By Isabelle Hall
N,N-dimethyltryptamine (DMT) is a component of the psychoactive drink ayahuasca (meaning ‘vine of the dead’ or ‘vine of the soul’ in Quechua) , made by boiling or steeping Banisteriopsis caapi vineand Pyschotria viridis leaves.1 The latter contains DMT, with the Banisteriopsis included as a source of β-carbolines such as harmine, which reversibly inhibit the action of monoamine-oxidase A enzymes that would otherwise degrade and inactivate the DMT. The beverage istraditionally consumed within Amazonian communities, for example in social settings, or during healing rituals for spiritual diagnoses.2 Various effects have been recorded following usage of ayahuasca, including auditory and visual hallucinations, euphoria, and ego-dissolution – a compromised or distorted sense of self.2,3 Symptoms mimicking those of a near-death experience (NDE) may also occur, such as feelings of inner peace, communication with other ‘entities’, and out-of-body experiences in which one imagines travelling to another realm.1
Further research has confirmed the significant overlap between phenomenological features of the experiences of people who have come close to dying and those who have used DMT, an endogenous hallucinogen synthesised in a range of plants and mammalian species, including humans. Efforts to understand how such a relationship could exist have focused on the mechanism of this compound. DMT is a partial agonist of the 5-HT receptors, which bind to serotonin. Other work has indicated that the 5-HT2A receptor is the main target influencing behaviour, as studies on mice have shown that the head-twitch response used as a measure of hallucinogenic activity in rodents, is absent following administration of DMT to 5-HT2A knockout mice. Interactions between DMT and other serotonergic and glutaminergic receptors may contribute in various ways – the visual effects cannot be explained entirely by activation of the 5-HT2A receptor, as there are other drugs capable of binding to this site with higher affinity, without producing such hallucinations.4
Neuroimaging research has also begun to determine which brain regions are most involved in the response to DMT and other hallucinogens. Functional magnetic resonance imaging has demonstrated that administration of DMT causes hypoactivity in the extrastriate regions of the occipital cortex during visual cues, as well as in temporal regions following auditory alerts.5 Based on work with other compounds such as psilocybin, it appears that hallucinogens broadly affect excitation within areas including the frontolateral/frontomedial cortex (the frontal cortex containing a particularly high density of 5-HT2A receptors), occipital cortex and medial temporal lobe, as well as inhibiting the default mode network, which comprises a set of network nodes important to cortical integration.4,6
One theory explaining why the DMT experience could mimic features of an NDE is that the extreme stress inflicted on the body during a life-threatening event may lead to the release of endogenous DMT, partly for its neuroprotective potential.7 These effects arise through its role as a ligand for the sigma-1 receptor, which is involved in functions such as neuronal morphogenesis, and regulation of cellular bioenergetics and oxidative stress. DMT is an agonist of this receptor, and other compounds with this ability have neuroprotective properties, for example controlling expression of pro-apoptotic genes, and assisting the response to intracellular calcium overload.8 However, it is uncertain whether this would be the case for humans as well. While DMT could contribute to aspects of an NDE, it is also unlikely that endogenous levels would increase to the point of altering the subject’s perception, and so it could not be considered the sole cause in such cases.7
Another potential explanation is that the DMT experience imitates the proposed serotonin flood which may affect the brain during an NDE. In dying rats, extracellular serotonin levels in cortical regions have been shown to increase threefold, during which EEG recordings indicated cessation of neuronal activity. This rise may also be related to the neuroprotective role of serotonin, as the body attempts to minimise harm caused by the life-threatening experience, or it occurs to enhance mood and make death easier for the subject. Alternatively, it may simply be a consequence of stored neurotransmitters including serotonin being released from vesicles within neurons during cell death.9
Research into this field has enhanced our understanding of the shared features of DMT use and NDEs, and suggests that near-death experiences, which have often been described as mystical in nature, can be explained in terms of psychedelic effects. Further work should seek to elucidate how the contributing factors work together to cause an NDE, as well as exploring other compounds which mimic this state, such as ketamine. Progress here may assist development of drug-based therapy for those in palliative care, who may benefit from the reduction in death-related anxiety characteristic of an NDE.7
References:
(1) Timmermann C, Roseman L, Williams L, Erritzoe D, Martial C, Cassol H, et al. DMT Models the Near-Death Experience. Frontiers in Psychology. 2018;9:1424. Available from: doi: 10.3389/fpsyg.2018.01424
(2) Hay M. The Colonization of the Ayahuasca Experience. Available from: https://daily.jstor.org/the-colonization-of-the-ayahuasca-experience/ [Accessed 17th January 2022]
(3) Dos Santos RG, Bouso JC, Hallak JEC. Ayahuasca, dimethyltryptamine, and psychosis: a systematic review of human studies. Therapeutic Advances in Psychopharmacology. 2017;7(4):141-57. Available from: doi: 10.1177/2045125316689030
(4) Barker SA. N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function. Frontiers in Neuroscience. 2018;12:536. Available from: doi: 10.3389/fnins.2018.00536
(5) Daumann J, Wagner D, Heekeren K, Neukirch A, Thiel CM, Gouzoulis-Mayfrank E. Neuronal correlates of visual and auditory alertness in the DMT and ketamine model of psychosis. Journal of Psychopharmacology. 2010;24(10):1515-24. Available from: doi: 10.1177/0269881109103227
(6) Alves PN, Foulon C, Karolis V, Bzdok D, Margulies DS, Volle E, et al. An improved neuroanatomical model of the default-mode network reconciles previous neuroimaging and neuropathological findings. Communications Biology. 2019;2(1):1-4. Available from: doi: 10.1038/s42003-019-0611-3
(7) Martial C, Cassol H, Charland-Verville V, Pallavicini C, Sanz C, Zamberlan F, et al. Neurochemical models of near-death experiences: A large-scale study based on the semantic similarity of written reports. Consciousness and Cognition. 2019;69:52-69. Available from: doi: 10.1016/j.concog.2019.01.011
(8) Frecska E, Szabo A, Winkelman MJ, Luna LE, McKenna DJ. A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity. Journal of Neural Transmission. 2013;120(9):1295-303. Available from: doi: 10.1007/s00702-013-1024-y
(9) Wutzler A, Mavrogiorgou P, Winter C, Juckel G. Elevation of brain serotonin during dying. Neuroscience Letters. 2011;498(1):20-1. Available from: doi: 10.1016/j.neulet.2011.04.051
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