Charles S. Grob, M.D. Harbor-UCLA Medical Center

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1 Inhalant Abuse in Adolescents Charles S. Grob, M.D. Harbor-UCLA Medical Center

5 Inhalants and their common chemical constituents Aerosols (may contain chlorofluorocarbons and fluorocarbon propellants) Deodorants and hairsprays Fabric protector sprays Spray paints (toluene, methyl isobutyl ketone) Vegetable oil sprays

6 Inhalants and their common chemical constituents Gases Bottled gas (propane) Cigarette lighter fluid (butane) Medical anaesthetics (ether, chloroform, nitrous oxide) Whipped cream (nitrous oxide)

7 Inhalants and their common chemical constituents Nitrites Amyl nitrites Butyl nitrites

8 Inhalants and their common chemical constituents Volatile solvents Correction fluids (1,1,1-trichloroethane) Dry-cleaning fluids (trichloroethylene, 1,1,1-trichloroethane) Glues (n-hexane, toluene, xylene) Nail polish remover (acetone, esters) Paint thinners and removers (dichloromethane, toluene, xylene) ye e) Petrol (benzene, n- hexane, toluene, xylene)

9 Inhalant Effects

10 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 The relatively l early age of regular users, as well as the associated severe biological and psychosocial py consequences, creates a significant public health problem There is no apparent safe level of use

11 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

12 INHALANT PHARMACOLOGY Rapid onset of excitatory effect Short duration of effect following single exposure High 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

13 NEUROTRANSMITTER EFFECTS OF INHALANTS Acute NMDA receptor inhibition Acute release of epinephrine As intoxication progresses, dopamine and GABA pathways are activated Chronic exposure w/withdrawal - - > hyperexcitability/hyperglutamatergic state similar to what occurs during withdrawal from alcohol Long-term exposure - - > persistent t dopaminergic dysfunction Enhanced serotonin-3 receptor p functioning similar to effects of CNS depressants and alcohol

14 INHALANT FACTS Use peaks between 7 th 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

15 RISK FACTORS FOR INHLANT ABUSE Child abuse Family instability Hx. foster care Low SEC Dropping out of school Delinquency Suicidal behavior Anti-social personality

16 SELF ADMINISTRATION OF INHALANTS Sniffing - inhaling vapors from open can or container Bagging - inhaling vapors that have been captured in a bag Huffing Inhaling volatile substances that have been soaked in a cloth

17 Signs of Abuse Drunk or disoriented appearance Paint or other stains on face, hands, or clothing Hidden empty spray paint or solvent containers and chemical soaked rags or clothing Slurred speech Strong chemical odors on breath or clothing Nausea or loss of appetite Red or runny nose Sores or rash around the nose or mouth

18 STAGES OF INHALANT INTOXICATION Stage > euphoria, excitation, exhilaration Stage > CNS depression, with slurred speech, drowsiness, agitation, tremor, visual hallucinations, weakness, headaches Stage > obtundation, ataxia, confusion, delirium Stage > stupor, seizures, coma, death

19 DIFFERENTIAL DIAGNOSES FOR INHALANT INTOXICATION Hypoxia Hypoglycemia Ethanol intoxication Drug intoxication Trauma Infection

20 LABORATORY EVALUATION MAY REVEAL Hypokalemia Hypophosphatemia Hypocalcemia Metabolic Acidosis Methemoglobinemia Carbon Monoxide poisoning

21 NEUROLOGIC CONSEQUENCES OF INHALANT ABUSE Ataxia Neuropathy Tremor Delirium Dementia Encephelopathy Cerebral atrophy Widespread d cerebellar damage Delays in mylenation and synaptic pruning Neurotoxicity demonstrated in pre-clinical models

23 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

24 PSYCHIATRIC CONSEQUENCES OF INHALANT ABUSE Anxiety Apathy Agitation Depression Inattention Insomnia Psychosis

25 MEDICAL CONSEQUENCES OF INHALANT ABUSE Skin damage Cardiovascular damage 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 )

26 INHALANT FATALITIES 50% of deaths caused by SSDS 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 ti fibrillation ill > death SSDS most often associated with toluene, propane, butane, aerosols

27 TREATMENT OF INHALANT ABUSE Supportive treatment of acute overdose (eg. airway, breathing, 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

29 Youth and Hallucinogens Charles S. Grob, M.D. Harbor-UCLA Medical Center

30 Topics Epidemiology Chemistry and Psychopharmacology Range of effects Aboriginal use of plant hallucinogens in rites of initiation iti Current Clinical Research with Psilocybin

31 Psychedelics (hallucinogens): Substances that produce changes in thought and mood that otherwise occur only during dreaming or at times of religious exaltation. (Jaffe)

