Psychedelics and Psychotropics Lecture Review

Course Objectives

• Define psychedelic
• Explain the physiological effects of various psychedelic compounds
• Link biological targets of different psychedelics to their unique effects
• Compare the addiction/abuse spectrum of psychotropics to other drugs of abuse
• Discuss therapeutic considerations for psychedelics

MDMA (Ecstasy)

• Full name: 3,4-methylenedioxymethamphetamine
• Properties:
  • Strong 5-HT (serotonin) releasing properties
  • Reinforcing due to dopamine effects
• Effects:
  • Increased energy
  • Enhanced sensory perceptions
  • Pleasant sensations
  • Altered concept of time
  • Physiological effects include:
  • Increased heart rate
  • Dry mouth
• Side Effects (at high doses):
  • Hallucinations
  • Agitation
  • Panic attacks

General Overview of Psychotropic/Psychedelic Agents

• Primary Effects: Altered perceptions, encompassing possible true hallucinations; variable impact on memory.
• Indigenous use dates back over 5,000 years.
• Terminology:
  • "Psychedelic" coined by Humphrey Osmond in 1956, means "manifesting the soul/mind".
  • "Entheogenic": use in indigenous religious and spiritual practices.

Origins of LSD

• Chemical Name: Lysergic acid diethylamide
• Synthesis: First synthesized by Alfred Hofman in 1938.
• Accidental Ingestion: Accidentally ingested in 1943, leading to significant effects:
  • Described feelings of uneasiness, vertigo, altered perceptions, dreamlike state.
• Historical Context:
  • Derivatives include alkaloids from ergot fungus, linked to historical events like ergotism, Salem witch trials, and the 1518 Dancing Plague.

Physiological Effects of LSD

• Effects are highly variable, dependent on set and setting.
• Common effects:
  • Enhanced self-awareness
  • Prominent mood changes at higher doses
  • Pupil dilation
  • Synesthesia: blending of senses
  • Hyperthermia and increased blood pressure
  • Salivation and lacrymation (tear production)
  • Hyperactive reflexes

Pharmacology of LSD

• Mechanism of Action:
  • Activates multiple 5-HT receptors, particularly 5HT2a, which is associated with hallucinations and altered perceptions.
  • Increases neuroplasticity, allowing for the formation of new connections in the brain.

Tolerance and Withdrawal

• Tolerance: Rare; repeated daily use is unusual.
• Withdrawal Phenomena: Not reported; however, can precipitate psychoses in susceptible individuals.
• Dependence: No evidence of dependence or addiction.
• Hallucinogen Persisting Perception Disorder: Potential for flashbacks and long-term episodic visual disturbances triggered by stress, anxiety, or fatigue.

Therapeutics of Psychedelics

• Emerging Uses:
  • LSD/psilocybin under Phase II clinical trials for treatment-resistant depression.
  • MDMA in Phase III clinical trials for PTSD.
• Other potential treatments: OCD, substance abuse (alcohol/nicotine), anxiety, terminal illness pain management.
• 4-Stage Treatment Framework:
  1. Assessment: Evaluate mental and physical suitability for treatment.
  2. Preparation: Guided by trained therapists for navigating the experience.
  3. Experience Session: Administration of the drug in a controlled setting with therapists.
  4. Integration Session: Discuss the treatment experience and its relevance to the illness.

Microdosing

• Limited scientific evidence suggests microdosing is effective.
• Potential benefits observed, particularly in isolated groups, such as the geriatric population.