Ketamine Applications in Mental Health Disorders

Ketamine, long established as an anaesthetic agent, has in recent years emerged as a rapid‐acting intervention for a range of psychiatric conditions. At subanaesthetic doses, it elicits profound but transient alterations in consciousness and produces relief of depressive symptoms and suicidal ideation within hours. Its principal mechanism involves non-competitive antagonism of the N-methyl-D-aspartate (NMDA) receptor, triggering a cascade of synaptic changes that enhance neuroplasticity and modulate large-scale brain networks. Clinical studies have demonstrated efficacy in treatment-resistant depression, bipolar depression and acute suicidality, while early investigations extend to post-traumatic stress disorder, obsessive–compulsive disorder, eating disorders and substance use disorders. Ketamine may be delivered intravenously, intramuscularly or intranasally, often in conjunction with psychotherapeutic support to capitalise on its acute psychoactive effects. Contemporary research continues to refine optimal dosing schedules, administration routes and integration with psychotherapy, with the aim of maximising durability of benefit and ensuring patient safety. Globally, these developments signal a paradigm shift in the management of conditions refractory to conventional pharmacological approaches.

Research from Nature Portfolio

Functional neuroimaging studies in healthy volunteers have delineated how varying low doses of ketamine evoke distinct altered states of consciousness, from depersonalisation to dissociative amnesia, each mediating differential modulation of insular and affective circuit activity. These findings shed light on the neural correlates of acute mood-elevating effects and suggest that specific phenomenological subcomponents of the ketamine experience predict affective outcomes. Complementing these mechanistic insights, a recent perspective has examined the relationship between dissociative symptoms and antidepressant response, concluding that while dissociation often accompanies benefit, it is neither necessary nor sufficient for therapeutic action. Together, these works advance understanding of the molecular, network and experiential factors underpinning ketamine’s rapid efficacy and guide the development of next-generation glutamatergic treatments.

Ketamine Applications in Mental Health Disorders publication trend

The graph below shows the total number of articles in ketamine applications in mental health disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Subanaesthetic dose: A ketamine dosage below that required for surgical anaesthesia, typically used to elicit therapeutic effects without full sedation.

Dissociation: A transient alteration in consciousness or identity, often reported during ketamine administration, characterised by depersonalisation or derealisation.

N-methyl-D-aspartate (NMDA) receptor: A subtype of glutamate receptor in the central nervous system that ketamine antagonises, leading to modulation of synaptic transmission and plasticity.

Neuroplasticity: The capacity of neural circuits to reorganise synaptic connections in response to experience or pharmacological intervention, linked to ketamine’s rapid antidepressant effects.

References

1. Ketamine’s acute effects on negative brain states are mediated through distinct altered states of consciousness in humans. Nature Communications (2023).
2. The role of dissociation in ketamine’s antidepressant effects. Nature Communications (2020).
3. Safety and Tolerability of the Acute Ketamine Treatment in Treatment-Resistant Depression: Focus on Comorbidities Interplay with Dissociation and Psychomimetic Symptoms. Pharmaceuticals (2023).
4. Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review. BJPsych Open (2021).
5. Ketamine—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms. Pharmacological Reports (2021).
6. Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature. Brain Sciences (2021).
7. Toward Synergies of Ketamine and Psychotherapy. Frontiers in Psychology (2022).