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61 Cards in this Set
- Front
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Hallucinogens |
A diverse group of compounds with a wide range of effects |
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Hallucinogen Classification |
Sub-classification based on which neurotransmitter system is affected: 1. Acetylcholine agents 2. Indole Derivatives - Serotonin 3. Catechol Derivatives - Norepinephrine 4. Hallucinogenic Anesthetic - PCP |
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Acetylcholine agents (Mode of Action) |
Acetylcholine agents block AChE, preventing inactivation of AChE. This increases postsynaptic effects of AChE. |
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Acetylcholine agents (Mode of Action) |
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Acetylcholine agents: Physostigmine (Eserine) |
Comes from west African plants Crosses the blood-brain barrier and affects the CNS. Causes confusion, hallucinations, loss of reflexes, seizures, death |
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Dangers of Acetylcholine agents |
Some compounds cause irreversible inhibition of AChE. Very toxic varieties are “nerve gases,” Sarin and Soman. ACh accumulation and overstimulation of cholinergic synapses throughout the CNS and PNS lead to muscle paralysis and death by asphyxiation. |
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Acetylcholine agents: Antimuscarinics |
Muscarinic receptor antagonists that inhibit parasympathetic effects
Atropine, scopolamine, and I-hyoscyamine are alkaloids from a group of plants that includes deadly nightshade and henbane |
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Antimuscarinics: Atropine |
Used in ophthalmology to dilate pupils Reduce secretions that clog airways and counteract poisoning by cholinergic agonists |
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Antimuscarinics: Scopolamine |
Drowsiness Fatigue Dreamless sleep Euphoria Amnesia |
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Datura Species |
Psychotic delirium Disorientation Confusion Virgins under the influence made predictions that always came true |
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Pharmacological Effects of Antimuscarinics |
Dilate pupils Increase heart rate Reduce salivation Reduce sweating |
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CNS Effects of Antimuscarinics |
Mild: Drowsiness Mild euphoria Confusion Loss of control Amnesia High: Drowsiness, Euphoria Confusion Slurred speech, silly behavior, blurred vision Amnesia No potential abuse since user cannot remember the experience |
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Medeival Witches The Serpent and the Rainbow |
Witches used all three plants for poisons and ointments Ointment was put on broom and legs to create a feeling of levitation In haiti Datura called zombie's cucumber and produced zombies Initial death caused by tetrodotoxin (Lowers metabolic rate to a death like state. Looks dead but not really.) Person is buried alive then dug up Given paste made of sweet potato, corn syrup, datura Taken to a zombie farm (sugar plantation) |
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Phenethylamine Hallucinogens (Catechol Derivatives) |
Drugs that affect the norepinephrine system such as mescaline With chronic high doses, Amphetamine can produce hallucinogenic effects |
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Mescaline |
Mescaline is a catechol derivative that comes from peyote It is structurally similar to norepinephrine and amphetamine |
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Peyote |
Peyote cactus is native to the US southwest and northern Mexico
Peyote has been used for thousands of years by Native Americans for religious and healing rituals The crown of the cactus is cut off and dried to form a peyote button Peyote buttons can be eaten raw or cooked, or the mescaline can be extracted and consumed as a powder Aldous Huxley tried mescaline in 1953 and described his experienced which increased the use of hallucinogens in the 1960s |
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Mescaline |
Complete absorption with oral intake Onset: 30-90m Duration: 10h Not metabolized before excretion At low doses, effects are similar to amphetamine Effects: Hallucinations Anxiety Euphoria Static tremors No delirium, amnesia, orclouding of consciousness |
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Mescaline visuals |
Form constant - lattices, cobwebs, tunnels, spirals, patterns Complex images - landscapes, faces, familiar objects (images stored in memory) |
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Mescaline vs Amphetamine |
It is unclear why mescaline produces visuals but not amphetamine They are similar in chemical structure Seems to involve the serotonin system 5HT2a postsynaptic receptor agonist |
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MDMA |
Synthetic amphetamine Effects more similar to mescaline than amphetamines until high doses Reinforcing An entactogenic drug - main effects on introspection |
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MDMA (Mode of Action) |
Stimulates the release and inhibits the reuptake of serotonin, causing positive mood changes Also stimulates release of DA, which causes stimulant effect Positive mood changes show tolerance |
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MDMA Effects |
Effects not always predictable Most users report the experience as pleasant With repeated use, the positive effects decrease, and negative effects increase (muscle tension, insomnia, blurred vision, anxiety) |
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MDMA Health problems |
