Comparing Iboga with Psychedelics & Entheogens
Psychedelics are a group of natural and synthetic psychoactive substances that alter one’s perceptions, thoughts, and emotions and can cause changes in sensory experiences.
They have been used in religious and spiritual practices for most of human history and, in the last 100 years, have become the subject of scientific research for their therapeutic potential.
Psychedelics have different effects and lead to different experiences, depending on their mechanism of action and unique properties. They also differ regarding the duration of their effects, medicinal potential, safety, and contraindications.
Similarities include the fact that all psychedelics interact with the various chemical receptors in the brain, they should be taken at an empty stomach and can be contraindicated in people with schizophrenia or psychosis.
Depending on their effects, psychedelics can be classified as classic hallucinogens, empathogen–entactogens, dissociatives, and atypical hallucinogens. Chemically, most psychedelics are also subdivided into tryptamines, phenethylamines, and lysergamides.
However, some atypical psychedelics, such as the ones naturally found in the shrub Tabernanthe Iboga have much more complex structures and effects which continue to be investigated to this day.
Tabernanthe Iboga originates from Equatorial West Africa and contains several alkaloids, such as Ibogaine which contribute to its psychedelic effects. The inner root bark of this shrub, called Iboga, has been used for thousands of years in the West-African Bwiti tradition. Its effects are unique as it targets a wide range of receptors in the brain.
Other notable psychedelics with various mechanisms of action, medicinal potential, and spiritual effects include psilocybin mushrooms, MDMA, DMT, Bufo’s 5-MEO-DMT, LSD, Peyote mescaline, and ketamine.
In this article, you will discover more about the physical, psychological, and spiritual effects of these psychedelics, their potential benefits and risks, and how they differentiate from Iboga.
Mechanism of action and effects of Tabernanthe Iboga
The alkaloids in Iboga, such as Ibogaine, work by affecting numerous receptors and endogenous substances in the brain that control the proliferation and differentiation of nerve cells.
These endogenous substances are called neurotrophic factors and play a major role in stimulating neuroplasticity in the brain (1). More specifically, the ones stimulated by Iboga are Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Glial cell-Derived Neurotrophic Factor (GDNF) (2).
Iboga is a unique long-term activator of GDNF which is thought to play a key role in its long-lasting medicinal benefits. According to the research, Iboga can upregulate the neurotrophic factors’ levels and block the transporters of serotonin and dopamine in the brain.
This ultimately leads to an increase in serotonin and dopamine levels, which, apart from the psychedelic effects, also holds the potential for the management of addictions, depression, anxiety, and other psychiatric conditions such as PTSD (3).
The alkaloids in Iboga also interact with several opioid, glutamate, nicotinic, and sigma receptors in the brain. This contributes to the unique effects and the wide range of potential medicinal benefits of Iboga.
Overall, the psychoactive effects of Iboga can last more than 24 hours, as Ibogaine and its metabolites have a half-life of 28-49 hours (4).
Due to its effects on the brain neurotransmitters, Iboga also can lead to minor and transitory adverse reactions, such as xerostomia (dry mouth) and ataxia (difficulty performing movements).
The alkaloids in Iboga are also heavily metabolized in the liver and block some of the ion channels in the heart (5). Thus, people with cardiovascular problems or disturbed liver metabolism due to disease and medications are contraindicated from Iboga therapy.
Iboga has been under active research since the 20th century, and it’s officially approved for anti-addiction therapy and detox in several countries worldwide.
However, Iboga’s use dates back thousands of years as it is related to an ancient spiritual tradition in Africa called Bwiti.
The Bwiti use Iboga to strengthen their community, promote spiritual growth, and perform initiation rituals to guide their young men and women into adulthood.
They continue to use the roots of the shrub to this day as a potent for physical recovery, spiritual discovery, and healing.
Psilocybin Mushrooms vs. Iboga
What is Psilocybin?
Psilocybin is a naturally occurring psychedelic substance found in over 200 species of mushrooms, but most commonly in those referred to as “magic mushrooms.”
It is a prodrug of psilocin, which is the substance responsible for the psychoactive effects of magic mushrooms.
When consumed, psilocybin is converted into psilocin, which then acts primarily on the serotonin receptors in the brain to produce its characteristic effects (10). Thus, psilocybin is classified as a classic psychedelic, more specifically, a tryptamine.
Psilocybin Effects and Side-effects Comparison with Iboga
Compared to Iboga and Ibogaine, the effects of psilocybin are much shorter as the active alkaloid psilocin has a half-life of about 60 minutes.
Therefore, once psilocybin is consumed, the effects occur within 30-60 minutes. They peak within 1-2 hours and last for up to 4-6 hours. Frequent consumption of psilocybin diminishes its effects and can lead to tolerance.
