The New York Times
September 10, 2007Drugs Banned, Many of World’s Poor Suffer in Pain
By DONALD G. McNEIL Jr.
WATERLOO, Sierra Leone — Although the rainy season was coming on fast, Zainabu Sesay was in no shape to help her husband. Ditches had to be dug to protect their cassava and peanuts, and their mud hut’s palm roof was sliding off.
But Mrs. Sesay was sick. She had breast cancer in a form that Western doctors rarely see anymore — the tumor had burst through her skin, looking like a putrid head of cauliflower weeping small amounts of blood at its edges.
“It bone! It booonnnne lie de fi-yuh!” she said of the pain — it burns like fire — in Krio, the blended language spoken in this country where British colonizers resettled freed slaves.
No one had directly told her yet, but there was no hope — the cancer was also in her lymph glands and ribs.
Like millions of others in the world’s poorest countries, she is destined to die in pain. She cannot get the drug she needs — one that is cheap, effective, perfectly legal for medical uses under treaties signed by virtually every country, made in large quantities, and has been around since Hippocrates praised its source, the opium poppy. She cannot get morphine.
That is not merely because of her poverty, or that of Sierra Leone. Narcotics incite fear: doctors fear addicting patients, and law enforcement officials fear drug crime. Often, the government elite who can afford medicine for themselves are indifferent to the sufferings of the poor.
The World Health Organization estimates that 4.8 million people a year with moderate to severe cancer pain receive no appropriate treatment. Nor do another 1.4 million with late-stage AIDS. For other causes of lingering pain — burns, car accidents, gunshots, diabetic nerve damage, sickle-cell disease and so on — it issues no estimates but believes that millions go untreated.
Figures gathered by the International Narcotics Control Board, a United Nations agency, make it clear: citizens of rich nations suffer less. Six countries — the United States, Canada, France, Germany, Britain and Australia — consume 79 percent of the world’s morphine, according to a 2005 estimate. The poor and middle-income countries where 80 percent of the world’s people live consumed only about 6 percent.
Some countries imported virtually none. “Even if the president gets cancer pain, he will get no analgesia,” said Willem Scholten, a World Health Organization official who studies the issue.
In 2004, consumption of morphine per person in the United States was about 17,000 times that in Sierra Leone.
At pain conferences, doctors from Africa describe patients whose pain is so bad that they have chosen other remedies: hanging themselves or throwing themselves in front of trucks.
Westerners tend to assume that most people in tropical countries die of malaria, AIDS, worm diseases and unpronounceable ills. But as vaccines, antibiotics and AIDS drugs become more common, more and more are surviving past measles, infections, birth complications and other sources of a quick death. They grow old enough to die slowly of cancer.
About half the six million cancer deaths in the world last year were in poor countries, and most diagnoses were made late, when death was inevitable. But first, there was agony. About 80 percent of all cancer victims suffer severe pain, the W.H.O. estimates, as do half of those dying of AIDS.
Morphine’s raw ingredient — opium — is not in short supply. Poppies are grown for heroin, of course, in Afghanistan and elsewhere. But vast fields for morphine and codeine are also grown in India, Turkey, France, Australia and other countries.
Nor is it expensive, even by the standards of developing nations. One hospice in Uganda, for example, mixes its own liquid morphine so cheaply that a three-week supply costs less than a loaf of bread.
Nonetheless, it is still routinely denied in many poor countries.
“It’s the intense fear of addiction, which is often misunderstood,” said David E. Joranson, director of the Pain Policy Study Group at the University of Wisconsin’s medical school, who has worked to change drugs laws around the world. “Pain relief hasn’t been given as much attention as the war on drugs has.”
Doctors in developing countries, he explained, often have beliefs about narcotics that prevailed in Western medical schools decades ago — that they are inevitably addictive, carry high risks of killing patients and must be used sparingly, even if patients suffer.
Pain experts argue that it is cruel to deny them to the dying and that patients who recover from pain can usually be weaned off. Withdrawal symptoms are inevitable, they say — as they are if a diabetic stops insulin. But the benefits outweigh the risks.
Too Poor for Medicine
In Mrs. Sesay’s case, Alfred Lewis, a nurse from Shepherd’s Hospice, is doing what he can to ease her last days.
When he first saw her, her tumor was wrapped with clay and leaves prescribed by a local healer. The smell of her rotting skin made her feel ashamed.
She had seen a doctor at one of many low-cost “Indian clinics” who pulled at the breast with forceps so hard that she screamed, misdiagnosed her tumor as an infected boil, and gave her an injection in her buttocks that abscessed, adding to her misery.
Nothing can be done about the tumor, Mr. Lewis explained quietly. “All the bleeders are open,” he said. “Her risk now is hemorrhage. Only a knife-crazy surgeon would attend to her.”
Earlier diagnosis would probably not have changed her fate. Sierra Leone has no CAT scanners, and only one private hospital offers chemotherapy drug treatment. The Sesays are sharecroppers; they have no money.
So Mr. Lewis was making a daily 10-mile trip from Freetown, the capital, to change her dressing, sprinkle on antibiotics, and talk to her. He asked a neighbor to plait her hair for her, so she would look pretty. Mrs. Sesay said she could not be bothered.
“It’s necessary for to cope,” he said. “For to strive for be happy.”
“I ‘fraid for my life,” she said.
“Are you ‘fraid for die?”
“No, I not ‘fraid. I ready.”
“So what is your relationship to God? You good with God?”
“I pray me one.”
He asked her, half-jokingly, if she still had sex with her husband.
No, she said, since the illness, he stayed in his room and she stayed in hers. She, too, was joking. In their hut, there is only the one room.
Life has become hard, she added, and her husband is getting too old for farm labor. She, too, is getting old, she said — she is somewhere in her 40s.
“We are really being punish.”
For her pain, Mr. Lewis gave her generic Tylenol and tramadol, a relative of codeine that is only 10 percent as potent as morphine. It was all he could offer. “I would consider putting her on morphine now, if we had morphine,” Mr. Lewis said.
In New York, she would have already started on it, or an equivalent like oxycodone or fentanyl.
Even if his hospice could get it, Mr. Lewis could not give it to her.
Under Sierra Leone law, morphine may be handled only by a pharmacist or doctor, explained Gabriel Madiye, the hospice’s founder. But in all Sierra Leone there are only about 100 doctors — one for every 54,000 people, compared with one for every 350 in the United States.
In only a few places — in Uganda, for example — does the law allow trained nurses to prescribe morphine.
And pharmacists will not stock it.
“It’s opioid phobia,” Mr. Madiye said. “We are coming out of a war where a lot of human rights violations were caused by drug abuse.”
During the war, the rebel assault on the capital was called Operation No Living Thing. Child soldiers were hardened with mysterious drugs with names like gunpowder and brown-brown, along with glue and alcohol.
Esther Walker, a British nurse who sometimes works with Mr. Lewis, said she once gave a lecture on palliative care at the national medical school.
There were 28 students, and she asked them, “Who has seen someone die peacefully in Sierra Leone?”
“Not one had,” she said.
The Burden on the Young
In the poorest countries like this one, even babies suffer.
Momoh Sesay, 2, (no relation to Zainabu) is a pretty lucky little guy — for someone who tumbled into a cooking pot of boiling water.
He lost much of the skin on his thighs, and his belly is speckled with burns as if he had been sloshed with pink paint.
But he was fortunate enough to live close to Ola During Children’s Hospital, the leading pediatric institution.
No doctor was in. There was not even any electricity. At night, nurses thread IV lines into babies’ tiny limbs by candlelight. “And our eyes are not magnets,” one of them, Josephine Maajenneh Sillah, complained.
But they knew Momoh would die of shock and pumped in intravenous fluids and antibiotics.
If he had been born in New York, Momoh would have had skin grafts. Here, that is unthinkable.
Momoh was given saline washes, and his dead skin was scrubbed off with debridement, a painful procedure. In New York, he would have had morphine.
So probably would Abdulaziz Sankoh, 7, in another bed, who has sickle cell disease. He moans at night when twisted blood cells clump together and jam the arteries in his spindly legs, slowly killing his bone marrow.
As would Musa Shariff, an 8-month-old boy whose scalp is so swollen by meningitis that his eyelids cannot close. Dr. Muctar Jalloh, the hospital director, said he would not prescribe morphine to babies or toddlers if he had it. Only in the case of third-degree burns, like Momoh’s, did he say: “I would consider it — maybe.”
That flies in the face of Western medicine, which allows careful use even in premature infants.
The strongest painkiller that Momoh, Abdulaziz and Musa can take, if their parents can afford $1.65 per vial, is tramadol. It is impossible to know what morphine would cost if it were here, but it is sold in India at 1.7 cents a pill by the same company that makes tramadol.
The nurses know the prices because they sell the drugs that are available. They have not been paid for three years, they say, so they support themselves in part by filling the prescriptions that the doctors write. Kind as they are — they do extend credit, and are sometimes moved to charity by the children — it is a business.
That is the other reason Dr. Jalloh said he would not order morphine. “I wouldn’t want to leave my staff in charge of morphine,” he said. “The potential for abuse is so high.”
Worries About Abuse
If morphine were to be imported to Sierra Leone, it would be overseen by two agencies: the National Pharmacy Board and the National Drugs Control Agency.
Kande Bangura, the rangy, sharp-eyed former police commander who runs the drug control agency, said the country had a serious drug-abuse problem, especially among former child soldiers.
It also is a smuggling route. He spread out pictures of an autopsy on a British citizen with Nigerian roots who had dropped dead in line at Freetown’s airport. His intestines were found to be packed with condoms full of cocaine, one of which had burst.
Mr. Bangura said he had no objections to morphine, however, “as long as it’s for medical use and is strictly controlled by the country’s chief pharmacist.”
Wiltshire C. N. Johnson, the chief of the enforcement arm of the National Pharmacy Board, explained why painkillers were not imported.
Scarce funds must go to the top five causes of death, he said: diarrhea, pneumonia, tuberculosis, malaria and sexually transmitted diseases. “I’m not saying that palliative care doesn’t top the list, too,” he said. “But it’s officially a very small percentage of the requirement.”
He also had fears like those of Dr. Jalloh. “There’s no way we’re going to put morphine in the hands of a pharmacy technician,” he said. “In the wrong hands, drugs, like guns, are a greater evil than a cure.”
Mr. Madiye, who predicted exactly those answers before the interviews started, vented his frustration later.
He founded Shepherd’s Hospice in 1995, saw it destroyed in the civil war and rebuilt it. But he cannot get the one drug that would let him give people like Zainabu Sesay the dignified deaths that in the West would be their birthright.
“How can they say there is no demand when they don’t allow it?” he asked. “How can they be so sure that it will get out of control when they haven’t even tried it?”
07 October 2013
01 July 2013
Preferring more pain to less
In his recent Why feeling more pain may be better for you, Tom Stafford reminds us of the classic Kahneman study which yielded both the Peak End rule and succor to sadistic proctologists.
If that description didn't tempt you to go read the column, here's the super short version: Kahneman found that when asked how bad a painful experience was, people recall (roughly) the average of how bad it was at it's worst --the 'peak'-- and how bad it was at the end --the, uh, 'end'. This, Kahneman claims, raises a real ethical dilemma:
Imagine a physician conducting a colonoscopy; the patient is in intense pain. The examination is complete and the physician could terminate the procedure now, providing instant relief --and a permanently negative evaluation of the whole episode. Should the physician seek the patient's consent to extend the pain for a while in order to form and retain an improved opinion of the procedure….a patient who has had two otherwise identical procedures that differ in the abruptnees of relief will prefer [the one with] more total pain but provides a better end….When the experiencing self and the remembering self disagree, whom are we to believe? (1994, p.21)
Stafford doesn't answer this question. Rather he turns to the Peak-End Rule as a broader phenomena (as other research shows) to make a different point
"But I think the most important lesson of the Peak-End experiments is something else. Rather than saying that the duration isn't important, the rule tells me that it is just as important to control how we mentally package our time. What defines an “experience” is somewhat arbitrary. If a weekend break where you forget everything can be as refreshing as a two-week holiday then maybe a secret to a happy life is to organise your time so it is broken up into as many distinct (and enjoyable) experiences as possible, rather than being just an unbroken succession of events which bleed into one another in memory."
I have to politely demur on what's the most interesting lesson. I've spent the last 10 years ---my entire professional career thus far--- thinking about some of the deep philosophical issues Kahneman's question raises.
Presumably, as Kahneman notes, none of us as patients would agree (while in pain) to the physician prolonging our pain. But we would then look jealously upon our friend whose doctor didn't ask her permission and whose colonoscopy was (as she recalls it) easier than our own. From our deathbed perspectives, my life contained more suffering. It was in that respect worse than hers.
Of course, we're both mistaken about how our total suffering compares. Arguably, in some cases, our lives can be better or worse than we believe them to be. If your loved ones' affection had been a cruel facade behind which they constantly ridiculed you, even though you never found out, your life was still worse than you thought it was. But are mistakes about how much we suffered like this?
Look at what's going on here. We need to decide what makes pain bad. We need to figure out how to aggregate goods (e.g., do we simply add up the good and bad?). We need to understand what constitutes human well-being ---to decide what makes a life as a whole good. We need to deal with organic unities (i.e., whether the arrangement of a good and a bad may yield an overall value that's different from the simple sum --schadenfreude is a common example). We need to deal with the asymmetries of past and future pains. Indeed, this road takes us straight to fundamental questions about the nature of intrinsic value. (That's the road I followed to my dissertation)
John Broome took this issue up in his 1996 'More pain or less?' with the straightforward claim that the person's mistaken evaluations are irrelevant. Pains are intrinsically bad. There should be less of it.
Stephanie Beardman who was finishing up at Rutgers just as I entered, came up with a more sophisticated response in her The choice between current and retrospective evaluations of pain (here's a pdf). In it she sets out several alternative interpretations of Kahneman's results and articulates some ways in which our preferences about past experiences may be more sophisticated than they at first seem.
Since she does a lot of what philosophers do best ---laying out the conceptual territory--- some of you empirically-minded folks may find it a useful source for developing uninvestigated hypotheses. It's also just a very nice gateway to some of the deep philosophical issues lurking just beneath the surface of seemingly easy questions. (Though be forewarned, it's a gateway drug too. A few early conversations with Stephanie definitely played a role in my getting hooked). In any event, you should read it.
