Data on Long Term Use of Opium, Opiates

On May 22, 2019, Don’t Punish Pain held rallies across the U.S. That evening, KATU of Portland, OR, broadcast a report by Jackie Lebrecque, featuring footage from Oregon’s Capitol Building in Salem, phone comments from Dr. Jessica Gregg, General Internal Medicine and Addiction Medicine at OHSU, and brief remarks from Dr. Kevin Olson, medical oncologist and member of Oregon’s Health Evidence Review Commission (HERC), which determines which medical treatments and services are covered by Medicaid in Oregon.

At minute 1:20 of the story, reporter Jackie Lebrecque says, “There’s not much research on the long term use of opioids for pain management, and that lack of evidence makes it hard for policymakers to make decisions.” The Dr. Olson appears on camera and says, “The evidence we reviewed was murky at best.” He also said, “We were very aware of the vulnerability that chronic pain patients have, and the need to treat them.” While it is heartwarming that the chair of such an important state commission is aware pain patients are vulnerable, it might be more helpful for the chair of a commission on health evidence to show some intellectual curiosity or ingenuity in seeking better information.

In our current drug-war climate there’s likely not a lot of grant money available to study patients who have lived productive lives using high dose opioid prescriptions for long periods of time. Available recent studies are flawed by small sample size, high drop out rates and short time frames with no follow up – and I suspect frequently insufficient dosage. But this doesn’t mean that there isn’t any better information that could inform decisions about pain treatment and policy. This 2-part series will explore available published data. Part One explores extensive studies on the health, fitness and functioning of opiate addicts performed in the 1920s. Part Two discusses the development of heroin overdose narratives during the 1940s, and the strong evidence that undermines the idea that opiates can easily, and accidentally, kill.

Part One: Decades of Opiate Use, No Damage or Dysfunction

Introduction

This slim volume the AMA published in 1929, “Opium Addiction” contains rich data on long-term opiate exposure. Initiated by the New York Committee on Drug Addictions, and performed by A.B. Light and E.G. Torrance at Philadelphia General Hospital’s narcotic ward, many meticulous tests were performed over a 3 year period on 861 self-identified addicts in hopes of determining reliable physical findings to use to identify addiction. While their original goal wasn’t met, they generated extraordinarily informative data showing many ways that opiates don’t cause damage or malfunctions in human bodies.

In discussion of the prior literature, the authors note a lack of vital statistics on users’ health and fitness, and that regular long term use had few detectable signs that could easily go unnoticed.

The “TL DR” is that 861 subjects with long histories of opiate use had no permanent damage and no serious dysfunction of their organs. There were a few minor functional effects, such as constricted pupils, slowed bowel function and slightly high or low white or red blood cell counts. The one clearly negative outcome was lowered fitness results for subjects resuming morphine after a period of withdrawal.

Here are ways the subjects were normal: respiration, circulation, pulse, BP, heart rhythms, red blood cell counts, blood sugar, sed rate, liver function. No subjects had abscesses. None had liver dysfunction.

With morphine in their systems, subjects’ behavior was sociable and cooperative, even helpful. During withdrawal for periods of 24 or 48 hours, their behavior was exasperating to completely uncooperative. Very high doses, of hundreds or thousands of milligrams, didn’t cause unconsciousness or intoxication, but ordinary behavior.

Condition and Function of Subjects Regularly Administered Morphine

Participants were mostly men ages 20-40, and reported being addicted for 5-20 years. Daily doses ranged from 5 to 20 grains (324 to 1296 mg). Most were normal weight, some underweight, and some overweight, even obese (Underweight was common at the time. Half of WWI & WWII conscripts were rejected for malnutrition). Most had tried treatment before. Many were employed. Jobs including chauffeur, book binder, sales, farmer, printer, driving instructor, draftsman, garage foreman, miner, ships cook, railroad, brass finisher, reporter.

First, groups of 4-100 subjects were administered their habitual doses of morphine and blood components, blood pressure, pulse, temperature, respiration, GI, kidney and liver functions, stair climbing, food intake, and metabolic rate were measured. None of the subjects checked for persistent thymus had one.

The authors noted the tests “…revealed no fundamental differences from normal in addicts to whom morphine was administered to supply their needs, except a slight delay in average response of gastric secretions….albumin in the urine in 17 percent of the cases and wide fluctuations of the individual determinations of the basal metabolism although the average metabolic rate was within normal limits.”

