1. Inhalants and GHB Presented and put together by: Allie Stoecker, Molly Schlichenmayer, and Kaylyn Evans

2. 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

3. 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

5. 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

6. 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

7. 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

8. Neural Effects (cont.) CNS-depressant effects due to interactions with various ionotropic receptors – Enhance the function of GABA A and glycine receptors – Inhibit the activity of NMDA-glutamate receptors

9. 15.2 PET images of brain uptake and distribution of radiolabeled toluene in a baboon

10. 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

11. GHB Gamma-Hydroxybutyrate Closely related to GABA, but crosses BBB more easily Produces sedation and sometimes anesthesia Administered per os Rapidly absorbed

12. 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)

13. 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

14. 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

15. Hypotheses for Mechanism of Action 1. Mediated by activation of pre- &/or postsynaptic GABA B receptors – Possibly a direct GABA B 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

16. Both GHB and Inhalants are CNS depressants