Transcript Mental and behavioral disorders due to psychoactive substance use

Drug abuse & addiction and
treatment of addiction
MUDr. T. Páleníček, PhD
Prague Psychiatric Center,
3. LFUK
Main drug classes
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Stimulants: nicotine, cocaine, amphetamines, piperazines (BZP), caffeine
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Depressants: alcohol, barbiturates, BZD
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Hallucinogens: LSD, mescaline, psilocin, DOB, harmin, DMT (Ayahuasca) etc.
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Entactogens: MDMA (ecstasy), MDA, MBDB, 2C-B, piperazines (TFMPP,
mCPP), PMA etc.
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Cannabinoids: THC
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Dissociative anesthetics: Ketamine, PCP
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Narcotics: opioids
• natural: morphine
• synthetic: phentanyl, heroin, meperidine, methadon, oxycodeine
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Others: inhalants, sedatives and hypnotics
Prevalence of drug use
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Lifetime prevalence:
– Amphetamine 15–34 years
– Ecstasy 15–34 years
– Cocaine 15–34 years
– Cannabis 15–64 years
– Cannabis 15-34 years
5%
5.6 %
5.6 %
22.1 %
31.1 %
Cannabis
last year prevalence in young population 15-24 years
15.8 %
Estimated numbers of:
– Problem opioid users in EU 1.2 -1.5 milions
New HIV infections between i.v. drug users in 2007
– Highest rates in Estonia
HCV and HBV antibody positivity in i.v. users
– Czech Rep. – less than 25%
4.7 per million of population
40 % (18 – 95 %)
2009 Annual report on the state of the drugs problem in Europe, EMCDDA
Prevalence of HIV and Hep C in EU
Annual report 2012: the state of the drugs
problem in Europe, EMCDDA
Cannabis use in EU
Annual report 2012: the state of the drugs
problem in Europe, EMCDDA
Cannabis use in EU
Annual report 2012: the state of the drugs
problem in Europe, EMCDDA
Opioid and Cocaine use in EU
Annual report 2012: the state of the drugs
problem in Europe, EMCDDA
Overdoses
Deaths associated with overdoses in the Czech Rep.
unspecified
Synthetic drugs
Cocaine
Amphetamines
Opioids
Solvents
Illegul drugs and solvents in
total
benzodiazepines
Prevalence in the Czech Rep.
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Lifetime prevalence:
–
–
–
2008
2012
Total
number of problem drug users
Any drug in population 15–64
years
36,5 %
-
Cannabis in population 15–64 years
34,3 %
29,7%
Cannabis in population 15-34 years
53,7 %
45,9%
28,8 %
18,3%
Use of cannabis
in last year in population 15-34 let
Estimated numbers of:
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–
–
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2008
2012
Problem drug users
32 500
40 200
Intravenous drug users
31 200
38 600
Problem drug users of meth
21 200
30 900
Problem drug users of opiates
11 300
9 300
2011
• HIV incidence in i.v. users < 1 % - in total 96 cases (7 new in 2011)
• VHC incidence – 812 newe cases in 2011, in total approximately 12% of positive i.v.
users
Výroční zpráva o stavu ve věcech drog v České republice v roce 2008,2011,2012
Národní monitorovací středisko pro drogy a drogové závislosti, Úřad vlády ČR
Prevalence - opioid and meth
use in the Czech Rep.
Number of problem drug users per 1000 in population 15-64 years and number of problem opiate
and methamphetamine users in Czech regions
Heroin users
Subutex users
Methamphetamine users
Výroční zpráva o stavu ve věcech drog v České republice v roce 2008
Národní monitorovací středisko pro drogy a drogové závislosti, Úřad vlády ČR
Lifetime prevalence with illegal drugs in 11 – 13
years old children in % in the Czech Rep.
