ch 15: psychedelic and hallucinogenic drugs

502-524

what are the hallucinogens (2) + their classifications? (3)

• drugs that distort perceptions of reality at relatively low doses

• most are schedule III → although most are safe + non-addictive

  • psychedelics

  • deliriants

  • dissociatives

deliriants vs dissociatives? (2)

• deliriants: result in mental confusion + inability to differentiate reality from fantasy

• dissociatives: cause analgesia, amnesia, catalepsy, and a sense of detachment from environment

psychedelics produce __(4)__ without producing __(1)__ → types (2) + examples (6)

• produce vivid sensory experiences, altered perceptions, cognitive distortions, altered awareness

• do not produce a state of toxic delirium

  • indoleamines: structurally similar to 5-HT

  • phenylethylamines: structurally similar to DA + NE

• LSD, mescaline, psilocybin, bufotenine, DMT, 5-MeO-DMT

hallucination vs illusion (2)

• hallucination: sense perception for which there is no external stimulus

• illusion: altered + distorted perceptions, thoughts, feelings, insights, awareness

mescaline

• derived from dried top of the peyote cactus

psilocybin (3)

• alkaloid from several mushroom species

• dried + eaten or made into tea

• converted into psilocin after ingestion → psychoactive agent

where are DMT, 5-MeO-DMT and 5-HO-DMT found, how are they consumed and synthetic analogs? (3)

1. found in plants indigenous to South America and frog venom

2. smoked or snorted → produce brief but intense hallucinatory experience

3. synthetic analogs; alpha-methyl tryptamine (AMT), foxy methoxy

ayahuasca (4)

1. hallucinogenic drink made by natives from the Amazon from 2 plants

   1. contains DMT

   2. the other supplies alkaloids ß-carbolines which inhibit MAO activity

2. used in spiritual/religious ceremonies

Lysergic acid diethylamide (LSD) (3)

• synthesized from fungal alkaloids on rye

• CIA carried on unethical experiments w LSD

  • Charles Manson

how have some researchers tried using LSD as a tool in psychotherapy or psychoanalysis (2)

1. psycholytic therapy: drug-induced psychosis meaning psychic loosening or opening

2. psychedelic therapy: patient was given a high dose of LSD in hopes of gaining insight into his/her problems

NBOMes (3)

• appeared in 2010s → continue to be widely distributed

• subject to first-pass metabolism when consumed orally → taken sublingual or buccal routes

• v. potent → cases of toxicity have severe even fatal consequences

salvinorin A (3)

• psychoactive ingredient in Salvia divinorum → inactivated in the GI tract

• leaves can be chewed or extracts made

• absorbed through the mouth or smoked

ibogaine low vs high dose (4)

• derived from bark and roots of a west African shrub → chewed or made into a powder

  • can help counteract opioid withdrawal symptoms + cravings

• low doses: psychostimulant → ↑ energy, ↓hunger, produce euphoric feeling

• high doses: produce psychedelic effect

PCP and Ketamine (2) + routes of administration (4)

• ketamine: short-acting anesthetic

  • may have potential to treat depression

• ingested, snorted, smoked, injected

hallucinogens are taken ____ and typically take effect in ____ → onset of action faster when __(3)__. duration of action depends on factors like __(3)__ → they are metabolized by ___ and excreted in ____

1. orally

2. 20-60 minutes

3. snorted, smoked, or given IV

4. dosage, purity, drug taken ie. DMT= 30 mins, LSD = 1 hr

5. liver

6. urine

3 stages of an LSD trip (3)

1. sympathomimetic physiological effects

2. alterations in perceptions + sensations → synesthesia

3. self-perceptions change → leading to distortions of space and time, cognitive ∆s and emotional swings

bad LSD trips are characterized by (3)

• frightening hallucinations, confusion, disorientation, agitation, depression, terror, intense anxiety or panic, paranoia

• can leave long-lasting psychological scars

• can exacerbate a pre-existing psychiatric illness or affective disorder

other acute effects of LSD (2)

• flashbacks: visual disturbances that occur long after the drug has left the body

• high therapeutic index → no evidence of organ damage

psilocybin vs mescaline trip (4)

psylocybin

• less emotionally intense → more visual and euphoric → fewer panic rxns

• risk of OD is v low

mescaline trip

• gradual onset → fewer ∆s in mood + sense of self

• more toxic + more side effects

salvia (1) vs PCP (3) vs ketamine (1) trips

salvia: vivid visual imagery, sensory disturbances, time distortions

PCP:

• variable effects depending on dose, environment, characteristics of the user

• stimulant, depressant, analgesic, hallucinogenic, anaesthetic

• high doses can cause convulsions, rep failure, coma, death

ketamine

• effects similar to PCP but shorter duration + fewer hallucinations

LSD trip can be divided in 4 phases ____, plateau, ___, and comedown. phase 1 occurs ___ after LSD ingestion

1. onset

2. peak

3. 30 minutes to an hour

onset phase of LSD trip (3)

• visual effects

• intensification of colors

• appearance of geometric patterns or strange objects that can be seen with one’s eyes closed

plateau phase of LSD trip (3)

• 2 hrs

• sense of time slowing

• visual effects become more intense

peak phase of LSD trip (4)

