Is ketamine related to phencyclidine (PCP), also known as angel dust?

Is Ketamine Related to PCP (Angel Dust)?

Yes, ketamine is chemically and pharmacologically related to phencyclidine (PCP, "angel dust")—both are dissociative anesthetics that work primarily through the same mechanism of action as non-competitive antagonists at the NMDA receptor, though they have important clinical differences. 1, 2

Chemical and Pharmacological Relationship

Shared Mechanism of Action

• Both ketamine and PCP are dissociative anesthetics that produce their primary effects through antagonist activity at the phencyclidine (PCP) binding site of the NMDA receptor complex for glutamate 1, 3
• The American Society of Anesthesiologists confirms that ketamine acts as a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, producing a cataleptic state that blocks sensory recognition of painful stimuli and memory 4
• Both drugs produce similar dissociative effects including analgesia, cardiovascular and respiratory stimulation, dissociation, hallucinations, and altered consciousness 1

Chemical Classification

• Ketamine and PCP both belong to the arylcyclohexylamine class of compounds 2
• PCP was the original compound in this class, developed as an anesthetic in the 1950s, while ketamine was developed later as a safer alternative with fewer adverse psychiatric effects 2

Critical Clinical Differences

Safety Profile

• Ketamine has a significantly better safety profile than PCP, with lower incidence of adverse psychiatric effects and generally produces greater CNS depression than PCP 5
• Ketamine selectively modulates cerebellar GABA(A) receptors containing alpha6 and delta subunits at anesthetically relevant concentrations, while PCP does not—this unique property may explain ketamine's superior clinical profile 5
• Emergence reactions (floating sensations, vivid dreams, hallucinations, delirium) occur in 10-30% of adults receiving ketamine, which is substantially lower than PCP's psychiatric complication rate 4, 6

Clinical Use

• Ketamine remains in legitimate medical use for anesthesia, analgesia, and recently for treatment-resistant depression, while PCP has no accepted medical use and is purely an illicit drug 4, 2
• The FDA and medical societies have established clear dosing guidelines for ketamine (IV induction: 1-2 mg/kg; IM: 4 mg/kg for procedures), whereas PCP is never used clinically 4

Important Caveats for Clinical Practice

Street Drug Concerns

• Both ketamine and PCP have been used as recreational drugs, with ketamine sometimes diverted from medical supplies or synthesized illicitly 1, 7
• Ketamine has been used as a "date-rape drug" due to its sedative and amnestic properties, with effects occurring within 20 minutes and lasting up to 3 hours 6
• PCP is a significant contaminant/additive of many illegal drugs sold today due to its ease of preparation by clandestine chemists 2

Contraindications and Precautions

• Ketamine should be avoided in patients with uncontrolled cardiovascular disease, active psychosis, severe hepatic dysfunction, or elevated intracranial/ocular pressure 4, 8
• The drug produces dose-dependent increases in heart rate, blood pressure, and cardiac output through sympathetic nervous system stimulation 4, 8
• Co-administration of benzodiazepines (particularly midazolam) can minimize emergence reactions but increases risk of respiratory depression 4, 6

Historical Context

• PCP was coined "the most dangerous drug in America" in the late 1970s and led to the development of ketamine as a safer alternative 2
• The PCP hypothesis of schizophrenia (later the NMDA receptor hypofunction hypothesis) emerged from studying PCP-induced psychosis and continues to drive therapeutic discovery today 2