If that description didn't tempt you to go read the column, here's the super short version: Kahneman found that when asked how bad a painful experience was, people recall (roughly) the average of how bad it was at it's worst --the 'peak'-- and how bad it was at the end --the, uh, 'end'. This, Kahneman claims, raises a real ethical dilemma:
Imagine a physician conducting a colonoscopy; the patient is in intense pain. The examination is complete and the physician could terminate the procedure now, providing instant relief --and a permanently negative evaluation of the whole episode. Should the physician seek the patient's consent to extend the pain for a while in order to form and retain an improved opinion of the procedure….a patient who has had two otherwise identical procedures that differ in the abruptnees of relief will prefer [the one with] more total pain but provides a better end….When the experiencing self and the remembering self disagree, whom are we to believe? (1994, p.21)
Stafford doesn't answer this question. Rather he turns to the Peak-End Rule as a broader phenomena (as other research shows) to make a different point
"But I think the most important lesson of the Peak-End experiments is something else. Rather than saying that the duration isn't important, the rule tells me that it is just as important to control how we mentally package our time. What defines an “experience” is somewhat arbitrary. If a weekend break where you forget everything can be as refreshing as a two-week holiday then maybe a secret to a happy life is to organise your time so it is broken up into as many distinct (and enjoyable) experiences as possible, rather than being just an unbroken succession of events which bleed into one another in memory."
I have to politely demur on what's the most interesting lesson. I've spent the last 10 years ---my entire professional career thus far--- thinking about some of the deep philosophical issues Kahneman's question raises.
Presumably, as Kahneman notes, none of us as patients would agree (while in pain) to the physician prolonging our pain. But we would then look jealously upon our friend whose doctor didn't ask her permission and whose colonoscopy was (as she recalls it) easier than our own. From our deathbed perspectives, my life contained more suffering. It was in that respect worse than hers.
Of course, we're both mistaken about how our total suffering compares. Arguably, in some cases, our lives can be better or worse than we believe them to be. If your loved ones' affection had been a cruel facade behind which they constantly ridiculed you, even though you never found out, your life was still worse than you thought it was. But are mistakes about how much we suffered like this?
Look at what's going on here. We need to decide what makes pain bad. We need to figure out how to aggregate goods (e.g., do we simply add up the good and bad?). We need to understand what constitutes human well-being ---to decide what makes a life as a whole good. We need to deal with organic unities (i.e., whether the arrangement of a good and a bad may yield an overall value that's different from the simple sum --schadenfreude is a common example). We need to deal with the asymmetries of past and future pains. Indeed, this road takes us straight to fundamental questions about the nature of intrinsic value. (That's the road I followed to my dissertation)
John Broome took this issue up in his 1996 'More pain or less?' with the straightforward claim that the person's mistaken evaluations are irrelevant. Pains are intrinsically bad. There should be less of it.
Stephanie Beardman who was finishing up at Rutgers just as I entered, came up with a more sophisticated response in her The choice between current and retrospective evaluations of pain (here's a pdf). In it she sets out several alternative interpretations of Kahneman's results and articulates some ways in which our preferences about past experiences may be more sophisticated than they at first seem.
Since she does a lot of what philosophers do best ---laying out the conceptual territory--- some of you empirically-minded folks may find it a useful source for developing uninvestigated hypotheses. It's also just a very nice gateway to some of the deep philosophical issues lurking just beneath the surface of seemingly easy questions. (Though be forewarned, it's a gateway drug too. A few early conversations with Stephanie definitely played a role in my getting hooked). In any event, you should read it.
12 April 2013
Digital Humanities SoCal Research Slam
For those in Southern California…..
Details here
DH SoCal Research Slam
Location: California State University, Northridge
Date: May 4, 2013
Deadline: April 15, 2013
DH SoCal is a network dedicated to building community and collaboration amongst digital humanists in Southern California. On May 4, 2013 we are holding our first research slam at California State University, Northridge. This one-day event will be designed to showcase Digital Humanities work being done in California and to create opportunities for interaction between digital humanists from around the region.
We invite proposals for poster presentations, short talks, and issue-based discussion panels in any area of the Digital Humanities. To propose a topic, please fill out the form below by April 15, 2013. The precise format of the event will depend on the number and types of submissions we receive. We will make every effort to accommodate all submissions, and you will be notified shortly after the deadline.
Please join us, show off what you are working on, and learn about the exciting work being done by other DHers in Southern California.
Details here
01 April 2013
Respiratory depression with oral tramadol
Respiratory depression following oral tramadol in a patient with impaired renal function
S. K. Barnung*, M. Treschow and F. M. Borgbjerg
Received 2 September 1996; revised 14 December 1996; accepted 6 January 1997. Available online 6 October 1998.
http://dx.doi.org/10.1016/S0304-3959(97)03350-2S. K. Barnung*, M. Treschow and F. M. Borgbjerg
Received 2 September 1996; revised 14 December 1996; accepted 6 January 1997. Available online 6 October 1998.
27 January 2013
Chronic pain in children
ScienceDirect - Pain : The impact of chronic pain in children and adolescents: Development and initial validation of a child and parent version of the Pain Experience Questionnaire
doi:10.1016/j.pain.2007.06.002 How to Cite or Link Using DOI (Opens New Window)
Copyright © 2007 International Association for the Study of Pain Published by Elsevier B.V.
The impact of chronic pain in children and adolescents: Development and initial validation of a child and parent version of the Pain Experience Questionnaire
Abstract
Psychosocial factors are crucial for understanding and treating chronic pain in adults, but also in children. For children, very few questionnaires for a multidimensional pain assessment exist. In adults, the Multidimensional Pain Inventory (MPI; [Kerns RD, Turk DC, Rudy TE. The West Haven-Yale Multidimensional Pain Inventory (WHYMPI). Pain 1985;23:345–56]) has been widely used to determine patients’ adjustment to chronic pain. Using one section of the MPI as a model, we developed and evaluated the Pain Experience Questionnaire (PEQ) – child and parent version – that assesses the psychosocial impact of chronic pain in children and adolescents. As substantiated by confirmatory factor analysis in a sample of 111 children and adolescents (7–18 years) with chronic pain, the child PEQ entails the subscales pain severity, pain-related interference, affective distress and perceived social support. The parent version contains the subscales severity of the child’s pain, interference and parental affective distress. Child and parent PEQ subscales were internally consistent. Age was unrelated to PEQ subscale scores. Girls and their mothers endorsed significantly greater pain severity, interference and affective distress. Validity analyses yielded a pattern of correlations with measures of depression, trait anxiety, pain activity, child behaviors, pain-related cognitions, and parenting behavior that is consistent with psychometric data of the adult MPI and previous findings on psychosocial aspects of chronic pediatric pain. Significant differences between children depending on patient status (participants in experimental or treatment studies, outpatients, inpatients) suggest external validity of the PEQ. Despite the preliminary nature of the psychometric evaluation, the child and parent PEQ seem promising for a comprehensive assessment of pediatric pain.
Keywords: Pediatric pain; Psychosocial impact; Assessment; Questionnaire; Child report; Parental report
22 January 2013
ScienceDirect - Pain : Catastrophizing and perceived partner responses to pain
Pain : Catastrophizing and perceived partner responses to pain:
"Catastrophizing and perceived partner responses to pain
Jennifer L. Boothby, , a, Beverly E. Thornb, Lorraine Y. Overduina and L. Charles Wardc
Received 31 July 2003; Revised 12 February 2004; accepted 23 February 2004 AIB-16214
Abstract
This study examined the relationship between catastrophizing and patient-perceived partner responses to pain behaviors. The Catastrophizing subscale of the Cognitive Coping Strategy Inventory and the West Haven–Yale Multidimensional Pain Inventory were completed by 62 adult chronic pain patients. Consistent with past research, catastrophizing and patient-perceived solicitous partner behaviors were positively correlated with negative pain outcomes. The communal coping theory of catastrophizing suggests that catastrophizing might be undertaken to solicit support and empathy from others. However, catastrophizing was not related to perceived solicitous partner behavior in this study. Rather, catastrophizing was associated with perceived punishing partner responses. Implications are that catastrophizing and perceived solicitous partner behaviors are independently associated with pain and that catastrophizing may not be reinforced by empathy from significant others."
"Catastrophizing and perceived partner responses to pain
Jennifer L. Boothby, , a, Beverly E. Thornb, Lorraine Y. Overduina and L. Charles Wardc
Received 31 July 2003; Revised 12 February 2004; accepted 23 February 2004 AIB-16214
Abstract
This study examined the relationship between catastrophizing and patient-perceived partner responses to pain behaviors. The Catastrophizing subscale of the Cognitive Coping Strategy Inventory and the West Haven–Yale Multidimensional Pain Inventory were completed by 62 adult chronic pain patients. Consistent with past research, catastrophizing and patient-perceived solicitous partner behaviors were positively correlated with negative pain outcomes. The communal coping theory of catastrophizing suggests that catastrophizing might be undertaken to solicit support and empathy from others. However, catastrophizing was not related to perceived solicitous partner behavior in this study. Rather, catastrophizing was associated with perceived punishing partner responses. Implications are that catastrophizing and perceived solicitous partner behaviors are independently associated with pain and that catastrophizing may not be reinforced by empathy from significant others."
06 December 2012
Quench the Fire Run
Dear SoCal friends,
Causalgia (aka CRPS II or RSD) should be very high on your list of things that you do not want. If you're the sort who runs without being chased, come out this Sunday and support the USC Pain Center.
Also, MacGyver will be there!
Love,
Adam
02 November 2012
Malingering in people with pain
Blackwell Synergy - Pain Medicine, Volume 1 Issue 3 Page 280-282, September 2000 (Article Abstract
Volume 1 Issue 3 Page 280-282, September 2000
(2000) A Case of Malingering: Feigning a Painful Disorder in the Presence of True Medical Illness
Pain Medicine 1 (3) , 280–282 doi:10.1046/j.1526-4637.2000.00028.x
The potential for malingering must always be considered among patients presenting with pain. When malingering is identified, care may be discontinued. This case report describes a patient who feigned sickle cell crisis, a painful condition, in the presence of other identifiable and potentially painful medical illnesses.
26 August 2012
24 July 2012
Nocebo effects
Here's a nice post on some of the latest research on nocebo effects --the placebo's evil twin.
Are Warnings About the Side Effects of Drugs Making Us Sick? | NeuroTribes
I haven't looked into the nocebo effects for pain in too much detail. But I've profited immensely from carefully working through the placebo effect literature. I expect this could be similarly useful, especially in the differences between placebos and nocebos
I'd love to hear about any good philosophical work on nocebos.
05 July 2012
27 June 2012
More Sphenopalatine Ganglioneuralgia
I'm not yet over losing my ranking as the internet's number one source for all things sphenopalatine ganglioneuralgia. So, in a futile attempt to reclaim my crown, I share this little bit about ice cream headaches:
01 June 2012
ScienceDirect - Pain : Nicotine differentially activates inhibitory and excitatory neurons in the dorsal spinal cord
ScienceDirect - Pain : Nicotine differentially activates inhibitory and excitatory neurons in the dorsal spinal cord:
Matilde Cordero-Erausquin, Stéphanie Pons, Philippe Faure and Jean-Pierre Changeux,
Récepteurs et Cognition, CNRS URA2182, Institut Pasteur, 25 rue du Dr Roux, 75724, Paris Cedex 15, France
Abstract
Nicotinic agonists have well-documented antinociceptive properties when administered subcutaneously or intrathecally in mice. However, secondary mild to toxic effects are observed at analgesic doses, as a consequence of the activation of the large family of differentially expressed nicotinic receptors (nAChRs). In order to elucidate the action of nicotinic agonists on spinal local circuits, we have investigated the expression and function of nAChRs in functionally identified neurons of neonate mice spinal cord. Molecular markers, amplified at the single-cell level by RT-PCR, distinguished two neuronal populations in the dorsal horn of the spinal cord: GABAergic/glycinergic inhibitory interneurons, and calbindin (CA) or NK1 receptor (NK1-R) expressing, excitatory interneurons and projection neurons. The nicotinic response to acetylcholine of single cells was examined, as well as the pattern of expression of nAChR subunit transcripts in the same neuron. Beside the most expressed subunits 4, 2 and 7, the 2 subunit transcript was found in 19% of neurons, suggesting that agonists targeting 2* nAChRs may have specific actions at a spinal level without major supra-spinal effects. Both inhibitory and excitatory neurons responded to nicotinic stimulation, however, the nAChRs involved were markedly different. Whereas GABA/glycine interneurons preferentially expressed 462* nAChRs, 327* nAChRs were preferentially expressed by CA or NK1-R expressing neurons. Recorded neurons were also classified by firing pattern, for comparison to results from single-cell RT-PCR studies. Altogether, our results identify distinct sites of action of nicotinic agonists in circuits of the dorsal horn, and lead us closer to an understanding of mechanisms of nicotinic spinal analgesia."
Matilde Cordero-Erausquin, Stéphanie Pons, Philippe Faure and Jean-Pierre Changeux,
Récepteurs et Cognition, CNRS URA2182, Institut Pasteur, 25 rue du Dr Roux, 75724, Paris Cedex 15, France
Abstract
Nicotinic agonists have well-documented antinociceptive properties when administered subcutaneously or intrathecally in mice. However, secondary mild to toxic effects are observed at analgesic doses, as a consequence of the activation of the large family of differentially expressed nicotinic receptors (nAChRs). In order to elucidate the action of nicotinic agonists on spinal local circuits, we have investigated the expression and function of nAChRs in functionally identified neurons of neonate mice spinal cord. Molecular markers, amplified at the single-cell level by RT-PCR, distinguished two neuronal populations in the dorsal horn of the spinal cord: GABAergic/glycinergic inhibitory interneurons, and calbindin (CA) or NK1 receptor (NK1-R) expressing, excitatory interneurons and projection neurons. The nicotinic response to acetylcholine of single cells was examined, as well as the pattern of expression of nAChR subunit transcripts in the same neuron. Beside the most expressed subunits 4, 2 and 7, the 2 subunit transcript was found in 19% of neurons, suggesting that agonists targeting 2* nAChRs may have specific actions at a spinal level without major supra-spinal effects. Both inhibitory and excitatory neurons responded to nicotinic stimulation, however, the nAChRs involved were markedly different. Whereas GABA/glycine interneurons preferentially expressed 462* nAChRs, 327* nAChRs were preferentially expressed by CA or NK1-R expressing neurons. Recorded neurons were also classified by firing pattern, for comparison to results from single-cell RT-PCR studies. Altogether, our results identify distinct sites of action of nicotinic agonists in circuits of the dorsal horn, and lead us closer to an understanding of mechanisms of nicotinic spinal analgesia."
