mar 10 lsd & schizophrenia + marijuana

LSD & Schizophrenia Overview

  • Presenter: Steven J. Barnes

  • Additional Focus: Marijuana & Schizophrenia

Schedule Overview

  • Wednesday, March 11, 3-4 pm: Midterm 2 Q&A Session (Zoom)

  • Thursday, March 12: Midterm 2

  • Tuesday, March 17: Focus on Schizophrenia & Marijuana

  • Thursday, March 19: Following topics

Psychedelics Overview

  • Sensory-aesthetic experiences:

    • Characterized by perceptual changes such as:

    • Increased vividness of colors

    • Appearance of movement of static objects

    • Fractal and kaleidoscopic imagery

    • Enhanced sensitivity to music

    • Altered sense of touch and texture

    • Altered body awareness

    • Synesthesia

    • Reference: Garcia-Romeu & Richards, 2018

LSD: Acute Effects

  • Subjective Experience:

    • Spiritual experience

    • Blissful state

    • Insightfulness

    • Disembodiment

    • Impaired control and cognition

    • Anxiety

    • Complex imagery

    • Elementary imagery

    • Audio-visual synesthesia

    • Changed meaning of percepts

    • Study reference: Schmid et al., 2014

LSD: Graphical Representations

  • Experience of LSD vs. Placebo:

    • Graphs depict various subjective experiences over time:

    • Good drug effect vs. bad drug effect

    • Feelings of stimulation, concentration, fear

    • Specifically noted scales for drug liking and experience intensity

    • Timescale represented in hours

Time Course of Subjective Experiences

  • Psychedelic Effects Over Time:

    • Phases:

    • Peak experience characterized by intense states (mystical experiences).

    • Afterglow characterized by a persistent feeling of elevated mood lasting days to weeks.

    • Long-term residual effects include changes in mindset and personality traits.

  • Concepts:

    • Psychotropic effects unfold over several hours based on drug and dosage

    • Importance for therapeutic interventions

LSD Mechanisms of Action

  • Two Phases of Effect:

    • Early phase involves serotonergic activity

    • Late phase may involve dopaminergic activity leading to paranoia

  • Key Receptors Affected by LSD:

    • Serotonin Type 2a Receptor:

    • Main receptor associated with psychological effects

    • Abnormalities noted in schizophrenia

    • Dopamine Type 1 and Type 2 Receptors:

    • Associated with thought disorder and paranoia during the trip

    • Serotonin Type 1a Receptor:

    • Possibly responsible for some visual effects

  • References from Chen & Tesmer, 2017.

Serotonin Hypothesis of Schizophrenia

  • Three Key Points:

    1. Effects of LSD and psilocybin/psilocin are mediated by the Serotonin Type 2a receptor.

    2. Abnormalities in the Serotonin Type 2a receptor observed in schizophrenia patients.

    3. Serotonin Type 2a receptor antagonism affects atypical antipsychotics (e.g. risperidone).

Glutamatergic Hypofunction Theory of Schizophrenia

  • Theory Overview:

    • Dysfunction of glutamate NMDA receptors on GABAergic interneurons leads to:

    • Decreased GABAergic transmission

    • Imbalance of inhibition and excitation

Immune Dysfunction Theory of Schizophrenia

  • Key Points Supporting the Theory:

    1. Certain infections increase psychosis risk by up to 60%.

    2. Higher schizophrenia risk in individuals with autoimmune diseases.

    3. Genes associated with schizophrenia also linked to immune system functions.

    4. Psychosis features in 'anti-NMDA receptor encephalitis', an autoimmune disorder affecting NMDA receptors.

Marijuana and Psychosis

  • Association with High-Potency Cannabis Use:

    • Daily use of high-potency cannabis correlated with:

    • Increased risk of new or relapse into psychosis (dose-dependent, more common in males).

    • Earlier onset of psychosis compared to lower potency cannabis.

    • CBD shown to elicit responses in schizophrenia akin to atypical antipsychotics.

Potential for Addiction with Cannabis

  • Addiction Statistics:

    • 22% of cannabis users (with THC) fulfill DSM-5 criteria for cannabis-use disorder (CUD).

    • High-potency cannabis drastically raises addiction potential:

    • 6-7 times increased risk of CUD compared to low-potency cannabis (<15% THC).