Comprehensive Study Guide on Hallucinogens: Psychedelics, Dissociatives, and Deliriants

Page 1: Overview and Classification of Hallucinogens The Hallucinogens represent a diverse group of substances with varying properties. They are alternately known by several terms including psychedelic, psychotomimetic, psychodysleptic, and psycholytic. While defined as hallucination-producing, it is noted that they may not produce true hallucinations in all instances. Historically and currently, they are much studied for their psychotherapeutic value. ## Characteristics of Hallucinogenic Drugs (Hollister, 1994) - Primary Effect: Changes in thought, perception, and mood. - Cognitive Effects: Minimal (such as memory impairment). - Nervous System Activity: Not characterized by excessive stimulation or lowered activity such as stupor or narcosis. - Autonomic Nervous System (ANS) Side Effects: Minimal, though some sympathetic activity may occur. - Dependence: No physical dependence. - Addiction: Minimal addictive craving. ## Classification by Neurotransmitter System - Serotonin: $LSD$, psilocybin, lysergic acid amide ($LAA$), and $DMT$. - Norepinephrine: Mescaline, $DOM$ ($STP$), and $MDMA$ (Ecstasy). - Acetylcholine: Atropine, ibotenic acid, scopolamine, and hyoscyamine. - Glutamate: $PCP$ and ketamine. ## Classification by Effect Produced ### Psychedelics (Classic Hallucinogens) - These are perception-altering substances. - Examples: $LSD$, Psilocybin, and Mescaline. - Mechanism: Primarily Serotonergic; typically acting as an agonist. - Etymology: Humphrey Osmond coined the term Psychedelic, meaning Mind manifesting, from the Greek psyche (mind) and delos (manifesting). These are conscious-altering substances. ### Dissociatives - These produce analgesia, amnesia, and catalepsy (a trance state), along with a sense of detachment from the surrounding environment. - Examples: Ketamine, $PCP$, and Nitrous Oxide. - Mechanism: Primarily Antiglutamatergics (Glutamate Antagonists). ### Deliriants - These produce delirium, characterized by extreme confusion and an inability to control one's actions. - Examples: Atropa belladonna (deadly nightshade) and Datura stramonium. - Mechanism: Primarily Anticholinergics (Acetylcholine Antagonists). # Page 2: LSD Origins and Historical Context Certain hallucinogens are noted for providing insight, understanding, awareness, and new perspectives, including Psilocybin, Harmine, Mescaline, and Cannabis. ## Lysergic Acid Diethylamide (LSD) $LSD$ is a synthetic chemical derived from ergot, a parasitic fungus that grows on grains. Ergot itself is highly toxic and causes ergotism, also known as St. Anthony’s Fire. Symptoms of ergotism include a reduction in blood flow to extremities, a tingling sensation on the skin, convulsions, disordered thinking, and hallucinations. ### Historical Case Study: The Salem Witchcraft Trials ($1692$ - $1693$) The trials began when two girls showed extreme symptoms including fits, convulsions, and strange utterances. They accused Tituba, a West Indian slave. As accusations spread, the trials resulted in the execution of $20$ people. A possible cause identified is ergot poisoning, as rye bread was the main crop and weather conditions were ideal for fungus infection. ## The Modern History of LSD - Albert Hofmann: A chemist studying lysergic acid for medicinal value. In $1938$, he created $LSD-25$ (the $25^{th}$ variation). In $1943$, he accidentally came into contact with the substance. By $1953$, Sandoz held the patent. - Humphrey Osmond: A psychiatrist interested in the drug. - Aldous Huxley: Writer and author of The Doors of Perception. - Dr. Timothy Leary: A Clinical Psychologist at Harvard University who performed self-research. He became an advocate for the Acid Generation and coined the phrase Turn on, Tune In, Drop Out. He was later arrested for marijuana possession, became a software executive, and died in $1997$. # Page 3: LSD Acute Effects and MDMA Overview ## LSD Acute Effects $LSD$ is perhaps the most powerful psychoactive drug. It is rapidly absorbed and considered quite safe in terms of biological toxicity. It is typically sold in powder pellets or as a liquid on blotter paper. - Acute Physical Effects: Minor sympathetic nervous system activity. - Psychological Effects: Emotional changes and hallucinations, including the psychedelic trip and synesthesia. - Experience: Characterized by extreme variability; an $8$ hour draining experience. - Pharmacology: Acts as both a serotonergic agonist and antagonist. - Adverse Effects: No evidence of long-term toxicity, chromosomal damage, or violent behavior. It does not produce long-term psychosis. - Risks: High potential for a bad trip involving paranoia, mood swings, and time dilation. - Flashbacks: Disturbed perceptions or distorted sensory experiences that can last minutes to years. This may be the basis for Hallucinogen Persisting Perception Disorder ($HPPD$). - Dependence: The risk is quite low. ## MDMA (Methylenedioxymethamphetamine) Known as Ecstasy, $XTC$, or Essence, it is the second most used illicit drug. - Origin: Developed and patented by Merck in $1912$. - Chemical Structure: Similar to epinephrine, causing sympathetic nervous system activity. - History: Used in psychotherapy in the $1970s$. Re-classified as a Schedule $I$ drug in $1985$. Street use peaked in the $1990s$ to $2000s$. - Physical Effects: Strong stimulant properties with low toxicity. - Physical Risks: Hypertension, dehydration, and hyperthermia. Fatal complications are due to stimulant effects rather than hallucinogenic ones. # Page 4: MDMA Systems and Therapeutic Applications ## Neurotransmitter Effects of MDMA $MDMA$ affects three major systems: 1. Norepinephrine: Acts as a re-uptake inhibitor. Causes stimulant effects, increases heart rate and blood pressure, increases blood vessel constriction, and metabolic heat generation (risk of hyperthermia). 