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THE SCIENCE OF RECOVERY: AN ADVANCED SEMINAR

THE SCIENCE OF RECOVERY: AN ADVANCED SEMINAR. CARDWELL C. NUCKOLS, PhD cnuckols@elitecorp1.com WWW.CNUCKOLS.COM. THE SCIENCE OF RECOVERY.

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THE SCIENCE OF RECOVERY: AN ADVANCED SEMINAR

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  1. THE SCIENCE OF RECOVERY: AN ADVANCED SEMINAR CARDWELL C. NUCKOLS, PhD cnuckols@elitecorp1.com WWW.CNUCKOLS.COM

  2. THE SCIENCE OF RECOVERY “…this business of resentment is infinitely grave. We found that it is fatal. For when harboring such feeling we shut ourselves off from the sunlight of the Spirit. The insanity of alcohol returns and we drink again. And with us, to drink is to die.” Big Book page 66

  3. THE SCIENCE OF RECOVERY GRATITUDE (LOVE) A CHANGE IN WORLDVIEW GRANDIOSITY(CHARACTER DEFECTS)

  4. WHAT DO YOU SEE?

  5. NUCLEUS BASALIS

  6. THE SCIENCE OF RECOVERY: NEUROPLASTICITY THE NUCLEUS BASALIS IS… THE MODULATORY CONTROL CENTER FOR PLASTICITY NOVELTY

  7. THE SCIENCE OF RECOVERY: NEUROPLASTICITY YOU ARE NEUROPLASTICIANS! WHAT ENHANCES PLASTICITY? • NOVELTY • THERAPEUTIC RELATIONSHIPS • PHYSICAL EXERCISE • MINDFULNESS

  8. NEUROPLASTICITY • BRAIN AT ALL AGES IS RESPONSIVE TO ENVIRONMENTAL STIMULI • SYNAPSES CAN CHANGE IN MINUTES WHEN STIMULATED • NEUROPLASTICITY IS MODULATED BY • GENETIC FORCES • EPIGENETIC FORCES

  9. ADDICTION AND RECOVERY

  10. THE SCIENCE OF RECOVERY:GENETICS • GENETICS • A1 ALLELE OF THE DOPAMINE D2 RECEPTOR GENE • FOUND IN ONE-THIRD OF POPULATION • LOW DOPAMINE TONE

  11. THE SCIENCE OF RECOVERY:GENETICS • TWIN STUDIES SUGGEST GENES AND ENVIRONMENTAL FACTORS EACH INFLUENCE THE VULNERABILITY TO DEVELOPING ADDICTION • STRESS IS ONE, IF NOT THE PRINCIPLE, ENVIRONMENTAL FACTOR THAT INCREASES ADDICTION POTENTIAL • IN BOYS WITH THE A1 ALLELE STRESS WAS SIGNIFICANTLY CORRELATED WITH COGNITIVE FUNCTIONAL PROBLEMS NOBLE AND BENTON. THE D2 DOPAMINE RECEPTOR GENE AND FAMILY STRESS. INTERACTIVE EFFECTS ON COGNITIVE FUNCTIONING IN CHILDREN. BEHAV GENET, 1997; 27:33-43.

  12. THE SCIENCE OF RECOVERY:GENETICS • GENETIC VULNERABILITY • SONS OF ALCOHOLICS HAVE DECREASED SENSITIVITY TO ALCOHOL • ENORMOUS AMOUNT OF DEVELOPMENTAL STRESS • EITHER CAN CAUSE IRREGULARITIES IN BRAIN CHEMISTRY SUCH AS DOPAMINE BLUNTING

  13. THE SCIENCE OF RECOVERY:GENETICS • Treatment dropout linked to elevated stress response (Drug and Alcohol Depd. 105 (3):202-208, 2009) • Salivary cortisol can predict how long a drug user will remain in treatment • Cortisol measured at base for both men and women in a residential treatment center before giving them stressful tasks • Prior to the stressors cortisol levels were similar for the 21 participants who dropped out as compared to the 81 who completed treatment

  14. THE SCIENCE OF RECOVERY:GENETICS • Treatment dropout linked to elevated stress response (Drug and Alcohol Depd. 105 (3):202-208, 2009) (continued) • The patients who dropped out had cortisol levels 3-5 times higher than those patients who remained in treatment • For each unit of increase in cortisol after the stressful tasks, there was a four-fold increase in risk of dropping out

  15. THE SCIENCE OF RECOVERY:GENETICS • WHEN YOU DISCONTINUE TO DRINK CIRCUITS ARE STILL PRESENT • CORTICOTROPIN RELEASING FACTOR (CRF) SYSTEM PRODUCES A CHRONIC STRESS RESPONSE THAT IS A SET-UP FOR RELAPSE • 60-70% OF RELAPSE OCCUR UNDER CONDITIONS OF NEGATIVE EMOTIONAL STATE

  16. THE SCIENCE OF RECOVERY:GENETICS • A shortage of D2 receptors, some researchers surmise, could predispose a person to addiction. • Nora Volkow, NIDA Director, led two studies that involved artificially increasing the number of D2 receptors in rats by administering adenoviral vectors directly into their brains. Viral vectors transmit their genetic material and makeup into foreign cells, in this case increasing the number of D2 receptors in the new cells to match their own.

