How Brain Science Began

Civilization’s debt to opium.

The history of brain science probably began about 4,000 B.C., somewhere in Sumeria, when human beings first discovered the extraordinary effects of the unripened seed pods of the poppy plant. Modern neuroscience owes a great debt of gratitude to this tame-looking plant drug and its sticky, incredibly potent byproduct called opium. Neuropharmacology—the study of the action of drugs on the nervous system—would never have advanced so quickly without it.

Historically, the emphasis has been on opium’s cash value, not its value to science. A trade staple on the Silk Route for centuries, opium was very nearly the perfect business. The present-day drug companies, known collectively as Big Pharma, are not the first capitalists in the world to exert an unprecedented grip on drug retailing.

From roughly 1720 to the late 1800s, the merchants of the British East India Company ran a brisk and lucrative opium business with the Oriental “heathens.” In 1839, the British went to war with China to maintain unlimited trading rights. The British won the war, retained the right to market opium in the Orient, and picked up the island of Hong Kong in the bargain.

Opium’s effects are concentrated at specific receptor sites, while alcohol’s range of action is more diffuse. Nonetheless, the two drugs have similar effects along the limbic reward pathway. Morphine comes right from the source, isolated from the crude opium resin found on Papaver somniferum—the opium poppy. Morphine is known as a “pure mu agonist,” meaning it locks securely into the “mu” subset of endorphin receptors, and activates them. This alters the transmission of pain messages, and induces a contented, euphoric state of relaxation. Codeine, another natural painkiller, is found in opium in very small concentrations. Most medical codeine is synthesized from morphine.

The body’s own opiates are referred to as endogenous opioids. Endorphins and enkephalins are interchangeable terms for these chains of amino acids. An important mechanism of action in this process is morphine’s inhibitive effect on GABA. By inhibiting the inhibitor, so to speak, neurotransmitter levels increase down the line, particularly in the nucleus accumbens. Hence, feelings of pleasure.

Alcohol stimulates the mu receptor as well, so we are back to the same basic chain of limbic activation triggered by drinking. GABA is the bridge that connects the alcohol high and the heroin high.

Rapid cellular tolerance is the hallmark of opiate addiction. Brain cells quickly become less responsive to the same doses of the drug. “The body’s natural enkephalins are not addicting because they are destroyed rapidly by peptide-degrading enzymes as soon as they act at opiate receptors,” writes Solomon Snyder. “Therefore, they are never in contact with receptors long enough to promote tolerance…. As analgesics, the enkephalin derivatives developed by drug companies have not been superior to morphine, or even as good as morphine.” Even the brain’s own morphine is not as good as morphine. Nothing is as good as morphine.

Recent evidence for the heritability of opiate addiction looks strong. “Harvard did some really superb studies using a huge cohort of military recruits in the U.S. Army,” according to Mary Jeanne Kreek, a specialist in opiate addiction at Rockefeller University in New York. “Heroin addiction has even a larger heritable component than any of the other addictions, so that up to 54% of heroin addictions seem to be on a genetic basis or a heritable basis.” Estimates of alcohol’s heritability generally run to 40 or 50 per cent.

--Excerpted from The Chemical Carousel: What Science Tells Us About Beating Addiction. (Spring 2009).

Pain Patients Sue State of Washington

Do doctors suffer from "opiophobia?"

The opium family of painkillers has always been a bane and a boon to the human race, as evidenced by nurses injecting morphine into agonizingly wounded soldiers, and street junkies selling the clothes off their back for another fix.

However, as I wrote in an earlier post, "The Morphine Scandal," the ironies fly thick and fast: In many cases, pain relief is the one thing doctors can offer their patients, and the one thing they withhold. Studies show that 70 per cent of patients present with painful conditions. Typically, non-addicted patients take morphine therapeutically for pain at doses in the 5 to 10 mg. range. But experienced morphine addicts regularly take several hundred milligrams a day—a huge difference.

Now, a lawyer for a pain relief advocacy group has filed suit against the state of Washington, claiming that overly stringent guidelines on prescription pain medications have had a negative effect on pain management across the country. Attorney Laura D. Cooper, who filed the suit on behalf of a group of Washington residents being treated for pain, said in an Associated Press article by Donna Gordon Blankinship that the state's regulations were comparable to setting a limit on the amount of insulin a doctor could prescribe for diabetic patients. Cooper alleged that the Washington standards have been used as guidelines by insurance companies and workman's compensation boards.

The AP article also quoted Siobhan Reynolds of the Internet-based Pain Relief Network: "The ramifications are enormous. You never see on a death certificate that people died of pain, but people die of pain all the time."

The lawsuit features an excerpt from a University of Wisconsin textbook on pain medicine, Bonica's Management of Pain, 3rd edition:

"Opiophobia is the syndrome of failure to administer adequate opioid analgesics because of the fear of producing addiction or toxicity. The etiology of opiophobia is multifactorial: Peer pressure (provider and patient), regulatory agency pressure (real or perceived), and lack of education on opioids and the fundamentals of pain management all contribute to its persistence.... All of these factors contribute to the underuse of these relatively simple and very effective medications, due to no fault of the patients. "

According to Drug Law Blog, the complaint "asks the court to declare that the state guidelines 'do not constitute enforceable law of any kind and should be stricken and removed from all state publications of every variety,' and seeks other additional relief, including an injunction against enforcement."

