From Monoamines Neurotransmitters to Psychedelics : a Paradigm Shift in Psychiatry
When the brain changes, behavior follows
Neuropsychiatric disorders are clinically defined as disturbances in an individual’s cognition, mood, behavior and motivation.
They arise from a complex interplay between biological, neurological and environmental factors including brain damage, genetic predispositions, neurochemical imbalances.
A silent but massive burden
Mental disorders affect nearly 1 in 7 people worldwide, representing more than one billion individuals.
They are among the leading causes of disability globally, with a profound impact on daily functioning, quality of life, and productivity.
Access to effective care remains limited, and stigma continues to shape how these conditions are perceived and treated.
Reaching the top 10 global diseases in terms of prevalence, neuropsychiatric disorders are not marginal, they are a central public health challenge.
Depression is more than sadness
Neuropsychiatric disorders can include neurodevelopmental disturbances, psychotic troubles, and mood disturbances like Major Depressive Disorder (MDD).
MDD is a complex and multifactorial condition characterized by persistent low mood, loss of interest or pleasure, and cognitive impairment, affecting 280 million people.
It involves disruptions across multiple levels, from brain circuits regulating emotions to neurotransmitter systems.
Antidepressants reshaped our understanding of depression
The discovery of antidepressants in the 1950s led to a major breakthrough in psychiatry, showing that increasing monoamine levels in the brain could improve depressive symptoms.
This gave rise to the monoamine hypothesis, in which depression is linked to imbalances in serotonin, norepinephrine, and dopamine.
Most antidepressants used today act on these systems, whether through selective serotonin reuptake inhibitors (SSRI) or other pharmacological classes (SNRI, ATC/ATeC, IMAO…).
However, they remain limited by slow onset and unpredictable patient response.
These gaps have driven the search for new therapeutic approaches…
Psychedelics are reopening the field
Psychedelics, such as LSD, psilocybin, DMT, and MDMA are emerging as a promising new direction in depression research.
By targeting the serotonin 5HT2A receptor, psychedelics promote neuroplasticity, a key mechanism believed to drive their therapeutic potential.
Unlike conventional antidepressants, psychedelics can produce rapid effects, sometimes after a single administration, with benefits that may persist over time.
Both hallucinogenic and non-hallucinogenic compounds are currently being explored, opening the door to a new generation of treatments.
sources
- World Health Organization : https://www.who.int/news-room/fact-sheets/detail/mental-disorders
- Global burden of mental disorders in 204 countries and territories, 1990–2021: results from the global burden of disease study 2021
- Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163:28–40. doi: 10.1176/appi.ajp.163.1.28.
- NHS: https://www.nhs.uk/medicines/antidepressants/
- Monoaminergic Neurotransmission: The History of the Discovery of Antidepressants from 1950s Until Today: https://www.eurekaselect.com/article/14216
- American psychological association: https://www.apa.org/monitor/2024/06/psychedelics-as-medicine
- Mental Health America: https://mhanational.org/resources/psychedelics-and-mental-health/
- Johns Hopkins Medicine: https://www.hopkinsmedicine.org/psychiatry/research/psychedelics-research
Manon Villalba, PhD
Research Engineer at SynapCell
Manon Villalba, PhD is a Research Engineer at SynapCell, specializing in electrophysiology and pharmacology for preclinical CNS research. She contributes to the development of advanced EEG-based approaches to characterize brain activity, neural dynamics, and drug-induced effects in translational models. With expertise in sleep research, EEG signal processing, and neurophysiology, she supports the acquisition and analysis of multichannel brain signals. At SynapCell, she contributes to the development of robust, translatable EEG-based biomarkers supporting CNS drug discovery.
Antoine Paccard, MSc
Data Unit Manager at SynapCell
Manon Villalba, PhD is a Research Engineer at SynapCell, specializing in electrophysiology and pharmacology for preclinical CNS research. She contributes to the development of advanced EEG-based approaches to characterize brain activity, neural dynamics, and drug-induced effects in translational models. With expertise in sleep research, EEG signal processing, and neurophysiology, she supports the acquisition and analysis of multichannel brain signals. At SynapCell, she contributes to the development of robust, translatable EEG-based biomarkers supporting CNS drug discovery.