01 May 2012
10 February 2012
Labor pain
ScienceDaily (Jun. 4, 1997) — For almost 20 years, researchers have been examining a centuries-old phenomenon -- women helping women through childbirth. Continuous support from an experienced female companion, called a "doula" from the Greek word for servant, has been demonstrated to have impressive benefits, including shorter labors, less need for analgesia, and reduced likelihood of cesarean delivery. These findings about a time-proven, risk-free method come at a time when the focus in childbirth is on increased use of technology and medical intervention.
In a recent study, researchers John Kennell, M.D., and Susan K. McGrath, Ph.D., from the Department of Pediatrics at the Case Western Reserve University (CWRU) School of Medicine, looked at the childbirth experience of women at a Houston maternity hospital. Thirty-nine women were randomly chosen to be supported by a doula. Another 45 first-time mothers were randomly chosen to receive epidural analgesia to help control the pain of labor and delivery but were not supported by a doula. The day after delivery, both groups of women were asked to evaluate their pain levels and ability to cope with pain at three different times during childbirth. They rated their pain as ranging from "no pain" to "maximum pain" at the following times: 1) before receiving pain intervention (epidural analgesia or doula support), 2) after pain relief intervention, and 3) 24 hours after delivery. (Women who delivered by cesarean section were not included in the pain evaluation analysis.)
For women in both groups, pain was rated highest before the pain relief intervention, significantly less after the intervention, and much less again 24 hours after delivery. More importantly, when the pain evaluations from women in the doula group were compared to those from women in the epidural group, the two groups experienced equivalent levels of pain at all three measurement points.
Laboring women supported by a doula (with no pain relief medication) experienced the same levels of pain as women who received epidural analgesia, both during and after labor. Additionally, there were no differences in a laboring woman's ability to cope with pain whether she had an epidural or the continuous emotional support of an experienced doula.
According to the researchers, doula support is an effective, risk-free, non-pharmacologic, and inexpensive pain relief method that may be a viable alternative to epidural analgesia for many women in labor. Without the negative side effects and expense of an epidural, doula support offers the laboring woman a significant reduction in the pain of childbirth while also decreasing the chance for a cesarean delivery. Physicians, midwives, and consumers should consider these results when choosing obstetric pain relief.
The research team also included Vijay S. Varadarajulu, a premedical student at CWRU.
Adapted from materials provided by Johns Hopkins Children's Center.
Need to cite this story in your essay, paper, or report? Use one of the following formats:
APA
MLA
Johns Hopkins Children's Center (1997, June 4). Doula Support Found To Be A Risk-Free Alternative For Pain Relief During Childbirth. ScienceDaily. Retrieved March 19, 2008, from http://www.sciencedaily.com /releases/1997/06/970604100308.htm
Epidural Leads To Less Pain, More Assisted Deliveries
ScienceDaily (Nov. 22, 2005) — Women who receive epidurals during labor report less pain than those who choose opiates or natural childbirth, according to a systematic review of evidence.
Yet epidurals bring an increased risk of delivery assisted by forceps or vacuum. The pluses and minuses mean that a woman’s decision about pain relief is not clear-cut.
“Each woman will have to weigh how much it means to her to have a spontaneous vaginal delivery versus having more pain in labor,” said lead author Dr. Millicent Anim-Somuah of the Liverpool Women’s Hospital in England.
On a more positive note, mothers who receive the spinal injections are no more likely than others to require Caesarian sections or to suffer chronic backaches. Their infants are equally healthy soon after birth.
Epidural analgesia involves injecting a local anesthetic into the lower back to block pain impulses from the uterus and birth canal. Obstetricians introduced the technique in 1946, and 58 percent of American women now choose this form of pain relief during childbirth, according to the authors.
The review appears in the most recent issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
The reviewers analyzed 21 studies involving more than 6,000 women. Most of the participants were in the United States, England and Australia.
“It’s always been suspected that epidurals slow down your labor,” said Anim-Somuah. The study confirmed that the nerve block lengthens the stage during which the mother must push the baby through the birth canal. This leads to greater use of medication to stimulate contractions and a 38 percent increase in risk of instrumental delivery.
The precise timing of the epidural injection may be an important factor, says Todd Liu, M.D., a fellow of the American College of Obstetricians and Gynecologists who practices in New Jersey.
“Should you get your epidural when you first feel a contraction or when you are in a strong labor pattern?” Liu asked. “I would guess that there would be a higher [Caesarian section] rate if epidurals are given too early.”
Finally, there are certain “rare but potentially severe adverse effects” associated with epidurals, says the review. These include spinal cord injuries and permanent paralysis in the mother. These are so rare that incidence rates are currently unknown.
Randomized controlled trials like those included in Cochrane reviews are not well-suited to studying such uncommon events, said Anim-Somuah. “There should be some ongoing data collection as to whether these are occurring with epidurals.”
For now, Liu said, “My usual recommendation is that if labor is going to be long (usually with the first baby) and labor pains are very intense … then it is worth getting an epidural and accepting the potential risk.”
A potential weakness of the review is that only one trial studied childbirth without any painkillers at all.
Adapted from materials provided by Center for the Advancement of Health.
Need to cite this story in your essay, paper, or report? Use one of the following formats:
APA
MLA
Center for the Advancement of Health (2005, November 22). Epidural Leads To Less Pain, More Assisted Deliveries. ScienceDaily. Retrieved March 19, 2008, from http://www.sciencedaily.com /releases/2005/11/051122210414.htm
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From Chloroform To Epidurals: New Book By UF Physician Examines History Of Labor Pain Relief
ScienceDaily (Mar. 1, 2000) — GAINESVILLE, Fla.---Is the pain of childbirth an ancient curse, a meaningful passage to the beginning of a new life or simply a bout of agony to be endured with a generous helping of anesthesia?
Views of labor pain have shifted with the times, shaped by culture, but also by advances in medicine. Physicians have found reasonably effective ways of diminishing the most excruciating sensations, yet the 150-year history of anesthesia reveals what a complicated journey it has been, according to a University of Florida anesthesiologist.
"On the surface, it seems to be such a simple issue-there is pain and we can relieve it. Yet there are many philosophical and social ramifications, which have been viewed in very different ways through the years," said Dr. Donald Caton whose recently published book, "What A Blessing She Had Chloroform," delves into the medical and social history of relieving labor pain.
"Childbirth is such a very personal thing, so you see a range of reactions," Caton said. "Today, some women refuse anesthesia outright because they feel pain is part of the birth experience. Some refuse it for biblical reasons, citing the Book of Genesis story and its linking of punishment with childbirth."
And under the banner of feminism, women have alternated between demanding that anesthesia be given or insisting that it not.
The diversity of attitudes has at times caught the medical field off-guard. Caton, a professor of anesthesiology at UF's College of Medicine, says that early in his career he was surprised when some women would refuse his assistance. Now he sees obstetric pain relief as a fascinating case study of how science and culture evolve, influencing each other along the way.
Soon after the first modern anesthetic was introduced in 1846, some women began to push for its use in labor. Physicians, however, had to grapple with issues of safety -- and at a time when they were only beginning to learn how to investigate such questions scientifically.
"In 1820, they still had been learning that the body is composed of earth, air, fire and water and that disease is caused by an imbalance of those elements," Caton said. "So when anesthesia became available, physicians had a lot to sort through. It was first used for surgery, which makes sense because without pain relief, some operations simply couldn't be performed.
"But childbirth was seen as a natural process, and physicians had a very difficult time trying to figure out if the pain of it was a necessary part of that process. They needed to determine whether eliminating or at least diminishing pain would in itself cause labor to stop."
Though it would take into well into the next century to answer those questions, that didn't keep physicians from experimenting. In 1847, Scottish obstetrician James Young Simpson administered ether to a woman in delivery, just a few weeks after a Massachusetts dentist had publicly demonstrated its use for surgery. That same year, Fanny Wadsworth Longfellow, wife of the poet, became the first woman in the United States to give birth with the aid of pain relief.
In England, Queen Victoria was an early recipient. Then in 1859, when her oldest daughter gave birth, the queen offered the phrase that would become the title of Caton's book: "What a blessing she had chloroform."
But while physicians continued to study the effects of labor medications, obstetric anesthesia was far from routine. By the early 20th century, American feminists had become more and more impatient that labor pain relief was not widely available.
They campaigned for a new European technique called Twilight Sleep. Unfortunately, the combination of morphine and a disorienting drug called scopolamine was far from the perfect solution. Pain was still significant, and too high a dose could prove toxic. What little Twilight Sleep had to offer was of dubious value: the possibility that women would forget the birthing experience.
As the 20th century wore on, though, anesthesiologists became adept at relieving pain in a manner they believed to be safe for both mother and child. However, their confidence in its safety led to higher and higher doses, which sparked a backlash. English obstetrician Grantly Dick Read advocated a return to natural childbirth, and later French obstetrician Fernand Lamaze did as well. A new wave of feminism in 1960s and 1970s took up the cause against medicalized childbirth, arguing that physicians were taking away women's right to experience labor and delivery.
Today, Caton believes, the vehemence of the natural childbirth movement has passed. Women appear to have less pressure on them to choose or reject anesthesia. Currently, about 60 percent of women in the United States receive some form of pain relief for vaginal delivery, usually an epidural, a type of regional anesthesia.
"At the same time," Caton points out, "there is this residual idea in the culture as seen through literature, religion and politics that maybe pain has meaning and has important social benefits," such as establishing family bonds, inspiring people to try harder or as a method of controlling criminals.
"In childbirth, you continue to see that for some women, experiencing childbirth pain is extremely important to their personal and social development," Caton said. "But then there are a lot of people who think, 'I have local anesthesia when I go to the dentist's office, I'm certainly going to have it when I have my child.' So most of them do."
Adapted from materials provided by University Of Florida Health Science Center.
Need to cite this story in your essay, paper, or report? Use one of the following formats:
APA
MLA
University Of Florida Health Science Center (2000, March 1). From Chloroform To Epidurals: New Book By UF Physician Examines History Of Labor Pain Relief. ScienceDaily. Retrieved March 19, 2008, from http://www.sciencedaily.com /releases/2000/02/000228103624.htm
In a recent study, researchers John Kennell, M.D., and Susan K. McGrath, Ph.D., from the Department of Pediatrics at the Case Western Reserve University (CWRU) School of Medicine, looked at the childbirth experience of women at a Houston maternity hospital. Thirty-nine women were randomly chosen to be supported by a doula. Another 45 first-time mothers were randomly chosen to receive epidural analgesia to help control the pain of labor and delivery but were not supported by a doula. The day after delivery, both groups of women were asked to evaluate their pain levels and ability to cope with pain at three different times during childbirth. They rated their pain as ranging from "no pain" to "maximum pain" at the following times: 1) before receiving pain intervention (epidural analgesia or doula support), 2) after pain relief intervention, and 3) 24 hours after delivery. (Women who delivered by cesarean section were not included in the pain evaluation analysis.)
For women in both groups, pain was rated highest before the pain relief intervention, significantly less after the intervention, and much less again 24 hours after delivery. More importantly, when the pain evaluations from women in the doula group were compared to those from women in the epidural group, the two groups experienced equivalent levels of pain at all three measurement points.
Laboring women supported by a doula (with no pain relief medication) experienced the same levels of pain as women who received epidural analgesia, both during and after labor. Additionally, there were no differences in a laboring woman's ability to cope with pain whether she had an epidural or the continuous emotional support of an experienced doula.
According to the researchers, doula support is an effective, risk-free, non-pharmacologic, and inexpensive pain relief method that may be a viable alternative to epidural analgesia for many women in labor. Without the negative side effects and expense of an epidural, doula support offers the laboring woman a significant reduction in the pain of childbirth while also decreasing the chance for a cesarean delivery. Physicians, midwives, and consumers should consider these results when choosing obstetric pain relief.
The research team also included Vijay S. Varadarajulu, a premedical student at CWRU.
Adapted from materials provided by Johns Hopkins Children's Center.
Need to cite this story in your essay, paper, or report? Use one of the following formats:
APA
MLA
Johns Hopkins Children's Center (1997, June 4). Doula Support Found To Be A Risk-Free Alternative For Pain Relief During Childbirth. ScienceDaily. Retrieved March 19, 2008, from http://www.sciencedaily.com /releases/1997/06/970604100308.htm
Epidural Leads To Less Pain, More Assisted Deliveries
ScienceDaily (Nov. 22, 2005) — Women who receive epidurals during labor report less pain than those who choose opiates or natural childbirth, according to a systematic review of evidence.
Yet epidurals bring an increased risk of delivery assisted by forceps or vacuum. The pluses and minuses mean that a woman’s decision about pain relief is not clear-cut.
“Each woman will have to weigh how much it means to her to have a spontaneous vaginal delivery versus having more pain in labor,” said lead author Dr. Millicent Anim-Somuah of the Liverpool Women’s Hospital in England.
On a more positive note, mothers who receive the spinal injections are no more likely than others to require Caesarian sections or to suffer chronic backaches. Their infants are equally healthy soon after birth.
Epidural analgesia involves injecting a local anesthetic into the lower back to block pain impulses from the uterus and birth canal. Obstetricians introduced the technique in 1946, and 58 percent of American women now choose this form of pain relief during childbirth, according to the authors.
The review appears in the most recent issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
The reviewers analyzed 21 studies involving more than 6,000 women. Most of the participants were in the United States, England and Australia.
“It’s always been suspected that epidurals slow down your labor,” said Anim-Somuah. The study confirmed that the nerve block lengthens the stage during which the mother must push the baby through the birth canal. This leads to greater use of medication to stimulate contractions and a 38 percent increase in risk of instrumental delivery.
The precise timing of the epidural injection may be an important factor, says Todd Liu, M.D., a fellow of the American College of Obstetricians and Gynecologists who practices in New Jersey.
“Should you get your epidural when you first feel a contraction or when you are in a strong labor pattern?” Liu asked. “I would guess that there would be a higher [Caesarian section] rate if epidurals are given too early.”
Finally, there are certain “rare but potentially severe adverse effects” associated with epidurals, says the review. These include spinal cord injuries and permanent paralysis in the mother. These are so rare that incidence rates are currently unknown.
Randomized controlled trials like those included in Cochrane reviews are not well-suited to studying such uncommon events, said Anim-Somuah. “There should be some ongoing data collection as to whether these are occurring with epidurals.”
For now, Liu said, “My usual recommendation is that if labor is going to be long (usually with the first baby) and labor pains are very intense … then it is worth getting an epidural and accepting the potential risk.”
A potential weakness of the review is that only one trial studied childbirth without any painkillers at all.
Adapted from materials provided by Center for the Advancement of Health.
