Pharmacologic Approach to Addiction

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Pharmacologic Approach to Addiction

• Elizabeth Hakas, M.D.
• VA Pittsburgh Healthcare System
• Substance Abuse Assessment Team
• elizabeth.hakas_at_va.gov

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Medications for Addiction

• Reduce cravings
• Reduce reward for use of substances
• Act indirectly to treat underlying anxiety,
  depression
• FDA Pregnancy categories A, B, C, D, X.

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Non-Pharmaceutical Approaches

• 12-Step programs (AA, NA, etc.)
• Inpatient and outpatient rehab programs
• Therapy
• Complementary Medicine approaches acupuncture,
  meditation, herbal medicine, hypnosis, etc.

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Today.

• More limitations today we are discussing
  substance abuse only. Other habits, phenomena,
  like excessive gaming, gambling addiction,
  compulsive overeating and sexual compulsion may
  have similar neural origins.
• We will discuss alcohol and benzodiazepines,
  opiates, tobacco, cocaine, and briefly,
  methamphetamine/other stimulants, marijuana and
  hallucinogens.

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Neurobiology of Addiction

• Thinking regarding addiction has evolved
• Reward pathway
• Dopamine
• Nucleus accumbens

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Substance Abuse

• DSM-IV criteria
• Maladaptive pattern of substance use
• One or more of the following (over a 12 month
  period)
• School-work-home problems/Use in physically
  hazardous situations/Legal issues/Interpersonal
  issues

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Substance Dependence

• DSM-IV criteria
• Maladaptive pattern of substance use
• Three or more of the following (over a 12 month
  period)
• Tolerance/Withdrawal/Excessive use/Unsuccessful
  attempts to cut down/Lots of time spent
  acquiring-using-recovering from substance/Other
  activities diminished/Psychological or medical
  problems related to use

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Veterans and substance use

• Iraq war returnees13 self-identify as having
  issues with alcohol use.
• Most common substances abused for male vets
  alcohol, cocaine, opiates. Slighter higher use of
  cocaine in female veterans and lower use of
  alcohol.

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Addiction in the military in the news

• 10/2008 USA Today article on use and abuse of
  narcotic painkillers in active duty military
  members. 10 of those polled admitted to narcotic
  Rx abuse in the past year.
• 8/2007 Salon.com article OIF/OEF vets and heroin.
• 8/2008 Reuters article on EtOH abuse.

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Alcohol

• Mechanism of action
• CNS depressant
• NMDA system
• GABA

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Alcohol

• Pharmacologic Options
• Natrexone
• Acamprosate (Campral)
• Disulfiram (Antabuse)
• Topiramate (Topamax)
• Adjuncts for anxiety, etc.

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Naltrexone

• Opioid receptor antagonist
• PO/IM formulations
• Reduces cravings
• Reduces relapses

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Acamprosate/Campral

• Calcium Acetyl Homotaurinate
• GABA analog
• 666 mg po TID

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Disulfiram/Antabuse

• Inhibits acetaldehyde dehydrogenase
• Increases acetaldehyde levels
• Use of EtOH causes flushing, nausea, vomiting
• Lots of downsides

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Topiramate

• Monosaccharide
• GABA-nergic
• Multi-center study showed improved
  alcohol-related behaviors.
• Side effects can be bothersome.

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Adjuncts/Other

• Baclofen, ondansetron, varenicline, and
  anti-anxiety meds like carbemazepine (Tegretol),
  buspirone.

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Benzodiazepines/Sedatives

• Mechanism of Action
• GABA
• GABA receptors
• Benzodiazepine receptors
• Chloride ion channels are opened
• Cell membrane hyperpolarization occurs

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Benzodiazepines/Sedative-hypnotic drugs

• Pharmacologic Treatment Options
• Slow taper
• Must treat withdrawal symptoms carefully if rapid
  taper is attempted.
• Post-detox treatment depends on underlying
  symptoms.
• Carbemazepine, imipramine, buspirone.
• Therapy!!

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Opiates/Opioids

• Opiates are the narcotic alkaloids found in
  opium, as well as their derivatives.
• Opioids are synthetic narcotics that resemble the
  naturally occurring opiates. They bind to or
  otherwise affect the opiate receptors on cell
  surfaces.