Neurotoxicity (axonal pruning) of serotonin neurons: axon endings fall off so they lose their connections Hyperthermia, which increases the neurotoxicity, and can cause malignant hyperthermia, which is life threatening - Treated with dentrolene May result in excessive fluid intake hypnatraemia - dilution of electrolytes (Na, K) Some ecstasy users have died of hyperthermia while other have died of hyponatraemia Days following ecstasy use have poor moods (Can take years to recover) |
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Persistent MDMA Induced Psychiatric Problems |
memory impairments anxiety and hostility attention deficits depression loss of interest in sex neuroendocrine abnormalities impulsivenness sleep disorders may persist 6 months to 2 years |
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Myristicin and Elemicin |
2 active ingredient in nutmeg Occasionally encountered as abused drugs when nothing else is available Large amounts brewed as tea 2-3 hour delay Euphoria and perceptual changes, but unpleasant side effects (nausea, vomiting, tremors) |
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Pharmacology of Hallucinogenic Drugs |
Most hallucinogenic drugs have either a serotonin-like or a catecholamine-like structure |
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The Serotonin like Hallucinogens (Indoleamine) |
D-lysergic acid diethyl amine (LSD) Psilocybin and psilocin (Shrooms) Ololiqui Dimethyltryptamine (DMT) More powerful emotional and sensory |
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LSD |
Lysergic acid diethylamide (LSD) is a synthetic compound based on fungal alkaloids. First synthesized in 1938 from ergot, a parasitic fungus on rye as an analeptic. Ergot is very toxic. It produces powerful contractions of the uterus that can help trigger labor and reduce post-birth uterine hemorrhage. |
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Saint Anthony's Fire |
Ergotism: Convulsive - (Muscle spasms) (Salem witch trials - grils ate rye with ergot) Gangrenous - (Burning pain, limb becomes numb, gangrene develops, severe constriction) |
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LSD in the 50s |
Thought to produce model psychosis and therefore was used by psychiatrists to sympathize with patients Later given to patients: Reduced defensiveness Allowed repressed material to surface Heightened patient suggestibility Later used recreationally and not medically |
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LSD Potency |
LSD is very potent. A single dose in crystalline form is barely visible. Several doses can be placed on the head of a pin) Larger amounts representing many doses are dissolved in water, then droplets containing single-dose units are applied to a sheet of paper |
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LSD Pharmacokinetics |
Rapidly absorbed Largest concentration in the liver, where it is metabolized Relatively small amount reach the brain Onset: 30-60m Duration: 12h |
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LSD (Mode of Action) |
LSD binds with high affinity to at least eight different serotonergic receptor subtypes. Main agonist action at 5-HT2A and 5-HT2C receptors, especially in the medial prefrontal cortex and anterior cingulate cortex. Hallucinations seem to depend on the 5HT-2a agonist effect |
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Hallucinogens (5-HT2A) |
Activation of 5-HT2A receptors seems to be the critical mechanism of action. In one study, hallucinations were blocked by 5-HT2A receptor antagonists ketanserin and risperidone, but not by haloperidol, an antagonist at D2 but not 5-HT2A receptors. |
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Physiological Effects |
Responses reflect activation of the sympathetic nervous system and include pupil dilation, small increases in heart rate, blood pressure, body temperature Dizziness, nausea, and vomiting are more likely after consumption of peyote or mushrooms |
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Psychological Effects |
Unpredictable Influenced by: 1. Personality of user 2. Expectations 3. Previous experience 4. Attitudes toward drug use 5. Motivation for using LSD 6. Setting 7. Social setting |
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Trip |
An LSD trip can be divided into four phases: 1. Onset 2. Plateau 3. Peak 4. Come-down Phases of Experience 1. Somatic phase (body high) 2. Sensory phase (visuals) 3. Psychotic phase (delusions, realizations never experienced before which can be peaceful or frightening) |
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Users Experience |
Vivid visual hallucinations Slowing of the subjective sense of time Feelings of depersonalization Strong emotional reactions Disruption of logical thought |
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Bad/Good Trip |
Good trip: spiritually enlightening Bad trip: disturbing and frightening Good/bad trip depends on the dose, the individual, and social factors One cannot predict in advance the outcome of an LSD trip. |
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LSD vs Schizophrenia Experience |
Very different LSD: -Mostly visual hallucinations -Distortions of existing environment -Pleasant or neutral -Responsive to suggestion -Large concern about interpersonal relations Schizophrenia: -Mostly auditory hallucinations superimposed on the environment -Threatening and unpleasant -Resistant to suggestion -Lack of concern about interpersonal relations |
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Mushrooms (Psilocybin) |
May be eaten raw, cooked, brewed into tea 200 times less potent than LSD Psilocybin, after ingestion, is converted to psilocin - the active hallucinogen Agonist at 5-HT1A and 5-HT2A receptors |
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Morning Glory Seeds |
1/10 as potent as LSD Intense side effects (nausea, vomiting, headache, dilated pupils, drowsiness) |
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DMT |
