PCOL:3102 Hallucinogens

hallucinogens

drugs that alter a person’s awareness of their surroundings as well as their thoughts and feelings

two classes of hallucinogens

classic and dissociative

classic hallucinogens

increase SEROTONIN signaling

ex. LSD, psilocybin

dissociative hallucinogens

interfere with GLUTAMATE signaling

ex. PCP, ketamine

LSD

• potent synthetic hallucinogen

• very low effective dose (10-15 ug)

• dried on paper squares, tablets, and liquid

• lipid-soluble → easily gets into the brain

• pharmacokinetic tolerance

  • in 3-4 consecutive doses, drug inactivated immediately in body but regain effects after short abstinence (3-4 days)

• withdrawal and overdose rarely seen

psilocybin

• magic mushrooms; a prodrug that has a long history in religious practices

• high effective dose (4-10 mg)

• dried/fresh mushrooms and psilocybin is a prodrug that is converted to active metabolite psilocyn

• lipid soluble → easily gets into brain

• pharmacokinetic tolerance

  • in 3-4 consecutive doses, drug inactivated immediately but regain effects after short abstinence (>week)

• withdrawal and overdose rarely seen

LSD vs psilocybin

they’re pharmacologically similar and both:

• are typically taken orally

• resemble SER and increase SER signaling producing neuropsychological sympathetic effects

• highly lipid soluble granting them easy access to the brain

• subject to pharmacokinetic and pharmacodynamic tolerance

• rarely associated with withdrawal or overdose

however, they’re not completely the same:

• effective dose of LSD is very low compared to psilocybin

• psilocybin is a prodrug converted to active metabolite psilocyn while LSD is not

• psilocyn is metabolized by UGT while LSD is metabolized by CYPs

cross tolerance

resistance to a drug’s effects due to prior exposure to a pharmacologically similar drug

cross tolerance in hallucinogens

• body may develop cross tolerance to multiple hallucinogens due to their similar actions at serotonin receptors

• so if person takes LSD, they will be tolerant to the effects of psilocybin since both are so pharmacologically similar to each other

side effects of hallucinogens

• CNS: hallucinations

• sympathetic: increased HR and BP, loss of appetite, dry mouth, sweating

• can cause long-term effects such as persistent psychosis and hallucinogen persistent perception disorder

how do classic hallucinogens produce their neuropsychological effects?

by activating the 5-HT2A receptors to promote post-synaptic SER signaling

how do classic hallucinogens cause sympathetic side effects?

SER neurons project all over the place and they specifically project down the brain stem which is the pre-ganglionic neurons of the sympathetic NS

hallucinogen persistent perception disorder

• a trip that doesn’t end

• a condition in which someone who has taken hallucinogens continues to experience visual and other perceptual distortions after quitting drug use

• this can persist for weeks, months, years