Prevention and treatment of drug dependence:new challenges and perspectives

Gilberto GerraChief

Health and Human Development SectionUNODC

PREVENT METHAMPHETAMINES USEAND TREAT METHAMPHETAMINES USE DISORDERS

PREVENT COCAINE USEAND TREAT COCAINEDEPENDENCE

BZDshydrocodone

PREVENT PRESCRIPTION DRUGS USE AND TREAT DEPENDENCE

N,N-dimethyltryptamine (DMT) N,N-dipropyltryptamine (DPT) N,N-diethyltryptamine (DET)5-methoxy-DMT (5-MeO-DMT)

‘…..Similar to combining DMT/DPT/5-MeO-DMT with ketamine, combining 4-acetoxy-DET with ketamine also provides an incredible synergy. Highly recommended for the cosmic-mystical near-death inclined!..... Xenon gas while on mushrooms or LSD comes in at a close second. ’

F. Schifano, 2008

UNDERSTAND AND PREVENT combinations of psychedelics

CANNABINOID AGONISTS DESIGNERS?

Delay the age of onset

youths aged 12 to 17 have constituted about two thirds of the new marijuana users (OAS, 2001)

significantly elevated ORs for a cannabis use disorderat each of teenage years (ages 12-18; range of ORs=3.9-7.2), (Winters and Lee, 2008)

ALCOHOL AND TOBACCO

PREVENT THE USE OFLEGAL DRUGS

Have drug dependencerecognized as a disease

Isolation and Social Status Can Change NeurobiologyIsolation and Social Status Can Change Neurobiology

IndividuallyHoused

GroupHoused

Becomes DominantNo longer stressed

Becomes SubordinateStress remains

Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002.

Brain DA D2 Receptors

  LL SL SS 

NOVELTY SEEKING 15,72 19,41 21,75* 

BDHI DIRECT AGGRESSION 51,03 55,70 59,58* 

LL SL SS

smokers 26.53% 50.00% 23.47%

never-smoking subjects

37.63% 52.69% 9.68% *

* chi2=7.33, p<0.05

DRD2-TaqI A1 allele polymorphisms 30%

methamphetamines controls abusers

Han et al., 2008

Higher noveltyseeking scoresamongmeth-abuserswith allele A1

 

Genotypes 9-9 

10-10 

9-10 

9-11 

10-11 

 Offenders  

 17.3%

  42.3%

 36.5%

 0%

  3.8%

 Non-offenders  

 3.8%

 48.1%

 44.3%

 5.8%

 0%

  

2= 4.39 p= 0.04

n.s. n.s n.s. n.s.

DAT genotypes among heroin dependent patients

Gerra et al., Addiction Biology, 2005

Heroin abuse was significantly associated with proenkephalin (PENK) polymorphic 3' UTR dinucleotide (CA) repeats

79% of subjects homozygous for the 79-bp allele were heroin abusers

Nikoshkov et al., 2008

temperament predicted substance use only through shared environmental

factors

Genetic risk Environmental risk

Legrand et al., 1999

low levels of environmental risk may buffer against

the potentially unfavorable effects of high familial risk

substance use

Relevance of childhood neglect, 5-HTT gene variants and hypothalamus-pituitary-adrenal axis dysregulation to substance abuse susceptibility

Risk of experimenting with illicit drugs

5HTTSS

neglect

HPAaxis

Gerra et al.,In press

Gerra et al., in press

reduced maternal care perception was found to represent

a key intermediate factor of the association between SS polymorphism and drug use, suggesting that genetic factors

and parental behavior concur to drug use susceptibility

Once controlled for CECA-Q scores the relative risk associated to the SS genotype drops strikingly

adolescents with the S allele of the 5-HTT gene and with family relations being "neutral" or "bad" had a 12- to 14-fold increased risk for high alcohol intoxication frequency

Nilsson et al., 2005

American Journal of Medical Genetics Part B (Neuropsychiatric Genetics) 141B:1–7 (2007)

_____________________________________________________________________________

Perceived Parenting Behavior in the Childhood of Cocaine Users: Relationship With Genotype and Personality TraitsG. Gerra,1* A. Zaimovic,1 L. Garofano,2 F. Ciusa,1 G. Moi,1 P. Avanzini,3 E. Talarico,3 F. Gardini,4 F. Brambilla,1 M. Manfredini,5 and C. Donnini5

1Centro Studi Farmaco-tossicodipendenze, Ser.T., AUSL, Parma, Italy2Reparto Investigazioni Scientifiche (RIS), Carabinieri di Parma, Parma, Italy3Servizio Immuno-trasfusionale, Azienda Universita`-Ospedale di Parma, Italy4Dipartimento di Medicina Interna, Azienda Universita`-Ospedale di Parma, Italy5Dipartimento di Genetica Antropologia Evoluzione, Universita` degli Studi di Parma, Parma, Italy

  

