Psychedelic Drugs

• Many Types Psychedelics / • Broken out by the type of NT it affects – Psychology 472 – Catecholamine-like – Serotonin-like Pharmacology of Psychoactive – Psychedelic Anesthetics Drugs Listen to the audio lecture while viewing these slides

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Pharmacokinetics Pharmacodynamics

• Most taken orally • Site of action depends on the drug • Some smoked (e.g., PCP, DMT) • Taken by circulatory system to receptor sites • Metabolized by the liver – Some material can remain for a long time – Most drugs are metabolized in 6-8 hours

Anticholinergic PNS

• •Causes • Is an (ACH) antagonist – Dry mouth • Blocks ACH from binding on its receptors –Dry skin • Is widely distributed in plants – Increased body temperature – (deadly nightshade) – Blurred vision – Stramonium (Jamestown weed, stinkweed, – Tachycardia Jimsonweed, Thorn Apple) – Hypertension – Mandrogona Officunarum (Mandrake) –others • Acts on both the PNS and CNS

1 Low Dosages CNS Effects •Drowsiness • Mild Euphoria • Depends on the dose •Amnesia • Fatigue • Delirium • Dreamless Sleep •Others • Generally clouds consciousness and produces amnesia

Moderate Doses High Doses

• Get more restlessness • Develops into a Psychotic State • Excitement – Delirium • Hallucinations – Mental Confusion • Euphoria – Stupor – Coma • Disorientation – Respiratory Depression •Others

Catecholamine-Like Issues • • DOM (STP)., MDA, DMA, MDMA, TMA • Can create excitement and loss of control MDE • Clouds consciousness (Cannot recall what • Myristin, you did) • Decreases memory • Resemble NE and Dopamine • Results • Are mixed serotonin and dopamine receptor – Is not as attractive as other hallucinogens agonists

– Low use rates • Generally, bind on the 5-HT2a receptor

2 Mescaline Use

• Comes from the Peyote plant • Is primarily used in Native American • Is a spineless cactus with a small crown or religious ceremonies. “button” on its top. • Is legally available for religious use • Button is cut and dried • Used to gain insight by the user – (called mescal button) • Is softened in the mouth and swallowed

Effects Brain Effects

• Is absorbed rapidly and completely • Works on frontal lobe (especially right • Get adequate brain concentrations in 1-2h hemisphere) • 353.5 - 4 hours causes effects (usually visual) • Produces unusual psychic effects and • Lasts for approx. 10 hours hallucinations • Is not metabolized before being excreted. – One of a few drugs to do so

DOM (STP), MDE, DMA, TMA Behavioral Effects MDA, MDMA, • Anxiety • Are similar to mescaline and • Tremors • Visual hallucinations (Bright lights , • Produce similar effects geometric designs, • Psychedelic effects increase as doses • Color and space perception is impaired increase • Can often recall information • Are more potent than mescaline

3 Dimethoxy-Methamphetamine (DOM) Designer Psychedelics • Also called STP • Effects are similar to mescaline but 100 • Are structural variations of times more potent • Many types • Is less potent than LSD – Methylene-dioxy-ampp()hetamine (MDA) • Highly associated with overdoses – Dimethoxy-methyl-amphetamine (DMA) – Convulsions, Death – Methylene-dioxy-ethylamphetamine (MDE) • Got a bad reputation also called Eve – Trimethoxy amphetamine (TMA) • Not often used anymore

MDA Effects • Is a metabolite of MDMA (Ecstasy) • May be the active ingredient of MDMA • Resemble mescaline and LSD • Causes serotonin and dopamine release • Are a mix of catecholamine and serotonin – Actually stimulates serotonin receptors more interactions than MDMA • Side effects are similar to MDMA – Causes more psychedelic-like effects – Has more stimulant / psychedelic hallucinogenic qualities – Less intense empathogenic properties • Is less predictable than MDMA

MDMA / Ecstasy Effects

• Variety of street names • Resembles MDA in structure –XTC • Is less hallucinogenic than MDA – Adam • Fewer visual distortions –M –M • Lots of side effects – Essence –E –Others

4 Effects on Neurons

• Causes an increase of serotonin in the synaptic cleft • Then blocks the reuptake of serotonin from the synaptic cleft • Does the same thing with Dopamine neurons

Reported Positive Effects

• Enhanced mood • Increased emotional sensitiveness • Little anxiety • No hallucinations • Heightened sensory awareness • Increased psychomotor drive

5 Side Effects

Adverse Neuronal and Brain Effects • Down Regulation • Reduces the number of post synaptic receptors

Major Long Term Effects

• Is a potent and selective neurotoxin to serotonin neurons • Serotonin levels and metabolites are reduced • Damages presynaptic elements – Terminals degenerate • Damage remains at least two years and probably forever

6 Conclusions about MDMA

• Is seen as safe by users • Is really bad stuff even at low doses • Look at reviews in NIDA

