These are some notes I compiled in response to a list of questions asked by a colleague. Not casual reading! This is just meant to be a high level overview of some interesting points for people particularly interested.

How does iboga work pharmacologically?
Ibogaine is metabolized in the liver, primarily by the enzyme cytochrome P450 2D6 (CYP2D6). This metabolism results in the formation of noribogaine. Noribogaine is the main metabolite.

Ibogaine acts on multiple neurotransmitter systems in the brain, including the glutamatergic, serotonergic, and dopaminergic systems. Ibogaine (and noribogaine) are potent and long-lasting inhibitors of the serotonin transporter, (a protein called SERT) which has the effect of increasing serotonin levels in the brain and may contribute to its anti-addictive effects. It also appears to interact with NMDA receptors in the brain, which may play a role in its effects on addiction and other disorders.

Ibogaine has been shown to block the human ether-a-go-go-related gene (hERG) potassium ion channels, which are important for the repolarization of cardiac cells. This results in a delay in repolarization, leading to the prolonged QT interval and associated risks.

Info about SSRIs vs SERT inhibitors:
SSRIs are a specific type of SERT inhibitor that selectively target the serotonin transporter, while other SERT inhibitors (ie, ibogaine & noribogaine) may have broader effects on other neurotransmitter systems. Therefore ibogaine and noribogaine are not SSRIs, but are SERT inhibitors. This means that SSRIs (and MAOIs and other serotonergic substances) and iboga are contraindicated.

-Neuroplasticity
Animal studies have shown that ibogaine treatment can increase the growth of new neurons in the hippocampus, a region of the brain related to learning and memory. In addition, ibogaine has been shown to increase the expression of genes involved in synaptic plasticity, which is the ability of neurons to form new connections with other neurons.

BDNF stands for brain-derived neurotrophic factor, which is a protein that plays a key role in the growth, development, and maintenance of neurons in the brain. BDNF is involved in many important processes in the brain, including learning, memory, and mood regulation.

Studies have shown that ibogaine can increase the expression of BDNF in the brain. This is thought to be one of the ways in which ibogaine exerts its anti-addictive effects, as BDNF is involved in the regulation of reward pathways in the brain that are implicated in addiction. In addition, some research suggests that BDNF may also be involved in the antidepressant effects of ibogaine, as depression is associated with decreased levels of BDNF in the brain.

-Metabolism (effects on metabolism)
Ibogaine has been found to have various effects on metabolism, although the exact mechanisms are not yet fully understood. Some studies suggest that ibogaine may increase energy expenditure and metabolism, leading to weight loss. Additionally, ibogaine has been shown to alter glucose and lipid metabolism, although the specific effects vary depending on the dose and duration of treatment. Other research has suggested that ibogaine may modulate mitochondrial function and antioxidant activity, which could affect metabolism.

Regarding modulating mitochondrial function:
There is some evidence that ibogaine may modulate mitochondrial function, although the precise mechanisms are not fully understood. One study found that ibogaine treatment in rats led to an increase in the activity of the electron transport chain in the mitochondria of brain cells, which may contribute to its anti-addictive effects. Another study in mice found that ibogaine may help to protect mitochondria from oxidative stress by increasing levels of the antioxidant enzyme superoxide dismutase.

In addition, ibogaine has been shown to increase the expression of genes involved in mitochondrial biogenesis and energy metabolism, such as PGC-1α and AMPK. These changes suggest that ibogaine may have a positive impact on overall mitochondrial health and function. However, more research is needed to fully understand the effects of ibogaine on mitochondrial function and its potential therapeutic applications.

How does iboga affect cardiovascular system?
Ibogaine can have several effects on the cardiovascular system, including the potential to prolong the QT interval, which can lead to cardiac arrhythmias, and the potential to lower blood pressure. These effects can be particularly problematic in individuals with preexisting cardiac or cardiovascular conditions. Additionally, ibogaine has been associated with cases of bradycardia (slow heart rate) and tachycardia (fast heart rate), as well as changes in heart rate variability. Overall, ibogaine’s effects on the cardiovascular system require careful monitoring in order to minimize potential risks.

What about the “intelligence” of the plant?
In the Bwiti tradition of Gabon, the plant spirit is known as Maboundi, Mebandza, and sometimes just Bwiti. The word “Bwiti” translates to “dead” or “ancestor”. Many people meet a wise, all-knowing entity associated with iboga. This entity may seem to be God himself. Some Westerners have called this entity Dr. Iboga and described him as a master psychologist and cinematographer (often with a great sense of humor). This entity seems to manifest as a very defined personality with access to incredible knowledge (such as the Akashic records) and it’s own specific agenda, which seems to be the enlightenment and healing of those who meet him.

