in the morning. Vomiting is common, as it seems to be with the ingestion of ayahuasca, another psychedelic alleged to be helpful in treating addictions. Patients generally lie still in a quiet, darkened room throughout their treatment.
The subjective effects of the Acute phase appear to have common elements described by individuals treated with ibogaine. The onset of the acute phase occurs within 1 to 3 hours of ingesting ibogaine and lasts about 4 to 8 hours. The predominant experiences reported seem to involve “visions” or “waking dreams” of long-term memories. Descriptions from individuals in this state are more consistent with an experience of dreams, rather than hallucinations. Subjects also emphasize their experience of being placed in, or entering/exiting visual landscapes, rather than an intrusive visual or auditory hallucination.
Ibogaine-related visual experiences are reported to be strongly associated with eye closure and suppressed by eye opening. The term “oneiric” (Greek, oneiros, dream) has been preferred to the term “hallucinogenic” in describing the subjective experience of the acute state. Not all subjects experience visual phenomena from ibogaine, which may be related to dose, bioavailability, and interindividual variation.
The Evaluative phase comes about 4 to 8 hours after ingestion, and lasts 8 to 20 hours. The volume of material recalled in the waking visions slows. The emotional tone is described as neutral or reflective. Attention still has an inner subjective focus directed at evaluating the experiences of the Acute phase, rather than the external environment. “Patients in this and the acute phase above are apparently easily distracted and annoyed by ambient environmental stimuli and prefer as little environmental sensory stimulation as possible in order to maintain an attentional focus on inner experience.”
Twelve to 24 hours after ingestion of ibogaine marks the beginning of the Residual Stimulation phase. It lasts somewhere between 24 and 72 hours; maybe longer. There is a return to normal attention to the person’s external environment. “The intensity of the subjective psychoactive experience lessens, with mild residual subjective arousal or vigilance.” Some people report a reduced need for sleep for several days up to a few weeks following treatment. In summary, Alper concluded:
The available evidence suggests that ibogaine and the iboga alkaloids may have efficacy in addiction on the basis of mechanisms that are not yet known and which can possibly be dissociated from toxic effects, and may present significant promise as a paradigm for the study and development of pharmacotherapy for addiction.
Despite the carefully described observations noted here, Pollan still urged caution with psychedelic therapy: “None of these psychedelic therapies have yet proven themselves to work in large populations; what successes have been reported should be taken as promising signals standing out from the noise of data, rather than definitive proofs of cure.” But he didn’t stop there with his investigation into psychedelic therapies.
He turned to the work of Robin Carhart-Harris and his theory of the entropic brain. He said it represented a first stab at a unified theory of mental illness and helped explain several psychiatric disorders. According to Pollan, Carhart-Harris believes that “depression, anxiety, obsession, and the cravings of addiction are how it feels to have a brain that has become excessively rigid or fixed in its pathways and linkages.” These disorders are manifested in a brain with more order than is good for it. “On the spectrum he lays out (in his entropic article) ranging from excessive order to excessive entropy, depression, addiction, and disorders of obsession all fall on the too-much-order end.”
In “The entropic brain” article, Robin Carhart-Harris et al proposed a theory of consciousness they called the entropic brain hypothesis. This hypothesis proposes that the quality of any conscious state depends on the system’s entropy measured vie key parameters of brain function. Increased subjective uncertainty accompanies states of increased system entropy. Psychedelics work therapeutically “by dismantling reinforced patterns of negative thought and behavior by breaking down the stable spatiotemporal patterns of brain activity upon which they rest.” Pollan thought this effect, which he called “the dissolution of the ego,” was the most important and therapeutic of all the phenomenological effects people who are on psychedelics report. See the graphic below from “The entropic brain.”
In particular, the changes in activity and connectivity in the default mode network on psychedelics suggest it may be possible to link the felt experience of certain types of mental suffering with something observable—and alterable—in the brain. If the default mode network does what neuroscientists think it does, then an intervention that targets that network has the potential to help relieve several forms of mental illness, including the handful of disorders psychedelic researchers have trialed so far.
