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.

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.

The Sontag 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.)

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

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

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.

xkcd: Lanes

(Click to make bigger)

Check out the rollover --the text which displays when your mouse hovers over the picture-- on the original post for how the picture reflects the stages of breast cancer.

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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.

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.

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This post was inspired by

Heterogenerity of Reward Mechanisms

SpringerLink - 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.

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.

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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.

The Strange Powers of the Placebo Effect

Some of the interesting features of the placebo effect:

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

* 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.

(Via: Pallimed: A Hospice & Palliative Medicine Blog: Are You Glad Darvocet Got Pulled by the FDA? Are You Sure?)

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'

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

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.