   PBI

Paternal care

 PBI

Maternal care

 BDHIDirect

aggression

 abstinent subjects

 

 25,490,42

 27,590,38

 45.32.9

cocaine users LL-SL 5-HTTgenotypes

 22,560.9

 24.610.5

 59.32.9

cocaine usersSS 5-HTT

genotypes

18.780.4

 18.890.45

 63.252.5

Perceived parenting behaviour in the childhood of cocaine users: relationship with genotype and personality traits (Gerra et al., 2007)

18

27

PERCEPTION OF PARENTAL CARE

- 10% risk

- 20% risk

RISK OF COCAINE USE IN THE ADULT

PBI SCORE

- 90% risk

Adverse childhood experiences

neglect abuse

Monkeys who suffer maternal deprivation in childhood tend to be fearful, more aggressive, less exploratory,

and subject to binge drinking on exposure to alcohol

Ichise et al., 2006

Early maternal deprivationreduces serotonin transporter

- Childhood psychiatric disorders

- Early onset adult psychiatric disorders

Self-medication mechanism

Addiction and premorbid psychiatric disorders:

- social phobia - bipolar affective disorder - depression- anxiety- conduct disorder - oppositional defiant disorders

were strongly associated with the subsequent development of substance dependence (attributable risks ranging from 44 to 86%)

Merikangas and Avenevoli, 2000

Arch Gen PsychiatryProspective effects of attention-deficit/hyperactivity disorder, conduct disorder, and sex on adolescent substance use and abuse.Elkins et al., 2007

Hyperactivity/impulsivity predicts later substance problems, even after growth in later-emerging CD is considered

Inattention alone poses less risk

Partial Recovery of Brain Dopamine Transportersin Methamphetamine (METH)

Abuser After Protracted Abstinence

Normal Control METH Abuser(1 month detox)

METH Abuser(24 months detox)

Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.

ADDICTION CAN BE TREATED

Midbrain SERT density significantly increased during psychotherapy

Baseline 12 months

DRUG USE IS ONE OF THE TOP 20 RISK FACTORS TO HEALTH WORLDWIDE

TOP 10 IN HIGH INCOME COUNTRIES

HIV/AIDS HEPATITIS TUBERCULOSIS SUICIDE – PSYCHIATRIC DISORDERSCARDIOVASCULAR DISEASESOVERDOSE DEATHS

30% of HIV infection is due to injecting drug users

when criminal activities related to drugs are includedTHE COST OF DRUG DEPENDENCE CAN AMOUNT TO 2% OF THE GDP

…eliminating or reducing illicit demand for narcotic drugs and psychotropic substances with a view of reducing human suffering

STOP PUNISHMENT AND UNETHICAL TREATMENT METHODS

STOP VIOLATIONOF HUMAN RIGHTSPRESENTED AS TREATMENT

STOP MARGINALIZATION AND DISCRIMINATION

- Reach individuals not motivated to treatment- Protect their health and respond to HIV epidemic- Provide unconditioned social assistance- Offer low threshold, accessible treatment for drug dependence

Provide a comprehensive package of

harm reduction measuresa. reliable information and counseling b. low-threshold pharmacological interventions (example opioid-agonists and antagonist drugs) easily accessiblec. adequate social assistance for marginalized drug dependentsd. vaccination programmes against Hepatitis to all drug abuserse. medication and emergency kits for management of overdoses in appropriate placesf. needle/syringe exchange programmes under sound medical practiceg. voluntary HIV counseling and testing, and antiretroviral treatmenth. prevention and services for the management of sexually transmitted infections for drug abusers involved in sex work;i. availability of measures to prevent acute consequences of stimulants abuse (free water…)j. interventions in emergency rooms k. well-equipped street-workers and peer outreach workers unitsl. measures to prevent car and workplace accidentsm. social assistance for children of drug dependent individuals

NOT IN ALTERNATIVE TO DEMAND REDUCTION BUT COMPLEMENTARY TO DEMAND REDUCTION

BASIC FIRST LINE HEALTH/ SOCIAL ASSISTANCE

SUSTAINABLELIVELIHOOD OPPORTUNITIES

SCHOOL INSTEAD OF STREET

TREATMENT OFCONCOMITANTPSYCHIATRIC DISORDERS

Estimated coverage of drug education in schools based ONLY on information

Data from selected key countries in Asia, Latin America and Africa

20%

80%

Receive information Do NOT receive information

Estimated coverage of drug education in schools that is EVIDENCE-BASED

Data from selected key countries in Asia, Latin America and Africa

5%

95%

Covered by evidence-based drug education

NOT covered by evidence-based drug education

scare tactics and moralistic appeals

curricula that rely solely on information about drugs and their dangers

curricula that only work to promote self-esteem and emotional well-being

single shot assemblies

testimonials by former addicts

counseling in peer-group context

recreation and community service activities

Levine et al. 1999

WHAT IS NOT WORKING IN PREVENTION

training in resistance skills

normative education

life skills: communication

life skills: decision making

life skills: emotional communication

life skills: impulse control

life skills: self esteem

trained teacher

interactive method

WHAT IS WORKING IN SCHOOL PREVENTION

Faggiano et al., Cochrane 2005

interactive approaches

life skill practice

normative education, which portrays true use rates and corrects misperceptions

positive school climates:a combination of clear policies and procedures, training and support for school staff, students and families and partnerships with communitymembers Nancy Tobler (1992)

