In Canada, the use of both prescription medications and psychedelics has become increasingly prevalent. As of 2022, approximately 16.5% of Canadians—about 6.3 million individuals—were prescribed at least one antidepressant, with fluoxetine remaining one of the most commonly used options (IQVIA, 2023). Benzodiazepine use, including drugs like alprazolam, ranges between 5% to 10% nationwide, with...
Major depressive disorder (MDD) is a leading cause of disability worldwide, yet many patients have inadequate responses to current treatments. Dimethyltryptamine (DMT), a serotonergic psychedelic with rapid onset and short duration, shows promise as a potential antidepressant (AD), although clinical evidence in MDD remains limited. We conducted a phase IIa, double-blind, placebo-controlled,...
The serotonergic psychedelic psilocybin induces neural plasticity and profoundly alters consciousness. The benzodiazepine midazolam blunts neural plasticity and induces conscious sedation and amnesia at low doses. In our recent open label pilot study, we administered oral psilocybin (25 mg) along with intravenous midazolam at doses allowing a full psychedelic experience while blunting memory...
The therapeutic potential of psilocybin in treating psychiatric disorders has gained attention recently. While most research has focused on isolated psilocybin, evidence suggests that whole mushroom extracts exhibit greater efficacy, implicating a possible entourage effect of additional bioactive compounds. This study aimed to elucidate the holistic neuropharmacological effects of...
Psychiatric disorders represent a leading cause of global disability yet current therapeutic strategies, based mainly on monoaminergic modulation, exhibit limited efficacy and high relapse rates for a significant patient population. This has catalyzed a paradigm shift toward understanding the biological underpinnings of mental illness. This review synthesises evidence from three rapidly...
Rapid-acting antidepressants like ketamine and serotonergic psychedelics show promise for treatment-resistant depression (TRD), but the molecular mechanisms that contribute to their therapeutic effects remain unclear. Induced pluripotent stem cells (iPSCs) offer a platform to model human cortical neurons and investigate drug effects in a human-relevant system. Here, iPSCs from individuals with...
Multiple lines of neuroscientific evidence have converged on a set of closely related findings: the mammalian brain endogenously synthesizes N,N-dimethyltryptamine (DMT) at neurotransmitter-comparable concentrations (Dean et al., 2019); psychedelic compounds suppress the default mode network (DMN) and dissolve ego boundaries (Carhart-Harris et al., 2012; Tagliazucchi et al., 2016); the brain...
Modern advances in artificial intelligence have accelerated the development of computational tools for protein–ligand structure prediction, yet their real-world performance remains uneven across receptor classes and ligand chemotypes. Recently published cryo-EM structures of several different psychedelics bound to the serotonin 5HT2A receptor provide a unique opportunity to explore how modern...
When Time Stops: Inside the Mind’s Clock is a theoretical preprint monograph exploring how subjective time perception may relate to brain dynamics, informational complexity, and cytoskeletal processes. The work introduces the Scalar Clock Model, in which subjective duration is represented by a scalar variable (φ) whose accumulation rate may be influenced by large-scale neural activity and...
The mechanistic link between molecular pharmacology and global brain dynamics remains unresolved - a "scale bridge" problem central to consciousness research. We propose the Receptor-Constrained Dynamical Topology (RCDT) hypothesis: that the functional impact of neuromodulatory drugs propagates from local ligand-receptor binding events through spatially heterogeneous gain modulation to produce...