(Prev-Centrum, 2003 a 2005; Miovská, 2006)
years old
Group A (experimental)
years old
years old
years old
Groups B + C (controls)
Cannabis
Ecstasy
Meth
Heroin
Solvents
(Výroční zpráva o stavu ve věcech drog v České republice v roce 2005, národní monitorovací středisko pro drogy a drogové závislosti (NMS))
Mental and behavioral disorders due
to psychoactive substance use
F10. – Mental and behavioral disorders due to use of alcohol
F11. – Mental and behavioral disorders due to use of opioids
F12. – Mental and behavioral disorders due to use of cannabinoids
F13. – Mental and behavioral disorders due to use of hypnotics
F14. – Mental and behavioral disorders due to use of cocaine
F15. – Mental and behavioral disorders due to use of other stimulants, including
caffeine
F16. – Mental and behavioral disorders due to use of hallucinogens
F17. – Mental and behavioral disorders due to use of tobacco
F18. – Mental and behavioral disorders due to use of volatile solvents
F19. – Mental and behavioral disorders due to multiple drug use and use of other
psychoactive substances
Mental and behavioral disorders due
to psychoactive substance use
F1x.0 - Acute intoxication
F1x.1 - Harmful use
F1x.2 - Dependence syndrome
F1x.3 - Withdrawal state
F1x.4 - Withdrawal state with delirium
F1x.5 - Psychotic disorder
F1x.6 - Amnesic syndrome
F1x.7 - Residual and late-onset psychotic disorder
F1x.8 - Other mental and behavioral disorders
F1x.9 - Unspecified mental and behavioral disorder
Acute intoxication
Condition that follows the administration of a psychoactive substance.
Disturbances are directly related to the acute pharmacological effects of the
substance and resolve with time, with complete recovery, except where tissue
damage or other complications have arisen.
disturbances in:
level of consciousness
Cognition
Perception
affect or behaviour
other psycho-physiological functions and responses.
Complications:
Trauma
Inhalation of vomitus
Delirium
Coma
Convulsions
Other medical complications.
• Acute drunkenness in alcoholism
Depends on:
The drug used
The dose used
Actual somatic or psychological condition
• "Bad trips" (drugs)
• Drunkenness NOS
• pathological intoxication
• Trance and possession disorders in
psychoactive substance intoxication
Alcohol - effects
Alcoholemia
[%]
Effects
0.02-0.03
Mood elevation, slight muscle relaxation
0.05-0.06
Relaxation, decreased reaction times, impaired fine motor
functions
0.08-0.09
Impaired balance, speech, vision, muscle coordination,
euphoria
0.14-0.15
Severe impairment of motor control as well as psychic
functions.
0.20-0.30
Severe intoxication, minimal control of motor or psychic
functions
0.40-0.50
Unconsciousness, deep coma, dead from suppression of
breath center
Harmful use
A pattern of psychoactive substance use that is causing damage to
health:
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physical (as in cases of hepatitis from the self-administration of injected drugs)
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mental
(e.g. episodes of depressive disorder secondary to heavy consumption of
alcohol).
Not present:
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dependence
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Psychotic disorder
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Other specific disorders associated with alcohol or drug use
Duration: at least 1 month, or several
shorter periods during last 12 months
Dependence
Cluster of behavioral, cognitive, and physiological phenomena that develop after
repeated substance use and that typically include:
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strong desire to take the drug
difficulties in controlling its use
persisting in its use despite harmful consequences
higher priority given to drug use than to other activities and obligations
increased tolerance
(physical withdrawal state)
Faster reapperance of the syndrom after prolonged abstinence
Includes:
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Chronic alcoholism
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Dipsomania
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Drug addiction
• abstinent
Duration: at least 1
• abstinent in protected areas
month,
or several
• abstinent
on substitution
therapy
•shorter
active in use
periods during
• continuously uses
last 12 months
• use (dipsomania)
Drug addiction - neurobiology
Drug addiction - neurobiology
All known compounds that induce dependence ↑ the dopamine
release in nucleus accumbens
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Acute drug effects –
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Transition to addcition –
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↑ DA in nucleus accumbens (and in PFC) (mesolimbic areas) → euforia
Induction of early genes e.g. cFos
Short term neuroplastic alterations (hours – days)
Neuronal changes accumulate, but still not persistent
Stimulation of synthesis of proteins with long biological half life (e.g. ∆FosB –
transcription regulator which modulates synthesis of AMPA GLU receptors)
Changes in DA and GLU systems play probably the key role in development of
dependence (changes in expression of mGLUR1, DAT, RGS9-2, D2 autoreceptors…)
Dependece
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Many changes become irreversible or long lasting
As a result of that is a vulnerability to relapse
Many changes involve glutamatergic system, mainly projections from prefrontal cortex
to striatum (nucleus accumbens)
Withdrawal and delirium
A group of symptoms of variable clustering and severity occurring on
absolute or relative withdrawal of a psychoactive substance after
persistent use of that substance.