Linda Dusenbury (1995)

Parental care/neglect

Trauma/abuse

Stress, post conflict, instability, poverty

School connectedness

Bonding to the communityValues and believes

RISK RESILIENCE

Return on Investment(Benefit-cost ratios) of Selected Programs

• Pre-school education– Early Childhood Education.........................................$2.36

• Child welfare– Nurse Family Partnership...........................................$2.88

• Youth development– Guiding Good Choices (PDFY)...............................$11.07

• Juvenile offender programs– Dialectical behavior therapy....................................$38.05

*Source: Aos, Lieb, Mayfield, Miller & Pennucci (2004)

Future Annual Benefitsfrom Preventing a Single Alcohol Use Disorder

0

1000

2000

3000

4000

5000

6000

7000

18 26 34 42 50 58 66 74Years of age

Estimated variety and coverage of treatment offered

0 20 40 60 80 100

Asia

Africa

Latin America

Variety Coverage

Data from selected key countries in Asia, Latin America and Africa

Main problem drugs as reflected in treatment demand in

2006 (or latest year available)

26 million problem drug users 4.9 million persons treated in 2006

US$ 21 bn0.16% of GDP

the lowest estimate: 4 bn0.03 % of GDP

the highest estimate: 52bn0.4 % of GDP

ESTIMATES CONCERNING THE COST OF DRUG DEPENDENCE TREATMENT AND CAREIN LOW AND MIDDLE INCOME COUNTRIES

UNODC, unpublished data

Addictive Disease core

Compulsive behaviors/drug seeking in spite of adverse consequences

Behavioral under-control – risk taking

Reduced reward perception

Impairment of emotional perception and communication

Inability to cope with stress

Social isolation, low self esteem and depressive traits

Unstable mood and affects, anxiety

Barriers to drug dependence treatment and care

Stigma/discrimination

No services available

Lack of professional competence

Services far from home

PunishmentConsequences of registration

Services not for free or high threshold

Services not incorporated in the health care system

No complementary sustainable livelihood measures

MAKE A VARIETY OF TREATMENT METHODS ACCESSIBLE

WHAT IS WORKING IN TREATMENT

Brief interventionVocational trainingMotivational therapyCognitive-behavioural therapyContingency therapyFamily therapySelf help 12 step

Long term opioid-agonistsSlow release opioid-antagonistsAlpha-adrenergic agonists

VaccineModafinilDA D3 antagonistAntiepileptic GVGN-acetylcysteineCRF-antagonists

Promising tools

Relapse Rates Are Similar for Drug Dependence And Other Chronic Illnesses

0

10

20

30

40

50

60

70

80

90

100

Drug Dependence

Type I Diabetes

Hypertension Asthma

40 t

o 60

%40

to

60%

30 t

o 50

%30

to

50% 50

to

70%

50 t

o 70

%

50 t

o 70

%50

to

70%

Source: McLellan, A.T. et al., JAMA, Vol 284(13), October 4, 2000.

Per

cen

t of

Pat

ien

ts W

ho

Rel

apse Addiction Treatment Does WorkAddiction Treatment Does Work

Evaluation of A Hypothetical Treatment

0

1

2

3

4

5

6

7

8

9

10

Pre During During During Post

Sym

pto

m S

ever

ity HYPERTENSIONHYPERTENSION

0

1

2

3

4

5

6

7

8

9

10

Pre During During During Post

Stage of Treatment

Sym

pto

m S

ever

ity ADDICTIONADDICTION

Just Like Hypertension,Addiction Is A

Chronic Disease ThatRequires Continued Care

Source: McLellan, AT, Addiction 2002.

Mobilization for drug dependence treatment and care: a large partnership…

…starting fromUNODC and WHO

1) Advocacy

2) Training, good practice dissemination

3) Low cost treatment centers

4) Evaluation and research

5) National-regional networks

6) Guidelines and therapeutic tools

2009-2013

20 developing countries in the first biennium

30 developing countries in the second biennium

A partnership for drug dependence treatment and care

Low cost treatment centres /non-professional teams

Counselling/brief intervention/vocational therapy

Medications: nurses/primary care

Social assistance

Families involvement

Health care-HIV-Hepatitis prevention

Outreach/ low threshold interventions

mainstreaming addiction treatment and

HIV/Hepatitis prevention in health care system

and municipalities social programs

FROM HOPELESSNESS

TO HOPE