Scientists Test the Effects of Inhaling Synthetic 5-MeO-DMT

Some changes occured to biomarkers for stress and inflammation. The subjective effects reveal more evidence of the entourage effect.

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A December 2019 article published in Psychopharmacology examined the effects of inhaling synthetic 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine).1 The goals of the study were to understand how 5-MeO-DMT effects inflammation and stress biomarkers and assess its effects on anxiety, depression, stress, mindfulness, and satisfaction with life.

5-MeO-DMT is a psychedelic compound that occurs naturally in plants and it is one of several compounds found in so-called toad venom or toad secretions, particularly that of the Sonoran Desert toad Bufo alvarius. PSR has written extensively about toad secretions and 5-MeO-DMT in the past, including 5-MeO-DMT, Toad Secretions, and the Entourage Effect and Studies Find 5-MeO-DMT Improves Symptoms of Anxiety and Depression.

Study Design

The study took place in Prague in the Czech Republic and used 11 volunteers (8 males, 3 females). They received assessments at baseline, immediately post-session, and at a 7-day follow-up after taking various doses of vaporized synthetic 5-MeO-DMT. At each assessment, participants gave a saliva sample which was analyzed using a test called ELISA, which stands for enzyme-linked immunosorbent assay. Their psychedelic experiences were evaluated at each assessment using a battery of tests described later.

Limitations of the Study

The authors noted some limitations in this study, including small sample size and no placebo control group. A very significant limitation was the inconsistency of the dosing of the participants with vaporized 5-MeO-DMT. The authors stated that the doses “depended largely on the personal desires of the participant.” Three people took one dose, one person took two doses, five took three doses, and two had four doses.

The researchers said that each dose ranged from about 17 to 61 mg, and the summed total doses were between 17 and 61 mg. On top of this, there was a wide variation in the average duration of the participant’s inhalations, how long they held their breath, and how far apart multiple doses were administered. In spite of these limitations, the study made some interesting findings.

Measuring Stress and Inflammation Using Biomarkers

In this study, doing the ELISA test determined the levels of cortisol, IL-6 (interleukin-6), CRP (C-reactive protein), and IL-1ß (interleukin-1beta) in the saliva samples of the participants at each assessment point.

Cortisol is released by the adrenal glands in response to stress. It causes the release of sugars into the blood and it increases the ability of the brain to utilize sugar. Cortisol also makes the body release substances that repair tissues as a proactive measure in case of injury. IL-6 is a cellular signaling protein involved in inflammation and the immune response brought on by tissue injury or infection.2 Overproduction of IL-6 is frequently involved in autoimmune and chronic inflammatory diseases.

Healthcare professionals use the blood levels of CRP to monitor the level of inflammation in patients who are dealing with infection and trauma.3 CRP works as a surveillance molecule, providing early defense signaling for the body’s immune system. IL-1ß is a cell signaling protein made by white blood cells called macrophages that is important in the inflammatory response. This molecule supports other white blood cells that fight infection by helping them pass through the walls of blood vessels to areas of infection. IL-1ß is also responsible for fevers that accompany infection.

For the subjective portion of the study, the researchers used five questionnaires: DASS-21 (Depression, Anxiety, and Stress Scale 21), SWL (Satisfaction With Life scale), FFMQ-39 (Five Facets Mindfulness Questionnaire), EDI (Ego Dissolution Inventory), and 5D-ASC (5-Dimensional Altered States of Consciousness rating scale).

Results of the Study

Overall, the ELISA testing indicated that the vaporized synthetic 5-MeO-DMT affected only two of the four biomarkers tested. Also, the data analysis revealed a variety of negative and positive correlations between the levels of stress and inflammation biomarkers and the subjective experiences of the participants. The authors review these relationships in detail and compare them to the literature in their discussion. Below are some of the highlights

Effects of 5-MeO-DMT on CRP and IL-1ß

Salivary CRP and IL-1ß levels were not significantly affected by the inhalation of any dose of vaporized 5-MeO-DMT.

Effects of 5-MeO-DMT on Cortisol

Inhalation of vaporized 5-MeO-DMT significantly increased cortisol levels in saliva immediately post-session. The data showed no correlation between this change and the ratings of mental health or aspects of the psychedelic experience.

The authors theorize that the pure synthetic 5-MeO-DMT may have “mimic[ed] an intense neuroendocrine stress-like state in the participants,” which would account for the increase cortisol levels. They explained that this theory would be in line with the literature, which indicates inhaled tryptamines are fast-acting and have stress-mimicking neuromodulatory effects on human physiology.

Effects of 5-MeO-DMT on IL-6

There was a significant decrease in IL-6 concentration in the participant’s saliva immediately post-session. The authors suggest that the decrease may be due to the suppression of inflammation caused by the increased cortisol levels. They explained, “Thus, the observed decrease in salivary IL-6 levels may be the direct consequence of increased cortisol secretion independent of any psycho-neuroimmune feedback effects, or 5-HT2A and sigma-1 receptor modulatory actions of 5-MeO-DMT.”

