Science on 5-MEO-DMT
5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) is a psychedelic of the tryptamine class. It is found in a wide variety of plant species (for example the ‘Yopo tree’), and at least one toad species, the Sonora Desert toad (also called Colorado River toad or Bufo Alvarius). Like its close relatives N,N-DMT and bufotenin (5-HO-DMT), it has been used as an entheogen in South America. Theo means ‘God’, endogenous means ‘present in the body’. Entheogen can therefore be translated as ‘coming from the God within’.
The 5-MeO-DMT is analogous of regular DMT (also called N,N-DMT), which is one of the main active ingredients of Ayahuasca, a millenarian decoction used as a sacrament by South American indigenous tribes, known to induce powerful hallucinogenic states when administered with monoamine oxidase inhibitors (MAOI; (Araújo, Carvalho, Bastos, Guedes de Pinho, & Carvalho, 2015). 5-MeO-DMT is nicknamed ‘The God Molecule’, whereas DMT is labelled as ‘The Spirit Molecule’. The latter one is highly popularised by the book of Rick Strassman: ‘DMT, the spirit molecule – A doctor’s revolutionary research into the biology of Near-death and mystical experiences’. Although 5-Meo-DMT is chemically slightly different that DMT, its perceived effects on our ‘visual displays’ are hugely different. By many users, 5-MEO-DMT is considered to be much more potent than DMT, ranging from an estimated 10 times to an ‘infinity times’ higher potency. In my experience, this only holds if one passes through the gate or experiences a complete ego-death. This article will not focus on the trip experience but on what is known about this medicine, for as far as science is concerned. The body of knowledge of 5-MEO-DMT (and other psychedelics in general) is growing rapidly these days, mainly for its therapeutical use in the treatment of depression, anxiety and addiction. However, the legal restrictions and the lack of experimental models still offer resistance in reaching the full research potential.
5-MeO-DMT is a serotonin agonist that acts in a non-selective manner in 5-HT2A >5-HT2C >5-HT1A receptors (Szabo, Kovacs, Frecska, & Rajnavolgyi, 2014). N-N-DMT has been reported elsewhere to also acts in many glutamate, dopamine, and acetylcholine receptors (Carbonaro & Gatch, 2016).
Article 1: A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus
Written by Lima da Cruz, Moulin, Petiz, & Leão (2019)
Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells. Neurogenesis is positively associated with cognitive performances. The subgranular zone (SGZ) of the dentate gyrus (DG), which is part of the hippocampus, is one of the few regions in which neurogenesis is maintained throughout adulthood. It is believed that new-born neurons in this region encode temporal information about partially overlapping contextual memories. Many environmental factors, such as exercise, stress, and antidepressants have been reported to change the rate of neurogenesis within the hippocampus of rodents (Hanson, Owens, & Nemeroff, 2011; Santarelli, 2003). The study showed that a single intracerebroventricular (ICV) injection of 5-MeO-DMT increases the number of Bromodeoxyuridine (BrdU+) cells in adult mice DG. Moreover, it was found that 5-Meo-DMT treated mice had a higher number of new-born DG Granule cells (GC) and that these DG GC have more complex dendritic morphology after 5-MeO-DMT administration. Lastly, new-born GC treated with 5-MeO-DMT, display shorter afterhyperpolarization (AHP) potentials and higher action potential (AP) threshold compared. The findings show that 5-MeO-DMT affects neurogenesis and this effect may contribute to the known antidepressant properties of DMT-derived compounds.
