The Psychedelics PowerPoint
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The Psychedelics
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Psychedelics
Agents that have the ability to alter
sensory perception
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Serotoninlike psychedelics
LSD (lysergic acid diethylamide)
Psilocybin (mushrooms)
5-HT2 agonistsPsychedelic syndrome
Disturbances in thinking
IllusionsVisual hallucinations
Impaired ego functioning
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LSD
1st synthesized in 1938 by AlbertHofmann
Unnoticed until 1943
Rapid absorption via oral admin25 – 300 micrograms!
60 minutes
Peak blood level = 3 hours6-8 hr duration of action
Few physiological effects
Increase in body temp, pupil dilation
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Physiological Effects
Increase HR and BP
Increase blood sugar
Dizziness, nausea
Effective dose = 50 mg
Lethal = 14,000 mg
(a remarkably non-lethal compound)
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LSD
Intense psychological effects
25 – 50 mgPupillary dilation and glassy eyes
Alterations inThinking
Emotion
Arousal
Self-imageSlowed/distorted time
Colored lights
Distorted images
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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-HTreceptors of LC
Suppress output
Makes LC more sensitive to novelty
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LSD
Brain areas
The Cortex
Psychedelics produce prolonged EPSPs in
glutaminergic neurons
Especially in medial prefrontal cortex
Information processing and perception
– Hallucinations?
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LSD-induced psychedelic
experience
1. The somatic phaseOccurs after absorption
CNS stimulation and autonomic changes(Sympathomimetic)
2. The sensory (or perceptual) phaseSensory distortions and pseudohallucinations
Desired effects
3. The psychic phase
Maximum drug effectTrue hallucinations
Psychotic episodes
Altered time perception
A “bad trip”
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LSD Tolerance
Develops rapidly (psycho and physio)
Dissipates after several days of not
taking the drug
Also cross-tolerance with other
psychedelics
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Other Serotoninlike Hallucinogens
DMT
Naturally occurring, short-acting
Easily synthesized
Structurally related to serotonin
Ayahuasca –a psychoactive beverage
Contains DMT,and an MOA inhibitor
ProducesIntense visual hallucinations
Intoxication
Loss of awareness and surroundings
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Other Serotoninlike Hallucinogens
Psilocybin and psilocin
Agents found in many species of
mushrooms
Psilocin is the active psychedelic agent
1/200th as potent as LSD
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Resemble NE and DA andamphetamines
Addition of one or more methoxy groups
(OCH3)Psychedelic properties on top ofpsychostimilant properties
Methoxylated amphetamine derivatives
Mescaline
MDMA (ecstacy)
DOM (STP)
Catecholaminelike Psychedelics
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Exert amphetamine-likepsychostimulant 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
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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
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Catecholaminelike Psychedelics
DOM, MDA, TMA, MDMA (ecstacy) All structurally similar
Similar effects
DOMToxic, not widely used
MDA
Metabolite of MDMAMore potent hallucinogen
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Ecstacy-Behavior and Performance
Increased muscular tensionBruxism
Restless legs
Increased body temperature
Back and leg stiffness for days
Loss of appetiteBlurred vision
Insomnia
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Ecstacy
Serotonin neurotoxinReversible? 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 neuronsBroken down, forming free radicals
Degeneration of 5-HT axons, terminal buttons and reuptaketransporters
Somatic effectsMemory (visual/verbal)
Decision making
Lack of self-control
Panic attacks
Paranoia
depression