Introduction
If I may say so, Americans do like their drugs, why is that ??, is life not enough inhabiting a wonderful body that provides everything you need, to feel happy, to soak up the sunshine and experience nature, and loving relationships. I know life has its downside, but we have the strength and the willpower to overcome adversity, and to live without greed and power. I know I sound like a philosopher with aged wisdom, but why destroy your God given body for a euphoric high, when your body possesses the natural means to feel high. I am talking about endorphins…what are they? Let’s dig a little deeper and try to understand natural highs without ingesting a poison to achieve it. Finally how did a one paragraph letter ignite a drug crisis that left thousands of people dead and many more hopelessly addicted.
Endorphins
Natural Feel-good Chemicals
I have always maintained in my articles that the human body is a masterly example of biological excellence, considering the almost infinite number of processes that are activated every day. As Christopher Bergland ( the athletes way) describes it “ life in the human body is designed to be a blissful experience…and our biological design is generous, but lays dormant in many”. Bergland is, among other things an endurance athlete and he knows what the body is capable of, possessing a wealth of ‘feel good chemicals’ that are released in the brain to bring pleasure and happiness especially when we move. As I have said before the body is designed to move like an automobile, which will eventually deteriorate if it sits on a driveway stationary for any length of time. We have mentioned some of these ‘feel good chemicals’ which include ‘Serotonin’, ‘Dopamine’, ‘GABA’ (Gamma-Aminobutyric Acid), and ‘Adrenaline’. Other naturally occurring chemicals include Endorphins, Oxytocin and Endocannabinoids.
POMC ( Proopiomelanocortin )
Endorphins ( a word comprised of 2 words endogenous ( internal) and morphin) are structurally similar to proteins but contain as little as 5-40 Amino acids. Endorphins are not neurotransmitters but they modify them by way of a chemical neuromodulatory action. Endorphins (referred to as β-endorphin molecules ) are produced from a larger precursor polypeptide ( 241 amino acid residues ) called pro-opiomelanocortin (POMC) using enzymatic splicing, that is synthesised within the pituitary gland. Besides endorphins, the hormone that we discussed previously as part of the HPA (stress axis). ACTH ( Adrenocorticotropin ), and α-MSH ( to regulate appetite, sexual behavior and melanin (natural pigment substance for the skin) production ) are also manufactured in the pituitary. In the HPA (Stress axis) it is the CRH (Corticotropin Releasing Hormone) secreted from the Hypothalamus that activates the POMC process and once it reaches the designed level of precursor substance, the Pituitary sends an inhibitory feedback signal back to the hypothalamus to halt the CRH signal. Endorphins as its name suggests is primarily secreted for pain management, and relief from strenuous activities such as childbirth, exercise and combat, for example. We have mentioned the Pituitary in terms of endorphin production, but these β-endorphin molecules are also synthesized within the immune system cells, since they also possess mRNA transcripts for POMC polypeptides which include T & B-Lymphocytes, Monocytes, and macrophages which they secrete during an inflammatory response.
Turning pain off ( Analgesia)
β-endorphins are released into the peripheral nervous system ( this includes the autonomic nervous system and the somatic nervous system that voluntary control skeletal muscle) and bind to opioid receptors in both pre & post synaptic nerve terminals that provide analgesia ( inability to feel pain). This is achieved by inhibiting tachykinins ( neuro-peptides that excite neurons, acting as vasodilators ( widening of blood vessels), and muscle contraction. These tachykinins which are expressed throughout the nervous and immune system, contribute to multiple disease processes, including acute and chronic inflammation and pain, fibrosis, affective and addictive disorders, functional disorders of the intestine and urinary bladder, infection, and cancer. The result of β-endorphins secretion, in addition, inhibits the release of GABA, an inhibitory neurotransmitter for the excitatory Glutamate ( that we discussed in the previous article), but in this case inhibits excess dopamine production, which we don’t want during analgesia. In the Central nervous system (CNS – The Brain & the spinal cord control) opioid receptors ( referred to as ‘mu-opioid’) are most abundant in descending pain control circuits located in the amygdala, mesencephalic reticular formation, periaqueductal gray matter (PAG) and rostral ventral medulla. We came across some of these regions when we discussed sleep circuitry, so please refer to the brain diagram in article Part 20
The letter
To the Editor: Recently, we examined our current files to determine the incidence of narcotic addiction in 39,946 hospitalized medical patients’ who were monitored consecutively. Although there were 11,882 patients who received at least one narcotic preparation, there were only four cases of reasonably well documented addiction in patients who had a history of addiction. The addiction was considered major in only one instance. The drugs implicated were meperidine in two patients, Percodan in one, and hydromorphone in one. We conclude that despite widespread use of narcotic drugs in hospitals, the development of addiction is rare in medical patients with no history of addiction.
