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Neuropsychopharmacology

Overview of addiction and pharmacological treatment of addiction, particularly with respect to the opioid epidemic.

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Neuropsychopharmacology:
Exploiting Biology to Treat
Addiction
By Colleen Farrelly
Review of Addiction Processes
 Biochemical Balances and Imbalances
 Neuroadaptation
 Withdrawal Process
 Example:
 Ventral Tegmental Area and Nucleus Accumbens
 Parts of mesolimbic dopamine system
 Primed for dopamine release when addicted
 Receptors adapt, creating a withdrawal response at cell level
 Law of Opposites responsible for this phenomena
 Cellular proteins change
 Gene regulation/epigenetics to up- or down-regulate
neurotransmitter
Synaptic Plasticity and Age
 Connections between neurons
Synaptogenesis and pruning occur in youth:
 Frontal cortex
 Mesolimbic system
 Connected through dopamine at synapses
Synapses static in those areas after but can
strengthen or weaken existing connections
Why age at first use matters
Pharmacological Properties and
Interactions
 Agonists
 Lock and key
 Produce effect
when bound
 Antagonists
 Blockers of a
binding site
 Partial Agonists
 Partial keys that
can block and
produce effect
Main Functions of Pharmaceuticals
in Addiction Treatment
 Overdose Reversal
 Maintenance
 Detoxification
 Aversion Therapy
 Anti-Craving
 Pain Management
www.chinesemarketresearch.com
Overdose Reversal Drugs
 Mainly used in opiate
overdoses
 Naloxone
 Chemical properties
 Antagonist
 Strength
 1 mg block 25 mg heroin
 Taper dose by 10%-60%
until overdose reversed
 Non-addicting
 Others treat overdose
symptoms only
 Ro 15-4513 http://en.wikipedia.org/wiki/Naloxone

