Emerging Substances of Abuse – Spice/K2 (Synthetic Cannabinoids)

INVESTIGATION OF GENETIC VARIATIONS IN THE MESOLIMBIC DOPAMINE SYSTEM AND ELEVATED RISK OF OPIOID ABUSE IN CHRONIC PAIN PATIENTS

Daniel A Schwarz MD1, Tobore Onojighofia MD2, Bilikis Akindele MD2, Brian J. Meshkin BA2, Lynn Webster MD3, Gregory Smith, MD4, Mehrdad Zoleikhaeian, BS5

Disclosures Commercial Sponsor: Proove Biosciences, Inc 1-Pain Recovery Specialists, PLLC, Southfield, MI: Consultant 2-Proove Biosciences, Inc, Annapolis, MD (Employee/Stock Options) 3-CRI, Lifetree, Salt Lake City, UT: Consultant 4-Comprehensive Pain Relief Group, Torrence, CA: CMO/Consultant 5-Proove Biosciences, Inc, Irvine, CA (Employee/Stock Options)

There is no commercial bias within this presentation.

Hepatic/CYP Metabolism 60% Medications Metabolized by Phase I Clinically affect Codeine (2D6) Little effect on most Opioids

Copyright © Glenn Duncan, 2012. Providing continuing education to professionals in the behavioral health field. Do not reproduce without written consent. Also providing on-site training and consultation. Phone 1-732-547-2735

Emerging Substances of Abuse – Spice/K2 (Synthetic Cannabinoids) Hepatic/CYP Metabolism • Oxycodone • Hydrocodone

*

2D6

Oxymorphone

2D6

Hydromorphone

• NO clinical effect documented poor/rapid • *Only 15% of pathway (3A4 primary) • NO SNP variant affects 3A4 except Statin

The Current System is Broken

• 60% of patients fail to their control pain with current pain medications • 3x as many people are addicted to and die from Rx pain meds than all illegal narcotics combined

Genetic Pre-Disposition

• A doctor’s ability to identify a patient who will abuse pain medication is no better than 50/50 • According to NIDA and ASAM, up to 60% of all substance abuse is due to genetic factors

Copyright © Glenn Duncan, 2012. Providing continuing education to professionals in the behavioral health field. Do not reproduce without written consent. Also providing on-site training and consultation. Phone 1-732-547-2735

Emerging Substances of Abuse – Spice/K2 (Synthetic Cannabinoids) Pain and Addiction Mesolimbic reward system: Dopamine

CNS Genetics

• 12-gene SNP panel to assess Opioid Risk • Dopamine: DRD1, D2, D4; DAT, DBH and COMT • Serotonin: 5-HT2A, 5-HTTPLR and MTHFR • Opioid: OPRM1 and OPRK1 • GABA: GABRG2

Copyright © Glenn Duncan, 2012. Providing continuing education to professionals in the behavioral health field. Do not reproduce without written consent. Also providing on-site training and consultation. Phone 1-732-547-2735

Emerging Substances of Abuse – Spice/K2 (Synthetic Cannabinoids) Narcotic Risk Score Combined Score 12 to 36 Normal = 1, Hetero = 2 and Homozygous = 3

Pt

Research Supports Prevalence and Risk for Abuse

C

0

10

20

≥ 20 Positive PV 80% Risk Abuse

30

STUDIES

PILL

• Genotype Prevalence in Chronic Pain pts on Narcotics vs Controls

OSCAR

• Genotype Pain Pts with Dx Substance Abuse vs Without

RACER

• Genotype vs. Detox/Rehab Maintenance Outcomes

P.I.L.L. Study Objective: Genotype Prevalence Chronic Pain

Patients on Rx Opioids vs. Control Population

Initial Pilot Study: Single-Site 100 pts 4/12 SNPs significant

Copyright © Glenn Duncan, 2012. Providing continuing education to professionals in the behavioral health field. Do not reproduce without written consent. Also providing on-site training and consultation. Phone 1-732-547-2735

Emerging Substances of Abuse – Spice/K2 (Synthetic Cannabinoids) OSCAR Study

OSCAR Study

R.A.C.E.R. Study Objective: Can genotype identify successful outcome to detox/maintenance?

Retrospective Analysis: Chronic pain pts with prescription substance abuse rehab + maintenance

Copyright © Glenn Duncan, 2012. Providing continuing education to professionals in the behavioral health field. Do not reproduce without written consent. Also providing on-site training and consultation. Phone 1-732-547-2735

Emerging Substances of Abuse – Spice/K2 (Synthetic Cannabinoids) R.A.C.E.R. Results Methods: 159 Subjects; 148 completed 90-day medical detox/rehab + 2yr Medically Assisted Treatment Results: NR ≥ 19 predict successful outcome (90% PPV) Genetically predisposed SUD better outcome v SUD patients not genetically predisposed.

Background

• PGx Narcotic Risk Requires CNS > Hepatic DME • Validated CNS Genotypes Chronic Pain vs Controls • 80% PPV 12-gene NR > 20 Chronic Pain Abuse • Better recovery results in patients genetically predisposed to SUD

Objective Quantify the prevalence of variants from the mesolimbic dopaminergic, serotonergic and opioid SNPs among chronic pain patients taking prescription opioid medications vs. established controls.

Copyright © Glenn Duncan, 2012. Providing continuing education to professionals in the behavioral health field. Do not reproduce without written consent. Also providing on-site training and consultation. Phone 1-732-547-2735

Emerging Substances of Abuse – Spice/K2 (Synthetic Cannabinoids) Methods • Real-time Polymerase Chain Reaction (qPCR) • TaqMan® Assays (Life Technologies, Carlsbad, CA) • 12 Gene SNPs Mesolimbic “Reward” Pathway • Dopamine: DRD1, DRD2, DRD4, DAT, DBH, COMT • Serotonergic: 5-HT2a and 5-HTTPLR, and MTHFR • Opioid: OPRK1 and OPRM1 plus GABRG2

Methods • IRB approved cross sectional study • 5263 subjects diagnosed with chronic pain and taking prescription opioids • The values for the controls were computed with data from the International HapMap project Consortium, by the BBS genotyping center using the bbs: phase3_draft1 platform.

Methods • Chi square test was done to find an association between the SNPs in chronic pain patients vs. controls using SAS/JMP software v10.

Copyright © Glenn Duncan, 2012. Providing continuing education to professionals in the behavioral health field. Do not reproduce without written consent. Also providing on-site training and consultation. Phone 1-732-547-2735

Emerging Substances of Abuse – Spice/K2 (Synthetic Cannabinoids) Results SNPs with higher prevalence in study compared to controls

• DRD2(15% v. 5% p