Part 7: Dissociatives — Ketamine, Dextromethorphan, and Nitrous Oxide

Clinical Reference for Healthcare Professionals.

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1. Ketamine Hydrochloride

Field	Detail
INN / Salt	Ketamine Hydrochloride
Drug Class	Arylcyclohexylamine (Dissociative Anesthetic)
Schedule	Schedule X + NDPS considerations
Indian Brands	Ketalar, Ketaject, Aneket
Legitimate Uses	General anesthesia (especially in pediatrics and field surgery), treatment-resistant depression (sub-anesthetic doses)

Mechanism of Action

Ketamine is a non-competitive NMDA (N-methyl-D-aspartate) receptor antagonist. By blocking glutamate (the brain’s primary excitatory neurotransmitter) from binding to NMDA receptors, it produces a state of “dissociative anesthesia” — the patient appears awake with open eyes but is completely detached from their body and surroundings. At sub-anesthetic doses, it also interacts with opioid, dopaminergic, and serotonergic pathways.

Why It Is Abused

At low recreational doses, Ketamine produces euphoria, visual distortions, and a feeling of floating. At higher doses, it produces the “K-Hole” — a profound dissociative experience where the user feels completely separated from their physical body, often described as a near-death-like experience. It is primarily diverted from veterinary and hospital anesthesia supplies.

Side Effects & Dangers of Abuse

• Ketamine Bladder (Ulcerative Cystitis): Chronic abuse causes severe, debilitating inflammation and ulceration of the bladder lining, resulting in agonizing urinary frequency and blood in urine.
• Cognitive Impairment: Chronic use causes persistent memory deficits and difficulty with abstract thinking.
• Hypertension & Tachycardia: Unlike most anesthetics, Ketamine raises blood pressure and heart rate.
• Psychological Dependence: Strong craving and tolerance development.
• “Bad Trips”: Terrifying dissociative episodes with paranoia and psychosis.

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2. Dextromethorphan Hydrobromide (DXM)

Field	Detail
INN / Salt	Dextromethorphan Hydrobromide
Drug Class	Morphinan (Antitussive / Dissociative at High Doses)
Schedule	OTC (Over-the-Counter) — No prescription required
Indian Brands	Benadryl DR, Alex, D’Cold Total, many cough syrups
Legitimate Uses	Cough suppression (antitussive)

Mechanism of Action

At therapeutic doses (10-30mg), DXM acts on sigma receptors and medullary cough centers to suppress coughs. However, at recreational doses (300-1500mg), it and its active metabolite dextrorphan act as NMDA receptor antagonists, producing dissociative and hallucinogenic effects similar to Ketamine and PCP. At these high doses, it also exhibits serotonergic and adrenergic activity.

Why It Is Abused

DXM is one of the most accessible drugs of abuse because it is available in over-the-counter cough syrups without a prescription. Abusers consume entire bottles of cough syrup (“Robotripping” or “DXM tripping”). The effects are described in “plateaus” based on dosage — from mild euphoria to full-blown dissociation and hallucinations.

Side Effects & Dangers of Abuse

• Serotonin Syndrome: If combined with SSRIs (Escitalopram, Fluoxetine), it can cause fatal serotonin toxicity.
• Toxicity from Additives: Many cough syrups also contain Acetaminophen (paracetamol), which causes fatal liver failure at the doses required for a DXM “high.” Others contain Chlorpheniramine, causing anticholinergic toxicity.
• Hypertension & Tachycardia: Acute cardiovascular stress.
• Psychosis: Persistent hallucinations and paranoia with chronic abuse.

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3. Nitrous Oxide (N₂O)

Field	Detail
INN / Salt	Nitrous Oxide
Drug Class	Inorganic Gas (Inhalation Anesthetic / Analgesic)
Schedule	Not scheduled as a pharmaceutical; regulated as industrial gas
Sources	Dental offices, medical supply, commercial “whipped cream chargers” (“whippets”)
Legitimate Uses	Dental anesthesia, supplemental anesthetic in surgery, analgesic during labor

Mechanism of Action

Nitrous oxide acts primarily as an NMDA receptor antagonist (blocking excitatory glutamate signaling) and also modulates opioid, GABAergic, and dopaminergic pathways. Critically, it irreversibly oxidizes the cobalt ion in Vitamin B12, inactivating it.

Why It Is Abused

Inhaled from balloons or directly from “whippet” canisters, nitrous oxide produces a brief (30-60 seconds), intense burst of euphoria, dissociation, and giggly lightheadedness. Its extreme brevity drives compulsive re-dosing. Its accessibility (sold legally in stores as whipped cream propellant) makes it exceptionally easy to obtain.

Side Effects & Dangers of Abuse

• Asphyxiation: Displaces oxygen. Inhaling directly from a pressurized canister can be instantly fatal.
• Frostbite: Cold gas can cause severe burns to the lips, mouth, and throat.
• Vitamin B12 Depletion (Subacute Combined Degeneration): Chronic abuse destroys functional B12, causing irreversible nerve damage — peripheral neuropathy (numbness/tingling in hands and feet), spinal cord degeneration, and gait instability.
• Megaloblastic Anemia: B12 deficiency disrupts red blood cell formation.

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Next: Part 8: Anticholinergics and Antihistamines