2 Neuroscience2.12 Neurobiology of specific treatments
2.12.1 Ketamine psychedelics and plasticity
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Written by Resident Doctor Committee · Published
New in the 2027 syllabus
The College added this topic for exams from January 2027.
Different routes into plasticity
These treatments act on different receptors, but each is thought to lead to plasticity. Plasticity here means an increased capacity of the brain to change.
Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist. NMDA receptors are a type of glutamate receptor. Ketamine's antidepressant effect can start faster than that of conventional monoamine reuptake inhibitors.
Esketamine is the S-enantiomer of ketamine (one of its two mirror-image forms). The two share a target, but that does not make them interchangeable. Preparations, routes and treatment protocols differ.
Classical psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), act mainly through serotonin 5-HT2A receptor signalling. They cause marked changes in perception and thinking.
Neuroplastogens are compounds being studied for their ability to promote neural plasticity. The term describes a proposed effect, not one receptor class.
Proposed mechanisms
AMPA receptors are another type of glutamate receptor. They are named after alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, an agonist used to characterise them.
Intervention | Proposed downstream processes | Limits of the evidence |
|---|---|---|
Ketamine | Changes in glutamate signalling, AMPA receptor activity and neurotrophin-related synaptic change | Several mechanisms are still under investigation |
Classical psychedelics | Cortical 5-HT2A signalling, with changes in connectivity and plasticity | Cell or animal findings alone do not establish how the treatment works in humans |
Non-hallucinogenic plasticity-promoting compounds | Attempts to keep the plasticity effects while changing the subjective effects | Clinical benefit and safety need direct testing |
Two signalling pathways come up often: brain-derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR). In experimental models they link neural activity to synaptic growth and protein synthesis. No single pathway fully explains why patients improve.
Reading the research critically
More plasticity is not the same as recovery. A greater capacity for change does not guarantee helpful learning or lasting improvement in symptoms.
Setting and psychological support may affect outcomes in psychedelic trials. This makes it hard to separate the drug's effect from expectations and the treatment context.
Blinding is difficult because the subjective drug effects often reveal who had the active drug. Trial design and the choice of comparison condition therefore matter.
Safety and clinical use
Ketamine can cause dissociation and a rise in blood pressure.
Psychedelics can cause acute distress or perceptual disturbance.
Clinical use depends on the evidence, the indication, contraindications and a monitored protocol. A promising mechanism in experiments does not make a treatment routinely available.