As for concerns about addiction, recent evidence for the heritability of opiate addiction looks strong. “Harvard did some really superb studies using a huge cohort of military recruits in the U.S. Army,” according to Mary Jeanne Kreek, a specialist in opiate addiction at Rockefeller University in New York. “Heroin addiction has even a larger heritable component than any of the other addictions, so that up to 54% of heroin addictions seem to be on a genetic basis or a heritable basis.”

Photo Credit: Opioid.org

The Morphine Scandal

Patients in Pain Due to "Opium Phobia"

“Opium has been recently made from white poppies, cultivated for the purpose, in Vermont, New Hampshire, and Connecticut.... comparatively large quantities are regularly sent East from California and Arizona, where its cultivation is becoming an important branch of industry, ten acres of poppies being said to yield, in Arizona, twelve hundred pounds of opium.”

--Massachusetts Government Health Report, 1871

By the mid-1800s, as many people know, opium could be legally purchased in the United States as laudanum, patent medicines, and various elixirs. Less well known is the fact that opium was a godsend during the bloody years of the Civil War. Maimed and disabled soldiers found relief in morphine, the potent alkaloid of opium named after Morpheus, the Greek god of dreams. Used against constant, intractable pain, opium and its derivatives were among the most humane medical drugs ever discovered. How could a physician withhold them?

Today, after countless drug wars have merged into a single, inflexible federal stance on “drugs,” morphine and its derivatives remain so stigmatized, so entangled in drug wars and global narco-politics, that the danger of losing sight of their humanitarian applications looms larger than ever.

At least half of all cancer patients seen in routine practice report inadequate pain relief, according to the American College of Physicians. For cancer patients in pain, adequate relief is quite literally a flip of the coin.

A September 10 New York Times report by Donald G. McNeil Jr. highlights studies by the World Health Organization which amply document the ongoing scandal in pain management. At least 6 million cancer and AIDS patients currently receive no appropriate pain treatment of any kind. In addition, WHO estimates that four out of five patients dying of cancer are also suffering severe pain. The numbers of untreated patients suffering intractable, unrelieved pain from nerve damage, burns, gunshots, sickle cell anemia, and a host of other medical conditions can only be guessed at.

Figures gathered by a different U.N. agency, the International Narcotics Control Board, make clear that “citizens of rich nations suffer less.” To put it starkly, the use of morphine per person in the United States is 17,000 times higher than per person usage in Sierra Leone. Doctors in Africa paint a grim picture of patients hanging themselves or throwing themselves in front of trucks as an alternative to life without pain relief. The U.S., Canada, Britain, France, Germany, and Australia together account for roughly 80 per cent of the world’s medicinal morphine use. Other countries, particularly the poor and undeveloped nations, scramble for what’s left.

The ironies fly thick and fast: In many cases, pain relief is the one thing doctors can offer their patients, and the one thing they withhold. Studies show that 70 per cent of patients present with painful conditions. Typically, non-addicted patients take morphine therapeutically for pain at doses in the 5 to 10 mg. range. But experienced morphine addicts regularly take several hundred milligrams a day—a huge difference.

As for concerns about addiction, recent evidence for the heritability of opiate addiction looks strong. “Harvard did some really superb studies using a huge cohort of military recruits in the U.S. Army,” according to Mary Jeanne Kreek, a specialist in opiate addiction at Rockefeller University in New York. “Heroin addiction has even a larger heritable component than any of the other addictions, so that up to 54% of heroin addictions seem to be on a genetic basis or a heritable basis.”

Opium, the main ingredient, is in abundant supply worldwide, and is relatively cheap to grow. The problem, as David E. Joranson of the University of Wisconsin’s Pain and Policy Studies Group told the Times, is the “intense fear of addiction, which is often misunderstood. Pain relief hasn’t been given as much attention as the war on drugs has.”

Moreover, generations of doctors have been taught in medical school that morphine must be used sparingly, with great caution, even if this “opium phobia” results in agony for patients, including infants. (Morphine is safe and effective for use in premature babies.)

The problem is not a new one. Ten years ago, a report by the American Academy of Pain Medicine laid the blame squarely on doctors, who were routinely underutilizing opiate derivatives for pain relief. Not much has changed. It is no secret that the move to HMOs has compounded the problem, as effective pain relief often gives way to the need to move patients out of beds as quickly as possible.

In 2001, the American College of Physicians called for more extensive pain-management education in the nation’s medical schools, noting that doctors are not learning enough about how to treat pain, or about how to talk to patients ABOUT pain, despite what Scott Fishman of the Division of Pain Medicine at the University of California, Davis, calls a “revolution” in the development of new pain medications.

We also need to recognize the problem of under prescribing morphine and other
addictive painkillers for children in hospital settings. If we continue to stringently prohibit the use and sale of opiates, then we had better remember to make one important exception: Pain abatement in medical applications “There’s a certain amount of hysteria about narcotics among doctors,” maintains one researcher. Patients suffering from serious pain cannot get adequate and sustained relief in many cases, because doctors and nurses remain reluctant to provide it.

This, rather than flashy cocaine seizures at the border, represents the lasting outcome of drug wars.

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