Onset and course:
 temporally restricted
 depends on the drug and dose used that was abused before abstinence
.30 uncomplicated
Delirium tremens = short life threatening state of confuse
and somatic complications during alcohol abstinence in
strongly addicted, sometimes after alcoholic excess
.31 with convulsions
Prodromes  sleeplessness, anxiety and fear, convulsions
F1x.4 Withdrawal
with delerium
Manifested delirium 
F1x.3 Withdrawal
.40 without convulsions
.41 with convulsions
• blunted consciousness and fuzziness
• hallucinations and illusions
• intense tremor
• delusions, agitation, sleeplessness, reversed sleep cycle
and increased vegetative functions
Diagnosis of delirium (ICD 10)
Příznaky mírné nebo závažné musí být přítomné ve všech následujících
oblastech:
(a) impairment of consciousness and attention
(b) global disturbance of cognition (impairment of immediate recall and of
recent memory; disorientation for time, place and person);
(c) psychomotor disturbances (hypo- or hyperactivity and unpredictable shifts
from one to the other)
(d) disturbance of the sleep-wake cycle
(e) emotional disturbances, (e.g. depression,
anxiety or fear, irritability, euphoria, apathy)
Začátek je obvykle rychlý, průběh během dne kolísá a celkový stav trvá
nejdéle 6 měsíců.
Pathophysiology of alcohol
withdrawal and delirium
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Alcohol facilitates the effects of GABA on GABA A receptors
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In chronic abuse there is generally decreased excitability of brain via GABA
system, there is down regulation of GABA A receptors
Concomitantly long-time alcohol abuse inhibits glutamatergic system
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This leads to up regulation of NMDA receptors
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During alcohol cessation the main consequence is hyperexcitability of he brain
(NMDA mediated effects dominate) → withdrawal symptoms, increased
excitability, altered sleep cycle, convulsions
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Altered homeostasis, altered permeability of membranes + worsening of
oxidative metabolism → defect of neurotransmitter synthesis (mainly
acetylcholine → delirium)
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Also altered serotonin, noradrenalin and dopamine systems
Somatic and neurological
symptoms of delirium
Neurological: tremor, Asterixis („flapping tremor" originally in hepatic hepatopathy)
Dysnomia = amnestic afazia
dysgrafia.
Vegetative:
tachycardia
increased blood pressure
Sweating
face blush (getting red)
mydriasis.
Prognosis
1) Full recovery: usually in 1 – 4
weeks, in elderly patients tends
to také longer ….
2) Fatalities: 20 – 30 %
3) Transition to dementia
Complications
falling from the bed with an injury,
4) Transition to functional
psychotic disorder : 10 %
attack against imaginary invaider with injury,
agitation which complicates the medical care,
transition to dementia, amnestic syndrome or organic personality disorder
Therapy of delirium tremens
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identification of cause, eliminate influence of anticholinergics (delirogens)
start symptomatic treatment and supportive care
correction of water and ion disbalance (infusions, ions, vitamins)
adequate alimentation
sufficient sleep
safe environment
reorientation and not disturbing patient in between 21 and 6 during the sleep.
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Pharmacotherapy:
a) sedation
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benzodiazepines: (e.g. midazolam, lorazepam, tenazepam)
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clomethiazol (Heminevrin)
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combination of BZD and antipsychotics
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antipsychotics: (haloperidol, sulpirid, tiaprid)
b) nootropics (e.g. piracetam – f.o. Kalikor, Nootropil, 2400 – 3200 mg/day or
pyritinol 300 - 500 mg/day etc.).
Amnesic syndrome
Excludes: nonalcoholic Korsakov's psychosis or syndrome ( F04 )
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Chronic prominent impairment of recent and remote memory
Disturbances of time sense and ordering of events
Difficulties in learning new material
Confabulation may be marked but is not invariably present.
Other cognitive functions are usually relatively well preserved
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Amnestic disorder, alcohol- or drug-induced
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Korsakov's psychosis or syndrome, alcohol- or other psychoactive substanceinduced or unspecified
Prognosis:
25% - full recovery
50% - partial recovery
Therapy: Thiamin 50-100mg
p.o. for months
Psychotic disorder
A cluster of psychotic phenomena that occur during or following psychoactive
substance use but that are not explained on the basis of acute intoxication alone and do not
form part of a withdrawal state.
