Chapter 15: Hallucinogens, PCP, and Ketamine Flashcards
Altered States of Consciousness (ASC) rating scale
Psychometric scale developed to quantify the subjective effects of hallucinogenic agents.
dimethyltryptamine (DMT)
Hallucinogenic drug found in several South American plants.
dissociative anesthesia
An unusual type of anesthetic state characterized by environmental detachment. It is produced by certain noncompetitive NMDA receptor antagonists such as ketamine and PCP.
flashback
Reexperience of the perceptual drug effects, specifically those of a hallucinogen, following termination of drug use; when flashbacks occur a long time after prior drug use and are intense the individual is experiencing hallucinogen persisting perception disorder (HPPD)–not common
Hallucinogen Rating Scale
Psychometric scale developed to quantify the subjective effects of hallucinogenic agents.
indoleamines
Indole derivatives containing an amine group. They include serotonin and the hallucinogens LSD, psilocybin, psilocin, DMT, and 5-MeO-DMT.
ketamine
Drug that binds to the PCP site and acts as a noncompetitive antagonist of the NMDA receptor. It is a dissociative anesthetic used in both human and veterinary medicine, and it is also used recreationally.
lysergic acid diethylamide (LSD)
Hallucinogenic drug that is synthesized from lysergic acid and based on alkaloids found in ergot fungus. It is thought to produce its effects mainly by stimulating 5-HT2A receptors in the brain.
mescal button
Crown of the peyote cactus, Lophophora williamsii, which can be dried and ingested to obtain the hallucinogenic drug mescaline; chewed or cooked raw or extracted as a pure powder.
mescaline
Hallucinogenic drug produced by several cacti species, especially that of the peyote cactus, Lophophora williamsii.
5-methoxy-dimethyltryptamine (5-MeO-DMT)
Hallucinogenic drug found in certain South American plants. Its street name is “foxy” or “foxy methoxy.”
para-chlorophenylalanine (PCPA)
Drug that irreversibly inhibits tryptophan hydroxylase, blocking 5-HT synthesis.
peyote button
Species of cactus, Lophophora williamsii, that produces mescaline.
phencyclidine (PCP)
Drug that binds to the PCP site and acts as a noncompetitive antagonist of the NMDA receptor. It is a dissociative anesthetic that was once used medicinally but is now only taken recreationally.
phenethylamine
Class of drugs that includes mescaline as well as NE- and amphetamine-related substances.
psilocin
Metabolite of psilocybin. Psilocin is the actual psychoactive agent.
psilocybin
Hallucinogenic drug found in several mushroom species; take 1-5g for effect.
psychedelic
Substance that alters perceptions, state of mind or awareness; “mind-opening”
psychedelic therapy
Therapeutic method that involved giving patients a single high dose of LSD to help them understand their problems by reaching a drug-induced spiritual state.
psychotomimetic
Substance that mimics psychosis in a subject, such as by inducing hallucinations or delusions.
salvinorin A
Active compound in the hallucinogenic plant Salvia divinorum; acts as a κ-opioid receptor agonist.
synesthesia
Mixing of sensations such that one kind of sensory stimulus creates a different kind of sensation, such as a color producing the sensation of sound.
hallucinogens
substances whose primary effect is to cause perceptual and cognitive distortions without producing a state of toxic delerium
what happens to psilocybin when ingested?
it is enzymatically converted to psilocin, which is the actual psychoactive component
ayahuasca
hallucinogenic brew from stalks and leaves containing DMT and vines containing several types of alkaloids called beta-carbolines, which are known to inhibit the enzyme MAO
synthetic DMT analogs
AMT and Foxy
how is DMT and 5-MeO-DMT taken?
it is found in a number of plans and is typically turned into a drink
is LSD natural?
no it is synthetic
analeptics
circulatory and respiratory stimulants
psycholytic therapy
based on the concept of drug-induced psycholysis–meaning psychic loosening or opening. Involved giving LSD in low but gradually increasing doses to promote the release of repressed memories and to enhance communication.
administration of LSD
orally
administration of salvia
chew fresh salvia leaves, smoke dried and crushed leaves, consume concentrated salvinorin A-containing extract either sublingually or through smoking; few if any psychoactive effects are produced by swallowing salvia but is rapidly and easily absorbed into the lungs if smoked
does salvia exert psychoactive effects if you eat it?
few if any psychoactive effects are produced by swallowing salvia; it is inactivated in the GI tract
subjective effects of saliva
- becoming objects
- visions of various two-dimensional surfaces, films, and membranes
- revisiting places from the past, especially childhood
- loss of the body and/or identity
- various sensations of motion or being pulled or twisted by forces of some kind
- overlapping realities; the perception that one is in several locations at once
Potency of hallucinogenic drugs
from most to least
- LSD (oral)
- salvia (smoking)
- psilocybin (oral)
- DMT (smoking)
- mescaline (oral)
duration of drug effects
effects generally begin within 30 to 90 minutes following ingestion. LSD and mescaline effects last between 6-12 hours or longer, with psilocybin-containing mushroom trips being a bit shorter. DMT and salvia’s effects are felt within seconds, reach a peak over minutes and are done within an hour
what can impact drug effect’s duration
the dose and when the user last ate
trip phases
- onset
- platea
- peak
- come-down
trip onset
occurs 30-60 minutes after taking LSD; visual effects occur, colors intensify and appearance of geometric patters or strange objects that can be seen when eyes are closed
trip plateau
after onset and lasts ~2 hours; sense that time begins to slow and the visual effects become more intense
trip peak
begins about after three hours and lasts for 2-3 hours; feeling like in another world where time is suspended, may experience synesthesia, continuous stream of bizarre, distorted images
trip come-down
lasts ~2 hours; most drug effects are gone after the come down but user may not feel normal until the next day
what are psychological changes that are associated with taking hallucinogenic drugs?
