Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
July 16, 2025
Amel Bouloufa, Sarah Delcourte, Renaud Rovera et al.
12 citations
Acute administration of LSD produces fast antidepressant- and anxiolytic-like effects in rats, along with hallucinatory-like effects and suppression of serotonin neuron activity. These effects are blocked by a selective 5-HT2B receptor antagonist, indicating they depend on activation of 5-HT2B receptors. Depletion of serotonin also prevents LSD's effects in the forced swim test and head-twitch response. In mice, LSD fails to produce antidepressant- or anxiolytic-like effects, and its hallucinogenic-like effect is not altered by 5-HT2B receptor blockade. The findings suggest LSD acts as a rapid-onset antidepressant in rats but not in mice, through mechanisms involving 5-HT2B receptor activation.
Neuroscience & Biobehavioral Reviews
October 10, 2025
Amel Bouloufa, Sarah Delcourte, Thomas Delannay et al.
3 citations
Major depressive disorder affects over 350 million people worldwide, and about 30% of those with the condition have treatment-resistant depression that does not respond adequately to standard antidepressants targeting serotonin, noradrenaline, or dopamine. Psychedelic medicines such as lysergic acid diethylamide (LSD) are being investigated as potential treatments because they affect both serotonergic and glutamatergic systems and may induce rapid, long-lasting antidepressant effects by facilitating neuroplasticity and adjusting neural communication even after the drug is cleared. Ongoing clinical trials are testing LSD's efficacy and safety in treatment-resistant depression while addressing placebo design and risk minimization.
Frontiers in pharmacology
January 1, 2025
Sarah Delcourte, Amel Bouloufa, Renaud Rovera et al.
3 citations
Bright light stimulation (BLS) alone was ineffective against anxiety- and depressive-like behaviors in a novel mouse model of refractory depression, induced by social isolation and chronic despair during the active dark phase. However, BLS potentiated the effects of antidepressant treatments, including ketamine, through a circuit involving rod retinal photoreceptors, lateral habenula (LHb) astroglia, and serotonin (5-HT). Chemogenetic activation of LHb astroglia or serotonin depletion blocked this potentiating effect. The findings suggest BLS enhances antidepressant efficacy via a previously unknown neural pathway.
L'Encephale
April 9, 2026
Amel Bouloufa, Sarah Delcourte, Thomas Delannay et al.
Major depressive disorder affects over 350 million people worldwide, and about one-third of patients do not achieve remission with standard antidepressants, a condition known as treatment-resistant depression. Lysergic acid diethylamide (LSD) modulates the 5-HT2A serotonin receptor and the glutamatergic system, which are involved in neuroplasticity, and early clinical studies suggest rapid and sustained antidepressant responses. Clinical trials are underway to test LSD's safety and efficacy for major depressive disorder, though methodological challenges include creating meaningful placebos and the need for specialized therapist training. LSD-assisted therapy remains experimental, but its therapeutic potential is increasingly recognized given the limitations of current treatments for treatment-resistant depression.
Biologie aujourd'hui
January 1, 2025
Amel Bouloufa, Sarah Delcourte, Nasser Haddjeri
About 30% of people with major depressive disorder do not respond to at least two standard antidepressants, a condition called treatment-resistant depression. LSD (lysergic acid diethylamide) is being investigated as a potential fast-acting antidepressant because it modulates both the serotonin system, especially the 5-HT2A receptor, and the glutamatergic system, which may enhance neuroplasticity and produce rapid, sustained mood improvements. Ongoing clinical trials are testing LSD-assisted therapy for treatment-resistant depression, but methodological challenges include designing proper placebo controls and providing adequate psychological support during the acute psychedelic experience. Further research is needed to confirm its clinical utility and establish safe protocols.