Exploring Mysticism and Parapsychology. This blog is also an attempt to promote awareness of a Modern Universal Paradigm known as Multi-Dimensional Science. It offers a "Scientific" testable Hypothesis for a more "objective" understanding of claimed Psychic and Spiritual Phenomena. A link to this subject should be found on this page or alternatively it can be found easily via a word search.Please note that the Internet articles here may not always reflect the views of the Blogger.
The book is still published with enthusiastic comments from the likes of Edith Sitwell and Cyril Connolly adorning its cover (Connolly later admitted he hadn't read it)[citation needed]. This reception – of his first book at the age of 24 – was a high critical watermark for Wilson, a reputation that sank as fast as it had rocketed.[4] It is still, however, an insightful work of literary and philosophical criticism – a timeless preoccupation which perhaps garners more mainstream attention than his subsequent writings on the occult and crime[citation needed]. The book is structured in such a way as to mirror the Outsider's[clarification needed] experience: a sense of dislocation, or of being at odds with society. These are figures like Dostoevsky's "Underground-Man" who seem to be lost to despair and non-transcendence with no way out.
More successful – or at least hopeful – characters are then brought to the fore (including the title character from Hermann Hesse’s novel Steppenwolf). These are presented as examples of those who have insightful moments of lucidity in which they feel as though things are worthwhile/meaningful amidst their shared, usual, experience of nihilism and gloom. Sartre's Nausea is herein the key text – and the moment when the hero listens to a song in a cafe which momentarily lifts his spirits is the outlook on life to be normalized. Wilson then engages in some detailed case studies of artists who failed in this task and tries to understand their weakness – which is either intellectual, of the body or of the emotions. The final chapter is Wilson's attempt at a "great synthesis" in which he justifies his belief that western philosophy is afflicted with a needless "pessimistic fallacy" – a narrative he continues throughout his oeuvre under various names (St. Neot Margin for example) and illustrated in several metaphors ("every day is Christmas day").
Blurb from the inside cover of a late 1990s edition of The Outsider: "The Outsider is the seminal work on alienation, creativity and the modern mind-set. First published over thirty years ago, it made its youthful author England's most controversial intellectual. Many of Wilson's critics were angry that a 24-year-old non-academic had put out a piece of work that describes 'human alienation' in populist society so well, even offering up creating one's own religion or reinventing one's spirituality as a solution to one's own malaise. The book is still published in hardback and paperback, is still a staple in many bookstores' sociology section. The book is sometimes shelved in the psychology sections, religion sections as well."
In 1956 The Outsider made him an overnight sensation, but ever since Colin Wilson has been an outsider himself - a knicker fetishist, a social misfit and the author of 110 books that even his publisher didn't want. He hopes his new autobiography will finally convince the world of his greatness
This is the first time I have interviewed a self-declared genius, also the first time I have interviewed a self-declared panty fetishist, so Colin Wilson is quite a catch. He has been declaring his genius ever since The Outsider came out in 1956 and he awoke to find himself famous. He wrote it in the Reading Room of the British Museum while living in a sleeping bag on Hampstead Heath. He was a Leicester factory worker's son who had left school at 16 and avoided National Service by claiming to be homosexual. He supported himself in odd jobs while reading seemingly every book ever written, and writing The Outsider, which was hailed as England's answer to Albert Camus.
But he went from literary lion to pariah in less than a year. His immediate crime was too much party-going, too much name-dropping, too much publicity, but his subsequent, much worse, crime was writing too many books - 110 at the latest count - on subjects ranging from serial killers to alien abductions to The Lost City of Atlantis. The critics at first attacked him then ignored him - he has not had a serious review for years. But now, at 73, he has written an autobiography, Dreaming to Some Purpose, of considerable charm. It is jaw-droppingly - one might say cringe-makingly - honest and often unintentionally hilarious.
I particularly enjoyed his account of how, as a panty-fetishist and visiting lecturer at an American university, he contrived to look up his students' skirts with the aid of a glass-bottomed mug. But the story of his struggle to become a writer, and the tenacity with which he stayed one - despite the fact that even his publisher advised him to give up - is heroic and strangely moving.
I go to meet him at his home in Cornwall, where he has lived for almost 50 years. He picks me up from St Austell in his ancient Jaguar and seems like the sort of amiable tweed-jacketed cove you see in glucosamine sulphate ads. But as we tootle along the lanes his con versation became increasingly odd - he periodically throws out the word 'fucker' with extraordinary venom, accompanied by a sly sideways glance to see if I am shocked. The fucker in question was Humphrey Carpenter, who had been to interview him and then betrayed him: 'We got on terribly well, I thought, though I did notice that Humphrey fell asleep when I was explaining what I meant by non-pessimistic existentialism.'
'How awful,' I murmur, resolving to avoid the subject of non-pessimistic existentialism at all costs.