Furthermore, psilocybin is best consumed on an empty stomach because food can slow down and reduce the effects of the psychedelic.
Compared to Iboga, the effects of psilocybin are limited to the serotonin receptors. It may also upregulate BDNF, but there isn’t enough evidence to suggest any effect on GDNF.
Psilocybin gained popularity as a recreational drug in the 1950s and 1960s, and research into its potential therapeutic uses began to emerge in the following decades. It has since been studied for its potential to treat a range of mental health conditions, such as:
- Resistant depression (11)
- Anxiety and demoralization due to life-threatening illnesses (12)
- Alcohol and tobacco addictions (13)
The main therapeutic potential of psilocybin is as a tool for managing resistant depression. Studies report that the substantial antidepressant effects of psilocybin-assisted therapy may persist for at least 12 months following acute intervention in some patients (14).
Furthermore, psilocybin mushrooms stand out compared to other psychedelics with a great safety profile. They rarely lead to minor side effects such as transient nausea, slightly elevated blood pressure and heart rate, and post-use headache.
Some individuals may also experience adverse psychological reactions such as discomfort, transient anxiety, emotional discomfort, paranoia, or confusion.
Contraindications for psilocybin use include therapy with lithium compounds. Other antidepressants may reduce the effectiveness of the psychedelic, although acute monoamine oxidase inhibitor (MAOI) use intensifies the effects.
Spiritual and Tradition Comparison with Iboga
Taking psilocybin can lead to mystical experiences, which lead to increased openness, mindfulness, or spirituality in the long term.
Similar to Iboga, psilocybin use dates way back, all the way to prehistoric times in many parts of the world.
It has been used in traditional spiritual and religious practices by the indigenous shamanic rituals in Central and South America.
Similarly to Iboga, some of its spiritual traditions and religious use, is now influenced by Christianity, due to colonization. Much like how some practitioners of the spiritual tradition related to Iboga (Bwiti) fused with Chrisitanity after colonizers came, much of the people who used mushrooms as their sacrament did too.
It is important to note that not all of the spiritual traditions using these sacraments did this. You can still find versions of the traditions that are not influenced by Christianity, although it is harder with Mushroom traditions than Iboga.
MDMA vs. Iboga
In contrast to Iboga and Ibogaine, MDMA is a fully synthetic psychedelic. It is also known as Ecstasy or Molly and is a synthetically produced serotonergic amphetamine.
MDMA stands for 3,4-Methylenedioxymethamphetamine and was first synthesized by the German pharmaceutical company Merck Serono in 1912 but eventually became illegal in 1985.
Chemically it is classified as phenethylamine, while functionally, it is an empathogen–entactogen (15). This means it acts to “generate within” a state of empathy, emotional openness, and a sense of communion.
MDMA Effects and Side-effects Comparison with Iboga
Unlike Iboga, MDMA has a short half-life, and its effects last 3-6 hours. They occur soon after injection and reach a maximum within 60-120 minutes of the first dose. Due to the short half-life, MDMA is often dosed in 2-3 intakes within 2 hours between each.
Doses taken after the effect wears off have reduced effectiveness due to the development of acute tolerance. Food can significantly decrease absorption.
MDMA has complex effects that interact with serotonin, dopamine, and norepinephrine signaling. It also stimulates the release of oxytocin and antidiuretic hormones (vasopressin).
The serotonergic signaling is most affected, which also mediates its psychedelic effects. Compared to Iboga, MDMA does not appear to have a significant effect on BDNF, GDNF or NGF.
Furthermore, MDMA’s potential uses appear to be quite limited compared to that of Iboga. MDMA is an experimental drug for the management of PTSD, and its use in MDMA-assisted therapies is under active investigation.
Such interventions involve a combination of standard psychological therapy and the benefits of the altered state of consciousness produced by MDMA, which allow for a deeper healing process.
MDMA results in reduced emotional reactivity, suppressed fear, and uplifted mood. Studies suggest that the psychedelic can help strengthen the relationship between the therapist and the patients (16).
Furthermore, the therapist can engage the patients in the therapy more successfully and the patient is able to reflect upon painful memories and traumas without fear.
A meta-analysis of all 6 randomized placebo-controlled trials reports that MDMA-assisted psychotherapy treatment reduced the patients’ PTSD scores much more effectively than psychotherapy alone (17).
As a result, about 50% of the patients on MDMA-assisted psychotherapy no longer met PTSD diagnosis criteria, compared to only 20% of the control group.
Common side effects usually occur soon after use and include low mood, insomnia, irritability, and poor cognition. Some users also report nausea, fatigue, and lack of appetite.
High doses or combinations with lithium compounds, MAOIs, stimulants, and anti-HIV/AIDS medication can lead to serotonin toxicity and seizures and are contraindicated. Recreational use also carries a risk of addiction.
