hallucinogens Flashcards
what is the primary effect of hallucinogens
altered state of consciousness
what are some common effects of hallucinogens
distortions of perception, hallucinations, feelings of ecstasy, dissolution of self boundaries, feelings of unity with the world
what are some alternative names for hallucinogens
psychedelics, psychotomimetics, entheogens
what are some examples of classic hallucinogens
psilocybin, mescaline, LSD
what type of receptors do classical hallucinogens primarily act on
serotonin, especially 5-HT2A receptors
what plant does psilocybin come from
magic mushrooms
what plant does mescaline come from
peyote cactus
what are some examples of dissociative anaesthetics
phencyclidine and ketamine
what effect do dissociative anaesthetics have at higher dose
anaesthesia - loss of all sensation
what effects do dissociative anaesthetics have at lower doses
altered states of consciousness, including disconnection from environment and out of body experiences
what type of receptors do dissociative anaesthetics primarily act on
NMDA receptors
what rating scale is used to compare these drugs
five dimensional altered states of consciousness - 5DASC rating scale
what are the five primary dimensions measured by the 5DASC rating scale
oceanic boundlessness, anxious ego-disintegration, visionary restructuralisation, impaired control and cognition, vivid imagery
what does oceanic boundlessness refer to
positively experienced loss of ego boundaries
what does anxious ego-disintegration refer to
thought disorder and loss of self-control
what does visionary restructuralisation refer to
perceptual alterations and altered meaning on percepts
what does impaired control and cognition refer to
difficulties with thinking and decision making
what does vivid imagery refer to
intense and lifelike mental images
what are the two main factors that influence subjective experience of hallucinogenic drugs
set and setting
how predictable are the psychopharmacological actions of hallucinogenic drugs compared to other drugs
less predictable
what does set refer to in the context of hallucinogenic experiences
the user’s expectations, mindset and beliefs
how do expectations influence the effects of hallucinogenic drugs
expectations can shape the type of experience, such as increasing the probability of religious or spiritual experiences
what does setting refer to in the context of hallucinogenic experiences
the environment in which the drug is taken
how does the environment influence the effects of hallucinogenic drugs
the environment can shape the type of experience such as increasing the probability of religious or spiritual experiences
can an individuals response to the same drug vary
yes
what factors contribute to the variability in responses to the drugs
the personality of the drug taker - set and setting
who described the LSD as ‘a powerful unspecific amplifier or catalyst of biochemical and physiological processes in the brain
stanislov grof 1972
who stated that the phenomena induced by LSD cannot be predicted or understood in purely pharmacological terms
barr et al 1972
how long have hallucinogens been used
for millennia
what was the common context for the use of natural hallucinogens in ancient times
rituals
who often controlled the use of hallucinogens in these rituals
suitably experienced people
when did plant-derived hallucinogens and LSD enter mainstream culture in north america and europe
first half of the 20th century
who was a prominent figure in the popularisation of LSD in 1960s
timothy leary
when was PCP developed and for what purpose
mid 1950s as an anaesthetic
when was ketamine synthesised and why
1962 - a safer alternative to PCP
in what situations is ketamine still used as an anaesthetic to humans
when anaesthesia infrastructure and support are limited and in children
is ketamine used as an anaesthetic in animals
yes
what led to the illegality of classical hallucinogens
their association with the 1960s counterculture
who isolated and identified mescaline
heffter 1897
who synthesised LSD
Hoffman 1938
when was the first LSD study in humans conducted
1947
who discovered the psychoactive effects of LSD
Savage 1952
who synthesises ketamine
domino 1962
when was ketamine approved as a depression treatment in the US
2019
what is MDMA
an amphetamine with strong effects on serotonin transmission
what are the stimulant properties of MDMA
increased alertness and energy
what are the main types of effects produced by MDMA
stimulant hallucinogen like effects
what are the hallucinogen-like properties of MDMA
increased sociability, talkativeness, altered state of consciousness with emotional and sensual overtones
how does MDMA compare to marijuana and psilocybin in terms of effects
similar effects, but psilocybin has a hallucinatory component that MDMA lacks
what unique pattern of effects distinguishes MDMA from hallucinogens and stimulants
high oceanic boundlessness, low visionary restructuralisation, and low dread of ego dissolution
how does the alteration of consciousness produced by MDMA compare to that produced by LSD
its weaker
what therapeutic use has been suggested by MDMA
psychotherapy, particularly for PTSD
what are some risks associated with MDMA use
use in the rave scene and ecstasy- related deaths
what neurotransmitters are associated with MDMAs effects
serotonin and noradrenaline
what percentage of 16-59 year olds reported using LSD in the crime survey 2017/18
0.4%
what percentage of 16-59 year olds reported using magic mushrooms in the crime survey 2017/18
0.4%
What percentage of 16-59 year olds reported using ketamine in the Crime Survey for England and Wales 2017/18?
0.8%
What age groups are compared for ecstasy use in the Crime Survey for England and Wales 2017/18?
