Lecture Notes on LSD

# Personality ## PSYCHEDELICS - Gen discription - CSD ## Definitional Issues - Heterogenous group of compounds which: - Can induce hallucinations - Separate individuals from reality - Can induce psychotic-like behavior - No one single term comprehensively classifies these drugs - Ha...

# Personality ## PSYCHEDELICS - Gen discription - CSD ## Definitional Issues - Heterogenous group of compounds which: - Can induce hallucinations - Separate individuals from reality - Can induce psychotic-like behavior - No one single term comprehensively classifies these drugs - Hallucinogen - appropriate because at high enough doses can induce hallucinations - Hallucinogen - not appropriate because it does not describe the range of psychological and behavioral and pharmacological effects the drugs can have - Psychotomimetic - appropriate because some of the effects resemble psychotic states - Psychotomimetic -- Not appropriate because other drugs e.g., meth more likely to produce psychotic behavior - Psychedelic - coined in 1957 Osmond, as it means the ability to alter sensory perception which I believe captures the essence of these drugs ## Types - Naturally occurring agents used for thousands of years - as most derived from plants - Ascribed magical properties (e.g., psilocybin and Aztecs, Native Americans and mescaline - Other Examples: Harmine, DMT, Myristine/Elmycin, Salvinorum A Ibotinic Acid - Psilocybin - the psychoactive ingredient in magic mushrooms - a type mushroom belonging to the genus Psilocybe - Mescaline - psychoactive ingredient in the peyote cactus - Harmine and harmaline - psychoactive substance found in the bark of a tropical vine that grows in South America; typically mixed into a drink - withdraw into a trance liked state and then visions experienced in a dream like state - used among native tribes in Western Amazon in healing rites - DMT -, N, N, Dimethyltryptamine – a compound found in a variety of insect and amphibian species, as well as in more than 50 plants - DMT can also be synthesized as a white or yellow crystalline powder to be smoked or injected; known as Dimitri on the street - DMT is the psychoactive ingredient in ayahuasca - a South American herbal brew made from a combination of plants - Myristince - found in nutmeg (1/3 tbsp for small person) - Salvia - found in the mint plant "Salvia Divinorum" - a plant indigenous in a region in Oaxaca - traditionally used for health purposes and healing purposes - Ibotinic Acid - psychoactive ingredient in the amanita muscaria mushroom – a ## Types - **Synthetic Agents** - Example: LSD, Ketamine, PCP - LSD - first synthesized in the late 1930s (1938) by Swiss chemist Albert Hoffman - Ketamine and PCP: dissociative anesthetics - PCP was developed and marketed in 1963 as an analgesic and anesthetic ## History Cont'd - Late 60s and "discovered" as agents to: - Enhance and expand reality, promote personal awareness, stimulate understanding of spiritual world - Present times: - Primarily used recreationally - Used in lower doses - Most people nowadays use psychedelics just for pleasure and not as personal growth ages or as tools to gain insight into the cosmos e.g., 1970s LSD – 100 mg Current 40 - 70 mg ## Hallucinations and Other Sensory Distortions - **Visual** - Color - colors appear brighter, more saturated - Contrast - and contrast is enhanced, with contours and edges of objects becoming more sharply defined As a result of this, enhanced contrast, objects can kinda "pop out" in your visual field and be seen as oscillating and undulating with accompanying changes in their size and number - People will report seeing tunnels, which become rotating black holes which threaten to swallow them - Size changes - Just generally objects can be perceived as smaller or larger than they are keyholes for example may seen gigantic enough to crawl thru or doors seem much too tiny to get thru or a person might seem like the are 2 inches tall but with arms that stretch up to the ceiling - Objects will also change in right in front of you so for example you might be looking at your face in a mirror and your face starts to elongate - **Auditory** - Sounds amplified, but not always clearer - for example, people's voice will be loud, but garbled - **Smell** - Is more acute – although recognition of a particular odor may be impaired e.g., someone may detect a small on someone else, such as the lingering smell of soap from a morning shower, but could not say what the smell - **Taste** - tastes difficult to decipher but can linger - **Touch** is more sensitive but also distorted - dirt and grime feels like sandpaper on hands, people may start to touch a sweater and get caught up in the valleys and ridges - **Synthesia** - where there is a fusing of the senses, colors will have sounds, sounds will have colors, sounds will have physical shapes, so for example, leaves falling to the ground sound like chimes ringing, a telephone rings or someone