Other Stuff Myristin, Elemicin • Have Herbal Ecstasy – Combines ephedrine and caffeine – Very dangerous for overdose – Hypertension – Cardiac Arrhythmias • Candyflipping – Combines MDMA and LSD – Produces a synergistic effect

7 Myristin, Elemicin Effects

• Myristin () • Feelings of unreality • Elemicin (Mace) • Euphoria • Are common spices • Visual Hallucinations • Usually put in tea 1-2 tsp • Disorientation • Effects occur in approximately 2-5 hours • Confusion

Side Effects Serotonin-Like

• Feelings of impending doom • Also called Indoleamines • Acute psychotic reactions • Lysergic Acid Diethylamide (LSD) • Nutmeg • Dimethyltryptamine (DMT) – Also produces nausea, vomiting, tremors • , , bufotenine – Usually prevents repeat usage • Ololiuqui ( ) •

Effects LSD

• Work on Serotonin receptors • First synthesized by Albert Hoffman in • Produce psychedelic effects 1938 • Causes distortion of sensory inputs • Major research using LSD began in the 1950’s as part of research investigating psychotic behavior • Has been used as part of psychotherapy in very low doses (not street levels)

8 Effects Alterations in Perception

• Is distributed through the body • Get changes in thinking, mood, emotion • Enters the brain in about 60 minutes • Time is slowed • Effects last about 6 -8 hours (depends on the •Sensoryyp input intensifies dose) • Visualize imagined objects • Visual alterations • Is very potent • Colors may be heard • Sounds may be seen •Others

Phases • Somatic Phase Tolerance – Where absorption occurs and body changes occur • Sensory/Perceptual Phase • Get tolerance to the drug – Where sensory distortions and pseudo hallucinations occur • Get cross tolerance to other psychedelics – DidhDesired phase • Lost after several days of not taking the • Psychic Phase drug – Changes in mood, • No physical dependence – Disruption of thought process – True hallucinations occur • Few withdrawal effects occur (if any) – Not desired - Bad Trip

Side Effects Dimethyl-Tryptamine (DMT)

• Increased • Is an active ingredient in some plants – Heart rate • Produces effects similar to LSD – Blood Pressure • Binds to serotonin receptors – Pupils Dilate • Is usually snorted or smoked (not Oral) –Drowsiness • Onset 2 minutes – Sometimes nausea • Effects last 30 minutes • Overall, Is a relatively safe drug • Called businessman’s lunch or LSD

9 Effects Psilocybin and Psilocin

• Increased HR, BP, Temperature, etc • Are agents found in some mushrooms • Increased endorphin levels • Resemble but are less powerful than LSD • Causes • Peak effects in about 2 hours – visual hallucinations • Lasts about 6-8 hours – Intoxication • Are taken orally – Loss of awareness to surroundings • Are used in some Native American ceremonies

Ololiuqui Conclusion

• Found in morning glory seeds • Most are safe • Used for spiritual communication • Cause a wide variety of sometimes • Are about 1/10 th as powerful as LSD powerful effects • Are still potent

Psychedelic Anesthetics (Sernyl)

• Phencyclidine (Sernyl) • Angel Dust, Super grass, Killer Weed, • (Ketalar) Rocket Fuel • Was developed as an anesthetic • Were developed for anesthesia • Abandoned because of reactions in surgery • Both produce a psychedelic state • Still used as an immobilizing agent in • Psychedelic effects are unique - Do not veterinary anesthesia in large animals involve Serotonin, ACH or Dopamine • Blocks Ca influx via Glutamate NMDA neurons receptors

10 Effects Side Effects

• Detachment, • Acute anxiety • Slurred Speech loss of coordination • Paranoia • Auditory hallucinations • Feelinggpg of impending doom • Violent hostility • Severe mood disorders • Symptoms often resemble an acute psychotic •Amnesia disorder and may become permanent •others • Resembles schizophrenia psychotic states • Can be very dangerous

Ketamine (Ketalar) Effects

• Other Names Special K, K Overt hallucinatory effects are short lasting (one • Is a general anesthetic for humans and hour) animals • Effects – Judgment • Produces effects similar to PCP –Senses • Produces visual effects similar to LSD – Coordination • Get from diverted supplies and vet. Clinics, etc. • Are starting to see at rave parties

Sites of Action for PCP and NMDA Receptors Ketamine • Block N-Methyl-D-aspartate • Is a glutamate ionotropic receptor for (NMDA)/glutamate receptors calcium ions • Glutamate is an excitatory NT • Are widely distributed in the brain and SC • Induces a schizophrenic effect • High concentrations in the hippocampus • NMDA blockers are among the best and cortex amnesic drugs known • May aid in protecting brain tissue following • May be useful for head trauma trauma or strokes

11 Hallucinogens In General

• For the most part, have high LD50 levels. • Are some of the most potent drugs • Create a wide variety of effects •

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