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Psychedelic substance 5-MeO-DMT induces long-lasting neural plasticity in mice

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The psychedelic substance 5-MeO-DMT causes a long-term increase in the number of tiny projections called dendritic spines in the brain, according to a new study published in neuropsychopharmacology. This study in mice sheds light on the behavioral and neural mechanisms of 5-MeO-DMT.

Serotonergic psychedelics (such as psilocybin and LSD) have shown promise as potential treatments for psychiatric disorders such as depression and anxiety. Short-acting compounds are of particular interest as they may improve patient access to therapy due to the reduced required dosing time. In humans, 5-MeO-DMT is rapidly degraded in the body, resulting in a shorter duration.

“My lab started researching psychiatric drugs such as ketamine and hallucinogens about 10 years ago. In particular, we believe that psychedelics have a lot of therapeutic potential, which drives our interest in this subject.” said the study authors Alex Kwan (@kwanalexc), associate professor at Cornell University Meinig Graduate School of Biomedical Engineering.

5-MeO-DMT, found in Sonoran desert toads, has several unique pharmacological properties. It targets serotonin receptors, particularly his 5-HT1A and 5-HT2A subtypes, and is similar to psilocybin, but with higher affinity for 5-HT1A receptors. However, little is known about the long-term effects of 5-MeO-DMT. To address this, the researchers conducted a mouse study.

The researchers used two innate behavioral assays to test the acute behavioral effects of 5-MeO-DMT in mice: head twitch and social ultrasonic vocalization (USV). The head spasm response is the rapid movement of the head from side to side by the mouse. This is considered an indicator of activation of serotonin 5-HT2A receptors in the brain.

Social USVs are high-frequency vocalizations emitted by mice during social interactions, especially when mice of the opposite sex are present. By analyzing these vocalization features, researchers can gain insight into social behavior.

The results showed that 5-MeO-DMT induced more transient acute behavioral effects than psilocybin, consistent with human data. Both psilocybin and his 5-MeO-DMT were found to significantly reduce social USV production and alter vocalization patterns. Ketamine, another drug with psychedelic properties, had similar effects.

The duration of effect of 5-MeO-DMT was consistently shorter across the various doses tested compared to psilocybin. 5-MeO-DMT significantly reduced social USV production in mice, even more so than psilocybin and ketamine.

The researchers also used longitudinal two-photon microscopy to examine the effects of 5-MeO-DMT on the structure of the medial frontal cortex. Similar to psilocybin, 5-MeO-DMT increased dendritic spine density by approximately 10–15% within 1 day of administration, and this increase was sustained for at least 1 month.

However, unlike psilocybin, 5-MeO-DMT did not affect spine size. Spine size is related to synaptic strength, and despite an overall increase in the number of dendritic spines, the average strength of synapses in the medial frontal cortex was 5-MeO-DMT during the measurement period. suggests that it is not affected by .

“Classical psychedelic 5-MeO-DMT, although its effects are short-lived, can still induce long-lasting neuroplasticity and wiring changes in the brain,” Kwan told PsyPost.

“One of the surprising things is how long the rewiring of neuronal connections in the brain persisted after a single dose of 5-MeO-DMT. We have shown that it can induce associated plasticity for a long period of time.”

“Considering that 5-MeO-DMT acts in the human body for about 15 minutes, whereas psilocybin has a duration of activity of about 3-6 hours, the plasticizing effect of 5-MeO-DMT is also shorter. I thought it might be,” explained Kwan. “However, our initial predictions were not correct, and it turns out that 5-MeO-DMT can also induce long-lasting plasticity.”

Although this study provides valuable insight into the effects of 5-MeO-DMT, there are some limitations that should be considered. Although this study was performed in mice, mice may not fully represent the complex cognitive and behavioral responses seen in humans.

“The caveat is that it’s difficult to convert doses between humans and animals,” says Kwan. “There are some formulas for converting doses to human mice to account for differences in body surface area. However, these are inaccurate. Animals metabolize differently and process drugs differently. , it is difficult to know exactly how many equivalent doses we are testing in mice, and in the future we would like to test how different doses of this drug affect neuroplasticity. increase.”

“We would like to thank the non-profit Usona Institute for synthesizing and sharing the compound,” he added. “Their collaboration made this research possible.”

the study, “5-MeO-DMT modifies innate behavior in mice and promotes structural neuroplasticityby Sarah J. Jefferson, Ian Gregg, Mark Dibbs, Clara Liao, Hao Wu, Pasha A. Davudian, Samuel C. Woodburn, Patrick H. Wale, and Jeffrey S. Sprouse, Alexander M. Sherwood, Alfred P. Kay, Christopher Pittenger, Alex C. Kwan.

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