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Inhalant Abuse in Adolescents Charles S. Grob, M.D. Harbor-UCLA Medical Center Inhalants and their common chemical constituents Aerosols (may contain chlorofluorocarbons and fluorocarbon propellants) D d Deodorants t and d hairsprays h i Fabric protector sprays Spray paints (toluene, methyl isobutyl ketone) Vegetable oil sprays Inhalants and their common chemical constituents Gases Bottled gas (propane) Cigarette lighter fluid (butane) Medical anaesthetics (ether, chloroform nitrous oxide) chloroform, Whipped cream (nitrous oxide) Inhalants and their common chemical constituents Nitrites Amyl nitrites Butyl nitrites Inhalants and their common chemical constituents Volatile solvents Correction fluids (1,1,1-trichloroethane) Nail polish remover (acetone, esters) Dry-cleaning Dry cleaning fluids (trichloroethylene, 1,1,1-trichloroethane) 1,1,1 trichloroethane) Paint thinners and removers (dichloromethane (dichloromethane, toluene, xylene) y e e) Petrol (benzene, nhexane, toluene, xylene) Glues (n-hexane, toluene, xylene) Inhalant Effects INHALANT MISUSE The deliberate inhalation of chemical vapors to produce intoxication or altered mental states (eg. euphoria), despite the potential for toxic damage to vital organs Th relatively The l ti l early l age off regular l users, as well as the associated severe biological and psychosocial p y consequences, q , creates a significant public health problem There is no apparent safe level of use INHALANT EFFECTS ON NEURODEVELOPMENT Early adolescence is a period of critical neurodevelopmental maturation (eg. synaptic pruning and increased mylenation) Chronic inhalant exposure during early adolescence - - > greater structural and functional brain disturbance - - > cognitive impairment INHALANT PHARMACOLOGY Rapid onset of excitatory effect Short duration of effect following single exposure High g concentrations and sustained effect achieved after repetitive exposure Highly lipophilic with rapid access to the CNS Sustained high brain/blood ratio Sustained CNS depressant effect NEUROTRANSMITTER EFFECTS OF NEUROTRANSMITTER EFFECTS OF INHALANTS Acute NMDA receptor inhibition Acute release of epinephrine As intoxication progresses, dopamine and GABA pathways are activated h i d Chronic exposure w/withdrawal - - > hyperexcitability/hyperglutamatergic state – similar to what occurs during withdrawal from alcohol L Long-term t exposure - - > persistent i t t dopaminergic dysfunction Enhanced serotonin-3 receptor functioning – p g similar to effects of CNS depressants and alcohol INHALANT FACTS INHALANT FACTS Use peaks between 7th and 9 th grade Second most frequent drug of abuse after marijuana in early adolescence Lifetime prevalence for all ages (2006) – 12% In U.S. – highest among Native Americans and Latinos lowest among African Americans Inexpensive, legal and easy to find Most common inhalants in adolescents – glue, shoe polish and gasoline Most common inhalants in adults – gasses, especially nitrous oxide (whippets) and nitrites (poppers) High rates among street children throughout South America, Eastern Europe and Asia RISK FACTORS FOR INHLANT ABUSE Child abuse Family instability Hx. foster care Low SEC Dropping out of school Delinquency Suicidal behavior Anti-social personality SELF‐ADMINISTRATION OF SELF‐ADMINISTRATION OF INHALANTS “Sniffing” - inhaling vapors from open can or container “Bagging” - inhaling vapors that have been captured in a bag been captured in a bag “Huffing” – Inhaling volatile substances that have been soaked in a cloth Si Signs of Abuse f Ab Drunk or disoriented appearance Paint or other stains on face, hands, or clothing , , g Hidden empty spray paint or solvent containers g g and chemical‐soaked rags or clothing Slurred speech Strong chemical odors on breath or clothing g g Nausea or loss of appetite Red or runny nose y Sores or rash around the nose or mouth STAGES OF INHALANT STAGES OF INHALANT INTOXICATION Stage 1 - - > euphoria, excitation, exhilaration Stage 2 - - > CNS depression, with slurred speech, drowsiness, agitation, tremor, visual hallucinations, weakness, headaches Stage 3 - - > obtundation, ataxia, confusion, delirium Stage 4 - - > stupor, seizures, coma, death DIFFERENTIAL DIAGNOSES FOR DIFFERENTIAL DIAGNOSES FOR INHALANT INTOXICATION Hypoxia H Hypoglycemia l i Ethanol intoxication Drug intoxication Trauma Infection LABORATORY EVALUATION MAY LABORATORY EVALUATION MAY REVEAL Hypokalemia yp