Need to cite this story in your essay, paper, or report? Use one of the following formats:
APA
MLA
Center for the Advancement of Health (2005, November 22). Epidural Leads To Less Pain, More Assisted Deliveries. ScienceDaily. Retrieved March 19, 2008, from http://www.sciencedaily.com /releases/2005/11/051122210414.htm
--------
From Chloroform To Epidurals: New Book By UF Physician Examines History Of Labor Pain Relief
ScienceDaily (Mar. 1, 2000) — GAINESVILLE, Fla.---Is the pain of childbirth an ancient curse, a meaningful passage to the beginning of a new life or simply a bout of agony to be endured with a generous helping of anesthesia?
Views of labor pain have shifted with the times, shaped by culture, but also by advances in medicine. Physicians have found reasonably effective ways of diminishing the most excruciating sensations, yet the 150-year history of anesthesia reveals what a complicated journey it has been, according to a University of Florida anesthesiologist.
"On the surface, it seems to be such a simple issue-there is pain and we can relieve it. Yet there are many philosophical and social ramifications, which have been viewed in very different ways through the years," said Dr. Donald Caton whose recently published book, "What A Blessing She Had Chloroform," delves into the medical and social history of relieving labor pain.
"Childbirth is such a very personal thing, so you see a range of reactions," Caton said. "Today, some women refuse anesthesia outright because they feel pain is part of the birth experience. Some refuse it for biblical reasons, citing the Book of Genesis story and its linking of punishment with childbirth."
And under the banner of feminism, women have alternated between demanding that anesthesia be given or insisting that it not.
The diversity of attitudes has at times caught the medical field off-guard. Caton, a professor of anesthesiology at UF's College of Medicine, says that early in his career he was surprised when some women would refuse his assistance. Now he sees obstetric pain relief as a fascinating case study of how science and culture evolve, influencing each other along the way.
Soon after the first modern anesthetic was introduced in 1846, some women began to push for its use in labor. Physicians, however, had to grapple with issues of safety -- and at a time when they were only beginning to learn how to investigate such questions scientifically.
"In 1820, they still had been learning that the body is composed of earth, air, fire and water and that disease is caused by an imbalance of those elements," Caton said. "So when anesthesia became available, physicians had a lot to sort through. It was first used for surgery, which makes sense because without pain relief, some operations simply couldn't be performed.
"But childbirth was seen as a natural process, and physicians had a very difficult time trying to figure out if the pain of it was a necessary part of that process. They needed to determine whether eliminating or at least diminishing pain would in itself cause labor to stop."
Though it would take into well into the next century to answer those questions, that didn't keep physicians from experimenting. In 1847, Scottish obstetrician James Young Simpson administered ether to a woman in delivery, just a few weeks after a Massachusetts dentist had publicly demonstrated its use for surgery. That same year, Fanny Wadsworth Longfellow, wife of the poet, became the first woman in the United States to give birth with the aid of pain relief.
In England, Queen Victoria was an early recipient. Then in 1859, when her oldest daughter gave birth, the queen offered the phrase that would become the title of Caton's book: "What a blessing she had chloroform."
But while physicians continued to study the effects of labor medications, obstetric anesthesia was far from routine. By the early 20th century, American feminists had become more and more impatient that labor pain relief was not widely available.
They campaigned for a new European technique called Twilight Sleep. Unfortunately, the combination of morphine and a disorienting drug called scopolamine was far from the perfect solution. Pain was still significant, and too high a dose could prove toxic. What little Twilight Sleep had to offer was of dubious value: the possibility that women would forget the birthing experience.
As the 20th century wore on, though, anesthesiologists became adept at relieving pain in a manner they believed to be safe for both mother and child. However, their confidence in its safety led to higher and higher doses, which sparked a backlash. English obstetrician Grantly Dick Read advocated a return to natural childbirth, and later French obstetrician Fernand Lamaze did as well. A new wave of feminism in 1960s and 1970s took up the cause against medicalized childbirth, arguing that physicians were taking away women's right to experience labor and delivery.
Today, Caton believes, the vehemence of the natural childbirth movement has passed. Women appear to have less pressure on them to choose or reject anesthesia. Currently, about 60 percent of women in the United States receive some form of pain relief for vaginal delivery, usually an epidural, a type of regional anesthesia.
"At the same time," Caton points out, "there is this residual idea in the culture as seen through literature, religion and politics that maybe pain has meaning and has important social benefits," such as establishing family bonds, inspiring people to try harder or as a method of controlling criminals.
"In childbirth, you continue to see that for some women, experiencing childbirth pain is extremely important to their personal and social development," Caton said. "But then there are a lot of people who think, 'I have local anesthesia when I go to the dentist's office, I'm certainly going to have it when I have my child.' So most of them do."
Adapted from materials provided by University Of Florida Health Science Center.
Need to cite this story in your essay, paper, or report? Use one of the following formats:
APA
MLA
University Of Florida Health Science Center (2000, March 1). From Chloroform To Epidurals: New Book By UF Physician Examines History Of Labor Pain Relief. ScienceDaily. Retrieved March 19, 2008, from http://www.sciencedaily.com /releases/2000/02/000228103624.htm
21 December 2011
Arthritis National Research Foundation
Arthritis sucks. Rheumatoid Arthritis is especially sucky.
Here's a gentle description of what happened to my grandmother from the Arthritis National Research Foundation.
So, this is me urging you to donate to the ARNF or other organization supporting scientific research into the causes and treatment of arthritis.
Donate to the ARNF
(If you're wealthy, I will love you forever if your donation puts my Uncle in his place.)
Here's a gentle description of what happened to my grandmother from the Arthritis National Research Foundation.
She once swam competitively, but no longer could. She had difficulty doing the shopping for her family. Everyday pleasures were dulled by pain. The simplest movements required tremendous effort and concentration.
Joyce Sontag was a victim of rheumatoid arthritis (RA), a debilitating, progressive autoimmune disease. She was diagnosed with the disease at the age of 35 and lived 37 long years fighting the disease's progress in her body and in her life. Sadly, her family watched this decline without being given much hope for relief or remission, other than the treatment of symptoms.
Mrs. Sontag was hospitalized at the Long Beach Memorial Medical Center when she died from complications of rheumatoid arthritis in 1993. The treatments she received for RA from the late 1950s to the 1990s often had more negative side effects than positive effects for pain relief. The disease spread beyond the joints to other organs. Gradually, Mrs. Sontag became more and more debilitated, suffering acute weight loss and spinal column degeneration.
So, this is me urging you to donate to the ARNF or other organization supporting scientific research into the causes and treatment of arthritis.
Donate to the ARNF
(If you're wealthy, I will love you forever if your donation puts my Uncle in his place.)
16 December 2011
SERE training and torture
http://www.salon.com/news/feature/2007/06/21/cia_sere/print.html
The CIA's torture teachers
Psychologists helped the CIA exploit a secret military program to develop brutal interrogation tactics -- likely with the approval of the Bush White House.
By Mark Benjamin
Jun. 21, 2007 | There is growing evidence of high-level coordination between the Central Intelligence Agency and the U.S. military in developing abusive interrogation techniques used on terrorist suspects. After the Sept. 11 attacks, both turned to a small cadre of psychologists linked to the military's secretive Survival, Evasion, Resistance and Escape program to "reverse-engineer" techniques originally designed to train U.S. soldiers to resist torture if captured, by exposing them to brutal treatment. The military's use of SERE training for interrogations in the war on terror was revealed in detail in a recently declassified report. But the CIA's use of such tactics -- working in close coordination with the military -- until now has remained largely unknown.
According to congressional sources and mental healthcare professionals knowledgeable about the secret program who spoke with Salon, two CIA-employed psychologists, James Mitchell and Bruce Jessen, were at the center of the program, which likely violated the Geneva Conventions on the treatment of prisoners. The two are currently under investigation: Salon has learned that Daniel Dell'Orto, the principal deputy general counsel at the Department of Defense, sent a "document preservation" order on May 15 to the chairman of the Joint Chiefs of Staff and other top Pentagon officials forbidding the destruction of any document mentioning Mitchell and Jessen or their psychological consulting firm, Mitchell, Jessen and Associates, based in Spokane, Wash. Dell'Orto's order was in response to a May 1 request from Sen. Carl Levin, the Democratic chairman of the Senate Armed Services Committee, who is investigating the abuse of prisoners in U.S. custody.
Mitchell and Jessen have worked as contractors for the CIA since 9/11. Both were previously affiliated with the military's SERE program, which at its main school at Fort Bragg puts elite special operations forces through brutal mock interrogations, from sensory deprivation to simulated drowning.
A previously classified report by the Defense Department's inspector general, made public last month, revealed in vivid detail how the military -- in flat contradiction to previous denials -- used SERE as a basis for interrogating suspected al-Qaida prisoners at Guantánamo Bay, and later in Iraq and Afghanistan. Moreover, the involvement of the CIA, which was secretly granted broad authority by President Bush days after 9/11 to target terrorists worldwide, suggests that both the military and the spy agency were following a policy approved by senior Bush administration officials.
Close coordination between the CIA and the Pentagon is referred to in military lingo as "jointness." A retired high-level military official, familiar with the detainee abuse scandals, confirmed that such "jointness" requires orchestration at the top levels of government. "This says that somebody is acting as a bridge between the CIA and the Defense Department," he said, "because you've got the [CIA] side and the military side, and they are collaborating." Human-rights expert Scott Horton, who chairs the International Law Committee at the New York City Bar Association, also says that the cross-agency coordination "reflects the fact that the decision to introduce and develop these methods was made at a very high level."
On Wednesday, dozens of psychologists made public a joint letter to American Psychological Association president Sharon Brehm fingering another CIA-employed psychologist, R. Scott Shumate. Previous news reports led the American Medical Association and the American Psychiatric Association to ban their members from participating in interrogations, but the issue has remained divisive within the American Psychological Association, which has not forbidden the practice. "We write you as psychologists concerned about the participation of our profession in abusive interrogations of national security detainees at Guantanamo, in Iraq and Afghanistan, and at the so-called CIA 'black sites,'" the psychologists wrote. In violation of APA ethics, they said, "It is now indisputable that psychologists and psychology were directly and officially responsible for the development and migration of abusive interrogation techniques, techniques which the International Committee of the Red Cross has labeled 'tantamount to torture.'" [Ed. note: The full letter detailing the allegations of APA complicity can be read here.]
The letter cites a previously public biographical statement on Shumate that listed his position from April 2001 to May 2003 as "the chief operational psychologist for the CIA's Counter Terrorism Center." The bio also noted that Shumate "has been with several of the key apprehended terrorists" who have been held and interrogated by the agency since 9/11. At CTC, Shumate reported to Cofer Black, the former head of CTC who famously told Congress in September 2002, "There was a before 9/11, and there was an after 9/11. After 9/11 the gloves come off." Shumate's bio, obtained by Salon, has been removed from the InfowarCon 2007 conference Web site. Shumate did not return a phone call seeking comment.
The SERE-based program undermines assertions made for years by Bush administration officials that interrogations conducted by U.S. personnel are safe, effective and legal. SERE training, according to the Department of Defense inspector general's report, is specifically designed "to replicate harsh conditions that the service member might encounter if they are held by forces that do not abide by the Geneva Conventions."
"The irony -- and ultimately the tragedy -- in the migration of SERE techniques is that the program was specifically designed to protect our soldiers from countries that violated the Geneva Conventions," says Brad Olson, president of the Divisions for Social Justice within the American Psychological Association. "The result of the reverse-engineering, however, was that by making foreign detainees the target, it made us the country that violated the Geneva Conventions," he says.
There are striking similarities between descriptions of SERE training and the interrogation techniques employed by the military and CIA since 9/11. Soldiers undergoing SERE training are subject to forced nudity, stress positions, lengthy isolation, sleep deprivation, sexual humiliation, exhaustion from exercise, and the use of water to create a sensation of suffocation. "If you have ever had a bag on your head and somebody pours water on it," one graduate of that training program told Salon last year "it is real hard to breathe."
Many of those techniques show up in interrogation logs, human rights reports and news articles about detainee abuse that has taken place in Guantánamo, Afghanistan and Iraq. (The military late last year unveiled a new interrogation manual designed to put a stop to prisoner abuse.) An investigation released this month by the Council of Europe, a multinational human rights agency, added extreme sensory deprivation to the list of techniques that have been used by the CIA. The report said that extended isolation contributed to "enduring psychiatric and mental problems" of prisoners.
Isolation in cramped cells is also a key tenet of SERE training, according to soldiers who have completed the training and described it in detail to Salon. The effects of isolation are a specialty of Jessen's, who taught a class on "coping with isolation in a hostage environment" at a Maui seminar in late 2003, according to a Washington Times article published then. (Defense Department documents from the late 1990s describe Jessen as the "lead psychologist" for the SERE program.) Mitchell also spoke at that conference, according to the article. It described both men as "contracted to Uncle Sam to fight terrorism."
Mitchell's name surfaced again many months later. His role in interrogations was referenced briefly in a July 2005 New Yorker article by Jane Mayer, which focused largely on the military's use of SERE-based tactics at Guantánamo. The article described Mitchell's participation in a CIA interrogation of a high-value prisoner in March 2002 at an undisclosed location elsewhere -- presumably a secret CIA prison known as a "black site" -- where Mitchell urged harsh techniques that would break down the prisoner's psychological defenses, creating a feeling of "helplessness." But the article did not confirm Mitchell was a CIA employee, and it explored no further the connection between Mitchell's background with SERE and interrogations being conducted by the CIA.
A call to Mitchell and Jessen's firm for comment was not returned. The CIA would not comment on Mitchell and Jessen's work for the agency, though the contractual relationship is not one Mitchell and Jessen entirely concealed. They advertised their CIA credentials as exhibitors at a 2004 conference of the American Psychological Association in Honolulu.
In a statement to Salon, CIA spokesman George Little wrote that the agency's interrogation program had been "implemented lawfully, with great care and close review, producing a rich volume of intelligence that has helped the United States and other countries disrupt terrorist activities and save innocent lives."
Until last month, the Army had denied any use of SERE training for prisoner interrogations. "We do not teach interrogation techniques," Carol Darby, chief spokeswoman for the U.S. Army Special Operations Command at Fort Bragg, said last June when Salon asked about a document that appeared to indicate that instructors from the SERE school taught their methods to interrogators at Guantánamo.
But the declassified DoD inspector general's report described initiatives by high-level military officials to incorporate SERE concepts into interrogations. And it said that psychologists affiliated with SERE training -- people like Mitchell and Jessen -- played a critical role. According to the inspector general, the Army Special Operations Command's Psychological Directorate at Fort Bragg first drafted a plan to have the military reverse-engineer SERE training in the summer of 2002. At the same time, the commander of Guantánamo determined that SERE tactics might be used on detainees at the military prison. Then in September 2002, the Army Special Operations Command and other SERE officials hosted a "SERE psychologist conference" at Fort Bragg to brief staff from the military's prison at Guantánamo on the use of SERE tactics.