It is a relief to arrive at his bungalow and meet his wife, Joy, who is reassuringly normal, friendly and in no way likely to say 'fucker'. She bustles round making coffee and apologising for the parrot hopping round the room. The room - like the whole bungalow - is so densely encrusted with books you feel you could peel the pebble-dashed walls away and still leave the house standing.
He has never thrown a book away - he reckons he has about 30,000. They are all carefully arranged by subject, then author, and the paperbacks are sent away to be library-bound in plastic. Some sections are stored in sheds in the garden - a crime shed, a UFO shed, a biography shed - and the complete works of Colin Wilson shed. He wants to have another shed in the orchard but Joy is putting her foot down. When he dies, he says, he hopes the bungalow and sheds will be kept as a museum 'because people will probably turn up wanting to see it, like Dylan Thomas's cottage'.
'Although of course,' he adds, seeing my expression, 'it's not inevitable.'
The obvious time to have produced his autobiography would have been in 2006 - the 50th anniversary of The Outsider - but, as always, he was pressed for money, so he did it at the first whiff of a publisher's advance. The virtue of an autobiography, he explains, is that it will enable critics to see how his work is all intertwined. He admits he's written too many books on too many subjects, which has confused people. 'But now people can see there is one central point. William Faulkner in about 1947 let his work be anthologised in The Portable Faulkner and he suddenly became famous, a bestseller, and won the Nobel prize. So my volume of autobiography is The Portable Wilson!'
Hmm. The most engaging part of his book is the factual stuff, about his early struggle to be a writer and his relationship with Joy and their children. Where it drags is when he gets on to his ideas. His philosophy is basically existentialism with non-rational excrescences and characterised by bizarre nomenclature - Faculty X, Upside Downness, Peak Experiences, Right Men, The Dominant Five Per Cent, King Rats. It seems to constitute an attempt to classify human feelings and behaviour as written by a Martian who has never met an Earthling. This is, of course, Wilson's weakness and also, in a way, his charm - he has no understanding of other people whatever. When I ask if he would say he is low in emotional intelligence, he readily agrees: 'That is fair, yes.'
As a child he was so introverted, so uninterested in other people, he might have been diagnosed today with Asperger's syndrome. 'I wouldn't be surprised. I wasn't cut off from other people, but, as I keep saying in The Outsider, other people were the trouble. They kept intruding into my world whether I wanted them to or not, because what they did was to drag me away from the world of ideas and abstractions I wanted to be in. When I was a teenager I was a total romantic escapist. My world was books. I felt as Axel did in the Villiers de L'Isle-Adam play - 'As for living, our servants can do that for us.' But that all changed when I was 16 and discovered Rabelais. Suddenly I had that wonderful feeling - my God, life is good after all!'
In a way, sex was his salvation - he wanted to sleep with girls so was forced to talk to them. And he was lucky in that, at 18, he met a 14-year-old seductress who gave him a considerable sexual education. Then he met his first wife, Betty, and became a father when he was 19. He found to his surprise that he loved being married, but wasn't so keen on fatherhood (he is now - he has four children and five grandchildren - but thinks then he was too young) and never quite saw the point of baby Roderick.
There is an unintentionally funny scene in the autobiography when he decides to spend Christmas Day meditating and is furious when Betty interrupts to ask him to hold the baby. They separated soon afterwards. She reappeared when The Outsider came out, but by then he was in love with Joy. He admits that Betty is 'the one thing that often worries my conscience'.
He met Joy on one of his countless temporary jobs - he was a Christmas shop assistant and she was in charge of the cash registers. He fell for her immediately, partly because she was middle-class. 'I knew I could never bear a girl who talked with a Leicester accent or with any kind of local accent. And when I heard Joy, I thought "Oh marvellous, that's what I want." And when I asked her, "What books have you got on your shelf?" and she said she'd got Yeats and Ulysses, and Proust in French, I thought, "My God, that's the girl I really want!" Betty didn't read at all.'
He thought Joy was unattainable because she was wearing an engagement ring. 'But to my amazement, six weeks later there I was in bed with her. Couldn't get into her, mind - she was a totally impenetrable virgin - but just to lie there kissing and cuddling and feeling her bum through her pants was tremendously exciting. I was absolutely astounded - that was the greatest Peak Experience of my life.'
At this point Joy walks through the room and he tells her amiably: 'I was just saying how difficult it was the first time I got into bed with you.' Joy smiles her sweet smile and says: 'Well I'm just taking the rubbish out.'
He claims to adore women - though he thinks they are as different from men as horses from cows - but also admits to being a devoted panty fetishist. As a boy he used to try on his mother's knickers. He once stole panties from a washing-line: 'I mean, if somebody left her panties behind, certainly I would make use of them. I could masturbate with panties once, whereas now I couldn't masturbate anyway because I don't have the sexual energy but I make love to Joy virtually every day.'