Pollan said the default mode network (DMN) is a set of interacting brain structures first described by the Washington University neuroscientist Marcus Raichle. It is most active when the brain is in a resting state, linking parts of the cerebral cortex with deeper, older structures of the brain involved in memory and emotion. “Its key structures include, and link, the posterior cingulate cortex, the medial prefrontal cortex, and the hippocampus.”
Neuroimaging studies suggest that the DMN is involved in such higher-order “metacognitive” activities as self-reflection, mental projection, time travel, and theory of mind—the ability to attribute mental states to others. Activity in the DMN falls during the psychedelic experiences, and when it falls most precipitously volunteers often report a dissolution of their sense of self.
The approval of psychedelic therapy with ibogaine has some serious concerns to overcome, but there is enough evidence available to support doing further research and for the FDA to provide the funds for it. However, Michael Pollan may have the right of it in saying, “it isn’t clear that the effects of a psychedelic drug can ever be isolated … from the context in which it is administered.” Deborah Mash’s attempts to somehow separate the drug effect from the set and setting of the dream-like experience of ibogaine may radically, and negatively, effect its efficacy. Her efforts points to the limitations of scientific inquiry into the healing properties of hallucinogens. The Dalai Lama said: “The view that all mental processes are necessarily physical processes is a metaphysical assumption, not a scientific fact. I feel that, in the spirit of scientific inquiry, it is critical that we allow the question to remain open, and not conflate our assumptions with empirical fact.” In closing, Robin Carhart-Harris’s thoughts on the unique scientific value of psychedelics have relevance:
The unique scientific value of psychedelics rests in their capacity to make consciously accessible that which is latent in the mind. This paper takes the position that mainstream psychology and psychiatry have underappreciated the depth of the human mind by neglecting schools of thought that posit the existence an unconscious mind. Indeed, psychedelics’ greatest value may be as a remedy for ignorance of the unconscious mind.
Howard Lotsof said in 1962 while he was having breakfast with a chemist friend of his, the friend began rooting through a freezer, which was full of different psychoactive drugs. “He pulled out a small vial and said, ‘I think you’ll be interested in this.’” Howard asked what it was and the friend said it was an African hallucinogen that lasted 36 hours, so of course he took it. At home he laid down, and it continued to work and work, leaving him exhausted. After 33 hours he thought he would never take ibogaine again, until he realized he was not in narcotic withdrawal. You see, Howard was a 19-year-old heroin addict.
Afterwards, I was walking and I looked at this tree, and as I looked at it, I realized I no longer had any fear of death. Also, that I was no longer addicted to narcotics.
He administered it to a few of his addicted friends, who had similar results. Without withdrawal symptoms, ibogaine appeared to interrupt addiction and provide the user insight into why they used drugs often through ‘visions.’ This began a life-long pursuit of ibogaine as both an “addiction interrupter” and aid to psychotherapy. Despite the interest and research into ibogaine, it remains a Schedule I drug. This means it is illegal to use and difficult to research, within the US.
Psychedelic Times said Dr. Deborah Mash, who has been researching ibogaine for over two decades, thinks moving it from Schedule 1 into Schedule 2 is important for future research with ibogaine. She thought a consortium of credentialed people from academia, and the public and private sector could help stimulate the movement out of Schedule 1. She wants its consumption to be ethical and used for the right purpose. “We have an epidemic of heroin addiction in the US and we need this now more than ever before.”
One of the big barriers for studying ibogaine is that it is in Schedule 1. Ibogaine has no abuse potential. People don’t even like it! Animals don’t self-administer it. We have a way to scientifically look at drugs that might have abuse liability, and ibogaine does not have it. Moving it out of Schedule 1 and into Schedule 2 would open the door for many more people to be able to research it.
Dr. Mash obtained FDA approval to clinically test ibogaine on humans in 1993, but found every grant that she would write for ibogaine was rejected by the NIDA. Scientists at the institute recruited to review the application were concerned about ibogaine’s safety. Frustrated with this catch 22, she found some investors and opened a clinic on St. Kitts, for clinical trials and treatment, the Healing Visions Institute for Addiction Recovery. By 2004, Mash had collected the data she needed to once again approach the FDA, and she closed Healing Visions, which always struggled with money. She said: “This was never run for profit… It was always for research and development.”
