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DMT (N,N-Dimethyltryptamine): Risks & Emerging Research

Written by Mathew Eng, PharmD | Last updated:
Evguenia Alechine
Jonathan Ritter
Puya Yazdi
Medically reviewed by
Evguenia Alechine, PhD (Biochemistry), Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Mathew Eng, PharmD | Last updated:

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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 health risks and emerging research.

Disclaimer: DMT is classified as a Schedule I substance. This means that it is an illegal drug with high potential for harm and no known medical uses. We highly advise against the use of DMT until future studies determine its safety and efficacy in medically-supervised and safe settings. The only aim of this post is to outline research findings

What is DMT?

DMT (N,N-Dimethyltryptamine) is a psychedelic compound belonging to the tryptamine family of molecules.

The possession and use of DMT are illegal. In most countries, including the United States, DMT is a Schedule I substance. Drugs under this classification are considered to have no accepted medical use, a lack of accepted safety, and a high potential for abuse.

DMT is naturally found in many 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. The function of this naturally occurring DMT is unclear [1, 2, 3].

Mechanism of Action

According to research, DMT exerts its effects through several mechanisms, which are listed below.

  • DMT binds to and activates receptors of the serotonin system (5-HT1A, 5-HT2A, and 5-HT2C) [4, 5, 6].
  • Activation of serotonin receptors causes the release of glutamate, which activates glutamate receptors [7].
  • DMT binds to and activates the sigma-1 receptor (Sig-1R), which may help reduce inflammation and cell death [8].
  • The psychedelic effects of DMT may also be attributed to the activation of the trace amine-associated receptor (TAAR6) [9].

DMT alone has little effect when consumed orally because it is quickly broken down by MAO enzymes in the body. MAO is an enzyme that is responsible for breaking down different neurotransmitters, such as dopamine and serotonin. For DMT to be orally active, it must be co-administered with an MAO inhibitor [10, 11].

History

Historically, South American tribes would prepare a brew called ayahuasca, a plant-based blend that contains DMT and an MAO-A inhibitor. The combined effect of both compounds allows for DMT to be absorbed into the bloodstream before being broken down [12].

Tribes consumed these drinks in spiritual and religious ceremonies. It induces euphoria and hallucinations that are believed to have mystical and healing powers [10].

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 [7].

Legal Status

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

However, certain religious groups in the U.S. have been granted exemptions and are allowed to import, brew, and distribute ayahuasca tea, which contains DMT [13].

How is DMT Different From Ayahuasca?

Ayahuasca is a brew made from several plants. It typically contains DMT as well as small compounds called β-carbolines, which inhibit the enzyme MAO-A. This enzyme is responsible for breaking down DMT and neurotransmitters (dopamine, serotonin, and noradrenaline) [14, 7].

By inhibiting MAO enzymes, ayahuasca may prolong the effects of DMT and modify feelings of euphoria and arousal [14, 7].

Ayahuasca is a 2 to 6-hour experience that slowly builds over time until a peak is reached, and the effects wear off slowly. Vaporized and intravenous DMT are short-lived experiences (15 min) in which effects peak quickly (within 2 minutes) and then quickly taper off [14, 15, 16].

Ayahuasca contains a mixture of plants that have other active compounds in addition to DMT, such as harmala alkaloids [14].

Because ayahuasca is brewed from different plants, drink composition may be different each time it is prepared, potentially leading to inconsistent effects [14, 17].

Effects of DMT

Psychological Effects of DMT

The psychological effects of DMT can vary depending on a number of factors, including dose, setting, personality, and pre-existing health conditions. Psychological effects may include [16]:

  • 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 may include [18]:

Health Risks and Side Effects

Due to a lack of clinical research, the side effects and long-term health risks of DMT are unclear. Some potential side effects include [16, 19, 20, 21]:

  • Increased blood pressure, heart rate, and body temperature
  • Nausea and vomiting
  • Prolonged psychotic states, which can depend on the user’s mental state and history of mental illness
  • Structural changes in the brain from prolonged use, which may lead to changes in personality
  • Panic, especially in users with a history of mental illness

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 [21, 22].

DMT Areas of Research

Clinical Research

Certain psychedelic drugs, such as LSD and psilocybin have gained renewed interest for their potential to treat drug addictions, PTSD, and other mental disorders. However, out of all of these substances, DMT is one of the least researched [23, 24].

One issue is that research often focuses on ayahuasca instead of DMT alone. While ayahuasca does contain DMT, it also contains a number of other active compounds. It is unclear how much DMT contributes to the effects of ayahuasca, and there is very little research done on DMT alone [23, 24].

Animal And Cell Research (Lacking Evidence)

No clinical evidence supports the use of DMT for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.

Hypoxia

According to research, DMT may activate Sig-1R, a receptor that protects against cell death and inflammation. In a cell study, DMT activated Sig-1R and increased the survival of neurons and immune cells that were deprived of oxygen (hypoxia) [25, 8].

Inflammation

Sigma receptors (including Sig-1R) are found on many immune cells, suggesting they may play a role in immune function [26].

Cell studies suggest that DMT may reduce the production of the inflammatory cytokines IL-1β, IL-6, and TNFα and increase the production of the anti-inflammatory cytokine IL-10 by activating Sig-1R [27].

About the Author

Mathew Eng

Mathew Eng

PharmD
Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.
Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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