Dissociatives

Substances that disconnect perception from reality — from therapeutic ketamine to recreational nitrous. Pharmacology and risks of each.

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Ketamine

Mechanism: NMDA receptor antagonist | Duration: IM/IV: 45-90 min. Insufflated: 1-2 hrs

Dosing: Therapeutic: 0.5mg/kg IV. Recreational: 50-200mg insufflated

Risks: Bladder toxicity with chronic use (ketamine cystitis). Psychological dependence. Aspiration risk.

Therapeutic: Depression (Spravato/esketamine FDA-approved). Chronic pain. PTSD (research).

DXM (Dextromethorphan)

Mechanism: NMDA antagonist, sigma-1 agonist, serotonin reuptake inhibitor | Duration: 4-8 hours

Dosing: OTC cough medicine. Recreational: 100-1500mg

Risks: Serotonin syndrome with SSRIs/MAOIs. OTC formulations may contain acetaminophen (liver damage), guaifenesin, or antihistamines.

Therapeutic: Auvelity (DXM + bupropion) FDA-approved for depression (2022).

PCP (Phencyclidine)

Mechanism: NMDA antagonist, dopamine reuptake inhibitor, sigma agonist | Duration: 4-8 hours

Dosing: 5-10mg

Risks: Violent/erratic behavior. Psychosis. Seizures. Hyperthermia. Rhabdomyolysis. Most dangerous dissociative.

Therapeutic: None. Withdrawn as anesthetic due to adverse effects.

Nitrous Oxide (N2O)

Mechanism: NMDA antagonist, GABA modulator, endogenous opioid release | Duration: 30 seconds - 2 minutes

Dosing: Single charger (8g)

Risks: B12 depletion with chronic use (peripheral neuropathy). Asphyxiation risk. Falls/injuries. Frostbite.

Therapeutic: Dental anesthesia. Labor pain management. Procedural sedation.

Salvia Divinorum

Mechanism: Kappa-opioid receptor agonist | Duration: 5-20 minutes (smoked)

Dosing: Dried leaf: 200-500mg. Extract: 100-500ug salvinorin A

Risks: Intense, potentially terrifying experience. Dysphoria. Complete loss of identity/reality. Falls and injuries.

Therapeutic: Research interest in pain but clinical application limited.