MDMA can cause a significant increase in blood pressure and heart rate, so it’s also contraindicated for people with cardiovascular problems and uncontrolled hypertension.
The psychedelic has a predominant liver metabolism. Thus, liver disorders or medications that inhibit the function of liver enzymes, such as CYP2D6, CYP1A2, etc., can lead to an increased risk of toxicity.
Spiritual and Tradition Comparison with Iboga
Since MDMA is a newly synthesized chemical, there is not a spiritual tradition or history associated with it. However, many people have had very deep experiences when taking it at musical events or with those that they love.
DMT vs Iboga
What is DMT?
DMT stands for N, N-Dimethyltryptamine, and it’s a classic psychedelic with a tryptamine structure. As such, it is structurally quite similar to serotonin and exerts its psychoactive effects by activating the serotonergic system.
DMT is now widely used in is crystalline or extract form where it is smoked in either a pipe, or more popularlyl in a vaporizer.
DMT is naturally found in many plants and organisms, but the most commonly used source is from the leaves of the Psychotria viridis shrub, aka Chacruna (18). It must be combined with MAOIs, such as the beta-carboline found in the vines of Banisteriopsis caapi, aka soul vine, to become orally active.
The combination of Psychotria viridis and Banisteriopsis caapi is well known as Ayahuasca tea. For at least a millennia, the indigenous peoples in South America, more specifically the Upper Amazon Basin, have used the mixture for various religious and spiritual purposes.
Different shamans also often add other ingredients and create their own unique blends to optimize the brew’s effectiveness.
DMT Effects and Side-effects Comparison with Iboga
Unlike Iboga, DMT is not orally active. That’s because of the presence of MAO (monoamine oxidase) enzymes in the gastrointestinal system, which neutralize DMT before it reaches the bloodstream (19).
Instead, it can be smoked or injected, which leads to a rapid onset of its effects and they occur within seconds (20). In such cases, the DMT has a half-life of around 3 mins. Therefore, the effects reach a peak within 2-5 minutes and last up to 7-15 minutes.
In order to become orally bioavailable, DMT must be combined with MAOIs. A natural example of MAOI is beta-carboline found in Banisteriopsis caapi, which blocks the degradation of DMT in the digestive system and significantly slows down its neutralization in the body.
The combination with MAOIs increases the half-life of DMT by up to an hour and the total duration of the effects by up to 4-6 hours. The onset of the psychedelic effects occurs within 20-60 minutes and reaches a peak within 60-120 minutes. Furthermore, repeated dosage does not lead to the development of tolerance, regardless of the route.
The combination does not lead to toxicity because this type of metabolic inhibition is incomplete, and DMT can be metabolized by alternative routes such as N-oxidation, N-demethylation, and cyclization (21).
Studies suggest that the combination of DMT and MAOIs, such as beta-carboline, may have therapeutic potential for conditions such as recurrent and treatment-resistant depression (22), (23). According to these trials, the response rate ranges from 64% to 82% and lasts for at least a week after a single dose of Ayahuasca.
In contrast to Iboga, DMT does not appear to significantly affect the levels of neurotrophic growth factors in the brain. However, the addition of MAOIs help upregulate BDNF.
Other trials also report the potential benefits of Ayahuasca for patients with PTSD and addictions, but the research is still preliminary (24) (25). DMT can have several side effects, such as an increase in blood pressure, heart rate, body temperature, vomiting, and seizures (26).
The increase in blood pressure is likely related to the presence of MAOI in Ayahuasca which blocks the breakdown of tyramine – an amino acid that occurs naturally in the body and it’s found in certain foods.
Tyramine helps regulate blood pressure, and combining MAOIs with foods that contain high amounts of it, such as aged cheese, soy sauce, fava beans, red wine, and others, can lead to dramatic hypertensive episodes (27). There have also been cases of persistent tinnitus after DMT use (28).
Furthermore, high doses of DMT can lead to a complete loss of control and potentially traumatic experiences. Some may also have a near-death experience, and hyperreal hallucinations may lead to delusions, egomania, or derealization.
Spiritual and Tradition Comparison with Iboga
Since DMT is a newly synthesized chemical, there is not a spiritual tradition or history associated with it, althought there are new Churches and spiritual relationships being developed with it throughout the world. Of course, Ayahuasca, which contains DMT has also been used for thousands of years by indigenous communities in the Amazon.
If you would like to learn more about this, we have created a whole article about the differences between Ayahuasca and Iboga.
5-MeO-DMT (Bufo) vs. Iboga
What are 5-MeO-DMT and Bufo?
5-MeO-DMT stands for 5-methoxy-dimethyltryptamine. It is another classic psychedelic that interacts primarily with the serotonergic system in the brain.