speaks to you and you seen bands of colours rippling thru the air ## Nature of Hallucinations - Hallucinations will occur in stages: - Stage 1: visual images (e.g., spirals, grids, geometric patterns) recognized as not being real; first seen with eyes closed than projected on surfaces when eyes opened - Stage 2: meaningful images of people, animals, places - Images can change rapidly; and changes will typically have a pattern - Now, as noted in your textbook, researchers Kluver in the 1960s and then Siegel, in the 1970, found that hallucinations, under the influence of psychedelics will occur in stages - First off, what people will see are bright lights referred to as phosphenes that will then take the form of spots or circles, or spirals or grids and lattices that are recognized as not being real - Then, the images they are seeing become more meaningful - people, animals, and places and interesting Siegel has reported a common image is numerous eyes looking at you large human eye surrounded by smaller eyes (about 30) that some will describe as leering and also found quite scary and seen with different hallucinogens - Now, the images can change quite rapidly as fast as 10 times per second and changes will typically have a pattern with each image being related to the one preceding it e.g., a series of lines will twist themselves into a spiralling tunnel - and then the mouth of the tunnel will writhe and pulse and then a snake is being seen and when it opens its mouth it disgorges a number of items like stars and snowflakes and fans and then the fans rotate and change into records on a turntable and then the records turn into tires and then the tires become a Ferris Wheel with twinkling lights and then the lights melt into a rainbow and then now you are seeing the sky and things below the sky ## Nature of Hallucinations Cont'd - Colors shift from blues to reds as drugs effects intensify - At high doses, people will get swept up into hallucination ## Biology of Hallucinations - Brain areas believed to be involved in hallucinations are - **Thalamus** - Traffic officer for incoming sensory information - Activity modulated by glutamate, GABA, dopamine, and serotonin - **Cerebral Cortex** - Primary and secondary cortex - Default Mode Network - Connected brain areas in the frontal and parietal lobes that are active when someone is not focused on outside world - Thalamus - subcortical structure that acts like a traffic officer in regards to processing and relaying incoming sensory information; does some basic processing of incoming sensory and then forwards info up to various cortical areas; visual to occipital, auditory to temporal, tactile to parietal - Activity in thalamus modulated by glutamate, GABA, dopamine, and serotonin; neurons that project from thalamus to higher centers are primarily excitatory - - **Primary sensory cortex**: does processing of sensory information, - **Secondary sensory cortex**: integrates the analyses done by primary cortex into a percept - A third area is a hypothesized neural network called the default mode network which is a group of connected brain areas in the frontal and parietal lobes that is active when someone is not focused on the outside world ## Biology of Hallucinations - Psychedelics alter neurotransmitter activity in thalamus - Changes in the overall balance between excitatory and inhibitory - Disrupted activity in thalamus leads to poor filtering of sensory information - Disrupted activity in thalamus leads to disruption in the connections to the cortical areas - Release of control on the Default Mode Network such that it becomes more active and more top-down processing of incoming sensory information - Psychedelics altering of neurotransmitter activity - Block NMDA - Agonist action at DA and 5-HT type 2A receptor - Block GABA receptors - filtering is done by nuclei in the thalamus referred to as the lateral genicular nucleus and the ventral posterior nuclear - Poor filtering occurs because of dopamine and serotonin activity - Thalamus controls critical nodes of the default mode - So rather than arriving at a percept based solely on the analysis of the sensory information, matching our percepts simply based on the physical properties of the sensory our memories and expectations drive the processing ## Biology of Hallucinations - Over and above effects on neurotransmitter activity in the thalamus, psychedelics alter neurotransmitter activity in prefrontal cortex, limbic system, temporal and parietal cortices, and brainstem - Also suppress activity of locus coeruleus; enhances response of locus coeruleus to novelty ## Biology of Hallucinations - Imaging studies have shown that - There is increased/overactivity from normal states in primary and secondary cortex - Auditory hallucinations associated with disrupted activity in middle and superior temporal lobes - Visual hallucinations associated with disrupted activity in occipital lobe - Tactile hallucinations - disrupted activity in primary somatosensory cortex and posterior parietal cortex ## LSD - **General Description:** - First use in therapy - In 60s, recreational use began - Very potent drug - Effective dose can be only 10 micrograms, with only one-hundredth of a percent being absorbed into brain ## LSD - **ADME** - Odorless, tasteless, no colour - Usually consumed orally as "hits" - Forms include: "hits" - 25 to 300 micrograms Forms include: - powderpellets aka microdots - Gelatin chips aka window panes: LSD in gelatin - Absorbent pieces of perforated paper soaked in a solution with LSD in it or liquid LSD dropped on it; paper torn into small ¼ in ch by ¼ in pieces along perforate lines and the resultant tab is placed on the tongue and sucked - Creation of blotter an art form; decorated by a variety of symbols - Typically larger dose of LSD in gelatin chips vs blotters ## LSD - **ADME Cont'd** - Rapidly absorbed into bloodstream, and distributed (most ends up in liver) - Extensively metabolized (excreted in feces and bile) - Effects can last up to 12 hours - peak effects: 90 min to 5 hours ## LSD - **Mechanism of Action** - (1) Agonist of serotonin: activates 5-HT2A receptors - (1) Suppresses activity/output of locus coeruleus (LC) - (2) Enhances response of the LC to novelty - Locus coeruleus receives input from many sensory neurons throughout the body and its neurons project to almost every area of the brain, where it promotes the release of NE - Locus coeruleus involved in fear and emotional responses and novelty detector "Seeing things for the 1*st* time" ## LSD - **Mechanism of Action** - (2) Affects activity in the medial prefrontal cortex via glutaminergic neurons - (3) Inhibits firing and release of serotonin by raphe nuclei, which may be responsible for LC suppression - Re: 2 - medial prefrontal cortex is an area that plays a role in information processing and perception - Re:2 - what it does in this area is increases the duration of activity of neurons that release glutamate, so this increases neural activity ## LSD - **Effects** - **First Phase** - Begins within 30 min - Minor physiological effects - Sensation of release of inner tension; the "ah" moment - Physiological effects; slight increase in bp, body temp, dilated pupils, possible nausea ## LSD - **Effects** - **Second Phase** - Occurs within 30 min and 2 hours - Characterized by 4 different effects - 1. Images seen with the eyes closed "closing my eyes I saw millions of colour droplets, like rain, like a shower of stars, all different colours" - 2. Synthesia "I clapped by hands and saw sound waves passing before my eyes" - Synthesia; e.g., sights experiences as sounds, sounds experienced as visual images - e.g., leaves falling to the ground may sound like chimes ringing ## LSD - **Effects** - **Second Phase** - Characterized by 4 different effects - 3. Perception of a multilevel reality "I was sitting on a chair and I could see the molecules. I could see right through things to the molecules" ## LSD - **Effects** - **Second Phase** - Characterized by 4 different effects - 4. Strange and exaggerated appearances of objects or experiences "A towel falling off the edge of my bathtub looked like a giant lizard crawling down" - Example: when my girlfriend was peeling an orange for me, it was like she was ripping a small animal apart - Objects can change before your eyes e.g., one moment your hands look normal and then the next moment they elongate reaching for the ceiling ## LSD - **Effects** - **Third Phase** - Begins within approx. hours - Characterized by: - 1. Great swings in emotions or panic ## LSD - **Effects** - **Third Phase** - Characterized by: - 2. Feeling of timelessness "Had an hour gone by since I last looked at the clock? Maybe it was a lifetime. Maybe it was no time at all” - Re: time distortion – in most cases time is perceived as slowing down e.g. 10 seconds seems like 20 but in some studies the reverse has been seen. ## LSD - **Effects** - **Third Phase** - Characterized by: - 3. Feeling of ego disintegration, or separation of one's mind from one's body ## LSD - **Effects** - **Second Phase** - Characterized by 4 different effects - 4. Strange and exaggerated appearances of objects or experiences "A towel falling off the edge of my bathtub looked like a giant lizard crawling down" - Example: when my girlfriend was peeling an orange for me, it was like she was ripping a small animal apart - Objects can change before your eyes e.g., one moment your hands look normal and then the next moment they elongate reaching for the ceiling ## LSD - **Effects** - **Other effects include:** - (1) Euphoria - (2) Development of Insight - (3) Impaired Cognition (e.g., confusion) - (4) Bizarre thoughts or feelings (e.g., can fly) - Insight into issues or emotions ## LSD - **Toxicity** - Low level of "physiological toxicity" - Harmful consequences of sensory/psychological alterations - Other consequences include: - (1) Flashbacks aka