DMT is a powerful hallucinogenic and psychedelic compound that has been traditionally used by many cultures for ritual and medicinal purposes. Commonly referred to as “the spirit molecule,” it produces intense visual and auditory hallucinations as well as euphoria and anxiety. Read on to learn more about DMT, including its mechanisms, effects, and risks.

Introduction

DMT (N,N-Dimethyltryptamine) is a psychedelic compound belonging to the tryptamine family of molecules. It is structurally similar to serotonin and is considered as one of the most intense psychedelic experiences.

DMT is found in numerous plants and animals, including humans. It is found in trace amounts in the mammalian brain, lungs, and spinal cord and is a byproduct of normal metabolism. DMT levels increase in the rodent brain during periods of extreme stress [R, R, R].

Pure DMT is ineffective when consumed orally. For DMT to be orally active, it must be co-administered with an MAO-A inhibitor. MAO-A is an enzyme found in the gut that is responsible for breaking down (through oxidation) different neurotransmitters (dopamine and serotonin) as well as DMT [R, R].

It is found in trace amounts in the mammalian brain, lungs, and spinal cord and is a byproduct of normal metabolism. DMT levels increase in the rodent brain during periods of extreme stress [R].

Historically, South American tribes would prepare a brew called ayahuasca, which contains DMT and an MOA-A inhibitor. The combined effect of both compounds allows for DMT to be absorbed into the bloodstream before being broken down. This results in a longer and more intense high than smoking or intravenous delivery of DMT [R].

They consumed these drinks in spiritual and religious ceremonies. It induces euphoria and hallucinations that are believed to have mystical and healing powers [R].

DMT was first synthesized in 1931 by Canadian chemist Richard Manske, and was first isolated in 1946 from Mimosa hostilis, a plant that was used by indigenous Brazilians in a sacred beverage called jurema [R].

Internationally, trade of DMT is monitored closely and its use is restricted to scientific research and medical use. In the US, it is classified as a Schedule I drug, meaning it has no medical use and has a high potential for abuse.

DMT acts on the body in a very similar manner to psilocybin, the active compound in magic mushrooms [R, R].

Although a number of different roles for DMT in the body have been hypothesized, it’s purpose is not fully understood. The earliest studies predicted that DMT played an important role in dreams and in death, but these have not been proven. Current research suggests DMT may act as a neurotransmitter involved in sense perception [R, R, R].

Mechanisms of Action

  • DMT binds to and activates the sigma-1 receptor (Sig-1R), which protects against inflammation and cell death [R].
  • DMT binds to and activates receptors of the serotonin system (5-HT1A, 5-HT2A, and 5-HT2C) [R, R, R].
  • Activation of serotonin receptors causes the release of glutamate, which activates glutamate receptors [R].
  • Additionally, the psychedelic effects of DMT are attributed to the activation of the trace amine associated receptor (TAAR6) [R].

How DMT is Used

In the 1960’s, DMT became known in the United States for its rapid onset and short duration, earning the name “the businessman’s trip” [R].

In recent years, recreational use of DMT has been increasing, with 31% of users reporting its psychotherapeutic benefits as the main reason for consumption [R].

Pure DMT is a white, crystalline substance that is most often vaporized at doses ranging from 20-70 mg or injected at doses of 10-30 mg, depending on the intensity of the experience desired. This can range from a mild psychedelic state to a profound and immersive experience, in which the user may feel as if they have communicated with alternative life-forms in a separate dimension [R, R].

When vaporized or injected, the effects are rapid and begin within seconds and peak within 2 minutes. In less than half an hour, users return to baseline (with few residual effects) [R].

Continuous use does not produce tolerance, and users typically find themselves less inclined to use DMT over time. It is therefore considered to be non-addictive [R, R].

DMT is thought to play a role in relieving anxiety and improving mood. This is due to its activation of serotonin receptors (5-HT1A, 5-HT2A, and 5-HT2C), a site of action for many modern antidepressants and antianxiety medications [R, R].

It is also thought to relieve anxiety by activating the trace amine (TA) receptors, which are involved in emotions and mood [R].

DMT may be beneficial in treating depression. Some people report long-term mood improvement and less anxiety after experimenting with DMT [R].

