DMT - A Psychedelic Compound With Promising Mental Health Benefits

James Odell, OMD, ND, LAc

Over the last few decades, there has been growing scientific interest in the endogenous neurotransmitter and hallucinogen N, N-dimethyltryptamine (DMT) secreted by the pineal gland and present in numerous plants and animals worldwide. 

This article will outline DMT history, current research regarding its biosynthesis, and its potential therapeutic application (specifically mental health benefits) in bioregulatory medicine. 

What is DMT?

DMT is an indole (the product of bacterial decomposition of tryptophan) alkaloid widely found in nature and an endogenous compound produced in the human body.1 

Its presence across species suggests it has an important biological role conserved throughout evolution. 

When administered exogenously, due to its hallucinogenic properties, DMT has been used to study “outside the body” experiences and dreams, while also being used as a model for psychological research.2, 3 Its unique physiological effects consumed from plants have been traditionally used in many cultures and are now being explored as therapy for various health conditions.

DMT History

DMT was first synthesized in 1931 by the Canadian chemist Richard Manske and named “Nigerine”,4 after  first being isolated from the seeds of the plant Mimosa nigeriana (later recognized as Mimosa hostilis), which is native to regions of South America and Africa. The name "Nigerine" comes from the Latin word "niger", meaning "black," which was likely chosen because of the dark color of the plant's seeds.

Later, the compound was recognized as dimethyltryptamine (DMT), based on its chemical structure, and the name "Nigerine" fell out of use.At that time, it was not explored for its important physiological role and potential therapeutic use. In 1946 the microbiologist Oswaldo Gonçalves de Lima discovered DMT's natural occurrence in plants.5 

Note: For more information about DMT in plants visit https://psychedelicspotlight.com/a-guide-to-plants-containing-dmt/

DMT's hallucinogenic properties were not discovered until 1956 when the Hungarian chemist and psychiatrist Dr. Stephen Szara, extracted DMT from the Mimosa hostilis plant and administered the extract to himself intramuscularly. With his colleagues, he characterized the biochemistry of the first three psychedelic congeners of tryptamine: dimethyl-, diethyl-, and dipropyl-tryptamine (DMT, DET, and DPT), describing their pharmacological dynamics and effects.6 Szara continued research into DMT and published several informative papers.7, 8, 9 

Szara’s research marked the beginning of understanding the historical use of many DMT-containing plants as a cultural and religious ritual sacrament and their effect on the psyche.10 

In 1977, Samuel Christian identified DMT as a neuroregulatory agent in the mammalian brain.11 Since then numerous animal DMT research has demonstrated its unique neuroregulatory effects on neurotransmitters.12, 13, 14

Sources of DMT in Reptiles, Plants, and Laboratories

Humans have a long history of using natural resources, especially plants, to induce heightened and non-ordinary states of consciousness. Psychoactive, hallucinatory substances such as DMT derived from plants have been linked to acquiring spiritual knowledge and have also been used cross-culturally in spiritual rituals.

• The Sonoran Desert Toad - 5-MeO-DMT has been identified as the primary psychoactive component of the parotoid gland venom of Bufo alvarius (Incilius alvarius), the Sonoran Desert toad, where it accounts for about 20–30% of its dry weight. The venom of the Bufo alvarius also contains bufotenine from which 5-MeO-DMT is converted through O-methyl transferase. When vaporized by heat and taken into the lungs in the form of smoke, this indole-based alkaloid produces an incredibly intense psychedelic experience of extremely short duration. Effects following administration of 5-MeO-DMT are similar to those of other tryptamine psychedelics such as psilocybin and DMT and are known to include a diverse set of acute subjective effects including visual, auditory, and time perception distortions, emotional experiences, and memory impairment. The text “Bufo Alvarius, the Psychedelic Toad of the Sonoran Desert” by Albert Most was seemingly the first guide for collecting, drying, and smoking the venom of the Sonoran Desert toad. It created an opportunity for further research, and its popularity as a psychedelic spread quickly.15  Unfortunately, the toad is becoming endangered and is now protected under law.

  
  

  

  • Synthetic Production - 5-MeO-DMT can be synthetically made in the lab. The main difference between toad venom of the Bufo alvarius and synthetic 5-MeO-DMT is that the former contains a range of pharmacologically active compounds in addition to 5-MeO-DMT. These include cardioactive agents such as bufagins (i.e., bufandienolides), catecholamines, such as epinephrine and norepinephrine, indolealkylamines, such as bufothionine, serotonin, cinobufotenine, bufotenine, and dehydrobufotenine, and noncardiac sterols, such as cholesterol, provitamin D, gamma sitosterol, and ergosterol. It is presently unknown if any of these additional compounds synergistically modulate the effects of 5-MeO-DMT in ways that would be relevant for therapeutic applications. 