Well that's nice to know. I keep praying Joy won't walk through the room again, but I suppose she must be embarrassment-proof by now. She is everything to him - his only point of contact with the real world. He has few or no close friends, especially now he has given up drinking (after a mini-stroke a year ago) and no longer goes to the pub. He used to have a sort of local fan club who met on Saturdays and produced a newsletter called The Colin Wilson Quarterly, but he no longer attends. Occasionally 'disciples' arrive - there was a girl called Kathy who turned up on the doorstep. 'We had this terrible fortnight when she kept undoing my flies and taking out my prick every time Joy left the room.' But he didn't like to evict her because he was afraid she would commit suicide.
He is exceptionally tolerant of nutters and happy to engage in long correspondence with people who have theories about, say, alien abduction - or with Ian Brady, the Moors murderer, with whom he corresponded for 10 years till Brady dumped him. But ordinary social contact - apart from with his family - seems completely missing from his life. Missing, but not missed. He says that about 10 years ago Joy insisted on going out for a drink on New Year's Eve. 'We finished off drinking champagne at midnight in our local pub and it took me a year to shake off all the people that I'd met!'
He used to say he planned to live to 300 but after his mini-stroke he now says he hopes to make 93, the age at which his hero George Bernard Shaw died. What does he expect his obituaries to say? 'I don't really care. I said at the end of Voyage to a Beginning [his first autobiography, written 40 years ago] that I regarded myself as the most important writer of the 20th century and I'd be a fool if I didn't know it, and a coward if I didn't say it. And I still feel that. With a little luck, the world will agree with me by the time I die.'
Does he think he's had much influence as a philosopher? 'Oh no. None at all. Daphne Du Maurier, who I knew when we first moved here, said to me that everyone who has a great success finds that the next 10 years are very difficult - they have a period when people take no notice of them. And I thought, No, not 10 years, I couldn't bear it! But I've been forgotten for almost 50 years. It's been a bit discouraging but I've learnt to swim against the current. But when I'd done this new autobiography, I looked at it and thought my God, this is a bloody good book! Now they'll see what I'm getting at! Now they'll see the overall view, because everything's in here - this is my life!'
"Sugar pill" redirects here. For Kids of 88 album, see Sugarpills.
The placebo effect can be produced by inert tablets, by sham surgery, and by false information, such as when electrical stimulation is turned "off" in those with Parkinson's disease implanted brain electrodes.[1]
A placebo (/pləˈsiboʊ/plə-SEE-boh; Latinplacēbō, "I shall please"[2] from placeō, "I please") is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient. Sometimes patients given a placebo treatment will have a perceived or actual improvement in a medical condition, a phenomenon commonly called the placebo effect.
In medical research, placebos are given as control treatments and depend on the use of measured deception. Common placebos include inert tablets, vehicle infusions, sham surgery,[3] and other procedures based on false information.[1] However, placebos can also have a surprisingly positive effect on a patient who knows that the given treatment is without any active drug, as compared with a control group who knowingly did not get a placebo.[4]
In one common placebo procedure, however, a patient is given an inert pill, told that it may improve his/her condition, but not told that it is in fact inert. Such an intervention may cause the patient to believe the treatment will change his/her condition; and this belief may produce a subjective perception of a therapeutic effect, causing the patient to feel their condition has improved — or an actual improvement in their condition. This phenomenon is known as the placebo effect.
Placebos are widely used in medical research and medicine,[5] and the placebo effect is a pervasive phenomenon;[5] in fact, it is part of the response to any active medical intervention.[6] Archie Cochrane suggested in 1972[7] "It is important to distinguish the very respectable, conscious use of placebos. The effect of placebos has been shown by randomized controlled trials to be very large. Their use in the correct place is to be encouraged […]"
The placebo effect points to the importance of perception and the brain's role in physical health. However, the use of placebos as treatment in clinical medicine (as opposed to laboratory research) is ethically problematic as it introduces deception and dishonesty into the doctor-patient relationship.[8] The United Kingdom Parliamentary Committee on Science and Technology has stated that: "...prescribing placebos... usually relies on some degree of patient deception" and "prescribing pure placebos is bad medicine. Their effect is unreliable and unpredictable and cannot form the sole basis of any treatment on the NHS."[3]
Since the publication of Henry K. Beecher's The Powerful Placebo[9] in 1955, the phenomenon has been considered to have clinically important effects.[10] This view was notably challenged when, in 2001, a systematic review of clinical trials concluded that there was no evidence of clinically important effects, except perhaps in the treatment of pain and continuous subjective outcomes.[10] The article received a flurry of criticism,[11] but the authors later published a Cochrane review with similar conclusions (updated as of 2010[update]).[12] Most studies have attributed the difference from baseline until the end of the trial to a placebo effect, but the reviewers examined studies which had both placebo and untreated groups in order to distinguish the placebo effect from the natural progression of the disease.[10] However these conclusions have been criticized because of the great variety of diseases—more than 40—in this metastudy. The effect of placebo is very different in different diseases. By pooling quite different diseases the results can be leveled out.
