• Mayuri Vaish

DMT's effects on the brain

N,N Dimethyltryptamine (DMT) is a chemical compound, often used as a psychedelic drug consumed by many. DMT works by acting as an agonist: i.e., it mimics certain neurotransmitters that promote excitation of specific neurons in the brain, which consequently manifest in adverse behavioral effects.

One of its main mechanisms is by acting as a 5-HT (serotonin) receptor agonist; i.e. it mimics the neurotransmitter serotonin and binds to serotonergic neurons. Specifically, it binds to three kinds of serotonin receptors - 5-HT1A, 5-HT2A, and 5-HT2C. However, primarily the binding of 5-HT1A is thought to contribute to DMT’s psychedelic effects.[1][2][3] [4]

Moreover, DMT has shown to activate Trace Amine-Associated Receptors (TAAR receptors), which binds many amine compounds, such as dopamine and tyramine. DMT binds to TAAR1 too because, much similar to serotonin and dopamine, DMT is a monoamine compound. TAAR1 is also a G-coupled protein receptor, which means that it can modulate the activity of surrounding neurons for a longer period of time by activating secondary messenger proteins for neurotransmission. As such, DMT binding can alter the release of serotonin, dopamine and noradrenaline in the brain, which affects mood and contributes to DMT’s psychoactive effects.[6]

DMT is also suggested to work by binding to sigma receptors. Knowledge about sigma receptors is more obscure; it essentially assists in the folding/unfolding of the endoplasmic reticulum (ER) within a cell. Sigma receptors achieve this through calcium signalling, i.e. allowing firing of a neuron through Calcium influx. It thus counters ER stress, caused by its unfolding, by producing antioxidant proteins.[7] It is thus associated with synaptic plasticity and neuroprotective effects[8], and is debated as a potential therapeutic compound for cancer. Nevertheless, its therapeutic evidence is inconclusive.


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