Chemically, it is a tryptamine that can be synthetically produced but it is also found naturally in certain plants and animals.
The psychedelic occurs naturally in the venom of the Colorado River toad, also known as the Sonoran Desert toad or simply Bufo. The venom is called Bufotoxin, and 5-MeO-DMT comprises about 30% of its dry weight.
The venom of the toad also contains dangerous digoxin-like toxins, which pose serious cardiovascular risks (29). Thus it cannot be consumed directly. Instead, history suggests that 5-MeO-DMT has been consumed primarily through plant sources.
It is naturally found in plants such as the Yopo tree. It has been used for 3000 years in the form of crushed seeds known as ‘Yopo,’ which are still taken today in spiritual ceremonies in Venezuela, Columbia, and Brazil.
5-MeO-DMT Effects and Side-effects Comparison with Iboga
5-MeO-DMT has a similar structure to DMT but it is 4-10 times more potent, and its effects last slightly longer. Users have reported overwhelming experiences, including auditory and visual hallucinations, which occur rapidly and are often described as a mystical union, feelings of non-duality, and experiences of a transpersonal nature.
Furthermore, 5-MeO-DMT has an oral bioavailability of about 30%, even without the addition of MAOIs. In fact, adding MAOIs can lead to toxicity because 5-MeO-DMT can also block serotonin reuptake (30).
Therefore, 5-MEO-DMT should not be used in Ayahuasca instead of DMT because of the risk of serotonin toxicity and even death.
The rapid onset and extreme intensity of the effects of 5-MeO-DMT limit its potential medical and recreational use. Currently, there are very few studies investigating its medicinal benefits.
One such study of 362 people who used 5-MeO-DMT recreationally reported significant effects on anxiety and depression (31). Out of all participants, 41% had anxiety, and 48% had depression. Around 80% of those suffering from the conditions experienced improvement.
It’s important to note that even moderate doses of 5-MeO-DMT can leave you completely incapacitated. Side effects may include nausea, vomiting, and chest pressure. Following the experience, users have reported sleep disturbances, persistent anxiety, and panic attacks.
Due to the increase in heart rate and blood pressure, 5-MeO-DMT should not be combined with stimulants. This psychedelic also has a low potential for addiction (32).
LSD vs. Iboga
What is LSD?
LSD (lysergic acid diethylamide) is a classic psychedelic that is fully synthetic and it is colloquially popular as “acid” (33). It was originally derived in 1938 by the Swiss chemist Albert Hofmann from a type of fungus known as Ergot.
The psychedelic was manufactured by the Swiss pharmaceutical company Sandoz in the 50s until it was banned in the 70s due to its high abuse potential. Chemically, LSD is a lysergamide which means it contains both tryptamine and phenethylamine structures.
LSD Effects and Side-effects Comparison with Iboga
LSD mechanism of action primarily affects the serotonergic signaling in the brain. Yet, it has more complex effects than other classic psychedelics and also activates dopamine and glutamate receptors (34).
LSD may also affect the levels of certain hormones such as prolactin, oxytocin, and epinephrine (35). Similarly to Iboga, low doses of LSD may also upregulate the levels of BDNF, GDNF, and NGF.
When taken orally, LSD has potent effects, which occur even in micrograms. Their onset is within 30-60 minutes of ingestion, the effect reaches a peak of 90-240 minutes, and lasts for 8-12 hours. Repeated dosing leads to tolerance.
Users commonly report amplified sensory experiences, especially towards music. They also describe euphoria, loosened association, mystical experiences, and dream-like hallucinations. Some may experience anxiety, panic, terror, suspiciousness, or paranoia.
LSD has much more limited therapeutic potential than Iboga. It may have benefits in alcoholism, as studies suggest that a single therapeutic dose can significantly decrease alcohol misuse (36). Unfortunately, some of the effects diminish after several months of the intervention.
A recent review of the literature also confirms that LSD shows a significant potential for therapeutic benefits in alcoholism (37). The researchers suggest that the psychedelic may also have some benefits for patients with anxiety and depression.
Currently, LSD is also investigated for its potential effects during micro-dosing, which involves taking small doses that are insufficient to cause any psychoactive effects (under 25 mcg), although the research so far shows no clear benefit of this strategy.
Common side effects of LSD include hypertension and increased heart rate. LSD is usually well tolerated physically, and serious side effects such as seizures, hyperthermia, and rhabdomyolysis are rare.
LSD may be poorly tolerated psychologically by some patients. Some users have reported the occurrence of Hallucinogen Persisting Perception Disorder (HPPD), which is a rare clinical condition (38).
Patients with HPPD continue to experience perceptual distortions months to years after complete cessation of the initial substance use, but these side effects have not been reported with LSD use in controlled settings.