  17. THE SCIENCE OF RECOVERY:GENETICS • In one study involving rats and alcohol, the increased number of D2 receptors led the rodents to consume less alcohol, compared with their baseline intake. • In the other study, the D2-receptor increase caused rats to significantly reduce their intake of cocaine.

  18. THE SCIENCE OF RECOVERY:GENETICS • Association between DA D2 receptor numbers and drug self-administration (PET) • Increased D2 receptors reduced alcohol consumption • Decreased D2 receptors higher risk • DA D2 receptor levels influenced by stress and social hierarchy

  19. THE SCIENCE OF RECOVERY:GENETICS • Michael Nader, a researcher at Wake Forest School of Medicine, is investigating ways to raise D2-receptor levels naturally. • One experiment he helped conduct focused on five separate groups of four monkeys. Each had been self-administering cocaine to the point of habit and were then deprived of the drug for an eight-month period. To create a picture of D2-receptor availability, the monkeys were given a radioactive tracer that competes with dopamine for receptors.

  20. THE SCIENCE OF RECOVERY:GENETICS • The monkeys were then randomly put in social groups of four and given the opportunity to self-administer the drug again. • Positron emission tomography (PET) imaging of the monkeys over time showed fluctuations in dopamine levels, which allowed the researchers to estimate the changing numbers of available D2 receptors. • After only three months, the socially dominant monkeys in each group had naturally increased their numbers of D2 receptors.

  21. THE SCIENCE OF RECOVERY:GENETICS • There was no increase in the subordinate monkeys. Further, the subordinate monkeys reverted to using cocaine at much higher levels than the dominant monkeys. • "There is an interesting relationship between D2-receptor numbers and vulnerability to drug addiction," Nader said. "It appears that individuals with low D2 measures are more vulnerable compared to individuals with high D2-receptor numbers."

  22. THE SCIENCE OF RECOVERY:GENETICS • Why did the socially dominant monkeys show D2-receptor increases? • One hypothesis is environmental enrichment.For the monkeys, it seems, being dominant was the enriching trigger. • One physiological consequence of involvement in 12-step meetings, therefore, could be an increase in the natural production of D2 receptors.

  23. THE SCIENCE OF RECOVERY:GENETICS • Social interventions can change neurobiology • Increased DA D2 receptors • Reduced self-administration • Behavioral interventions could counteract the aversive effects of drug abuse and reinforce the power of group approaches

  24. THE STRIATUM • The basal ganglia are nestled inside cortex, surrounding the thalamus (see image above).  The striatum (part of the basal ganglia circuitry) is composed of the putamen, caudate, and nucleus accumbens.  Other important parts of the basal ganglia are the globus pallidus (which has an internal and an external segment, GPi and GPe respectively) and the subthalamic nucleus (STN).

  25. NEURAL PATHWAYS

  26. CORTICOSTRIATAL CIRCUITRY • This impairment could arise from two general pathologies in corticostriatal circuitry: addicts could have pathologically strengthened drug-seeking behaviors,or they could have pathological impairments in the capacity to control drug-seeking behaviors. These two possibilities are not mutually exclusive. • Corticostriatal circuitry has two subcircuits: the limbic subcircuit, which comprises brain regions such as the prefrontal cortex, the amygdala, the nucleus accumbens (NAc) and the ventral tegmental area (VTA); and the motor subcircuit, which contains the motor cortex, the dorsal striatum and the substantia nigra.

  27. CORTICOSTRIATAL CIRCUITRY

  28. CORTICOSTRIATAL CIRCUITRY • Corticostriatal projections are responsible not only for generating learnt, well-established behaviors such as in drug taking, but also for changing behaviors in response to a variable environment, and thereby generating new adaptive behaviors • Addicts have difficulty modulating drug-seeking behaviorswith information that should suppress the behavior

  29. CORTICOSTRIATAL CIRCUITRY • The NAc serves as a gateway through which information that has been processed in the limbic subcircuit gains access to the motor subcircuit. • Relapse to compulsive drug seeking arises from an impaired ability of the limbic subcircuit to effectively process and/or use the negative environmental contingencies associated with relapse. The result is that behavior is dominated by the previously learnt, well-establisheddrug-seeking strategies.