16-29 and 18-24
what type of harm do classical hallucinogens generally cause
virtually no physical harm or dependence
what potential distress can classical hallucinogens cause
potential distress caused by subjective experiences depening on set and setting
what is a risk for individuals with mental health problems who use hallucinogens
increased risk of adverse effects
what are some potential harms associated with ecstasy and dissociative anaesthetics
dependence and potential neurodegeneration
approximately how many ecstasy related deaths were reported in england, wales and scotland in 2017
130
what factors may contribute to ecstasy related deaths
overheating and dehydration
how are drugs classified under the UK misuse of drugs act and what do they determine
into three classes, A B and C based on harm
- penalties for offenses such as supply, production and possession
how many schedules regulated the clinical use of controlled substances in the UK
5
what are the two main classes of classical hallucinogens
indoleamine and phenethylamine
what is the primary neurotransmitter system affected by classical hallucinogens
serotonin receptors
what are some examples of indoleamine hallucinogens
psilocybin, LSD, DMT, 5-MeO-DMT
what are some examples of phenethylamine hallucinogens
mescaline, amphetamine derivatives
what chemical group is often present in phenethylamine hallucinogens and may contribute to their effects
methoxy groups
what types of serotonin receptors do classical hallucinogens act on
5-HT receptors, especially 5-HTA and 5-HT2C subtypes
which serotonin receptor subtype is considered critical for the main psychological effects of classical hallucinogens
5-HT2A receptors
what is the primary neuropharmacological mechanism of classical hallucinogens
stimulation of 5-HT receptors
what type of receptors are 5-HT2A receptors
G protein coupled receptors
where are serotonergic raphe nuclei located
in the midbrain
what parts of the brain do serotonergic raphe nuclei innervate
large parts of the brain, including cortical and subcortical forebrain regions
what is the main effect of 5-HT2A receptor activation on neurons
it has stimulatory effects
what are specific effects of 5-HT2A receptor activation
increased transmitter release and increased activity
what type of neurons may 5-HT2A receptor activation stimulate
excitatory neurons
what brain region is suggested to be important for hallucinogenic effects through 5-HT2A receptor activation
the prefrontal cortex
what happens to the subjective effects of psilocybin and LSD when 5-HT2A receptors are blocked
they are significantly reduced
what drug is used to block 5-ht2a receptors
ketanserin
what happens to the subjective effects of psilocybin and LSD when dopamine D2 receptors are blocked
they are less affected compared to 5-HT2A blockade
what drugs are used to block dopamine D2 receptors
risperidone and haloperidol
what happens to the behavioural effects of classical hallucinogens in animal studies when 5-HT2A receptors are blocked
they are blocked
what neurotransmitter release is stimulated by MDMA
serotonin
how does MDMA likely stimulate serotonin release
through interaction with the 5HT transporter
what type of serotonin receptors mediate some of MDMAs subjective effects
5HT2A receptors
what other neurotransmitter release is stimulated by MDMA
dopamine
what brain region is involved in the dopamine release stimulated by MDMA
the nucleus accumbens
what effects of MDMA are thought to be contributed to by dopamine release
stimulant and reward/reinforcing properties
what are two examples of dissociative anaesthetics
phencyclidine and ketamine
what is the primary neuropharmacological mechanism of dissociative anaesthetics
blockade of channel pore of the NMDA type glutamate receptor
what type of antagonist are dissociative anaesthetics at the NMDA receptor
non competitive antagonist
how does NMDA receptor blockade increase neural excitation
by reducing the activity of inhibitory neurons
what role does disinhibition play in the psychological effects of dissociative anaesthetics
its a key factor
what neurotransmitter release is stimulated by NMDA receptor antagonist
dopamine
what brain regions are involved in the dopamine release stimulated by NMDA receptor antagonists
prefrontal cortex and nucleus accumbens
how might dopamine release be mediated
by increased neural excitation in cortical regions
what type of receptors do classical hallucinogens act on
5HT2A receptors - antagonists
what is the effect of psyilocybin on prefrontal cortical activation, as measured by PET
increased activation
what did CarhartHarris et al report regarding psilocybin’s effect on cortical activation using FMRI
reduced cortical activation
what imaging technique was used in the Carhart-Harris et al study
FMRI
can dissociative anaesthetics and MDMA cause dependence
yes
how does potential for dependence compare to other drugs for abuse
it may be weaker
what neurotransmitter system may mediate this dependence
the meso-corticolimbic dopamine system
what type of studies suggest that dissociative anaesthetics and MDMA can cause neurodegeneration
animal studies
what type of neurons are selectively affected by MDMA induced neurodegeneration
serotonergic
is there evidence of MDMA induced neurodegeneration in humans
yes for recreational use
what is ketamine bladder or ketamine induced ulcerative cystitis
thickening of the bladder wall and low bladder capacity
what other effects are associated with chronic ketamine use
kidney dysfunction and k-cramps
what two groups were studied regarding MDMAs effects on serotonergic neurons
squirrel monkeys and human recreational users
what dosage and administration schedule of MDMA was used in the squirrel monkey study
5mg 2x daily for 4 days
what was observed in the squirrel monkey brain regions after MDMA administration
damage to sertonergic neurons
how long did the study follow the effects of MDMA in the squirrel monkeys
up to 7 years
what did the meta-analysis of neuroimaging studies investigate in human MDMA users
SERT expression in different brain regions
what was observed regarding SERT expression in heavy MDMA users
decreased SERT expression in multiple brain regions
what brain regions were affected in human MDMA users
parietal, temporal, occipital, cingulate cortices, thalamus, and hippocampus
what is suggested about the long term effects of MDMA serotonergic neurons
long term damage
how does the effect of MDMA on serotonergic neurons compare between humans and squirrel monkeys
the effect is smaller in humans than in monkeys
how does overall SERT expression compare between control subjects and heavy MDMA users
SERT expression is greater in controls
what conditions are being researched for psilocybin/LSD assisted psychotherapy
substance abuse, sever depression and cancer anxiety
what conditions are being researched for MDMA assisted psychotherapy
PTSD and alcohol dependence
what is a concern regarding MDMA use in therapy
toxicity for serotonergic neurons
what form of ketamine was approved for treatment-resistant depression in 2019
esketamine - ketamine nasal spray
do well controlled clinical trials support the antidepressant effect of ketamine
yes
do all patients respond o ketamine treatment for depression
no
in what regions was esketamine nasal spray approved for treatment
the US and Europe including the UK
- not approved by NICE