2. Dopamine: Acts as a re-uptake inhibitor. Increases energy and activity; stimulates the reward pathway. 3. Serotonin: Acts as a re-uptake inhibitor and direct serotonin releaser. Alters mood, appetite, and sleep. - Oxytocin: Triggered by serotonin release, leading to increased sexual arousal, trust, emotional closeness, social bonding, and empathy. - Brain Chemistry: Impairs the transporter mechanism for reuptake; it is unclear if this is temporary or permanent. ## Psychological and Therapeutic Effects - Effects: Enhanced tactile sensations, mood, cognitive insights, perceptual distortions, heightened self-awareness, and empathy. - Clinical Uses: Since the $1970s$ - $1980s$, it has been proposed for trauma victims ($PTSD$), individuals facing impending death, and conditions like anxiety and depression. - Ongoing Research: $MAPS$ clinical trials started in $2008$. Currently in Phase $III$ of clinical trials. The goal is $FDA$ approval for $PTSD$ treatment by $2022$. # Page 5: Other Serotonergic and Dissociative Hallucinogens ## Mescaline and DOM - Mescaline: Derived from the peyote plant; used for over $3000$ years in Mexico. Can produce severe GI disruptions. Active ingredient isolated in $1897$ and synthesized in $1919$. - DOM: A synthetic derived from mescaline ($1963$). Often used with $LSD$. Street name: $STP$ (Serenity, Tranquility, Peace). Perceptual effects include blurred vision, multiple images, distorted shapes, and slowed time. Reputation for bad trips lasting $7$ to $8$ hours, or up to $14$ to $20$ hours. Moderately more sensual than $LSD$. ## Psilocybin - Produced in over $200$ mushroom species (magic mushrooms). - History: Earliest use in Northern Africa in $9000BC$. Identified in $Psilocybe Mexicana$ in $1959$. - Effects: $4$ to $5$ hour trip, less potent than $LSD$. - Regulatory Status: Research was banned from the $1970s$ to $2018$. In $2019$, the $FDA$ provided breakthrough therapy status for depression. Trials cover depression, Lyme disease, nicotine and opioid addiction, $PTSD$, and alcohol dependency. ## Other Classical Hallucinogens - Lysergic Acid Amide (LAA): Found in Morning Glory seeds; potency is $rac{1}{10}$ to $rac{1}{30}$ of $LSD$. Lasts $6$ to $10$ hours. - Dimethyltryptamine (DMT): Found in tree bark and nuts; usually inhaled or smoked. Known as the businessperson’s LSD due to effects lasting only minutes. - Harmine: From the bark of the Banisteriopsis vine in South America. Induces strong trances lasting $1$ to $2$ hours. # Page 6: Dissociatives and Ibogaine ## Dissociative Mechanisms Dissociatives produce feelings of detachment from the world, environment, and self. - Pharmacology: Glutamate antagonists typically affecting $NMDA$ receptors. - Main Effects: Dissociation, hallucinogenic effects, and euphoria. - Psychological states: Dissociation (detachment from world), Depersonalization (detachment from body/thoughts), and Derealization (feeling the world is not real). ## PCP and Ketamine - Phencyclidine (PCP): Also known as Angel Dust. Developed as a surgical anesthetic. Reclassified to Schedule $1$. Can be taken orally, $IV$, inhaled, or smoked. Effects are unpredictable and can include mania, paranoia, depression, anxiety, psychosis, and hallucinations lasting up to two weeks. - Ketamine: Also known as Special K. Developed in $1952$ as an anesthetic for humans and animals. Current Schedule $3$ for chronic pain. In $2019$, the $FDA$ approved Spravato (s-enantiomer) for depression. ## Ibogaine - Derived from the African shrub Tabernanthe iboga. First extracted in $1901$. - Effects: Mild stimulant effects, promotes empathy. The timeframe is $24$ to $48$ hours (exhausting). - Pharmacology: Structurally related to serotonin but affects many pathways. - Anti-addiction: Alleviates opioid withdrawal symptoms and eliminates future cravings. Studied for treating cocaine, alcohol, and nicotine addiction. Clinical trials exist in Europe and Canada, with clinics in Mexico, Brazil, and the Caribbean, but not in the $US$. # Page 7: Deliriants and Anticholinergic Effects ## Specific Deliriants - Atropine and Benadryl. - Amanita muscaria: Contains ibotenic acid. Found in the Northern Hemisphere and Central America. Known as Nectar of the Gods; used by Berserkers. - Henbane: From the Anglo-Saxon hennbana (killer of hens). Also called Stinking nightshade. Used to flavor German pilsners until $1516$. - Datura: Known as Jimson weed, Hell’s Bells, Devil’s weed, Angel’s trumpet, or Devil’s Trumpet. Source of scopolamine. Can cause psychosis and temporary blindness for up to two weeks. - Atropa belladonna: Known as deadly nightshade, banewort, or naughty man’s cherries. Source of Atropine. Native to Europe and North Africa. Produces living dreams and potential delirium. ## Clinical Condition: Delirium Delirium is an Acute Confusional State characterized by serious disturbances in mental abilities, confused thinking, reduced attention/awareness, and consciousness disruptions. ## Anticholinergic (ACh Antagonists) Characteristics These principally affect Muscarinic $ACh$ Receptor sites. - Cognitive Effects: Delirium, drowsiness, confusion, temporary memory loss, restlessness, convulsions, psychosis, and vivid/unpleasant hallucinations. - Physical Effects: Low blood pressure, heart rhythm disturbances, hyperthermia, dry mouth and eyes, blurred vision, temporary blindness, and constipation. - User Experience: Generally unpleasant and unlikely to be repeated.