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

• 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