  
  

  • Plant Sources - Ayahuasca is a hypernym for a range of psychotropic concoctions and is traditionally associated with Amazonian cultures.16, 17, 18, 19 Ayahuasca, a traditional Amazonian decoction with psychoactive properties, is made from bark of the Banisteriopsis caapi vine (containing beta-carboline alkaloids) and leaves of the Psychotria viridis bush (supplying the hallucinogen N,N-dimethyltryptamine, DMT). The primary ingredient in ayahuasca is Banisteriopsis caapi, which may be boiled and brewed as a tea (alone), although it is often mixed with other plants, most commonly Psychotria viridis (known as chacruna, chacrona, or chaqruy in the Quechua languages). Banisteriopsis caapi is grown in tropical areas of northern South America while Psychotria viridis is thought to have been limited to lowland areas of the Amazon basin.20, 21, 22, 23 Recently scholars have sought evidence of “ayahuasca” use during pre-Columbian times. 

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    Banisteriopsis caapi

    
    
    
    

Psychotria viridis 

DMT and Spiritual Experiences

Originally used by indigenous shamans for spirit communication, magical experiences, healing, and religious rituals across several South American countries, ayahuasca has been incorporated into folk medicine and spiritual healing, and several Brazilian churches use it routinely to foster a spiritual experience. 

When these two plants are combined in ayahuasca preparations they have dynamic interacting effects when consumed. The β-carboline alkaloids prevent the breakdown of the DMT in the digestive tract and then act as monoamine oxidase inhibitors, thus allowing the DMT to activate the central nervous system, causing vivid hallucinogenic experiences for consumers.24

The preparation of ayahuasca takes several hours, often over a day. First, plant materials are added separately to a large pot of water and boiled until the water volume is reduced by half. The individual brews are then combined and boiled further until significantly reduced. This final brew is consumed during ayahuasca ceremonies.

Scholars have debated the historical use of ayahuasca, with some suggesting it has relatively recent origins, while others argue that it may have been used for centuries, or even millennia. Archaeological evidence of the use of psychoactive plants in the northeastern Amazon dates to 1500–2000 BCE.25

Professor Steven Barker has taken DMT research to the philosophical level, considering questions of its involvement in spiritual evolution. He focuses not only on its pharmacology and hallucinogenic properties but also explores its traditional use in religious rituals. Such preparations give the impression of "being in touch with the universe". Drugs such as ayahuasca have inspired a robust tourist trade and an explosion of shamanic rituals.26

DMT and its Potential Therapeutic Use for Mental Health Benefits

The administration of psychedelic plants as therapeutics has begun to show great promise for the treatment of depression, post-traumatic stress disorders, the psychological impacts of terminal illness, and substance abuse disorders, including alcohol and opioids.27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39  

Most of these studies have examined the use of psilocybin from mushrooms or ayahuasca instead of DMT alone. In the history of the use of DMT-containing “remedies,” ayahuasca has perhaps the longest record.40, 41, 42 Long-term use of ayahuasca has been shown to produce measurable changes in the brain itself, such as differences in midline brain structures as determined from MRI studies.43  While such effects may not appear to be of therapeutic value, long-term ayahuasca users (>10 years) have shown reduced ratings of hopelessness, anxiety, and panic attacks.44

Long-term ayahuasca use has also produced marked improvement in depressive symptoms with no concomitant mania or hypomania for up to 21 days after a single dose.45 These data suggest evidence for a potential antidepressant effect for DMT. Ayahuasca is a complex mixture also containing monoamine oxidase inhibitors (MAOIs), or harmala-like alkaloids, which, as a class of drugs, are also used to treat depression.46 Harmala alkaloids are short-term monoamine oxidase inhibitors. MAOs are important in the breakdown of monoamines ingested in food and also serve to inactivate monoamine neurotransmitters. Because of the latter, they are involved in various psychiatric and neurological diseases, some of which can be treated with monoamine oxidase inhibitors (MAOIs) which block the action of MAOs.47, 48, 49 

Current Research of DMT

It is impossible to say from these studies that DMT itself or the elevation of other brain neurotransmitters in combination is responsible for the perceived positive clinical effects, or even if the hallucinations produced by DMT consumed under these conditions are somehow therapeutic.

