Ketamine
Ketamine is a clinically established dissociative anaesthetic, an arylcyclohexylamine and NMDA-receptor antagonist used since the 1970s for anaesthesia and analgesia. Since the 2000s it has been studied and licensed (as the S-enantiomer esketamine) for treatment-resistant depression. It is also a widely used recreational dissociative, where chronic heavy use is strongly associated with ulcerative cystitis and bladder damage.
01 Overview
Ketamine produces dose-dependent effects ranging from mild dissociation and analgesia at sub-anaesthetic doses to a fully dissociated, immobile state known colloquially as a 'K-hole' at high doses. It is valued clinically because it preserves airway reflexes and cardiovascular tone better than most anaesthetics, making it useful in emergency and field settings. Esketamine nasal spray (Spravato) is approved in the US and EU for treatment-resistant depression under supervised administration.
Recreational use is common in insufflated and oral forms. The principal harm of repeated heavy use is ketamine-induced uropathy: a painful ulcerative cystitis that can progress to a small, contracted bladder and, in severe cases, irreversible urinary-tract damage. Cognitive impairment and dependence also occur with sustained heavy use.
02 Mechanism
Non-competitive antagonist at the NMDA glutamate receptor, reducing excitatory neurotransmission; downstream increases in glutamate release and AMPA/BDNF-mediated synaptic signalling are thought to underlie its rapid antidepressant effect.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Light | 10–30 mg | Insufflated | Mild dissociation and stimulation. |
| Common | 30–75 mg | Insufflated | Marked dissociation. |
| Common | 40–100 mg | IM | Rapid, intense onset. |
| Common | 75–150 mg | Oral | Slower onset, longer duration than insufflation. |
| Heavy | 100–150 mg | Insufflated | K-hole territory; immobilisation. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Dissociation and analgesiaDetachment from body and environment with potent pain relief; the basis of both clinical and recreational use. | Dose-dependent | Clinical | |
| Rapid antidepressant effectSub-anaesthetic doses produce rapid reduction in depressive symptoms in treatment-resistant depression, though effects are often transient. | Onset within hours | Clinical | |
| Euphoria and altered perceptionSought-after subjective effects at recreational doses. | Observational |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Ketamine-induced cystitis (uropathy)Ulcerative cystitis causing urinary frequency, urgency, pain and haematuria; can progress to a contracted bladder and irreversible upper-tract damage. | Severe | Common with chronic heavy use | Clinical | |
| Cognitive impairmentDeficits in memory and executive function reported in frequent heavy users, partly reversible with abstinence. | Moderate | Common with heavy use | Observational | |
| Dissociative sedation and airway riskHigh doses cause immobilisation, vomiting and risk of aspiration or accidents while incapacitated. | Severe | Dose-dependent | Clinical |