Not all serotonergic psychedelics are alike - they induce distinct patterns of altered metabolic activity and connectivity
OpenAlex – May 28, 2024
Source: OpenAlex
Summary
Psilocybin, a powerful hallucinogen, uniquely alters brain activity compared to LSD and 2C-B. Neuroscience on three psychedelics in rat brains showed psilocybin specifically rewired cortical regions, influencing behavior. Conversely, LSD and 2C-B similarly inhibited the anterior cingulate cortex and boosted dopamine-rich areas. These distinct pharmacological actions, influencing neurotransmitter receptors, are crucial for Medicine and Psychedelics and Drug Studies. Understanding these differences in brain activity can guide treatments for neuropsychiatric disorders, including anxiety, and inform future drug development.
Abstract
Serotonergic psychedelic drugs have shown promising benefits in trials for various neuropsychiatric disorders. While the acute effects of these psychedelics last only a few hours, the positive therapeutic effects can persist long after a single administration. Serotonergic psychedelics produce their psychedelic effects by activating serotonin 2A receptors, but they differ in other pharmacological aspects. To guide the safest and most effective treatment for specific neuropsychiatric disorders, it is crucial to gain a better understanding of the distinct acute and long-term effects of these drugs on the living brain. Here we demonstrate how three different serotonergic psychedelics; psilocybin, LSD and 2C-B, induce distinct acute and long-term patterns in rat brain metabolic activity and connectivity. The doses administered were chosen to reflect psychedelic effects in humans. We found that, psilocybin induced a distinct pattern of acute and long-term effects, particularly focusing on changes in connectivity between cortical regions such as the orbitofrontal, medial prefrontal, and insula cortex, as well as with the dorsal striatum, thalamus, and hippocampus. In contrast, LSD and 2C-B showed more similar effects, with their acute and long-term impacts centered on the acute inhibition of the anterior cingulate cortex. This was accompanied by increased activity and connectivity between the amygdala and hypothalamus, along with heightened activity in the dopamine cell-rich regions of the ventral tegmental area and substantia nigra. Our findings of distinct acute and long-term changes in metabolic activity and connectivity within these networks provide new insights into the shared and drug-selective mechanisms underlying the therapeutic effects of psychedelic substances in neuropsychiatric disorders. These insights could offer guidance on which drugs might be beneficial for certain psychiatric diseases.