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

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
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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
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 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
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