Dr. Alberto Solà who was one of the clinicians trained by Dr. Mash at Healing Visions, now owns and operates Clear Sky Recovery, which acknowledges Dr. Mash as a cofounder. The website for Clear Sky Recovery claims, “We are the world’s foremost experts in medically-based ibogaine treatment.” They assert Clear Sky Recovery is the only ibogaine treatment center in the world whose founders are regularly published in peer-reviewed medical journals on the topic “of dosing human, drug dependent individuals with ibogaine.” Watch “Heroin Cure?”, a segment for America Tonight Investigation on the Clear Sky Recovery website, which is linked above, for more information on ibogaine and Clear Sky Recovery.
In “Heroin Cure?” Dr. Mash said at first, she didn’t believe the claims about ibogaine: “How could one molecule have an effect on alcohol, nicotine, cocaine, opiates. It didn’t make sense.” She wanted to see the results firsthand, so she travelled to the Netherlands, where ibogaine trials were going on and watched a detox in action. “I saw people who were at the end of the rope, completely detoxed; looked like new human beings; no signs of withdrawal; and ready to change their life.” She wanted to know what that taught us about the brain, so she organized a clinical trial of ibogaine and received approval from the FDA. It was eventually suspended as the result of no ongoing grant support for the research.
Despite the glowing testimonials on the Clear Sky Recovery website, there are several individuals who are opposed to ibogaine treatment. Dr. Phil Skolnick, a drug development expert at NIDA, the National Institute on Drug Abuse, said he would not recommend it. “Might ibogaine work for some people? It’s absolutely possible. Has its safety and efficacy been established in a rigorous way, absolutely not.” He added there was data in the literature indicating animals administered ibogaine could get brain lesions.
Dr. Mash countered, saying that was exactly why further research was needed and worth doing. She added: “One dose of ibogaine is not going to have toxicity to the brain.” But funding for the necessary research isn’t being offered. Dr. Skolnick, who worked in pharmaceutical companies for several years admitted that addiction medications are rarely embraced. “Pharma has generally been indifferent to addictions; to developing medications to treat addictions.”
Dr. Mash said her intent was to either show that ibogaine worked, or to debunk it. “Either ibogaine works, or it doesn’t. But we in the scientific community need to test, to study. This is too big of a problem, the drug addiction in our society—it’s too large to leave this stone unturned.” She also cautioned that ibogaine has some serious side effects, like cardiac arrest. She was critical of the protocol followed in a MAPS-funded clinical trial in New Zealand, discussed in Part 1, where one of the patients died. She said in an article for Markets Insider,
This recent death underscores the persistent problem associated with the use of ibogaine in unregulated, nonmedical settings by unqualified persons. Ibogaine has complicated pharmacokinetics that contribute to concerns for careful dosing, potential drug interactions, and issues of cardiovascular safety.
A 2006 article in the journal Medical Hypotheses, “Fatalities after taking ibogaine” hypothesized deaths may be the result of cardiac arrhythmias, “caused by a dysregulation of the autonomic nervous system.” Kenneth Alper and others reviewed all the available autopsy reports for known ibogaine-related deaths outside of West Central Africa between 1990 and 2008. The evidence did not suggest a characteristic syndrome of neurotoxicity. Advanced preexisting medical conditions (mainly cardiovascular, and/or one or more typically abused substances) either explained or contributed to the deaths of 12 of 14 cases. “Other apparent risk factors include seizures associated with withdrawal from alcohol and benzodiazepines and the uninformed use of ethnopharmacological forms of ibogaine.”
A 12-minute YouTube showed Dr. Alper giving a report at the ICEERS Ibogaine Conference on the above study. He said the risk factor for ibogaine fatalities were the same as for drug overdose. The risk factors with ibogaine fatalities were: significant preexisting medical, particularly cardiac disease; pulmonary embolisms related to things like travel, immobility within a treatment; using opiates or stimulants during a treatment; and using indigenous forms of uncertain origin and composition, like iboga root bark, by the inexperienced or uninformed patients. He said there was one overriding risk factor for providers. In many cases providers were influenced by someone to do a treatment under circumstances they normally would not; “they bent their own rules.” Dr. Alper believed the widespread adoption of exclusion criteria and pretreatment evaluation before ibogaine treatment; and the inclusion of internists and medical physicians in the pretreatment evaluation were the key factors in decreasing the risk of fatalities with ibogaine.
