Drugs of abuse, addiction medicines and herbal remedies

Transcript

SoheeA client tells you, almost proudly, that he's done drinking. He's been drinking heavily every day for years, and this weekend he's going to quit cold turkey. On his own.

RyanAnd another client, using heroin, says she's terrified to stop because withdrawal might kill her.

SoheeTwo clients, two beliefs about withdrawal. One of them has it backwards, and the exam expects you to know which.

RyanWelcome to EPPP Prep, the podcast. I'm Ryan.

SoheeI'm Sohee. Today: drugs of abuse, sorted by the brain systems they act on, plus the medicines used to treat opioid addiction, and one popular herbal remedy that deserves more respect than it gets.

RyanLet's resolve the opening first, using the OpenStax psychology textbook. For alcohol and barbiturates, it says withdrawal can be life-threatening in people with a long history of very high doses. That's serious enough that people trying to stop should do it only under medical supervision.

SoheeAnd opioids? The textbook says opioid withdrawal resembles a severe case of the flu. It can be extremely unpleasant, but it's not life-threatening.

RyanSo the drinker's plan is the risky one. That's an important test point, and an even more important clinical one. One caution for the second client, though. The naltrexone label notes that after opioid detox, tolerance is likely to be reduced, so going back to a previously tolerated amount could be life-threatening.

SoheeWhy the difference? It helps to know the core terms. Tolerance is when a person needs more and more of a drug to get the effects they used to get at lower doses.

RyanPhysical dependence means changes in normal bodily functions, so the person experiences withdrawal when they stop. Psychological dependence is an emotional need for the drug, for example using it to relieve distress.

SoheeAnd here's the key idea. Withdrawal symptoms are usually the opposite of the drug's effects. Withdrawal from sedative drugs often produces unpleasant arousal and agitation.

RyanSo let's go class by class. Depressants first. Alcohol, barbiturates and benzodiazepines all act as agonists of the GABA system, short for gamma-aminobutyric acid. GABA quiets the brain, so these drugs quiet it too, which is why some are prescribed for anxiety and insomnia.

SoheeAt low doses, alcohol is associated with euphoria. As the dose increases, people report sedation. It slows reaction time, lowers alertness and reduces behavioral control. Heavy use can cause loss of consciousness or trouble remembering events.

RyanAnd during pregnancy, alcohol can cause fetal alcohol spectrum disorder. With repeated use, people develop physical dependence with tolerance and withdrawal, and the textbook calls the abuse potential of these depressants relatively high.

SoheeStimulants next. They increase overall neural activity, and many act as dopamine agonists. Dopamine activity is associated with reward and craving, which is why drugs that affect it often carry abuse liability.

RyanWe met the mechanisms in episode one. Cocaine blocks dopamine reuptake. Amphetamines block reuptake and also stimulate release.

SoheeAnd the paradox of attention-deficit/hyperactivity disorder, ADHD. Why give a stimulant for hyperactivity? The textbook says the therapeutic effect comes from increased neurotransmitter activity in brain areas tied to impulse control, including the prefrontal cortex and basal ganglia.

RyanRepeated stimulant use has a cost. It can deplete the monoamine neurotransmitters, dopamine, norepinephrine and serotonin, which can lead to dysphoria and cognitive problems. And people may then use compulsively, partly to get back to their pre-use baseline.

SoheeTwo everyday stimulants work differently. Caffeine is an adenosine antagonist. Adenosine promotes sleep, so blocking it decreases sleepiness.

RyanAnd nicotine acts on acetylcholine receptors. In the central nervous system, acetylcholine plays a role in arousal and reward.

SoheeOpioids. Our bodies make small amounts of opioid compounds that bind to opioid receptors, reducing pain and producing euphoria. Opioid drugs mimic that system, which is why their potential for abuse is so high.

RyanOne vocabulary point. Opiates are the natural ones, derived from opium in the poppy plant. The synthetic versions are correctly called opioids.

SoheeAnd the textbook describes how the opioid crisis evolved, with dealers adding highly potent synthetic opioids like fentanyl and carfentanil to heroin, so potent that even small doses can cause overdose and death. The public health response included more access to treatment and to overdose-reversal drugs like naloxone. Hold on to that name. It's coming back.

RyanLast class, hallucinogens. They produce profound changes in sensory and perceptual experience. And they're varied in their mechanisms. Mescaline and LSD are serotonin agonists. PCP and ketamine are antagonists of the NMDA glutamate receptor.