One legend states that the first person to ever ingest iboga became the guide of the plant effectively trapped or possibly volunteering to be the “genie in the bottle”. Although this presence is often masculine, it can manifest as a feminine principle as well. When asked the direct question “Who are you?” the iboga spirit often answers, “You.” This fits in with the traditions of some Bwiti sects who say that “When you meet Bwiti, you are Bwiti” which could be considered a nondual realization of “meeting God” and understanding “I Am that I Am” and that “I Am One with God”.

Another valid perspective is that, similar to a character in a dream, the apparent personality of the Iboga spirit is kind of a repository of the journeyer’s wisdom archetype. To me, for example, the spirit of Iboga (who I call Bwiti or Dr. Iboga), is simultaneously the God\The Spirit of the Plant\My Higher Self\A “Grandfather” Spirit (like a masculine counterpart to the “Grandmother Spirit” of Ayahuasca)\An Archetypal “Dream Character” of Wisdom. The first time I “met iboga” he had the voice of Morgan Freeman. (Again, this seems to be almost a playful nod to my own archetypal perspective of God)

Another aspect of the “intelligence” of the plant is the intuitive sense that many people have of feeling that the pharmacological effects work with very specific intention, almost like the molecules themselves are directed exactly to the places in the body where they can do the most good, targeting specific organs, receptor sites, etc.

Physical healing:
Hepatitis C
Ibogaine HCl has been shown to significantly reduce the viral load of the hepatitis C genotype 3. There is mounting evidence (over the last 30+ years) that iboga can actually put Hepatitis C into remission. Repetitive low-dose ibogaine provided continuous depression of viral load. Viral load still suppressed after ibogaine therapy.

Flood dosing, sub-flood dosing, and microdosing may all have applications to treat Hep C. Lower doses may be safer if liver health is already compromised significantly by the virus.

Parkinson’s
Parkinson’s disease is a chronic and progressive neurological disorder that affects movement and can also cause non-motor symptoms such as depression and anxiety. The disease is caused by a loss of dopamine-producing neurons in the brain.

Some researchers have suggested that ibogaine may have neuroprotective properties that could help slow down the progression of Parkinson’s disease. Additionally, ibogaine may also have antidepressant effects, which could help alleviate some of the non-motor symptoms of Parkinson’s disease

Anecdotally, ibogaine treatments seem like one of the most promising avenues to treatment of Parkinson’s. Lots of research needs to be done to figure out the most safe and effective dosing protocols.

Multiple Sclerosis
MS is a chronic autoimmune disease that affects the central nervous system, causing a range of symptoms that can include muscle weakness, fatigue, and difficulty with balance and coordination. The exact cause of MS is not fully understood, but it is believed to be an autoimmune disorder in which the immune system mistakenly attacks the myelin sheath that covers nerve fibers in the central nervous system. The destruction of myelin disrupts the communication between nerve cells, leading to a range of devastating of neurological symptoms. There is currently no known cure for MS, although the neurogenerative properties of ibogaine may help alleviate symptoms.

Fibromyalgia
Fibromyalgia is a disorder of the central nervous system that results in abnormal pain processing, leading to widespread pain and tenderness in muscles, joints, and other soft tissues. The exact cause of fibromyalgia is not fully understood but there is anecdotal evidence that it may alleviate some of the chronic pain associated with the disease. There is plenty of room for research on whether the relief is long-lasting past the initial treatments, or whether ongoing microdosing of ibogaine would be most beneficial.

Chronic pain
There is evidence that ibogaine treatments may alleviate some of the symptoms of chronic pain disorders such as neuropathy. The mechanisms of action may be multiple and varied, inducing neurogenesis and actually healing nerve damage.

Another way that ibogaine may be useful to treat chronic pain is similarly to the purpose of CBT. Cognitive Behavioral Therapy. In CBT for chronic pain, the therapist works with the patient to identify and challenge negative thoughts and beliefs about pain, such as catastrophizing or feeling helpless. The therapist may also help the patient develop coping skills and relaxation techniques to manage pain and related symptoms.

Ibogaine treatments seem to catalyze a process that may have similar effects and outcomes as CBT, to help the patient reorient their psychological perception of pain, disability, etc, which can be invaluable for quality of life.

Microiboga:
“Affects the whole body” – what does this mean?
All mental, emotional, spiritual, and physical systems are interrelated. Increasing any aspect of health and well-being has peripheral holistic benefits. For example, relief from anxiety and depression may alleviate stress to the immune system, cardiovascular system, digestive system, etc. This may have a cascade effect of well-being which causes a person to want to spend more time outdoors, getting more exercise and sunlight, which may increase their sense of self-confidence. All of this may inspire more betterment practices such as meditation, drinking more water, etc.

Microdosing iboga has many obvious benefits to the nervous system which has numerous peripheral and “stacking” benefits.