Contraindications against LSD use include therapy with tricyclic antidepressants and lithium compounds, as it increases the risk of seizures. Another contraindication are medications that affect liver metabolism and, more specifically, inhibit the CYP3A4 enzymes which may slow down the metabolism of LSD and increase the risk of toxicity.
Spiritual and Tradition Comparison with Iboga
Since LSD is a relatively newly synthesized chemical, there is not many formal spiritual traditions associated with it. However, since the 1960’s, many people have used it for spiritual growth and discovery. There have been some Churches. Organizations, and certainly many spiritual seekers who have utilized and benefitted from LSD as a tool.
Mescaline (Peyote) vs. Iboga
What is Mescaline?
Mescaline, chemically known as 3,4,5-trimethoxyphenethylamine, is the only phenethylamine that is also a classic psychedelic.
It has a phenethylamine structure similar to MDMA but acts as a classic psychedelic because it interacts primarily with serotonergic signaling and leads to the release of serotonin to a much larger degree than dopamine or noradrenaline.
The psychedelic occurs naturally in several species of cacti, most notably Peyote and San Pedro, which are indigenous to Central America and South America.
Mescaline is likely one of the most ancient natural psychedelics used by humans. Peyote mescaline has been used for millennia by the Native Americans as a sacrament for their sacred rituals and to commune with the divine.
Peyote contains hundreds of alkaloids, although mescaline is thought to be primary to Peyote’s effects. Some of the other alkaloids may potentiate the effects of mescaline, while others may be inert or have physical effects.
Mescaline Effects and Side-effects Comparison with Iboga
Chemically, mescaline was first isolated in 1895. Since then, it has been investigated for its medicinal potential alongside LSD to treat alcohol addictions, but unfortunately, research is scarce (39).
Of of the main natural sources – Peyote – is endangered in the wild, and has a traumatic history in terms of colonialism and Native American genocide.
Another much more sustainable source of mescaline is the cactus San Pedro which is usually prepared in South America as a decoction known as Huachuma.
Due to lack of studies, much of its therapeutic potential remains largely unknown to the scientific community. Mescaline has a longer half-life than other classic psychedelics but is still much shorter than Iboga – about 6 hours.
Similarly to Iboga and other psychedelics, mescaline should be taken on an empty stomach. Once consumed, the onset of the effects occurs within 30-60 minutes and reaches a maximum of around 3-6 hours. The total duration of the effects is 10-14 hours.
Repeated dosing leads to tolerance, and mescaline has a cross-tolerance with classic psychedelics such as LSD.
Mescaline has a slower onset and extended duration of action, similar to classic tryptamines. It also leads to lower dopamine release, which reduces its addictive potential compared to other phenethylamines, such as MDMA.
Unlike other psychedelics, mescaline is not just metabolized in the liver, but also in the peripheral tissues. Much of it is excreted unchanged by the kidney and can even be re-isolated from the urine.
This is why one of the main contraindications for mescaline use is kidney disease, as such conditions may slow down its excretion and prolong or increase the effects. Potential side effects include nausea, vomiting, increased blood pressure, heart rate, and body temperature.
Spiritual and Tradition Comparison with Iboga
While Mescaline was more recently synthesized, Peyote has been used as an entheogen for thousands of years. (49) It is probably one of the longest used entheogens after Iboga in human history.
Spiritual traditions of Peyote have a similarities in to Iboga. Just as some practitioners of the spiritual tradition associated with Iboga (Bwiti) adopted Christianity, one of the main groups also created a Christian fusion tradition related to the sacrament.
The religion is now known as the Native American Church (NAC), and Peyote continues to be its official sacrament. Similar to Fang Bwiti, the Native American Church also utilizes Christianity, the religion of the colonizers.
It is important to note that not all of the spiritual traditions using these sacraments did this. You can still find versions of the traditions that are not influenced by Christianity.
NAC members have a religious exemption from the federal government to use Peyote as a sacrament. Otherwise, seeds and cacti are illegal to possess and grow in the US.
Ketamine vs. Iboga
What is Ketamine?
Unlike all other psychedelics in this list, including Iboga, ketamine is a dissociative psychedelic. It causes users to feel detached from their bodies or the physical environment as a whole.
Ketamine is fully synthetic, has potent anesthetic effects, and acts as a non-competitive glutamate antagonist towards the NMDA receptors in the nervous system (40). It also interacts with the opioid, muscarinic, dopamine, norepinephrine, and serotonin receptors.
Ketamine was first developed in the early 1960s. It was synthesized by Calvin Stevens, a scientist at Parke-Davis, a pharmaceutical company now a part of Pfizer (41).
Ketamine was initially developed as a general anesthetic for surgical procedures and has since become widely used in both human and veterinary medicine.
