Inhalants and GHB Presented and put together by

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