Psychedelics - LSD Final Exam Study Guide PDF

Learning Outcomes: Psychedelics: Overview and Definitions: Psychedelics are a diverse group of drugs capable of altering perception, cognition, and behavior. Hallucinogen: Inadequate term, as it doesn't fully capture the variety of effects. Psychotomimetic: Not the best choice, as...

Learning Outcomes: Psychedelics: Overview and Definitions: Psychedelics are a diverse group of drugs capable of altering perception, cognition, and behavior. Hallucinogen: Inadequate term, as it doesn't fully capture the variety of effects. Psychotomimetic: Not the best choice, as it inaccurately suggests these drugs cause psychosis like methamphetamine. Psychedelic: Preferred term since it accurately reflects the sensory perception alterations these drugs induce Psychedelics: Types Key Points: Naturally Occurring Psychedelics:  ○ Psilocybin: Found in magic mushrooms (genus Psilocybe). Used for thousands of years, ascribed magical properties in various cultures. Active ingredient is psilocybin, which induces hallucinations and altered states of consciousness. ○ Mescaline: Active ingredient in the peyote cactus. Used by Aztec and Native American cultures in religious rituals and healing practices. Known for its visual hallucinations and spiritual significance. ○ Harmine: Found in the bark of a tropical vine in South America. Typically brewed into a drink and used in healing rites by native tribes in the Western Amazon. Induces trance-like states and dream-like visions. ○ DMT (N, N, Dimethyltryptamine): Found in various plants, insects, and amphibians. Can be synthesized as a crystalline powder or smoked/injected. Known on the street as Dimitri. Primary psychoactive ingredient in Ayahuasca, a traditional South American herbal brew used for spiritual and healing purposes. ○ Myristicin/Elemicin: Found in nutmeg (approx. 13 tbsp for a small person). Acts as a psychoactive compound when ingested in large quantities, though it is toxic in high doses. ○ Salvinorin A: Found in Salvia divinorum, a plant native to Oaxaca, Mexico. Traditionally used for healing and spiritual rituals. Known for producing intense hallucinations and altered perceptions. ○ Ibotenic Acid: Found in Amanita muscaria mushrooms. Causes hallucinations and intense dream-like states. Synthetic Psychedelics: LSD (Lysergic acid diethylamide): ○ First synthesized in the late 1930s by chemist Albert Hoffman. ○ Powerful hallucinogen that induces altered perceptions, visual hallucinations, and distorted reality. ○ Has been widely used both recreationally and in experimental psychological settings. Ketamine & PCP (Phencyclidine) : ○ A dissociative anesthetic developed in the 1960s.  ○ Known for producing a dissociative state where users may feel detached from their body and environment. ○ Developed in 1963 as an analgesic and anesthetic. ○ Known for its dissociative and hallucinatory effects. ○ Can induce aggressive behavior and psychotic states Psychedelics: History Key Points: Late 1960s to 1970s: ○ Psychedelics were celebrated as tools to enhance and expand reality. ○ Users sought personal awareness, spiritual insight, and understanding of the supernatural. Example: One LSD user described the drug as a way to connect with the spiritual world and explore the cosmos. ○ Commonly used in higher doses during this time: Typical LSD dose in the 1970s: ~100 micrograms (μg). Present Use: ○ Psychedelics are now primarily used recreationally, often in lower doses: Current LSD doses range from 40–70 μg. ○ Focus has shifted from personal growth and spiritual exploration to pleasure and recreational use. ○ The cultural perception has also evolved, with less emphasis on their mystical properties and more on their entertainment value Psychedelics: Hallucinations Key Points: Visual Distortions: ○ Enhanced Perception: Colors appear brighter and more vivid. Contrast is enhanced, making objects "pop" in the visual field. ○ Oscillations and Undulations: Objects may appear to move, oscillate, or undulate. Changes in size and number are common (e.g., a single object may appear as multiple). ○ Size Alterations: Objects can seem smaller or larger (e.g., a keyhole may appear large enough to crawl through). ○ Transformation of Objects: Objects may morph in real-time (e.g., your reflection elongates). Small/light objects are more likely to move or mold compared to large, heavy ones.  