Several ayahuasca studies suggest potential applications in the treatment of addictions, particularly opioids, and alcohol.50, 51, 52, 53 The Takiwasi Center, located in Tarapoto, a city in the Amazonian region of northern Peru, has designed successful addiction treatment protocols using ayahuasca.54

Note: As with all drugs, the route, form, and/or dose of a substance administered or applied can play a defining role in its overall pharmacology and therapeutic use. 

Many years of shamanic wisdom have indicated potential therapeutic uses for ayahuasca, and several present-day studies suggest that it may be useful for treating various psychiatric disorders and addictions. The side effect profile appears to be relatively mild, but more detailed studies need to be conducted. Several prominent researchers believe that government regulations about DMT and plants containing DMT should be relaxed so that credible researchers can conduct comprehensive clinical trials.

The Pineal Gland and DMT

Since Christian’s identification of DMT as a neuroregulatory agent in 1977, research has now shifted from DMT’s occurrence in plants and is focused on it as an endogenous hallucinogenic compound secreted by the pineal and brain.55, 56 The pineal gland has been the subject of considerable interest from researchers for decades. The study (Scientific Research on The Pineal Gland: A Bibliometric Analysis from Its First Publication) shows that the literature review revealed a total of 8719 publications about the pineal gland. 

The pineal gland is a small neuroendocrine gland located in the midline of the skull and forms part of the epithalamus and hypothalamus, regulating the secretion of numerous chemicals such as melatonin, as well as DMT. It is made up of pinealocytes, glial cells, interstitial cells, perivascular phagocytes, and sometimes calcified aggregates. It is the pinealocytes that make this organ highly vascularized, with permeable capillaries. This organ therefore contains neural tissue, as it requires neuroendocrine connections.  The number of pinealocytes slightly decreases with age and can become calcified, a process related in part to fluoride exposure. 

The pineal gland helps regulate body temperature and skin coloration and emits secretions to surrounding emotional, visual, and auditory brain centers. It secretes N-acetyl-5-methoxytryptamine (melatonin), which is one of the key regulators of circadian and seasonal biological rhythms. Melatonin is also involved in  DNA repair and epigenetic regulation.57, 58, 59, 60 The pineal also makes a mono-amine oxidase (MAO) inhibitor called pinoline (Methoxytetrahydrobetacarboline (MeOTHBC)) which acts on the GABA receptors and whose chemical structure is virtually identical to the harmala alkaloids. The pineal gland also secretes DMT in small amounts, and this may account for our ability to dream.

Historically, the pineal gland has been viewed to play a vital role in spiritual receptivity. This idea has been a part of Ayurvedic medicine for millennia, which connects the pineal with the “third eye, or Ajna chakra”. This chakra is associated with intuition, vision, and higher consciousness. Activating the third eye is often seen as a means to gain insight into the nature of reality, transcend ordinary perception, and connect with higher states of being. 

Kundalini is said to be a powerful, primal energy that represents the unmanifested potential within us. The first references of kundalini can be found in the Upanishads, between 500 BC and 1000 BC. The concept of kundalini energy extends across Vedic, tantric, and Hindu systems and is often referred to as kundalini shakti, meaning divine, limitless power. In Hinduism, kundalini is believed to be a goddess, whose power lies dormant, coiled at the base of the spine at the Muladhara chakra, translated as the root chakra in English. Through dedicated practices like yoga, meditation, and concentration, individuals can awaken Kundalini energy, allowing it to rise through the chakras along the spine. This awakening is often accompanied by transformative experiences, such as heightened awareness, emotional release, and spiritual awakening. It is proposed that Kundalini practice may allow the pineal to secrete DMT, offering a heightened state of awareness. 

The pineal gland has been further discussed by the philosopher René Descartes, who asserted that it was a physiological link between body and soul.61 

Strassman has proposed that the pineal gland excretes large quantities of DMT during extremely stressful life episodes, notably in the event of birth and death. He conjectured that “pineal tissue in the dying or recently dead may produce DMT for a few hours, and perhaps longer, and could affect our lingering consciousness”.62 

DMT is an Endogenous “Neurotransmitter”

It is now understood that DMT is a unique neurotransmitter and is responsible for the modulation of serotonergic or other neurotransmitter systems. DMT works by blocking the action of serotonin in the brain. Tryptamines refer to a broad class of classical or serotonergic hallucinogens. Serotonergic hallucinogens are drugs that affect serotonin, which is a substance that acts as a neurotransmitter and carries signals throughout the body.