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Neuropsychopharmacology

  • 1. Neuropsychopharmacology: Exploiting Biology to Treat Addiction By Colleen Farrelly
  • 2. Review of Addiction Processes  Biochemical Balances and Imbalances  Neuroadaptation  Withdrawal Process  Example:  Ventral Tegmental Area and Nucleus Accumbens  Parts of mesolimbic dopamine system  Primed for dopamine release when addicted  Receptors adapt, creating a withdrawal response at cell level  Law of Opposites responsible for this phenomena  Cellular proteins change  Gene regulation/epigenetics to up- or down-regulate neurotransmitter
  • 3. Synaptic Plasticity and Age  Connections between neurons Synaptogenesis and pruning occur in youth:  Frontal cortex  Mesolimbic system  Connected through dopamine at synapses Synapses static in those areas after but can strengthen or weaken existing connections Why age at first use matters
  • 4. Pharmacological Properties and Interactions  Agonists  Lock and key  Produce effect when bound  Antagonists  Blockers of a binding site  Partial Agonists  Partial keys that can block and produce effect
  • 5. Main Functions of Pharmaceuticals in Addiction Treatment  Overdose Reversal  Maintenance  Detoxification  Aversion Therapy  Anti-Craving  Pain Management www.chinesemarketresearch.com
  • 6. Overdose Reversal Drugs  Mainly used in opiate overdoses  Naloxone  Chemical properties  Antagonist  Strength  1 mg block 25 mg heroin  Taper dose by 10%-60% until overdose reversed  Non-addicting  Others treat overdose symptoms only  Ro 15-4513 http://en.wikipedia.org/wiki/Naloxone
  • 7. Maintenance Drugs encyclopedias.families.com  Methadone Maintenance Programs  History  Dr. Dole and Dr. Nyswander 1963  Purposes  Heroin detoxification  Substitute addictions to lower crime  Oral route vs. injection  Better immunological and neuroendocrinal function observed in patients  Controversy  U of Michigan Study  Generally not shown to lower crime or illicit drug use
  • 8. Detoxification: The First Step  Why it is necessary  Opiate withdrawal vs. alcohol withdrawal  Sweating, vomiting, chills, cramps, cold sweats with heroin but limited to unpleasant effects rather than possible death  Tremor, sweating, nausea, headache, possible seizures, possible hallucinations, and death with alcohol  Agonist drugs used in opiate detoxification  Substitute dose decreasing ~10% per day  Can use any agonist  Alpha-2-adrenergic receptors like Clonidine may have street use (caution)  Agonist drugs used in alcohol detoxification  Dose until symptoms subside  Work on GABA and glutamate  Valium and Haloperidol sometimes administered
  • 9. Maintaining Sobriety  Two types of anti- relapse drugs  Aversion Therapy  Main idea is to make relapse uncomfortable through exploiting biochemical metabolism  Example: Disulfiram  Anti-Craving  Main idea is to take away desire through synaptic connection interference  Example: Naltrexone
  • 10. Disulfiram Case Study  Classical conditioning premise Switch drinking as pleasant to unpleasant  Alcohol metabolism reactions Disulfiram blocks aldehyde dehydrogenase  Acetaldehyde levels in the blood rise  Creates nausea, vomiting, and headache  Origins of Disulfiram  Jens Hald testing a parasite drug on himself  Drank whiskey and discovered the effect
  • 11. Anti-Craving Drugs: Naltrexone  Craving neurochemistry  Stress + stimuli reinstates pairing of drug and reward  “Reinstatement Paradigm”  Stress or stimulus triggers a dopamine release in anticipation of the drug  Much like Pavlov’s dogs  Blocks the pleasure, spares the pain  Success rates  Opiates  74% success rate over ten year period for treating impaired physicians  Alcohol  Taken 3 times a week, fairly benign side effects  77% of patients in one study were sober after 3 months, compared to 45% of controls www.contral.com
  • 12. Pain Relief in Recovering Addicts  Concerns  Problems in prescription drug abuse  Higher dosage needs  Tolerance  Lowering of spike threshold  Solutions  NSAIDS  Aspirin and Ibuprofen  Smallest effective dose  Types of narcotics used in pain relief
  • 13.  Many failures so far: Clonidine’s street use Heroin to cure morphine addiction Methadone sold for heroin money LSD as cure for alcoholism
  • 14. Overdose Reversal  Best success out of the five Very effective and necessary  Have to seek medical attention Person alone Illegal drug use
  • 15. Maintenance Programs  Positive aspects  Allows for functioning in society with the addiction  Less threat of transmitted diseases  Negatives  Overdose possible  Does not solve addiction and its consequences  Compliance issues
  • 16. Detoxification  Positives Safer withdrawal More likely to stay in treatment  Negatives Not a long-term solution to addiction
  • 17. Aversion Therapy  Pros  Effective in certain patients  Especially those in individual or group counseling  Little medication needed  Cons  Very effective  As little as 7 ml alcohol triggers reaction  Many patients relapse  Compliance issues  Leaves system in as little as two weeks
  • 18. Anti-Craving Drugs  Pros  Does not cause illness if relapse  Effective at managing cravings  Very effective in motivated patients  Cons  Compliance  Does not solve addiction  Patient needs to be motivated  Companies have to produce them  Some actually increase the risk of relapse in certain addictions  Bupropion to quite smoking and relapse risk for comorbid cocaine addiction
  • 19. Pain Management  Positive aspects Important to relieve pain  Reason for relapse  Negative aspects Narcotics are addicting Overdoses are possible
  • 20. Sources  Abrams, Michael. “The End of Craving.” Discover Magazine, May 2003: pg. 24-25  DeWors, George Manter. White Knuckles and Wishful Thinking: Learning from the  Moment of Relapse in Alcoholism and Other Addicitons. Hogrefe and Huber  Publishers, Seattle, WA: 2000  Feldman, Robert S., Meyer, Jerrald S., Quenzer, Linda F. Principles of Neuropsychopharmacology. Sinauer Associates, Inc., Sunderland, MA: 1997 Karch, Steven B., MD. Drug Abuse Handbook. CRC Press, Boston, MA:1998  Meyers, Jerrold S., Quenzer, Linda F. Psychopharmacology: Drugs, The Brain, and  Behavior. Sinauer Associates, Inc., Sunderland, MA:2005  Perrine, Daniel M. The Chemistry of Mind- Altering Drugs. American Chemical Society, Washington D.C.: 1996  Purves, Dale, Augustine, George J., et al. Neuroscience. Sinauer Associates, Inc., Sunderland, MA: 2004  Stimmel, Barry, MD. Pain and Its Relief Without Addiction. The Haworth Medical  Press, New York, New York: 1997  www.chinesemarketresearch.com  www.contral.com www.encyclopedias.families.com