A placebo has been defined as "a substance or procedure… that is objectively without specific activity for the condition being treated".[11] Under this definition, a wide variety of things can be placebos and exhibit a placebo effect. Pharmacological substances administered through any means can act as placebos, including pills, creams, inhalants, and injections. Medical devices such as ultrasound can act as placebos.[13][14]Sham surgery,[15][16][17] sham electrodes implanted in the brain,[1] and sham acupuncture, either with sham needles or on fake acupuncture points, have all exhibited placebo effects.[18] Bedding not treated to reduce allergies has been used as a placebo to control for treated bedding.[19] The physician has even been called a placebo;[20] a study found that patient recovery can be increased by words that suggest the patient "would be better in a few days", and if the patient is given treatment, that "the treatment would certainly make him better" rather than negative words such as "I am not sure that the treatment I am going to give you will have an effect".[21] The placebo effect may be a component of pharmacological therapies: Pain killing and anxiety reducing drugs that are infused secretly without an individual's knowledge are less effective than when a patient knows they are receiving them. Likewise, the effects of stimulation from implanted electrodes in the brains of those with advanced Parkinson's disease are greater when they are aware they are receiving this stimulation.[22] Sometimes administering or prescribing a placebo merges into fake medicine.
The placebo effect has sometimes been defined as a physiological effect caused by the placebo, but Moerman and Jonas have pointed out that this seems illogical, as a placebo is an inert substance that does not directly cause anything. Instead they introduced the term "meaning response" for the meaning that the brain associates with the placebo, which causes a physiological placebo effect. They propose that the placebo, which may be unethical, could be avoided entirely if doctors comfort and encourage their patients' health.[11] Ernst and Resch also attempted to distinguish between the "true" and "perceived" placebo effect, as they argued that some of the effects attributed to the placebo effect could be due to other factors.[23]
The placebo effect has been controversial throughout history. Notable medical organizations have endorsed it,[24] but in 1903 Richard Cabot concluded that it should be avoided because it is deceptive. Newman points out the "placebo paradox", – it may be unethical to use a placebo, but also unethical "not to use something that heals". He suggests to solve this dilemma by appropriating the meaning response in medicine, that is make use of the placebo effect, as long as the "one administering… is honest, open, and believes in its potential healing power".[8] Another possible resolution of the ethical dilemma might come from the "honest placebo" effect found in a 2010 study[4] carried out by researchers in the Program in Placebo Studies at the Harvard Medical School, where patients with irritable bowel syndrome experienced a significant beneficial effect even though they were told the pills they were taking were placebos, as compared to a control group who received no pills.
Although the placebo effect and theories on its underlying mechanisms are mostly understood in terms of human psychology, studies have also indicated that non-human animals such as dogs can also have symptoms reduced by placebo treatments.[25]
The word 'placebo', Latin for "I will please", dates back to a Latin translation of the Bible by St Jerome.[26] It was first used in a medicinal context in the 18th century. In 1785 it was defined as a "commonplace method or medicine" and in 1811 it was defined as "any medicine adapted more to please than to benefit the patient", sometimes with a derogatory implication[27] but not with the implication of no effect.[28] Placebos were widespread in medicine until the 20th century, and they were sometimes endorsed as necessary deceptions.[24] In 1903 Richard Cabot said that he was brought up to use placebos,[24] but he ultimately concluded by saying that "I have not yet found any case in which a lie does not do more harm than good".[8] In 1961 Henry K. Beecher found[29] that surgeons he categorized as enthusiasts relieved their patients' chest pain and heart problems more than skeptic surgeons.[8] In 1961 Walter Kennedy introduced the word nocebo.[24] Beginning in the 1960s, the placebo effect became widely recognized and placebo controlled trials became the norm in the approval of new medications.[30] Later, researchers became interested in understanding the placebo effect, rather than just controlling for its effects, and in 2011, a Program in Placebo Studies was established at the Harvard Medical School.
The placebo effect is highly variable in its magnitude and reliability and is typically strongest in measures of subjective symptoms (e.g., pain) and typically weak-to-nonexistent in objective measures of health points (e.g., blood pressure, infection clearance).[citation needed]
A 2001 meta-analysis of clinical trials with placebo groups and no-treatment groups found no evidence for a placebo effect on objectively measured outcomes and possible small benefits in studies with continuous subjective outcomes (particularly pain).[10] A 2004 follow-up analysis found similar results and increased evidence of bias in smaller trials that calls into question the apparent placebo effect on subjective outcomes.[31]
Because the placebo response is simply the patient response that cannot be attributed to an investigational intervention, there are multiple possible components of a measured placebo effect. These components having varying relevance depending on study design and the types of observations.[32] While there is some evidence that placebo interventions can alter levels of hormones[33] or endogenous opioids,[34] other prominent components include expectancy effects, regression to the mean,[35][36] and flawed research methodologies.