Article 2: Fast-acting psychedelic associated with improvements in depression/anxiety
Written by Davis, So, Lancelotta, Barsuglia, & Griffiths (2019)
Researchers have discovered that use of the synthetic psychedelic 5-methoxy-N,-N-dimethyltryptamine (5-MeO-DMT) appears to be associated with unintended improvements in self-reported depression and anxiety when given in a ceremonial group setting. In a survey of 362 adults, approximately 80 percent of respondents reported improvements in anxiety and depression after use. These improvements were related to more intense acute mystical effects during the 5-MeO-DMT experience, as well as increases in the rating of the personal meaning and spiritual significance of the experience. Improvements were also related to stronger beliefs that the experience contributed to enduring well-being and life satisfaction. Davis et. al. (2019): ‘‘Because 5-MeO-DMT is short-acting and lasts approximately 30-90 minutes, it could be much easier to use as an adjunct to therapy because current therapies usually involve a 60 – 90 minute session.’’
Article 3: Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT
Written by Dakic et al., (2017)
Proteins associated with long-term potentiation are modulated by 5-MeO-DMT
These changes in key components, and further regulation of several other proteins and secondary messengers suggest a complex regulation of this pathway. AMPAR, and the signalling cascade leading to c-Raf, mitogen-activated protein kinase 1/2 (MEK1/2), and extracellular regulated kinase 1/2 (ERK1/2) are upregulated, suggesting pathway activation (Fig. 5). Based on the literature, activated ERK1/2 is transported to the nucleus and activates CREB, resulting in the expression of a large number of downstream genes (Alberini, 2009).
5-MeO-DMT leads to inhibition of NF-κB signalling pathway
Among the canonical pathways identified are nuclear factor of activated T-cells (NFAT) and nuclear factor kappa B (NF-κB) signalling via toll-like receptor (TLR) and Gq-coupled receptors, which are all inhibited by 5-MeO-DMT treatment (Fig. 4). Interestingly, the direct targets of 5-MeO-DMT, receptors 5-HT2A and 5-HT2C, are Gq-coupled. Furthermore, NF-κB is very well known to be the main transcriptional regulator of inflammatory, pro-inflammatory and anti-inflammatory cytokines and chemokines (Szabo et al., 2014).
Article 4: A single inhalation of vapour 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
Written by Uthaug et al., (2019)
The first objective of this study was to assess sub-acute and long-term effects of inhaling vapour from dried toad secretion containing 5-MeO-DMT on impact and cognition. The second objective was to assess whether any changes were associated with the psychedelic experience. The results were that ratings of satisfaction with life and convergent thinking significantly increased right after intake and were maintained at follow-up 4 weeks later. Ratings of mindfulness also increased over time and reached statistical significance at 4 weeks. Ratings of depression, anxiety, and stress decreased after the session and reached significance at 4 weeks. Participants that experienced high levels of ego dissolution or oceanic boundlessness during the session displayed higher ratings of satisfaction with life and lower ratings of depression and stress.
Article 5: Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells
Written by Szabo et al., (2014)
The orphan receptor sigma-1 (sigmar-1) is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models. Here it is demonstrated for the first time the immunomodulatory potential of N,N-DMT and 5-MeO-DMT on human moDC functions via sigmar-1 that could be harnessed for the pharmacological treatment of autoimmune diseases and chronic inflammatory conditions of the CNS or peripheral tissues. The findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor.
Based on the above-mentioned papers, the following conclusions can be drawn. Note that some of the papers used rodents instead of humans; some conclusions are therefore limited.
1. 5-MeO-DMT affects neurogenesis and this effect may contribute to the known antidepressant properties of DMT-derived compounds.
2. After 5-MEO-DMT use, approximately 80 percent of respondents reported improvements in anxiety and depression after use. These improvements were related to increases in rating personal meaning and spiritual significance of the experience. Improvements were also related to stronger beliefs that the experience contributed to enduring well-being and life satisfaction.
3. 5-MEO-DMT administration stimulates the expression of a large number of genes.
4. 5-MEO-DMT acts as an endogenous regulator of inflammation and immune homeostasis. To some, the results imply that 5-MEO-DMT works anti-inflammatory.
5. 5-MEO-DMT increases ratings of satisfaction with life and convergent thinking right after administration and continued to increase over a period of 4 weeks. Ratings of depression, anxiety, and stress decreased after the session and reached significance at 4 weeks.