depersonalization, emotional shifts to euphoric, anxious, or fearful states, disruption of logical thought
physiological effects of LSD
activation of the sympathetic nervous system–pupil dilation, small increases in heart rate, blood pressure and body temperature; can also cause dizziness, nausea, vomiting
what are the two types of structures of hallucinogenic drugs?
serotonin-like (idoleamine) and catecholamine-like (phenethylamine)
serotonin-like (idoleamine) drugs
LSD, psilocybin, psilocin, DMT, 5-MeO-DMT, synthetic tryptamines
catecholamine-like (phenethylamine) drugs
mescaline
catecholamine-like (phenethylamine) structure
structure is similar to NE and amphetamine
chemical structure of salvinorin A
neoclerodane diterpene
what does LSD bind to with high affinity?
at least 8 different serotonin receptors
Common sites of interaction for both catecholamine-like (phenethylamine) and serotonin-like (idoleamine) drugs?
5-HT2a and 5-HT2c; one or both of these receptor subtypes may play a role in the subjective and behavioral effects
5-HT2a receptor activation
is the critical mechanism of action of the compounds in producing hallucinatory experiences in humans
how does salvinorin A exert effects?
has little/no effect on 5-HT receptors, but is a potent agonist at the k-opioid receptor; little is known about how it produces its hallucinogenic effects
neural mechanisms underlying hallucinogenesis
activation of 5-HT2a receptors enhances glutamate-mediated excitation of pyramidal neurons in layer V of the prefrontal cortex; this excess glutamate is being released from thalamocortical afferents which interferes with thalamic filtering of sensory information being sent to the cortex
what are hallucinogenic drugs hypothesized to interfere with?
the normal gating or screening of sensory information passing through a circuit that includes the prefrontal cortex, thalamus, and striatum
withdrawal and dependence
do not produce physical withdrawal after chronic use; are not reinforcers in animals; some evidence for dependence/tolerance in people
dependence
a hallucinogen dependence syndrome has been identified in some individuals with early exposure
tolerance
most produce rapid tolerance with repeated use; down regulation of 5HT-2a may underly tolerance;
bad trip
related to an interaction between the drug, the individual’s emotional state going into the trip, and the external environment
PCP as an anesthetic
produces an unusual anesthesia; people show no responsiveness to painful stimuli, but they are not in a typical state of relaxed unconsciousness, but instead exhibited a trance-like or catatonic-like state characterized by a vacant facial expression, fixed and staring eyes, and maintenance of muscle tone
why was PCP initially thought to be clinically promising?
because it did not produce the respiratory depression associated with barbiturate anesthesia
post operative reactions to PCP
blurred vision, dizziness, mild disorientation, hallucinations, severe agitation, violence
why did ketamine get produced?
as a safer version of PCP; is less potent and shorter acting
what can PCP and ketamine be considered?
anestetic agents
what form does PCP come in?
powdered or pill form and can be ingested throughout any common route
what form does ketamine come in?
it is marketed as an injectable liquid, but street sellers evaporate it to yield a powder that is either snorted directly or compressed into pill form
effects of subanestetic dose of PCP
feeling detached from their body, vertigo, floating, numbness, dream-like state, drowsiness, apathy, loneliness, negativism, hostility, cognitive disorganization, difficulty maintaining attention, deficiencies in abstract thinking, halting speech
effects of low doses of ketamine
results similar to those of PCP
doses of ketamine in the anesthetic range
people lose all mental contact with their environment for 10+ minutes–> dissociative anesthesia
role of NMDA for both ketamine and PCP
is the principle molecular target; noncompetative antagonists at the NMDA receptor complex; binds inside the receptor’s ion channel
NMDA
ionotropic receptor for the excitatory amino acid neurotransmitter glutamate; widely distributed in the brain (cerebral cortex, hippocampus) and play a role in glutamate signaling
noncompetative antagonists at the NMDA receptor complex
they block the receptor at a site different from the site at which glutamate or NMDA binds
what side effect does NMDA play a role in for PCP and ketamine?
cognitive deficits; increased presynaptic glutamate release within the cortex –is a secondary consequence of NMDA receptor antagonism; increased glutamate activity in the anterior cingulate cortex is associated with psychotic symptoms
are PCP and ketamine addictive?
both are very reinforcing
reinforcing effects of PCP and ketamine
both activate midbrain DA cell firing and stimulate DA release in the prefrontal cortex; however, there are both DA and non-DA mechanisms underlying reinforcing effects
can you produce dependence/tolerance for ketamine?
yes-
antitussives
medications that suppress the cough reflex
adverse effects of chronic ketamine use
urological symptoms (bladder pain, incontinence), memory deficits, delusional thinking, gray and white matter abnormalities, increased D1 receptor binding in the prefrontal cortex, which may be the result of decreased presynaptic DA transmission
adverse effects of chronic PCP use
decreased NMDA receptor binding, reduced number of symmetrical spine synapses in the prefrontal cortex, apoptotic cell death in the developing brain
effects of chronic PCP and ketamine use in monkeys
reduction in tyrosine hydroxylase immunoreactivity (used as a marker of DA axons and terminals)
