Inhalant Abuse in AdolescentsInhalant Abuse in Adolescents

Inhalant Abuse in AdolescentsInhalant Abuse in Adolescents

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

Inhalants and their commonInhalants and their common chemical constituents

Aerosols (may contain chlorofluorocarbons and fluorocarbonchlorofluorocarbons and fluorocarbonpropellants)D d t d h iDeodorants and hairspraysFabric protector spraysSpray paints (toluene, methyl isobutyl ketone)Vegetable oil sprays


GasesBottled gas (propane)Cigarette lighter fluid (butane)Cigarette lighter fluid (butane)Medical anaesthetics (ether, chloroform nitrous oxide)chloroform, nitrous oxide)Whipped cream (nitrous oxide)


NitritesAmyl nitritesButyl nitritesButyl nitrites


Volatile solventsCorrection fluids

Nail polish remover (acetone, esters)

Correction fluids (1,1,1-trichloroethane)Dry cleaning fluids

Paint thinners and removers (dichloromethane Dry-cleaning fluids

(trichloroethylene, 1,1,1-trichloroethane)

(dichloromethane, toluene,xylene)1,1,1 trichloroethane)

Glues (n-hexane, toluene, xylene)

y e e)Petrol (benzene, n-hexane, toluene, xylene)toluene, xylene)

Inhalant Effects

INHALANT MISUSEThe deliberate inhalation of chemical vapors to produce intoxication or altered mental states (eg. euphoria), despite the potential for toxic damage to vital organsTh l ti l l f lThe relatively early age of regular users, as well as the associated severe biological and psychosocial consequences, creates a p y q ,significant public health problemThere is no apparent safe level of use

INHALANT EFFECTS ONINHALANT EFFECTS ON NEURODEVELOPMENTEarly 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 PHARMACOLOGYRapid onset of excitatory effectShort duration of effect following singleShort duration of effect following single exposureHigh concentrations and sustained effect gachieved after repetitive exposureHighly lipophilic with rapid access to the CNSSustained high brain/blood ratioSustained CNS depressant effect

NEUROTRANSMITTER EFFECTS OFNEUROTRANSMITTER EFFECTS OF INHALANTSAcute NMDA receptor inhibitionAcute NMDA receptor inhibitionAcute release of epinephrineAs intoxication progresses, dopamine and GABA

h i dpathways are activatedChronic exposure w/withdrawal - - > hyperexcitability/hyperglutamatergic state –hyperexcitability/hyperglutamatergic state similar to what occurs during withdrawal from alcoholL t > i t tLong-term exposure - - > persistent dopaminergic dysfunctionEnhanced serotonin-3 receptor functioning –p gsimilar to effects of CNS depressants and alcohol

INHALANT FACTSUse peaks between 7th and 9 th grade

INHALANT FACTS

Second most frequent drug of abuse after marijuana in early adolescenceLifetime prevalence for all ages (2006) – 12%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 findMost common inhalants in adolescents – glue, shoe polish and gasolinepolish and gasolineMost common inhalants in adults – gasses, especially nitrous oxide (whippets) and nitrites (poppers)High rates among street children throughout SouthHigh rates among street children throughout South America, Eastern Europe and Asia

RISK FACTORS FOR INHLANT ABUSE

Child abuseFamily instabilityFamily instabilityHx. foster careLow SECLow SECDropping out of schoolDelinquencyDelinquencySuicidal behaviorAnti-social personalityAnti-social personality

SELF‐ADMINISTRATION OFSELF‐ADMINISTRATION OF INHALANTS

“Sniffing” - inhaling vapors from open can or containeropen can or container“Bagging” - inhaling vapors that have been captured in a bagbeen captured in a bag“Huffing” – Inhaling volatile substances that have been soakedsubstances that have been soaked in a cloth