What are special benefits of microiboga besides addiction recovery, withdrawals, parkinson’s?
From a spiritual perspective, iboga seems to be a “root chakra” psychedelic. It contributes to an overall sense of groundedness and “spiritual sobriety”, that is, a sense of clarity, purpose, and confidence. The wisdom teachings of the Iboga Spirit which are very obvious in flood doses may still be heard as whispers by those sensitive and open enough to listen.

What are the differences between microiboga and micro-other substances?
Many of the effects of microdosing iboga overlap with microdosing other psychedelics, like mushrooms, san pedro, LSD, and others, however over time the unique character may become more obvious. All of these different medicines have different teachings. LSD may lead to more creative thinking, benefits that may be appreciated more by artists, technology developers, etc. San Pedro is often understood to be more “heart-opening” and may increase the depth and appreciation of interpersonal relationships. Mushrooms can be good for depression and neurogenesis, etc. Microdosing iboga is unique in that it has probably the most profound cumulative beneficial pharmacological effects on the nervous system of any of the substances just mentioned.

Microdosing iboga can profoundly reset nervous system disorders. More than any of the other substances, it seems to induce a type of grounded clarity, and a genuine feeling of holistic well-being. It seems to be a short-cut directly to this feeling, whereas microdosing mushrooms or LSD may create anxiety or other unwanted effects for some people. Everyone is unique of course, and microdosing iboga may still cause anxiety for some people.

Microiboga and SSRI effects? Withdrawals? How is different than other microdosing protocols
Pharmacologically, combining Iboga with SSRIs, even in low quantities could be dangerous because ibogaine and the metabolite noribogaine are SERT inhibitors. (Similar mechanism to SSRIs) Because of the particularly long half-life of noribogaine, the dangerous effects could build over time but may not be obvious immediately. This does open up the potential for using microdose iboga to alleviate the withdrawal symptoms of SSRIs but this is a very complex topic and people may react very differently depending on their unique neurochemistry and what specific SSRI they have been using.

A microdosing protocol to detox from SSRIs would probably involve tapering down the SSRI completely before beginning a microdose protocol. There is a possibility of very carefully using microdose iboga during the taper protocol, but only under very close medical supervision, and with careful attention to staggering the dosing schedule to avoid the possibility of serotonin syndrome. Really this is all a bit too complex for a couple of paragraphs, and is a very dangerous (but important) area of study because even SSRIs themselves can have tremendous side-effects, like suicidal ideation, etc, and ibogaine may amplify the negative side-effects of these medications.

Most important aspects of microiboga pharmacologically, especially contrasted to flood dose?
Overall microdosing ibogaine has dramatically fewer risks than flood doses. The QT interval prolonging effect is reduced, as is stress on the liver. There is less danger of a psychotic episode in people who are prone (although related psychological disorders like schizophrenia and bipolar disorder are contraindicated anyway). There is however a potential for someone with a contraindicated psychological disorder to see some of the nervous system benefits with less risk of catalyzing an acute psychotic episode. Additionally, a person with an otherwise contraindicated psychological disorder may find psychological benefits that can be integrated more slowly and gently through a microdosing protocol… It’s even conceivable (although I’m not aware of specific experiments, probably because people are reluctant to do this research) that microdosed iboga may offer some an ability to integrate complex psychological disorders like schizophrenia.

Borderline Personality Disorder (BPD), for example, is a contraindicated mental disorder for iboga treatment, and yet some people have self-medicated or even gone to clinics and have seen incredible benefits and alleviation of their symptoms.

Another potential risk of microdose iboga is the fact that a flood dose is usually held within a safe “container”, and supervised by professionals. The risk of someone combining contraindicated substances if they are microdosing over a long period of time is much greater.

How does microiboga affect cardiovascular system? Dangers?
Presumably the same side-effects associated with a flood dose, such as prolonged QT interval and lower blood pressure, may be expected during microdose protocols, but these are absolutely dose dependent and so microdosing may be much safer for some people. Again, the issue here is properly staggering the doses to account for the long half-life of noribogaine. Checking in periodically during the program to get an EKG is highly recommended.

How does microiboga work to interrupt addiction?
Slowly but surely. The neurological benefits are cumulative, but microdosing protocols have less of an acute psychological effect which may be very valuable for many situations. Ie, seeing visions of your childhood traumas cast into a shadowy pit to be released, and hearing the voice of a wisdom teacher that seems to be the voice of God are absolutely helpful for someone attempting to break the hold of a serious addiction. That said, many people quit coffee, cigarettes, alcohol, SSRIs, and even heroin and fentanyl without ibogaine through their own self-motivation. These people especially may benefit from microdosing iboga to interrupt addiction, as an adjunct to a process they are already committed to. In these cases, microdosed iboga can be just the advantage they need.