Currently, it is an FDA-approved fast-acting anesthetic and is commonly used in surgical and trauma settings for short-term pain relief and sedation.
Ketamine is actually a racemic mixture which means it consists of equal parts of two enantiomers, R- and S-ketamine (42). S-ketamine has a 2-4x higher affinity for the NMDA receptor and is 2-4x more potent as an analgesic and anesthetic than R-ketamine.
It binds to the opioid receptors and increases dopamine levels, which can lead to addictive behavior. At the same time, S-ketamine is less likely to cause psychosis-like symptoms.
Ketamine Effects and Side-effects Comparison with Iboga
Compared to Iboga, the effects of ketamine are much shorter. This is due to the short half-life of ketamine which is only 2-4 hours. Ketamine also has extensive first-pass metabolism in the levels, which reduces its oral bioavailability down to only 17%.
Thus, ketamine is also often used intranasally and as intramuscular or intravenous injections. The effect occurs immediately after intravenous administration but lasts only 15 minutes, while oral administration can lead to effects lasting from 4 to 12 hours.
In addition to its main use as an anesthetic, off-label use of ketamine has been found to have beneficial effects in treating certain mental health conditions, especially treatment-resistant depression.
Unlike Iboga, ketamine requires regular intake to exert these benefits. For example, research shows that single use of a subanesthetic dose of ketamine has a robust and rapid effect on depression, which was seen immediately after the administration, and its benefits were sustained for days or weeks (43).
Ketamine may also help reduce depressive symptoms in individuals with suicidal ideation.
However, the symptoms of depression eventually reoccur, so repeated dosing is required. According to the latest meta-analysis, which covered 2665 patients, repeated dosing demonstrates that even the most treatment-resistant patients may benefit from ketamine (44).
Some preclinical studies have suggested that R-ketamine is more effective than S-ketamine for depression (45).
Yet, clinical research suggests that S-ketamine might exert similar antidepressant effects as ketamine in drug-resistant depression and is better tolerated by patients (46).
Ketamine is also investigated for its potential to reduce anxiety and pain. Research suggests that ketamine may also help treat addiction in patients with cocaine dependence, although the effect appears to be lower compared to Iboga (47).
Ketamine use can lead to side effects such as nausea, vomiting, and increased blood pressure and heart rate. Users also often report dizziness, vertigo, headache, and changes in taste perception.
Unlike Iboga, chronic ketamine use can also lead to addiction and the development of lower urinary tract problems. Ketamine can cause bladder dysfunction and impaired bladder emptying (48).
This increases the risk of urinary infections. Long-term or frequent use of ketamine can lead to the development of chronic bladder problems, such as cystitis or bladder pain syndrome, which can be difficult to treat.
Contraindications include psychosis, schizophrenia, and recent use of opioids, benzodiazepines, or alcohol.
Spiritual and Tradition Comparison with Iboga
Since Ketamine is a relatively newly synthesized chemical, there are not many formal spiritual traditions associated with it. Some may also argue whether Ketamine is even a Psychedelic at all.
- Lu B, Figurov A. Role of neurotrophins in synapse development and plasticity. Rev Neurosci. 1997;8(1):1-12. doi:10.1515/revneuro.1918.104.22.168
- Marton S, González B, Rodríguez-Bottero S, et al. Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits. Front Pharmacol. 2019;10:193. Published 2019 Mar 5. doi:10.3389/fphar.2019.00193
- Bulling S, Schicker K, Zhang YW, et al. The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. J Biol Chem. 2012;287(22):18524-18534. doi:10.1074/jbc.M112.343681
- Glue P, Lockhart M, Lam F, Hung N, Hung CT, Friedhoff L. Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability. J Clin Pharmacol. 2015;55(2):189-194. doi:10.1002/jcph.404
- Koenig X, Hilber K. The anti-addiction drug ibogaine and the heart: a delicate relation. Molecules. 2015;20(2):2208-2228. Published 2015 Jan 29. doi:10.3390/molecules20022208