The placebo effect is related to the perceptions and expectations of the patient; if the substance is viewed as helpful, it can heal, but, if it is viewed as harmful, it can cause negative effects, which is known as the nocebo effect. In 1985, Irving Kirsch hypothesized that placebo effects are produced by the self-fulfilling effects of response expectancies, in which the belief that one will feel different leads a person to actually feel different.[37] According to this theory, the belief that one has received an active treatment can produce the subjective changes thought to be produced by the real treatment. Placebos can act similarly through classical conditioning, wherein a placebo and an actual stimulus are used simultaneously until the placebo is associated with the effect from the actual stimulus.[38] Both conditioning and expectations play a role in placebo effect,[39] and make different kinds of contribution. Conditioning has a longer-lasting effect,[40] and can affect earlier stages of information processing.[41] The expectancy effect can be enhanced through factors such as the enthusiasm of the doctor, differences in size and color of placebo pills, or the use of other interventions such as injections. In one study, the response to a placebo increased from 44% to 62% when the doctor treated them with "warmth, attention, and confidence."[42] Expectancy effects have been found to occur with a range of substances. Those that think that a treatment will work display a stronger placebo effect than those that do not, as evidenced by a study of acupuncture.[43][44]
Because the placebo effect is based upon expectations and conditioning, the effect disappears if the patient is told that their expectations are unrealistic, or that the placebo intervention is ineffective. A conditioned pain reduction can be totally removed when its existence is explained.[45] It has also been reported of subjects given placebos in a trial of anti-depressants, that "Once the trial was over and the patients who had been given placebos were told as much, they quickly deteriorated."[46]
A placebo described as a muscle relaxant will cause muscle relaxation and, if described as the opposite, muscle tension.[47] A placebo presented as a stimulant will have this effect on heart rhythm, and blood pressure, but, when administered as a depressant, the opposite effect.[48] The perceived consumption of caffeine has been reported to cause similar effects even when decaffeinated coffee is consumed,[49][50] although a 2003 study found only limited support for this.[51] Placebos represented as alcohol can cause intoxication[52] and sensorimotor impairment.[53] Perceived ergogenic aids can increase endurance,[54] speed[55] and weight-lifting ability,[56] leading to the question of whether placebos should be allowed in sport competition.[57] Placebos can help smokers quit.[58] Perceived allergens that are not truly allergenic can cause allergies.[59] Interventions such as psychotherapy can have placebo effects.[60]pp 164–173 The effect has been observed in the transplantation of human embryonic neurons into the brains of those with advanced Parkinson's disease.[61]
Because placebos are dependent upon perception and expectation, various factors that change the perception can increase the magnitude of the placebo response. For example, studies have found that the color and size of the placebo pill makes a difference, with "hot-colored" pills working better as stimulants while "cool-colored" pills work better as depressants. Capsules rather than tablets seem to be more effective, and size can make a difference.[62] One researcher has found that big pills increase the effect[63] while another has argued that the effect is dependent upon cultural background.[64] More pills,[65] branding,[66] past experience,[67] and high price[68] increase the effect of placebo pills. Injection[69] and acupuncture[18] have larger effect than pills. Proper adherence to placebos is associated with decreased mortality.[70] Motivation may contribute to the placebo effect. The active goals of an individual changes his/her somatic experience by altering the detection and interpretation of expectation-congruent symptoms, and by changing the behavioral strategies a person pursues.[71][72] Motivation may link to the meaning through which people experience illness and treatment. Such meaning is derived from the culture in which they live and which informs them about the nature of illness and how it responds to treatment. Research into the placebo treatment of gastric and duodenal ulcers shows that this varies widely with society.[11] The placebo effect in treating gastric ulcers is low in Brazil, higher in northern Europe (Denmark, Netherlands), and extremely high in Germany. However, the placebo effect in treating hypertension is lower in Germany than elsewhere.[73] Social observation can induce a placebo effect such when a person sees another having reduced pain following what they believe is a pain reducing procedure.[74]
The placebo effect can work selectively, under the influence of various psychological factors. If a placebo cream is applied on one hand with the expectation that it is an analgesic, it will reduce pain only in that hand and not elsewhere on the body.[75] If a person is given a placebo under one name, and they respond, they will respond in the same way on a later occasion to that placebo under that name but not if under another.[76]
Functional imaging upon placebo analgesia shows that it links to the activation, and increased functional correlation between this activation, in the anterior cingulate, prefrontal, orbitofrontal and insular cortices, nucleus accumbens, amygdala, the brainstem periaqueductal gray matter,[77][78][79] and the spinal cord.[80][81][82][83]
These changes can act upon the brain's early stages of information processing: Research using evoked brain potentials upon painful laser pulses, for example, finds placebo effects upon the N2–P2, a biphasic negative–positive complex response, the N2 peak of which is at about 230 ms, and the P2 one at about 380 ms.[41] They occur not only during placebo analgesia but after receiving the analgesic placebo (the areas are different here, and involve the medial prefrontal cortex, posterior parietal cortex and inferior parietal lobule).[84]