SoheeThe textbook adds that hallucinogens generally aren't thought to have the same abuse potential as the other classes.

RyanPause and think. Match the drug to the mechanism. Caffeine. Nicotine. LSD. Ketamine.

SoheeCaffeine blocks adenosine. Nicotine acts on acetylcholine receptors. LSD is a serotonin agonist. Ketamine blocks the NMDA glutamate receptor. The tempting error is saying caffeine works mainly through dopamine. The textbook says any dopamine effects are indirect, and its primary mechanism is adenosine.

RyanNow the treatment side. The U.S. Food and Drug Administration, the FDA, says there are three approved medications for opioid use disorder: buprenorphine, methadone and naltrexone, and all three have been shown to be safe and effective.

SoheeAnd the exam loves their mechanisms, because they span the whole spectrum. Methadone is a full opioid agonist. The Suboxone label lists it alongside heroin and morphine as full agonists.

RyanBuprenorphine is a partial agonist at the mu-opioid receptor. The label says its opioid effects are limited by a ceiling effect. In studies, higher doses reached a point where they produced no further effect, while a full agonist kept producing bigger effects.

SoheeAnd Suboxone combines buprenorphine with naloxone, an opioid antagonist. If someone dependent on full agonists injects it, the naloxone is likely to produce withdrawal.

RyanPartial agonists have a twist too. Because of buprenorphine's partial agonist properties, if it's taken before a full agonist's effects have worn off, it may precipitate withdrawal.

SoheeThen naltrexone. The extended-release injection, Vivitrol, is an opioid antagonist. It's approved to treat alcohol dependence, and to prevent relapse to opioid dependence after detoxification.

RyanThe label says it blocks the effects of outside opioids for about 28 days. And here's the safety point. After detox, tolerance is reduced. So at the end of a dose interval, after a missed dose, or after stopping, a person who uses their old amount can overdose, sometimes fatally.

SoheeAnd the label warns that trying to overcome the blockade with large amounts of opioids can be fatal too.

RyanPause and think. A man stable on methadone is switched straight to an injection of naltrexone. What might happen, and why?

SoheePrecipitated withdrawal. Naltrexone is an antagonist, and the Vivitrol label warns that switching from agonist to antagonist therapy can bring on severe withdrawal, and that people coming off buprenorphine or methadone may be vulnerable for as long as two weeks. A precipitated withdrawal can be severe enough to require hospitalization.

RyanAnd notice the treatment philosophy in these labels. Suboxone should be used as part of a complete treatment plan that includes counseling and psychosocial support. Medication plus psychological care, which is exactly where psychologists come in.

SoheeFinally, complementary and alternative agents. Let's take St. John's wort, an herbal supplement. An open-access review says its popularity can be attributed to its effectiveness for mild to moderate depression.

RyanBut it's not inert. The National Institute of Mental Health, NIMH, warns that combining antidepressants with St. John's wort can cause serotonin syndrome, which is rare but life-threatening.

SoheeAnd the review describes a second problem. A component called hyperforin induces the drug-processing enzymes known as cytochrome P450, or CYP, enzymes. Extracts high in hyperforin have increased the clearance of other drugs, decreasing their concentration and effectiveness, sometimes to the point of treatment failure.

RyanIts list of affected drugs includes oral contraceptives, bupropion, oxycodone and cyclosporine, among others. So St. John's wort can make other medicines less effective.

SoheeThat's why NIMH tells people to tell their provider about all medications, vitamins and supplements. A client may not think of a supplement as a drug. You can ask.

RyanRecap. Alcohol and barbiturate withdrawal can be life-threatening and needs medical supervision. Opioid withdrawal is miserable, like a bad flu, but not life-threatening.

SoheeDepressants are GABA agonists. Stimulants mostly boost dopamine; caffeine blocks adenosine; nicotine acts on acetylcholine. Opioids mimic the body's own opioid system. LSD and mescaline act on serotonin, PCP and ketamine block NMDA glutamate receptors.

RyanMethadone is a full agonist, buprenorphine a partial agonist with a ceiling, naloxone and naltrexone are antagonists. After naltrexone, lower tolerance means higher overdose risk.

SoheeAnd St. John's wort can cause serotonin syndrome with antidepressants, and can weaken other drugs by inducing the enzymes that process them.

RyanIf you've ever sat with someone in the grip of addiction, or loved someone who was, this material may hit closer than most. That's okay. Knowing the science is one more way to be useful to the people who need you.

SoheeTake a breather, and next time we move to the big treatment trials. Thanks for listening to EPPP Prep.

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