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hallucinations (typically auditory, but often in more than
one sensory modality)
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Examples:
perceptual distortions
delusions (often of a paranoid or persecutory nature)
psychomotor disturbances (excitement or stupor)
abnormal affect (from intense fear to ecstasy)
Alcoholic Hallucinosis
Alcoholic Jealousy
Alcoholic Paranoia
Alcoholic psychosis
some degree of clouding of consciousness
Disorder vanish (at least partially) within 1 month, fully within 6 months
F1x.5 Psychotic disorder
.50 Schizofrenia-like
.51 predominantly delusional
• Onset up to two week after
withdrawal
• Persistence of psychotic
symptoms > 48 hours
.52 predominantly hallucinatory
.53 predominantly polymorphic
.54 predominantly depressive psychotic symptoms
.55 predominantly manic psychotic symptoms
.56 mixed
Residual and late-onset
psychotic disorder
A disorder in which alcohol- or psychoactive substance-induced changes of
cognition, affect, personality, or behaviour persist beyond the period during which a
direct psychoactive substance-related effect might reasonably be assumed to be
operating
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Alcoholic dementia NOS
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Chronic alcoholic brain syndrome
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Dementia and other milder forms of persisting impairment of cognitive
functions
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Flashbacks
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Late-onset psychoactive substance-induced psychotic disorder
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Posthallucinogen perception disorder
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Residual:
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affective disorder
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disorder of personality and behaviour
Bio-psycho-social model Biological level
• Biological factors e.g. some problematic circumstances during
pregnancy:
• if mother was alcoholic or drug addicted
• exposition of fetus to addictive substances (e.g. fetal alcoholic
syndrome)
• circumstances of birth (hypoxia, use of psychotropic
substances, hypnotics, sedatives)
• factors that influence neurobiology of an individual including all
psychomotor maturing of a child during early postnatal period
• presence of trauma, disease and other traumatic and limitating
factors
• genetic factors
(Kamil Kalina a kolektiv, Drogy a drogové závislosti, mezioborový přístup. Vydal © Úřad vlády České republiky, 2003, Národní monitorovací středisko pro
drogy a drogové závislosti, 2002
Bio-psycho-social model psychological level
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Influence of psychogenic factors
• Perinatal period (transpersonal approaches)
• Postnatal care – harmonic development, setting interpersonal and personal
borders
• Support during adolescence
• Support during the crises of identity
• Adequate support during pathological states, including mental health (depression,
anxiety, psychosis)
• If there is a lack of support, it can be often the self-medication that can lead to the
development of substance abuse and addiction
• Some of them are associated with existing abuse and enforce further abuse, e.g.:
• alcohol has anxiolytic and antidepressant effects on the beginning of use, later
becomes itself the cause of depression and anxiety, that stimulates further
drinking
• activation of paranoid states in chronic stimulant abuse, identity disorders
during the abuse of hallucinogenic drugs etc.
(Kamil Kalina a kolektiv, Drogy a drogové závislosti, mezioborový přístup. Vydal © Úřad vlády České republiky, 2003, Národní monitorovací středisko pro
drogy a drogové závislosti, 2002
Bio-psycho-social model Social level
• Concentrates on the context where everything is happening, especially the
relationships with ¨surrounding environment, which formats maturing of an
individual and eventually can negatively disturb it :
• race discrimination
• family status in the society
• the level of social indemnity
• the quality of individual relationships in the family, eventually absence of the family
• countryside vs. big cities
• not enough time of adult people for youngsters
• absence of rituals positively forming maturing of young person
• a child in a family grows beside an addicted person
• Young people search identification models outside of the family, in their naturally
occurring addictive position they search for strong individuals or groups. They search for
feelings of acceptance, belonging, etc.
