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Chapter 12

PSYC62H3 Chapter 12: Psychedelic Drugs [Detailed Notes]

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Zachariah Campbell

Chapter 12: Psychedelic Drugs Psychedelic drugs induce a reality-altering experience consisting of hallucinations, sensory distortions, or delusions. Classified into three general categories: hallucinogens, mixed stimulant-psychedelics, and dissociative anesthetics. Hallucinogens  Hallucinogens represent a large class of psychedelic drugs that produce hallucinations as their main pharmacological effects.  The most representative of this drug class is lysergic acid diethylamide (LSD), which goes by the street name acid, window pane, and blotter. This is a schedule 1 drug.  Other hallucinogens include psilocybin, mescaline, and dimethlytryptamine.  Psilocybin is the main psychoactive constituent in hallucinogenic mushrooms belonging to the genus Psilocybe. User refers to these mushrooms as magic mushrooms or shrooms. After oral administration, psilocybin rapidly converts to its active metabolite psilocin, a hallucinogenic substance that likely account for most of psilocybin’s effects.  Mesacaline is found in peyote, a small, spineless cactus. Users obtain mescaline by chewing disk-shaped buttons within the cactus crown.  Dimethyltrypatamine (DMT) s found in Mimosa hostilis, Virola calophylla and other hallucinogenic American plants. Origins of LSD and Other Hallucinogens  In the past, hallucinogenic plants were used as psychic medicines to treat maladies, communicate with gods, and perform magic.  Albert Hofmann, a chemist who worked for Sandoz Laboratories discovered LSD’s hallucinogenic effects.  The U.S. Army tested LSD as an aid for inducing captured enemy prisoners to talk more freely and also used in chemical weaponery.  During psychoanalysis era, psychiatrists used LSD to gain access to supposedly unconscious thoughts in their patients.  Many practitioners especially feared producing prolonged bad trips, lasting as long as 48 hours. Occasionally, bad trips led to suicides. LSD Ingestion and Effects  LSD and most other hallucinogens are normally orally administered.  LSD is potent, with effective amounts beginning at only 0.025 mg. Researchers consider 0.075-0.15 mg a moderate dose range capable of achieving a significantly altered state of consciousness.  Due to potency, a common preparation method involves applying drops of a solution of LSD onto small squares of blotter paper or the glue sides of postage stamps. In either case, LSD sticks to the paper, and recreational users ingest the drug by licking the paper.  LSD reaches peak absorption after 60 minutes. The cells in the liver metabolize LSD producing 2-oxo-3- hydroxy-LSD. LSD’s elimination half-life is 3 hours, which facilitates pharmacological effects lasting as long as 8 hours. LSD and the Serotonin Neurotransmitter System  The chemical structure of LSD resembles serotonin’s chemical structure, allowing LSD to act on serotonin receptors.  LSD functions as a receptor agonist with a high binding affinity for 5-HT1A, 5-HT2A, 5-HT6, and 5-HT7 receptors. In particular, LSD activates serotonin receptors located postsynaptically on other neurotransmitter neurons, such as glutamate and GABA neurons.  In the visual cortex, LSD activates both 5-HT1A and 5-HT2A receptors. Hallucinogen activation of serotonin receptors can interfere with modal object completion, which is a perception of object boundaries inferred from incomplete representations of the object. o The N170 waveform is strongly associated with modal objet completion. These reduced N170 waveform amplitudes correlated with overall decreased activity in the occipital lobe.  Second, hallucinogens alter functioning in the locus coeruleus. In the locus coeruleus, LSD’s activation of post synaptic 5-HT2A receptors increases the activity of both glutamate and GABA neurons. LSD causes normally suppressed sensory information from the locus coeruleus to become more refined and sailent.  In the prefrontal cortex, LSD activation of 5-HT2A receptors also causes increased glutamate release. Enhanced glutamate release, in turn, increases activity in the prefrontal cortex, the central integration area of processed sensory information.  The LSD-like hallucinogen psilocybin produced a significant increase in the metabolism of labeled glucose, an index of neuronal activity in the prefrontal cortex. In addition psilocybin elicited enhanced activity in the temporomedial cortex, a region involved in complex visual processing. LSD’s Mild Physiological Effects and Profound Hallucinogenic Effects  Although few, if any, physiological effects occur with normally used amounts, LSD and other serotonin- like hallucinogens exhibit pronounced subjective experiences.  A true hallucination is a perception of images or sounds that are not real. Drugs such as LSD, alter the perception of things that are real.  Normal LSD doses cause distorted, waiving, or kaleidoscopic forms of real images in a visual field, these are called pseudo-hallucinations.  True hallucinations can occur with LSD, but they are rare.  