DMT: Past, Present and Future - Part 2
As we move towards the possibility of DMT and 5-MeO-DMT (5-MeO) being used as therapeutics, a considerable amount of information about the compounds has been elucidated. Studies exploring effects on the brain and how the molecules modulate signalling pathways have been completed. Studies concerning the subjective effects of DMT and how they relate to the neurological effects have also been carried out. In the second part of this series, we will explore this current knowledge and explain its significance in relation to subjective effects.
Presence in the Brain
DMT, despite being discussed in popular culture as otherworldly, is endogenous in many forms of life, including in humans. It exists in low concentrations in brain tissue, and levels are elevated and raised in response to external stressors. It is unknown, however, what precisely these low concentrations achieve. At first, it was believed that levels were too low to achieve anything noteworthy and that the DMT was inert in the brain. With further research, it was found that DMT can activate trace-amine-associated receptors [1]. Moreover, it was discovered that DMT can be sequestered in neurotransmitter storage vesicles at biologically relevant concentrations [1]. This bolsters the idea that the DMT found in our brains may have pertinent activity.
Understanding Brain Waves
This article will focus on how DMT and 5-Meo alter brain function. One way of measuring brain activity is by looking at brain waves. Brain waves are electrical impulses that are the result of groups of neurons communicating with each other. These waves can be measured by an electroencephalogram (EEG). There are five recognised classes of waves: gamma, beta, alpha, theta, and delta. Gamma waves have the highest frequency and indicate a concentrated state. Delta waves have the lowest frequency and are indicative of sleep. A summary of the waves and their corresponding behavioural states can be found below [2].
The most concrete and reliable physiological feature of DMT is a decrease in alpha brain waves [3]. The presence of alpha waves is characteristic of rest, relaxation, and lack of focus. They are usually highest during wakeful rest. A decrease in alpha waves would be experienced during intense focus. In EEG studies, the most prominent modulations in signalling are in the first 2–5 minutes. The DMT experience is usually taken in with closed eyes, and at rest, so it is interesting that the brain signalling indicates otherwise. The density of alpha-band oscillations in the parietal and occipital cortex are inversely correlated with visual imagery intensity [4]. In other words: the fewer alpha oscillations during the DMT experience, the more intense the visual hallucinations. This is corroborated by the common effect of DMT feeling like one is “seeing with the eyes shut.”
In addition to the decrease in alpha oscillations, studies of inhaled DMT have also shown an increase in delta and gamma oscillations [5]. If we recall the table above, this would mean increases in the highest and lowest frequency wave bands. Increases in gamma waves have been associated with mystical experiences and appear to be partially accomplished through 5-HT-2a receptor activation [6].
The modulation of waves across a wide range of frequency bands appears to work in tandem to produce the otherworldly, dream-like state of DMT and 5-MeO. The emergence of theta and delta oscillations has been associated with dreaming and related visionary states [3]. When coupled with the decreased alpha oscillations, this could be the explanation for DMT breakthrough experiences and entity interactions. In essence, DMT may herald the shift from visual processing of exogenously derived information to endogenously derived information, much like dreaming [3]. This can be paralleled by the fact that, on occasion, dreams can be profound experiences, much like DMT trips. It is worth noting that these changes in theta and delta oscillations have not been reported in compounds such as LSD and psilocybin [7].
Clinically speaking, the invocation of a concentrated, introspective, and relaxed state is a productive set of characteristics to maximise the benefit of a psychedelic-assisted therapy session. The mystical experience is associated with positive outcomes in therapeutic applications [6], and many participants in DMT studies, as well as other psychedelic studies, cite the mystical experience as one of, if not the most, meaningful experience of their lives.
Alteration of Cortical Travelling Waves
DMT has been implicated in altering cortical travelling waves [4]. The direction of these waves changes depending on if one is in a state of visual perception or closed-eye restfulness. These dynamics are called oscillatory waves. They travel from the occipital (lower back of the head) region to the frontal region during visual perception (forward travelling waves). On the other hand, during closed-eye restfulness, the direction appears to be the inverse (backwards travelling waves). Alamia et al. outlined that, upon administration, DMT causes a decrease in backwards-travelling waves and an increase in forward-travelling waves. This is indicative of visual perception. Additionally, all alpha waves were decreased, with the exception of the forward-travelling alpha band [4].
5-Meo DMT and EEG scans
5-Meo decreases alpha frequencies acutely, much like DMT. The duration and intensity of the subjective effects correlate with the magnitude of the observed EEG effects [8]. Similarly to DMT, 5-Meo also elicits an increase in theta and delta power. While the EEG effects are similar to DMT, it is hard to discern the cause of the different subjective experiences between the two. The additional methoxy group will have an effect on 5-HT receptor binding and may help to explain the differing natures of the trips. There is a strong link between the activation of 5-HT2a receptors and the strength of hallucinogenic effects. However, considering its potent psychedelic activity, 5-MeO shows a relatively low affinity for 5-HT2a receptors and shows the highest affinity for 5-HT1a [9]. The majority of 5-HT receptor subtypes are postsynaptic, including 5-HT2a . Some are presynaptic, meaning they modulate serotonin release, 5-HT1a being one of these. This may help to explain the differing visual nature of the 5-MeO breakthrough experience compared to DMT.
The third and final article in this series will explore the clinical utility of both DMT as well as 5-MeO-DMT and explain the benefits and challenges that may arise in the future.
Sources:
[1] Carbonaro, Theresa M, and Michael B Gatch. “Neuropharmacology of N,N-dimethyltryptamine.” Brain research bulletin vol. 126,Pt 1 (2016): 74–88. doi:10.1016/j.brainresbull.2016.04.016
[2] Science Direct. Brain Waves, https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/brain-waves
[3] Timmermann, Christopher et al. “Neural correlates of the DMT experience assessed with multivariate EEG.” Scientific reports vol. 9,1 16324. 19 Nov. 2019, doi:10.1038/s41598–019–51974–4
[4] Alamia, Andrea et al. “DMT alters cortical travelling waves.” eLife vol. 9 e59784. 12 Oct. 2020, doi:10.7554/eLife.59784
[5] Pallavicini, Carla et al. “Neural and subjective effects of inhaled N,N-dimethyltryptamine in natural settings.” Journal of psychopharmacology (Oxford, England) vol. 35,4 (2021): 406–420. doi:10.1177/0269881120981384
[6] Tagliazucchi, Enzo et al. “Baseline Power of Theta Oscillations Predicts Mystical-Type Experiences Induced by DMT in a Natural Setting.” Frontiers in psychiatry vol. 12 720066. 5 Nov. 2021, doi:10.3389/fpsyt.2021.720066
[7] Beckley Foundation, Ayahuasca/DMT: https://www.beckleyfoundation.org/ayahuascadmt/
[8] Ermakova, Anna O et al. “A narrative synthesis of research with 5-MeO-DMT.” Journal of psychopharmacology (Oxford, England) vol. 36,3 (2022): 273–294. doi:10.1177/02698811211050543
[9] Halberstadt, Adam L et al. “Behavioral effects of α,α,β,β-tetradeutero-5-MeO-DMT in rats: comparison with 5-MeO-DMT administered in combination with a monoamine oxidase inhibitor.” Psychopharmacology vol. 221,4 (2012): 709–18. doi:10.1007/s00213–011–2616–6
Featured photo by Milad Fakurian on Unsplash.