Different areas in the higher brain have different functions. The prefrontal involvement could be related to recalling the placebo and maintaining its cognitive presence in a "self-reinforcing feedback loop" (during pain an individual recalls having taken the placebo and reduced pain reinforces its status as an analgesic).[85] The rostral anterior cingulate cortex (rACC) and its subcortical connectivity could be related to the expectation of potential pain stimuli[86][87]
The higher brain works by regulating subcortical processes. High placebo responses link with enhanced dopamine and mu-opioid activity in the circuitry for reward responses and motivated behavior of the nucleus accumbens, and, on the converse, anti-analgesic nocebos responses were associated with deactivation in this part of the brain of dopamine and opioid release.[78] (It has been known that placebo analgesia depends upon the release in the brain of endogenous opioids since 1978.[88]) Such analgesic placebos activation changes processing lower down in the brain by enhancing the descending inhibition through the periaqueductal gray[78] on spinal nociceptive reflexes, while the expectations of anti-analgesic nocebos acts in the opposite way to block this.[80]
The brain is also involved in less-studied ways upon nonanalgesic placebo effects:
Depression: Placebos reducing depression affect many of the same areas that are activated by antidepressants with the addition of the prefrontal cortex[90][91]
Caffeine: Placebo-caffeinated coffee causes an increase in bilateral dopamine release in the thalamus.[92]
Glucose: The expectation of an intravenous injection of glucose increases the release of dopamine in the basal ganglia of men (but not women).[93]
Methylphenidate: The expectation of intravenous injection of this drug in inexperienced drug users increased the release of dopamine in the ventral cingulate gyrus and nucleus accumbens, with this effect being largest in those with no prior experience of the drug.[94]
Present functional imaging upon placebo analgesia has been summarized as showing that the placebo response is "mediated by "top-down" processes dependent on frontal cortical areas that generate and maintain cognitive expectancies. Dopaminergic reward pathways may underlie these expectancies".[95] "Diseases lacking major 'top-down' or cortically based regulation may be less prone to placebo-related improvement".[96]
The brain has control over the body processes affected by placebos. Pain, motor fatigue, and fever are directly organized by the brain[citation needed]. Other processes usually regulated by the body such as the immune system are also controlled indirectly through the sympathetic and parasympathetic nervous system[citation needed].
Research upon conditioning in animals shows the brain can learn control over them[citation needed]. In conditioning, a neutral stimulus saccharin is paired in a drink with an agent that produces an unconditioned response. For example, that agent might be cyclophosphamide that causes immunosuppression. After learning this pairing, the taste of saccharin by itself through neural top-down control created immunosuppression, as a new conditioned response.[97] Such conditioning has been found to affect a diverse variety of not just basic physiological processes in the immune system but ones such as serum iron levels, oxidative DNA damage levels, and insulin secretion. This work was originally done on rats, however the same conditioning of basic physiological processes can also occur in humans[citation needed]. Recent reviews have argued the placebo effect is due to top-down control by the brain for immunity[98] and pain.[99] Pacheco-López and colleagues have raised the possibility of "neocortical-sympathetic-immune axis providing neuroanatomical substrates that might explain the link between placebo/conditioned and placebo/expectation responses."[98]:441
A recent fMRI study has shown that a placebo can reduce pain-related neural activity in the spinal cord, indicating that placebo effects can extend beyond the brain.[100]
Evolutionary medicine identifies many symptoms such as fever, pain, and sickness behavior as evolved responses to protect or enhance the recovery from infection and injury. Fever, for example, is an evolved self-treatment that removes bacteria or viruses through raised body temperature. These evolved responses, however, also have a cost that depending upon circumstances can outweigh their benefit (due to this, for example, there is a reduction in fever during malnutrition or late pregnancy). According to the health management system theory proposed by Nicholas Humphrey, the brain has been selected to ensure that evolved responses are deployed only when the cost benefit is biologically advantageous. To do this, the brain factors in a variety of information sources, including the likelihood derived from beliefs that the body will get well without deploying its costly evolved responses. One such source of information is the knowledge the body is receiving care and treatment. The placebo effect in this perspective arises when false information about medications misleads the health management system about the likelihood of getting well so that it selects not to deploy an evolved self-treatment.[101]
Placebo effects can last for a long time: over 8 weeks for panic disorder,[102] 6 months for angina pectoris,[103] and two and half years for rheumatoid arthritis.[104] Placebo effects after verbal suggestion for mild pain can be robust and still exist after being repeated ten times even if they have no actual pharmacological pain killing action.[45]
