Tag Archives: ibogaine for heroin withdrawal

03/24/20

The Unique Scientific Value of Ibogaine Part 3

credit: MAPS.org

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 Times referred 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.

03/10/20

The Unique Scientific Value of Ibogaine, Part 1

credit: Wikimedia Commons

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.

For more information on Bill W. and LSD, see “As Harmless as Aspirin?”