1. Drug abuse & addiction and treatment of addiction
MUDr. T. Páleníček, PhD
Prague Psychiatric Center,
3. LFUK

2. Main drug classes
Stimulants: nicotine, cocaine, amphetamines, piperazines (BZP), caffeine
Depressants: alcohol, barbiturates, BZD
Hallucinogens: LSD, mescaline, psilocin, DOB, harmin, DMT (Ayahuasca) etc.
Entactogens: MDMA (ecstasy), MDA, MBDB, 2C-B, piperazines (TFMPP, mCPP), PMA etc.
Cannabinoids: THC
Dissociative anesthetics: Ketamine, PCP
Narcotics: opioids
natural: morphine
synthetic: phentanyl, heroin, meperidine, methadon, oxycodeine
Others: inhalants, sedatives and hypnotics

3. 2009 Annual report on the state of the drugs problem in Europe, EMCDDA
Prevalence of drug use
Lifetime prevalence:
Amphetamine 15–34 years 5 %
Ecstasy 15–34 years 5.6 %
Cocaine 15–34 years 5.6 %
Cannabis 15–64 years %
Cannabis years %
Cannabis
last year prevalence in young population years %
Estimated numbers of:
Problem opioid users in EU milions
New HIV infections between i.v. drug users in per million of population
Highest rates in Estonia
HCV and HBV antibody positivity in i.v. users 40 % (18 – 95 %)
Czech Rep. – less than 25%
2009 Annual report on the state of the drugs problem in Europe, EMCDDA

4. Prevalence of HIV and Hep C in EU
Annual report 2012: the state of the drugs problem in Europe, EMCDDA

5. 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

6. 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

7. Opioid and Cocaine use in EU
Annual report 2012: the state of the drugs problem in Europe, EMCDDA

8. Illegul drugs and solvents in total
Overdoses
Deaths associated with overdoses in the Czech Rep.
unspecified
Synthetic drugs
Cocaine
Amphetamines
Opioids
benzodiazepines
Illegul drugs and solvents in total
Solvents

9. Prevalence in the Czech Rep.
Lifetime prevalence:
Any drug in population 15–64 years 36,5 % -
Cannabis in population 15–64 years 34,3 % 29,7%
Cannabis in population years 53,7 % 45,9%
Use of cannabis
in last year in population let 28,8 % 18,3%
Estimated numbers of:
Problem drug users
Intravenous drug users
Problem drug users of meth
Problem drug users of opiates
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
Total number of problem drug 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

10. Prevalence - opioid and meth use in the Czech Rep.
Number of problem drug users per 1000 in population 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

11. 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
years old
years old
years old
Group A (experimental)
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))

12. 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

13. 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

14. 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.
Depends on:
The drug used
The dose used
Actual somatic or psychological condition
Complications:
Trauma
Inhalation of vomitus
Delirium
Coma
Convulsions
Other medical complications.
Acute drunkenness in alcoholism
"Bad trips" (drugs)
Drunkenness NOS
pathological intoxication
Trance and possession disorders in psychoactive substance intoxication

15. Alcohol - effects Alcoholemia [%] Effects 0.02-0.03
Mood elevation, slight muscle relaxation
Relaxation, decreased reaction times, impaired fine motor functions
Impaired balance, speech, vision, muscle coordination, euphoria
Severe impairment of motor control as well as psychic functions.
Severe intoxication, minimal control of motor or psychic functions
Unconsciousness, deep coma, dead from suppression of breath center

16. Harmful use Duration: at least 1 month, or several
A pattern of psychoactive substance use that is causing damage to health:
physical (as in cases of hepatitis from the self-administration of injected drugs)
mental (e.g. episodes of depressive disorder secondary to heavy consumption of alcohol).
Not present:
dependence
Psychotic disorder
Other specific disorders associated with alcohol or drug use
Duration: at least 1 month, or several
shorter periods during last 12 months

17. Dependence Duration: at least 1 month, or several
Cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and that typically include:
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:
Chronic alcoholism
Dipsomania
Drug addiction
Duration: at least 1 month, or several
shorter periods during last 12 months
abstinent
abstinent in protected areas
abstinent on substitution therapy
active in use
continuously uses
use (dipsomania)

18. Drug addiction - neurobiology

19. Drug addiction - neurobiology
All known compounds that induce dependence ↑ the dopamine release in nucleus accumbens
Acute drug effects –
↑ DA in nucleus accumbens (and in PFC) (mesolimbic areas) → euforia
Induction of early genes e.g. cFos
Short term neuroplastic alterations (hours – days)
Transition to addcition –
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
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)

20. 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
Delirium tremens = short life threatening state of confuse and somatic complications during alcohol abstinence in strongly addicted, sometimes after alcoholic excess
Prodromes  sleeplessness, anxiety and fear, convulsions
Manifested delirium 
blunted consciousness and fuzziness
hallucinations and illusions
intense tremor
delusions, agitation, sleeplessness, reversed sleep cycle and increased vegetative functions
F1x.3 Withdrawal
.30 uncomplicated
.31 with convulsions
F1x.4 Withdrawal with delerium
.40 without convulsions
.41 with convulsions

21. 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.