• collective of equals – often it is said „he/she has found a bad group of friends“
(Kamil Kalina a kolektiv, Drogy a drogové závislosti, mezioborový přístup. Vydal © Úřad vlády České republiky, 2003, Národní monitorovací středisko pro
drogy a drogové závislosti, 2002
Treatment of addiction
• Motivation
• Decision to stop
• First contact with professionals (K-centre, hospital …)
• Again motivation and testing the decision to stop
• Detoxification
• Therapy – ambulant, in hospital, in community
• Subsequent care – getting back to society
• Relapse
Therapeutic system
Outside healthcare system:
• Contact centers (KC)
In healthcare system:
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Acute states (detox, withdrawal
symptoms, toxic psychosis)
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Therapeutic programs (ambulant, in
psychiatric centers, clinics)
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After-treatments programs
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Substitution therapy
• Family therapy
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Family therapy
• Counseling
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Counseling
• Social welfare institutions
• Therapeutic communities
• After-treatment centers
• Harm reduction
Treatment of alcohol
dependence
Pharmacological interventions
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Disulfiram (up to 500mg/die)
Acamprosate (more than a 1g/die 2x2tbl a 333mg)
Naltrexon (25-100mg/die)
Antidepressants, anticonvulsants, ondansetron, antipsychotics,
buspiron, GHB
Psychotherapy
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motivational enhancement therapy, 12 step facilitation programs
and CBT seems to be most effective
Psychodynamic psychotherapy and brief interventions are
probably not much effective
Other – family therapy, behavioral partner therapy, education
Treatment of opioid dependence
Pharmacological interventions
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methadon (up to 60-100mg/die slow titration)
bubrenorphine (8-16mg/die slow titration)
Bubprenorphine + naloxone (4:1) – Subuxon (sublingual tablets)
Diamorphine (heroin)
Naltrexon, naloxon
LAAM
GHB, ibogain
Psychotherapy
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motivational enhancement therapy, supportive expressive therapy,
family therapy, contingency management and CBT seems to be most
effective
Therapeutic communities
Other – family therapy, behavioral partner therapy, education
Substitution therapy
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Pharmacological intervention directed towards involvement of withdrawal symptoms and craving
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Opiates and nicotine
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Per oral administration of medication (or plasters with nicotine)
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Methadone, Subutex (0.4mg, 2mg and 8mg; buprenorphine for per oral use), Temgesic (0.2mg and
0.3mg; buprenorphine for parenteral administration), Diolan (ethylmorphine HCl), heroin, nicotine
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Special centers or physicians
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Helping with motivation to undergo other treatments (re-socialization)
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Minimization of risks associated with drug use, criminality, social problems etc. = harm reduction
Indication:
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Severe and long lasting dependence on high doses of opiates, or combined addiction
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Repeated unsuccessful attempts of treatments
Factors that support involvement in the program
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Anamnestic positive experience with substitution therapy
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Opioid dependence in HIV positive patients, repeated criminal activity associated with the drug use, if
normal treatment is not possible
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Treatment of pregnant patients if detoxification is not possible
Substitution therapy
Replacement of primary drug … :
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Illegally obtained
With short action
Often with toxic adjuvants
With unknown concentration
Administered in risky way (i.v., non-sterile)
…with a substance (medication) with favorable profile:
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With long-lasting action in the organism
With defined concentration
Without toxic adjuvants and effects
Administered usually p.o.
Used lege artis
Opioid substitution contraindications
Methadone
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If classical treatment is possible and convenient
Primary dependence on other substances (e.g. stimulants)
Non-occurrence of physical dependence
Age lower than 16 years
Severe hepatic illness
Acute alcohol intoxication
Subutex
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Same as for methadone plus:
IMAO treatment and 14 days after ending such treatment
Severe respiratory insufficiency
Relative contraindications for both:
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Encroaching of the substitution program in anamnesis
Combined dependence (e.g. Methadone + alcohol)
Incapability to stop using illegal drugs despite a high dose of substitution drug
Forthcoming imprisonment without possibility to continue in the substitution program in the prison
Treatment of stimulant
dependence
Pharmacological interventions
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Antidepressants – not effective
Dopaminergic agonists – no effects
Disulfiram – moderate effects
Antiepileptics (tiagabiaine) – moderate effects
Anti adrenergics (betablckers) – moderate effects
Baclofen – moderate effects
Naltrexon, buspiron, ibogain
Psychotherapy
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motivational enhancement therapy, supportive expressive therapy,
family therapy, contingency management, CBT, dynamic psychotherapy,
cue exposure therapy
Therapeutic communities
Other – family therapy, behavioral partner therapy, education
Treatment of nicotine
dependence
Pharmacological interventions
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Substitution with nicotine (chewing gums, plasters, spray, bonbons)
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1,5x - 2x increase the probability of smoking cessation
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8-12 chewing gums a 2mg daily, might be combined with 24h
plasters
Antidepressants – bupropion (Wellbutrin, Zyban) cca 300 mg/day, 2-3
months
Varenicline – parcial agonist of incotine receptors (Champix)
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1.-3. day 0,5 mg 1x daily, 4.-7. day 0,5 mg 2x daily; since 8. day until the
end of treatment 1 mg 2x daily.
