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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