22. Pathophysiology of alcohol withdrawal and delirium
Alcohol facilitates the effects of GABA on GABA A receptors
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
This leads to up regulation of NMDA receptors
During alcohol cessation the main consequence is hyperexcitability of he brain (NMDA mediated effects dominate) → withdrawal symptoms, increased excitability, altered sleep cycle, convulsions
Altered homeostasis, altered permeability of membranes + worsening of oxidative metabolism → defect of neurotransmitter synthesis (mainly acetylcholine → delirium)
Also altered serotonin, noradrenalin and dopamine systems

23. 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.
Complications      
falling from the bed with an injury,
   attack against imaginary invaider with injury,
   agitation which complicates the medical care,
transition to dementia, amnestic syndrome or organic personality disorder
Prognosis
Full recovery: usually in 1 – 4 weeks, in elderly patients tends to také longer ….
Fatalities: 20 – 30 %
Transition to dementia
Transition to functional psychotic disorder : 10 %

24. Therapy of delirium tremens
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.
Pharmacotherapy:
sedation
benzodiazepines: (e.g. midazolam, lorazepam, tenazepam)
clomethiazol (Heminevrin)
combination of BZD and antipsychotics
antipsychotics: (haloperidol, sulpirid, tiaprid)
nootropics (e.g. piracetam – f.o. Kalikor, Nootropil, 2400 – 3200 mg/day or pyritinol mg/day etc.).

25. Amnesic syndrome Prognosis: 25% - full recovery 50% - partial recovery
Excludes: nonalcoholic Korsakov's psychosis or syndrome ( F04 )
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
Amnestic disorder, alcohol- or drug-induced
Korsakov's psychosis or syndrome, alcohol- or other psychoactive substance-induced or unspecified
Prognosis:
25% - full recovery
50% - partial recovery
Therapy: Thiamin mg p.o. for months

26. Psychotic disorder Onset up to two week after withdrawal
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.
hallucinations (typically auditory, but often in more than
one sensory modality)
perceptual distortions
delusions (often of a paranoid or persecutory nature)
psychomotor disturbances (excitement or stupor)
abnormal affect (from intense fear to ecstasy)
some degree of clouding of consciousness
Disorder vanish (at least partially) within 1 month, fully within 6 months
Examples:
Alcoholic Hallucinosis
Alcoholic Jealousy
Alcoholic Paranoia
Alcoholic psychosis
F1x.5 Psychotic disorder Schizofrenia-like
.51 predominantly delusional
.52 predominantly hallucinatory
.53 predominantly polymorphic
.54 predominantly depressive psychotic symptoms
.55 predominantly manic psychotic symptoms
.56 mixed
Onset up to two week after withdrawal
Persistence of psychotic symptoms > 48 hours

27. 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
Alcoholic dementia NOS
Chronic alcoholic brain syndrome
Dementia and other milder forms of persisting impairment of cognitive functions
Flashbacks
Late-onset psychoactive substance-induced psychotic disorder
Posthallucinogen perception disorder
Residual:
affective disorder
disorder of personality and behaviour

28. 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

29. Bio-psycho-social model - psychological level
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

30. 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

31. 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

32. Outside healthcare system:
Therapeutic system
Outside healthcare system:
Contact centers (KC)
Social welfare institutions
Therapeutic communities
After-treatment centers
Harm reduction
Family therapy
Counseling
In healthcare system:
Acute states (detox, withdrawal symptoms, toxic psychosis)
Therapeutic programs (ambulant, in psychiatric centers, clinics)
After-treatments programs
Substitution therapy
Family therapy
Counseling

33. Treatment of alcohol dependence
Pharmacological interventions
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
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

34. Treatment of opioid dependence
Pharmacological interventions
methadon (up to mg/die slow titration)
bubrenorphine (8-16mg/die slow titration)
Bubprenorphine + naloxone (4:1) – Subuxon (sublingual tablets)
Diamorphine (heroin)
Naltrexon, naloxon
LAAM
GHB, ibogain
Psychotherapy
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

35. Substitution therapy
Pharmacological intervention directed towards involvement of withdrawal symptoms and craving
Opiates and nicotine
Per oral administration of medication (or plasters with nicotine)
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
Special centers or physicians
Helping with motivation to undergo other treatments (re-socialization)
Minimization of risks associated with drug use, criminality, social problems etc. = harm reduction
Indication:
Severe and long lasting dependence on high doses of opiates, or combined addiction
Repeated unsuccessful attempts of treatments
Factors that support involvement in the program
Anamnestic positive experience with substitution therapy
Opioid dependence in HIV positive patients, repeated criminal activity associated with the drug use, if normal treatment is not possible
Treatment of pregnant patients if detoxification is not possible

36. Substitution therapy Replacement of primary drug … :
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:
With long-lasting action in the organism
With defined concentration
Without toxic adjuvants and effects
Administered usually p.o.
Used lege artis

37. Opioid substitution - contraindications
Methadone
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
Same as for methadone plus:
IMAO treatment and 14 days after ending such treatment
Severe respiratory insufficiency
Relative contraindications for both:
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

38. Treatment of stimulant dependence
Pharmacological interventions
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
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

39. Treatment of nicotine dependence
Pharmacological interventions
Substitution with nicotine (chewing gums, plasters, spray, bonbons)
1,5x - 2x increase the probability of smoking cessation
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)
1.-3. day 0,5 mg 1x daily, 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
Minimal interventions, counseling, behavioral approaches incl. CBT, motivational interventions

40. Detoxification units Important features: Indication:
usually requirement for further treatment
usually lasts 1 or more weeks
Symptoms of acute withdrawal with respect to the abused drugs (including physical symptoms after opiates, BZD, delirium tremens)
Use of pharmacological interventions – buprenorphin (Temgesic, Subutex, Suboxone), BZD, barbiturates, vitamins, hepatoprotectives
Many patients break down already on this level
Indication:
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:
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)

41. Detoxification – treatment approaches
Ad 1) without specific (substitution) medication
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
opioid assisted detoxification
methadon – after finding of an optimal dose continuous decline to 0 in 5-14 days
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, …)

42. 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

43. 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 non-alcoholic drugs solve the alcohol and cannabis consumption, others require strict abstinence from all drugs and addictive behaviors

44. 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

45. = 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)

46. Other issues Dual diagnosis Treatment of pregnant women
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

47. Thanks for attention