Like cortisol, the data showed no correlation between this change and the ratings of mental health or aspects of the psychedelic experience.

Subjective Effects of Synthetic 5-MeO-DMT

After analyzing the data, the researchers noticed differences in the subjective effects the participants experienced after inhaling vaporized 5-MeO-DMT compared to a previous study they did where people inhaled vaporized toad secretions, which contain a cocktail of compounds.4 They found the moderate levels of ego dissolution and altered states of consciousness experienced in this research were similar to the previous study using toad secretions but 20-30% lower in magnitude. Also, the percentage of participants who achieved maximum ego dissolution was lower compared to the previous research. They also observed that,

Inhalation of vaporized synthetic 5-MeO-DMT primarily induced experience of unity, a blissfull state, and elementary imagery whereas inhalation of vaporized toad secretion [the previous study] induced experience of unity, spiritual experience, and a blissfull state.

The authors hypothesized that the different results from the studies may be due to the smaller sample size in this study or the differences in dose. The authors did not mention the possibility that the spiritual experience and increased magnitude of ego dissolution and altered consciousness with whole toad secretions compared to pure 5-MeO-DMT could be due to the entourage effect.

The researchers also made the interesting observation that:

[T]he magnitude of their psychedelic experience was not significantly correlated [to] the total dose of 5-MeO-DMT that participants received. The current data thus seems to suggest that any dose of 5-MeO-DMT can elicit a psychedelic experience but at an unpredictable magnitude.

These results suggest that by itself, vaporized 5-MeO-DMT is unpredictable, and its effects are modulated (likely via allosteric modulation of the serotonin 5-HT2A receptor) by the other compounds present in toad secretions. The authors suggest other factors at work may be the concentration of the compound in the blood, different rates of drug metabolism in the participants, openness to the psychedelic experience, and inhalation technique.

Within the current study, the authors observed that after dosing, non-judgment significantly increased compared to baseline. They also noted that ratings of depression decreased immediately post-session and persisted into the 7-day follow-up. Also, the participant’s scores of anxiety and stress decreased from the baseline into the follow-up.

The ratings of the psychedelic experience were negatively correlated with ratings of depression, stress, and anxiety and positively correlated with non-judgment scores. The authors theorized that these observations strongly suggest that 5-MeO-DMT contributed to these changes in the subjective measurements of the participants.

There is Little Understanding of 5-MeO-DMT

This study indicates that inhaling pure synthetic 5-MeO-DMT vapor causes changes in some inflammatory and stress biomarkers in humans. The mechanisms of action appear to be in line with the human physiology and pharmacology literature. Inhalation of synthetic 5-MeO-DMT vapor also may improve feelings of anxiety, stress, and depression and increase feelings of non-judgment.

In addition, when comparing to the author’s previous work, the results suggest that the effects of inhaling vaporized pure synthetic 5-MeO-DMT are quite different from that of a cocktail of toad secretions. Specifically, toad secretions result in a greater magnitude of ego dissolution and altered states of consciousness compared to 5-MeO-DMT alone. Also, the results suggest that toad secretions elicit a spiritual experience, whereas 5-MeO-DMT does not. From this, it is feasible to conclude that this may be the result of the entourage effect, i.e., there are multiple active compounds in toad secretions.

This work provides some new information on 5-MeO-DMT that scientists can apply to future studies. However, an overwhelming amount of information about 5-MeO-DMT (and many other psychedelics) remains a mystery. A deeper and more comprehensive understanding of how and why the subjective effects of vaporized pure synthetic 5-MeO-DMT are different from vaporized toad secretions is essential. To start, what are all the compounds in toad secretions and what is their chemistry? What controls people’s responses to 5-MeO-DMT at a molecular and cellular level? Tapping into the chemical variability of natural compounds that nature has created will give researchers the necessary knowledge to fill an unmet need for making formulations of specific compounds.

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    References
  1. Uthaug MV, Lancelotta R, Szabo A, Davis AK, Riba J, Ramaekers JG. Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment. Psychopharmacology. December 2019. doi:10.1007/s00213-019-05414-w
  2. Tanaka T, Narazaki M, Kishimoto T. IL-6 in Inflammation, Immunity, and Disease. Cold Spring Harb Perspect Biol. 2014;6(10). doi:10.1101/cshperspect.a016295
  3. Du Clos TW. Function of C-reactive protein. Annals of Medicine. 2000;32(4):274-278. doi:10.3109/07853890009011772
  4. Uthaug MV, Lancelotta R, van Oorsouw K, et al. A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology. April 2019. doi:10.1007/s00213-019-05236-w