Transcript Inhalants and GHB

Inhalants and GHB
Presented and put together by:
Allie Stoecker, Molly Schlichenmayer, and Kaylyn Evans
Inhalants
• From the book: “Represent a novel group of abused
substances” (pg. 366).
• Characteristics:
– 1) either volatile liquids or gases at room temp.
– 2) used by sniffing fumes, inhaling fumes, or
spraying an aerosol directly into one’s nose or
mouth
– 3) do not belong to another defined class of
abused substances
4 Groups of Inhalants
• Volatile solvents = liquid at room temp. but give off
fumes that can be inhaled
– Adhesives, correction fluids, paint thinners & removers
• Aerosols = sprays that contain various solvents and
propellants
– Hair spray, vegetable oil cooking sprays
• Gases
– Whipped cream dispensers, propane tanks, butane lighters
• Nitrites = compounds of nitrogen
– Amyl nitrite, butyl nitrile, cyclohexyl nitrite
Behavioral Effects
• First 3 classes are taken for euphoric effects
• Nitrites are taken to heighten sexual arousal &
pleasure
• Many of the effects are similar to alcohol intoxication
– Initially: euphoria, stimulation, disinhibition, followed by
drowsiness and light-headedness
– Heavier exposure: stronger depressant effects including
slurred speech, poor coordination, sensory distortions
– Even higher does: anesthesia, loss of consciousness, coma
– Some individuals experience delusional ideas
Behavioral Effects - Tolerance
• Repeated use has been found to sometimes
lead to tolerance
• Rewarding and reinforcing effects
– Little is known about the mechanisms of RFT
• Possible Inhalant Withdrawal Syndrome:
– Nausea, tremors, irritability, sleep disturbances
– But this still remains controversial
Neural Effects
• Reduces CNS excitability and causes
behavioral impairments
• First 3 groups act directly on nerve cells
• But not all will work the same way on the
brain
– Different chemical compositions
• Substances are highly lipid soluble, so cross
BBB easily and quickly
Neural Effects (cont.)
• CNS-depressant effects due to interactions
with various ionotropic receptors
– Enhance the function of GABAA and glycine
receptors
– Inhibit the activity of NMDA-glutamate receptors
15.2 PET images of brain uptake and distribution of radiolabeled toluene in a baboon
Health Risks
• Will make you dumb(er)!
– Performed more poorly on several neuropsychological
tests, showing cognitive impairment
• Repeated use can damage the liver, kidneys and
lungs
• Brain is vulnerable to toxicity
– Damage to the white matter thru loss of myelin
• Sudden Sniffing Death Syndrome
– A single use can lead to a fatal cardiac arrhythmia
GHB
• Gamma-Hydroxybutyrate
• Closely related to GABA, but crosses BBB more
easily
• Produces sedation and sometimes anesthesia
• Administered per os
• Rapidly absorbed
History
• Henri Laborit
• 1980’s – body-builders
• Banned in 1990, but then became a “club
drug” and later a “date rape” drug
• 2000, Schedule I drug
• Sometimes still used in patients with
narcolepsy (to reduce the incidence of
cataplexy)
Behavioral Effects
• Low doses: produce alcohol-like experience
• Higher doses: lethargy, ataxia, slurred speech,
dizziness, nausea, vomiting
– Paradoxical CNS excitation at high doses
• Overdose is dangerous due to respiratory
depression and comatose condition
Neural Effects and Tolerance
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Possibly inhibits DA release
Evidence for reinforcement is inconsistent
Fewer adverse effects
Reports of dependence are only from case
studies and self-reports
– Withdrawal symptoms are reported
• Insomnia, anxiety, tremors, psychosis for higher doses
Hypotheses for Mechanism of Action
• 1. Mediated by activation of pre- &/or
postsynaptic GABAB receptors
– Possibly a direct GABAB agonist with low affinity
– Possibly metabolized to GABA in the brain
• 2. Mediated by specific GHB receptor
– But receptor structure is not known
– Seem to be non-uniformly distributed
– High levels of binding in some areas, but not in others
• Endogenous GHB and exogenous GHB thought to
activate central receptors
Both GHB and Inhalants are CNS
depressants