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Doctors in Scotland were amazed when a 66-year-old woman underwent what is normally a very painful operation on her hand for severe arthritis and required little to no pain medication afterward. Similarly, two years ago, she was diagnosed with severe osteoarthritis in her hip with significant joint degeneration, yet she complained of no discomfort before, during, or after her hip replacement surgery.

In fact, the patient told her doctors, there have been times she had burned herself and withdrew her hand from the flame only when she smelled burning flesh. She also scored remarkably low on anxiety and depression tests.

Thinking the woman’s exceptional insensitivity to pain might be rooted in her genes, researchers in the United Kingdom sequenced and analyzed her genome and found a previously unidentified mutation, they reported Wednesday in the British Journal of Anaesthesia. That mutation, in a region they named FAAH-OUT, seems to turn down the activity of a neighboring gene called FAAH, which is known to be involved in pain sensation, mood, and memory.


FAAH is a protein that breaks down anandamide, also known as the “bliss molecule,” which is a neurotransmitter that binds to cannabinoid receptors. These are some of the same receptors that are activated by marijuana. With less FAAH activity, this patient was found to have more circulating levels of anandamide, which may explain her resistance to feeling pain.

While it’s risky to make too much of one patient’s case, the researchers said their discovery could have exciting implications for the treatment of acute and chronic pain. Prior genetic targets for pain treatment have focused on sodium ion channels and the transmission of pain signals from the peripheral nervous system to the brain. The FAAH and FAAH-OUT genes instead alter how pain signals are interpreted by the brain.


While previous studies and trials of experimental drugs directed at FAAH have failed, the researchers said FAAH-OUT may offer a new way to target the endocannabinoid receptor. At a time when about 130 Americans die daily from opioid overdoses, scientists and drug companies are actively pursuing alternative non-opioid medications for acute and chronic pain.

“This discovery opens up numerous possibilities of developing drugs using the endocannabinoid pathway to modify how pain is experienced,” said Dr. Dev Srivastava, one of the investigators and a consultant in anesthesia and pain medicine at Raigmore Hospital in Inverness, Scotland. “This could be developed into a wonder drug to treat surgical patients or those with cancer or chronic pain.”

However, as with the Scottish patient, complete elimination of pain sensation can be problematic. Similar to patients who suffer from painful diabetic neuropathies, the resulting decreased sensation to extremities can sometimes result in repeated injuries that are not noticed by the patient. Dr. James Cox, another author and senior lecturer at the Wolfson Institute for Biomedical Research at University College London, said, “Pain is an essential warning system to protect you from damaging and life-threatening events.”

Another disadvantage to endocannabinoids and their receptor targets is that poor memory and learning may be unwanted byproducts. Researchers said the Scottish woman reported memory lapses, which mirrors what is seen in mice missing the FAAH gene.

The investigators were also quick to caution patients and providers that, while this research demonstrates analgesic effects within the endocannabinoid pathway, this does not mean that recreational cannabis works the same or can be used as a substitute for pain control. The opioid crisis in the United States began with people becoming addicted to legal pain medications and was followed by spikes in use of heroin and illicitly made fentanyl. If endocannabinoid-pathway medications become prevalent, illegal counterparts could similarly become a concern.

  • Prefer to stay anonymous on this. I am one of those people who do not experience pain in the way most people seem to. I do indeed want anesthesia when I have surgery of any sort: I can feel the kind of pain that cutting causes. But afterwards I have very little or no discomfort, until the wound gets to that phase of healing that involves a kind of soreness/itching. I can live with that. Same experience with accidental wounds that pierce the skin: I’ll feel the initial wounding, but then the pain disappears. I rarely will notice a bump that causes bruising, or the bruise itself (unless it is enough to stretch the skin). My brother is the same way. We both experience extreme headaches, though, so clearly this is a complex business.

    I am still angry with the surgeon who prescribed me a codeine medication after surgery despite the warning on my chart that it would make me extremely nauseous, and was not necessary. I reminded him of this prior to surgery. He refused to believe me. He gave the medication to me anyway, and I was not told what it was. The result was projectile vomiting, torn stitches, internal bleeding, and separation of abdominal muscles. Prolonged recovery, but I still did not need analgesics. They believe me now, but I will never go back to that hospital again.

    If people like me can give researchers a clue about how other people can be treated for post-surgical pain, I’m all for it. I do not understand the folks who are so quick to jump on the nay-sayer bandwagon when right now we are just beginning to understand how this works. My brother and I might have a completely different mechanism at work, and there could be others. How can anyone say that research into these mechanisms would inevitably result in a medication that is expensive? As another writer said, it could well be something simple and readily available. Especially when there are botanicals in use now that relieve pain and inflammation that haven’t been evaluated appropriately.

  • This new fresh approach, backed by scientific research, deserves furthering ASAP – also for its potential of addressing the current vast opioid crisis. That these findings incidentally also prove the merits of cannabinoids is a nice bonus. During research the indeed worrisome issue of memory loss should also be properly investigated and hopefully mitigated. This is the kind of newer science that the world needs, as older / aged sciences seem to have run their course (i.e. Alzheimers research, after so many failed trials based on the same approach this too needs a totally new angle of attack).

  • This is interesting, but there have been other cases, and the research was overstated. In fact nearly all of the research on this topic lately is done in limited short term animal studies, which our media misreports as is it was meaningful.

  • I think it was a poor choice to compare cannabis to opioids. Medical cannabis is used as an alternative to opioids for the very reason that is has low addictive potential. Synthetic forms of cannabis already exist, but have not gained popularity. Even if we pretend that cannabis “addiction” is comparable to opioid addiction, the obvious “street” alternative to medically prescribed cannabis is cannabis bought from a dealer.

  • People dying from opioid overdoses, are primarily those using street drugs (addicts), and/or intentional suicide by opioids by desperate patients when their unbearable pain is not, or is undertreated.

    People don’t die from taking opioids as prescribed.

    The government is chasing the wrong monster when all their attention and resources on illicit drugs (heroin/fentanyl) shipped in from outside the US and opening mental health clinics and hospitals.

    Opioids for pain have been used successfully for thousands of years and only very recently, have become a problem. Why?

    So you develop a new very expense drug to replace an opioid.
    Who will be able to afford it? What difference will it make in addicts who have always found something to get high on. And suicides? It will do nothing to stop the increasing rate.

    Sorry..sounds like an interesting approach to pain but if unaffordable, it is worthless.

    • We don’t know at this point if drugs to increase anandamide levels will be expensive. Paracetamol (Acetaminophen) is a drug that increases anandamide levels modestly, and that may be primarily or solely reponsible for its therapeutic benefits. A drug that would inhibit FAAH and greatly increase adandamide levels might not be hyper-expensive or complicated.

      What we do know at this point that focusing on opioids to manage pain has backfired for a lot of people, with many addicted people and many deaths. The grand experiment in mass prescribing opioids isn’t working, especially if prescriptions to habituated patients are reduced, forcing them into illicit street drugs for relief.

      We need another pathway for major pain relief, and I’m not willing to make assumptions or dismiss this work at this stage based on assumptions about cost or whatever that are not backed by any data.

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