The middle-aged male, a known heavy drinker, presented with a curious gait. With each step, he lifted his knees high enough to permit his floppy toes to touch the floor just before the heel, creating a “tap-click, tap-click” sound.(1) The patient reported that he’d been “just fine” until waking up a few days ago with “floppy feet.”
In 2023, the differential diagnosis of bilateral foot drop includes lumbar radiculopathy, peripheral neuropathy, axonal or demyelinating disease and would precipitate an expensive workup. In 1930, however, many jazz musicians, or even a circus employee, as recounted in Sara Gruen’s novel Water for Elephants,(2) would have easily diagnosed the problem as “jake leg” or partial paralysis caused by adulterated liquor.
Prohibition began in the United States on Jan. 17, 1920, following ratification of the Eighteenth Amendment. For those determined to drink, patent medicines became convenient substitutes for alcohol. Jamaica ginger, popularly known as “jake,” was 140 to 160 proof (70% to 80% alcohol by volume) and widely available until it captured the attention of the Prohibition-enforcing Treasury Department.
To forestall purveyors from simply labeling food-dyed alcohol as medicine, federal regulations of the era mandated sufficient solid content in patent medicine concoctions. To provide enough solid content, bootleggers created fake “jake” by adding various adulterants to alcohol, eventually settling on the plasticizing agent tri-ortho-cresyl phosphate (TOCP).
While initially thought to be non-toxic, TOCP, an organophosphate, coming first to the attention of popular musicians and eventually the medical community, turned out to be a slow-acting neurotoxin.(3) By late 1930, the offending product was pulled from circulation, but for many victims, perhaps 30,000, the damage was done. Jamaica ginger itself was problematic in the way any hard liquor can be, but the synthetic “jake” created to circumvent federal regulations caused more serious and often irreversible damage. Prohibition, ethically challenged entrepreneurs, an adulterant with toxic properties, and addicted consumers combined to produce a unique tragedy of the marketplace.
Opiophobia to Epidemic
Today’s opioid epidemic(4) is a similar tragedy of the marketplace that has evolved over the course of decades. Prior opioid epidemics, such as the one that occurred after the Civil War, had made physicians wary of the potential for opioid addiction, and medical training generally incorporated those concerns until a 1980 report suggested that addiction was rare in patients with pain.(5) This publication (actually just a one-paragraph letter to the New England Journal of Medicine) became widely quoted even though its conclusions that opioids did not cause addiction were extrapolated far beyond the highly specific population studied.
By the 1990s, physicians were frequently chided for “opiophobia” in journals(6) and by the lay media. New, long-acting formulations made available higher doses of opiate with supposed “abuse-deterrent” matrices to further reassure doctors and regulators. By the mid-1990s, physicians were bombarded with commercially funded educational campaigns against the under-treatment of pain.(7)
The American Pain Society introduced pain as the fifth vital sign in 1996.(8) The Joint Commission added pain management to its 2001 quality standards, and although particular remedies were never specified, many providers over-read or misinterpreted the requirements. Well-intentioned recommendations, based on questionable evidence, led to a loosening of standards for prescribing opioids, and opioid prescriptions skyrocketed.
The complicity of pharmaceutical firms in fueling the epidemic was only belatedly recognized. Lawsuit settlements against Purdue Pharma (OxyContin) or the Sackler family now exceed $6 billion.(9) Sadly, the number of overdose deaths involving opioids (including both prescription opioids and heroin) continues to increase.
The Pendulum Swings Back
In recent years, the alarm sounded by this latest epidemic has promulgated new policies nationwide to monitor and limit opioid prescriptions. Updated CDC guidelines (available at https://stacks.cdc.gov/view/cdc/38025 ) advocate non-opioid therapy for chronic pain, careful risk-benefit consideration, dose titration, and establishment of treatment goals with quarterly or more frequent review.(10) Physicians appropriately became more cautious, and access to prescription drugs became more difficult as the Drug Enforcement Administration targeted “pill mills.”