Hallucination Persisting Perception Disorder (HPPD) - There are no reports of brain damage in humans associated with high dosage use and animal studies show that the lethal dose for animals is 300 to 600X the normal recreational dose taken by humans - As noted in your text, there are no known cases of anyone dying from an overdose of LSD - HPPD is listed in the DMS-V - Now, although physiologically it is relatively benign - this is not to say that LSD is innocuous and should be freely available because the powerful sensory and psychological alterations can have harmful and disturbing consequences - Scary hallucinations can lead to panic attackes which can lead to cardiovascular trauma like heart attackes - Delusions can lead to risky, potentially harmful behaviors e.g., stopping cars with one hand, jumping out windows - LSD combined with MDMA, antipsychotics, anticholingergics (scopolamine) - potentially lethal hyperthermia - Video talked about Serotonin Syndrome - excess serotonin – headache, agitation, confusion, hallucinations, elevated bp and hr, diarrhea, shivering, sweating, hyperthermia, muscle rigidity, twitching, tremors - fatal in 10-15% ## LSD - Reexperiencing of LSD trip or spontaneous memories of a trip complete with images, sensations, and emotions - Typically only last a few seconds - Tend to occur within first few days after a trip, then decrease in frequency, eventually disappear (caveat: some reports of years after drug taken) - Triggered by darkness, stress, idiosyncratic factors - Unknown mechanism - Flashbacks: brief re-experiencings of an LSD or spontaneous memories trip complete with images, sensations and emotions - prominent view is that they are spontaneous memories of experiences of a LSD trip completed with images, sensations and emotions - Primarily visual in nature - Typically last only a few seconds - although some people have experienced ones that have last an hour or so - Tend to occur within the first few days after a trip, and then decrease in frequency and eventually disappear altogeteher - although, flashbacks have been reported years after the drug was last taken - Darkness seems to trigger them in many people i.e., will experience them just as they are about to go to sleep, although there are some idiosyncratic triggers as well, e.g, one case study reported that an individual couldn't listen to a particular Beatles record without re-experiencing the depersonalization he had felt when he has last used the drug - For another person I read about, it was flickering lights that triggered the flashbacks - Marijuana use has also been associated with flashbacks; there is a higher incidence of them in marijuana users - Mechanims for them in unknown: they are not related for example to the pharmacological ## HPPD - Re-experiencing of the perceptual disturbances causing significant distress in social, occupational and other areas of functioning - Occurs primarily after LSD use, but not exclusively - Can last for weeks, months, or years - No strong correlation between occurrence and frequency of hallucinogen use - Prevalence is approx. 4.2% - Possible genetic factors re: risk of developing - HPPD is listed in the DMS-V - In order for the flashbacks to reach level of HPPD they need to be causing significant distress in social, occupational and other areas of functioning - Occurs primarily after LSD but will also be seen with psilocybin - No strong correlation – ie the more you use doesn't mean the more likely you are to have them; they can occur with minimal use/exposure - Prevalence among people who have used hallucinogens is approx. 4.2% - Re-experiencing....visual disturbances/images are the most prominent symptoms - flashes of colour, intensification of colours - halos around objects, objects very small or very large perception of movement in the visual field ## LSD - Tolerance to both psychological and physical effects develops - Tolerance due to down regulation of 5-HT2A receptors - Disappears within approx. a week - Cross tolerance with other psychedelics - Tolerance develops within 1-3 days with daily use - Cross tolerance with psilocybin (which is structurally similar and is also a serotonin agonist - although at different receptors - Cross tolerance with mescaline - No cross tolerance with marijuana ## LSD - No physiological dependence - Some psychological dependence in some people - Re: reasons why dependency rarely seen not an easy high, hence people less likely to crave it and/or do drug for extended periods of time which is what is typically needed for dependence to develop in the words of one user - ## LSD - The LSD experience requires a monumental effort. To go through eight hours of an LSD high - sensory bombardment, psychic turmoil, emotional insecurity, alternations of despair and bliss, one exploding insight upon the heels of another, images hurting through the mind as fast as the spinning fruit of a slot machine - is draining and exhausting in the extreme.