Hallucinogens 4

• PCP


  Phencyclidine, a fully synthetic drug developed and marketed by Parke-Davis and Company (1963) as an analgesic and anesthetic
• Ketamine


  A fully synthetic drug first synthesized in 1962 and marketed in 1969 as a safer alternative to PCP, since it's less potent and has a milder emergence of effects
• PCP developed and marketed by Parke-Davis and Company


  1963
• Ketamine first synthesized


  1962
• Ketamine marketed as a safer alternative to PCP

  1969
• PCP


  • Initially used as surgical anesthetic, later used by veterinarians as an animal tranquilizer
  • Banned in 1965 due to side effects (namely agitation and psychosis) but found its way onto US streets in the 60s by the drug culture protesting Vietnam War
• Ketamine


  • Still used today mostly as a veterinary anesthetic (e.g. Ketaset)
  • Has a reputation as being a "date rape drug"
• Routes of Administration


  PCP and ketamine are lipid soluble weak bases and easily cross BBB
• PCP use


  1. Smoking most common recreational method - usually involves saturateing plant material (ie: mint) with PCP and rolling into cigarette (dipper)

  2. Effects felt within few minutes of smoking, but peak effects felt within 60-90 min and typically last for 4-8 hours

  3. Liquid PCP known as "wet"

  4. Blood levels decline rapidly at first but PCP can persist in blood for several weeks as drug is slowly released from body tissues (adipose)
• Ketamine use


  1. Usually administered intranasally - users snort small lines called "bumps"

  2. Compared to PCP, effects of ketamine are short-lived, lasting between 30-60 minutes
• Mechanism of Action (Neuropharmacology)

  • PCP and ketamine are both noncompetitive antagonists of NDMARs (ionotropic glutamate receptors)
  • They bind to site deep within pore of the ion channel - block the channel and render glutamate ineffective
  • Drugs have inhibitory effects in the brain
  • Inhibitions of NMDA receptors in frontal cortex appears to contribute to appearance of psychotic symptoms (delusions, catatonia)
  • Inhibitions of hippocampal NMDARs contributes to memory impairments
• PCP and Ketamine


  • Are reinforcing and have misuse potential
  • Animals will self-administer given right concentrations
  • Both cause accumbal dopamine release by inhibition VTA-GABA neurons - disinhibits DA neurons (reinforcing effect)
• Effects on perception and behavior

  • At lower recreation dosages, dissociative anesthetics can cause euphoria, relaxation, sedation, warmth, tingling, and analgesia (more trance like than hallucinogenic)
  • At higher doses, they can produce sudden mood swings, confusion, disorientation, delirium, aggression/agitation and disordered/delusional/psychotic thoughts similar to those exhibited in schizophrenia – referred to as emergence delirium
  • Produce a sense of dissociation: a feeling of detachment from and lack of continuity with the environment and/or self (K-hole)
  • Near death feeling/out of body experience
• Side effect, harmful/lethal effects

  • PCP psychosis: major harmful effect that may last several months after use and is indistinguishable from schizophrenia (positive, negative, cognitive symptoms)
  • Chronic use results in a significant reduction in gray matter volume (including frontal cortex) along with learning and memory and other cognitive impairments
  • Lethal effects include respiratory arrest and coma, which are potentiated by other CNS-depressant drugs (alcohol and barbiturates)
• Ketamine assisted psychotherapy


  • Ketamine can be used as adjunct to therapy - helps in depression, anxiety, PTSD, end-of-life stress, and SUDs
  • Short duration of action makes it medically useful
  • Therapy usually consists of one or two in-clinic ketamine dosing sessions under clinical supervision and integrated with counseling
  • Ketamine therapy produces a short-lived (1-2 hr) change in subjective experience/consciousness, which has potential to produce long-lasting changes in affect, insight, cognition, behavior