Board-Certified Psychiatrist (ABPN)|U.S. + Israel Licensed|Telepsychiatry since 2013|Psychiatrist present during every IM session|Prescription treatment · Ages 18+ · Medical evaluation required

Desktop Recommended for Best Experience

For the best experience completing forms, assessments, and navigating patient resources, we recommend using a desktop or laptop computer.

This site is informational. Treatment requires full medical evaluation. Not for emergencies — if in crisis, contact local emergency services or a crisis line.

Visual Neuroscience Library · Episode 5

Stress Networks: From Threat Toward Safety

How Ketamine May Affect Amygdala and Salience Networks

2 min

The brain constantly evaluates whether a situation is safe or threatening. Networks involving the amygdala and the salience network help assign emotional significance to experiences and guide attention toward what matters most. Research suggests ketamine may modulate activity in these circuits, potentially softening the intensity of threat responses and creating space for new learning about safety. How these network changes translate into clinical improvement — especially for trauma and anxiety — remains an active area of investigation.

What is reasonably well supported

• Ketamine affects glutamate signaling in regions including the amygdala and prefrontal cortex, which are involved in threat processing and safety learning. • Neuroimaging studies show acute changes in amygdala and salience-network activity following ketamine administration. • Preclinical research supports that ketamine can facilitate the extinction of conditioned fear responses in animal models. • Rapid reductions in anxiety and trauma-related symptoms are reported in some clinical studies.

What remains uncertain

• Whether reduced threat reactivity is necessary for clinical improvement, or a secondary effect. • How salience-network changes relate to the subjective experience of feeling safer versus changes in attention. • How psychotherapy can best leverage any window of reduced threat reactivity for safety learning. • Whether individual differences in baseline amygdala activity predict treatment response.

Clinical framing

Some patients describe feeling less reactive to stressors or more able to tolerate difficult emotions after ketamine treatment. These experiences vary and are not guaranteed. Ketamine should be framed as potentially creating an opportunity for the brain to update threat and safety associations — ideally supported by therapeutic exposure and integration work — not as "calming," "healing," or "resetting" the amygdala.

References and further reading

Ketamine-induced changes in resting state connectivity, 2 h after the drug administration in patients with remitted depression

Pending review

Burrows M, Kotoula V, Dipasquale O, Stringaris A, Mehta MA

Journal of Psychopharmacology· 2023Randomized Controlled Trial

Double-blind placebo-controlled human imaging study reporting reduced sgACC-amygdala connectivity approximately two hours after ketamine. Added as supporting evidence for network modulation; pending clinician review.

View sourcePMID: 37491833; DOI: 10.1177/02698811231189432

Ketamine accelerates fear extinction via mTORC1 signaling

Verified

Girgenti MJ, Ghosal S, LoPresto D, Bang E, Duman CH, Duman RS

Neuropsychopharmacology· 2017Preclinical

Preclinical study showing ketamine accelerates fear extinction through mTORC1/protein-synthesis-dependent mechanisms in amygdala–prefrontal circuits — the mechanistic basis for ketamine's effects on threat/safety learning. Verified; DOI 10.1038/npp.2016.361.

View sourcePMID: 28043916

This content is educational and does not constitute medical advice, a treatment recommendation, or a guarantee of outcome. All diagrams and explanations are conceptual and simplified for general understanding. They are not direct representations of individual patient data. Individual suitability for ketamine-assisted psychotherapy requires a screening call and full psychiatric evaluation. Research on ketamine's effects on brain networks is active and evolving.

Want to learn if KAP is right for you?

Start with a free 15–20 minute screening call.

Book Free Screening →