Parkinson’s, neurodegenerative diseases, summary of how it works to improve these conditions, what other diseases it may be useful to treat?
Ibogaine seems to have complex and comprehensive neuroprotective and neurologically healing effects and its efficacy is worth researching for any number of neurological diseases, such as Alzheimer’s, Traumatic Brain Injury (This is a huge area of research, lots of great anecdotal evidence for therapeutic potential here), Migraines, Dementia, Cerebral Palsy, Spinal Cord Injuries, Migraines and even recovering from Strokes. Essentially, nearly any disease or injury related to the nervous system may potentially see a therapeutic value in ibogaine treatment.

Main risks besides cardiovascular and psychological? What non-cardiovascular underlying conditions may be contraindicated?
>Many of the same neurological issues which may benefit from ibogaine treatment may also end up causing dangerous contraindications. For example, although many people with TBI may benefit from ibogaine therapy, there is no one-size-fits-all TBI and there could be an increase risk of seizures due to neurotransmitter level changes caused by ibogaine.
>Active benzodiazepine withdrawals are absolutely contraindicated due to increased risk of seizure.
>Epilepsy is contraindicated
>There is evidence that ibogaine and its metabolites have some hepatotoxicity. Liver damage is a very real risk although microdosing may mitigate this risk for many people.

Can microiboga lead to sleep disturbances if taken too late during the day?
Yes, absolutely. There are other substances which may help to alleviate this side-effect such as the neurotransmitter GABA (available as a supplement) and melatonin. Dialing in the dose, staggering properly, etc, may also help to mitigate this issue.

Accumulation of active chemicals accounting for half-life, does microiboga build over time?
Yes, and this requires a different staggering protocol than other microdosing protocols like mushrooms, LSD, etc. This may involve lowering the dose over time, or staggering doses more and more as the protocol unfolds in order to stabilize ibogaine\noribogaine levels in the body.

Besides psychological and sleep disturbance, other side effects?
Potential increased risk of seizures in some people with certain preexisting conditions such as epilepsy.

Summary of most important research about microdosing iboga, emphasis on tolerability and risk factors, biggest questions and mysteries. Do studies on long-term effects exist?
I am not aware of any clinical studies done on long-term microdosing effects of iboga. Nearly every study has been focused on the acute effects of high-dose ibogaine. That said, anecdotally, many people have reported amazing benefits that accumulate over time. Potential risks may include cumulative hepatotoxicity, as well as building up noribogaine levels to a point where cardiovascular risks become a concern, although by following some simple guidelines these risks can be mitigated. There is plenty of opportunity for research in this area.

Other:
T.Manii vs T.Iboga
Tabernanthe iboga can contain anywhere from 3-6% ibogaine by weight, while the root bark of Tabernanthe manii typically contains lower levels, ranging from 0.5-1.5% ibogaine by weight. Overall both plants contain many of the same alkaloids, such as ibogamine, tabersonine, coronaridine, etc, although in varying levels. Standaradized extracts may have very similar properties, although Tabernanthe iboga is known to contain several alkaloids that are not found in Tabernanthe manii or are present in only trace amounts. These include iboluteine, conopharyngine, ibogaline, and tabernanthine. What the actual effects are of these trace alkaloids has not been studied closely. For the most part the standardized extracts probably have very similar properties, risks, and benefits, although I would still differentiate between the source plants for patients.

Microiboga effects on spiritual\religious life
Out of all the microdosed psychedelics and plant medicines that I have tried (all of the common ones, and some uncommon ones), I have found iboga to be the most deep, comprehensive, grounding, and sobering. Perhaps this is because I’ve already done a flood dose and the feeling of the microdose reminds me to intentionally access the sense of spiritual sobriety, confidence, and courage that the flood dose initially let me access. Either way… Iboga isn’t about “getting high” even in the subtle spiritual sense that microdosing LSD or mushrooms might be. It’s about deeply enhancing and strengthening one’s connection to their core identity, sense of self-worth, and confidence. It is an excellent adjunct to meditation and just about any spiritual discipline one could imagine. Great for hiking and being in wilderness as well, without the feelings of “spaciness” than some other microdosed substances may engender. Overall I personally believe that Iboga, even microdosed, is a medicine of SELF-MASTERY. Anyone on a path like this could probably benefit.

Safety considerations:
Contraindicated medications:
Antidepressants like SSRIs, MAOIs, and TCAs – risk of serotonin syndrome
Opioids – risk of amplifying effects, respiratory failure\ OD
Stimulants – increased risk of hyperactivity & seizures
Alcohol – increased risk of liver damage
Barbiturates
Antipsychotic Medications
Beta-blockers and calcium channel blockers
Anticonvulsant Medications
Blood thinners
NSAIDs
Erectile Dysfunction medications
THIS IS NOT AN EXHAUSTIVE LIST

Notes compiled by Ian MacKenna
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