32 Psychedelics (hallucinogens): Examples include: Lysergic Acid Diethylamide Psilocybin Ayahuasca DMT Peyote Mescaline MDMA Ibogaine PCP Ketamine

33 Epidemiology

34 Epidemiology In 2001, almost 1.4 million youths aged 12 to 17 had used hallucinogens at least once in their lifetime.

35 Epidemiology In 2004, 3% of 9th grade students and 4% of 12th grade students reported using LSD/psychedelics at least once in the past year Minnesota Student Survey Minnesota Student Survey, Minnesota Dept. of Health

36 Epidemiology Over the years, twelfth grade students were slightly more likely to report use than 9th grade students. For both grades, reported use of LSD/psychedelics peaked in 1998 and then declined in 2001 and Minnesota Student Survey, Minnesota Dept. of Health

37 Epidemiology Youths Aged 12 to 17 Reporting Lifetime Use of Specific Hallucinogens: 2001 National Household Survey on Drug Abuse, 2003

38 Epidemiology Males are more likely than females to report using LSD/psychedelics in the past year Minnesota Student Survey Minnesota Student Survey, Minnesota Dept. of Health

39 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 lti 12 and older declined d17 percent, tfrom 4.7 million to 3.9 million.

40 Epidemiology 2003 National Survey on Drug Use and Health (NSDUH) from the Substance Abuse and Mental Health Services Administration Past year use of hallucinogens among young adults was down 20 percent (from 8.4% to 6.7%).

41 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

42 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

43 Chemistry and Psychopharmacology

44 Three Chemical Classes of Psychedelic Molecules R N R R N R C O N R H RO NH 2 Phenethylamines RO N H Tryptamines N H Lysergamides

45 Peyote (Native American Church) H 3 CO NH 2 H 3 CO OCH 3 Mescaline Lophophora Williamsii (peyotl)

46 Ritual mushroom use by Aztecs R H 3 C N CH 3 N H Psilocybe Aztecorum Teonanacatl god s flesh R = OH; Psilocin i R = OPO 3 ; Psilocybin

47 Ergot The sclerotia of Claviceps purpura, from which ergot alkaloids, and ultimately lysergic acid, are derived. O N N CH 3 N H

48 Chemical relationship Between LSD and Serotonin Catalyzed 5-HT Research R N R O C N R N H Lysergamides Serotonin

50 Range of Effects

51 How to obtain biological data for hallucinogens? Here, take these, I want to see what they do to you

52 Acute Effects of Hallucinogens PHYSIOLOGICAL EFFECTS: Increased blood pressure and heart rate Increased body temperature re Abnormal rapid breathing Mydriasis Sweating

53 Acute Effects of Hallucinogens PHYSIOLOGICAL EFFECTS: Nausea and loss of appetite Dizziness Chills, flushing Shaking Abdominal discomfort Poor coordination

54 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.

55 Acute Effects of Hallucinogens PSYCHOLOGICAL EFFECTS: Disassociative reactions Illusion: mistaken perception of real stimuli Delusion: irrational thinking Confusion

56 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 Distorted body image (person feels as if they are floating or being pulled down by gravity)

57 Acute Effects of Hallucinogens PSYCHOLOGICAL EFFECTS: Delusions of grandeur leading to selfdestructive behaviors Fear over loss of control Paranoia Acute anxiety Acute panic (a 'bad trip')

58 Acute Effects of Hallucinogens How to help someone through a bad trip: Make sure that the user, and all people around them, are safe. Move and speak calmly in a confident manner. Address them by name; remind them of who they are.

59 Acute Effects of Hallucinogens How to help someone through a bad trip: Tell them who you are. If possible, don t leave them alone. This may mean staying with them for several hours. Reassure him/her that the experience they are having is time-limited, and remind them that it was caused by a drug.

60 Traditional Use of Plant Hallucinogens in Rites of Initiation

61 Kernos Vessel for dispensing i kykeon k The Eleusinian mysteries, from ca BC until 400 AD

62 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)

63 Peyote Ritual

64 Traditional Use Elder facilitated, culturally sanctioned pubertal rites of initiation Induction of ritualized and symbolic 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)

65 Traditional Use Ayahuasca in Cross-Cultural 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)

66 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 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)

67 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 type experiences having substantial and sustained personal meaning and spiritual significance Grob et al (2007): The use of psilocybin in patients with advanced cancer and existential anxiety it

Inhalants. Chapter 6. -Gandhi

Inhalants. Chapter 6. -Gandhi Chapter 6 Inhalants Keep your thoughts positive because your thoughts become your words. Keep your words positive because your words become your behaviors. Keep your behaviors positive because your behaviors