The chief of the Army Special Operations Command's Psychological Directorate was Col. Morgan Banks, the senior SERE psychologist, who has been affiliated with the training for years and helped establish the Army's first permanent training program that simulated captivity, according to a 2003 biographical statement. Banks also spent the winter of 2001 and 2002 at Bagram Airfield in Afghanistan "supporting combat operations against Al Qaida and Taliban fighters," according to one of his bios, which also said that Banks "provides technical support and consultation to all Army psychologists providing interrogation support."
In 2005, Banks helped draft ethical guidelines for the APA that say a psychologist supporting an interrogation is providing "a valuable and ethical role to assist in protecting our nation, other nations, and innocent civilians from harm." But as Salon reported last summer, six of the 10 psychologists who drafted that policy, including Banks, had close ties to the military. Some psychologists worry that the APA policy has made the organization an enabler of torture. Those ethics guidelines "gave the APA imprimatur to any of these techniques," says Steven Reisner, an APA member who has been closely tracking psychologists' role in interrogations. The policy, Reisner says, was developed by "psychologists directly involved in the interrogations."
Another of the six psychologists on the panel that drafted the guidelines who had ties to the military was Shumate. His bio for that APA task force said he worked as a "director of behavioral science" for the Defense Department. It never mentioned that he also worked for the CIA.
-- By Mark Benjamin
Link
The CIA's torture teachers
Psychologists helped the CIA exploit a secret military program to develop brutal interrogation tactics -- likely with the approval of the Bush White House.
By Mark Benjamin
Jun. 21, 2007 | There is growing evidence of high-level coordination between the Central Intelligence Agency and the U.S. military in developing abusive interrogation techniques used on terrorist suspects. After the Sept. 11 attacks, both turned to a small cadre of psychologists linked to the military's secretive Survival, Evasion, Resistance and Escape program to "reverse-engineer" techniques originally designed to train U.S. soldiers to resist torture if captured, by exposing them to brutal treatment. The military's use of SERE training for interrogations in the war on terror was revealed in detail in a recently declassified report. But the CIA's use of such tactics -- working in close coordination with the military -- until now has remained largely unknown.
According to congressional sources and mental healthcare professionals knowledgeable about the secret program who spoke with Salon, two CIA-employed psychologists, James Mitchell and Bruce Jessen, were at the center of the program, which likely violated the Geneva Conventions on the treatment of prisoners. The two are currently under investigation: Salon has learned that Daniel Dell'Orto, the principal deputy general counsel at the Department of Defense, sent a "document preservation" order on May 15 to the chairman of the Joint Chiefs of Staff and other top Pentagon officials forbidding the destruction of any document mentioning Mitchell and Jessen or their psychological consulting firm, Mitchell, Jessen and Associates, based in Spokane, Wash. Dell'Orto's order was in response to a May 1 request from Sen. Carl Levin, the Democratic chairman of the Senate Armed Services Committee, who is investigating the abuse of prisoners in U.S. custody.
Mitchell and Jessen have worked as contractors for the CIA since 9/11. Both were previously affiliated with the military's SERE program, which at its main school at Fort Bragg puts elite special operations forces through brutal mock interrogations, from sensory deprivation to simulated drowning.
A previously classified report by the Defense Department's inspector general, made public last month, revealed in vivid detail how the military -- in flat contradiction to previous denials -- used SERE as a basis for interrogating suspected al-Qaida prisoners at Guantánamo Bay, and later in Iraq and Afghanistan. Moreover, the involvement of the CIA, which was secretly granted broad authority by President Bush days after 9/11 to target terrorists worldwide, suggests that both the military and the spy agency were following a policy approved by senior Bush administration officials.
Close coordination between the CIA and the Pentagon is referred to in military lingo as "jointness." A retired high-level military official, familiar with the detainee abuse scandals, confirmed that such "jointness" requires orchestration at the top levels of government. "This says that somebody is acting as a bridge between the CIA and the Defense Department," he said, "because you've got the [CIA] side and the military side, and they are collaborating." Human-rights expert Scott Horton, who chairs the International Law Committee at the New York City Bar Association, also says that the cross-agency coordination "reflects the fact that the decision to introduce and develop these methods was made at a very high level."
On Wednesday, dozens of psychologists made public a joint letter to American Psychological Association president Sharon Brehm fingering another CIA-employed psychologist, R. Scott Shumate. Previous news reports led the American Medical Association and the American Psychiatric Association to ban their members from participating in interrogations, but the issue has remained divisive within the American Psychological Association, which has not forbidden the practice. "We write you as psychologists concerned about the participation of our profession in abusive interrogations of national security detainees at Guantanamo, in Iraq and Afghanistan, and at the so-called CIA 'black sites,'" the psychologists wrote. In violation of APA ethics, they said, "It is now indisputable that psychologists and psychology were directly and officially responsible for the development and migration of abusive interrogation techniques, techniques which the International Committee of the Red Cross has labeled 'tantamount to torture.'" [Ed. note: The full letter detailing the allegations of APA complicity can be read here.]
The letter cites a previously public biographical statement on Shumate that listed his position from April 2001 to May 2003 as "the chief operational psychologist for the CIA's Counter Terrorism Center." The bio also noted that Shumate "has been with several of the key apprehended terrorists" who have been held and interrogated by the agency since 9/11. At CTC, Shumate reported to Cofer Black, the former head of CTC who famously told Congress in September 2002, "There was a before 9/11, and there was an after 9/11. After 9/11 the gloves come off." Shumate's bio, obtained by Salon, has been removed from the InfowarCon 2007 conference Web site. Shumate did not return a phone call seeking comment.
The SERE-based program undermines assertions made for years by Bush administration officials that interrogations conducted by U.S. personnel are safe, effective and legal. SERE training, according to the Department of Defense inspector general's report, is specifically designed "to replicate harsh conditions that the service member might encounter if they are held by forces that do not abide by the Geneva Conventions."
"The irony -- and ultimately the tragedy -- in the migration of SERE techniques is that the program was specifically designed to protect our soldiers from countries that violated the Geneva Conventions," says Brad Olson, president of the Divisions for Social Justice within the American Psychological Association. "The result of the reverse-engineering, however, was that by making foreign detainees the target, it made us the country that violated the Geneva Conventions," he says.
There are striking similarities between descriptions of SERE training and the interrogation techniques employed by the military and CIA since 9/11. Soldiers undergoing SERE training are subject to forced nudity, stress positions, lengthy isolation, sleep deprivation, sexual humiliation, exhaustion from exercise, and the use of water to create a sensation of suffocation. "If you have ever had a bag on your head and somebody pours water on it," one graduate of that training program told Salon last year "it is real hard to breathe."
Many of those techniques show up in interrogation logs, human rights reports and news articles about detainee abuse that has taken place in Guantánamo, Afghanistan and Iraq. (The military late last year unveiled a new interrogation manual designed to put a stop to prisoner abuse.) An investigation released this month by the Council of Europe, a multinational human rights agency, added extreme sensory deprivation to the list of techniques that have been used by the CIA. The report said that extended isolation contributed to "enduring psychiatric and mental problems" of prisoners.
Isolation in cramped cells is also a key tenet of SERE training, according to soldiers who have completed the training and described it in detail to Salon. The effects of isolation are a specialty of Jessen's, who taught a class on "coping with isolation in a hostage environment" at a Maui seminar in late 2003, according to a Washington Times article published then. (Defense Department documents from the late 1990s describe Jessen as the "lead psychologist" for the SERE program.) Mitchell also spoke at that conference, according to the article. It described both men as "contracted to Uncle Sam to fight terrorism."
Mitchell's name surfaced again many months later. His role in interrogations was referenced briefly in a July 2005 New Yorker article by Jane Mayer, which focused largely on the military's use of SERE-based tactics at Guantánamo. The article described Mitchell's participation in a CIA interrogation of a high-value prisoner in March 2002 at an undisclosed location elsewhere -- presumably a secret CIA prison known as a "black site" -- where Mitchell urged harsh techniques that would break down the prisoner's psychological defenses, creating a feeling of "helplessness." But the article did not confirm Mitchell was a CIA employee, and it explored no further the connection between Mitchell's background with SERE and interrogations being conducted by the CIA.
A call to Mitchell and Jessen's firm for comment was not returned. The CIA would not comment on Mitchell and Jessen's work for the agency, though the contractual relationship is not one Mitchell and Jessen entirely concealed. They advertised their CIA credentials as exhibitors at a 2004 conference of the American Psychological Association in Honolulu.
In a statement to Salon, CIA spokesman George Little wrote that the agency's interrogation program had been "implemented lawfully, with great care and close review, producing a rich volume of intelligence that has helped the United States and other countries disrupt terrorist activities and save innocent lives."
Until last month, the Army had denied any use of SERE training for prisoner interrogations. "We do not teach interrogation techniques," Carol Darby, chief spokeswoman for the U.S. Army Special Operations Command at Fort Bragg, said last June when Salon asked about a document that appeared to indicate that instructors from the SERE school taught their methods to interrogators at Guantánamo.
But the declassified DoD inspector general's report described initiatives by high-level military officials to incorporate SERE concepts into interrogations. And it said that psychologists affiliated with SERE training -- people like Mitchell and Jessen -- played a critical role. According to the inspector general, the Army Special Operations Command's Psychological Directorate at Fort Bragg first drafted a plan to have the military reverse-engineer SERE training in the summer of 2002. At the same time, the commander of Guantánamo determined that SERE tactics might be used on detainees at the military prison. Then in September 2002, the Army Special Operations Command and other SERE officials hosted a "SERE psychologist conference" at Fort Bragg to brief staff from the military's prison at Guantánamo on the use of SERE tactics.
The chief of the Army Special Operations Command's Psychological Directorate was Col. Morgan Banks, the senior SERE psychologist, who has been affiliated with the training for years and helped establish the Army's first permanent training program that simulated captivity, according to a 2003 biographical statement. Banks also spent the winter of 2001 and 2002 at Bagram Airfield in Afghanistan "supporting combat operations against Al Qaida and Taliban fighters," according to one of his bios, which also said that Banks "provides technical support and consultation to all Army psychologists providing interrogation support."
In 2005, Banks helped draft ethical guidelines for the APA that say a psychologist supporting an interrogation is providing "a valuable and ethical role to assist in protecting our nation, other nations, and innocent civilians from harm." But as Salon reported last summer, six of the 10 psychologists who drafted that policy, including Banks, had close ties to the military. Some psychologists worry that the APA policy has made the organization an enabler of torture. Those ethics guidelines "gave the APA imprimatur to any of these techniques," says Steven Reisner, an APA member who has been closely tracking psychologists' role in interrogations. The policy, Reisner says, was developed by "psychologists directly involved in the interrogations."
Another of the six psychologists on the panel that drafted the guidelines who had ties to the military was Shumate. His bio for that APA task force said he worked as a "director of behavioral science" for the Defense Department. It never mentioned that he also worked for the CIA.
-- By Mark Benjamin
Link
01 September 2011
Marijuana pharmacology
Marijuana And the Brain
by John Gettman
High Times, March, 1995
In 1970, marijuana was placed on Schedule 1 of the Drug Enforcement Administration's controlled-substances list, largely because scientists feared that, like opiates, it had an extremely high potential for abuse and addiction. But the discovery of THC receptor sites in the brain refutes that thinking, and may force both scientists and the DEA to re-evaluate their positions.
Introduction
The next century will view the 1988 discovery of the THC receptor site in the brain as the pivotal event which led to the legalization of marijuana. Before this discovery, no one knew for sure just how the psychoactive chemical in marijuana worked on the brain. Throughout the 1970s and 1980s, researchers made tremendous strides in understanding how the brain works, by using receptor sites as switches which respond to various chemicals by regulating brain and body functions. The dominant fear about marijuana in the 20th century has been that its effects were somehow similar to the dangerously addictive effects of opiates such as morphine and heroin. Despite widespread decriminalization of marijuana in the United States in the 1970s, this concern has remained the basis for federal law and policies regarding the use and study of marijuana. The legal manifestation of this fear is the continued classification of marijuana as a Schedule I drug, a category shared by heroin and other drugs that are banned from medical use because of their dangerous, addictive qualities. While only 11 states have formally decriminalized possession of small amounts of marijuana, 45 states distinguish between marijuana and other Schedule I drugs for law-enforcement and sentencing purposes. Until the 1980s, technological limitations obstructed scientific understanding of the neuropharmacology of THC, of how the active ingredient in marijuana actually affects brain functions. Observations and conclusions about this subject, though based on some biological studies, were largely influenced by observations of behavior. This has allowed cultural prejudice to sustain the faith that marijuana is somehow related to heroin, and that research will eventually prove this hypothesis. Actually, the discovery of the THC receptor site and the subsequent research and observations it has inspired conclusively refute the hypothesis that marijuana is dope. Many important brain functions which affect human behavior involve the neurotransmitter dopamine. Serious drugs of abuse, such as heroin and cocaine, interfere with the brain's use of dopamine in manners that can seriously alter an individual's behavior. A drug's ability to affect the neural systems related to dopamine production has now become the defining characteristic of drugs with serious abuse potential.
According to the congressional Office of Technology Assessment, research over the last 10 years has proved that marijuana has no effect on dopamine-related brain systems - unless you are an inbred Lewis rat (see below), in which case abstention is recommended. The discovery of a previously unknown system of cannabinoid neural transmitters is profound. While century-old questions, such as why marijuana is nontoxic, are finally being answered, new, fascinating questions are emerging - as in the case of all great discoveries. In the words of Israeli researcher Raphael Mechoulam, the man who first isolated the structure of THC, "Why do we have cannabinoid receptors?" Mechoulam's theory will resonate well with marijuana smokers in the United States. He observes that "Cannabis is used by man not for its actions on memory of movement or movement coordination, but for its actions on memory and emotions," and asks, "Is it possible that the main task of cannabinoid receptors . . . (is) to modify our emotions, to serve as the links which transmit or transform or translate objective or subjective events into perceptions and emotions?" At a 1990 conference on cannabinoid research in Crete, Mechoulam concluded his remarks by saying, "Let us hope, however, that through better understanding of cannabis chemistry in the brain, we may also approach the chemistry of emotions."