Physical and Functional Measures During and Following Withdrawal

The first two withdrawal tests followed one group for 24 hours, one for 48. Data was collected on composition of blood, circulation and metabolism. The 24 hour test initially included 8 subjects, of whom 4 became too uncooperative for accurate observation. The remaining 4 had no morphine or food for 24 hours. Every 3 hours, their pulse, BP respiration, temperature and BMR were recorded, and samples of blood and urine taken.

Withdrawal for 24 hours led to mild symptoms with minor changes in pulse, white blood cell counts and BMR. Behavior changes and irritability began before physical suffering. The 4 subjects who completed 24 hours withdrawal appeared to be suffering head colds – watery eyes, sneezing and stuffy noses, and some yawning.

Subjects withdrawn for 48 hours had severe symptoms, including one with double vision. Eight had increased white blood cells; all, slight concentration of the blood; 7, slight rise in cholesterol. All lost weight. When morphine was re-administered, blood oxygen increased. Blood concentration and white cell counts decreased after several hours.

Other than concentration of the blood and slight cholesterol increase, no symptoms were noted that weren’t previously reported.

The authors characterize subjects’ “incessant begging and annoying behavior” as sufficient to warp the conclusions of casual observers. They report sometimes leaving the ward believing the subjects’ problems were emotional, not organic, and best addressed by incarceration. Other times, violent muscle twitching, vomiting, perspiration, yawning and sickly appearance convinced them they were witnessing physical suffering.

The next test featuring withdrawal began with scopolamine, an anti-nausea treatment then routine treatment in the narcotics ward. Once confusion from the scopolamine cleared, subjects were observed, and basal metabolic rate, temperature, physical fitness, blood, urine, and reactions to epinephrine and atropine sulphate were tested. EKG tests on 8 subjects showed nothing abnormal before or after treatment.

The main change in the scopolamine tests was weight. Only one subject gained weight, all others lost. For over 48 hours, subjects’ body temperature was slightly high, but none had abscesses or infections. Following scopolamine, fitness measures declined, but lung capacity remained the same, and liver tests were normal. Average blood sugar readings after epinephrine injections were slightly high at first, then slightly below normal.

According to the authors, participants’ behavior and appearance weren’t useful for predicting behavior. They describe two subjects who use identical amounts of morphine. After scopolamine, one was eating and boasting about being done with the drug; the other was in bed, miserable, refusing food and complaining of weakness. The authors speculate that the former would have had opportunities for acquiring morphine when discharged from the hospital that the latter didn’t have.

Extremely High Dose Tests

Several tests were of high doses for 5 participants, one intravenous user, and 4 who used intramuscular injections, with usual doses between 6 grains (390 mg) and 17 grains (1100 mg). Each received multiple injections of 2 grains (130 mg) of morphine, from a total of 10 grains (648 mg) intramuscular injections over 35 minutes, to 30 grains (1944 mg) intravenously over 2 hours 24 minutes.

Blood pressure, respiration, pulse, blood sugar, urea, nitrogen and dry matter of blood were all normal. Minor changes were measured, such as oxygen saturation and red and white cell counts. Participants maintained normal functioning and consciousness.

Following 48 hours withdrawal, two subjects received multiple IV injections of 2 grains (130 mg), then several of 4 grains (260 mg). One received 20 grains (1300 mg) in 56 minutes, the other, 11 grains (700 mg) in 76 minutes. Pulse, blood pressure, respiration were unchanged. both had bright red flushing on their skin.

During these tests, subjects showed interest in their surroundings, smoked cigarets, and one read the newspaper. All requested their usual dose at the next interval and ate regular meals.

Participants showed no physiological changes, particularly in the central nervous system, and no depressed respiration or sleepiness. The morphine measured in their blood was low compared to the amounts administered. The researchers speculated that morphine was being sequestered in the muscles or rapidly destroyed by the body.

This section’s conclusion made a few points. Withdrawal symptoms completely resolve within 7-10 days, whatever type of cure, including cold turkey. If resuming morphine, doses as low as 1/8 grain (8 mg) to 1/4 grain (16 mg) relieves cravings and provide a kick. The authors say that addicts who resume their pre-cure dose levels can suffer serious or deadly results. After leaving, one of the study participants died after such a dose. While reports of such deaths are not infrequent, they may be unreliable.