  30. THE SCIENCE OF RECOVERY: DOPAMINE (DA) TONE Ventral Tegmental Area Nucleus Accumbens Dopamine ArcuateNucleus OpioidPeptides Naltrexone

  31. THE SCIENCE OF RECOVERY: DOPAMINE (DA) TONE • TWO TYPES OF LOW DA TONE (CONTINUED) • SYMPTOMS WILL BE THOSE OF REDUCED DA TONE AT NAc REGARDLESS OF THE LOCATION OF FEEDBACK PROBLEM • FROM TREATMENT PERSPECTIVE WHAT DIFFERENTIATES WHETHER DA OR OPIOID CAUSATION OF LOW DA TONE IS…. • HISTORY OF DRUG USAGE AND EFFECTS THAT USER EXPERIENCES

  32. THE SCIENCE OF RECOVERY: DOPAMINE (DA) TONE • SUFFICIENT • DA TONE IN REWARD CIRCUITRY YIELDS ADEQUATE • ATTENTION • MOTIVATION • ATTACHMENT • HEDONIC TONE

  33. THE SCIENCE OF RECOVERY: DOPAMINE (DA) TONE • REDUCED OR LOW DA TONE • ANHEDONIC RELATIVE TO THOSE AROUND THE INDIVIDUAL • SENSE OF NOT FITTING IN • POOR ATTENTION • POOR LEVEL OF MOTIVATION • RESTLESS • IRRITABLE • DISCONTENTED

  34. PREFRONTAL CORTICAL DOPAMINE • Optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. • Imaging studies of alcoholics have demonstrated less dopamine in the striatum Volkow  ND;  Wang  GJ;  Telang  F;  Fowler  JS;  Logan  J;  Jayne  M;  Ma  Y;  Pradhan  K;  Wong  C:  Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement.  J Neurosci 2007; 27:12700–12706

  35. PREFRONTAL CORTICAL DOPAMINE • Less dopamine in the prefrontal cortex, which governs executive functions, is important because it could impair the addicted person’s ability to learn and utilize informational/behavioral strategies critical to relapse prevention. This is supported by literature that links prefrontal cortical dopamine with executive functions, such as attention, working memory, behavioral flexibility, and risk/reward decision making, all of which are impaired in addictive disorders such as alcoholism. Floresco  SB;  Magyar  O:  Mesocortical dopamine modulation of executive functions: beyond working memory.  Psychopharmacology (Berl) 2006; 188:567–585

  36. PREFRONTAL CORTICAL DOPAMINE • It is tempting to speculate that the failure to incorporate past negative consequences in a decision to drink alcohol during abstinence is related to decreased prefrontal cortical dopamine in alcoholism. • Unclear whether decreased dopamine transmission in alcoholism represents a premorbid trait or alcohol-induced state Narendran, et al. Decreased Prefrontal Cortical Dopamine Transmission in Alcoholism. Am J Pscyhiatry. 2014;171:881-888. doi:10.1176/appi.ajp.2014.13121581

  37. THE SCIENCE OF RECOVERY: DOPAMINE (DA) TONE • INCREASING DA TONE AT NAc • THREE POSSIBLE APPROACHES • INCREASE AMOUNT OF DA RELEASED-CURRENTLY HAVE MEDS LIKE SUBOXONE THAT WILL DO THIS • INCREASE NUMBER OF RECEPTORS-MEDS NOT AVAILABLE FOR THIS • REDUCING REUPTAKE OF DA-HAVE MEDS THAT WILL DO THIS (PROVIGIL)

  38. THE SCIENCE OF RECOVERY: THE OPIATE EXPERIENCE

  39. THE SCIENCE OF RECOVERY: DOPAMINE (DA) TONE • SUBUTEX-Buprenorphine. sublingual (SL) • 2mg and 8mg tablets • SUBOXONE-Buprenorphine/Naloxone SL tablets AND FILM • Zubsolv SL • PARTIAL AGONIST • Increasing dose does not increase effect like a full agonist

  40. THE SCIENCE OF RECOVERY: DOPAMINE (DA) TONE • BUPRENORPHINE-Very high affinity for mu opioid receptor • Mu receptor will choose buprenorphine over other opioids • Buprenorphine will displace other opioids • Slow dissolution from mu receptor • Half-life on receptor is 34-36 hrs • Heroin on and off receptor in millisecond • At Buprenorphine dose of 16mg almost no binding to other opioids

  41. PHARMACOLOGICAL • NALTREXONE (Revia, Vivitrol) • Pure antagonist • Poor compliance • Less than 10% for street addicts • Better compliance • Healthcare professionals • Parole/Probation • New suspension with q30d administration should dramatically increase compliance and reliability of drug

  42. VIVITROL Carton Components

  43. VIVITROL

  44. VIVITROL

  45. VIVITROL

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