Si f AbSigns of Abuse

Drunk or disoriented appearancePaint or other stains on face, hands, or clothing, , gHidden empty spray paint or solvent containers and chemical‐soaked rags or clothingg gSlurred speechStrong chemical odors on breath or clothingg gNausea or loss of appetiteRed or runny noseySores or rash around the nose or mouth

STAGES OF INHALANTSTAGES OF INHALANT INTOXICATION

Stage 1 - - > euphoria, excitation, exhilarationStage 2 - - > CNS depression, with slurred speech, drowsiness, agitation, tremor, visual hallucinations, weakness, headachesStage 3 - - > obtundation, ataxia, confusion, deliriumdeliriumStage 4 - - > stupor, seizures, coma, death

DIFFERENTIAL DIAGNOSES FORDIFFERENTIAL DIAGNOSES FOR INHALANT INTOXICATION

HypoxiaH l iHypoglycemiaEthanol intoxicationDrug intoxicationTraumaTraumaInfection

LABORATORY EVALUATION MAYLABORATORY EVALUATION MAY REVEAL

HypokalemiaypHypophosphatemiaHypocalcemiaHypocalcemiaMetabolic AcidosisMethemoglobinemiaMethemoglobinemiaCarbon Monoxide poisoning

NEUROLOGIC CONSEQUENCES OF INHALANT ABUSE

AtaxiaNeuropathyTremorDeliriumDementiaDementiaEncephelopathyCerebral atrophyWid d b ll dWidespread cerebellar damageDelays in mylenation and synaptic pruningNeurotoxicity demonstrated in pre-clinicalNeurotoxicity demonstrated in pre clinical models

NEUROPSYCHOLGOICAL CONSEQUENCES OF INHALANT ABUSE

Impaired attentionImpaired speed of informationImpaired speed of information processingImpaired learning and memoryImpaired learning and memoryImpaired executive abilitiesImpaired tests of verbal intelligenceImpaired tests of verbal intelligenceCognitive impairment consistent with white matter pathologywith white matter pathology

PSYCHIATRIC CONSEQUENCES OFPSYCHIATRIC CONSEQUENCES OF INHALANT ABUSE

AnxietyApathyp yAgitationDepressionInattentionInsomnia PsychosisPsychosis

MEDICAL CONSEQUENCES OFMEDICAL CONSEQUENCES OF INHALANT ABUSE

Skin damageCardiovascular damagegLiver toxicityRenal failureBone Impaired immune system response to viral infections and tumor growthIncreased HIV risk (particularly withIncreased HIV risk (particularly with abuse of iso-butyl nitrites – “poppers”)

INHALANT FATALITIES50% of deaths caused by SSDS –Sudden Sniffing Death Syndromeg yInhalants - - > sensitize myocardial cell membranes to depolarize. If user is startled or engages in vigorous activity ‐‐ > increased release of catecholamines ‐ ‐

t i l fib ill ti d th> ventricular fibrillation ‐ ‐ > deathSSDS most often associated with toluene propane butane aerosolstoluene, propane, butane, aerosols

TREATMENT OF INHALANT ABUSETREATMENT OF INHALANT ABUSESupportive treatment of acute overdose (eg. airway, breathing, circulation)g, )Beta-blockers may be used to protect against fatal arrhythmiasNo medication can reverse the effects of most inhalantsLong-term treatment of inhalant abuse includes:

counselingstrict abstinencedrug treatment protocols (eg. 12-Step programs)

Need for more basic and clinical research on treatment and prevention

Y th dYouth andHallucinogensg

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

Topics

Epidemiologyp gyChemistry and Psychopharmacology Range of effectsRange of effects Aboriginal use of plant hallucinogens in it f i iti tirites of initiation

Current Clinical Research with Psilocybin

PsychedelicsPsychedelics ((hallucinogenshallucinogens):):

Substances that produce changes in thought and moodchanges in thought and mood that otherwise occur only during dreaming or at times of religiousdreaming or at times of religious exaltation.

