Hallucinogens and Dissociative Drugs Research Report
What Are the Effects of Common Dissociative Drugs on the Brain and Body?

How Do Dissociative Drugs Work?

Laboratory studies suggest that dissociative drugs, including PCP, ketamine, and DXM, cause their effects by disrupting the actions of the brain chemical glutamate at certain types of receptors—called N-methyl-D-aspartate (NMDA) receptors—on nerve cells throughout the brain (Morgan, 2012; Morris, 2005). Glutamate plays a major role in cognition (including learning and memory), emotion, and the perception of pain (the latter via activation of pain-regulating cells outside of the brain). PCP also alters the actions of dopamine, a neurotransmitter responsible for the euphoria and “rush” associated with many abused drugs.

Salvia divinorum works differently. While classified as a dissociative drug, salvia causes its effects by activating the kappa opioid receptor on nerve cells (Cunningham, 2011; MacLean, 2013). These receptors differ from those activated by the more commonly known opioids such as heroin and morphine.

What Are the Short-Term Effects of Dissociative Drugs?

Dissociative drugs can produce visual and auditory distortions and a sense of floating and dissociation (feeling detached from reality) in users. Use of dissociative drugs can also cause anxiety, memory loss, and impaired motor function, including body tremors and numbness. These effects, which depend on the amount of the drug taken, are also unpredictable—typically beginning within minutes of ingestion and lasting for several hours, although some users report feeling the drug’s effects for days. See text box for general effects of dissociative drugs.

General Common Effects of Dissociative Drugs
Low to Moderate Doses High Doses
  • Numbness
  • Disorientation, confusion, and loss of coordination
  • Dizziness, nausea, vomiting
  • Changes in sensory perceptions (such as sight, sound, shapes, time, and body image)
  • Hallucinations
  • Feelings of detachment from self and environment
  • Increase in blood pressure, heart rate, respiration, and body temperature
  • Hallucinations
  • Memory loss
  • Physical distress, including dangerous changes in blood pressure, heart rate, respiration, and body temperature
  • Marked psychological distress, including feelings of extreme panic, fear, anxiety, paranoia, invulnerability, exaggerated strength, and aggression
  • Use with high doses of alcohol or other central nervous system depressants can lead to respiratory distress or arrest, resulting in death

In addition to these general effects, different dissociative drugs can produce a variety of distinct and dangerous effects. For example, at moderate to high doses, PCP can cause a user to have seizures or severe muscle contractions, become aggressive or violent, or even experience psychotic symptoms similar to schizophrenia. At moderate to high doses, ketamine can cause sedation, immobility, and amnesia. At high doses, ketamine users also report experiencing terrifying feelings of almost complete sensory detachment likened to a near-death experience (called a “K-hole,” similar to a bad LSD trip). Salvia users report intense but short-lived effects—up to 30 minutes—including emotional mood swings ranging from sadness to uncontrolled laughter.

DXM, which is safe and effective as a cough suppressant and expectorant when used at recommended doses (typically 15 to 30 milligrams), can lead to serious side effects when abused. For example, use of DXM at doses from 200 to 1,500 milligrams can produce dissociative effects similar to PCP and ketamine and increase the risk of serious central nervous system and cardiovascular effects such as respiratory distress, seizures, and increased heart rate from the antihistamines found in cough medicines.

What Are the Long-Term Effects of Dissociative Drugs?

While the long-term use of most dissociative drugs has not been investigated systematically, research shows that repeated use of PCP can lead to tolerance and the development of a substance use disorder that includes a withdrawal syndrome (including craving for the drug, headaches, and sweating) when drug use is stopped. Other effects of long-term PCP use include persistent speech difficulties, memory loss, depression, suicidal thoughts, anxiety, and social withdrawal that may persist for a year or more after chronic use stops.