1. Prevention and treatment of drug dependence: new challenges and perspectives Gilberto Gerra Chief Health and Human Development Section UNODC

2. PREVENT METHAMPHETAMINES USE AND TREAT METHAMPHETAMINES USE DISORDERS

3. PREVENT COCAINE USE AND TREAT COCAINE DEPENDENCE

4. BZDs hydrocodone PREVENT PRESCRIPTION DRUGS USE AND TREAT DEPENDENCE

5. 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

6. CANNABINOID AGONISTS DESIGNERS?

7. 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 disorder at each of teenage years (ages 12-18; range of ORs=3.9-7.2), (Winters and Lee, 2008)

9. ALCOHOL AND TOBACCO PREVENT THE USE OF LEGAL DRUGS

10. Have drug dependence recognized as a disease

12. Isolation and Social Status Can Change Neurobiology Individually Housed Group Housed Becomes Dominant No longer stressed Becomes Subordinate Stress remains Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002. Brain DA D2 Receptors

13. LLSLSS NOVELTY SEEKING15,7219,4121,75* BDHI DIRECT AGGRESSION51,0355,7059,58*

14. LLSLSS smokers26.53%50.00%23.47% never- smoking subjects 37.63%52.69%9.68% * * chi2=7.33, p<0.05

15. DRD2-TaqI A1 allele polymorphisms 30% methamphetamines controls abusers Han et al., 2008 Higher novelty seeking scores among meth-abusers with allele A1

16. Genotypes9-9 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.sn.s. DAT genotypes among heroin dependent patients Gerra et al., Addiction Biology, 2005

17. 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

18. temperament predicted substance use only through shared environmental factors Genetic riskEnvironmental risk Legrand et al., 1999 low levels of environmental risk may buffer against the potentially unfavorable effects of high familial risk substance use

19. Relevance of childhood neglect, 5-HTT gene variants and hypothalamus-pituitary-adrenal axis dysregulation to substance abuse susceptibility Risk of experimenting with illicit drugs 5HTT SS neglect HPA axis Gerra et al., In press

20. Gerra et al., in press

21. 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

22. 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

23. 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 Traits G. 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, Italy 2Reparto Investigazioni Scientifiche (RIS), Carabinieri di Parma, Parma, Italy 3Servizio Immuno-trasfusionale, Azienda Universita`-Ospedale di Parma, Italy 4Dipartimento di Medicina Interna, Azienda Universita`-Ospedale di Parma, Italy 5Dipartimento di Genetica Antropologia Evoluzione, Universita` degli Studi di Parma, Parma, Italy

24. PBI Paternal care PBI Maternal care BDHI Direct aggression abstinent subjects 25,49  0,42 27,59  0,38 45.3  2.9 cocaine users LL-SL 5-HTT genotypes 22,56  0.9 24.61  0.5 59.3  2.9 cocaine users SS 5-HTT genotypes 18.78  0.4 18.89  0.45 63.25  2.5 Perceived parenting behaviour in the childhood of cocaine users: relationship with genotype and personality traits (Gerra et al., 2007)

25. 18 27 PERCEPTION OF PARENTAL CARE - 10% risk - 20% risk RISK OF COCAINE USE IN THE ADULT PBI SCORE - 90% risk

26. Adverse childhood experiences neglectabuse

27. 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 deprivation reduces serotonin transporter

31. - Childhood psychiatric disorders - Early onset adult psychiatric disorders Self-medication mechanism

32. 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

33. Arch Gen Psychiatry Prospective 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

34. Partial Recovery of Brain Dopamine Transporters in Methamphetamine (METH) Abuser After Protracted Abstinence Normal Control METH Abuser (1 month detox) METH Abuser (24 months detox) 0 3 ml/gm Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001. ADDICTION CAN BE TREATED

35. Midbrain SERT density significantly increased during psychotherapy Baseline 12 months

36. 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 DISORDERS CARDIOVASCULAR DISEASES OVERDOSE DEATHS 30% of HIV infection is due to injecting drug users when criminal activities related to drugs are included THE COST OF DRUG DEPENDENCE CAN AMOUNT TO 2% OF THE GDP

