Transcript Richard A. Rawson, Ph.D.

Amphetamine and Methamphetamine:
Consequences and Strategies
Richard A. Rawson, Ph.D.
UCLA Integrated Substance Abuse Programs
Department of Psychiatry and Biobehavioral Sciences,
David Geffen School of Medicine at UCLA
April 2013
What we know…globally
• ATS comprise the 2nd most widely used illicit drug category in
the world, following cannabis (UNODC, 2012).
• The type of ATS abused varies by region
– Amphetamines in Europe and the Middle East
– Methamphetamine in the US, Australia, and SE Asia
• Different precursors used in the manufacturing process
• Increasing reports of abuse of MDMA and synthetic cathinones
Methamphetamine
Methamphetamine is a powerful central
nervous system stimulant that powerfully
activates multiple systems in the brain,
including reward and memory circuitry as
well as the autonomic nervous system.
Methamphetamine is closely related
chemically to amphetamine, but the
central nervous system effects of
methamphetamine are greater.
Captagon®
• Historically was a pharmaceutical (fenethylline); hasn't
been legitimately made in years
• All tablets seized now are fake; illicitly manufactured,
consisting of low levels of amphetamine (~ 10-20 mg/
tablet), caffeine, and bulking agents.
• Almost exclusively trafficked for Mid East markets.
– Increasingly trafficked through Syria from Turkey and Lebanon
destined for the Gulf States, in particular, Saudi Arabia
– Smuggled through Syria to Iraq
SOURCES: UNODC, personal communication with M. Nice, 12/12/12; 2009 World Drug Report, p. 130.
EPHEDRINE
H
H
C
C
OH
CH
H
N
CH
3
METHAMPHETAMINE
H
H
C
C
H
CH3
H
N
CH3
3
Chemical Ingredients
• The active
ingredient in
making
“homemade”
methamphetamine
is ephedrine or
pseudoephedrine,
commonly found in
over the counter
cold remedies.
MDMA
O
O
NHCH3
CH3
Ecstacy Tabs
Ecstasy
• MDMA technically
3,4 - Methylenedioxymethamphetamine
• Hallucinogenic amphetamine
• Releases serotonin and blocks reuptake
• Dopamine and adrenergic effects
In 2010, there was estimated to be between
14-52 million ATS users globally.
SOURCE: UNODC, 2012 World Drug Report.
Methamphetamine Effects
• Methamphetamine half-life: 8-12 hours
• Methamphetamine paranoia: 7-14 days
• Methamphetamine protracted abstinence: 3-6 months
• Methamphetamine psychosis - May require
medication/hospitalization and may not be reversible
• Neurotoxicity: Can be substantial.
Amphetamine
Acute and Chronic Effects
Amphetamine
Acute Physical Effects
Increases:
Decreases:
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• Appetite
• Sleep
• Reaction time
Heart rate
Blood pressure
Pupil size
Respiration
Sensory acuity
Energy
Amphetamine
Acute Psychological Effects
Increases:
Decreases
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– Boredom
– Loneliness
– Timidity
Confidence
Alertness
Mood
Sex drive
Energy
Talkativeness
Dose and Route of Administration Influence
Physical Effects and Associated Conditions of
Amphetamine Use
Individuals who use high doses (either continually or in binges)
over a long period of time experience the most severe symptoms.
Routes of administration of ATS drugs are associated with different
physical consequences.
• Smoked and injected MA produce:
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more rapid plasma levels
increase risk of toxicity
require frequent re-administration
Increased severe-level patterns of use leading to dependence
produce an instant feeling of well-being, confidence, and euphoria
Physical Effects and Associated
Conditions
• Cardiovascular disease:
Cardiomyopathy, myocarditis, hypertension, arrhythmia,
myocardial infarction, rapid heartbeat, inflammation of the heart
lining.
• Pulmonary problems:
Pulmonary edema, bronchitis, pulmonary hypertension, chest
pain, asthma exacerbation, pulmonary granuloma.
Physical Effects and Associated
Conditions
• Neurologic problems:
strokes, seizures, chronic headache, cerebral swelling and
hemorrhage, involuntary movements and long-term neuronal
damage.
Physical Effects and Associated
Conditions
Other common medical consequences of
amphetamine use :
 Hepatic disease
 Skin infections and
lesions,
 Dental problems (broken
teeth, tooth decay, mouth
ulcers)




