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Once opioids shut off GABAergic neurons, the pleasure circuits fill with another neurotransmitter called dopamine. At one stop on this pleasure highway — the nucleus accumbens — dopamine triggers a surge of happiness.

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Both of these events reinforce the idea that opioids are rewarding. These areas of the brain are constantly communicating with decision-making hubs in the prefrontal cortex, which make value judgments about good and bad. Taking the drug soon becomes second nature or habitual, Evans said, much like when your mind zones out while driving home from work. The decision to seek out the drugs, rather than participate in other life activities, becomes automatic. The GABAergic neurons and other nerves in the brain still want to send messages, so they begin to adjust. They produce three to four times more cyclic AMP, a compound that primes the neuron to fire electric pulses, said Thomas Kosten, director of the division of alcohol and addiction psychiatry at the Baylor College of Medicine.

The pendulum swings back. Now, rather than causing constipation and slowing respiration, the brain stem triggers diarrhea and elevates blood pressure. Instead of triggering happiness, the nucleus accumbens and amygdala reinforce feelings of dysphoria and anxiety. All of this negativity feeds into the prefrontal cortex, further pushing a desire for opioids.

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Chronic pain patients have a very high risk of becoming addicted to opioids if they are also coping with a mood disorder. Cathy Cahill, a pain and addiction researcher at UCLA, said these big swings in emotions likely factor into the learned behaviors of opioid addiction , especially with those with chronic pain.

A person with opioid use disorder becomes preoccupied with the search for the drugs. Certain contexts become triggers for their cravings, and those triggers start overlapping in their minds.

A study found most patients — 81 percent — whose addiction started with a chronic pain problem also had a mental health disorder. Another study found patients on morphine experience 40 percent less pain relief from the drug if they have mood disorder. They need more drugs to get the same benefits. People with mood disorders alone are also more likely to abuse opioids.

A survey found patients with depression were twice as likely to misuse their opioid medications. Meanwhile, the country is living through sad times.

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Some research suggests social isolation is on the rise. While the opioid epidemic started long before the recession, job loss has been linked to a higher likelihood of addiction , with every 1 percent increase in unemployment linked to a 3. As an opioid disorder progresses, a person needs a higher quantity of the drugs to keep withdrawal at bay. A person typically overdoses when they take so much of the drug that the brain stem slows breathing until it stops, Kosten said.

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Many physicians have turned to opioid replacement therapy, a technique that swaps highly potent and addictive drugs like heroin with compounds like methadone or buprenorphine an ingredient in Suboxone. These substitutes outcompete heroin when they reach the opioid receptors, but do not activate the receptors to the same degree. These replacement medications also stick to the receptors for a longer period of time, which curtails withdrawal symptoms.

Buprenorphine, for instance, binds to a receptor for 80 minutes while morphine only hangs on for a few milliseconds. For some, this solution is not perfect. The patients need to remain on the replacements for the foreseeable future, and some recovery communities are divided over whether treating opioids with more opioids can solve the crisis. Plus, opioid replacement therapy does not work for fentanyl, the synthetic opioid that now kills more Americans than heroin.

But those are years away from use in humans. And Evans and Cahill said many clinics in Southern California are combining psychological therapy with opioid replacement prescriptions to combat the mood aspects of the epidemic. For secure communication, he can be reached via Signal She is also the lead producer of the NewsHour Shares broadcast series.

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