Psychological Effects of DMT

Although the psychological effects of DMT vary amongst users, there is generally some consistency in them. A number of effects can occur, most notably [R]:

  • Emotional arousal
  • Visual hallucinations
  • Perceptions of autonomous entities
  • Time distortion
  • Spiritual enhancement
  • Self-realization
  • Ego death
  • Euphoria
  • Anxiety

Physiological Effects of DMT

The effects of DMT on the body include [R]:

How is DMT Different From Ayahuasca?

Ayahuasca-ceremony

Although ayahuasca contains DMT, the effects of ayahuasca and vaporized and intravenous DMT differ greatly. Vaporized and intravenous DMT are short-lived experiences (15 min) in which effects peak quickly (within 2 minutes) and then quickly taper off [R, R].

Ayahuasca is a 2-6 hour experience that slowly builds over time until a peak is reached, and the effects wear off slowly [R, R].

Ayahuasca contains a mixture of plants that have other active compounds in addition to DMT, such as harmala alkaloids [R].

The brew also has a number of adverse effects such as increased blood pressure, nausea, and vomiting, whereas adverse effects are rare with vaporized DMT [R, R].

Ayahuasca also contains small compounds called βcarbolines. These compounds inhibit the enzyme MAO-A, which is responsible for breaking down DMT and the neurotransmitters dopamine, serotonin, and noradrenaline. MAO-A inhibition increases the levels of these neurotransmitters in addition to prolonging the effects of DMT. This combination modifies the feelings of euphoria and arousal of pure DMT [R, R].

Beta-carbolines may be responsible for the anti-addictive, anti-cancer, and antidepressant aspects of ayahuasca. They are also the reason why ayahuasca may interact negatively with different drugs such as modern antidepressants (MAO inhibitors), SSRI’s, and St. John’s Wort [R, R, R].

The antidepressant role of ayahuasca has been documented and studied in clinical settings, but DMT alone has not. However, improvements in depression seen with ayahuasca use are attributed to DMT activity in combination with the action of the β-carboline compounds [R].

Because ayahuasca is brewed from different plants, drink composition may be different each time it is prepared. Therefore, there may be less consistency in the subjective feelings that users get. Users may feel different effects each time they try ayahuasca [R, R].

DMT Research

DMT is a globally regulated substance and, therefore, there are limited studies regarding the potential health effects of vaporized or intravenous DMT in humans [R]. The clinical studies that do exist are dose-response studies that are unable to establish any benefits for DMT.

1) DMT May Reduce Aggression

By affecting the serotonin system in the brain, DMT may play a role in aggressive behaviors. Higher doses of DMT reduces aggression and fight intensity in rats provoked by shock [R, R].

2) DMT May Protect Against Hypoxia

DMT has been shown to activate the Sig-1R, which is a receptor that protects against cell death and inflammation. In a cell study, DMT activated the Sig-1R and increased the survival of neurons and immune cells that were deprived of oxygen (hypoxia) [R].

Targets of Sig-1R, such as DMT, show potential to treat neurodegenerative disorders like Alzheimer’s disease, ALS and multiple sclerosis [R, R, R, R].

3) DMT and Inflammation

Sigma receptors (including Sig-1R) are found on many immune cells, suggesting they may play a role in immune function [R].

DMT increased the production of the cytokines interferon-gamma and interferon beta in natural killer and dendritic cells. These cytokines help fight viral infections and improve immune function [R].

In immune cells (dendritic cells) that were exposed to toxins, DMT activated the Sig-1R, and reduced production of the inflammatory cytokines IL-1β, IL-6, and TNFα and increased production of the anti-inflammatory cytokine IL-10. This research suggests DMT may play a role in immune regulation and has the potential to treat autoimmune or chronic inflammatory diseases [R].

4) DMT and Cancer

Indolethylamine N-methyltransferase (INMT) is the enzyme that synthesizes DMT. Activity of the INMT gene that makes this enzyme is greatly reduced in certain forms of cancer [R]

Lower INMT activity is linked to more aggressive forms of prostate cancer [R].

By activating serotonin receptors, DMT helps coordinate the immune system, which may increase detection of cancerous tissues [R].

