Dissociatives: How They Differ From Classic Psychedelics

What dissociatives are

Dissociative drugs are, in the US National Institute on Drug Abuse (NIDA) grouping, drugs that primarily affect how the brain processes the chemical glutamate. They can make people feel disconnected from their body and environment. [1] NIDA names ketamine and PCP (phencyclidine) as the examples. [1] Dextromethorphan (DXM), the cough-suppressant ingredient, also belongs in the conversation, as explained below.

How they differ from classic psychedelics

[1]

NIDA explains that ketamine and PCP disrupt the action of glutamate at the N-methyl-D-aspartate (NMDA) receptor, and that glutamate plays a major role in learning, memory, emotion and the perception of pain. [1] This is a different brain system from the serotonin receptors targeted by classic psychedelics, so the two groups should not be treated as interchangeable. See Classic Psychedelics and Ketamine vs Classic Psychedelics.

Ketamine, esketamine and PCP

• Ketamine is FDA approved as an anesthetic for humans and animals. NIDA says ketamine itself is not FDA approved for any mental health disorder, even though clinics offer it off label. [2]
• Esketamine, a ketamine derivative, is FDA approved for treatment-resistant depression in adults. [2] Ketamine and esketamine are different products: see Ketamine vs Esketamine.
• PCP was developed as an anesthetic. NIDA says ketamine was developed decades ago as a less toxic alternative to it. [2]

Dextromethorphan (DXM)

A 2023 chemistry review states that DXM was introduced in 1958 as the first non-opioid cough suppressant, that its antagonism at NMDA receptors is thought to underlie its cough effect, and that amounts above therapeutic range mimic the activity of dissociative hallucinogens such as PCP and ketamine. [3] This page gives no amounts. The point is only that a common medicine ingredient can share an action with dissociative drugs, which is one more reason to follow labels and ask a pharmacist.

Risks documented by NIDA

• NIDA says PCP and ketamine can make symptoms worse in people who have schizophrenia and can cause short-term episodes of psychosis. [1]
• Long-term ketamine use may cause ketamine-induced uropathy, a treatable but potentially serious bladder condition with symptoms like a urinary tract infection. [1]
• PCP, like NBOMes and ibogaine, has been associated with a small number of reported deaths and serious adverse health effects. [1]
• Illicitly manufactured drugs can be contaminated with other dangerous substances, including fentanyl. [1]

Evidence labels used

Approved medicine here means what FDA has approved: ketamine as an anesthetic and esketamine for treatment-resistant depression in adults, as stated on NIDA's pages. [2][4] Everything else on this page is classification or safety information, not evidence of benefit. Research on ketamine and esketamine for depression is covered in Treatment-Resistant Depression, and the experience of dissociation is covered in Dissociation.

Safety note

Dissociative drugs can impair thinking and perception and have been linked to dangerous behavior and injuries, particularly when no one else is present to help in an emergency. [1] In the US, call 911 in an emergency and Poison Help at 1-800-222-1222 for suspected poisoning (poison help by country).

Education only

This page explains categories and documented risks. It gives no amounts, no sourcing advice and no advice to self-treat.