In ordinary times, an herbal supplement like kratom would not be attracting regulatory attention. But with drug overdoses killing more than 96,000 Americans in the last year, a new grim milestone, any drug in the opioid family is suspect. Scrambling to flatten the curve of the deadliest overdose crisis in recorded history, policymakers have set their sights on reducing access to opioids. And, by and large, they have. Opioid prescribing has fallen by 60 percent since it peaked in 2011, but overdose deaths continue to soar to new heights. The majority of overdose deaths today occur in the illegal market, and involve a deadly mix of illicit fentanyl, tranquilizers, and stimulants like methamphetamine. Opioid use, depression, pain, and suicide, it turns out, are uniquely intertwined. In every human body is an endogenous opioid system: an intricate network of neurons and neurotransmitters tasked with regulating and relieving pain. This system produces natural opioids like endorphin—which in Latin means morphine within—that are released when the brain receives pain signals. Studying the body’s built-in pain reliever, researchers suggest that an impaired opioid system could be causing symptoms of pain and depression, which leads people, like Avi, to self-medicate with opioids.“Some people benefit from opioids, so what do we do with them? It’s very, very tricky.”
Neglected, forgotten, or written off as primitive prescribing, opium casts a long shadow on the birth of psychopharmacology. According to Weber and Emrich, opium was long viewed as one of the most effective medications to manage what would today be called major depressive disorder, known throughout history as “melancholia.” A family dynasty of German psychiatrists called the Englekens popularized one of the earliest known methods of systematic opium administration for severely depressed patients: the Opiumkur (or opium cure). Patients were started on small doses of opium that would gradually increase over time; Weber and Emrich estimated daily opium doses were equivalent to a low dose of 20 to 30 milligrams of morphine. Once patients showed signs of improvement, their dose would plateau and then be gradually tapered down. The cautious dosing and long-term monitoring were implemented to mitigate the potential for dependence and withdrawal.In contrast to barbaric psychiatric treatments of the era—restraint devices, crude electrocution, lobotomies, and freezing ice baths—opium treatments were considered much more humane. Most importantly, the Opimkur actually produced rapid improvements in otherwise desperate patients, so much that the Englekens publicly advocated, in papers and lectures, for the use of “acute medical opium therapy in psychiatry.” But the Englekens’ methods also had critics and sparked a fierce medical discourse across Europe, one familiar to us now, over how to balance opium’s therapeutic properties against the risks of dependence and addiction.“By the time I found heroin, it literally saved my life.”
By the 1950s, the new antidepressants overtook opium therapy as the go-to medication to treat depression. Opium’s long reign in treating melancholy has since faded away from memory. But doctors, clinicians, and neuroscientists are increasingly looking to the brain’s enigmatic opioid system as a possible pathway to help depressed and suicidal people who do not find relief from first-line treatments.One part of our body’s internal opioid system plays a role in pain relief, euphoria, and, notably, social bonding.
“If a doctor had literally prescribed me an opiate, I don’t think I ever would have used heroin.”
This concept is hardly new. People with Attention-Deficit Hyperactivity Disorder (ADHD), whose symptoms include excessive talking, the inability to focus or sit still, are prescribed stimulants. Stimulants may cause the rest of us to talk incessantly and fidget, but people with ADHD have the opposite reaction from stimulants: they are calmed down, enabled to focus. Similarly, opioids cause most people to feel drowsy, sedated, and itchy, but people like Avi and Tilley describe an opposite effect. “I could get up, clean the house, and take a shower,” Tilley said about her opioid use. “I remember thinking to myself, this is what’s been missing in my system.” “If a doctor had literally prescribed me an opiate, I don’t think I ever would have used heroin,” Tilley said. “Almost 23 years later, how have we still not come across a way to prescribe a safe supply of opiates to people?” Dr. Sean Lynch, a psychiatry resident at New York’s Mt. Sinai Beth Israel Hospital, has seen cases similar to Avi and Tilley in his own practice. The illness of one severely depressed and suicidal patient, a 47-year-old military veteran, manifested as a deadly hydra of suicide attempts, opioid addiction, chronic pain, and treatment-resistant depression. One time while hospitalized, the veteran ripped out his IV and stabbed himself in the stomach with a needle; he also swallowed batteries and a plastic knife, which required an endoscopy to retrieve. The trauma of war can leave an indelible mark on a person’s psychology and physiology; the prevalence of addiction and suicide are higher among veterans than the general population.“We came back the next morning and he was teaching yoga to other patients. He became a new person.”
Our brain’s naturally-produced opioids are released when we are around loved ones, but our internal opioid levels drop off when we’re alone.
The results from Dr. Schatzberg’s trial are still a long way off, but if they replicate previous findings, they could help expand the horizons of opioids as an antidepressant. So far, efforts to get an opioid on the market for depression in America have failed. In 2018, the American pharmaceutical company Alkermes submitted the first of its kind drug proposal to the FDA, an opioid for major depressive disorder, but it failed FDA approval due to major methodological and statistical issues cited by the advisory committee. An opioid for treatment-resistant depression may still be years away from FDA approval. Avi has had an on-again, off-again relationship with opioids since she first tried them seven years ago in high school. For her, that’s a long enough arc to understand her relationship with opioids today. “In early 2020, I was basically abstinent from all opioids for almost a year,” Avi said. “I did not have a great time mentally.” The mental pain, the psychological aches and soreness, came roaring back, and eventually so did more aggressive opioid use to help her cope, mainly black-tar heroin. Last we spoke, Avi was trying to taper off heroin by using kratom and buprenorphine that she purchased from a dealer.Unfortunately, uber-potent fentanyl analogues have begun to infiltrate the street supply of black-tar heroin in the Pacific Northwest, which is causing an uptick in overdose deaths across the region. “I started to have issues when fentanyl started showing up,” Avi said. “That’s when I started having overdoses.” She found kratom when she started searching for a solution to keep her out of the chaotic heroin and fentanyl supply. “Kratom is one of my biggest harm-reduction measures,” she said, adding that it does not produce the same high as other opioids, but still gives her a sense of feeling safe, grounded, and at ease. “At some point, I may feel like daily or near daily opioid use is no longer serving me,” Avi said. “But as of right now, I really feel that having kratom, and sometimes other opioids, just stabilizes my brain chemistry.”If you or someone you know is considering suicide, help is available. Call 1-800-273-8255 to speak with someone now or text START to 741741 to message with the Crisis Text Line.Zachary Siegel is a journalist living in Chicago. His coverage of health, science, and addiction can be found in The New York Times Magazine, The Nation, The New Republic, and elsewhere. Follow him on Twitter.“I really feel that having kratom, and sometimes other opioids, just stabilizes my brain chemistry.”