Hypophosphatemia Hypocalcemia Metabolic Acidosis Methemoglobinemia Carbon Monoxide poisoning NEUROLOGIC CONSEQUENCES OF INHALANT ABUSE Ataxia Neuropathy Tremor Delirium Dementia Encephelopathy Cerebral atrophy Wid Widespread d cerebellar b ll damage d Delays in mylenation and synaptic pruning Neurotoxicity demonstrated in pre-clinical pre clinical models NEUROPSYCHOLGOICAL CONSEQUENCES OF INHALANT ABUSE Impaired attention Impaired speed of information processing Impaired learning and memory Impaired executive abilities Impaired tests of verbal intelligence Cognitive impairment consistent with white matter pathology PSYCHIATRIC CONSEQUENCES OF PSYCHIATRIC CONSEQUENCES OF INHALANT ABUSE Anxiety Apathy p y Agitation Depression Inattention Insomnia Psychosis MEDICAL CONSEQUENCES OF MEDICAL CONSEQUENCES OF INHALANT ABUSE Skin damage Cardiovascular damage g Liver toxicity Renal failure Bone Impaired immune system response to viral infections and tumor growth Increased HIV risk (particularly with abuse of iso-butyl nitrites – “poppers”) INHALANT FATALITIES 50% of deaths caused by SSDS – g y Sudden Sniffing Death Syndrome Inhalants - - > sensitize myocardial cell membranes to depolarize. If user is startled or engages in vigorous activity ‐ ‐ > increased release of catecholamines ‐ ‐ > ventricular fibrillation ‐ t i l fib ill ti ‐ > death d th SSDS most often associated with toluene propane toluene, propane, butane butane, aerosols TREATMENT OF INHALANT ABUSE Supportive treatment of acute overdose (eg. airway, breathing, g, circulation)) Beta-blockers may be used to protect against fatal arrhythmias No medication can reverse the effects of most inhalants Long-term treatment of inhalant abuse includes: counseling strict abstinence drug treatment protocols (eg. 12-Step programs) Need for more basic and clinical research on treatment and prevention Youth Y th and d Hallucinogens g Charles S. Grob, M.D. Harbor-UCLA Medical Center Topics Epidemiology p gy Chemistry and Psychopharmacology Range of effects Aboriginal use of plant hallucinogens in rites it off initiation i iti ti Current Clinical Research with Psilocybin Psychedelics (hallucinogens): Substances that produce changes in thought and mood that otherwise occur only during dreaming or at times of religious exaltation. (Jaffe) Psychedelics (hallucinogens): E Examples l include: i l d •Lysergic Acid Diethylamide •Psilocybin •Ayahuasca •DMT •Peyote •Mescaline •MDMA MDMA •Ibogaine •PCP •Ketamine Epidemiology Epidemiology In 2001, 2001 almost 1.4 1 4 million youths aged 12 to 17 had used hallucinogens at least once in their lifetime lifetime. Epidemiology In 2004, 2004 3% of 9th grade students and 4% of 12th grade students reported using LSD/psychedelics at least once in the past year. 1992 2004 Minnesota Student Survey 1992-2004 Survey, Minnesota Dept. of Health Epidemiology Over the y years,, twelfth ggrade students were slightly more likely to report use grade students. than 9th g For both grades grades, reported use of LSD/psychedelics peaked in 1998 and then declined in 2001 and 2004. 2004 1992-2004 Minnesota Student Survey, Minnesota Dept. of Health Epidemiology Youths Aged 12 to 17 Reporting Lifetime Use of Specific Hallucinogens: 2001 National Household Survey on Drug Abuse, 2003 Epidemiology Males are more likely than females to report using LSD/psychedelics in the past year. 1992 2004 Minnesota Student Survey 1992-2004 Survey, Minnesota Dept. of Health Epidemiology 2003 National Survey on Drug Use and Health (NSDUH) from the Substance Abuse and Mental Health Services Administration Overall, the use of hallucinogens continued to fall. Past year users of hallucinogens among the population l ti 12 andd older ld declined d li d 17 percent, t from f 4.7 million to 3.9 million. Epidemiology 2003 National Survey on Drug Use and Health (NSDUH) f from the th Substance S bt Abuse Ab and dM Mental t lH Health lth Services S i Administration Past year use of hallucinogens among yyoungg adults was down 20 percent p (from ( 8.4% to 6.7%). Epidemiology Among youths, blacks were less likely than whites, Asians, or Hispanics to have used any hallucinogen in their lifetime. National Household Survey on Drug Abuse, 2003 Epidemiology Figure 3. Percentages of Youths Aged 12 to 17 Reporting it Would Be Fairly or Very Easy to Obtain LSD, by Race/Ethnicity*: 2001 National Household Survey on Drug Abuse, 2003 Chemistry and Psychopharmacology Three Chemical Classes of Psychedelic Molecules R R RO NH2 N