(Jaffe)

E l i l d

PsychedelicsPsychedelics ((hallucinogenshallucinogens):):Examples include:

•Lysergic Acid Diethylamide•Psilocybin•Psilocybin•Ayahuasca•DMT•Peyote•Mescaline•MDMAMDMA•Ibogaine•PCP•Ketamine•Ketamine

Epidemiology

Epidemiology

In 2001 almost 1 4 million youths aged 12In 2001, almost 1.4 million youths aged 12 to 17 had used hallucinogens at least once in their lifetimein their lifetime.

Epidemiology

In 2004 3% of 9th grade students and 4%In 2004, 3% of 9th grade students and 4% of 12th grade students reported using LSD/psychedelics at least once in the pastLSD/psychedelics at least once in the past year.

1992-2004 Minnesota Student Survey1992 2004 Minnesota Student Survey,Minnesota Dept. of Health

Epidemiology

Over the years, twelfth grade students y , gwere slightly more likely to report use than 9th grade students. g

For both grades reported use ofFor both grades, reported use of LSD/psychedelics peaked in 1998 and then declined in 2001 and 2004then declined in 2001 and 2004.

1992-2004 Minnesota Student Survey,Minnesota Dept. of Health

EpidemiologyYouths Aged 12 to 17 Reporting Lifetime Use of Specific

Hallucinogens: 2001

National Household Survey on Drug Abuse, 2003

EpidemiologyMales are more likely than females to report using LSD/psychedelics in the past year.

1992-2004 Minnesota Student Survey1992 2004 Minnesota Student Survey,Minnesota Dept. of Health

Epidemiology2003 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

l ti 12 d ld d li d 17 t fpopulation 12 and older declined 17 percent, from 4.7 million to 3.9 million.

Epidemiology

2003 National Survey on Drug Use and Health (NSDUH) f th S b t Ab d M t l H lth S ifrom the Substance Abuse and Mental Health Services Administration

Past year use of hallucinogens among young adults was down 20 percent (from y g p (8.4% to 6.7%).

Epidemiology

Among youths, blacks were less likely thanAmong youths, blacks were less likely than whites, Asians, or Hispanics to have used any hallucinogen in their lifetime.


EpidemiologyFigure 3. Percentages of Youths Aged 12 to 17 Reporting it Would

Be Fairly or Very Easy to Obtain LSD, by Race/Ethnicity*: 2001


Chemistry and PsychopharmacologyChemistry and Psychopharmacology

Three Chemical Classes ofThree Chemical Classes ofPsychedelic MoleculesPsychedelic Molecules

RR C

N RR

NRR

N RC

HO

RONH2

RO

N

H

N

HPhenethylaminesPhenethylamines TryptaminesTryptamines LysergamidesLysergamides

Peyote (Native American Church)Peyote (Native American Church)Peyote (Native American Church)Peyote (Native American Church)

NH2H3CO

OCHH3CO

MescalineMescaline

OCH3

Lophophora Williamsii

MescalineMescaline

Lophophora Williamsii(peyotl)

Ritual mushroom use by Aztecs Ritual mushroom use by Aztecs Ritual mushroom use by Aztecs Ritual mushroom use by Aztecs

H C

R

N CH3H3C

N

R OH P il iR OH P il i

NH

R = OH; PsilocinR = OH; PsilocinR = OPOR = OPO33; Psilocybin; Psilocybin

Psilocybe AztecorumPsilocybe AztecorumTeonanacatl “god’s flesh”

The sclerotia of The sclerotia of ErgotErgotErgotErgot Claviceps purpuraClaviceps purpura, , from which ergot from which ergot alkaloids and alkaloids and

ErgotErgotErgotErgot

alkaloids, and alkaloids, and ultimately lysergic ultimately lysergic acid, are derived. acid, are derived.

