Download Inhalant Abuse in Adolescents

Inhalant Abuse in Adolescents
Charles S. Grob, M.D.
Harbor-UCLA Medical Center
Inhalants and their common
chemical constituents
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Aerosols (may contain
chlorofluorocarbons and fluorocarbon
„
propellants)
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D d
Deodorants
t and
d hairsprays
h i
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Fabric protector sprays
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Spray paints (toluene, methyl isobutyl
ketone)
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Vegetable oil sprays
Inhalants and their common
chemical constituents
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Gases
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Bottled gas (propane)
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Cigarette lighter fluid (butane)
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Medical anaesthetics (ether,
chloroform nitrous oxide)
chloroform,
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Whipped cream (nitrous oxide)
Inhalants and their common
chemical constituents
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Nitrites
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Amyl nitrites
Butyl nitrites
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Inhalants and their common
chemical constituents
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Volatile solvents
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Correction fluids
(1,1,1-trichloroethane)
Nail polish remover
(acetone, esters)
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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)
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Petrol (benzene, nhexane, toluene, xylene)
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Glues (n-hexane,
toluene, xylene)
Inhalant Effects
INHALANT MISUSE
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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
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Early adolescence is a period of critical
neurodevelopmental maturation
(eg. synaptic pruning and increased
mylenation)
Chronic inhalant exposure during early
adolescence
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- - > greater structural and functional
brain disturbance
- - > cognitive impairment
INHALANT PHARMACOLOGY
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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
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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
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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
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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
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“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
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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
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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
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Hypoxia
H
Hypoglycemia
l
i
Ethanol intoxication
Drug intoxication
Trauma
Infection
LABORATORY EVALUATION MAY LABORATORY
EVALUATION MAY
REVEAL
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Hypokalemia
yp
Hypophosphatemia
Hypocalcemia
Metabolic Acidosis
Methemoglobinemia
Carbon Monoxide poisoning
NEUROLOGIC CONSEQUENCES OF INHALANT ABUSE
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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
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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
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Anxiety
Apathy
p
y
Agitation
Depression
Inattention
Insomnia
Psychosis
MEDICAL CONSEQUENCES OF MEDICAL
CONSEQUENCES OF
INHALANT ABUSE
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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
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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
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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:
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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
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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
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Over the y
years,, twelfth ggrade students
were slightly more likely to report use
grade students.
than 9th g
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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
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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
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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:
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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
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Disassociative reactions
Illusion: mistaken perception of real stimuli
Delusion: irrational thinking
Confusion
Acute Effects of Hallucinogens
PSYCHOLOGICAL EFFECTS:
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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:
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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
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Anthropological evidence dating back to earliest evidence of human
existence
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Limited supply
- under control of tribal authority and reserved solely for ritual use
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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
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Elder facilitated, culturally sanctioned pubertal rites of
initiation
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Induction of ritualized and symbolic
y
death of the child
with emergence into initiatory rebirth of new adult identity
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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:
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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
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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
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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