Responding to supply and demand, the street price of pharmaceutical opioids skyrocketed, and at the same time, Mexican cartels extended street opioid distribution networks into smaller communities.(11) Synthetic fentanyl, potent and compact, was far easier to conceal and transport than opium poppy-derived heroin, and it came to be sold on the street as heroin. The higher potency of fentanyl relative to heroin or morphine is problematic, much as grain alcohol can be more dangerous than wine or beer. There is less margin for a dosing error, and of course, the potency of any particular white powder is an unknown.
As a critical care physician, following up on overdose patients after successful extubation, I’ve learned from patients that many were unaware that the “heroin” they were sold was actually fentanyl or an even more potent analogue. Our critical care team routinely sends off specific assays for fentanyl, which does not show up on many routine urine toxicology screens. As a result, we have learned that fentanyl has become ubiquitous in overdose patients, even those who thought they were purchasing cocaine or other drugs.
While not condoning the lack of personal responsibility that illegal drug use represents, we need to help our patients understand that consuming “street drugs” has become a form of Russian roulette. Casual users must recognize that snorting a few lines of cocaine at their college reunion could land them in the intensive care unit or the morgue with an unintended fentanyl overdose.
Although the rate of opioid prescribing has stabilized since 2010 (and decreased dramatically in some specialties),(12) overdose deaths continue to rise: 18,893 in 2014,(13) more than 100,000 in 2021.(14) Opioid overdose has always been a common hospital admitting diagnosis, especially in urban areas, but it has been infrequently lethal until the past decade. If the unconscious patient didn’t respond immediately to naloxone on presentation, he or she would be intubated in the emergency department, sent to the ICU on a ventilator (and possibly a naloxone infusion), and allowed to wake up over the next few hours. Hospital or ICU deaths were exceedingly rare, although getting these patients into recovery treatment could be a challenge to their long-term survival.
This scenario has now changed. I vividly recall pronouncing brain death in two young patients in a single night on call in the ICU in February 2015, which at that point doubled my total experience with fatal opioid overdoses observed in a 25-year ICU career. Now, I rarely get through a night on call without an overdose admission. Increasingly, overdose patients are as typically from surrounding rural areas as from the suburbs and inner city. No one is immune. Even in Massachusetts, where recreational cannabis is legal, we are seeing “street” cannabis that has been adulterated with fentanyl and other opioids
No Simple Solutions
Opioid addiction is a brain disease that begins after an initial exposure to opioids,(15) so reducing the use, dose, and length of therapy of prescription opioids is a necessary but insufficient first step. As physician leaders and educators of the next generation of physicians, we must adopt a three-pronged approach of investigation, education, and advocacy.
Investigation involves not only clinical research into addiction, but also developing an in-depth personal understanding of the scope of the problem. Journalist Sam Quinones’s “Dreamland: The True Tale of America’s Opiate Epidemic”(11) is an eye-opening account of how entrepreneurs independent of the traditional coastal drug cartels seized the market in America’s heartland.
Physician leaders should spend time in the emergency departments and intensive care units with the front-line physicians, nurses, and social workers caring for these patients, digesting the anecdotal evidence that has not yet reached medical journals. The delay between widespread community appreciation of “jake leg” before it reached medical journals is instructive; peer-reviewed publications necessarily lag reality in a rapidly changing situation.
Education of our trainees and colleagues should encourage adherence to CDC and other opioid prescription guidelines and carefully distinguish between short-course treatment for acute pain conditions versus chronic use. There needs to be more patient and public education on the widespread substitution of fentanyl for what may be sold as cocaine or other “recreational drugs” to casual users. Hospitals and healthcare systems can join with community partners to create opioid task forces that include public education, media appearances, and legislative solutions.
