Science advances
October 14, 2022
Eric L Garland, Adam W Hanley, Justin Hudak et al.
39 citations
Theta oscillations (4 to 8 Hz) in frontal midline brain regions, which support self-regulation, are inversely linked to default mode network activity involved in self-referential processing. Addiction involves impaired self-regulation and default mode network dysfunction. In a mechanistic study of 165 long-term opioid users, Mindfulness-Oriented Recovery Enhancement increased frontal midline theta during meditation compared to supportive psychotherapy. Theta during meditation was associated with self-transcendent experiences such as ego dissolution and bliss. Increased theta mediated the treatment's effect on reducing opioid misuse, suggesting mindfulness-induced theta stimulation may reset default mode network dysfunction to inhibit addictive behavior.
Science advances
April 26, 2024
Ben Rein, Kendall Raymond, Cali Boustani et al.
37 citations
MDMA, a psychoactive drug known for its prosocial effects, enhances empathy-like behaviors in mice by increasing serotonin signaling in the nucleus accumbens. The drug, whether given systemically or infused directly into this brain region, strengthens the social transfer of pain and analgesia, a behavioral test of empathy. Optogenetically stimulating serotonin release in the nucleus accumbens mimics MDMA's effects, confirming serotonin's role. MDMA also restores deficits in empathy-like behaviors in a mouse model of autism lacking the Shank3 gene. The findings indicate that serotonin signaling in the nucleus accumbens is a core mechanism underlying MDMA's empathogenic effects.
Science advances
August 15, 2025
Marcell J László, Judit P Vigh, Anna E Kocsis et al.
9 citations
In a rat stroke model, DMT reduces brain damage by decreasing swelling, restoring the blood-brain barrier, and shifting the body toward an anti-inflammatory state. DMT also suppresses inflammatory signals from brain and immune cells via the sigma-1 receptor. These effects suggest DMT could complement existing stroke therapies.
Science advances
July 11, 2025
Lujuan He, Xuenan Wang, Shilin Luo et al.
8 citations
Arketamine, the (R)-enantiomer of ketamine, produces faster and longer-lasting antidepressant-like effects than esketamine in mice subjected to chronic social defeat stress. Activating the proteins CREB and MeCP2 drives the production of brain-derived neurotrophic factor (BDNF) in microglia, the brain's immune cells. This microglia-derived BDNF strengthens excitatory synaptic transmission in the infralimbic region of the medial prefrontal cortex (mPFC). It also activates mPFC neurons that project to the nucleus accumbens (NAc) shell, a brain area involved in reward and mood. These mechanisms together underlie arketamine's antidepressant-like effects, highlighting the essential role of microglial BDNF in modulating this neural pathway.
Science advances
May 1, 2026
Anisul Arefin, Jihye Kim, Manas Pratim Chakraborty et al.
1 citation
Ketamine's antidepressant effects depend on the interplay between two types of neuromodulatory receptors: TrkB and mGluR5. mGluR5 amplifies BDNF-driven signaling through TrkB, enabling synaptic potentiation, while BDNF activation of TrkB drives mGluR5 endocytosis, impairing synaptic depression. Ketamine enhances these interactions by increasing surface and postsynaptic levels of TrkB. An mGluR5 positive allosteric modulator can further boost both modes of cross-talk and enhance ketamine's effects, revealing that receptor-receptor interplay can drive therapeutic action.