Buprenorphine and the NIDA CTN: Research to Practice Walter Ling & Richard Rawson ISAP/UCLA XIII World Congress of Psychiatry September 14, 2005 Cairo, Egypt

Potentially lethal dose Positive effect = addictive potential Negative effect Full agonist- morphine/heroin hydromorphone Antagonist - naltrexone dose Antagonist + agonist/partial agonist Agonist + partial agonist Super agonist- fentanyl Partial agonist - buprenorphine Mu efficacy and opiate addiction

Buprenorphine: Clinical Pharmacology Partial Agonist high safety profile/ceiling effect low dependence Tight Receptor Binding long duration of action slow onset mild abstinence

Good Effect

Respiration

Intensity of abstinence Himmelsbach scores Buprenorphine Morphine Days after drug withdrawal

Buprenorphine detoxification in community clinics Buprenorphine : Very brief pharmacology CTN Protocols 0001 & 0002 Buprenorphine vs clonidine: Inpatient detoxification Outpatient detoxification Treatment success /Number needed to treat Looking ahead: Implementation: Successes and barriers The rest of the world

The First CTN Protocols Short term inpatient detoxification –Buprenorphine/naloxone vs clonidine –(CTN 0001) Short term outpatient detoxification –Buprenorphine/naloxone vs clonidine –(CTN 0002)

Study Design Buprenorphine/Naloxone 13 days detoxification Open Randomized Study Bup/Nx:Clonidine = 2:1 Clonidine 13 days detoxification

Joint Probability N remaining in treatment X Total N of subjects N giving drug free urines N remaining in treatment

Demographics 0001 (Inpatient) Bup/NxClonidineTotal Sex No. (%) Male Female 47 (61) 30 (39) 21 (58) 15 (42) 68 (60) 45 (40) Race No. (%) White Black Hispanic Other 43 (56) 15 (19) 12 (16) 7 (9) 20 (56) 7 (19) 6 (17) 3 (8) 63 (56) 22 (19) 18 (16) 10 (9) Age in Years: Mean (Range 21-61) Employment % (full/part time)--66 Mean Education in Years (SD) (1.7) Mean Years of Heroin Use (SD)--6.6 (8.1)

Present and Clean 0001 (Inpatient) Present and Opiate Clean Bup/Nx%Clonidine% N 7736 Day 3 or Day 7 or Day 10 or Day 13 or

Percent Present and Clean 0001 (Inpatient)

Demographics 0002 (Outpatient) Bup/NxClonidineTotal Sex No. (%) Male Female 115 (73) 42 (27) 51 (69)) 23 (31) 166 (72) 65 (28) Race No. (%) White Black Hispanic Other 62 (40) 57 (36) 33 (21) 5 (3) 30 (40) 28 (38) 13 (18) 3 (4) 92 (40) 85 (37) 46 (20) 8 (3) Age in Years: Mean (Range 21-61) Employment % (full/part time) Mean Education in Years (SD) (2.1) Mean Years of Heroin Use (SD) (9.6)

Present and Clean 0002 (Outpatient) Present and Opiate Clean Bup/Nx%Clonidine% N Day 3 or Day 7 or Day 10 or Day 13 or

Percent Present and Clean 0002 (Outpatient)

NNT: Number Needed to Treat CTN 0001 (Inpatient) NNT for Bup/Nx 77/59 = 1.31 NNT for Clonidine 36/8 = 4.5 NNT Clonidine : BupNx = 3.44 CTN 0002 (Outpatient) NNT for Bup/Nx: 157/46 = 3.4 NNT for Clonidine: 74/4 = 18.5 NNT Clonidine : Bup/Nx = 5.44 NNT= Number of patients needed to treat to achieve 1 treatment success

Buprenorphine: what does it really mean? The great social experiment: return of opioid addiction treatment to medicine Slow progress in implementation: –External barriers: legislative compromises –Inertia and resistance: medication and recovery Application to the world and the region

Pharmacotherapy and Recovery Medications and recovery: incompatible? “Medication is not recovery” The great chemistry paradox –Addiction: chemistry went wrong –Role of “chemistry” (medicine) in recovery

You Can Change the Brain with Either Biological or Behavioral Treatments Remember…. Alan Leshner

How People Change “You can change some one’s life by altering his genes; but you can also do that by paying off his credit card” James Watson

Thanks to XIII Congress of Psychiatry: symposia organizing committee National Institute on Drug Abuse NIDA Clinical Trials Network Staff CTN Publications Committee Participating CTN Nodes and CTPs Reckitt Benckiser: supplier of study med Participating Patients You the audience