Why do some drugs cause hallucinations while others don't - even when they act on the same part of the brain?
That's the mystery at the centre of a new research project supported by CQDM and Brain Canada.
Physiology and pharmacology professor Peter Chidiac, in collaboration with researchers at McGill University and CHU Sainte-Justine in Montreal, will investigate new compounds that could offer the potential benefit of psychedelics in treating mental health conditions - without the hallucinogenic side effects.
Psychedelic compounds have shown promise in treating mental health conditions, but intense side effects limit their regular use.
The research project focuses on a serotonin receptor called 5HT2a, which plays a key role in how certain psychedelic drugs - like LSD or psilocybin - alter perception.
But not all drugs that activate this receptor cause hallucinations. Serotonin, for example, is a naturally occurring chemical that also activates 5HT2a, but without any of the psychedelic effects.
Researchers think the difference may lie in how 5HT2a works together with other nearby receptors in the brain. These receptor complexes, known as heteromers, may influence how the brain responds to different drugs.
In partnership with Diamond Therapeutics, Chidiac's lab will test new experimental compounds to see how they affect these receptor complexes, comparing them to known psychedelics and non-psychedelics, such as serotonin.
"What sets this research apart is our focus on how brain receptors work together in complexes, not just individually," Chidiac said. "By studying how these receptor combinations respond to different drugs, we hope to understand why some compounds trigger perceptual distortions while others don't - and use that knowledge to develop safer, targeted treatments for mental health conditions."
The goal is to find new psychiatric medications that activate the brain's healing pathways without the hallucinogenic effects, leading to safer, more effective treatments for conditions like depression, anxiety and PTSD.