- Schenberg EE, de Castro Comis MA, Chaves BR, da Silveira DX. Treating drug dependence with the aid of ibogaine: a retrospective study. J Psychopharmacol. 2014;28(11):993-1000. doi:10.1177/0269881114552713
- Davis AK, Barsuglia JP, Windham-Herman AM, Lynch M, Polanco M. Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short- and long-term outcomes and current psychological functioning. J Psychedelic Stud. 2017;1(2):65-73. doi:10.1556/2054.01.2017.009
- Mash DC, Kovera CA, Pablo J, et al. Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures. Ann N Y Acad Sci. 2000;914:394-401. doi:10.1111/j.1749-6632.2000.tb05213.x
- Alper KR, Lotsof HS, Frenken GM, Luciano DJ, Bastiaans J. Treatment of acute opioid withdrawal with ibogaine. Am J Addict. 1999;8(3):234-242. doi:10.1080/105504999305848
- Madsen MK, Fisher PM, Burmester D, et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels [published correction appears in Neuropsychopharmacology. 2019 Mar 8;:]. Neuropsychopharmacology. 2019;44(7):1328-1334. doi:10.1038/s41386-019-0324-9
- Davis AK, Barrett FS, May DG, et al. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial [published correction appears in JAMA Psychiatry. 2021 Feb 10;:]. JAMA Psychiatry. 2021;78(5):481-489. doi:10.1001/jamapsychiatry.2020.3285
- Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016;30(12):1181-1197. doi:10.1177/0269881116675513
- Garcia-Romeu A, Davis AK, Erowid F, Erowid E, Griffiths RR, Johnson MW. Cessation and reduction in alcohol consumption and misuse after psychedelic use. J Psychopharmacol. 2019;33(9):1088-1101. doi:10.1177/0269881119845793
- Gukasyan N, Davis AK, Barrett FS, et al. Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. J Psychopharmacol. 2022;36(2):151-158. doi:10.1177/02698811211073759
- Vollenweider FX. Brain mechanisms of hallucinogens and entactogens. Dialogues Clin Neurosci. 2001;3(4):265-279. doi:10.31887/DCNS.2001.3.4/fxvollenweider
- Sessa B. MDMA and PTSD treatment: “PTSD: From novel pathophysiology to innovative therapeutics”. Neurosci Lett. 2017;649:176-180. doi:10.1016/j.neulet.2016.07.004
- Smith KW, Sicignano DJ, Hernandez AV, White CM. MDMA-Assisted Psychotherapy for Treatment of Posttraumatic Stress Disorder: A Systematic Review With Meta-Analysis. J Clin Pharmacol. 2022;62(4):463-471. doi:10.1002/jcph.1995
- Chambers MI, Appley MG, Longo CM, Musah RA. Detection and Quantification of Psychoactive N,N-Dimethyltryptamine in Ayahuasca Brews by Ambient Ionization High-Resolution Mass Spectrometry. ACS Omega. 2020;5(44):28547-28554. Published 2020 Oct 27. doi:10.1021/acsomega.0c03196
- Ruffell S, Netzband N, Bird C, Young AH, Juruena MF. The pharmacological interaction of compounds in ayahuasca: a systematic review [published correction appears in Braz J Psychiatry. 2020 Nov-Dec;42(6):688]. Braz J Psychiatry. 2020;42(6):646-656. doi:10.1590/1516-4446-2020-0884
- Barker SA. Administration of N,N-dimethyltryptamine (DMT) in psychedelic therapeutics and research and the study of endogenous DMT [published correction appears in Psychopharmacology (Berl). 2022 Feb 11;:]. Psychopharmacology (Berl). 2022;239(6):1749-1763. doi:10.1007/s00213-022-06065-0
- Riba J, McIlhenny EH, Bouso JC, Barker SA. Metabolism and urinary disposition of N,N-dimethyltryptamine after oral and smoked administration: a comparative study. Drug Test Anal. 2015;7(5):401-406. doi:10.1002/dta.1685
- Osório Fde L, Sanches RF, Macedo LR, et al. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Braz J Psychiatry. 2015;37(1):13-20. doi:10.1590/1516-4446-2014-1496
- Palhano-Fontes F, Barreto D, Onias H, et al. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychol Med. 2019;49(4):655-663. doi:10.1017/S0033291718001356
- Inserra A. Hypothesis: The Psychedelic Ayahuasca Heals Traumatic Memories via a Sigma 1 Receptor-Mediated Epigenetic-Mnemonic Process. Front Pharmacol. 2018;9:330. Published 2018 Apr 5. doi:10.3389/fphar.2018.00330
- Nunes AA, Dos Santos RG, Osório FL, Sanches RF, Crippa JA, Hallak JE. Effects of Ayahuasca and its Alkaloids on Drug Dependence: A Systematic Literature Review of Quantitative Studies in Animals and Humans. J Psychoactive Drugs. 2016;48(3):195-205. doi:10.1080/02791072.2016.1188225