Hróbjartsson and Peter Gøtzsche published a study in 2001[10] and a follow-up study in 2004[31] questioning the nature of the placebo effect. The studies were performed as two meta-analyses. They found that in studies with a binary outcome, meaning patients were classified as improved or not improved, the placebo group had no statistically significant improvement over the no-treatment group. Likewise, there was no significant placebo effect in studies in which objective outcomes (such as blood pressure) were measured by an independent observer. The placebo effect could be documented only in studies in which the outcomes (improvement or failure to improve) were reported by the subjects themselves. The authors concluded that the placebo effect does not have "powerful clinical effects," (objective effects) and that patient-reported improvements (subjective effects) in pain were small and could not be clearly distinguished from reporting bias. Other researchers (Wampold et al.) re-analysed the same data from the 2001 meta-analysis and concluded that the placebo effects for objective symptom measures are comparable to placebo effects for subjective ones and that the placebo effect can exceed the effect of the active treatment by 20% for disorders amenable to the placebo effect,[105][106] a conclusion which Hróbjartsson & Gøtzsche described as "powerful spin".[107] Another group of researchers noted the dramatically different conclusions between these two sets of authors despite nearly identical meta-analytic results, and suggested that placebo effects are indeed significant but small in magnitude.[108]
Hróbjartsson and Gøtzsche's conclusion has been criticised on several grounds. Their meta-analysis covered studies into a highly mixed group of conditions. It has been reported that for measurements in peripheral organs the placebo effect seems to be more effective in achieving improvements in physical parameters (such as decreasing hypertension, improving FEV1 in asthma sufferers, or decreasing prostatic hyperplasia or anal fissure) than in improving biochemical parameters (such as cholesterol or cortisol) in various conditions such as venous leg ulcers, Crohn's disease, urinary tract infection, and chronic heart failure.[109] Placebos also do not work as strongly in clinical trials because the subjects do not know whether they might be getting a real treatment or a sham one. Where studies are made of placebos in which people think they are receiving actual treatment (rather than merely its possibility) the placebo effect has been observed.[110] Other writers have argued that the placebo effect can be reliably demonstrated under appropriate conditions.[111]
In another update by Hróbjartsson & Gøtzsche, published as a 2010 Cochrane systematic review which confirms and modifies their previous work, over 200 trials investigating 60 clinical conditions were included. Placebo interventions were again not found to have important clinical effects in general but may influence patient-reported outcomes in some situations, especially pain and nausea, although it was "difficult to distinguish patient-reported effects of placebo from response bias". The pooled relative risk they calculated for placebo was 0.93 (effect of only 7%) but significant. Effects were also found for phobia and asthma but were uncertain due to high risk of bias. In other conditions involving three or more trials, there was no statistically significant effect for smoking, dementia, depression, obesity, hypertension, insomnia and anxiety, although confidence intervals were wide. Several clinical (physical placebos, patient-involved outcomes, falsely informing patients there was no placebo) and methodological (small sample size, explicit aim of studying the placebo effect) factors were associated with higher effects of placebo. Despite low effects in general and the risk of bias, the authors acknowledged that large effects of placebo interventions may occur in certain situations.[112]
Similar to the placebo effect, inert substances have the potential to cause negative effects via the "nocebo effect" (Latinnocebo = "I will harm"). In this effect, giving an inert substance has negative consequences.[113]
Another negative consequence is that placebos can cause side-effects associated with real treatment.[114] One example of this is with those that have already taken an opiate, can then show respiratory depression when given it again in the form of a placebo.[115]
Withdrawal symptoms can also occur after placebo treatment. This was found, for example, after the discontinuation of the Women's Health Initiative study of hormone replacement therapy for menopause. Women had been on placebo for an average of 5.7 years. Moderate or severe withdrawal symptoms were reported by 40.5% of those on placebo compared to 63.3% of those on hormone replacement.[116]
A study of Danish general practitioners found that 48% had prescribed a placebo at least 10 times in the past year.[5] The most frequently prescribed placebos were antibiotics for viral infections, and vitamins for fatigue. Specialists and hospital-based physicians reported much lower rates of placebo use. A 2004 study in the British Medical Journal of physicians in Israel found that 60% used placebos in their medical practice, most commonly to "fend off" requests for unjustified medications or to calm a patient.[117] The accompanying editorial concluded, "We cannot afford to dispense with any treatment that works, even if we are not certain how it does."[118] Other researches have argued that open provision of placebos for treating ADHD in children can be effective in maintaining ADHD children on lower stimulant doses in the short term.[119]
Critics of the practice responded that it is unethical to prescribe treatments that do not work, and that telling a patient (as opposed to a research test subject) that a placebo is a real medication is deceptive and harms the doctor-patient relationship in the long run. Critics also argued that using placebos can delay the proper diagnosis and treatment of serious medical conditions.[120]
The following impracticalities exist with placebos: (See the BMJ posted responses to Spiegel's editorial rapid response online section.[118])
Roughly only 30% of the population seems susceptible to placebo effects, and it is not possible to determine ahead of time whether a placebo will work or not. (However the placebo effect is zero in studies of blood poisoning and up to 80% in studies of wound on the duodenum).