• begins after 3 hrs → lasts 2-3

• user feels in another world + time stopped

• sees bizarre distorted images that can be beautiful or menacing

• experiences synesthesia: colours are heard, sounds are felt

comedown phase of LSD trip (4)

• 2 hrs or longer

• most drug effects gone

• user may still not feel completely normal

• feelings of depersonalization, emotional shifts from euphoria to anxiety, fearful state, disruption of logical thought

altered states of conciousness (ASC) rating scale dimensions (5)

• developed to quantify the effects of hallucinogens

  • oceanic boundlessness: feeling one w the world

  • ego-disintegration anxiety: negative emotional responses bc of loss of ego boundaries

  • visionary restructuralization: distortions of visual perceptions

  • reduced vigilance: less important measure

  • auditory alterations: auditory hallucination

physiological responses to hallucinogens reflect ______ (3)

• activation of the sympathetic NS

  • dizziness

  • nausea

  • vomiting

hallucinogenic drugs with serotonin-like molecular structure (7) (indolamine)

1. LSD

2. psilocybin

3. psilocin

4. DMT

5. 5-MeO-DMT

6. synthetic tryptamines

7. ibogaine

hallucinogenic drugs with catecholamine-like molecular structure (3)

1. mescaline

2. NBOMs

3. amphetamine analogs DOM/TMA

4. known as phenethylamine psychedelics

What is the main receptor target of classic psychedelic hallucinogens, and what evidence shows it’s necessary for their effects? (3)

• Indoleamine and phenethylamine psychedelics (e.g., LSD, psilocybin, mescaline) are 5-HT₂A receptor agonists.

• 5-HT₂A knockout mice or humans pre-treated with the 5-HT₂A antagonist ketanserin show little to no psychedelic response,

• and brain imaging shows that neocortical 5-HT₂A receptor occupancy strongly correlates with subjective trip intensity.

What is the head-twitch response and how is it used in psychedelic drug research? (3)

• The head-twitch response is a rapid, repetitive side-to-side head jerk seen in rodents after 5-HT₂A agonist psychedelics.

• It increases dose-dependently

• is used as an animal behavioral measure of psychedelic effect strength (more drug → more head-twitches).

What happens to the default mode network (DMN) during a psychedelic trip?

DMN activity goes down, meaning less self-focused, ruminative “ego” activity.

How do psychedelics change sensory processing in the brain?

They reduce thalamic gating and increase cortical sensory processing, so more raw sensory info gets through and feels more intense.

In psychedelic therapy, what is meant by the “peak experience” and “afterglow”?

The peak experience is the most intense part of the trip (desired in therapy); the afterglow is a period of days–weeks after where mood and insight are improved.

What is the best predictor of a good therapeutic response to psychedelics?

The intensity of the psychedelic experience (how strong the trip feels to the person).

What neuroplasticity effect is thought to underlie psychedelics’ antidepressant actions?

Rapid glutamate-dependent plasticity: increased synapse growth and connectivity (more dendritic spines/synapses) in key brain regions.

Historically, what disorder was LSD explored to treat before it became Schedule I?

Alcohol dependence.

Are classic 5-HT psychedelics strongly addictive?

No. They are not strongly dependence-forming for most users, though a few heavy users can develop hallucinogen use disorder.

Why do classic psychedelics show rapid tolerance?

Repeated use causes down-regulation of 5-HT₂A receptors, so the same dose has less effect.

Name two serious long-term adverse effects of classic psychedelics.

Flashbacks and HPPD (hallucinogen persisting perception disorder) with ongoing visual disturbances.

What type of drugs are PCP and ketamine, and what is their receptor action?

They are dissociative anesthetics and act as uncompetitive antagonists at the NMDA glutamate receptor (block the channel from inside).

What kind of subjective state do anesthetic doses of ketamine/PCP produce?

A dissociated state (e.g., “K-hole”) with out-of-body feelings, time loss, and strong distortions of body and space.

How does NMDA blockade by PCP/ketamine affect cortical glutamate?

Blocking NMDA receptors on GABA interneurons reduces inhibition and increases cortical glutamate release.

How do PCP and ketamine support the glutamate hypothesis of schizophrenia?

• High doses of PCP/ketamine block NMDA receptors and produce schizophrenia-like symptoms (disordered thought, delusions, motor and negative symptoms),

• suggesting NMDA hypofunction can contribute to schizophrenia.

Do PCP and ketamine have reinforcing (rewarding) effects? How do we know?

Yes. Rodents and primates self-administer them, and they increase DA firing and release in reward areas (NAcc, dorsal striatum, PFC), producing dose-dependent “drug liking” in humans.

What’s the typical subjective effect of low vs high ketamine doses?

• Low dose: relaxed, mild dissociation (“going to K-land”).

• High dose: strong dissociation/altered state similar to LSD; many users avoid this intensity.

Name two clinical uses of ketamine.

• Rapid relief of depression (before SSRIs work)

• non-opioid analgesia for acute or chronic pain.

What are some long-term problems from chronic PCP/ketamine use? (4)

Memory and cognitive deficits, psychosis-like symptoms, and urinary tract/bladder damage (can lead to renal issues).

How addictive are classic psychedelics compared with PCP/ketamine?

• Psilocybin, LSD, mescaline → low abuse potential, not considered addictive; rapid, reversible tolerance and cross-tolerance.

• PCP/ketamine → some potential for dependence and more toxic chronic effects.