The overall hallucinogenic experience is called a trip. o A good trip is characterized by having highly desirable sensory distortions and pseudo- hallucinations. During good trips, a use may experience feelings of enhanced perception or insightfulness, as well as synethesia (experiencing sensory stimuli in an incorrect sensory modality). For example, often consists of experiencing sounds when seeing colours and vice versa. o A bad trip is associated wit disturbing true hallucinations, psychotic episodes, negative emotional states, altered perception of time, and out-of-body sensations.  A person’s expectations and previous experiences affect LSD’s subjective effects. Factors that can affect a person’s trip can include physical surroundings, current emotional state, comments made by friends and many other factors.  It has been suggested that scepticism about LSD’s effects largely suppress the LSD experience.  LSD also causes hypersuggestibility, a state that can jeopardize reality testing. During some trips, users have jumped off buildings in belief they could fly or stepped infront of traveling cars in the belief they lacked material substance. Hallucinogens and Flashbacks  Occasionally, users may randomly experience a striking memory of the previous trip. Such an experience is referred to as a flashback or as symptom of hallucinogen persisting perception disorder. o Flashback usually refers to a short, nondistressing recurrence of a previous trip. On the other hand, hallucinogen persisting perception disorder is characterized by recurring, longer-term and unpleasant experiences that are difficult to reverse. Mixed Stimulant Psychedelic Drugs  Mixed stimulant psychedelic drugs refers to substances that exhibit both psychostimulant and hallucinations as their primary pharmacological effects.  One of these drugs is 3,4 methylenedioxyethamphetamine (MDMA, or Ecstasy). o Ecstasy can refer to any number of stimulant or psychedelic preparations that may contain only small amounts or even no amount of MDMA.  Although MDMA is best known for its psychedelic and psychostimulant effects it is also known as entactogen meaning “touching within,” or as an empathogen, referring to enhanced empathy.  MDMA shares a similar chemical structure with amphetamine and possesses many of amphetamine’s psychostimulant effects. Yet MDMA also produces LSD-like hallucinations, so it fits into the mixed psychedelic-stimulant class of drugs.  This drug class also includes AMT and 5-MeO-DIPT.  MDMA is frequently used in raves, large organized parties held in dance clubs or warehouses where electronic dance music is played with accompanying light shows. MDMA and other psychedelic drugs enhance this club experience. MDMA Therapeutic and Recreational Use  Beginning in the late 1970s, MDMA emerged as a recreational drug. People sought it for spiritual enlightenment, improving sensuality in relationships, and pure enjoyment.  MDMA-assisted improvements in patients with post-traumatic stress disorder. MDMA Metabolism and the Length of Psychedelic Drug Effects  MDMA users prefer to administer MDMA orally, usually through swallowing an MDMA-containing tablet.  After swallowing the tablet, MDMA readily absorbs through the gastrointestinal tract, reaching peak blood plasma levels after approximately 2 hours. MDMA’s elimination half-life is approximately 9 hours.  MDMA is metabolized in the liver primarily by CYP2D6 enzymes and to a lesser extent by other enzymes such as CYP1A2.  CYP1A2 converts MDMA to MDA. Like MDMA, MDA exhibits psychedelic drug effects. Its users thus experience specific MDMA effects and then, after metabolic transformation, effects elicited by MDA as well.  Deficiencies in the CYP2D6 enzyme leads to accumulation of MDMA in the body leading to prolonged drug effects and an increased probability of adverse effects occurring at low to moderate doses.  Inhibition of MDMA metabolism can occur in people with fully functional CYPD26 enzymes as well. MDMA and Serotonin and Dopamine Neurotransmission  Acute administration of MDMA alters serotonin neurotransmission at axon terminals through two mechanisms.  First, MDMA inhibits serotonin transportation into synaptic storage vesicles. In doing so, MDMA prevents serotonin storage and permits serotonin to escape into the synaptic cleft.  Second, MDMA causes the reversal of serotonin reuptake transporters. By reversing serotonin membrane transporters, MDMA expels any unstored serotonin out into the synaptic cleft.  These increased serotonin levels lead to increased activation of serotonin receptors.  Like amphetamine, MDMA produces similar actions at dopamine axon terminals, leading to enhanced extracellular levels of dopamine in the brain.  However, MDMA’s effects on dopamine axonal terminals are weaker than its effects on serotonin axonal terminals. As a result, higher MDMA doses may be necessary to enhance dopamine levels.  Chronic administration of MDMA can produce severe damage to serotonin neurons.  Heavy MDMA users have less 5-HIAA in cerebrospinal fluid, suggesting less serotonin in their nervous systems. Also, PET reveals lower levels of serotonin membrane transporters in routine MDMA users. MDMA’s Psychedelic and Psychostimulant Effects  MDMA’s physiological effects resemble those of psychostimulant drugs such as amphetamine at higher doses. o Produces increased heart rate and blood pressure.  Low MDMA elicit few physiological effects. Howev
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