Inhalant Abuse in AdolescentsInhalant Abuse in Adolescents
Transcript of 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
Inhalants and their commonInhalants and their common chemical constituents
GasesBottled gas (propane)Cigarette lighter fluid (butane)Cigarette lighter fluid (butane)Medical anaesthetics (ether, chloroform nitrous oxide)chloroform, nitrous oxide)Whipped cream (nitrous oxide)
Inhalants and their commonInhalants and their common chemical constituents
NitritesAmyl nitritesButyl nitritesButyl nitrites
Inhalants and their commonInhalants and their common chemical constituents
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 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
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
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.
National Household Survey on Drug Abuse, 2003
EpidemiologyFigure 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
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
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
Acute Effects of Hallucinogens
PHYSIOLOGICAL EFFECTS:PHYSIOLOGICAL EFFECTS:Nausea and loss of appetite DizzinessDizzinessChills, flushing ShakingShakingAbdominal discomfort Poor coordinationPoor coordination
Acute Effects of Hallucinogens
PSYCHOLOGICAL EFFECTS:PSYCHOLOGICAL EFFECTS:Sense of relaxation and wellbeingAltered moodAltered moodSensory distortionsDepersonalizationImpaired concentration and motivationLoss of judgment, slowed reaction time.
Acute Effects of Hallucinogens
PSYCHOLOGICAL EFFECTSPSYCHOLOGICAL EFFECTS:Disassociative reactionsIllusion: mistaken perception of real stimuliDelusion: irrational thinkingConfusion
Acute Effects of Hallucinogens
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)
Acute Effects of Hallucinogens
PSYCHOLOGICAL EFFECTS:Delusions of grandeur leading to self-destructive behaviors F l f lFear over loss of controlParanoiaAcute anxietyAcute panic (a 'bad trip')
Acute Effects of Hallucinogens
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.
Acute Effects of Hallucinogens
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)( )
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