N, N-dimethyltryptamine (DMT) in rodent brain: Concentrations, distribution, and recent pharmacological data.

Renewed interest in psychedelic drugs highlights DMT's therapeutic effectiveness and its role as a neuroplastogen. DMT binds to intracellular sigma-1 and 5-HT2a receptors, with the latter located on the Golgi apparatus in cortical neurons, and fails to occupy cell surface 5-HT2a receptors. DMT is proposed as the endogenous ligand for intracellular 5-HT2a receptors, which serotonin cannot access. Brain levels of DMT are elevated by stress in rats and appear under inducible, adaptive physiological regulation. These findings suggest DMT may be involved in brain development and explain subjective effects of psychedelics.

Study at a glance

Abstract

Renewed interest in the clinical use of psychedelic drugs acknowledges their therapeutic effectiveness. It has also provided a changing frame of reference for older psychedelic drug study data, especially regarding concentrations of N, N-dimethyltryptamine (DMT) reported in rodent brains and recent discoveries in DMT receptor interactions in rat brain neurons and select brain areas. The mode of action of DMT in its newly defined role as a neuroplastogen, its effectiveness in treating neuropsychiatric disorders, and its binding to intracellular sigma-1 and 5HT2a receptors may define these possible roles. Recent data also show psychedelics promote neuroplasticity via activation of sigma-1 receptors associated with the endoplasmic reticulum and binding to 5-HT2a receptors predominantly related to the intracellular membrane of the Golgi apparatus in cortical neurons and the failure of DMT to occupy cell surface 5-HT2a receptors. While DMT has been proposed as the endogenous ligand for sigma-1, there is no identified ligand for intracellular 5-HT2a receptors, which serotonin cannot acquire. DMT is proposed to be the missing endogenous ligand. These data further suggest that DMT may be involved in brain development in rat pups. Brain levels of DMT have also been shown to be elevated by stress in the rat and appear to be under an inducible, adaptive, physiological regulatory system control. With DMT acting as the natural ligand for intracellular 5HT2a receptors in the Golgi, it may also explain the subjective effects observed from the administration of psychedelics in general and define some of the natural roles for DMT in particular.