Treatment length is 12 weeks
Nortryptiline, klonidine, moclobemid, selegiline, mecamylamine
Psychotherapy
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Minimal interventions, counseling, behavioral approaches incl. CBT,
motivational interventions
Detoxification units
Important features:
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usually requirement for further treatment
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usually lasts 1 or more weeks
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Symptoms of acute withdrawal with respect to the abused drugs (including physical symptoms after
opiates, BZD, delirium tremens)
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Use of pharmacological interventions – buprenorphin (Temgesic, Subutex, Suboxone), BZD,
barbiturates, vitamins, hepatoprotectives
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Many patients break down already on this level
Indication:
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Existing or developing withdrawal in patient without vital functions failure
age: patient older than 15 years (it is relative since there are detoxes for children as well)
Voluntary admission, informed consent
Contraindications:
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Severe intoxication, severe somatic or psychiatric state requiring care in a different or specialized
unit
Disagreement with the conditions of treatment
Involuntary admission (adult patient, in children parents are responsible)
Detoxification – treatment
approaches
Ad 1) without specific (substitution) medication
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basic daily program (according to the requirements of the patient), structured
therapeutic program (supportive psychotherapy, enhancement of motivation for
further treatment, influencing patients attitudes etc.)
Supportive pharmacotherapy: hypnotics, anxiolytics, hydratation, physiotherapy,
psychotherapeutic techniques (relaxation, art therapy, music therapy, …)
Ad 2) with specific medication
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opioid assisted detoxification
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methadon – after finding of an optimal dose continuous decline to 0 in 514 days
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buprenorphin - after finding of an optimal dose 3-4 day substitution with
subsequent abrupt stopping of the treatment
in BZD and barbiturate withdrawal - continuous decline of the dose which can
last several weeks (relatively quickly the 1st 1/2 of the dose, than carefully with
smaller reductions, withdrawal symptoms are life threatening, seizures could be
typically present if the decline is to fast)
Supportive pharmacotherapy: hypnotics, anxiolytics, antipsychotics, hydratation
physiotherapy, some very simple psychotherapeutic techniques (relaxation, art
therapy, music therapy, …)
Therapeutic interventions in
therapeutic community
• Strict rules of the treatment
• Often scoring system
• group psychotherapy
• Individual psychotherapy
• Psychotherapeutic techniques, work therapy etc.
• Family therapy
• Several weeks to several years
• Important factor for prognosis is finishing the
specified treatment
Aftercare
• Very important after finishing treatment
• re-socialization
• In the beginning usually daily, later weekly
• Work with relapse
• Some institutions in patients with dependence on nonalcoholic drugs solve the alcohol and cannabis consumption,
others require strict abstinence from all drugs and addictive
behaviors
Anticraving treatment
Not causal, it can be combined with other approaches
• Bupropion (Zyban, Wellbutrin) - nicotine
• GHB (gama-hydroxybutyrate) – alcohol
• Ibogain – opiate, alcohol dependence
• Ketamine – opiate, alcohol dependence
Prevention
• Primary – education, objective information (counseling), etc.
• Secondary – working with abstinent users
• Tertiary – minimization of risks
Harm reduction
= Minimization of risks
• Exchange of used needles for sterile ones, supplying condoms,
sterile water, citric acid, cellulose filters etc., substitution
therapy, drug testing (e.g. Ecstasy tablets testing on raves
which serves also as a contact method)
• In an institution or as a street-work
• Prevention of transmitting infectious diseases (HIV, hepatitis)
• Countries where it was restricted, e.g. Ukraine – extremely
high incidence of HIV and hepatitis among i.v. drug users
(90% or more are positive)
• Minimizations of tromboembolic complications, endocarditis,
sepsis
• Contact with clients that are difficult to target (serves as a
attractor)
Other issues
• Dual diagnosis
– in USA almost 50% of addicted
– Specific treatment, important is distinguishing from toxic
psychosis
• Treatment of pregnant women
• Combined addiction on several substances
(alcohol + gambling + speed, heroin + BZD, …)
• Treatment of associated diseases
– hepatitis, HIV, encephalopathy, neuropathy etc
Thanks for attention