Study Notes on Hallucinogens

Hallucinogens

Overview of Hallucinogens

• Definition:

  • Hallucinogens are substances that cause alterations in perception, mood, and cognitive processes.

• Categories:

  • Organized by their mechanism of action and effects into several types:

    • Serotonergic Hallucinogens: Affect the serotonin system.

    • Methylated Amphetamines: Affect serotonin and other monoamine systems.

    • Anticholinergic Hallucinogens: Affect acetylcholine (muscarinic) receptors.

    • Dissociative Anesthetics: Affect the glutamate system.

    • Salvia (Salvinorin A): Affects the kappa opioid receptor.

Types of Hallucinogens

Serotonergic Hallucinogens

• Examples:

  • LSD (Lysergic acid diethylamide)

  • Psilocybin (found in magic mushrooms)

  • DMT (N,N-Dimethyltryptamine, notably in ayahuasca)

  • Mescaline (found in Peyote)

• Historical Context:

  • Used since at least 1000 BC to induce visions in early civilizations:

    • Central America: Peyote and psilocybin

    • South America: Ayahuasca (DMT)

• Modern Relevance:

  • Limited impact on modern drug culture until the 1960s.

    • Notable event: In 1943, Albert Hofmann accidentally discovered LSD and began its distribution for psychotherapeutic applications.

    • He promoted the use of LSD among psychiatrists as a means to "break down ego" in psychotherapy.

  • Timothy Leary popularized its use in the 1960s, leading to an explosion in interest among artists and counterculture communities.

    • Decline in popularity during the 1970s and 1980s due to safety concerns (e.g. dangerous behaviors, potential birth defects).

    • Notable phrase: “Turn on, tune in, drop out.”

Mechanisms of Action

• Serotonergic Mechanism:

  • Agonism (activation) of serotonin receptors.

Pharmacokinetics of LSD

• Absorption and Onset:

  • Readily absorbed orally.

  • Crosses the blood-brain barrier.

• Onset of Effects:

  • Begins within 20-60 minutes.

• Duration of Effects:

  • Lasts 8-12 hours.

• Metabolism:

  • Rapidly metabolized and eliminated, becoming undetectable after 72 hours.

Pharmacokinetics of Other Serotonergic Hallucinogens

• Psilocybin:

  • Potency: Approximately 1% of LSD.

  • Duration: 4-6 hours.

• Mescaline:

  • Potency: Approximately 0.0003% of LSD.

  • Duration: 10-14 hours.

Psychotherapeutic Uses

• LSD:

  • Not effective for simulating schizophrenia.

• Psilocybin:

  • Shows promise in reducing anxiety and depression in cancer patients.

  • Administered carefully in controlled therapeutic settings as an adjunct treatment for:

    • Nicotine dependence

    • Alcohol use disorder

    • Depression

  • Mechanism of efficacy is not well understood (noted by Roland Griffiths from 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.

  • Synesthesia: Perception of stimuli across different modalities (e.g., hearing colors).

  • Mood and cognitive modifications.

  • Mystical experiences.

Adverse Effects

• Risks:

  • Generally low risk of chromosome damage but potential fetal effects.

  • Experiences of "bad trips" characterized by paranoid reactions (influenced by psychological state and environmental factors).

  • Prevention of bad trips through low-dose psilocybin therapy in calming environments.

  • Flashbacks: Recurrences of hallucinogen effects triggered by stress, darkness, and substance use.

Methylated Amphetamines

• Examples:

  • MDMA (Ecstasy)

  • MDA

  • DOM

• History:

  • Patented in 1914; gained traction in the 1970s for psychotherapeutic exploration.

  • MDMA was legal until 1985, classified as Schedule 1 due to increased popularity and animal studies showing brain damage.

• Cultural Trend:

  • Gained popularity as a club drug throughout the 1990s and 2000s, but recent trends indicate a decline in use.