CH3

O

NCH3N

NNH

Chemical relationship Between LSD and Chemical relationship Between LSD and Serotonin Catalyzed 5Serotonin Catalyzed 5--HT Research HT Research

R

N

C

R R

NRC

O NN

N

H

N

H

N

HLysergamides Serotonin

Range of EffectsRange of Effects

How to obtain biological data for

hallucinogens?

Here, take these, I want Here, take these, I want to see what they do to to see what they do to yy

youyou

Acute Effects of Hallucinogens

PHYSIOLOGICAL EFFECTS:Increased blood pressure and heart rateIncreased bod temperat reIncreased body temperatureAbnormal rapid breathingMydriasisSweatingg


PHYSIOLOGICAL EFFECTS:PHYSIOLOGICAL EFFECTS:Nausea and loss of appetite DizzinessDizzinessChills, flushing ShakingShakingAbdominal discomfort Poor coordinationPoor coordination


PSYCHOLOGICAL EFFECTS:PSYCHOLOGICAL EFFECTS:Sense of relaxation and wellbeingAltered moodAltered moodSensory distortionsDepersonalizationImpaired concentration and motivationLoss of judgment, slowed reaction time.


PSYCHOLOGICAL EFFECTSPSYCHOLOGICAL EFFECTS:Disassociative reactionsIllusion: mistaken perception of real stimuliDelusion: irrational thinkingConfusion


PSYCHOLOGICAL EFFECTS:PSYCHOLOGICAL EFFECTS:Distorted sense of time (e.g. minutes can seem as slow as hours; reliving old events)as slow as hours; reliving old events) Distorted sense of space Distorted body image (person feels as if theyDistorted body image (person feels as if they are floating or being pulled down by gravity)


PSYCHOLOGICAL EFFECTS:Delusions of grandeur leading to self-destructive behaviors F l f lFear over loss of controlParanoiaAcute anxietyAcute panic (a 'bad trip')


How to help someone through a bad trip:How to help someone through a bad trip:• Make sure that the user, and all people around

them are safethem, are safe.• Move and speak calmly in a confident manner.• Address them by name; remind them of who• Address them by name; remind them of who

they are.


How to help someone through a bad trip:p g p• Tell them who you are.• If possible, don’t leave them alone. This may p , y

mean staying with them for several hours.• Reassure him/her that the experience they are p y

having is time-limited, and remind them that it was caused by a drug.

Traditional Use of Plant Hallucinogens inTraditional Use of Plant Hallucinogens in Rites of Initiation

K V l f di i K V l f di i k kk kKernos Vessel for dispensing Kernos Vessel for dispensing kykeonkykeon

The Eleusinian mysteries, from ca. 1500 BC until 400 AD

Traditional UseAnthropological 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 RitualPeyote Ritual

Traditional Use

Elder facilitated, culturally sanctioned pubertal rites of initiationinitiation

Induction of ritualized and symbolic death of the child ywith emergence into initiatory rebirth of new adult identity

Implicit safeguards in indigenous initiatory andImplicit 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 UseAyahuasca in Cross-Cultural Perspective:Ayahuasca in Cross Cultural Perspective:

Subjects recruited from familiesSubjects recruited from families belonging to the UDV60 subjects with hoasca exposure60 subjects with hoasca exposure60 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 UseAyahuasca in Cross-Cultural Perspective

No difference on neuropsychological assessmentLower anxiety ratings in hoasca exposed adolescentsLower alcohol use in hoasca exposed adolescentspFindings 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 obsessive-compulsive disorderGriffiths et al (2006): Psilocybin can occasion mystical type experiences having substantial andmystical-type experiences having substantial and sustained personal meaning and spiritual significancegGrob et al (2007): The use of psilocybin in patients with advanced cancer and existential

i tanxiety

Inhalant Abuse in AdolescentsInhalant Abuse in Adolescents

Documents

Transcript of Inhalant Abuse in AdolescentsInhalant Abuse in Adolescents