hallucinations

PSYCHEDELICS

Introduction

  • Key Points of the Lecture:

    • How to become one with the universe.

    • The CIA’s mind-control experiments with LSD.

    • Explanation of the glutamate hypothesis of schizophrenia.

PSYCHEDELIC DRUGS

  • Definition:

    • Psychedelic drugs are mind-manifesting substances used for spiritual or mystical experiences.

    • They have hallucinogenic properties, causing changes in perception, visual hallucinations, and alterations in the awareness of both mind and body, as well as cognitive distortions.

    • Notably, these effects occur without toxic delirium.

PHENETHYLAMINE PSYCHEDELICS

  • Examples: Mescaline.

    • Source: Derived from the peyote cactus, which is native to the southwestern United States.

    • Usage History: Evidence points to its use as early as 3000 BCE for religious and healing rituals.

INDOLEAMINE PSYCHEDELICS

  • Major Examples: Psilocybin and psilocin.

    • Characteristics: Serotonin-like compounds found in various mushrooms worldwide.

    • Conversion: Psilocybin is enzymatically converted into psilocin.

    • Historical Evidence of Use:

    • Used by humans as early as 3500 BCE.

    • Significantly promoted by a 1957 Life magazine article featuring Gordon Wasson, titled "Seeking the Magic Mushroom.

  • Historical Context of LSD:

    • Discovery: Synthesized in 1938 by Swiss chemist Albert Hofmann, it is a potent synthetic drug.

    • Psychedelic Therapy: Early use in psychedelic therapy became prominent in the 1960s, particularly influencing hippie culture.

    • Legislation: Recreational use was banned in 1967.

RECENT HISTORY OF PSYCHEDELICS

  • Key Events Timeline:

    • 1938: Albert Hofmann synthesizes LSD.

    • 1898: Arthur Heffter isolates mescaline.

    • 1957: R. Gordon Wasson publishes an article on mushrooms.

    • 1943: Hofmann discovers LSD’s psychoactive properties.

    • 1959: Hofmann isolates psilocybin.

    • 2008: First reports of psychedelics’ therapeutic effects for end-of-life anxiety and anti-inflammatory effects.

    • 1988: 5-HT2 receptor identified as a target for LSD.

    • 1997-2016: Introduction of various neuroimaging studies on psilocybin and LSD, including fMRI studies and PET studies.

    • 1970: U.S. passes the Controlled Substances Act, impacting scientific research.

PSYCHEDELIC PHARMACOLOGY

  • General Characteristics:

    • Potency varies, with LSD being the most potent psychedelic.

    • Administration and Effects:

    • Most psychedelics are administered orally; effects typically begin within 30-90 minutes.

    • Duration of effects may last from minutes to several hours.

    • Trip Phases:

    • Onset

    • Plateau

    • Peak

    • Comedown.

  • Typical Dosages and Administration Routes:

    • Mescaline: Oral, 200–500 mg.

    • Psilocybin: Oral, 10–20 mg.

    • LSD: Oral, 50–100 µg (0.05–0.10 mg).

    • DMT: Smoking, 20–50 mg.

    • 25I-NBOMe: Sublingual/buccal, 250–800 µg (0.25–0.80 mg).

    • Salvinorin A: Smoking, 200–1,000 µg (0.2–1.0 mg).

    • Ibogaine: Oral, 500–800 mg.

PSYCHEDELIC EXPERIENCE

  • Common Effects:

    • Vivid visual hallucinations.

    • Altered perceptions of time and space.

    • Feelings of depersonalization.

    • Strong emotional responses and disruptive logical thought processes.

    • Synesthesia: A phenomenon where sensations cross (e.g., colors perceived as sounds).

    • Trip Quality:

    • “Good” Trip: Associated with mystically and spiritually enlightening experiences.

    • “Bad” Trip: Can be disturbing and frightening.

  • Physiological Responses:

    • Effects may include activation of the sympathetic nervous system, dizziness, nausea, and vomiting, with a higher incidence related to mushroom and peyote consumption.

MECHANISM OF ACTION

  • Receptor Interaction:

    • Indoleamine and phenethylamine psychedelics act primarily as 5-HT2A receptor agonists, enhancing calcium influx.

    • This interaction activates protein kinase C (PKC), contributing to their potent effects and extended trips by binding effectively to receptors.

  • Neurological Impact:

    • Stimulation of 5-HT2A, AMPA, and NMDA receptors triggers pyramidal neuron populations in layer 5 of the prefrontal cortex, disrupting normal cortico-striatal-thalamo-cortical loops.

    • Resulting in a decreased gating of sensory and cognitive inputs from subcortical structures.

  • Functional Imaging Studies:

    • LSD and related psychedelics show reduced activity within several brain networks, including the default mode network (DMN), visual networks, and auditory networks.

THERAPEUTIC APPLICATIONS

  • Potential Uses:

    • LSD has been studied for Alcohol Use Disorder (AUD) despite being classified as Schedule I in 1970.

    • Single exposure to a psychedelic may yield long-lasting therapeutic benefits.

    • The intensity of the psychedelic experience correlates with favorable outcomes in treating conditions like depression, obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD).

  • Psychoplastogens:

    • Refers to psychedelics noted for their anti-depressant effects through glutamate-dependent neural plasticity.

    • Mechanisms include increased dendritic complexity and synapse formation.

ADVERSE REACTIONS

  • Dependence and Tolerance:

    • Psychotropic psychedelics do not lead to dependency; few individuals meet DSM-5 criteria for hallucinogen use disorder.

    • Tolerance can develop, likely due to down-regulation of the 5-HT2A receptors.

    • Potential risks include experiencing bad trips, flashbacks, and hallucinogen persisting perception disorder (HPPD).

PCP AND KETAMINE

  • Overview:

    • Dissociative anesthetics, including phencyclidine (PCP) and ketamine, have unique psychoactive properties.

    • PCP was developed in the 1950s, primarily used as an anesthetic but also found street popularity in the 1960s, known as "angel dust".

  • Ketamine:

    • Developed to be a safer alternative for pediatric and veterinary anesthesia.

    • Often used recreationally, especially in club scenes, at varying doses leading to altered states of consciousness.

PHARMACOLOGY OF PCP AND KETAMINE

  • Mechanism:

    • Both substances act as uncompetitive antagonists at the NMDA receptor, blocking ion flow and trapping the drug within the channel, limiting glutamate's effect after binding.

  • Recreational Use:

    • Both exhibit reinforcing properties through increased dopamine release in the nucleus accumbens and mesolimbic tract firing.

    • PCP is less popular; ketamine is sought after for its relaxing effects at lower doses and intense experiences at higher doses.

KETAMINE THERAPEUTIC USE

  • Applications:

    • Offers rapid relief of depression symptoms, particularly prior to the onset of traditional SSRIs, and serves as a non-opioid analgesic for acute and chronic pain conditions.