hallucinogens

basics of phencyclidine (PCP)

dissociative anesthetic related to ketamine
used illicitly since the 1960s
sold under many names: angel dust, horse tranquilizer
many different preparations and can be taken orally, intranasally, i.v, or smoked

dose effects of PCP

low dose (1-5mg): alcohol-like effect (disinhibition)
moderate dose (5-10mg): distortion of space and time, psychotic reactions, detachment, anesthesia, anagleia, amnesia, mutism
high dose ( > 10mg): acute schizophrenia, violent or aggressive behavior, exaggerated strength, feelings of invulnerability
overdose: agitation, convulsions, coma, death due to self-injury, rhabdomyolysis. psychosis, renal failure, hyperthermia

the reinforcing effects of PCP self-administration

self-administered in animals to the point of intoxication
self-administration is not blocked by the coadministration of a dopamine receptor antagonist (sulpiride)

PCP mechanism of action

non-competitive antagonist at NMDA receptor (blocks the channel inside to pore)
inhibitory effects at nAChRs
potent D2 dopamine receptor partial agonist

cough syrup

very high doses of cough syrup cause a hallucinogenic effect
dextromethorphan (Robitussin)

ketamine as an antidepressant

lacks the 2-4 week delayed onset
treats treatment resistant depression

hallucinogen common features

hallucinogen (ability to evoke hallucinations or pseudohallucinations)
psychomimetic (ability to mimic endogenous psychosis)
phantasicum, psychedelic ("mind expanding)

the LSD family hallucinogens

contain an indole ring
structurally similar to serotonin
derived from lysergic acid

potential treatments with LSD

addiction, depression, anxiety, PTSD
non-supervised use can be very dangerous

chemical structure of MDMA

related to amphetamines and derived from phenylethlamine
similar structure to catecholamines (epinephrine, norepinephrine, dopamine)

major effects of LSD

sensory-perceptual pseudohallucinations, illusions, synesthesia
psychic experiences
somatic effects
dizziness, tremor, weakness, mydriasis, tachycardia, hypertension in overdose

LSD pharmacokinetics

typical dose: 50-150 micrograms yielding nM [blood]
microdose: 5-20 micrograms
effects seen within 30 mins and can last for 20 hours (peak effects around 2.5-3 hours)
half-life is roughly 3-5 hours and metabolized by cyt P450s

what are the potential effects of microdosing

doesn't produce typical psychedelic effects
MAY contribute to long-term mental health and positive well-being

hallucinogen mechanism of action

5-HT2A post-synaptic receptor agonist
LSD binds to 5-HT1/2/5/6/7 receptors
mescaline does not bind to 5-HT5/7 receptors
tolerance (decreased 5-TH2A binding and signaling) and cross-tolerance occur

LSD type hallucinogens

DMT (Dimethyltryptamine)
- naturally-occuring LSD-like substance in plants

Morning Glory Seeds
- lysergic acid amide (LSA)

Bufotenin (5-hydroxy-DMT)

Psilocybin and Psilocin
•magic mushrooms
•psilocybin is a pro-drug metabolized to psilcocin
• 100x less potent than LSD

ayahuasca

brewing DMT-containing shrub with MAOI-containing vine to antagonize the first-pass effect

mescaline

non-LSD family hallucinogen
isolated from the mescal button of the peyote cactus

adverse effects of hallucinogens

• Bad 'trips' - possibly triggering psychosis

• Flashbacks

• Hallucinogen persisting perception disorder (HPPD)

phenylethylamines

methoxyamphetamines
synthetic derivatives of mescaline
structural similarity to dopamine, epinephrine, norepinephrine
mixed hallucinogenic and stimulant effects
examples: DOM, TMA, MDMA

what are empathogen-entactogens

foster feelings of being closer to others and oneself
MDMA, MDA

MDMA mechanism of action

acts as 5-HT, DA, and NE transport inhibitor

• also enhances neurotransmitter release
  agonist at 5-HT2A/B/C and 5-HTA receptors
  agonist at D1/D2, adrenergic, and muscarinic receptors

combination of fluoxetine, amphetamine, and LSD effects

long-term use of ecstasy effects

loss of 5-HT neurons
higher levels of 5-HT2A receptors (compensation?)
memory loss