Auditory Distortions: ○ Amplified Sounds: Sounds become louder but not necessarily clearer (e.g., voices may be loud but garbled). Smell Distortions: ○ Increased Sensitivity: Smells are more acute, but recognition may be impaired. Example: A lingering smell (e.g., soap) might be noticed but not identified. Taste Distortions: ○ Lingering Taste: Flavors may linger longer than usual but are often difficult to decipher. Touch Distortions: ○ Increased Sensitivity: Touch becomes more sensitive but also distorted. Example: Dirt and grime might feel like sandpaper. ○ Immersive Tactile Experiences: Users may become engrossed in sensations, such as the texture of a sweater. Synaesthesia (Fusion of Senses): ○ Cross-Sensory Experiences: Colors may produce sounds, and sounds may have colors or physical shapes. Examples: Falling leaves may sound like chimes ringing. A telephone ringing may create bands of color radiating from the object Stages of Hallucinations: 1. Stage 1: Simple Visual Patterns ("Phosphenes"): ○ Description: Users see geometric patterns such as spirals, grids, and repeating shapes. These are first visible with eyes closed, then appear projected onto surfaces when eyes are opened. ○ Cognition: Users generally recognize these patterns as not real. ○ Term: These visual effects are referred to as phosphenes. 2. Stage 2: Meaningful Images: ○ Description: Hallucinations transition to complex and meaningful images of people, animals, or places. These images often change rapidly but follow a distinct pattern. ○ Common Images:  Eyes are frequently reported, such as a large human eye surrounded by smaller, leering eyes. This particular image is often described as unsettling or frightening and has been observed with various hallucinogens. ○ Characteristics: Images appear dynamic, shifting as the drug’s effects intensify. ***High-Dose Effects: ○ Immersive Hallucinations: At higher doses, individuals may become fully absorbed into the hallucination, losing touch with their surroundings. ○ Color Shifts: Colors evolve from blues to reds as the drug's effects intensify. Psychedelics: Biology of Hallucinations Key Brain Areas and Functions: 1. Thalamus: ○ Role: Acts as a traffic officer for incoming sensory information. Routes sensory input: Visual to occipital lobe. Auditory to temporal lobe. Tactile to parietal lobe. ○ Neurotransmitters Involved: Excitatory: Glutamate, dopamine, serotonin (5-HT2A). Inhibitory: GABA. ○ Effects of Psychedelics: Alter neurotransmitter balance, leading to poor filtering of sensory input. Disrupted connections between the thalamus and cortical areas result in abnormal sensory perception. 2. Cerebral Cortex: ○ Primary and Secondary Sensory Cortices: Process and integrate sensory input to form a percept. Increased activity in these areas during hallucinations. ○ Frontal and Parietal Cortices (Default Mode Network): Active when not focused on the outside world. Psychedelics release control of the default mode network, allowing top-down processing where expectations and memories drive sensory interpretation. 3. Other Key Areas: ○ Prefrontal Cortex: Involved in decision-making and perception.  ○ Limbic System: Regulates emotion, contributing to the emotional intensity of hallucinations. ○ Temporal Lobe: Disrupted activity here is linked to auditory hallucinations. ○ Occipital Lobe: Disruption leads to visual hallucinations. ○ Posterior Parietal Cortex: Associated with tactile hallucinations. Neurotransmitter Effects: Key Neurotransmitters: ○ Glutamate: Blocking NMDA receptors increases delta wave activity in the thalamus, slowing its function. ○ Serotonin (5-HT): Agonist action at 5-HT2A receptors disrupts sensory filtering. ○ Dopamine (DA): Contributes to poor sensory filtering. ○ GABA: Blocking GABA increases excitatory input, amplifying sensory disruptions. Locus Coeruleus: ○ Activity is suppressed but becomes more responsive to novel stimuli, heightening sensitivity to new experiences. Imaging and Effects on Brain Activity: Increased/Overactivity: ○ Observed in primary and secondary sensory cortices during hallucinations. Specific Sensory Hallucinations: ○ Auditory: Disrupted activity in middle and superior temporal lobes. ○ Visual: Linked to occipital lobe overactivity. ○ Tactile: Associated with dysfunction in the primary somatosensory cortex and posterior parietal cortex Psychedelics: LSD History: ○ Initially used in therapy. ○ Recreational use became popular in the 1960s. Potency: ○ Extremely potent; effective dose as low as 10 micrograms (μg). ○ Only 1/100th of a percent of the dose reaches the brain (compared to a typical 325 mg aspirin dose). Characteristics:  ○ Odorless, tasteless, and colorless. ○ Typically consumed in doses of 25–300 μg. LSD Methods of Administration: 1. Blotter Paper: ○ Absorbent perforated paper soaked with LSD solution. ○ Tabs (~1/4 inch) are torn along perforations, placed on the tongue, and sucked. ○ Often decorated with symbols or artwork as part of blotter art. 2. Gelatin Chips ("Window Panes"): ○ LSD suspended in gelatin, cut into small chips. ○ Contain higher doses of LSD compared to blotters. 3. Powdered Pellets ("Microdots"): ○ Small, solid, pill-like forms of LSD. 4. Liquid LSD: ○ LSD solution dropped directly onto blotter paper or taken orally. Pharmacokinetics: Absorption: ○ LSD is rapidly absorbed into the bloodstream when taken orally. Distribution: ○ Most of the drug is distributed to the liver, where it is metabolized. ○ Only ~1% of the dose reaches the brain. Metabolism: ○ Extensively metabolized in the liver; excreted through feces and bile. Duration of Effects: ○ Total duration: Up to 12 hours. ○ Peak effects occur within 90 minutes to 5 hours Psychedelics: LSD Mechanism of Action Key Points: Primary Mechanism: ○ LSD acts as a serotonin agonist, specifically targeting 5-HT2A receptors. ○ This activation causes widespread changes in brain activity and sensory processing. Effects on Brain Areas: 1. Locus Coeruleus (LC): ○ Role: Central to fear, emotional responses, and a novelty detector.  Receives sensory input from across the body and projects to nearly every brain region, promoting the release of norepinephrine (NE). ○ Effects of LSD: Suppresses LC output, reducing its baseline activity. Enhances LC's sensitivity to novel stimuli, amplifying responses to new sensory input. 2. Medial Prefrontal Cortex (mPFC): ○ Role: Critical for decision-making and cognitive integration. ○ Effects of LSD: Increases duration of activity in neurons releasing glutamate, boosting overall neural activity. Plays a role in the intensification of sensory and emotional experiences. 3. Raphe Nuclei: ○ Role: Primary source of serotonin in the brain. ○ Effects of LSD: LSD inhibits serotonin release from the raphe nuclei, contributing to suppression of LC activity. Neurochemical Effects: 5-HT2A Receptor Activation: ○ Causes altered sensory perception, hallucinations, and changes in emotional processing. Glutamate Release: ○ Increased glutaminergic activity in the mPFC enhances neural signaling and the subjective intensity of sensory and emotional input. Suppression of Serotonin: ○ Inhibition of serotonin output by the raphe nuclei reduces filtering of sensory information, contributing to hallucinatory effects Psychedelics: LSD Effects Key Points: LSD effects occur in three distinct phases, each with unique physiological, sensory, and psychological changes. 1st Phase: Initial Effects (0–30 minutes) Minor Physiological Effects: ○ Increased blood pressure (BP) and body temperature.  ○ Dilated pupils. ○ Possible nausea. Psychological Effect: ○ A sensation of release of inner tension, often described as an “ah” moment of relaxation or revelation 2nd Phase: Sensory and Perceptual Effects (30 minutes–2 hours) Characterized by four key effects: 1. Closed-Eye Visuals: ○ Vivid images with eyes closed, such as: Millions of stars, rainbow rain, or intricate patterns. 