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%

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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

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