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PSYC650 Psychopharmacology

PSYC650 Psychopharmacology. THC, Inhalants, and Psychedelics. THC. Cannabis Sativa Delta-9-tetrahydrocannibanol Highly lipophilic Binds to CB1 in brain, CB2 in periphery CB1 is presynaptic Inhibits GABA and CA+ Facilitates K+ Endogenous cannabinoid, anandamide. CB1: Power in Numbers.

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PSYC650 Psychopharmacology

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  1. PSYC650Psychopharmacology THC, Inhalants, and Psychedelics

  2. THC • Cannabis Sativa • Delta-9-tetrahydrocannibanol • Highly lipophilic • Binds to CB1 in brain, CB2 in periphery • CB1 is presynaptic • Inhibits GABA and CA+ • Facilitates K+ • Endogenous cannabinoid, anandamide

  3. CB1: Power in Numbers • More CB1 receptors in brain than opioid receptors • This large number accounts for the effect of THC • Cerebral cortex • Hippocampus • Basal ganglia • Cerebellum • THC tends to activate 20% of these at any given time

  4. CB2: Holding Down the Periphery • Heart • Spinal cord (yes, this is really CNS, not periphery) • Inflammation and pain • Analgesic • CB3? • Some evidence for more CB receptors on the horizon

  5. Smoking • Typically under 8% THC content in marijuana • Hashish 10-20% • Simsemilla 5-8% (dried tops of plants) • Marijuana usually has 2-5% but can be bred and processed to reach around 30% • 25-30% becomes available in smoke • Also ingestion, nasal spray, patch

  6. Excretion • In plasma for up to a week • Detectable in urine for about a month • Urinalysis

  7. A Handful of Effects • Increased heart rate • Increased blood pressure • Euphoria • Mild sensory enhancement • Dissociation • Impaired cognition and reaction time • Memory effects • Appetite effects • No considerable psychiatric or gateway effects • Only about 1/3 go on to use othe drugs

  8. Dependence • Tolerance • Withdrawal • Restlessness • Irritability • Anxiety • Reduced food intake • Insomnia • Nausea

  9. Potential Uses • Pain relief • Anti-inflammatory • Appetite stimulation • Antiemetic • Glaucoma • Migraines • Protective heart health

  10. Inhalants • Volatile substances tht produce chemical vapors that can be inhaled to induce psychoactive effects • The Pythia at Delphi • Incenses • Ether (13th Century) • By 1700 substitute for ETOH as an anesthetic • NO2 in 1776 • Recretational drug • Chloroform in 1831 • Another ETOH substitute

  11. Why so Popular? • Inexpensive • Ease of acquisition • Often legal in possession

  12. Adhesives Aerosols Solvents and gasses Nail polish remover Paint thinner White out Markers Toluene Gasoline Feces Cleaning agents Food products Whipped cream (whippets) Cooking spray Volatile Solvents

  13. Nitrites • Amyl “poppers” • Butyl “Rush” • Liquid incense • Head cleaner

  14. Routes of Admin • Huffing • Solvent-soaked cloth (like chloroform in spy movies) • Bagging • Sniffing • From open container

  15. Subjective effects • Volatile solvents • Similar feeling to alcohol and anesthetics • Dizziness • Disorientation • Stimulation • Light-headedness • Muscular incoordination • Possible loss of consciousness • Dilation of blood vessels • Headache • Blood levels peak quickly • Highly lipophilic • Not just anoxia: GABA, we think, is heavily involved

  16. Physiological Impact • Globally impacts the brain • Many effect the myelin sheath • Toulene impacts optic nerve, acoustic nerve and kidney • Lung damage • Trichlorethelene (paints and correction fluid) impacts liver

  17. Sudden Sniffing Death Syndrome • Unexpected disturbance to the heart rhythm • Uncommon, but potential to all inhalants

  18. Fetal Inhalant Syndrome? • Not well studied, not fully established • Low birthweight • Similar craniofacial effects as FAS • Retardation in growth • Speech and cognitive deficits

  19. LSD • Albert Hoffman in 1938 • Studying ergot • Lysergic Acid-25 • Shelved in 1938, but dusted it off in 1943 • Accidental dose and a very strange bike ride

  20. Kinetics and Dynamics • Direct 5-HT2A receptor in forebrain • May also stimulate 5-HT autoreceptors in raphe • Dorsal raphe is a main area for filtering sensory stimuli • Rich in serotonin • Hydrophilic • Very small, so crosses BBB easily • Also crosses placenta • Absorbed within 60 minutes • Usual duration is 6-8 hours • Peak concentration in blood in about 3 hours • Metabolized in liver and excreted via urine in about 24 hours • 1-10% is unchanged

  21. Somatic Increase in body temp Pupilary dilation Incresed HR, BP Dizziness Drowsiness Increased sweating 2. Perceptual Alterations in perceptions Thinking Emotions Arousal Self-image Psychic Depersonalization Hallucinations Loss of boundaries Acid Trip in 3 Phasesset and setting

  22. ADRs • Psychosis (persistent) • Affective disorder (persistent) • Exacerbation of preexisting mental illness • Post-hallucinogenic perceptual disorder (‘flashbacks’) • Lethality • Rare TI = 280 • Most deaths caused by accident, suicide, homicide • Tolerance • Withdrawal not noted

  23. 10 Which of the following is consistent with THC withdrawal? • Hypersomnolence • Anxiety • Thermoregulation issues • Muscular spasms

  24. 10 LSD, like many hallucinogenics, is primarily __________ in nature. • Dopaminergic • Noragenergic • Opiate • Serotoninergic

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