A BRIEF HISTORY OF THC RESEARCH
The receptor breakthrough occurred in 1988 at the St. Louis University Medical School where Allyn Howlett, William Devane and their associates identified and characterized a cannabinoid receptor in a rat brain. The breakthrough has a long history leading up to it. Major figures in American and British organic chemistry, such as Roger Adams, Alex Todd and Sigmund Loewe, did important work in determining the pharmacology of cannabis in the 1940s and 1950s, but their work ground to a halt due to the disinterest cultivated by the 1937 federal ban on marijuana. While synthetic compounds were created which were close to the actual compound, THC, they were not equivalent to it. The structure of one related chemical, cannabidiol, was determined. After repeating the isolation of cannabidiol, in 1963 Mechoulam began work with Yehiel Gaoni that led to the determination of the biosynthetic pathway by which the plant synthesizes cannabinoids. In 1964 Gaoni and Mechoulam isolated tetrahydrocannabinol (THC) and a few years later they reported the first synthesis of THC. Following the identification of the active constituent in marijuana, scientific research began to fill in the gaps and build on Mechoulam's initial breakthrough. The neutral and acidic cannabinoids in cannabis were isolated, and their structures were elucidated. The absolute configurations were determined, as was a reasonable scheme of biogenesis. Total synthesis of the chemical was obtained, and the structure-activity relationship was established. These developments laid the foundation for pharmacological research involving animals and man. This work, along with observations of marijuana's therapeutic applications, opened up investigation into the medical properties of cannabinoids in general and THC in particular. Medical research into the health effects of cannabis also matured throughout this period. In a comprehensive 1986 article in the Pharmacological Review, Leo Hollister of the Stanford University School of Medicine concluded that "compared with other licit social drugs, such as alcohol, tobacco and caffeine, marijuana does not pose greater risks." Hollister wondered if these currently licit drugs would have enjoyed their popular acceptance based on our current knowledge of them. Nonetheless, it has been widely held throughout the 1980s, as Hollister concluded, that "Marijuana may prove to have greater therapeutic potential than these other social drugs, but many questions still need to be answered." The primary question, though, was how do cannabinoids work on the brain? By 1986, scientists were already on the slippery slope that would lead to the discovery of the cannabinoid receptor. The triennial reports from the National Institute on Drug Abuse summarizing research on marijuana had begun to omit references to research on marijuana-related brain damage and instead focus on brain receptor research. A comprehensive article by Renee Wert and Michael Raoulin was published in the International Journal of the Addictions that year, detailing the flaws in all previous studies that claimed to show brain damage resulting from marijuana use. As Hollister independently concluded, "Brain damage has not been proved." The reason, obviously, is that the brain was prepared in some respects to process THC. Also in 1986, Mechoulam put together a book reviewing this research, Cannabinoids as Therapeutic Agents (CRC Press, Boca Raton, FL). One promising area of research was the use of cannabinoids as analgesics or painkillers. A synthetic cannabinoid named CP 55,940, 10-100 times more potent than THC, was also developed in 1986; this was the key to the cannabinoid receptor breakthrough. Receptors are binding sites for chemicals in the brain, chemicals that instruct brain cells to start, stop or otherwise regulate various brain and body functions. The chemicals which trigger receptors are known as neurotransmitters. The brain's resident neurotransmitters are known as endogenous ligands. In many instances, drugs mimic these natural chemicals working in the brain. Scientists are just now confirming their determinations as to which endogenous ligands work on the cannabinoid receptors; it is likely that the neurotransmitter which naturally triggers cannabinoid receptors is one known as anandamide. Research continues. To grossly oversimplify the research involved, a receptor is determined by exposing brain tissue to various chemicals and observing if any of them uniquely bind to the tissue. The search for a cannabinoid receptor depended on the use of a potent synthetic that would allow observation of the binding. CP 55,940 provided this potency, and it allowed Howlett, Devane and their associates, working with tissue from a rat brain, to fulfill precise scientific criteria for determining the existence of a pharmacologically-distinct cannabinoid in brain tissue. A year later the localization of cannabinoid receptors in human brains and other species was determined by scientists at the National Institute of Mental Health, led by Miles Herkenham and including Ross Johnson and Lawrence Melvin, who had worked with Howlett and Devane on the earlier study.
RECEPTORS IN THE BRAIN
The locations of the cannabinoid receptors are most revealing of the way THC acts on the brain, but the importance of this determination is best understood in comparison with the effects of other drugs on the brain. Neurons are brain cells which process information. Neurotransmitter chemicals enable them to communicate with each other by their release into the gap between the neurons. This gap is called the synapse. Receptors are actually proteins in neurons which are specific to neurotransmitters, and which turn various cellular mechanisms on or off. Neurons can have thousands of receptors for different neurotransmitters, causing any neurotransmitter to have diverse effects in the brain. Drugs affect the production, release or re-uptake (a regulating mechanism) of various neurotransmitters. They also mimic or block actions of neurotransmitters, and can interfere with or enhance the mechanisms associated with the receptor. Dopamine is a neurotransmitter which is associated with extremely pleasurable sensations, so that the neural systems which trigger dopamine release are known as the "brain reward system." The key part of this system is identified as the mesocorticolimbic pathway, which links the dopamine-production area with the nucleus of accumbens in the limbic system, an area of the brain which is associated with the control of emotion and behavior. Cocaine, for example, blocks the re-uptake of dopamine so that the brain, lacking biofeedback, keeps on producing it. Amphetamines also block the re-uptake of dopamine, and stimulate additional production and release of it. Opiates activate neural pathways that increase dopamine production by mimicking opioid-peptide neurotransmitters which increase dopamine activity in the ventral tegmental area of the brain where the neurotransmitter originates. Opiates work on three receptor sites, and in effect restrain an inhibitory amino acid, gamma-aminobutyric acid, that otherwise would slow down or halt dopamine production. All of these substances can produce strong reinforcing properties that can seriously influence behavior. The rewarding properties of dopamine are what accounts for animal studies in which animals will forgo food and drink or willingly experience electric shocks in order to stimulate the brain reward system. It is now widely held that drugs of abuse directly or indirectly affect the brain reward system. The key clinical test of whether a substance is a drug of abuse potential or not is whether administration of the drug reduces the amount of electrical stimulation needed to produce self-stimulation response, or dopamine production. This is an indication that a drug has reinforcing properties, and that an individual's use of the drug can lead to addictive and other harmful behavior. To be precise, according to the Office of Technological Assessment (OTA): "The capacity to produce reinforcing effects is essential to any drug with significant abuse potential." Marijuana should no longer be considered a serious drug abuse because, as summarized by the OTA: "Animals will not self-administer THC in controlled studies . . . . Cannabinoids generally do not lower the threshold needed to get animals to self-stimulate the brain regard system, as do other drugs of abuse." Marijuana does not produce reinforcing effects. The definitive experiment which measures drug-induced dopamine production utilizes microdialysis is live, freely-moving rats. Brain microdialysis has proven that opiates, cocaine, amphetamines, nicotine and alcohol all affect dopamine production, whereas marijuana does not. This latest research confirms and explains Hollister's 1986 conclusion about cannabis and addiction: "Physical dependence is rarely encountered in the usual patterns, despite some degree of tolerance that may develop." Most important, the discoveries of Howlett and Devane, Herkenham and their associates demonstrate that the cannabinoid receptors do not influence the dopamine reward system.
CANNABINOID RECEPTORS Research has enabled scientists to know which portions of the brain control various body functions, and this knowledge has been used to explain the pharmacological properties of drugs that activate receptor sites in the brain. There is a dense concentration of cannabinoid binding sites in the basal ganglia and the cerebellum of the base-brain, both of which affect movement and coordination. This discovery will aid in determining the actual physical mechanism by which THC affects spasticity and provides therapeutic benefits to patients with multiple sclerosis and other spastic disorders. While there are cannabinoid receptors in the ventromedial striatum and basal ganglia which are areas associated with dopamine production, no cannabinoid receptors have been found in dopamine-producing neurons, and as mentioned above, no reinforcing properties have been demonstrated in animal studies. There is one study by Gardner and Lowinson, involving inbred Lewis rats, in which doses of THC lowered the amount of electrical stimulation required to trigger the brain reward system. However, no one has been able to replicate the results with any other species of rat, or any other animal. The finding is believed to be the result of some inbred genetic variation in the inbred species, and is both widely mentioned in the literature and disregarded. According to Herkenham and his associates, "There are virtually no reports of fatal cannabis overdose in humans. The safety reflects the paucity of receptors in medullary nuclei that mediate respiratory and cardiovascular functions." This is also why cannabinoids have great promise as analgesics or painkillers, in that they do not depress the function of the heart or the lungs. In this respect, they are far superior to opiates, which decrease the entire physiological system because the receptors are all over the medulla as well as the brain. Marijuana is distinguished from most other illicit drugs by the locations of its brain-receptor sites for two predominant reasons: (1) The lack of receptors in the medulla significantly reduces the possibility of accidental, or even deliberate, death from THC, and (2) the lack of receptors in the mesocorticolimbic pathway significantly reduces the risks of addiction and serious physical dependence. As a therapeutic drug, these features are God's greatest gifts.
THE CHEMISTRY OF EMOTIONS
Mechoulam regrets that more has not been done in the therapeutic application of THC. In a 1986 interview with the International Journal of the Addictions, he said that, "Knowing what I know today, I would have worked more on the therapeutic aspects of cannabis. This area apparently needs a major push that is has not had up till now, particularly given that it has a therapeutic potential. One of the reasons that it has not been pushed was than most pharmaceutical companies years ago were afraid to get into that field. Companies were 'burnt' working on amphetamines and LSD. . . . They are afraid of notoriety." Clearly, cannabis acts on coordination of movement by way of the receptors in the cerebellum and basal ganglia, and on memory by way of the receptors in the limbic system's hippocampus, which "gates" information during memory consolidation. Mechoulam believes that in humans these actions "are rather marginal." "Cannabis," he states, "is used . . . for its actions on mood and emotion." The key to understanding the reason for the presence of cannabinoid receptors in the human brain lies in understanding the role of the receptors in the limbic system, which has a central role in the mechanisms which govern behavior and emotions. The limbic system coordinates activities between the visceral base-brain and the rest of the nervous system. "We know next to nothing on the chemistry of emotions," Mechoulam instructs. It is his hope that future research on the role of cannabinoid receptors in the brain will shed light on this new area of investigation and reflection.
THE FUTURE OF MARIJUANA LAWS
Advances in neurobiology are redefining the scientific basis for addiction. These advances have important ramifications for addiction treatment, and for the treatment of numerous organic diseases and conditions. More importantly for marijuana users, these advances in neurobiology will ultimately force changes in the law. The law is constantly being modified in response to technological changes. The passage of the Controlled Substances Act in 1972 was in part due to a greater understanding of drug abuse brought about by the medical research of the time. The law instituted a policy by which regulation and criminal penalties regarding controlled substances were to be correlated with the harmfulness of the substance. Specifically, the law lists the "actual or relative potential for abuse" as the first matter to be considered in determining the appropriate scheduling of a drug. Schedule I is for drugs which have a "high potential for abuse." While the scheduling of marijuana and its subsequent availability for research and medical use was the subject of a 22-year unsuccessful court battle spearheaded by the National Organization for the Reform of Marijuana Laws, the question of marijuana's abuse potential was never addressed during the litigation and related proceedings. The suit over medical marijuana sought to reschedule marijuana as a Schedule II drug, which also implies a "high potential for abuse." This made the abuse question irrelevant to the court proceedings. However, the abuse question is the pre-eminent issue in attempts to reform marijuana laws, and it is the weak link upon which the entirety of marijuana prohibition rests. The most recent research indicates that marijuana does not have a high potential for abuse, especially relative to other scheduled drugs such as heroin, cocaine, sedatives and amphetamines. The medical-marijuana petition was rejected by the administrator of the DEA because of the lack of scientific studies detailing marijuana's medical value. The court appeal essentially concerned whether or not this was a reasonable standard in light of the government's historic disinterest in funding such studies. While courts have ruled that DEA can rely on research studies, or the lack thereof, in its decision-making about the scheduling of marijuana, they have not ruled on the actual issues which determine the proper legal scheduling of marijuana. The discovery of cannabinoid receptor sites, and their relevance to the understanding of the pharmacology of THC in the brain, provides the basis for a new challenge to the legitimacy of marijuana's Schedule I status, a pivotal event in marijuana's eventual legalization.
Link
by John Gettman
High Times, March, 1995
In 1970, marijuana was placed on Schedule 1 of the Drug Enforcement Administration's controlled-substances list, largely because scientists feared that, like opiates, it had an extremely high potential for abuse and addiction. But the discovery of THC receptor sites in the brain refutes that thinking, and may force both scientists and the DEA to re-evaluate their positions.
Introduction
The next century will view the 1988 discovery of the THC receptor site in the brain as the pivotal event which led to the legalization of marijuana. Before this discovery, no one knew for sure just how the psychoactive chemical in marijuana worked on the brain. Throughout the 1970s and 1980s, researchers made tremendous strides in understanding how the brain works, by using receptor sites as switches which respond to various chemicals by regulating brain and body functions. The dominant fear about marijuana in the 20th century has been that its effects were somehow similar to the dangerously addictive effects of opiates such as morphine and heroin. Despite widespread decriminalization of marijuana in the United States in the 1970s, this concern has remained the basis for federal law and policies regarding the use and study of marijuana. The legal manifestation of this fear is the continued classification of marijuana as a Schedule I drug, a category shared by heroin and other drugs that are banned from medical use because of their dangerous, addictive qualities. While only 11 states have formally decriminalized possession of small amounts of marijuana, 45 states distinguish between marijuana and other Schedule I drugs for law-enforcement and sentencing purposes. Until the 1980s, technological limitations obstructed scientific understanding of the neuropharmacology of THC, of how the active ingredient in marijuana actually affects brain functions. Observations and conclusions about this subject, though based on some biological studies, were largely influenced by observations of behavior. This has allowed cultural prejudice to sustain the faith that marijuana is somehow related to heroin, and that research will eventually prove this hypothesis. Actually, the discovery of the THC receptor site and the subsequent research and observations it has inspired conclusively refute the hypothesis that marijuana is dope. Many important brain functions which affect human behavior involve the neurotransmitter dopamine. Serious drugs of abuse, such as heroin and cocaine, interfere with the brain's use of dopamine in manners that can seriously alter an individual's behavior. A drug's ability to affect the neural systems related to dopamine production has now become the defining characteristic of drugs with serious abuse potential.
