A recent study published in Neuron led by a collaborative team from Tata Institute of Fundamental Research (TIFR) Mumbai alongside members from American Cornell, Yale, and Columbia Universities made this groundbreaking research on how psychedelics like DOI (dimethoxy-4-iodoamphetamine) could treat anxiety. Traditionally alarming when heard, the term psychedelics has been associated with altered perceptions and hallucinatory effects. However new research suggests that psychedelics may offer therapeutic benefits without inducing side effects, marking a promising shift in mental health treatment.
Psychedelic agents are naturally derived substances such as psilocybin (found in magic mushrooms), and mescaline (from cacti), that were safely used, primarily as traditional healers and in religious rites among the tribes. Hence was being used long before we spoke about anxiety, and depression, though we knew it existed.
DOI is a lesser-known psychedelic drug designed by Dr. Alexander Shulgin in 1984, when compared to LSD it is not as common as a street drug and hasn’t been abused as other drugs. It is used as an antidepressant to produce hallucinations and reduce anxiety.
When injected directly into the brains of the rodents to identify the precise type of nerve cells targeted that can activate the ventral hippocampus in the brain and decrease anxiety. The focus of this groundbreaking study was the ventral hippocampus, a brain region associated with emotions and anxiety.
The team confirmed the anxiolytic activity of rodents by the behavioral model using an ‘elevated plus maze’. And the rodents explored more risky and open areas indicating reduced anxiety.
Further studies in collaboration with American Cornell, Yale, and Columbia University were carried out to know the exact site the drug acted upon and mapped the brain activity in the ventral hippocampus under the influence of DOI via serotonin (5HT2A) receptor that regulates stress and emotions. Further within the ventral hippocampus identified a particular neuronal firing of ‘PV positive’ (inhibitory neurons that release GABA) neurons while lowering anxiety.
Once the target neuron is identified simulating these neurons and the neuronal firing simply reduces anxiety without actually using the psychedelics. Crucially, this part of the brain doesn’t drive hallucinogenic effects, it opens up the possibility of designing a target-based drug on anxiety without evoking hallucinations
Study
The study’s implications are beyond anxiety treatment. These findings suggest that further research could lead to new therapies for OCD, depression, and others providing effective, non-hallucinogenic alternatives to current treatments. Given the similarities between the cellular structures of rodents and human brains, these results offer value that may soon translate to human clinical trials.
The human trials therapeutic use of psychedelics continue globally, this research acts as a crucial stepping stone toward understanding the broader effect of psychedelics on various brain circuits and mental disorders.
Reference:
Tiwari, P., et al. (2024). Ventral hippocampal parvalbumin interneurons gate the acute anxiolytic action of the serotonergic psychedelic DOI. Neuron. doi.org/10.1016/j.neuron.2024.08.016.
(Input from various sources)
(Rehash/Josna Lewis/MSM)