R C R N R H RO N Phenethylamines O N H Tryptamines N H Lysergamides Peyote (Native American Church) H3CO NH2 H3CO OCH3 Mescaline Lophophora Williamsii (peyotl) Ritual mushroom use by Aztecs H3C N CH3 R N H Psilocybe Aztecorum Teonanacatl “god’s flesh” R = OH OH; P Psilocin il i R = OPO3; Psilocybin Ergot The sclerotia of Claviceps purpura, from which ergot alkaloids and alkaloids, ultimately lysergic acid, are derived. O N N CH3 N H Chemical relationship Between LSD and Serotonin Catalyzed 5 5--HT Research R O N C R N R N N H Lysergamides Serotonin Range of Effects How to obtain biological data for hallucinogens? Here, take these, I want to see what they y do to you Acute Effects of Hallucinogens PHYSIOLOGICAL EFFECTS: Increased blood pressure and heart rate Increased body bod temperature temperat re Abnormal rapid breathing Mydriasis Sweating g Acute Effects of Hallucinogens PHYSIOLOGICAL EFFECTS: Nausea and loss of appetite Dizziness Chills, flushing Shaking Abdominal discomfort Poor coordination Acute Effects of Hallucinogens PSYCHOLOGICAL EFFECTS: Sense of relaxation and wellbeing Altered mood Sensory distortions Depersonalization Impaired concentration and motivation Loss of judgment, slowed reaction time. Acute Effects of Hallucinogens PSYCHOLOGICAL EFFECTS: EFFECTS Disassociative reactions Illusion: mistaken perception of real stimuli Delusion: irrational thinking Confusion Acute Effects of Hallucinogens PSYCHOLOGICAL EFFECTS: Distorted sense of time (e.g. minutes can seem as slow as hours; reliving old events) Distorted sense of space Distorted body image (person feels as if they are floating or being pulled down by gravity) Acute Effects of Hallucinogens PSYCHOLOGICAL EFFECTS: Delusions of grandeur leading to selfdestructive behaviors F over lloss off controll Fear Paranoia Acute anxiety Acute panic (a 'bad trip') Acute Effects of Hallucinogens How to help someone through a bad trip: • • • Make sure that the user, and all people around them are safe. them, safe Move and speak calmly in a confident manner. Address them by name; remind them of who they are. Acute Effects of Hallucinogens How to help p someone through g a bad trip: p • • • Tell them who you are. If ppossible,, don’t leave them alone. This mayy mean staying with them for several hours. Reassure him/her that the experience p they y are having is time-limited, and remind them that it was caused by a drug. Traditional Use of Plant Hallucinogens in Rites of Initiation Kernos K V Vessell for f di dispensing i kykeon k k The Eleusinian mysteries, from ca. 1500 BC until 400 AD Traditional Use Anthropological evidence dating back to earliest evidence of human existence Limited supply - under control of tribal authority and reserved solely for ritual use Tribal initiation rites - accepted plant hallucinogens to be of sacred origin and regarded them with awe and reverence (Grob and de Rios, 1992) ((de Rios and Grob, 1994)) Peyote Ritual Traditional Use Elder facilitated, culturally sanctioned pubertal rites of initiation Induction of ritualized and symbolic y death of the child with emergence into initiatory rebirth of new adult identity Implicit safeguards in indigenous initiatory and transitional rites and traditions are often lacking in contemporary culture (Grob and de Rios, 1992) (de Rios and Grob, 1994) Traditional Use Ayahuasca in Cross-Cultural Cross Cultural Perspective: Subjects recruited from families belonging to the UDV 60 subjects with hoasca exposure 60 controls without hoasca exposure * Hoasca Project (Callaway et al, 1994, 1996, 1999; Grob et al, 1996; McKenna et al, 1998) * Hoasca in Adolescence Study (de Rios and Grob, 2005) Traditional Use Ayahuasca in Cross-Cultural Perspective No difference on neuropsychological assessment Lower anxiety ratings in hoasca exposed adolescents Lower alcohol use in hoasca exposed p adolescents Findings consistent with earlier study with adult (UDV) subjects * Hoasca Project (Callaway et al, 1994, 1996, 1999; Grob et al, 1996; McKenna et al, 1998) * Hoasca in Adolescence Study (de Rios and Grob, 2005) CURRENT RESEARCH WITH PSYILOCYBIN Moreno et al (2006): Safety, tolerability and efficacy of psilocybin in patients with obsessivecompulsive disorder Griffiths et al (2006): Psilocybin can occasion mystical type experiences having substantial and mystical-type sustained personal meaning and spiritual significance g Grob et al (2007): The use of psilocybin in patients with advanced cancer and existential anxiety i t