According to the congressional Office of Technology Assessment, research over the last 10 years has proved that marijuana has no effect on dopamine-related brain systems - unless you are an inbred Lewis rat (see below), in which case abstention is recommended. The discovery of a previously unknown system of cannabinoid neural transmitters is profound. While century-old questions, such as why marijuana is nontoxic, are finally being answered, new, fascinating questions are emerging - as in the case of all great discoveries. In the words of Israeli researcher Raphael Mechoulam, the man who first isolated the structure of THC, "Why do we have cannabinoid receptors?" Mechoulam's theory will resonate well with marijuana smokers in the United States. He observes that "Cannabis is used by man not for its actions on memory of movement or movement coordination, but for its actions on memory and emotions," and asks, "Is it possible that the main task of cannabinoid receptors . . . (is) to modify our emotions, to serve as the links which transmit or transform or translate objective or subjective events into perceptions and emotions?" At a 1990 conference on cannabinoid research in Crete, Mechoulam concluded his remarks by saying, "Let us hope, however, that through better understanding of cannabis chemistry in the brain, we may also approach the chemistry of emotions."
A BRIEF HISTORY OF THC RESEARCH
The receptor breakthrough occurred in 1988 at the St. Louis University Medical School where Allyn Howlett, William Devane and their associates identified and characterized a cannabinoid receptor in a rat brain. The breakthrough has a long history leading up to it. Major figures in American and British organic chemistry, such as Roger Adams, Alex Todd and Sigmund Loewe, did important work in determining the pharmacology of cannabis in the 1940s and 1950s, but their work ground to a halt due to the disinterest cultivated by the 1937 federal ban on marijuana. While synthetic compounds were created which were close to the actual compound, THC, they were not equivalent to it. The structure of one related chemical, cannabidiol, was determined. After repeating the isolation of cannabidiol, in 1963 Mechoulam began work with Yehiel Gaoni that led to the determination of the biosynthetic pathway by which the plant synthesizes cannabinoids. In 1964 Gaoni and Mechoulam isolated tetrahydrocannabinol (THC) and a few years later they reported the first synthesis of THC. Following the identification of the active constituent in marijuana, scientific research began to fill in the gaps and build on Mechoulam's initial breakthrough. The neutral and acidic cannabinoids in cannabis were isolated, and their structures were elucidated. The absolute configurations were determined, as was a reasonable scheme of biogenesis. Total synthesis of the chemical was obtained, and the structure-activity relationship was established. These developments laid the foundation for pharmacological research involving animals and man. This work, along with observations of marijuana's therapeutic applications, opened up investigation into the medical properties of cannabinoids in general and THC in particular. Medical research into the health effects of cannabis also matured throughout this period. In a comprehensive 1986 article in the Pharmacological Review, Leo Hollister of the Stanford University School of Medicine concluded that "compared with other licit social drugs, such as alcohol, tobacco and caffeine, marijuana does not pose greater risks." Hollister wondered if these currently licit drugs would have enjoyed their popular acceptance based on our current knowledge of them. Nonetheless, it has been widely held throughout the 1980s, as Hollister concluded, that "Marijuana may prove to have greater therapeutic potential than these other social drugs, but many questions still need to be answered." The primary question, though, was how do cannabinoids work on the brain? By 1986, scientists were already on the slippery slope that would lead to the discovery of the cannabinoid receptor. The triennial reports from the National Institute on Drug Abuse summarizing research on marijuana had begun to omit references to research on marijuana-related brain damage and instead focus on brain receptor research. A comprehensive article by Renee Wert and Michael Raoulin was published in the International Journal of the Addictions that year, detailing the flaws in all previous studies that claimed to show brain damage resulting from marijuana use. As Hollister independently concluded, "Brain damage has not been proved." The reason, obviously, is that the brain was prepared in some respects to process THC. Also in 1986, Mechoulam put together a book reviewing this research, Cannabinoids as Therapeutic Agents (CRC Press, Boca Raton, FL). One promising area of research was the use of cannabinoids as analgesics or painkillers. A synthetic cannabinoid named CP 55,940, 10-100 times more potent than THC, was also developed in 1986; this was the key to the cannabinoid receptor breakthrough. Receptors are binding sites for chemicals in the brain, chemicals that instruct brain cells to start, stop or otherwise regulate various brain and body functions. The chemicals which trigger receptors are known as neurotransmitters. The brain's resident neurotransmitters are known as endogenous ligands. In many instances, drugs mimic these natural chemicals working in the brain. Scientists are just now confirming their determinations as to which endogenous ligands work on the cannabinoid receptors; it is likely that the neurotransmitter which naturally triggers cannabinoid receptors is one known as anandamide. Research continues. To grossly oversimplify the research involved, a receptor is determined by exposing brain tissue to various chemicals and observing if any of them uniquely bind to the tissue. The search for a cannabinoid receptor depended on the use of a potent synthetic that would allow observation of the binding. CP 55,940 provided this potency, and it allowed Howlett, Devane and their associates, working with tissue from a rat brain, to fulfill precise scientific criteria for determining the existence of a pharmacologically-distinct cannabinoid in brain tissue. A year later the localization of cannabinoid receptors in human brains and other species was determined by scientists at the National Institute of Mental Health, led by Miles Herkenham and including Ross Johnson and Lawrence Melvin, who had worked with Howlett and Devane on the earlier study.
RECEPTORS IN THE BRAIN
The locations of the cannabinoid receptors are most revealing of the way THC acts on the brain, but the importance of this determination is best understood in comparison with the effects of other drugs on the brain. Neurons are brain cells which process information. Neurotransmitter chemicals enable them to communicate with each other by their release into the gap between the neurons. This gap is called the synapse. Receptors are actually proteins in neurons which are specific to neurotransmitters, and which turn various cellular mechanisms on or off. Neurons can have thousands of receptors for different neurotransmitters, causing any neurotransmitter to have diverse effects in the brain. Drugs affect the production, release or re-uptake (a regulating mechanism) of various neurotransmitters. They also mimic or block actions of neurotransmitters, and can interfere with or enhance the mechanisms associated with the receptor. Dopamine is a neurotransmitter which is associated with extremely pleasurable sensations, so that the neural systems which trigger dopamine release are known as the "brain reward system." The key part of this system is identified as the mesocorticolimbic pathway, which links the dopamine-production area with the nucleus of accumbens in the limbic system, an area of the brain which is associated with the control of emotion and behavior. Cocaine, for example, blocks the re-uptake of dopamine so that the brain, lacking biofeedback, keeps on producing it. Amphetamines also block the re-uptake of dopamine, and stimulate additional production and release of it. Opiates activate neural pathways that increase dopamine production by mimicking opioid-peptide neurotransmitters which increase dopamine activity in the ventral tegmental area of the brain where the neurotransmitter originates. Opiates work on three receptor sites, and in effect restrain an inhibitory amino acid, gamma-aminobutyric acid, that otherwise would slow down or halt dopamine production. All of these substances can produce strong reinforcing properties that can seriously influence behavior. The rewarding properties of dopamine are what accounts for animal studies in which animals will forgo food and drink or willingly experience electric shocks in order to stimulate the brain reward system. It is now widely held that drugs of abuse directly or indirectly affect the brain reward system. The key clinical test of whether a substance is a drug of abuse potential or not is whether administration of the drug reduces the amount of electrical stimulation needed to produce self-stimulation response, or dopamine production. This is an indication that a drug has reinforcing properties, and that an individual's use of the drug can lead to addictive and other harmful behavior. To be precise, according to the Office of Technological Assessment (OTA): "The capacity to produce reinforcing effects is essential to any drug with significant abuse potential." Marijuana should no longer be considered a serious drug abuse because, as summarized by the OTA: "Animals will not self-administer THC in controlled studies . . . . Cannabinoids generally do not lower the threshold needed to get animals to self-stimulate the brain regard system, as do other drugs of abuse." Marijuana does not produce reinforcing effects. The definitive experiment which measures drug-induced dopamine production utilizes microdialysis is live, freely-moving rats. Brain microdialysis has proven that opiates, cocaine, amphetamines, nicotine and alcohol all affect dopamine production, whereas marijuana does not. This latest research confirms and explains Hollister's 1986 conclusion about cannabis and addiction: "Physical dependence is rarely encountered in the usual patterns, despite some degree of tolerance that may develop." Most important, the discoveries of Howlett and Devane, Herkenham and their associates demonstrate that the cannabinoid receptors do not influence the dopamine reward system.
CANNABINOID RECEPTORS Research has enabled scientists to know which portions of the brain control various body functions, and this knowledge has been used to explain the pharmacological properties of drugs that activate receptor sites in the brain. There is a dense concentration of cannabinoid binding sites in the basal ganglia and the cerebellum of the base-brain, both of which affect movement and coordination. This discovery will aid in determining the actual physical mechanism by which THC affects spasticity and provides therapeutic benefits to patients with multiple sclerosis and other spastic disorders. While there are cannabinoid receptors in the ventromedial striatum and basal ganglia which are areas associated with dopamine production, no cannabinoid receptors have been found in dopamine-producing neurons, and as mentioned above, no reinforcing properties have been demonstrated in animal studies. There is one study by Gardner and Lowinson, involving inbred Lewis rats, in which doses of THC lowered the amount of electrical stimulation required to trigger the brain reward system. However, no one has been able to replicate the results with any other species of rat, or any other animal. The finding is believed to be the result of some inbred genetic variation in the inbred species, and is both widely mentioned in the literature and disregarded. According to Herkenham and his associates, "There are virtually no reports of fatal cannabis overdose in humans. The safety reflects the paucity of receptors in medullary nuclei that mediate respiratory and cardiovascular functions." This is also why cannabinoids have great promise as analgesics or painkillers, in that they do not depress the function of the heart or the lungs. In this respect, they are far superior to opiates, which decrease the entire physiological system because the receptors are all over the medulla as well as the brain. Marijuana is distinguished from most other illicit drugs by the locations of its brain-receptor sites for two predominant reasons: (1) The lack of receptors in the medulla significantly reduces the possibility of accidental, or even deliberate, death from THC, and (2) the lack of receptors in the mesocorticolimbic pathway significantly reduces the risks of addiction and serious physical dependence. As a therapeutic drug, these features are God's greatest gifts.
THE CHEMISTRY OF EMOTIONS
Mechoulam regrets that more has not been done in the therapeutic application of THC. In a 1986 interview with the International Journal of the Addictions, he said that, "Knowing what I know today, I would have worked more on the therapeutic aspects of cannabis. This area apparently needs a major push that is has not had up till now, particularly given that it has a therapeutic potential. One of the reasons that it has not been pushed was than most pharmaceutical companies years ago were afraid to get into that field. Companies were 'burnt' working on amphetamines and LSD. . . . They are afraid of notoriety." Clearly, cannabis acts on coordination of movement by way of the receptors in the cerebellum and basal ganglia, and on memory by way of the receptors in the limbic system's hippocampus, which "gates" information during memory consolidation. Mechoulam believes that in humans these actions "are rather marginal." "Cannabis," he states, "is used . . . for its actions on mood and emotion." The key to understanding the reason for the presence of cannabinoid receptors in the human brain lies in understanding the role of the receptors in the limbic system, which has a central role in the mechanisms which govern behavior and emotions. The limbic system coordinates activities between the visceral base-brain and the rest of the nervous system. "We know next to nothing on the chemistry of emotions," Mechoulam instructs. It is his hope that future research on the role of cannabinoid receptors in the brain will shed light on this new area of investigation and reflection.
THE FUTURE OF MARIJUANA LAWS
Advances in neurobiology are redefining the scientific basis for addiction. These advances have important ramifications for addiction treatment, and for the treatment of numerous organic diseases and conditions. More importantly for marijuana users, these advances in neurobiology will ultimately force changes in the law. The law is constantly being modified in response to technological changes. The passage of the Controlled Substances Act in 1972 was in part due to a greater understanding of drug abuse brought about by the medical research of the time. The law instituted a policy by which regulation and criminal penalties regarding controlled substances were to be correlated with the harmfulness of the substance. Specifically, the law lists the "actual or relative potential for abuse" as the first matter to be considered in determining the appropriate scheduling of a drug. Schedule I is for drugs which have a "high potential for abuse." While the scheduling of marijuana and its subsequent availability for research and medical use was the subject of a 22-year unsuccessful court battle spearheaded by the National Organization for the Reform of Marijuana Laws, the question of marijuana's abuse potential was never addressed during the litigation and related proceedings. The suit over medical marijuana sought to reschedule marijuana as a Schedule II drug, which also implies a "high potential for abuse." This made the abuse question irrelevant to the court proceedings. However, the abuse question is the pre-eminent issue in attempts to reform marijuana laws, and it is the weak link upon which the entirety of marijuana prohibition rests. The most recent research indicates that marijuana does not have a high potential for abuse, especially relative to other scheduled drugs such as heroin, cocaine, sedatives and amphetamines. The medical-marijuana petition was rejected by the administrator of the DEA because of the lack of scientific studies detailing marijuana's medical value. The court appeal essentially concerned whether or not this was a reasonable standard in light of the government's historic disinterest in funding such studies. While courts have ruled that DEA can rely on research studies, or the lack thereof, in its decision-making about the scheduling of marijuana, they have not ruled on the actual issues which determine the proper legal scheduling of marijuana. The discovery of cannabinoid receptor sites, and their relevance to the understanding of the pharmacology of THC in the brain, provides the basis for a new challenge to the legitimacy of marijuana's Schedule I status, a pivotal event in marijuana's eventual legalization.
Link
29 July 2011
What cancer survival really means
I was really taken aback by this explanation of what cancer survival really means. I know that some of you are fighting cancer* or have someone in your lives who is. This may be useful.
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*Reflecting on this, I think I see a bit better why some say that 'fighting cancer' is the wrong language/metaphor. Though I'm not sure what to use instead. Help me out.
xkcd: Lanes
(Click to make bigger)
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*Reflecting on this, I think I see a bit better why some say that 'fighting cancer' is the wrong language/metaphor. Though I'm not sure what to use instead. Help me out.
19 July 2011
Foolproof method for succeeding in modern neurochemistry
Neurochemistry Post-Docs! Looking to publish interesting and important papers on the neurochemistry of reward but don't know what to study? Then Dr. Swenson's Revolutionary Topic Selection Method is for you!
For centuries, western philosophers have thought carefully about the nature and kinds of pleasure.* You too can benefit from their efforts!
Here's the key to Dr. Swenson's Revolutionary Topic Selection Method: These philosophers have been studying mental phenomena. You study neural phenomena. And mental phenomena are ultimately neural phenomena!
Other inferior neuropsychological research programs have tried using philosophical claims to select topics. But they would have you try to prove or disprove philosophical claims with neuroscience. That may win you friends amongst philosophers. But you don't want philosopher friends!** You want prestigious publications and lucrative grants!
That's where Dr. Swenson's Revolutionary Topic Selection Method can help! You needn't worry about proving or disproving philosophical claims. With Dr. Swenson's Revolutionary Topic Selection Method, you will use writers ranging from the ancient Greeks to the modern utilitarians to help you design experimental paradigms that are the key to scientific fame.