The mechanism behind the effectiveness of ibogaine is still unknown and the risk factor of sudden, unexplained death during ibogaine treatment is real enough for a report of fatalities to be done at an ibogaine conference held by the International Center for Ethnobotanical Education, Research, and Service (ICEERS). Further research is needed, but is hampered by ibogaine’s classification as a Schedule I drug, and the inconsistent protocols of most centers offering ibogaine treatment. Dr. Mash has expressed concern the adverse effects and unexplained deaths resulting from these treatment centers will hold back any serious consideration by the US research community of ibogaine as an addiction treatment. The stakes are high for the potential help of ibogaine treatment as well as risks for patients. Dr Skolnick said that addicts should not have to face risks with ibogaine in their addiction treatment when they risked so much when actively using. But out of desperation, many addicts are willing to take the risks associated with current ibogaine treatment.
The danger of medical complications with ibogaine for some individuals seems to limit the willingness of the FDA to fund research into ibogaine, despite its promise for treating addiction to multiple substances. The inability of pharmaceutical companies to develop ibogaine into a blockbuster, billion-dollar new molecular entity (NME) because it is an extract of the West African Tabernanthe iboga plant is another reason the research funds are not there. This lack of funding has stymied the scientific, medical investigation of ibogaine. Despite these roadblocks to ibogaine research, it has become a kind of patent medicine touted as a cure all for various addictions. At this time, ibogaine treatment centers necessarily exist outside the US, since ibogaine is a Schedule I substance. There are two registered clinical trials with ibogaine in Brazil, one looking at the safety and tolerability of ibogaine in alcoholic patients; and the other investigating the safety and efficacy of ibogaine for methadone detoxification.
The fact that ibogaine is a hallucinogen, whose effects are likened to waking dreams, is another factor in its failure to attract research funding. Yet many of its advocates view the waking dreams as a crucial part of the ibogaine healing process. Even Dr. Mash, who describes herself as agnostic to the supposed importance of subjective effects of the waking dreams, acknowledged how the therapists she works with believe the hallucinations are part of the healing process with ibogaine. At this point we approach the limits of hard scientific knowledge and the investigation of the neurochemical effects of ibogaine and turn toward its subjective effects, and that of other hallucinogens like psilocybin. Are these molecules a panacea for whatever ails us; or are they more of a placebo effect that will eventually result in a more modest assessment of their potential? We will reflect on this in Part 3.
Investigating the potential of psychedelic drugs to treat addiction has been around since the 1950s, when a British psychiatrist named Humphry Osmond first wondered in 1953 if a controlled LSD-produced delirium would help alcoholics stay sober. He would treat over 700 patients in the following ten years and Bill W., a co-founder of A.A., was one of them. Currently, there are a variety of psychedelics being investigated as treatments for conditions ranging from addictions with various drugs to PTSD. One of those is ibogaine, a psychoactive compound extracted from the West African Tabernanthe iboga plant.
Erowid said the first report of Tabernanthe iboga use as a stimulant and aphrodisiac in Gabon and the Congo was in 1864 by Griffon du Bellay, a doctor in the French Navy. A syncretic Christian church called “Bwiti,” who used Tabernanthe iboga in their initiation rites, was founded among the Fang people of Gabon in the late 19th century. In 1903 was the first report of iboga being used as a visionary plant in the Congo. By 1939 an extract of the Tabernanthe iboga plant was sold in tablet form under the name Lambarene for treating fatigue and depression. “It was popular among athletes who used it as a stimulant and to accelerate red blood cell production.”
In 1962 Howard Lotsof inadvertently discovered the anti-addictive properties of ibogaine when he realized after a several-hour trip on ibogaine, he had no withdrawal symptoms even though he had not used any heroin. He administered the drug to several of his addicted friends with similar results. He would later acquire patents for ibogaine as a treatment for acute addiction in 1985 and 1992. In 2009 he founded The Global Ibogaine Therapy Alliance (GITA), a non-profit corporation dedicated to supporting the sacramental and therapeutic uses of iboga. He has authored or coauthored several scientific papers on ibogaine and produced a web portal for scientific studies and lay information on ibogaine, the “Ibogaine Dossier.”
