Disorders due to Substance Use: Phencyclidine

Phencyclidine (PCP), ketamine, and related dissociative anesthetics induce a psychotic state that closely resembles schizophrenia by blocking neurotransmission at N-methyl-d-aaspartate (NMDA)-type glutamate receptors. PCP was first synthesized in the late 1950s, and became a major drug of abuse in the 1960s and 1970s. While rates of use have declined since then, primarily due to strict regulation of both PCP and its precursor compounds, both PCP and ketamine continue to be significant drugs of abuse and are associated with persistent cognitive dysfunction particularly during prolonged use. Dextromethorphan, a widely available over-the-counter cold remedy also acts as a weak NMDA receptor antagonist and may induce PCP-like symptoms at high doses. PCP derivatives such as methoxetamine and 3-methoxy-phenclycline (3-MeO-PCP) have also gained in popularity both because of increased potency and as an attempt to circumvent governmental regulation. The clinical presentation of PCP psychosis may be indistinguishable from that of acute schizophrenia, although neurological symptoms such as nystagmus and ataxia, when present, may assist in differential diagnosis. Although a positive drug test is determinative, newer PCP derivatives may be variably detected by existing assay systems. At high doses, PCP may cause seizures, coma, hypertension, and malignant hyperthermia, which may be fatal. Treatment is primarily supportive and should include a reduction in sensory stimulation. Although not classically addicting, PCP and related agents support self-administration in animal models and may be associated with tolerance and dependence during illicit use.