DMT Adverse Effects And Side Effects

DMT is generally considered a safe, non-toxic drug without too many adverse effects. Due to a lack of studies, long-term adverse effects are not known.

There have been no deaths reported from the use of pure DMT. However, in people with a history of psychiatric illness, DMT can be potentially toxic and detrimental to mental health [R].

Side effects include [R, R]:

  • Increased blood pressure, heart rate, and body temperature
  • Nausea and vomiting

Adverse effects include [R, R, R, R, R, R]:

  • Prolonged psychotic states. Some people may be more susceptible to a DMT-induced psychotic episode. The user’s current mental state and the setting they are in play a significant role in the outcome of the “trip”.
  • Structural changes in the brain from prolonged use, which can lead to changes in personality.
  • Panic, especially in users with a history of mental illness. However, because DMT does not last more than 20 minutes, the negative feelings of paranoia and anxiety that may be associated with a “bad trip” are typically overcome quickly.

There have been 3 reported cases in which patients suffered a long psychotic break that required hospitalization after experimenting with DMT. In all 3 cases, DMT was taken in combination with other substances and the patients had a history of psychotic symptoms [R, R].

Dosage

In the two dose-response clinical trials that have been conducted, intravenous DMT between .2 and .4 mg/kg were found to cause hallucinatory effects, while doses below .2 mg/kg only produced relaxation without any perceptual changes. Commonly used dosages for vaporized DMT are 20-50 mg [R].

Genes that Could Affect Reactions to DMT

A number of genetic variations can influence a user’s reaction to DMT. Depending on the type of variation, your genes could either increase or decrease the overall effectiveness of DMT. These genes include:

  • MAO-A (Monoamine oxidase A) codes for an enzyme that breaks down DMT in the body.
  • HTR2A: A gene that codes for the serotonin receptor, 5-HT2A.
  • HTR2C: A gene that codes for the serotonin receptor, 5-HT2C.
  • HTR1A: A gene that codes for the serotonin receptor, 5-HT1A.
  • GRM2: A gene that codes for the metabotropic glutamate receptor 2. mGluR2
  • SIGMAR1: A gene that codes for the sigma receptor 1.
  • TAAR6: A gene that codes for the trace amine associated receptor 6.

To gain a better understanding of the effect DMT could have on your body, test your genetics with SelfDecode.

User Reviews

“I was transported to that extremely alien-like realm that I had been to so many times before. I felt like I was being schooled on existence.”

“I did it all in one hit; before I could exhale, I was racing through a diamond geometric tunnel. I went to heaven. I went to hell. I lived every moment that has ever happened and will ever happen. I experienced life from every being. I am you and you are me; we are just living in separate meat sacks experiencing life from different perspectives. I saw colors that can’t be imagined. I experienced the most terrifying moments of my life and also the most pleasurable.”

“It is, as they say in Spanish, bastante, it’s enough – so much enough that it’s too much. Once smoked, the onset of the experience begins in about 15 seconds. One falls immediately into a trance. One’s eyes are closed and one hears a sound like ripping cellophane, like someone crumpling up plastic film and throwing it away…At that point one arrives in a place that defies description, a space that has a feeling of being underground, or somehow insulated and domed.”

Some users strongly disliked the experience and had bad trips:

“I cannot recall the transition to the void. There were no colors or visions, in the traditional sense. I realized immediately that I had actually poisoned myself, and this was not a DMT trip at all, this was death”

“I can still picture the entire thing in my head, and while I may not like DMT, I respect it. I went to church that Sunday for the first time in years. I feel somewhere inside now that I want to connect with God. I guess it could be that DMT awakened something inside of me, or maybe it just scared my disbelief of God out. In any case, I won’t use DMT again.”

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5 COMMENTS

  • Gordo

    I take exception with a few minor things in your write up, for example ayahuasca is not considered “more intense” than smoked or IV DMT, just longer lasting, it comes on much more gently. Also there is no evidence supporting your statement “has a high potential for abuse“ that is merely a general description for schedule one drugs, you should clarify that. As far as bio-hacking, I have an interest in this, but upon further research I’m starting to think it might actually be the harmine in ayahuasca that has the most potential benefit?