Ibogaine was completely synthesized in 1966, classified as a hallucinogen and made an illegal substance in the USA in 1967. It was classified then as a Schedule I substance, meaning it was considered to have a high potential for abuse and no acceptable medical use. Because of this action, most of the research into ibogaine’s use in addiction treatment has occurred outside of conventional clinical and medical settings and outside of the US.
The Ibogaine Dossier said there were two general types of ibogaine treatment. The first type is sometimes referred to as “initiatory,” and involves a dosage around 8 to 12 mg/kg; it’s used to orient users towards psychotherapeutic or spiritual insight. The other type of ibogaine treatment, which is used for addiction, involves a dosage of 15 to 25 mg/kg, twice as much as an initiatory dose. Lotsof’s early “research” reported that he gave up to 19 mg/kg to a total of 20 individuals.
A subset (n= 7) of Lotsof’s individuals were heroin addicts who reported the alleviation of physical dependence and cravings. Five of the seven individuals reportedly remained free of heroin for 6 months or more following their treatment with ibogaine. “The activity of the group eventually ceased in 1963 when FDA and law-enforcement agencies eliminated the ability of S&L Laboratories, as Lotsof put it, ‘to procure drugs and administer them to interested persons.’” The pharmaceutical industry was not interested at the time in developing ibogaine, viewing addiction as an economically unattractive area for medication development.
But Lotsof and others persisted in their efforts to do research and provide treatment with ibogaine. Lotsof organized a company, NDA International, which provided research funding to Dr. Stanley Glick at Albany Medical College, who demonstrated ibogaine decreased the intake of morphine in rats. See here and here for Glick’s 1991 articles on his research. Glick would continue his research on “iboga” for the next ten years and generate a body of work with over 60 peer-reviewed articles on ibogaine and related compounds. His work has been supported by the National Institutes of Health (NIH).
NDA International recruited and treated patients in the Netherlands because ibogaine treatment could not be legally provided in the US. A total of 40 to 45 individuals were treated between 1989 and 1993 in the Netherlands. “The data from these treatments, together with the 20 subjects treated in the United States by Lotsof between 1962 and 1963, provide the principal source of the case study evidence that has been presented to the National Institute on Drug Abuse (NIDA) and the FDA.” But the death of a female patient in the Netherlands in June of 1993 ended the treatments there by NDA International. Although the official Dutch inquiry into the woman’s death was not conclusive, it nevertheless decreased the enthusiasm to do further investigations with ibogaine.
Kenneth Alper said in “Ibogaine: A review” that while the death of the 24-year-old woman during a heroin detoxification treatment was a significant factor in the NIDA decision not to fund a clinical trial in 1995, “Forensic pathological examination revealed no definitive conclusion regarding the probable cause of death.” There was some evidence that suggested the possibility she had secretively used opioids, presenting another element of uncertainty for her death. He then added: “There is evidence suggesting that the interaction of opioids and ibogaine potentiates opioid toxicity.”
However, in 1991 there was some interest in ibogaine research sparked with Deborah Mash, a faculty member in the Department of Neurology of the University of Miami. In a 1996 radio interview, she said she became interested in ibogaine after hearing a presentation by Dr. Glick on his research with ibogaine and rats. Dr. Mash organized a clinical trial of ibogaine and received approval of an Investigational New Drug Application from the FDA. The study began in December of 1993, but was eventually suspended as result of the unavailability of grant support. She said the ibogaine molecule was unique, doing something to human consciousness, “something to the brain, something to craving and withdrawal signs that’s very different than anything we know about right now.”
Ibogaine has a very unique structure, it’s almost as if that plant has created a magical structure that has a very rigid backbone, that is somewhat seratonin-like. Seratonin is a neurotransmitter that is associated with drugs like Prozac and with depression and changes in the brain that are normal with aging. Ibogaine also has another alkaloydal piece that hangs off the side of this rigid backbone that seems to resemble cocaine. It’s a molecule that seems to have affinity for the opiate side, and has some affinity for the cocaine side and as a pharmacologist that really grabbed my attention. There’s something real fundamental about this molecule that maybe explains its efficacy, and if these anecdotal reports that were out there in the addict self-help movement were true and could be validated, then together with our knowledge of the structural chemistry of the molecule, we might get some fundamental insight into the process of addiction itself.
