The Psychedelics

Psychedelics
Agents that have the ability to alter
sensory perception
Serotoninlike psychedelics
LSD (lysergic acid diethylamide)
Psilocybin (mushrooms)
5-HT2 agonists
Psychedelic syndrome
Disturbances in thinking
Illusions
Visual hallucinations
Impaired ego functioning

LSD
1
st
synthesized in 1938 by Albert
Hofmann
Unnoticed until 1943
Rapid absorption via oral admin
25 300 micrograms!
60 minutes
Peak blood level = 3 hours
6-8 hr duration of action
Few physiological effects
Increase in body temp, pupil dilation
Physiological Effects
Increase HR and BP
Increase blood sugar
Dizziness, nausea
Effective dose = 50 mg
Lethal = 14,000 mg
(a remarkably non-lethal compound)
LSD
Intense psychological effects
25 50 mg
Pupillary dilation and glassy eyes
Alterations in
Thinking
Emotion
Arousal
Self-image
Slowed/distorted time
Colored lights
Distorted images
LSD
Brain areas
The Locus coeruleus
Projects to many brain areas
Releases NE
Fear and emotional responding
A novelty detector
LSD (all psychedelics) stimulates 5-HT
receptors of LC
Suppress output
Makes LC more sensitive to novelty
LSD
Brain areas
The Cortex
Psychedelics produce prolonged EPSPs in
glutaminergic neurons
Especially in medial prefrontal cortex
Information processing and perception
Hallucinations?
LSD-induced psychedelic
experience
1. The somatic phase
Occurs after absorption
CNS stimulation and autonomic changes
(Sympathomimetic)
2. The sensory (or perceptual) phase
Sensory distortions and pseudohallucinations
Desired effects
3. The psychic phase
Maximum drug effect
True hallucinations
Psychotic episodes
Altered time perception
A bad trip
LSD Tolerance
Develops rapidly (psycho and physio)
Dissipates after several days of not
taking the drug
Also cross-tolerance with other
psychedelics

Other Serotoninlike Hallucinogens
DMT
Naturally occurring, short-acting
Easily synthesized
Structurally related to serotonin
Ayahuasca a psychoactive beverage
Contains DMT,and an MOA inhibitor
Produces
Intense visual hallucinations
Intoxication
Loss of awareness and surroundings
Other Serotoninlike Hallucinogens
Psilocybin and psilocin
Agents found in many species of
mushrooms
Psilocin is the active psychedelic agent
1/200
th
as potent as LSD
Resemble NE and DA and
amphetamines
Addition of one or more methoxy groups
(OCH3)
Psychedelic properties on top of
psychostimilant properties
Methoxylated amphetamine derivatives
Mescaline
MDMA (ecstacy)
DOM (STP)
Catecholaminelike Psychedelics
Exert amphetamine-like
psychostimulant actions
Enhance energy, endurance, sociability
and sexual arousal
Psychedelic action likely 5-HT
Mixed dopamine and serotonin
agonists (entactogens)
Intermediate position between stimulant
and hallucinogen
Rapid acute tolerance
Dissipates in a few days
Catecholaminelike Psychedelics
Mescaline
Psychedelic agent found in peyote
Dried button is usually softened and
chewed
Use dates back 5000 yrs or so in NA
Rapidly and completely absorbed po
Peak brain level in 1-2 hrs
Lasts about 10 hrs
Not metabolized before excretion

Catecholaminelike Psychedelics
Catecholaminelike Psychedelics
DOM, MDA, TMA, MDMA (ecstacy)
All structurally similar
Similar effects
DOM
Toxic, not widely used
MDA
Metabolite of MDMA
More potent hallucinogen
Ecstacy-Behavior and Performance
Increased muscular tension
Bruxism
Restless legs
Increased body temperature
Back and leg stiffness for days
Loss of appetite
Blurred vision
Insomnia

Ecstacy
Serotonin neurotoxin
Reversible? May take years for some effects
Acute release of 5-HT and DA
Depletion of intraneuronal 5-HT
Released 5-HT causes increased DA release
Excess DA transported to depleted 5-HT neurons
Broken down, forming free radicals
Degeneration of 5-HT axons, terminal buttons and reuptake
transporters
Somatic effects
Memory (visual/verbal)
Decision making
Lack of self-control
Panic attacks
Paranoia
depression