Excretion of Morphine and Other Observations

Sixteen studies were performed on 10 subjects, receiving 15 grains (972 mg), 30 grains (1944 mg) or 60 grains (3888 mg) over 24 hours. Excretion via urine was remarkably consistent with the dose administered, regardless of subject’s height, weight, volume of urine or length of addiction. Amounts in feces were too variable to be useful.

One participant developed pneumonia. The authors report on p. 108, “The prompt recovery of the addict while receiving the 15 grains daily through the period of illness and recovery supports the belief in the harmlessness of the drug on organic functions when the body is accustomed to it.” This observation is important when considering the effects of long-term high dose opioid use by patients with medical conditions causing chronic and severe pain.

The Question of Minimal Lethal Dose

In light of contemporary concerns about opioid deaths, it’s necessary to acknowledge that there’s no minimal lethal dose of opiates.

According to Light and Torrance, on p. 105, “The lethal dose of morphine for man is not definitively stated in textbooks of pharmacology.” They cite amounts that various researchers purported to be deadly. Kunkel’s “Handbook of Toxicology” named 1 1/2 grains (97 mg) as a minimal lethal dose, with poor outcome likely from 4 grains (260 mg), but with favorable circumstance, one might survive 15 grains (972 mg). Sollmann’s manual of pharmacology posited a range of 3-6 grains (195-389 mg), with any dose over 4 grains (260 mg) unfavorable – but mentioned one recovery from a dose of 60 grains (3888 mg).

Light and Torrance’s data doesn’t support the previously-proposed lethal doses.

When considering potential harm, the authors’ observations on rapidly increasing doses are illuminating.

p.109 “The general condition of the healthy addict under these various dosages is of interest. It was not a difficult procedure to increase the daily dosage from 10 (0.648 Gm) to 60 grains (3888 mg) within two or three days. Practically all our patients showed a gain in weight in the hospital while receiving these various amounts. No symptoms of intoxication appeared during the administration of the large quantities.”

Reducing the dose, from 60 to 30 grains, from 30 to 15 and 15 to 7 1/2 worsened the disposition, but caused no withdrawal symptoms, and relieved constipation.

The decreased fitness measured when participants resumed morphine after withdrawal should be explored over a longer time frame. Whether intending to quit for good or to experience greater results from smaller doses, declines in fitness after withdrawal might be countered with exercise. As reported on page 113, “We have been unable to detect any marked physical deterioration or impairment of physical fitness aside from the addiction per se in the series of cases of opium addiction studied during the administration of morphine.”

My Observations

Light and Torrance’s portrayal of opiate users’ condition is almost entirely incompatible with all I’ve absorbed from a lifetime of American media representations, school drug education, and historical reports of intense resistance to giving up opium.

Theoretically deadly doses were injected into subjects without harm, without intoxication. Despite well-known warnings about depressed respiration, the subject who developed pneumonia and recovered while receiving morphine shows that when a body accustomed to opiates, they don’t interfere with healing or functioning during illness.

The one part of “Opium Addiction” that actually conformed to the familiar media and popular images of addicts is the obnoxious behavior during periods of withdrawal – whining, begging, uncooperative.

But is this obnoxiousness unique to drug users? Think of behavior on many reality shows. Morbidly obese patients on “My 600 Lb. Life” bully their families to obtain forbidden pizzas. Occupants of condemned houses flip out at relatives throwing away disgusting detritus. Bridesmaids are browbeaten into spending time and money on Bridezillas’ whims for months.

Light and Torrance close by expressing hope that lack of physical deterioration to circulatory, hepatic, renal or endocrine functions suggest a possibility of relieving the addict of addiction. Looking at their data, I see different potential for a better future.

If the goal is minimizing time, expense, suffering and turmoil focused on the drug, and maximizing health, function and interaction with community, we must ask if abstaining is the best, or even a viable method.

Withdrawing initiates physical and emotional suffering, disruption of activities, becoming unpleasant to be around, and frequently initiates repetitions of failure. Using for years doesn’t damage organs. Users with reliable supply are cooperative, helpful and not intoxicated. They can think about other things, which is hard to do when shivering, puking, feeling desperation, with one sure source of relief that’s out of reach.