This was not the end of Dr. Mash’s research and treatment efforts with ibogaine. In 1998 she coauthored a study into the safety, pharmacokinetics and dose effects of ibogaine and its metabolite, noribogaine in cocaine-dependent patients. In 2001 she coauthored a chapter in The Alkaloids: Chemistry and Biology, “Ibogaine in the treatment of heroin withdrawal.” Along with her coauthors, Dr. Mash found ibogaine to be effective in blocking opiate withdrawal. However, it has complex pharmacokinetics and an uncertain mechanism of action with regards to treating opiate dependency. The authors suggested “Identifying noribogaine’s mechanism of action may explain the way ibogaine promotes rapid detoxification from opiates after only a single dose.”
In a 2016 a study of noribogaine, Mash and others investigated the effects it had on substance-related disorders. Their findings suggested the metabolite noribogaine rather than ibogaine mediated the effects of ibogaine blocking withdrawal. “Noribogaine may hold promise as a non-addicting alternative to standard opiate replacement therapies to transition patients to opiate abstinence.” Then in 2018 Mash and others published a study whose results “Confirms the original claims made by Howard Lotsof.” It demonstrated that medically assisted ibogaine detoxification was a safe and effective method to discontinue substance dependence or misuse. Dr Mash has published additional studies with ibogaine besides those mentioned here.
MAPS, the Multidisciplinary Association for Psychedelics, has been supportive of research into the use of ibogaine to treat addiction and has an extensive listing of research updates, news and event announcements on a variety psychedelic drugs, including ibogaine. It also funded two observational studies of the long-term effects of ibogaine treatment in Mexico and New Zealand. The Mexican study reported on outcomes up to one year following opioid detoxification with ibogaine of 30 individuals with OUD (opioid use disorder). Participants were followed up at intervals of 1, 3, 6, 9 and 12 months. The results indicated that ibogaine had a substantial treatment effect in opioid detoxification and appeared to reduce drug use at one month, which was sustained up to 12 months in a subgroup of subjects. “No clinically significant cardiovascular or other medical events occurred in this study.”
The New Zealand study was a prospective observational case series of 14 participants seeking ibogaine treatment for opioid dependence and who were committed to regular contact for 12 months post-treatment follow up. “Consistent with preceding studies, evidence showed significant attenuation of withdrawal, sustained reduction in drug craving/use, and cessation of use in some cases.” This sustained reduction occurred in 12 of 14 participants. One patient died during treatment before they were formally enrolled. Two investigations suggested the participant’s death was due to a failed duty of care by the treatment provider. The death was likely “related to ibogaine ingestion and most probably related to a cardiac arrhythmia.” There will be more discussion of this potential adverse event with ibogaine treatment in part 2 of this article. In conclusion, the author noted that despite the limitations, which included its reliance on a small (n= 14) convenience sample already intending treatment,
This study has demonstrated that for some opioid-dependent individuals, ibogaine treatment can be effective in significantly reducing opioid withdrawal, craving and depressed mood, and reducing or ceasing opioid use. Given the modest success of existing treatments, some of which involve extensive, repeated administration and considerable risk, and the significant increase in opioid dependence globally, it seems prudent to more seriously examine the place of ibogaine in the context of treating this intractable problem.
Despite the apparent promise of the research reported above, the ghost of adverse events, particularly fatalities, haunts serious research into ibogaine for opioid treatment. It was what stopped the clinical trial in the Netherlands in June of 1993, and raised its head again in the New Zealand study described above. Yet, there seems to be a growing body of research interest into its use for opioid treatment. For example, there are two clinical trials registered for ibogaine in the treatment of alcoholism and methadone detoxification. Neither study is recruiting yet and neither study is to be done in the US.
The fact that ibogaine is largely unregulated as a treatment for addiction and used to promote spiritual and healing experiences—sometimes by the same provider—should give someone seeking it for addiction treatment pause. But addicts are often desperate individuals, willing to take the risk. We will look at some of the risks and concerns in Part 2.