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

38. STOP PUNISHMENT AND UNETHICAL TREATMENT METHODS

39. STOP VIOLATION OF HUMAN RIGHTS PRESENTED AS TREATMENT

40. STOP MARGINALIZATION AND DISCRIMINATION

41. - 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

42. Provide a comprehensive package of harm reduction measures a.reliable information and counseling b.low-threshold pharmacological interventions (example opioid-agonists and antagonist drugs) easily accessible c. adequate social assistance for marginalized drug dependents d. vaccination programmes against Hepatitis to all drug abusers e. medication and emergency kits for management of overdoses in appropriate places f. needle/syringe exchange programmes under sound medical practice g. voluntary HIV counseling and testing, and antiretroviral treatment h.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 units l.measures to prevent car and workplace accidents m.social assistance for children of drug dependent individuals NOT IN ALTERNATIVE TO DEMAND REDUCTION BUT COMPLEMENTARY TO DEMAND REDUCTION

43. BASIC FIRST LINE HEALTH/ SOCIAL ASSISTANCE SUSTAINABLE LIVELIHOOD OPPORTUNITIES SCHOOL INSTEAD OF STREET TREATMENT OF CONCOMITANT PSYCHIATRIC DISORDERS

44. Estimated coverage of drug education in schools based ONLY on information Data from selected key countries in Asia, Latin America and Africa

45. Estimated coverage of drug education in schools that is EVIDENCE-BASED Data from selected key countries in Asia, Latin America and Africa

46. 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

47. 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

48. 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 community members Nancy Tobler (1992) Linda Dusenbury (1995)

49. Parental care/neglect Trauma/abuse Stress, post conflict, instability, poverty School connectedness Bonding to the community Values and believes RISK RESILIENCE

53. 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)

54. Future Annual Benefits from Preventing a Single Alcohol Use Disorder 0 1000 2000 3000 4000 5000 6000 7000 1826344250586674 Years of age

55. Estimated variety and coverage of treatment offered Data from selected key countries in Asia, Latin America and Africa

56. 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

57. US$ 21 bn 0.16% of GDP the lowest estimate: 4 bn 0.03 % of GDP the highest estimate: 52bn 0.4 % of GDP ESTIMATES CONCERNING THE COST OF DRUG DEPENDENCE TREATMENT AND CARE IN LOW AND MIDDLE INCOME COUNTRIES UNODC, unpublished data

58. 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

59. Barriers to drug dependence treatment and care Stigma/discrimination No services available Lack of professional competence Services far from home Punishment Consequences of registration Services not for free or high threshold Services not incorporated in the health care system No complementary sustainable livelihood measures

60. MAKE A VARIETY OF TREATMENT METHODS ACCESSIBLE

61. WHAT IS WORKING IN TREATMENT Brief intervention Vocational training Motivational therapy Cognitive-behavioural therapy Contingency therapy Family therapy Self help 12 step Long term opioid-agonists Slow release opioid-antagonists Alpha-adrenergic agonists Vaccine Modafinil DA D3 antagonist Antiepileptic GVG N-acetylcysteine CRF-antagonists Promising tools

62. 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 HypertensionAsthma 40 to 60% 30 to 50% 50 to 70% Source: McLellan, A.T. et al., JAMA, Vol 284(13), October 4, 2000. Percent of Patients Who Relapse Addiction Treatment Does Work

63. Evaluation of A Hypothetical Treatment 0 1 2 3 4 5 6 7 8 9 10 PreDuring Post Symptom Severity HYPERTENSION 0 1 2 3 4 5 6 7 8 9 10 PreDuring Post Stage of Treatment Symptom Severity ADDICTION Just Like Hypertension, Addiction Is A Chronic Disease That Requires Continued Care Source: McLellan, AT, Addiction 2002.

65. Mobilization for drug dependence treatment and care: a large partnership… …starting from UNODC and WHO

66. 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

67. 2009-2013 20 developing countries in the first biennium 30 developing countries in the second biennium A partnership for drug dependence treatment and care

68. 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

69. mainstreaming addiction treatment and HIV/Hepatitis prevention in health care system and municipalities social programs

71. FROM HOPELESSNESS TO HOPE