“Addiction rare in patients treated with narcotics”
A ninety nine word letter was sent to the New england journal of medicine in 1980 that became the ignition switch for an opiate epidemic that was unleashed in American society during the 1990’s. Drug companies and unscrupulous prescribing physicians working for pain clinics took this almost inconsequential letter as undeniable proof that painkiller medicine was not addictive, so any amount would be prescribed causing hundreds of deaths. The author was a Hershel Jick MD and Jane Porter of the Boston Collaborative Drug Surveillance program who stated that 11,882 patients out of 39,946 had been prescribed at least one narcotic, and only 4 cases became addicted. The implicated drugs were Meperidine (Brand name Demerol, an opioid pain medication, as stated on drugs.com
‘misuse of this medicine can cause addiction, overdose or death’
(2 patients), and Percodan (brand name Endodan or percodan, a combination of aspirin and oxycodone, an opioid pain medication, as stated on drugs.com
‘misuse of this medicine can cause addiction, overdose or death’ )
and Hydromorphone (brand name Dilaudid or Exalgo opioid pain medication, as stated on drugs.com
‘misuse of this medicine can cause addiction, overdose or death’
for the other two. Their conclusion, within all narcotic drugs used in hospitals, addiction was rare in patients who had no prior history of drug addiction. Today Dr Jick regrets publishing this letter saying that no drug company or physician ever reached out to me and asked questions, but instead used it to fuel the insanity that followed.
The creation of a flock of beheaded ducks
If medical healthcare had stayed on the road of natural, herbal healing and dietary modalities, society would certainly be in a better position today from a health and financial perspective, very few, if any, dying in miserable agony from stage IV cancers, and the multiplicity of conditions that are triggered by the denial that healthy food full of nutrients is the way to maintain human health. Due to the greed and power of a couple of wealthy families they have managed to eradicate true health from the planet and are responsible for the millions of people who are dying every year from needless sickness throughout the world. Their criminal savagery has converted the human race in general, to feed on poisonous drugs. treating the sick who would not be sick, had they not infected peoples belief system including health practitioners turning those professionals into drug peddlers. Furthermore, by their greed fuelled medical education, it has forced medicine into creating medical divisions believing that the body resembles the blueprint of an automobile and one type of physician is incapable of fixing the body as a whole, creating a medical profession no better than a flock of beheaded ducks. What is sad is that most physicians are eminent intellectually capable professionals that have been led kicking a can down the road. This empire of ignorance with their state of the art technology, and biased science basing symptoms as the cause, has become so powerful that any alternative medical approach is immediately suppressed as pure quackery. But who really are the ducks ??. Anyway, I digress, my apologies….and now, after that little rant interlude……..are you sitting comfortably..then I will…. I will continue my story
A short history of Opiate development
Mundipharma Pharmaceuticals limited who were established in 1973 operating initially as Napp laboratories specialised in formulating drug extended delivery systems, created a system of slow release morphine tablets for cancer patients providing ‘slow burn’ pain relief. Their product was called ‘Continus’, which today has developed into a 7 day analgesic patch that slowly releases a drug into the body combining an opioid agonist with an antagonist. It was this technique of a slow release drug form and this inconsequential letter submitted to the NEJ of medicine, that became the basis of ‘scientific proof’ that opiates were non addictive.