2. Synaesthesia: ○ Blending of senses: Sounds experienced as visual images (e.g., seeing sound waves). Visual stimuli perceived as sounds. Example: Clapping hands and "seeing" the sound waves. 3. Multilevel Reality Perception: ○ Sensation of perceiving reality at multiple levels, e.g., seeing through molecules or layers of existence. 4. Strange and Exaggerated Perceptions: ○ Objects appear distorted or transform: Example: A towel falling may resemble a giant lizard crawling down. ○ Perceived movement and morphing of objects. 3rd Phase: Emotional and Cognitive Effects (3–5 hours) Emotional Swings: ○ Intense shifts in mood, ranging from euphoria to fear. Time Distortions: ○ Time feels slowed (e.g., 10 seconds seems like 20). ○ Some studies report time speeding up instead. Ego Disintegration: ○ Feeling of separation between mind and body. ○ Loss of self-identity or dissolution of the ego. Other Effects: ○ Euphoria and development of insight into personal issues or emotions. ○ Impaired cognition, bizarre thoughts, and delusions (e.g., belief in the ability to fly). Psychedelics: LSD Toxicity Key Points:  1. Physiological Toxicity: ○ Low toxicity: LSD has a low risk of physiological harm. ○ Lethal Dose: Animal studies suggest the lethal dose is 300–600x the recreational dose, with no reported human fatalities from LSD overdose. ○ No Brain Damage: Studies show no evidence of brain damage in humans, even at high doses. 2. Harmful Consequences of Sensory/Psychological Alterations: ○ Panic Attacks: Scary hallucinations can lead to panic attacks, potentially causing cardiovascular trauma (e.g., heart attacks). ○ Delusions and Risky Behavior: Delusional thinking may result in dangerous actions, such as trying to stop cars with one hand or jumping out of windows. 3. Hallucinogen Persisting Perception Disorder (HPPD): ○ Definition: Persistent sensory disturbances (e.g., re-experiencing visual patterns, sensations, and emotions from a previous trip). ○ Flashbacks: Triggers: Commonly occur in darkness, e.g., before sleep, or with idiosyncratic triggers like marijuana use. Duration: Flashbacks typically last a few seconds to an hour, decrease over time, but can occasionally persist for years. ○ Prevalence: HPPD affects ~4.2% of users. Can occur after LSD, psilocybin, and other psychedelics. ○ Impact: Causes significant distress in social, occupational, and other areas of functioning. ○ DSM-V Criteria: Flashbacks must cause significant distress to be classified as HPPD. 4. Potentially Fatal Drug Interactions: ○ LSD + Other Substances: Combining LSD with MDMA, antipsychotics, or anticholinergics (e.g., scopolamine) can lead to potentially lethal hyperthermia. ○ Serotonin Syndrome: Excess serotonin due to LSD or drug interactions can cause: Symptoms: Headache, confusion, hallucinations, elevated BP/HR, sweating, muscle rigidity, and hyperthermia. Fatality Rate: ~10–15% if untreated Psychedelics: LSD Tolerance and Dependence Key Points: 1. Tolerance: ○ Development:  Tolerance develops to both psychological and physical effects. Onset occurs within 1–3 days of daily use. ○ Mechanism: Caused by downregulation of 5-HT2A receptors (reduced receptor activity due to overstimulation). ○ Reversibility: Tolerance disappears approximately 1 week after stopping use. ○ Cross-Tolerance: Develops with other psychedelics like: Psilocybin (structurally similar serotonin agonist). Mescaline (similar pharmacological effects). No cross-tolerance with marijuana. 2. Dependence: ○ Physiological Dependence: Does not occur because LSD does not create withdrawal symptoms or alter homeostasis in the body. ○ Psychological Dependence: Rare, but possible in some individuals. Reasons why dependence is uncommon: 1. LSD does not provide an easy high or strong physical euphoria. 2. A full 8–12 hour trip is described as draining, deterring frequent or prolonged use. 3. Craving and repeated use, which are typical for dependence, are less likely with LSD