Detailed Notes on Hallucinogens

Hallucinogens Overview

  • Course: Psy 436 – Drugs & Behavior

General Overview of Hallucinogens

  • Hallucinogens include many plants and synthetic compounds.

  • They are organized based on their mechanisms of action and effects.

Types of Hallucinogens

  • Serotonergic Hallucinogens: Affect the serotonin system.

    • Examples: LSD, Psilocybin, DMT (ayahuasca), Mescaline (Peyote).

  • Methylated Amphetamines: Affect serotonin and other monoamine systems.

  • Anticholinergic Hallucinogens: Affect acetylcholine (muscarinic) receptors.

    • Examples: Atropine, Scopolamine.

  • Dissociative Anesthetics: Affect the glutamate system.

    • Examples: PCP (angel dust), Ketamine.

  • Salvia: Affects kappa opioid receptors.

    • Active Ingredient: Salvinorin A.

Serotonergic Hallucinogens

Overview

  • Used historically since before 1000 BC to induce visions by early civilizations in Central and South America (peyote, psilocybin, ayahuasca).

  • Gained modern prominence in the 1960s.

History and Usage

  • Albert Hofmann unintentionally discovered LSD in 1943 when he spilled some on his hand.

  • Encouraged use among psychologists to aid in psychotherapy by "breaking down ego".

  • Timothy Leary, a Harvard psychologist, popularized the use of LSD in therapy and art movements but brought concern due to associated risks.

Mechanisms of Action

  • Agonism (activation) of serotonin receptors.

Pharmacokinetics

  1. LSD:

    • Absorption: Readily absorbed via oral ingestion.

    • Distribution: Crosses blood-brain barrier.

    • Onset: Effects begin within 20-60 minutes.

    • Duration: Lasts 8-12 hours.

    • Metabolization: Eliminated quickly, undetectable after 72 hours.

  2. Psilocybin:

    • Potency: Much less potent than LSD (1%).

    • Duration: 4-6 hours.

  3. Mescaline:

    • Potency: Significantly less potent than LSD (0.0003%).

    • Duration: 10-14 hours.

Psychotherapeutic Uses

  • LSD is ineffective in simulating schizophrenia.

  • Psilocybin has been shown to reduce anxiety and depression in cancer patients.

  • Administered in controlled environments for treatment of:

    • Nicotine dependence

    • Alcohol use disorder

    • Depression

    • Mechanism of action for benefits is not well understood.

    • Research led by Roland Griffiths at Johns Hopkins University School of Medicine.

Effects of Serotonergic Hallucinogens

  • Physiological Effects:

    • Pupil dilation

    • Increased heart rate

    • Elevated body temperature

  • Psychological Effects:

    • Changes in visual perception

    • Experience of synesthesia (e.g., hearing colors)

    • Mood alterations

    • Mystical experiences.

Adverse Effects

  • Generally, no significant risk of chromosome damage, but potential fetal effects.

  • Bad trips: Paranoia, which can be influenced by psychological state and environmental settings.

    • Bad trips are less likely in psilocybin-assisted therapy due to controlled doses.

  • Flashbacks: Unexpected recurrence of hallucinogenic effects under specific conditions (e.g., stress).

Methylated Amphetamines

Overview

  • Examples: MDMA (Ecstasy), MDA, DOM.

  • History: MDMA was patented in 1914 but not widely used until the 1970s for psychotherapeutic purposes.

  • Legal status changed in 1985 when classified as Schedule 1 due to rising popularity and concerns of brain damage in animal models.

Mechanism of Action

  • Increases serotonin, dopamine, and norepinephrine via agonism and reuptake inhibition, exhibiting characteristics of both stimulants and hallucinogens.

Routes of Administration

  • Available modes: Oral, intranasal, intravenous.

  • Onset: Effects are quickly felt and last approximately 6-8 hours.

Physical Effects

  • Physiological: Pupil dilation, increased heart rate, elevated blood pressure, muscle tension, teeth grinding, appetite suppression, insomnia, increased body temperature.

  • Psychological: Feelings of euphoria, emotional warmth, increased empathy, and verbal behavior.

Adverse Effects

  • Short-term: Dehydration, heat exhaustion, muscle degradation, kidney failure, stroke, seizures, heart attack.

  • Long-term: Decreased efficacy in serotonin processing, depleted serotonin levels, potential depression, especially with higher doses.

Psychotherapeutic Uses

  • PTSD Treatment: In Phase 3 trials, 67% of participants using MDMA-assisted therapy showed no PTSD diagnosis after three sessions versus 32% in placebo group.

    • Average severity of PTSD symptoms can significantly decrease.

    • Temporary increases in blood pressure noted.

Anticholinergic Hallucinogens

Overview

  • Examples: Atropine, Scopolamine.

  • Historical use in “witches brews.”

  • Effects: Induce trance states, dry mouth, blurred vision, increased heart rate and body temperature, poor memory during influence.

  • Risks: Dangerous due to low therapeutic index.

Specific Plants

  • Belladonna

  • Jimsonweed

  • Angel’s trumpet

  • Mandrake

Dissociative Anesthetic Hallucinogens

Overview

  • Examples: PCP (angel dust), Ketamine.

  • Originally used in veterinary medicine as anesthetics.

  • Mechanism of action: Antagonism at glutamate receptors (specifically NMDA).

Effects

  • Physical: Euphoria, numbness, slurred speech, decreased coordination, sweating, increased heart rate, blurred vision.

  • Higher likelihood of complications in medical or psychiatric settings.

Salvia

Overview

  • Historically used in religious ceremonies.

  • Noted as the most potent naturally-occurring hallucinogen.

  • Mechanism of action: Agonism at κ opioid receptors.

Effects

  • Induces trance-like states and sensory disturbances, though bad trips are also common.

  • Scientific interest due to limited knowledge on κ opioid receptors.

  • Status: Not federally scheduled, but illegal in many states.