Dimethyltryptamine (DMT) and 5-Methoxy-Dimethyltryptamine (5-MeO-DMT) are found in several plants indigenous to South America. Native tribes make hallucinogenic snuffs from plants containing these compounds, and also a drink called ayahuasca 5-HT2A agonist |
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Bufotenin |
Indole derivative capable of producing hallucinations Found in the skin of the Bufo toad 5-HT2A and 5-HT2C agonist Fabing and Hawkins studied on humans: -Mental confusion and disorientation -Visual hallucinations -Cyanotic - deep purple -Nausea and vomiting -Mild euphoria |
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PCP and Ketamine: Background and History |
Phencyclidine (PCP) and ketamine are related compounds. PCP was developed in 1956 as an anesthetic. It did not result in respiratory depression, as with barbiturates, but it produced unusual characteristics and sometimes severe reactions. (seemed to be good anesthetic with a large therapeutic window) Clinical use stopped in 1965. |
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PCP and Ketamine (Use) |
PCP became an illicit street drug with names such as “angeldust” and “hog” Seem awake with eyes open Dissociative anesthetic Administration: oral, snorting, smoking, injection Never popular |
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PCP (Behavioral Effects) |
Low dose: drunken state, floaty euphoria, confusion, memory problems, numbing of hands and feet, incoordination Moderate dose: delusions, violent behavior, body-wide numbing, sensitivity to lights and sounds, distortions of body image (feel like you don't have limbs) High dose: Agitation, violence, unresponsiveness, delusions, hallucinations |
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PCP (Schizo Effects) |
1/3 of patient: apathy, ambivalence, inability to associate ideas, paranoia, auditory hallucinations 1. Normal people with this reaction for several hours 2. Normal people who develop psychosis for 2 weeks 3. Prior schizophrenic diagnosis, in whom PCP retriggers psychosis Cannot talk people on PCP down like with LSD |
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Ketamine |
Developed as a safer alternative to PCP, being less potent and shorter-acting Psychological reactions are less severe It is a valuable anesthetic for certain procedures, particularly in children, and is also used by veterinarians. |
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PCP and Ketamine (Mode of Action) |
PCP and ketamine are noncompetitive antagonists at NMDA receptors—ionotropic receptors for the excitatory neurotransmitter glutamate. The PCP/ketamine binding site is inside the receptor’s ion channel, separate from the site at which glutamate or NMDA binds. |
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PCP and Ketamine (Mode of Action Image) |
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PCP and Ketamine (Addiction) |
PCP and ketamine are highly reinforcing, as shown by drug self-administration, and have high abuse potential Both activate midbrain DA cell firing and stimulate DA release, particularly in the prefrontal cortex |
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PCP and Ketamine (Effects) |
Subjective effects: Detached from the body Vertigo or floating sensation Numbness Dreamlike state Affective reactions: Drowsiness Apathy Loneliness Negativism or hostility or euphoria Inebriation |
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PCP (Cognitive Effects) |
Cognitive disorganization: Difficulty in maintaining concentration Deficiencies in abstract thinking Halting speech Effects of PCP are said to be similar to symptoms of schizophrenia, presumably accounting for the waning of the drug’s popularity |
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PCP and Ketamine (Effects) |
For ketamine, low doses yield reactions similar to those of PCP. Doses in the anesthetic range produce a dissociated state with many subjective effects reported. This state is called the “K-hole,” and can be either spiritually uplifting or terrifying. PCP and ketamine have been named dissociative anesthetics. |
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DXM |
Dextromethorphan (DXM) is a common ingredient in cough syrup Noncompetitive NMDA receptor antagonist Abuse potential |
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Amanita Muscaria |
Mushroom containing muscarine, isotonic acid, and muscimol. Muscimol seems to be the main psychoactive ingredient. Muscimol is a GABA-A receptor agonist Vivid hallucinations, Macropsia (objects seem bigger (Mario)), drunkenness, agitation, limb twitching, raving Followed by several hours of partial paralysis, sleep, and dreams Muscimol is excreted and unchanged in the urine (can be reused 5 times) |
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Salvia |
Salvia is a member of the mint family native to Oaxaca, Mexico, and is historically used in religious rituals by Mazatec shamans The DEA considers Salvia to be a “drug of concern” that may soon be placed in the Schedule I category |
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Salvinorin A |
Salvinorin A is the main psychoactive ingredient The leaves can be chewed or extracts made and absorbed through the mouth or smoked. Salvinorin A is inactivated in the GI tract. Effects of Salvia have at least some similarity to the effects of LSD and other hallucinogens. |
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Salvinor A (Mode of Action) |
k-opioid receptor agonist Ineffective at the 5-HT2A receptor The most potent naturally occurring hallucinogen Intense Short duration: 1h Sensations of traveling through time and space, twisting and spinning, eyes closed: visual hallucinations of patterns and shapes |
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Salvia (Physiological Effects) |
Nausea Dizziness Incoordination Slurred speech Chills |