Serotonin regulates mood, digestion, sleep, and other important bodily functions. When serotonin levels in your body are too little or too high, it can negatively affect your mental and physical health. DMT acts as a non-selective agonist at most or all serotonin receptors, specifically at the 5-ht2a receptor. Stimulation of this receptor may help induce the hallucinogenic effects of DMT. At the same time, the serotonin produced inhibits both dopamine and adrenaline.

Also, it may well be that many existing pharmaceuticals already exert their pharmacology via DMT-related-effect mechanisms. This may be the case for the other hallucinogens, but it may also be true for part of the mode of action of certain serotonergic drugs, such as antidepressants.

Some reports have suggested that DMT may be actively taken up by the central nervous system. One study reported measuring a brain/plasma ratio for DMT of 5.4 after intraperitoneal (IP) injection of DMT in rats and suggested that this brain/plasma ratio seems “to indicate that the compounds cross the blood-brain barrier easily and are perhaps accumulated by an active transport”. Despite that speculation, they also report that DMT “had disappeared from the brain, liver, and plasma within 30 min.”63

Hallucinogens have been shown to produce brain patterning resembling dream states, apparently mediated through 5-HT2A receptor activation. DMT's effect in this regard has yet to be fully examined but raises speculation as to one of the possible roles of endogenous DMT. New receptors for DMT have been identified and a potential role for DMT as a neuroprotectant and/or neuro-regenerative agent has been suggested. 

Conclusion

Though relatively obscure, N,N-dimethyltryptamine (DMT) is an important molecule in psychopharmacology as it is the archetype for all indole-containing serotonergic psychedelics. Its structure can be found embedded within those better-known molecules such as lysergic acid diethylamide (LSD) and psilocybin. Unlike the latter two compounds, DMT is ubiquitous, being produced by a wide variety of plant and animal species. 

It is one of the principal psychoactive components of ayahuasca, a tisane made from various plant sources that has been used in spiritual ceremonies for centuries. Results indicated that structured ayahuasca consumption is medically safe and exhibits a potential protective psychological effect.64, 65 

Furthermore, DMT is one of the few psychedelic compounds produced endogenously by mammals, and its biological function in human physiology remains a mystery. Its psychoactive effects were first described in 1956 by Stephen Szára. DMT is now being used and investigated for its therapeutic effects in several clinical areas. An increasing number of papers suggest consumption of DMT-containing herbs offers promising benefits for mood and psychiatric symptoms in the areas of substance use disorders, anxiety, and depression. 

An important aspect of the possible therapeutic use of serotonergic tryptamines such as DMT is their modulatory effect on neuroplasticity. Neuropsychiatric diseases, such as major depressive disorder, anxiety, PTSD, or addiction have high comorbidity66 and share common underlying neural principles.67, 68, 69 

A plethora of previous reports suggests that decreased neuroplasticity and neural atrophy in the prefrontal cortex can play an essential role in the general pathophysiology of these disorders.70, 71, 72, 73, 74, 75

These disruptive structural changes in the prefrontal cortex could be rectified by compounds that can promote structural and functional neural plasticity, such as DMT.76, 77, 78, 79 Such unique natural compounds would provide a natural, safe solution to treat all these related disorders.80 

Not only is DMT both endogenous and exogenous in nature but also can be produced in a lab. The rapid onset and short duration of the DMT experience may render it more psychoemotionally comfortable and clinically convenient compared with longer-acting psychedelics. 

An important issue regarding the therapeutic potential of DMT is the lack of controlled, larger cohort clinical studies. Besides appropriate dosing, a standardized route of administration may also be critical concerning the therapeutic outcome.81, 82, 83  A variety of routes of administration such as vaporization and intranasal, intravenous, and IM administrations appear feasible to standardize. It is expected that clinical studies in the near future will incorporate these different routes of administration in their design to determine and compare their pharmacokinetic and pharmacodynamic profiles.

It has been 94 years since DMT was first synthesized by Manske, 69 years since Szara discovered its hallucinogenic properties, and 41 years since Christian et al. characterized DMT as a neurotransmitter. Research has further clarified its characteristics, and there is now a strong case to consider DMT as a likely neurotransmitter.

For over 50 years DMT research has been impeded in the United States by passage of the Congressional Amendment of 1965 and the Controlled Substances Act of 1970 by the United States Congress that classified DMT and other major hallucinogens as Schedule-I substances. Given the endogenous nature of DMT and its traditional use in spiritual rituals as contained in plants, it deserves special legal status for future research. Such studies are less likely to be conducted as part of drug development programs and are more likely to rely on independent, academic initiatives.

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