The Sackler Brothers
Let us go back a little further and talk about a little known family of billionaires named Sackler, Arthur, Mortimer and Raymond, a family of Jewish immigrants that settled in Brooklyn New York, who in 1952 purchased a small patent medicines company known originally as Purdue Frederick founded in 1892. Their products included a broad based sherry tonic ( to treat anemia to tuberculosis) called Gray’s Glycerine tonic, Senokot for constipation, Cerumenex ear wax remover, and Betadine an antiseptic, that the US government purchased in large quantities to prevent infection among soldiers fighting in Vietnam. Both Mortimer and Raymond attended medical school, both working as psychiatrists and to the brothers credit their research uncovered a link between psychosis and cortisone, but of course the arrogant ‘not invented here syndrome’ mentality of their medical peers ignored it. Coupled with Arthur’s work in psychiatry he devised a novel way (at the time) to advertise pharmaceuticals suggesting that medical journals should include pharmaceutical advertising. Pharmaceutical company Roche contracted Arthur to devise an advertising strategy for their new drug Valium, claiming that psychic tension ( stress ) was the underlying problem associated with heartburn, digestive conditions, insomnia and restless leg syndrome.
The birth of Oxycontin
Mortimer actually studied medicine in Glasgow Scotland (Anderson college of medicine) when he was 20 in 1937, a decision taken because of the discrimination that existed in New york against Jews at the time. However, when he spent his summer break back in New York in 1939, he was unable to return to Scotland because of the outbreak of WWII. So he was forced to complete his studies in New York. Purdue then purchased Napp Pharmaceuticals UK in 1966 and Mortimer Sackler settled in the UK running Napp, while his brother Raymond ran Purdue in New York. In 1972, Dame Cicely Saunders * founder of St Christopher’s hospice for palliative cancer patients in Bromley UK, approached Napp and asked if they could develop a pill form of morphine that could somehow be released slowly into the body,* which was the birth of what would later be called ‘OxyContin’. So in 1981, Napp introduced a timed release morphine pill in the UK and 6 years later it was introduced to the US, marketed as MS Contin. In 1996 Oxycontin (Oxycodone), the immediate release version of MS Contin, was introduced in the US. In 2015, Forbes magazine calculated the Sacklers net worth (shared between 20 heirs) as $14 billion, the lion’s share having been earned from the sales of Oxycontin, the narcotic painkiller regarded by many as among the most dangerous products ever sold on a mass scale.
* It was the work of Cicely saunders who coined the term ‘Total pain’ and wrote
“ A cry just to be rid of pain is not worthy of man…Man by his very nature finds that he has to question the pain he endures and seek meaning in it, the body has a wisdom of its own and will help the strong instinct to fight for life to change into an active kind of acceptance that may never be expressed in words.”
One patient, Mrs Hinson in a hackney hospice said
“ But it’s so wonderful to begin to feel safe again, without any further questioning of my mental as well as physical distress, or my social problems and spiritual needs for security.”
As I said in my rant, this is needless suffering and unnecessary loss of dignity due to ignorance even with Saunders who could have, if she had had the knowledge, that was buried in some archive, to cure these unfortunate people, who were in such dire pain they were clutching at religion as if somehow the body was punishing them for their sins.
In Sam quinones excellent book “Dreamland” he stated it was retired British physician Robert Twycross who approached some Napp sales reps and suggested manufacturing a timed release morphine pill, but nethertheless the seed was sown.
The Pain Doctors
Even in 1985, pain management was rife. Some hospitals used only barbaric surgery on patients who were in excruciating pain, such as Cordotomy ( a procedure that severs neurons that transmit pain signals within the spinal cord). As we can still read today on websites a necessary procedure performed on patients experiencing severe pain due to cancer or other incurable diseases. It was the work of Dr Kathleen foley and Russell Portenoy, at Sloan Kettering palliative care unit for cancer patients, Dr Lynn Webster from salt lake city and of course Cicely Saunders who opened the way for opiate use to relieve pain. These dedicated individuals strived to improve pain management, but then Foley and Portenoy in 1986 published a paper in the journal ‘Pain’ advocating the use of opiates for pain relief citing the one paragraph letter from Hershel Jick and Jane Porter as a reference. The article reviewed 38 patients maintained on opioid analgesics for non-malignant pain using Oxycodone, Methadone, Levorphanol, Propoxyphene, Meperidine, Codeine, and Pentazocine and concluded that opioid maintenance therapy can be safe, salutary and a more humane alternative to the options of surgery or no treatment.
