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Hallucinogens

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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:
    ClassMechanismExamples
    Serotonergic (Classical)5-HT2A agonismLSD, Psilocybin
    DissociativeNMDA antagonismKetamine, PCP
    DeliriantMuscarinic ACh antagonismAtropine
    Atypical/EntactogenMixed 5-HT, DA/NEMDMA

⭐ 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).

5-HT2A receptor complexed with psychedelic

Dissociative Drugs - Outta Body Beats

  • Mechanism: Non-competitive NMDA receptor antagonism (glutamate system).
  • Shared Effects: Dissociation, analgesia, amnesia, nystagmus, agitation, psychosis. Ketamine action on glutamatergic and GABAergic neurons
  • 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 PhraseKey Symptom(s)
      Blind as a batMydriasis
      Mad as a hatterDelirium
      Red as a beetFlushing
      Hot as a hareHyperthermia
      Dry as a boneAnhidrosis
      The bowel and bladder lose toneUrinary retention, ↓motility
      And the heart runs aloneTachycardia
    Atropa belladonna plant parts
  • 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.

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