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Heroin

• First made in 1874 in London by a British
  chemist, marketed by Bayer 1899 as a cough
  remedy.
• Synthesized from morphine.
• Takes about 3-6 weeks of regular use (as with all
  opioids) to develop physical dependence.

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Opiates/Opioids

• Mechanism of Action
• Modulation of neurotransmitters via opioid
  receptors
• Receptor types
• mu, kappa, delta, nociceptin/orphanin

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Opiates/Opioids

• Pharmacologic Treatment Options
• Naltrexone
• Methadone
• Buprenorphine

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Naltrexone

• Opioid receptor antagonist
• PO/IM formulations
• Reduces cravings
• Reduces relapses

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Methadone

• Methadone maintenance. (Can also be used for
  detox.)
• Can work well.
• Stigma
• Sedation
• Frequent clinic visits

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Buprenorphine

• Semi-synthetic opiate with partial
  agonist/antagonist properties at the opiate
  receptor
• Subutex vs. Suboxone
• Expensive and hard-to-get

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Tobacco

• Types of tobacco delivery systems/nicotine
  delivery systems cigarettes, cigars, snuff
  (pulverized and dry-snorted), dipping tobacco
  (moist, set in mouth), chewing tobacco.
• Mechanism of action tobacco contains nicotine
  and harmane, both psychoactive compounds.
• Nicotine Acts as a stimulant on the nicotinic
  acetylcholine receptors.
• Harmane MAO inhibitor.

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Tobacco

• Pharmacologic Treatment Options
• Nicotine Replacement
• Bupropion
• Chantix
• Nicotine vaccine

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Nicotine Replacement

• Gum, lozenges, patches.
• Varying doses.
• Pregnancy category D.
• Lactation ??

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Bupropion

• Increases brain dopamine and norepinephrine
  levels
• Works well with NRT

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Varenicline

• (Chantix)
• Partial agonist of nicotinic acetylcholine
  receptors.
• Quit date is set for after initiation of
  medication.
• Side effects nausea, weird dreams, risk of
  suicide.

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Nicotine Vaccine

• NicVAX
• Still under development.
• Anti-nicotine antibodies are created.
• When nicotine molecules enter the bloodstream,
  they are bound by these antibodies and are unable
  to enter the CNS.

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Cocaine

• Cocaine is an alkaloid found in the leaves of the
  Coca plant.
• Isolated in 1860 in Germany.
• Two main forms, salt and base.
• Blocks dopamine, serotonin and norepinephrine
  re-uptake.

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Cocaine

• Pharmacologic Treatment Options
• Modafinil-stimulant used for cocaine addiction,
  narcolepsy, sleepiness from OSA.
• Increases monoamines and elevates hypothalamic
  histamines.
• Disulfiram.

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Other Substances

• Methamphetamine and other stimulants.
• Amphetamine, cocaine, methylphenidate.
• Increase dopamine, epi, norepi and serotonin.
• Chronically deplete dopamine-thats the kicker!!
• Dissociative drugs-phenylcyclidine, ketamine,
  dextromethorphan (NMDA blockers)
• Hallucinogens-LSD, psilocybin (mushrooms)

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Other Substances

• Stimulant abuse-refer back to cocaine treatment.
• Dissociative drugs-usually acute treatment of
  intoxicated person is the main concern.

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Marijuana

• Mechanism of Action THC binds to cannabinoid
  receptors
• Reasons to Hate Marijuana

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Marijuana

• Pharmacologic Treatment Options various drugs
  have been tested and trials have not shown much
  success.

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Medications to Consider Avoiding

• Aside from narcotic pain meds and
  benzodiazepines
• Think twice before prescribing
• Tramadol (Ultram)
• Carisoprodol (Soma)
• Temazepam (Restoril)
• Eszopliclone (Lunesta)
• Zolpidem (Ambien)
• Zaleplon (Sonata)

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Contact Info

• SAAT Clerk Gail Becker 412-360-3692
• Elizabeth Hakas, M.D. 412-916-4127
• elizabeth.hakas_at_va.gov