Advocacy for change is perhaps the most important but also the most controversial role for the physician leader. Prescription drug “take-back” programs help remove unused opiates from medicine cabinets, and few would argue with improving access to treatment and effective medication therapy for those already suffering from addiction. Provision of naloxone in the event of overdose has become widespread despite objections that it could encourage more or riskier drug use, or discourage users from seeking treatment. These and other naloxone myths have largely been debunked.(16)
Drug consumption is not a healthy practice, but the reality is that harm-reduction strategy can save lives in those currently lacking maturity and personal responsibility to avoid intoxicants. Abstinence-based treatment approaches work for some individuals, but the insistence on abstinence can lead to loss of tolerance and increased risk of overdose with relapse. Too many patients now leave abstinence-based treatment or jail only to die on their initial relapse.
More controversial harm-reduction strategies include distribution of fentanyl testing strips(17) to identify contamination of street drugs, needle-plus-syringe exchange programs (which reduce the risk of HIV/AIDS and hepatitis transmission,(18) but not overdose risk), and supervised injection sites, more commonly found in Australia, Canada, and Europe(19) than in the United States.
While reports on mortality reduction with supervised injection are mixed, the Vancouver INSITE facility, the first supervised injection site in North America, calculates it saved as many as 48 lives over four years by intervening in overdose events.(20) Such estimates are dependent on mathematical modeling but would presumably be even higher given changes in the potency and composition of street drugs in the intervening decade. Supervised injection sites have been established in several cities in the United States; Rhode Island became the first state to legalize such sites during 2021.(21)
We are in the midst of a great experiment on legalization of cannabis for medicinal (38 states) or recreational (19 states) use, and it may be too early to say whether this approach would work for “harder” drugs. Alcohol prohibition laws may have reduced rates of alcoholism and public drunkenness, but created a black market and contributed to the growth of organized crime. The risk-benefit calculation for legalization is beyond the scope (and word limitations) of this article.
Street “Heroin” Is Today’s Jamaica Ginger
Today, “jake-leg” is a diagnosis of historical interest; a bit of medical trivia possibly useful as a teaching point on morning rounds. An unintended consequence of restricted prescription opioid availability has been the entrepreneurial opportunity for the unscrupulous. With severely limited access to pharmaceutical opioids, addicted individuals will seek whatever’s available to forestall withdrawal.
Street “heroin” is the new Jamaica ginger; fentanyl and its analogues are the new TOCP. Physician leaders should advocate for interventions proven effective for prevention and treatment as well as support monitored trials of new approaches to reduce the alarming increase in opioid overdose and death. Expanding access to therapy with buprenorphine and methadone is not a comprehensive solution, but it could reduce the carnage of fatal overdoses. Use of fentanyl testing strips might better inform routine or casual users of what they are actually consuming. Safe injection sites are geographically limited and highly controversial, but given the five-fold increases in overdose mortality since 2014, even the White House is now considering unconventional risk-reduction strategies.(22)
When current approaches are ineffective, it is time to examine what has been successful in other countries and in progressive cities and states within the United States. If the “cure” of well-intentioned abstinence therapy turns out to be more lethal than the “chronic disease” of opioid addiction, it’s time to rethink our approach.
Investigating and promoting health is more important than focusing only on treatment. For example, decades-long reduction in tobacco smoking has finally paid dividends with decreased cancer mortality rates,(23) even as we continue to investigate better therapies for remaining cases of lung cancer. As much as possible, physician leaders must highlight and address root causes rather than simply improving late treatment, which may be difficult, expensive, or not timely enough to prevent death.
Jake leg is a trivia question today primarily because the harm of illicit alcohol almost completely disappeared with the repeal of Prohibition. With reduced opioid exposure, better addiction care, and public safety initiatives, fatal opioid overdose could become a similarly arcane diagnosis to clinicians practicing decades from now.
Acknowledgments: The author thanks Peter D. Friedmann, MD, MPH, DFASAM, FACP, associate dean for research and professor of medicine at UMass-Chan Medical School-Baystate for his input and suggestions.
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