Mechanism of Action for Methylated Amphetamines

• Effects on Neurotransmitters:

  • Increase levels of serotonin, dopamine, and norepinephrine through agonism and reuptake inhibition (possesses characteristics of both stimulants and hallucinogens).

Routes and Duration of Effects for MDMA

• Administration Routes:

  • Oral

  • Intranasal

  • Intravenous

• Absorption:

  • Rapidly absorbed with effects lasting 6-8 hours.

Physical and Psychological Effects of MDMA

• Physical Effects:

  • Pupil dilation

  • Increased heart rate and blood pressure

  • Muscle tension

  • Teeth grinding

  • Appetite suppression

  • Insomnia

  • Elevated body temperature

• Psychological Effects:

  • Euphoria

  • Emotional warmth and empathy

  • Increased verbal expression (illustrated through a game example called “Cyberball”).

Adverse Effects of Methylated Amphetamines

• Immediate Risks:

  • Dehydration

  • Heat exhaustion

  • Muscle degradation

  • Kidney failure

  • Stroke

  • Seizures

  • Heart attack

• Long-term Impacts:

  • Decreased efficacy of serotonin processing

  • Depleted serotonin levels, leading to depression.

  • Dependency on the dosage: lower doses may lessen neurotoxic effects.

Psychotherapeutic Uses in PTSD

• MDMA-assisted Therapy:

  • Phase 3 trial results indicate that 67% of participants no longer had a PTSD diagnosis after 3 treatment sessions.

    • Comparison to placebo group: 32% also showed improvement with therapy without MDMA.

  • Average severity of PTSD symptoms tracked through CAPS-5 score (elevations observed pre- and post-treatment).

• Blood Pressure Monitoring during Therapy:

  • Notable temporary increases in blood pressure among MDMA-assisted therapy participants.

    • Systolic BP increased significantly in MDMA group compared to placebo group.

Multidisciplinary Association for Psychedelic Studies (MAPS)

• Overview:

  • A non-profit organization aimed at developing MDMA-assisted therapy into an FDA-approved treatment.

  • Critical research ongoing on safety and efficacy; therapy is not universally effective and maintains associated risks even in controlled settings. Visit maps.org for further information.

Anticholinergic Hallucinogens

• Examples:

  • Atropine

  • Scopolamine

• Historical Context:

  • Previously utilized in “witches brews.”

• Effects:

  • Induction of trance states.

  • Symptoms include dry mouth, blurred vision, increased heart rate and body temperature, impaired memory during use.

• Safety Concerns:

  • Known for a low therapeutic index (high risk of adverse reactions).

• Source Plants:

  • Belladonna

  • Jimsonweed

  • Angel's trumpet

  • Mandrake.

Dissociative Anesthetic Hallucinogens

• Examples:

  • PCP (Phencyclidine, known as angel dust)

  • Ketamine

• History and Traditional Use:

  • Originally employed as an anesthetic in veterinary medicine.

• Mechanism of Action:

  • Glutamate receptor antagonism, specifically targeting NMDA receptors.

• Effects:

  • Euphoria

  • Numbness

  • Slurred speech

  • Decreased coordination

  • Increased heart rate

  • Sweating

  • Blurred vision.

• Risks:

  • Higher likelihood of medical or psychiatric complications following use.

Therapeutic Use of Dissociative Anesthetics

• Ketamine:

  • Focused on treatment-resistant depression.

  • Can be effective long enough to allow traditional antidepressants to take effect (beneficial for about 50% of patients).

Salvia

• Usage History:

  • Traditional use in religious ceremonies.

• Potency:

  • Recognized as the most potent naturally occurring hallucinogen.

• Mechanism of Action:

  • Agonism at κ opioid receptors.

• Effects:

  • Induces trance states.

  • Causes sensory disturbances and impaired motor control.

  • Incidence of bad trips is also prevalent.

  • Scientific interest due to limited understanding of kappa opioid receptors.

• Legal Status:

  • Currently unscheduled federally but illegal in many states.