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