Skip to content

Inhaled N, N-dimethyltryptamine diminishes connectivity between the ventral tegmental area and the nucleus accumbens: relevance to pathologies of mesolimbic and mesocortical pathways

Gisela Lima, Carla Soares, Marta Teixeira, Marta Lapo Pais, Célia Cabral, Patrícia Rijo, Miguel Castelo-Branco

Scientific Reports December 12, 2025 DOI: 10.1038/s41598-025-31431-1 (opens in new tab)

Read Full Text
Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Within-subject pharmacoimaging study Peer reviewed
Sample size 11
Population Healthy participants with prior experience in psychedelics
Interventions N N-dimethyltryptamine (DMT)
Topics 5-MeO-DMT DMT
Keywords Ventral tegmental area Nucleus accumbens Anterior cingulate cortex Dopamine Thalamus Reward system Cortex anatomy Mesolimbic pathway Functional connectivity Brain mapping Ventrolateral prefrontal cortex Nerve net Midbrain Superior colliculi Orbitofrontal cortex
Key points DMT reduced connectivity between the right nucleus accumbens and left ventral tegmental area while increasing connectivity between reward/affective regions and the anterior cingulate cortex, suggesting potential therapeutic potential for reward-processing disorders.

Abstract

Reward processing is a broad psychological construct that can be parsed into distinct components known as "reinforcement learning" (learning), "reward responsiveness" (liking), and "motivation to obtain a reward" (wanting). Dysfunctions in reward processing in mesolimbic and mesocortical pathways are a core feature of many pathologies. Psychedelics have been proposed as a treatment option for multiple disorders affecting the reward system, but mechanistic studies are lacking. In this preliminary, hypothesis-generating pharmacoimaging study, we evaluated the effects of inhaled N, N-dimethyltryptamine (DMT) with a particular focus on the connectivity of the mesocorticolimbic circuitry. Our within-subject pharmacoimaging design included 11 healthy participants with prior experience in psychedelics. In the active condition, DMT was self-administered immediately before MRI acquisition, while in the control condition there was no administration. We found decreased connectivity between the right nucleus accumbens (NAc) and the left ventral tegmental area (VTA), increased connectivity between the right NAc and anterior cingulate cortex (ACC) and increased connectivity between the medial prefrontal cortex (mPFC) and the ACC. These results correlated with changes in volition and perception, as measured with the hallucination rating scale. In sum, we found reduced connectivity in the midbrain-NAc pathway, which connectivity is often increased in addiction, and increased connectivity between reward/affective regions and the ACC. These findings suggest a potential therapeutic potential of psychedelics in disorders affecting reward processing.

Comparable studies

Other experimental studies on 5-MeO-DMT, most cited first.

Study Year Design Participants
Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Human cerebral organoids 2017 Experimental study
Bufo alvarius: a potent hallucinogen of animal origin. Bufo alvarius toad venom 1994 Experimental study
Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment Volunteers 2019 Within-subjects experimental study n = 11
Unmasking of a neonatal somatovesical reflex in adult cats by the serotonin autoreceptor agonist 5-methoxy-N,N-dimethyltryptamine. Adult cats 1990 Experimental study n = 10
Studies on the Mechanism of Action of Monoamine Oxidase: Metabolism of N,N-Dimethyltryptamine and N,N-Dimethyltryptamine-N-Oxide 1962 Experimental study

Citations in the library

Cited by 1

Cites 29

and 24 more in the library

Related reading

Explore topics

5-MeO-DMT DMT Addiction