If you tell a lie often enough it becomes the truth
The medical community were always against the use of opiates because they were aware of their addiction potential, and for once they were absolutely correct, so they stuck to their guns and voraciously attacked the published paper and both Foley and Portenoy. Despite this backlash of criticism, in the 1990’s Portenoy and the American Pain Foundation who Portenoy wasa director of, encouraged the tracking of this epidemic of pain suggesting that Pain be considered the ‘5th vital’ sign alongside blood pressure, temperature etc. Despite again, the strong insistence from the medical profession that opioids were addictive, in 1998 the Federation of State Medical Boards passed a policy that doctors who prescribed large amount of narcotics as part of a treatment strategy would not be subject to regulatory action, influenced, I might add, by pharmaceutical companies including David Haddox a senior Purdue Pharma executive. In 1997 it was revealed the the Federation had received $2 million from the opioid producers. Even the joint commission, a US independent, not for profit enterprise who accredits/certifies 21,000 health care organizations and programs, published a guide sponsored by Purdue ( so much for independence) stating that “some clinicians have inaccurate and exaggerated concerns about addiction, tolerance and risk of death despite there being no evidence”.
Conclusions
If only the medical profession had been steadfast in their correct belief that opiates for pain management can eventually cause addiction, then the growing number of pain management physicians working in hospices etc and the pharmaceutical companies including Purdue advocating a more widespread use of opiates may have been avoided. Dr Kathleen foley, Russell Portenoy, Lynn Webster, Cicely Saunders were not out to personally profit from their revolutionary push to change the system, but to take away the pain and suffering from many of their patients. Purdue Pharma on the other hand were in business to sell their product, so obviously their focus was profit driven and cared little of any potential damage caused to patients. What is astounding, is this one paragraph letter from a physician who loved statistics and keeping records became the standard reference as an argument of opiate non addiction which had been blown up into a foundation for a major change in medical practice. It appeared in one textbook as a ‘Landmark report’, and in Scientific America is was referred to as ‘an extensive study’. How fickle some humans are. What was to follow was the unscrupulous practice of prescribing painkillers as if they were m&m’s, causing thousands of deaths, lawsuits and jail sentences once the truth emerged, which we will discuss in the next article.
Robert Wakefield:
What are your policies towards treatment of addiction?
Quote from the movie Traffic 2000
References/Acknowledgments :
- The Neurochemical of happiness Christopher Bergland 2012 Psychology today
- Endorphins Encyclopedia.com
- Understanding Endorphins & their importance in pain management Sprouse, Blum, Smith, Sugai, Porsa, 2010 NCBI
- Proopiomelanocortin Wikipedia
- Tachykinins & their receptors: Contribution to physiological control & the mechanisms of disease Steinhoff, Mentzer, Geppetti, Pothoulakis, Bunnett 2014 NCBI
- Addiction rare in patients treated with narcotics letter New England journal of medicine 1980 Hershel Jicks & Jane Porter
- Dreamland Book 2015 Sam Quinones
- Doctor who wrote a 1980 letter on painkillers regrets that it fed the opioid crisis Andrea Hsu 2017 Shots
- Meperidine, Percodan, Hydromorphone Drugs.com
- Mundipharma website – History/what we do
- Drugs mogul with a vast philanthropic legacy Financial Times 2010 article Phil Davidson
- The secretive family making billions from the opiate crisis Chris Glazek 2017 esquire
- Total Pain: the work of Cicely Saunders & the maturing of a concept David Clark 2014 University of Glasgow
- The money and influence behind “ Pain as the 5th Vital sign” TPR The poison review 2012
- movie ‘traffic’ 2000 quote quotes.net