2. INTRODUCTION Many studies conducted in 1950’s and 1960’s suggest that hallucinogen assisted psychedelic psychotherapy may offer an effective treatment for alcoholism and addictions. However, different and not a rigorous scientific methodologies make it difficult to generalize across studies.

3. Ketamine has several advantages over other psychedelics as an adjunct to psychotherapy: Safe Short acting Not scheduled as other psychedelics Allowed for general anesthesia In our previous studies it has been shown to be an effective treatment for alcoholism

4. New approaches to treatment of heroin addiction in Russia are particularly important because of: Epidemic of heroin addiction since mid-1990s All agonists (methadone, LAAM) and partial agonists-antagonists (buprenorphine) are prohibited by the law HIV epidemic among heroin addicts

5. Seventy detoxified heroin addicts were randomly assigned to one of two groups: §The patients of the experimental group received psychotherapy in combination with a “psychedelic” dose of ketamine (2.0 mg/kg i.m.) §The patients of the control group received the same psychotherapy combined with a very low, non-psychedelic (non-hallucinogenic), dose of ketamine (0.20 mg/kg i.m.)  Both the psychotherapist and subject were blind to the dose of ketamine Study design

8. Assessments. Psychiatric symptoms:

9. Psychological Assessments:

10. Treatment Assessment, Outcome and Follow-up:

12. Treatment Procedure:

13. Data Management and Statistical Analysis:

14. 0,00 0,50 1,00 1,50 2,00 2,50 IntensitySomaesthesiaAffectPerceptionCognitionVolition High dose Low dose Characteristics of ketamine experience with HRS *** ** ***

19. +

23. 0,00 2,00 4,00 6,00 8,00 10,00 12,00 14,00 16,00 Before KPT High dose After KPT High dose Before KPT Low dose After KPT Low dose Affective subscale Cognitive subscale Behavioral subscale KPT influence on the syndrome of anhedonia ++ +++ + + ++

24. 0,00 10,00 20,00 30,00 40,00 50,00 60,00 70,00 80,00 Lie (L) Validity (F) Correction (K) Hypochondriasis (Hs) Depression (D) Convertion hysteria (Hy) Psychopathic deviate (Pd) Masculinity-femininity (Mf) Paranoia (Pa) Psychastenia (Pt) Schizophrenia (Sc) Hypomania (Ma) Social introversion (Si) Iowa manifest anxiety (Tailor) (At) Sensitivity-Repression (S-R) Ego strength (Es) Self-sufficiency (Sf) High dose Before KPT High dose After KPT KPT influence on the Minnesota Multiphasic Personality Inventory + + + + ++ +

25. 0,00 10,00 20,00 30,00 40,00 50,00 60,00 70,00 80,00 90,00 Lie (L) Validity (F) Correction (K) Hypochondriasis (Hs) Depression (D) Convertion hysteria (Hy) Psychopathic deviate (Pd) Masculinity-femininity (Mf) Paranoia (Pa) Psychastenia (Pt) Schizophrenia (Sc) Hypomania (Ma) Social introversion (Si) Iowa manifest anxiety (Tailor) (At) Sensitivity-Repression (S-R) Ego strength (Es) Self-sufficiency (Sf) Low dose Before KPT Low dose After KPT KPT influence on the Minnesota Multiphasic Personality Inventory + + ++ + ++ +++ + +

27. 0,00 10,00 20,00 30,00 40,00 50,00 60,00 70,00 80,00 90,00 100,00 Index of the understanding of the meaning of lifeUnderstanding of purposes in life Meaning of the process of life Self- actualization Locus of control of self Locus of control of life High dose Before KPT High dose After KPT Low dose Before KPT Low dose After KPT KPT influence on the purposes in life * * * * * * * ** * * *

29. * * * ** * * * ** *

30. Side effects and complications:

33. Psychedelic afterglow §One of the insights gained from previous research with psychedelics concerns the transient psychotherapeutic and psychological effects of psychedelic psychotherapy. The effects of psychedelic psychotherapy are often very pronounced within several days or weeks after a treatment session, but then these effects quickly decline. This phenomenon was termed a “psychedelic afterglow.”

34. Previous KPT study: §About 50% of patients in a high ketamine dose group and 60% of patients in a low dose group relapsed within the first 3 months.

35. Hypothesis: §Could the efficacy of KPT in treating heroin dependence be increased by administering multiple KPT sessions and thus stabilizing the afterglow?

36. Study design: §In this study of the efficacy of single versus repeated sessions of ketamine-assisted psychotherapy in promoting abstinence in people with heroin dependence, 59 detoxified inpatients with heroin dependence received a ketamine- assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and were then randomized into two treatment groups: 1.Participants in the first group received two addiction counseling sessions followed by two KPT sessions, with sessions scheduled on a monthly interval (multiple KPT group). 2.Participants in the second group received two addiction counseling sessions on a monthly interval, but no additional ketamine therapy sessions (single KPT group).

37. Study design II: §All participants were treated alike and were given the same preparation for KPT. The KPT sessions, regardless of their number, were given under uniform circumstances at the same psychiatric hospital. Clinical evaluators blind to whether participants had received one or three KPT sessions performed psychological and clinical evaluations on all participants during treatment and follow-up periods.

38. Drop out: §Six out of 59 participants enrolled in the study relapsed and dropped out of treatment within the first month after the initial KPT session. Prior to the second session, the 53 remaining participants were randomized into the two treatment groups: § Twenty-six participants were assigned to the multiple KPT group and received two more KPT sessions, including addiction counseling sessions before KPT, separated by one-month intervals. §Twenty-seven participants were assigned to the single KPT group and received two addiction counseling sessions separated by one-month intervals. There were no statistically significant differences between these groups in the mean age, duration of heroin addiction, and gender.

39. Retention in Treatment: §In the multiple KPT group, four out of 26 participants (15.4%) relapsed and dropped out of treatment after the second KPT session but prior to the third. §In the single KPT group, seven out of 27 participants (25.9%) relapsed and dropped out of treatment after the first counseling session. §The difference in the retention in treatment phase between the two groups was not statistically significant.

40. Kaplan-Meier Survival Analysis P<0.01 Months 1614121086420 Cummulative Survival 1,2 1,0,8,6,4,2 0,0 Group of treatment Single KPT session single-censored Multiple KPT sessions multiple-censored

41. Kaplan-Meier Survival Analysis P<0.01

42. Rate of Abstinence: §At the end of the one-year follow-up, 13 out of 26 participants (50%) in the multiple KPT group remained abstinent compared to six out of 27 participants (22.2%) in the single KPT group (p < 0.05).

48. Conclusion § Three sessions of ketamine-assisted psychotherapy are more effective than a single session for the treatment of heroin addiction.

50. What does all of that mean?

51. Should we take a courage to bridge the gap between psychedelic psychotherapy and main stream?

52. Even though we can not do that right now…

53. We should start to go this way…

54. Think more about that…

55. Balance all the arguments…

56. Be very careful with every tiny detail…

58. THE FUTURE ?

59. Some men see things as they are, and say “why?” I dream of things that have never been, and say “why not?” Robert F Kennedy