Anorexia,
Stomach ulcers,
Colitis,
Kidney failure
Physical Effects and Associated
Conditions
• Transmission of blood-borne viruses (e.g.,
HIV, hepatitis C) as well as other infectious
diseases.
 HIV transmission particular risk among men who have
sex with men, sex workers and some occupations (eg.
truck drivers).
• Obstetric complications—low birth weight.
Methamphetamine Use Leads to Severe
Tooth Decay
Meth Mouth
Source: The New York Times, June 11, 2005
Psychological Effects and Associated
Conditions
Common psychiatric/psychological effects of
amphetamine use disorders include:
 Paranoia
 Aggression
 Violence
 Suicidality
 Hallucinations
 Psychosis
 Depression
 Anxiety
Psychological Effects and Associated
Conditions
Conditions commonly occurring among
individuals with amphetamine use disorders
include:
 Depression
 Anxiety
 ADHD
 Gambling disorders
 Sleep disorders
 Eating disorders
Amphetamine Use and Psychiatric
Disorders
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Rates of psychiatric disorders in ATS users are
notably higher (2X to 3 X) than prevalence
estimates in the general population.
Poorer outcomes are associated with psychiatric
illness in ATS users.
Abstinence promotes psychiatric symptom
recovery.
Screening for risk factors and addressing
psychiatric symptoms may optimize outcomes in
this population.
Psychological Effects and Associated
Conditions: Amphetamine-Induced
Psychosis
• Amphetamine-induced psychosis has been
extensively reported in the literature from Japan.
• Associated with individuals with long histories of
amphetamine use.
• Persistence of psychosis following cessation of
amphetamine use is variable, with some %
experiencing apparently permanent psychosis
Symptoms of Amphetamine-induced
Psychosis
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Persecutory delusions
Ideas of reference
Hallucinations (visual, auditory, olfactory, tactile)
Relative clear sensorium
Stereotypical and compulsive acts
Blunt affect, poverty of speech
Prone to excited delirium and violence
Amphetamine-using Populations
With Unique Clinical Concerns
Amphetamine injectors
Injection users report:
• More severe craving
• Higher rates of depression
• And other psychological symptoms before, during,
and after treatment
• Higher rates of drug use in treatment and higher
drop out rates from treatment
• Higher rates of HIV and hepatitis C
Men who have sex with men
(MSM)
• Rates of HIV seroprevalence have been reported
to be threefold higher among amphemtamineusing MSM than among non-amphetamine-using
MSM
• CDC reports that the connection between
amphetamine use, high-risk sexual behavior, and
HIV transmission in MSM communities poses a
major threat of high rates of HIV infection among
MSM
Women
• In the US, rates of amphetamine use among women
approach the rates among men.
• Women frequently use amphetamine for weight loss
and to control symptoms of depression.
• Over 70% of amphetamine-dependent women report
histories of physical and sexual abuse
• Amphetamine-using women are more likely than men
to present for treatment with greater psychological
distress
Children and prenatal issues
• The effects of amphetamine use by pregnant
women include growth retardation, premature
birth and, possibly, neurological disorders
among their children
Adolescents
• In communities where amphetamine-use levels are
high, there is a very high rate of amphetamine use
among teen girls admitted for substance abuse
treatment.
• Amphetamine use among adolescents is associated
with higher levels of emotional, psychiatric, and
delinquency problems, compared with adolescents
with other drug abuse diagnoses
Cognitive impairment
• Chronic use of amphetamine produces profound
disruption of cognitive functions
• Neuro-cognitive deficits are common among even
short-term users of amphetamine, sometimes
persisting for many months
• Cognitive processes impaired include: verbal and
working memory, response inhibition, perceptual
speed, attention, and fluency
Sexual behavior
• There is a strong association between
amphetamine use and sexual behavior.
• Decreased libido, inability to function sexually,
loss of sexual pleasure, and reduced frequency of
sexual activity are common concerns during the
early months of abstinence from amphetamine.
Retention, Retention Retention
• If patients attend treatment, all measures of
drug use, HIV risk and social functioning
are improved.
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Make treatment accessible
Make treatment flexible
Make treatment positively reinforcing
Make treatment useful
Find ways of rewarding attendance.
Clinical Challenges with ATS Dependent
Individuals
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Persisting Drug induced Paranoia
Limited Understanding of Addiction
Cognitive Impairment
Anhedonia
Sexual Reactivity and Meth Craving
Elevated Potential for Violence
Sleep Disorders
Elevated Rates of Psychiatric Co-morbidity
Medical Consequences of ATS
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Infectious diseases, including HIV
Cardiovascular problems
Pulmonary problems
Neurological problems
Skin problems
Dental problems
Sexual dysfunction
ATS Psychosis
• Can induce psychotic symptoms in
susceptible individuals
• Incidence varies with several risk factors
• Symptom complex- mimics the positive
symptoms of schizophrenia
• Some reports of prolonged, low level
symptoms
• Stress has been reported to reactivate the
psychosis
Symptoms of AmphetamineInduced Psychosis
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Persecutory delusions
Ideas of reference
Hallucinations (visual, auditory, olfactory, tactile)
Relative clear sensorium
Stereotypical and compulsive acts
Blunt affect, poverty of speech
Prone to excited delirium and violence
Medications Under Study as
Methamphetamine Treatments

No medication currently with efficacy

Promising medications for stimulants include
(Provigil, Naltrexone, Topiramate, Mirtazapine).

Amphetamines possible withdrawal medication.
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Immunotherapies are in early stages.

CM may potentiate medication effect.
Which behavioral and psychosocial
treatments have demonstrated efficacy
for stimulant dependence treatment?
Treatments for Stimulant-use Disorders
with Empirical Support
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Community Reinforcement Approach
Cognitive-Behavioral Therapy (CBT)
Contingency Management
Matrix Model
Although Motivational Interviewing does not have
specific evidence of efficacy, it is considered a very
useful tool in methamphetamine treatment efforts.
Conclusion
• Amphetamine use elevates dopamine levels in the
reward system of the brain producing euphoria and
addiction.
• Acute amphetamine use produces a set of physical
and psychological effects that are desired by users.
• Chronic amphetamine effects (in high doses) create a
wide range of damaging symptoms.
• Psychological and behavioral treatments currently
have best evidence of efficacy