Aug 12, 2020
Abigail Kay, MD, MS, joins host Lorenzo Norris, MD, to discuss
the treatment of patients with substance use disorders.
Dr. Kay is an addiction psychiatrist at Thomas Jefferson
University Hospital in Philadelphia and is associate dean of
academic affairs and medical student education at Sidney Kimmel
Medical College. Dr.
Norris is assistant dean of student affairs, and assistant
professor of psychiatry and behavioral sciences at George
Washington University, Washington.
Dr. Kay disclosed no conflicts of interest for the past year.
Before that, she reported receiving payment from the American
Society of Addiction Medicine, through a grant from the Substance
Abuse and Mental Health Services Administration, to teach a free
training to clinicians to be certified to prescribe buprenorphine.
Dr. Norris, who also serves as medical director of psychiatric and
behavioral sciences at George Washington University Hospital,
disclosed no conflicts.
- Substance use disorders have genetic and environmental factors.
The genetic component is sometimes overlooked because the
environmental factor – the exposure to using a substance – is
heavily focused as the only trigger for addiction.
- Methadone is a pure agonist at the mu-opioid receptor so the
higher dose the greater the effect. The average dose of methadone
to achieve blocking of cravings, withdrawal, and opiate
intoxication is 80-120 mg.
- Buprenorphine is a partial agonist: At low doses, it acts as an
agonist, and at high doses it acts as an antagonist with quite high
affinity for the receptor. As a partial agonist, it has a ceiling
effect with more than 90% of opiate receptors occupied at 24
- Dr. Kay suggests a helpful rule of thumb is to assume that, if
patients have an addiction, there’s a 50/50 chance that they have
another psychiatric disorder and vice versa. With this in mind, all
patients with substance use disorder should be evaluated for
comorbid psychiatric disorders and underlying medical
- Dr. Kay breaks down human cognition into the primitive brain
and thoughtful brain. The primitive brain keeps us alive by
preferentially focusing on sleeping, drinking, and eating.
Addiction to a drug hijacks the primitive brain, making it
prioritize the substance of choice above all else.
- Methadone is the “gold-standard” treatment for opioid use
disorder in the sense that all treatments are compared with its
efficacy and mechanism of action. Methadone is a pure agonist at
the mu-opioid receptor, meaning the higher dose the greater the
effect; the average dose of methadone is 80-120 mg. The goal of
treatment is to achieve a blocking dose, meaning a dose that blocks
the craving, the withdrawal, and the high if people were to use
illicit opiates on top of their methadone. Methadone is
administered only at federally approved sites, and one advantage is
that additional services, such as counseling, can be offered on
site after daily administration.
- Buprenorphine as a partial agonist can play both “roles” on the
mu-opioid receptor. At low doses, it acts as an agonist, and at
high doses, it acts as an antagonist with quite high affinity for
the receptor. In addition, as a partial agonist buprenorphine has a
ceiling effect: At 24 mg of buprenorphine occupies 92% of opiate
receptors and at 32 mg only an additional 1% of receptors are
occupied. Buprenorphine must be administered when the person is
already in withdrawal, because its affinity to the receptor
dislodges other opiates from the mu receptor thus precipitating
withdrawal. Buprenorphine works well for individuals who would
require an average 40-60 mg of methadone to achieve their blocking
dose. Because of the ceiling effect, some individuals continue to
crave opiates while on buprenorphine. This means that, despite the
greater convenience offered by buprenorphine, it is not the
treatment of choice for everyone.
- Naltrexone is a pure opioid antagonist requiring 10-14 days of
abstinence from opiates to prevent precipitating opioid withdrawal.
Naltrexone can be given as a once-monthly injection to address
cravings. The greatest risk with naltrexone is that, after 1 month
of treatment, people lose their tolerance and are at risk of opioid
overdose if they return to their previous amount of use.
Volkow ND. Hum Genet.
Volkow ND, Blanco C. J Clin Invest. 2020 Jan
SAMHSA.gov. Overview of MAT: https://www.samhsa.gov/medication-assisted-treatment/treatment.
Jones HE et al. N Engl J Med.
Kay A et al. J Addict Dis. 2010
Show notes by Jacqueline Posada, MD, who is associate producer
of the Psychcast and consultation-liaison psychiatry fellow with
the Inova Fairfax Hospital/George Washington University program in
Falls Church, Va. Dr. Posada has no conflicts of interest.
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