- Houle SKD, Evans D, Carter CA, Schlagenhauf P. Ayahuasca and the traveller: A scoping review of risks and possible benefits. Travel Med Infect Dis. 2021;44:102206. doi:10.1016/j.tmaid.2021.102206
- Sathyanarayana Rao TS, Yeragani VK. Hypertensive crisis and cheese. Indian J Psychiatry. 2009;51(1):65-66. doi:10.4103/0019-5545.44910
- Diab H, Malcolm B. Persistent Tinnitus after Inhaled N,N-dimethyltryptamine (DMT). J Psychoactive Drugs. 2021;53(2):140-145. doi:10.1080/02791072.2020.1847366
- Brubacher JR, Ravikumar PR, Bania T, Heller MB, Hoffman RS. Treatment of toad venom poisoning with digoxin-specific Fab fragments. Chest. 1996;110(5):1282-1288. doi:10.1378/chest.110.5.1282
- Shen HW, Jiang XL, Winter JC, Yu AM. Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Curr Drug Metab. 2010;11(8):659-666. doi:10.2174/138920010794233495
- Davis AK, So S, Lancelotta R, Barsuglia JP, Griffiths RR. 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. Am J Drug Alcohol Abuse. 2019;45(2):161-169. doi:10.1080/00952990.2018.1545024
- Davis AK, Barsuglia JP, Lancelotta R, Grant RM, Renn E. The epidemiology of 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption. J Psychopharmacol. 2018;32(7):779-792. doi:10.1177/0269881118769063
- Liester MB. A review of lysergic acid diethylamide (LSD) in the treatment of addictions: historical perspectives and future prospects. Curr Drug Abuse Rev. 2014;7(3):146-156. doi:10.2174/1874473708666150107120522
- De Gregorio D, Comai S, Posa L, Gobbi G. d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology. Int J Mol Sci. 2016;17(11):1953. Published 2016 Nov 23. doi:10.3390/ijms17111953
- Schmid Y, Enzler F, Gasser P, et al. Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects. Biol Psychiatry. 2015;78(8):544-553. doi:10.1016/j.biopsych.2014.11.015
- Krebs TS, Johansen PØ. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. J Psychopharmacol. 2012;26(7):994-1002. doi:10.1177/0269881112439253
- Fuentes JJ, Fonseca F, Elices M, Farré M, Torrens M. Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials. Front Psychiatry. 2020;10:943. Published 2020 Jan 21. doi:10.3389/fpsyt.2019.00943
- Kurtom M, Henning A, Espiridion ED. Hallucinogen-persisting Perception Disorder in a 21-year-old Man. Cureus. 2019;11(2):e4077. Published 2019 Feb 14. doi:10.7759/cureus.4077
- Bogenschutz MP, Ross S. Therapeutic Applications of Classic Hallucinogens. Curr Top Behav Neurosci. 2018;36:361-391. doi:10.1007/7854_2016_464
- Zorumski CF, Izumi Y, Mennerick S. Ketamine: NMDA Receptors and Beyond. J Neurosci. 2016;36(44):11158-11164. doi:10.1523/JNEUROSCI.1547-16.2016
- Li L, Vlisides PE. Ketamine: 50 Years of Modulating the Mind. Front Hum Neurosci. 2016;10:612. Published 2016 Nov 29. doi:10.3389/fnhum.2016.00612
- Muller J, Pentyala S, Dilger J, Pentyala S. Ketamine enantiomers in the rapid and sustained antidepressant effects. Ther Adv Psychopharmacol. 2016;6(3):185-192. doi:10.1177/2045125316631267
- Mandal S, Sinha VK, Goyal N. Efficacy of ketamine therapy in the treatment of depression. Indian J Psychiatry. 2019;61(5):480-485. doi:10.4103/psychiatry.IndianJPsychiatry_484_18
- Alnefeesi Y, Chen-Li D, Krane E, et al. Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review & meta-analysis. J Psychiatr Res. 2022;151:693-709. doi:10.1016/j.jpsychires.2022.04.037
- Zhang JC, Li SX, Hashimoto K. R (-)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine. Pharmacol Biochem Behav. 2014;116:137-141. doi:10.1016/j.pbb.2013.11.033
- Paul R, Schaaff N, Padberg F, Möller HJ, Frodl T. Comparison of racemic ketamine and S-ketamine in treatment-resistant major depression: report of two cases. World J Biol Psychiatry. 2009;10(3):241-244. doi:10.1080/15622970701714370
- Dakwar E, Nunes EV, Hart CL, et al. A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial. Am J Psychiatry. 2019;176(11):923-930. doi:10.1176/appi.ajp.2019.18101123
- Chen IC, Lee MH, Chen WC, Hu TC, Lin HY. Risk Factors of Lower Urinary Tract Syndrome among Ketamine Users. Low Urin Tract Symptoms. 2018;10(3):281-286. doi:10.1111/luts.12178
- El-Seedi HR, De Smet PA, Beck O, Possnert G, Bruhn JG. Prehistoric peyote use: alkaloid analysis and radiocarbon dating of archaeological specimens of Lophophora from Texas. J Ethnopharmacol. 2005 Oct 3;101(1-3):238-42. doi: 10.1016/j.jep.2005.04.022. PMID: 15990261.