    Anecdotally, after using ayshuasca one time, in the weeks that followed I experienced a significant “afterglow” and have felt like my brain has been performing at an enhanced capacity. This piqued my curiosity so I did additional research and found many others describing similar effects. A newly published paper explores this:

    The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509699/

    Another published just this year: https://www.ncbi.nlm.nih.gov/pubmed/?term=27918874
    Effects of the Natural β-Carboline Alkaloid Harmine, a Main Constituent of Ayahuasca, in Memory and in the Hippocampus: A Systematic Literature Review of Preclinical Studies.
    Harmine is a natural β-carboline alkaloid found in several botanical species, such as the Banisteriopsis caapi vine used in the preparation of the hallucinogenic beverage ayahuasca and the seeds of Syrian rue (Peganum harmala). Preclinical studies suggest that harmine may have neuroprotective and cognitive-enhancing effects, and retrospective/observational investigations of the mental health of long-term ayahuasca users suggest that prolonged use of this harmine-rich hallucinogen is associated with better neuropsychological functioning. Thus, in order to better investigate these possibilities, we performed a systematic literature review of preclinical studies analyzing the effects of harmine on hippocampal neurons and in memory-related behavioral tasks in animal models. We found two studies involving hippocampal cell cultures and nine studies using animal models. Harmine administration was associated with neuroprotective effects such as reduced excitotoxicity, inflammation, and oxidative stress, and increased brain-derived neurotrophic factor (BDNF) levels. Harmine also improved memory/learning in several animal models. These effects seem be mediated by monoamine oxidase or acetylcholinesterase inhibition, upregulation of glutamate transporters, decreases in reactive oxygen species, increases in neurotrophic factors, and anti-inflammatory effects. The neuroprotective and cognitive-enhancing effects of harmine should be further investigated in both preclinical and human studies.

    A study published last year: https://www.ncbi.nlm.nih.gov/pubmed/27957390
    Harmine stimulates proliferation of human neural progenitors. (harmine is the main alkaloid in b. caapi in ayahuasca)

    Along similar lines of brain health: https://www.ncbi.nlm.nih.gov/pubmed/27111702
    Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies.

    Seems like an active area of research that may be of particular interest to biogerontologists and others seeking to maintain peak brain health. Perhaps harmine is most important here, I don’t know. Harmine is very inexpensive in the form of syrian rue seed (which can be further extracted quite easily to isolate the desired alkaloids), and does not have the profound psychotropic affects like ayahuasca nor does it contain DMT, it is a reversible MAO inhibitor and certainly has numerous side effects and potential interactions so I’m not advocating its use or especially routine use, mostly just watching intently at this point and learning.

    I’m more interested in the published research than any anecdotes (including my own).
    As for “is there a frequency threshold beyond which the cognitive improvement becomes a cognitive impairment?”, the only thing I’ve seen so far along those lines is: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042421

    Personality, Psychopathology, Life Attitudes and Neuropsychological Performance among Ritual Users of Ayahuasca: A Longitudinal Study
    “…In conclusion, we found no evidence of psychological maladjustment, mental health deterioration or cognitive impairment in the ayahuasca-using group.”

    1. Will Hunter

      Hi, Gordo,

      Thank you for pointing that out. I have clarified that it is a Schedule I drug. The research on harmine and ayahuasca is very interesting. You might enjoy reading this post on ayahuasca: https://selfhacked.com/blog/ayahuasca/

  • Galya Campano

    Très intéressant! Merci!

  • Andrew

    Everyone wants to look at the serotonin system because that’s been the yardstick for so long around both depression and the psychedelic experience– largely because of the simplistic (naive?) Monoamine/SSRI theory used to support drugs sold to us by big pharma. I think you’ll find more interesting insight into DMT’s MOA by looking at NMDA receptors and modulation of glutamate excitotoxicity. We see this with the rise in use of ketamine for treatment resistant depression… I love your site, btw, and was happy to see the notification for an entry on DMT… Please take a gander:
    https://www.ncbi.nlm.nih.gov/pubmed/16342002

  • colin

    You dont hack DMT. DMT hacks you. Back into the unconditional love state from where we all came. Then our egos come back and attempt to describe the indescribable. The ego cannot “control” DMT. DMT dominates and relinquishes the ego. Thanks for digging into this topic

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