32: Psychedelics Flashcards
LSD and psilocybin are similar in structure to
serotonin
actions of LSD and psilocybin include
- binds to what receptors in brain?
- reduces what pattern of thinking?
- what factor is helpful for depression?
- dcr activity in the ___________ network-waht does this mean?
Binds and activates 5HT receptors in brain
↑ neuroplasticity and pathways = ↓ rigid thinking patterns
↑ brain derived neurotropic factor = can be helpful for depression
↓ activity in default mode network = be more present and less daydreaming in the past/ present
psilocybin is a
1. naturally occuring prodrug
2. serotonin 2A receptor agonist
3. mushroom produced drug
4. all of the above
4
psilocybin route of admin
PO, tea (hot water conv to psilocin), IV
psilocybin onset of action
10-40 min, duration 2-6hrs
psilocybin dose
10-50mg (10-50g fresh mushrooms, 1-5g dried)
Most common therapeutic dose: 25mg
physical effects of psilocybin
pupils? HR? bp?
pupil dilation, ↑(at peak)/↓HR (caution with heart conditions), hyper/hypotension, nausea
psych effects of psilocybin
- what is a good trip?
- bad trip?
- can it cause LT changes in personality if taken for more than how long?
- how does it affect suicidal ideaiton?
disorientation, lethargy
Good trip: giddiness, euphoria, joy, connected to others, nature, and universe
Bad trip: depression anxiety paranoia (↑ risk of used with other drugs/ alcohol, used during emotional low, in unsupportive environment)
Potential LT changes in personality of user (openness, spiritually active), >1yr: reduced psych distress, suicidal ideation/ planning/ attempts
sensory effects of psilocybin
radiant colors, altered sense of time, animated sensory experiences
ADRs of psilocybin
- how affects mental funcitonoing?
- P_____
- what kind of flashbacks?
impairment of mental functioning, psychosis (↑ risk in those prone- ex manic, BPD, schizo = must screen), flashbacks/ hallucinogen persisting perception disorder (HPPD- rare)
is it possible to OD on psilocybin
no
agitation from psilocybin can be treated with
BZDs and supportive care
name 2 clinical uses for psilocybin
MDD (esp tx resistant depression further along in research, better than SSRIs/ escitalopram), anxiety, end of life distress, tobacco cessation, alcohol use disorder, OCD, migraines, etc
what is an important factor in use of psilocybin clinically
Setting important- how you feel going into trip and the physical environment the therapy is done in
LSD is _______ derived
synthetically
what is the MOA of LSD (3)
- binds to ____ receptors
- incr what 2 NT signalling?
binds to most serotonin subtypes (cross activation), ↑ glutamate in cerebral cortex, ↑ D2 signaling
LSD onset, duration, metabolism, and excretion
onset 30-40min, duration 8-12h, metabolized by CYP450, excreted by kidneys
route of LSD
PO, SL, IV (less common)
common doses of LSD
40-500ug (dose v small = easy to take too much), clinical trials ~200ug
physical, psych, and sensory effects of LSD
Physical; pupil dilation, reduced appetite, wakefulness, others more varies
Psychological: similar to psilocybin
Sensory; similar to psilocybin (v animated)
More of an “outwards” experience than psilocybin (which is warmer, less isolating, not as forceful and allows building connections between people)
SEs of LSD
similar to psilocybin, some ↑ risk psychosis (not sig)
clinical uses of LSD (3)
alcohol withdrawal, depression, anxiety (preliminary)
Not as far along in trials as you need supervision for 12hrs
mescaline MOA
- where does mescaline come from?
5HT2A/5HT2C receptor agonist
- a cactus :)
msecaline dose
200-400mg mescaline sulfate or 178-356mg mescaline hydrochloride
76mm button = 25mg mescaline
onset, peak, and duratio nof mescaline
onset 45-90min, peak 4-6h, duration 8-14h
mescaline is metabolized by _______ through ______
liver through MAO breakdown
clinical uses of mescaline 2
alcohol use disorder, depression
DMT is actually a combinatio nof
ayahuasca and P viridis (DMT)
describe how the combo of ayahuasca and DMT work
Ayahuasca (vine Banisteriopsis caapi)= b-carbolines
Reversibly inhibit MAO to prevent breakdown of DMT orally and allow absorption + access to CNS
P. viridis = DMT
5HT (2A/1A/2C) agonist
DMT is a _____ agonist
5HT (2A/1A/2C)
duration of DMT tea
3hrs
DDI with DMT
dangerous with any drugs that increase 5HT (serotonin sx)
clinical uses of DMT
SUD, depression, anxiety
Potential therapeutic tool by enhancing self acceptance + allowing safe exposure to emotional events
5-MAO-DHT is a psychedelic found in
plants and some toad secretions
MDMA effects
Stimulant properties, capsules or tablets, club drug (raves, dances)
Trusting, loving, and warm feelings towards others
stronger touch sensations
MDMA has the most benefit in ________ due to ______________________________
PTSD
↑ ability to trust, feel comfy, and be able to access traumatic memories to work through = v effective in talk therapy (out, whereas LSD and psilocybin are more introspective)
MOA of MDMA
potent reuptake inhibitor of presynaptic 5HT, DA, NE
MDMA onset and duration
Onset within 30-60min, duration of action 4-6hrs
MDMA is metabolized in the _____ by _______
liver
CYP2D6
MDMA dose
50-150mg
MDMA ADR
jaw clenching (↑ NE), anxiety, GI disturbances, ↑ vitals (hyperthermia), sweating
effects of ketamine and PCP
stimulant, depressant, hallucinogenic, anesthetic, analgesic
Dissociation from surroundings, time distortions
K and PCP ADRs
paranoia, extremely aggressive behavior, confusion, slurred speech, muscle rigidity
PCP generally more dangerous than ketamine due to ↑ risk psychosis (↑ intense, ↑ violent/ self injurious behavior, ↑ resp depression)
LT AEs of PCP and ADRs
speech problems, depression, memory loss, violent behavior, flashbacks, syndrome similar to schizophrenia, strong cravings
clinical uses of ketatmine
TRD
why do psychedelics have low abuse potential
Does not cause physical dependence or withrawl. Due to introspective, mystical, and spiritually meaningful effects (not so much pleasure) = most ppl need time to recover = ↓ chance of overuse
psychedelics are not recommended in individuals with
hx or Fhx psychosis, mania, borderline personality disorder
what are the risks of OD like with psychedelics
V low OD risk (less than OTCs like aspirin)
psychedelics tend to interact with
antidepressants and antipsychotics
effects of antidepressants with psychedelics
↑ risk serotonin sx (esp with ayahuasca)
↓ psychedelic effect (AD ↓ eff by effect on 5HT receptors)
effects of antipsychotics with psychedelics
↓ psychedelic effects (b/c eff on 5HT receptors)
↑ risk AEs
5 psychedelics metabolized by 2D6
psilocybin, ayahuasca, MDMA, LSD, mescaline
what psychedelic is metabolized by 3A4
MDMA