Here's just one taste of what the system has to offer. Philosophers have, in various guises, debated whether some pleasures are better than others by virtue of being more refined and intellectually infused.
Now a lesser program might have you consider whether opera or pop music produces greater activity in dopaminergic pathways in subjects with past exposure to both. But that will impress only philosophers.
With Dr. Swenson's Revolutionary Topic Selection Method you will instead find in these disputes some promising leads for experimentation. You may, for example, design your experiments to investigate connections between the reward pathway activity, memories, and higher order processes. You don't care whether the refined music elicits more apparent reward. You care about whether pop music and opera elicit systematically different connections throughout the brain.***
Now, it is true that Dr. Swenson's Revolutionary Topic Selection Method can't promise experimental results that will woo philosophers.**** But Dr. Swenson's Revolutionary Topic Selection Method can help you select topics which will uncover processes which underlie our complex mental lives. And that's what you want.
And lucrative grants!
Act now and Dr. Swenson's Revolutionary Topic Selection Method can be yours for a pathetically small amount of money. First 10 callers get a free T-shirt and Shamwow.
*Yes, this comes dangerously close to 'since the dawn of time'. I cringe too.
**I'm serious.
***I know, music isn't the best example. But it's easy to set out. Thanks a lotOliver Sacks.
****Philosophers will nonetheless distort your results and woo themselves.
--------
This post was inspired by
Heterogenerity of Reward MechanismsSpringerLink - Neurochemical Research, Volume 35, Number 6: "The finding that many drugs that have abuse potential and other natural stimuli such as food or sexual activity cause similar chemical changes in the brain, an increase in extracellular dopamine (DA) in the shell of the nucleus accumbens (NAccS), indicated some time ago that the reward mechanism is at least very similar for all stimuli and that the mechanism is relatively simple. The presently available information shows that the mechanisms involved are more complex and have multiple elements. Multiple brain regions, multiple receptors, multiple distinct neurons, multiple transmitters, multiple transporters, circuits, peptides, proteins, metabolism of transmitters, and phosphorylation, all participate in reward mechanisms. The system is variable, is changed during development, is sex-dependent, and is influenced by genetic differences. Not all of the elements participate in the reward of all stimuli. Different set of mechanisms are involved in the reward of different drugs of abuse, yet different mechanisms in the reward of natural stimuli such as food or sexual activity; thus there are different systems that distinguish different stimuli. Separate functions of the reward system such as anticipation, evaluation, consummation and identification; all contain function-specific elements. The level of the stimulus also influences the participation of the elements of the reward system, there are possible reactions to even below threshold stimuli, and excessive stimuli can change reward to aversion involving parts of the system. Learning and memory of past reward is an important integral element of reward and addictive behavior. Many of the reward elements are altered by repeated or chronic stimuli, and chronic exposure to one drug is likely to alter the response to another stimulus. To evaluate and identify the reward stimulus thus requires heterogeneity of the reward components in the brain. "
(Via http://mindhacks.com/.)
LSD analogue and cluster headaches
Whoa. Check out this abstract an annual International Headache Congress paper.
In English: in small study, a chemical cousin of LSD pretty much cured cluster headaches in some patients. It may have done this through changes at the genetic level.
All the usual caveats apply --small study, limited time frame, et cetera. Still, whoa.
Here's a better summary.
-------
And, though there's no reason whatsoever to think there's any relationship with the long-term gene-level effects in this study, I've been looking for an excuse to post this: John's Hopkins Study Probes "Sacred Mushroom" Chemical. Amongs the results
Cluster headache attack cessation and remission extension of months or longer in six treatment-refractory patients administered only 3 doses of BOL-148
J. Halpern, M. Karst, T. Passie
Five male patients with treatment-refractory chronic cluster headache and one female patient with treatment-refractory mixed cluster/migrainous headache were administered 2-bromo-LSD (BOL-148) (20mcg/kg) at five-day intervals for a total of three treatments. Sixteen-week outcome data on the five male patients revealed a robust treatment response, with three of the five having no attacks for more than one month, thereby shifting their diagnosis back to the episodic form of cluster headache. Similarly, the female patient reported quiescence of cluster attacks for greater than one month and 'significant' improvement in migraine in the following weeks from last dose of BOL-148. This poster presents longterm outcome data on all 6 patients who received BOL-148. In follow-up with these patients, BOL-148 provided significant headache relief that lasted for several months to more than one-year. Data suggests that BOL-148 may function as an important new treatment, though, at present, there is no explanation for such long-term prophylactic effects with no later drug re-administrations. There is some evidence that BOL-148 is affecting epigenetic mechanisms and may open the possibility for a near-cure-like treatment for patients afflicted with vascular headaches."
In English: in small study, a chemical cousin of LSD pretty much cured cluster headaches in some patients. It may have done this through changes at the genetic level.
All the usual caveats apply --small study, limited time frame, et cetera. Still, whoa.
Here's a better summary.
-------
And, though there's no reason whatsoever to think there's any relationship with the long-term gene-level effects in this study, I've been looking for an excuse to post this: John's Hopkins Study Probes "Sacred Mushroom" Chemical. Amongs the results
Looking back over a year later, most of the experiment’s 18 volunteers (94 percent) rated a psilocybin session as among the top five most or as the topmost spiritually significant experience of his or her life....Most volunteers (89 percent) also reported positive changes in their behaviors, and those reports were corroborated by family members or others, the researchers say. The behavior changes most frequently cited were improved relationships with family and others, increased physical and psychological self-care, and increased devotion to spiritual practice.
22 February 2011
Darvocet decision a prelude a warm up for banning methadone?
Christian Sinclair over at Pallimed does some sleuthing into the FDA's rationale for pulling propoxyphene and comes away concerned:
He notes that
Combined with some FDA memo analysis (go read the post) he concludes
This would be bad news indeed.
He notes that
* Propoxyphene is a synthetic derivative of methadone.
* Methadone causes QT prolongation of questionable clinical significance in palliative care patients.
* QT prolongation is a risk factor for ventricular arrhythmias.
Combined with some FDA memo analysis (go read the post) he concludes
Well all this may be a whole lot of nothing but my real concern is that methadone may be a drug in the crosshairs of the FDA soon. It already has four strikes against it:
1) documented QT prolongation
2) stigma of heroin treatment programs
3) accelerating percent of all deaths related to opioids
4) methadone could be considered an orphan drug
This would be bad news indeed.
10 February 2011
Images from the History of Medicine (NLM)
Just discovered the National Library of Medicine's archive of images. Pretty neat (in a depressing sort of way).
Here's the main site:
http://www.nlm.nih.gov/hmd/ihm/
and here's a link to search results for pain:
Images from the History of Medicine (NLM) - Search Results: All Fields SimilarTo 'Pain'
14 January 2011
Open placebos
By now I'm sure you've all heard the exciting news: Placebos work even if the patients know that they are taking placebos!
At least in a controlled study. Where their doctors give them lots of attention. Where they, as participants in a study, may be hoping that the 'treatment' works. When they've been told that science says placebos can work. Et cetera....
No need for me to recapitulate the debates. Instead, links!
The original paper, Placebos Without Deception
Steve Silberman, author of the awesome Wired magazine article on placebos, has a nice rundown here.
I suppose you can guess Respectful Insolence's Orac's take from his introduction of the topic
Skepticism aplenty there.
Ed Young likes the study a bit better.
At least in a controlled study. Where their doctors give them lots of attention. Where they, as participants in a study, may be hoping that the 'treatment' works. When they've been told that science says placebos can work. Et cetera....
No need for me to recapitulate the debates. Instead, links!
The original paper, Placebos Without Deception
Steve Silberman, author of the awesome Wired magazine article on placebos, has a nice rundown here.
I suppose you can guess Respectful Insolence's Orac's take from his introduction of the topic
The investigators, led by Dr. Ted J. Kaptchuk of Harvard's Osher Research Center. The Osher Center, for those of you not familiar with it, is Harvard's center of quackademic medicine; only this time they seem to be trying to do some real research into placebo effects.
Skepticism aplenty there.
Ed Young likes the study a bit better.
02 September 2010
From Overheard in New York: sphenopalatine ganglioneuralgia
This cautionary tale from Overheard in New York provides me an opportunity to shamelessly boost my Google rating for sphenopalatine ganglioneuralgia (ice cream headache/brain freeze).
Overheard in New York | God Has Played a Cold Joke on Us All.: "God Has Played a Cold Joke on Us All.
Guy #1: Owwww! Fuck! Owwwwwwwww!
Guy #2: You won't get an ice cream headache if you drink it slower.
Guy #1: I'm trying, but it's too delicious!
--9th St. & 3rd Ave
And just for good measure: sphenopalatine ganglioneuralgia
Menstrual cramps even suckier than previously thought
In short, this suggests that menstrual cramps not only suck, they make other pains that happen to be around worse.
Brain morphological changes associated with cyclic menstrual pain: "Volume 150, Issue 3, Pages 462-468 (September 2010)
Cheng-Hao Tuab, David M. Niddambc, Hsiang-Tai Chaod, Li-Fen Chenbce, Yong-Sheng Chenf, Yu-Te Wubeg, Tzu-Chen Yehbe, Jiing-Feng Lirngh, Jen-Chuen HsiehabceCorresponding Author Informationemail addressemail address
Primary dysmenorrhea (PDM) is the most prevalent gynecological disorder for women in the reproductive age. PDM patients suffer from lower abdominal pain that starts with the onset of the menstrual flow. Prolonged nociceptive input to the central nervous system can induce functional and structural alterations throughout the nervous system. In PDM, a chronic viscero-nociceptive drive of cyclic nature, indications of central sensitization and altered brain metabolism suggest a substantial central reorganization. Previously, we hypothesized that disinhibition of orbitofrontal networks could be responsible for increased pain and negative affect in PDM. Here, we further tested this hypothesis....Abnormal decreases were found in regions involved in pain transmission, higher level sensory processing, and affect regulation while increases were found in regions involved in pain modulation and in regulation of endocrine function. Moreover, GM changes in regions involved in top-down pain modulation and in generation of negative affect were related to the severity of the experienced PDM pain. Our results demonstrate that abnormal GM volume changes are present in PDM patients even in the absence of pain. These changes may underpin a combination of impaired pain inhibition, increased pain facilitation and increased affect. Our findings highlight that longer lasting central changes may occur not only in sustained chronic pain conditions but also in cyclic occurring pain conditions."
17 August 2010
The most obnoxious email my hand surgeon has ever received
I managed to badly break my thumb during judo last week. I'm having surgery to repair it this Friday. After spending all this time learning about pain/pain medicine, I've learned just enough about drugs to be dangerous. Today, that danger has manifested in what I'm guessing is the most obnoxious email my hand surgeon has ever received from a patient.
For your enjoyment:
For your enjoyment:
Dear [Dr's assistant],
....The pharmacy has a prescription of Darvocet for me. But, I'd actually like to avoid both the propoxyphene and APAP in Darvocet. I'd appreciate it if you could ask Dr. xxxxxx to cancel that prescription and write me one for something different. He might find the following useful:
The Vicodin prescription [which I had been written for the initial pain of the injury] worked fine. Still, I had forgotten that there is some evidence of an interaction between acetaminophen and xxxxxx. See, for example, [3]. So I'd prefer something without APAP. It's not a big deal, but I'd prefer to keep on the safe side.
I'd prefer to avoid anything containing propoxyphene for two reasons. First, it's somewhat contraindicated with xxxxxxx (propoxyphene can potentiate the xxxxxxxxxx). Second, there are some concerns about its cardiotoxic metabolites. See [1] and [2]. I know it's a tiny risk. But, again, I'd prefer to stay on the safe side wherever possible.
To make things just a bit more complicated: I don't think anything with straight codeine will be very useful. I'm fairly certain that both my mother and my sister are poor metabolizes, so I don't want to trust my CYP2D6's any more than I have to. Moreover, according to Cochrane Reviews [7], with a NNT=12, codeine just doesn't seem very trustworthy.
Finally, just in case this is relevant, I'd prefer to use the narcotics to hit the acute pain hard for 1-2 days and then get off of them as quickly as possible. There seems to be evidence that early aggressive treatment helps cut the overall duration of post surgical pain and, more important to me, reduce the risk of chronic pain (see, e.g., [4], [5], [6], [8]). Thus I'd prefer very few doses of something strong to more of something weaker.
These are just some very weak preferences based on my rudimentary understanding of pain management protocols. I trust your judgment completely.
Thanks
Adam
References
[1] http://www.citizen.org/publications/publicationredirect.cfm?ID=7420
[2]http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm170268.htm
[3] Miners JO, Attwood J, Birkett DJ. Determinants of acetaminophen metabolism: effect of inducers and inhibitors of drug metabolism on acetaminophen's metabolic pathways. Clin Pharmacol Ther. 1984; 35:480-486.
[4] Leibeskind, J. C. (1991). "Pain Can Kill." Pain 44: 3-4.
[5] Merskey, H. (1999). Pain and Psychological Medicine. Textbook of Pain. P. D. Wall and R. Melzack. Edinburgh, Churchill Livingstone: 929-949.
[6] Harman, K. (2000). "Neuroplasticitiy and the Development of Chronic Pain." Physiotherapy Canada 52(64-71).
[7] Derry, S., R. A. Moore, et al. (2010) "Single dose oral codeine, as a single agent, for acute postoperative pain in adults." Cochrane Database of Systematic Reviews DOI: 10.1002/14651858.CD008099.pub2.
[8] Kehlet, H., T. S. Jensen, et al. (2006). "Persistent postsurgical pain: risk factors and prevention." Lancet 367(9522): 1618-1625.
Acute postoperative pain is followed by persistent pain in 10-50% of individuals after common operations, such as groin hernia repair, breast and thoracic surgery, leg amputation, and coronary artery bypass surgery. Since chronic pain can be severe in about 2-10% of these patients, persistent postsurgical pain represents a major, largely unrecognised clinical problem. Iatrogenic neuropathic pain is probably the most important cause of long-term postsurgical pain. Consequently, surgical techniques that avoid nerve damage should be applied whenever possible. Also, the effect of aggressive, early therapy for postoperative pain should be investigated, since the intensity of acute postoperative pain correlates with the risk of developing a persistent pain state. Finally, the role of genetic factors should be studied, since only a proportion of patients with intraoperative nerve damage develop chronic pain. Based on information about the molecular mechanisms that affect changes to the peripheral and central nervous system in neuropathic pain, several opportunities exist for multimodal pharmacological intervention. Here, we outline strategies for identification of patients at risk and for prevention and possible treatment of this important entity of chronic pain.
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