Hallucinogens

Hallucinogens Overview - Mind-Bending Basics

• Definition: Psychoactive agents causing profound alterations in perception, mood, and cognitive processes.
• Key Neurotransmitter Systems Involved:
  • Serotonin (5-HT)
  • Glutamate (NMDA receptors)
  • Acetylcholine (muscarinic receptors)
  • Dopamine (DA) / Norepinephrine (NE)
• Classification:

  Class	Mechanism	Examples
  Serotonergic (Classical)	5-HT2A agonism	LSD, Psilocybin
  Dissociative	NMDA antagonism	Ketamine, PCP
  Deliriant	Muscarinic ACh antagonism	Atropine
  Atypical/Entactogen	Mixed 5-HT, DA/NE	MDMA

⭐ Most hallucinogens lack significant classical addictive potential (e.g., withdrawal), though psychological dependence can occur.

Serotonergic Psychedelics - Trippy Trails

• Examples: Lysergic acid diethylamide (LSD), Psilocybin (magic mushrooms), Mescaline (peyote cactus).
  • 📌 LSD: Lucy in the Sky with Diamonds.
• Mechanism of Action (MoA): Primarily 5-HT2A receptor agonists.
• Key CNS Effects: Visual & auditory hallucinations, synesthesia (e.g., "seeing sounds"), altered time perception.
• Somatic Effects: Mydriasis, tachycardia, ↑BP.
• Duration (approx.): LSD (6-12h) > Mescaline (4-12h) > Psilocybin (4-6h).
• Adverse Effect: Hallucinogen Persisting Perception Disorder (HPPD) - flashbacks.

⭐ LSD is extremely potent; psychoactive doses are in micrograms (e.g., 20-80 µg).

Dissociative Drugs - Outta Body Beats

• Mechanism: Non-competitive NMDA receptor antagonism (glutamate system).
• Shared Effects: Dissociation, analgesia, amnesia, nystagmus, agitation, psychosis.
• Ketamine (📌 "Special K"):
  • Uses: Anesthesia (esp. pediatric, hemodynamically unstable), rapid antidepressant for Treatment-Resistant Depression (TRD).
  • Toxicity: Emergence reactions (hallucinations, delirium), bladder dysfunction (chronic high-dose).
• Phencyclidine (PCP) (📌 "Angel Dust", "Peace Pill"):
  • No clinical use. Illicit.
  • Toxicity: Rotatory nystagmus (classic sign!), prolonged psychosis, extreme violence, hyperthermia, rhabdomyolysis, seizures.

⭐ Ketamine, an NMDA antagonist, has shown rapid antidepressant effects in treatment-resistant depression.

Deliriants & MDMA - Toxic Trips & Empathy

• Deliriants (e.g., Atropa belladonna, Datura):
  • MoA: Muscarinic acetylcholine receptor antagonism.
  • 📌 Anticholinergic Toxidrome:

    Mnemonic Phrase	Key Symptom(s)
    Blind as a bat	Mydriasis
    Mad as a hatter	Delirium
    Red as a beet	Flushing
    Hot as a hare	Hyperthermia
    Dry as a bone	Anhidrosis
    The bowel and bladder lose tone	Urinary retention, ↓motility
    And the heart runs alone	Tachycardia

  
• MDMA (Ecstasy/Molly):
  • MoA: ↑ 5-HT, DA, NE (SERT inhibition, ↑release).
  • Effects: Euphoria, entactogenesis, energy.
  • Toxicities: Hyperthermia (>40°C), hyponatremia, serotonin syndrome, neurotoxicity, bruxism.

  ⭐ Severe MDMA-induced hyponatremia (<125 mmol/L) is a medical emergency (↑water intake, ↑ADH).

Hallucinogen Toxicity - Calming the Chaos

• General Management: Prioritize ABCs. Provide supportive care, reassurance ("talk-down" technique). Maintain a quiet, low-stimulus environment to minimize agitation.
• Pharmacological Interventions:
  • Benzodiazepines: Key for agitation, seizures, and sympathomimetic overdrive.
  • Cyproheptadine: Useful for managing serotonin syndrome.
  • Physostigmine: For severe anticholinergic toxicity (⚠️ use cautiously, requires ECG monitoring, note contraindications).
• Hyperthermia: Manage with aggressive cooling measures.
• Restraints: Chemical restraint (e.g., benzodiazepines) preferred over physical restraints to ensure safety.

⭐ Benzodiazepines are the cornerstone of management for agitation and seizures in most hallucinogen intoxications, regardless of the specific agent.

High‑Yield Points - ⚡ Biggest Takeaways

• LSD: Potent 5-HT2A agonist; causes visual hallucinations, synesthesia, flashbacks.
• Psilocybin (magic mushrooms): Converted to psilocin (active); 5-HT2A agonist with LSD-like effects.
• Mescaline (peyote): 5-HT2A agonist; causes prominent visual hallucinations.
• Phencyclidine (PCP): NMDA receptor antagonist; causes dissociation, nystagmus (rotatory), aggression, analgesia.
• Ketamine: NMDA antagonist; dissociative anesthetic, shorter acting, less psychotomimetic than PCP.
• MDMA (Ecstasy): ↑ Serotonin release/↓reuptake; causes empathy, euphoria, hyperthermia, hyponatremia.