PSYC650 Psychopharmacology Opiates, Stimulants, ADRs, and Interactions.
PSYC650 Psychopharmacology THC, Inhalants, and Psychedelics.
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Transcript of PSYC650 Psychopharmacology THC, Inhalants, and Psychedelics.
PSYC650Psychopharmacology
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
• 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
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
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
Excretion
• In plasma for up to a week• Detectable in urine for about a
month• Urinalysis
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
Dependence
• Tolerance• Withdrawal
– Restlessness– Irritability– Anxiety– Reduced food intake– Insomnia– Nausea
Potential Uses
• Pain relief• Anti-inflammatory• Appetite stimulation• Antiemetic• Glaucoma• Migraines• Protective heart health
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
Why so Popular?
• Inexpensive• Ease of acquisition• Often legal in possession
Volatile Solvents
• 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
Nitrites
• Amyl “poppers”• Butyl “Rush”
– Liquid incense– Head cleaner
Routes of Admin
• Huffing– Solvent-soaked cloth (like chloroform in
spy movies)
• Bagging• Sniffing
– From open container
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
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
Sudden Sniffing Death Syndrome
• Unexpected disturbance to the heart rhythm
• Uncommon, but potential to all inhalants
Fetal Inhalant Syndrome?
• Not well studied, not fully established
• Low birthweight• Similar craniofacial effects as FAS• Retardation in growth• Speech and cognitive deficits
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
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
Acid Trip in 3 Phasesset and setting
1. Somatic• Increase in body
temp• Pupilary dilation• Incresed HR, BP• Dizziness• Drowsiness• Increased sweating
2. Perceptual• Alterations in
perceptions• Thinking• Emotions• Arousal • Self-image3. Psychic
• Depersonalization• Hallucinations• Loss of boundaries
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
Which of the following is consistent with THC
withdrawal?
Hyp
erso
mno
lence
Anxi
ety
Ther
more
gulatio
n is
...
Musc
ular s
pasm
s
25% 25%25%25%
1010
1. Hypersomnolence
2. Anxiety3. Thermoregulati
on issues4. Muscular
spasms
LSD, like many hallucinogenics, is
primarily __________ in nature.
Dopam
iner
gic
Nora
gener
gic
Opia
te
Ser
otonin
ergic
25% 25%25%25%1. Dopaminergic2. Noragenergic3. Opiate4. Serotoninergic
1010