Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment

Summary & key facts

This paper reviews what scientists know about how ketamine and classic serotonergic psychedelics (like psilocybin and LSD) can lift depression quickly. The authors compare how the drugs work in the brain, point out that ketamine has the strongest clinical evidence so far, and say psychedelics show early promise but need more carefully controlled trials and long-term follow-up. They also note both types of drugs cause strong temporary changes in perception and awareness, share some common brain effects downstream, and raise practical concerns about safety, regulation, and possible misuse.

Key facts:

• About one third of people with major depression do not get better on conventional antidepressants, which is why researchers are looking for faster-acting options.
• Ketamine can reduce depressive symptoms within hours, with effects that peak around 24 hours and often fade after about 10 to 12 days after a single infusion.
• The US Food and Drug Administration approved an intranasal form of ketamine (esketamine) for treatment-resistant depression in 2019 and for depression with acute suicidal thoughts in 2020, and it must be given under special safety rules.
• Classic serotonergic psychedelics (for example psilocybin and LSD) affect serotonin brain receptors, while ketamine mainly changes glutamate-related systems; these are different main actions.
• Despite different starting points, both ketamine and serotonergic psychedelics seem to trigger some shared downstream brain processes, including activation of mTORC1 signaling and changes in GABAA receptor activity, which may help explain r
• Early clinical studies suggest that one or two doses of some psychedelics can reduce depression and anxiety for weeks or months in some people, but those studies are still limited and need more rigorous controls and longer follow-up.
• Both ketamine and psychedelics produce strong temporary changes in perception, mood, and self-awareness that usually require medical supervision during treatment.
• There are safety and policy concerns for both approaches: ketamine has potential for misuse and unknown long-term effects, and psychedelic research faces regulatory hurdles and a need for better-controlled trials.

Topics

Neurotransmitter Receptor Influence on Behavior Psychedelics and Drug Studies Tryptophan and brain disorders

Categories

Clinical Psychology Psychology Social Sciences

Tags

Antidepressant Hippocampus Internal medicine Ketamine Medicine Neuroscience Pharmacology Psychology Receptor Serotonergic Serotonin

Substances

Ketamine LSD MDMA Psilocybin

Conditions & symptoms

Depression Lack of energy or motivation Poor sleep Sadness or low mood