Psychedelics, a class of chemicals known for altering consciousness, have been part of human society for ages. Historically used in alternative medicine and spiritual practices, their potential therapeutic benefits, particularly in mental health, have recently regained attention. Traditional treatments for anxiety, including therapy and medication, are effective but often have limitations. 

This prompted researchers to explore alternatives, including psychedelic-inspired drugs, which may offer new hope for those struggling with anxiety. Psychedelic-inspired drugs like psilocybin and LSD are gaining traction for their therapeutic potential, according to Praachi Tiwari, the lead author of the paper published in Neuron.

Clinical studies have shown that psychedelics can significantly reduce anxiety symptoms. Still, they are not to be thought of as ​“magic bullets,” cautions Vidita Vaidya, corresponding author and Professor at the Tata Institute of Fundamental Research (TIFR), Mumbai. For instance, trials with psilocybin have demonstrated lasting effects beyond initial experience. Thus, researchers approach these substances cautiously, emphasising the need for extensive studies on their molecular mechanisms and target cells to ensure safety during drug testing and trials. A key aspect of their effects involves their interaction with serotonin or 5HT receptors in the brain. 

The behavioural effect of these molecules is based on their affinity to the serotonin receptors. Thus, different drugs could pose different behavioural changes. Furthermore, the receptor interactions and the neural substrates involved in serotonergic psychedelics is not completely understood. The authors here have conducted an in-depth understanding of the effects of a specific drug called DOI on the neural circuits and its mechanism in relieving anxiety.

DOI is a synthetic psychedelic molecule. It acts on serotonin2 family of receptors. To explore the effect of DOI on anxiety, Tiwari and collaborators conducted behavioural tests on mice using the elevated plus maze and the open field test—both standard methods for assessing anxiety in animals. 

A critical aspect of this research was identifying the specific brain region and the kind of neurons that are targeted by DOI to reduce anxiety. This work identified an important role of parvalbumin (PV) interneurons in the ventral hippocampus as the cellular trigger activated by DOI. DOI activates these interneurons, helping to regulate anxiety-related activity in the brain. 

The team mapped the presence of serotonin2A receptors on these PV interneurons as playing a central role in modulating the response to DOI. Vaidya suggests this insight could pave the way to novel therapeutic approaches that may help treat anxiety. 

Biju Viswanath, Additional Professor of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS) and the Rohini Nilekeni Centre for Brain and Mind (CBM), in Bengaluru, who is an expert on neurobiology of mental illness, adds that understanding which additional circuits are also involved in addition to the ventral hippocampus would be useful to fully grasp how DOI mediates its behavioural effects. 

The resurgence of interest in psychedelics marks a pivotal moment in mental health care. As researchers uncover their potential to alleviate anxiety and improve emotional well-being, the possibility of bench-to-bedside of these drugs becomes increasingly plausible. With further investigation and a deeper understanding of their nuanced effects, psychedelics may offer a much-needed alternative for treating anxiety and other mental health ailments when administered at the appropriate dosage. 

The potential benefits of psychedelics extend beyond anxiety alone; they may also offer new solutions for depression and addiction. 

However, psychedelics should not be considered magic bullets, given their hallucinogenic actions, it is vital to proceed further only based on careful preclinical and clinical research. While the study on DOI and its effects on anxiety represents a significant step forward in psychedelic research, it has a few drawbacks. 

DOI has dosage-dependent effects and needs extensive clinical trials, which are absent as of now. Viswanath adds that while DOI might not be a magic pill for anxiety, the field of psychedelic-inspired drugs holds promise for improving overall mental health.