Patients rightfully want immediate relief or improvement from their illness or symptoms. A non-placebo can often provide that, while a placebo might not.
Legitimate doctors and pharmacists could open themselves up to charges of fraud since sugar pills would cost pennies or cents for a bottle, but the price for a "real" medication would have to be charged to avoid making the patient suspicious.
About 25% of physicians in both the Danish and Israeli studies used placebos as a diagnostic tool to determine if a patient's symptoms were real, or if the patient was malingering. Both the critics and defenders of the medical use of placebos agreed that this was unethical. The British Medical Journal editorial said, "That a patient gets pain relief from a placebo does not imply that the pain is not real or organic in origin...the use of the placebo for 'diagnosis' of whether or not pain is real is misguided."
The placebo administration may prove to be a useful treatment in some specific cases where recommended drugs cannot be used. For example, burn patients who are experiencing respiratory problems cannot often be prescribed opioid (morphine) or opioid derivatives (pethidine), as these can cause further respiratory depression. In such cases placebo injections (normal saline, etc.) are of use in providing real pain relief to burn patients if those not in delirium are told they are being given a powerful dose of painkiller.
Referring specifically to homeopathy, the House of Commons of the United Kingdom Science and Technology Committee has stated:
In the Committee's view, homeopathy is a placebo treatment and the Government should have a policy on prescribing placebos. The Government is reluctant to address the appropriateness and ethics of prescribing placebos to patients, which usually relies on some degree of patient deception. Prescribing of placebos is not consistent with informed patient choice-which the Government claims is very important-as it means patients do not have all the information needed to make choice meaningful.
Beyond ethical issues and the integrity of the doctor-patient relationship, prescribing pure placebos is bad medicine. Their effect is unreliable and unpredictable and cannot form the sole basis of any treatment on the NHS.[3]
A survey in the United States of more than 10,000 physicians came to the result that while 24% of physicians would prescribe a treatment that is a placebo simply because the patient wanted treatment, 58% would not, and for the remaining 18%, it would depend on the circumstances.[121]
Placebos do not work for everyone.[122][123]Henry K. Beecher, in a paper in 1955,[9] suggested placebo effects occurred in about 35% of people. However, the response rate is wide, ranging from 0% up to nearly everyone. In a dental postoperative pain model, placebo analgesia occurred in 39%.[123] In research upon ischemic arm pain, placebo analgesia was found in 27%.[122] The placebo analgesia rate for cutaneous healing of left hand skin was 56%.[124]
Though not everyone responds to a placebo, neither does everyone respond to an active drug. The percentage of patients who reported relief following placebo (39%) is similar to the percentage following 4 mg (36%) and 6 mg (50%) of hidden morphine.[125]
In the 1950s, there was considerable research to find whether there was a specific personality to those that responded to placebos. The findings could not be replicated[126] and it is now thought to have no effect.[127]
The desire for relief from pain, "goal motivation", and how far pain is expected to be relieved increases placebo analgesia.[71] Another factor increasing the effectiveness of placebos is the degree to which a person attends to their symptoms, "somatic focus".[72] Individual variation in response to analgesic placebos has been linked to regional neurochemical differences in the internal affective state of the individuals experiencing pain.[128]
Those with Alzheimer's disease lose the capacity to be influenced by placebos, and this is attributed to the loss of their prefrontal cortex dependent capacity to have expectations.[129] Children seem to have greater response than adults to placebos.[130]
In social anxiety disorder (SAD) an inherited variant of the gene for tryptophan hydroxylase 2 (enzyme that synthesizes the neurotransmitter serotonin) is linked to reduced amygdala activity and greater susceptibility to the placebo effect.[131][132][133] The authors note "additional work is necessary to elucidate the generalizability of the findings".
In a 2012 study, variations on the COMT (catechol-O-methyltransferase) gene related to dopamine release are found to be critical in the placebo effect among the patients with irritable bowel syndrome participating in the trial, a research group in Harvard Medical School reported. Patients with a variation of met/met, for having two copies of the methionineallele were shown to be more likely to respond to the placebo treatment, while the variation of val/val, for their two copies of valine allele responded the least. The response of patients with one copy each of methionine and valine fell in the middle. Release of dopamine in patients with the met/met variations is thought to link to reward and 'confirmation bias' which enhance the sense that the treatment is working. The role of the COMT gene variations are expected to be more prominent in studies where patients report more subjective conditions such as pain and fatigue rather than objective physiological measurements.[134][135]
The placebo effect occurs more strongly in some conditions than others. Dylan Evans has suggested that placebos work most strongly upon conditions such as pain, swelling, stomach ulcers, depression, and anxiety that have been linked with activation of the acute-phase response.[60]
The placebo effect is believed to reduce pain in two different ways. One way is by the placebo initiating the release of endorphins, which are natural pain killers produced by the brain.[136] The other way is the placebo changing the patient's perception of pain. "A person might reinterpret a sharp pain as uncomfortable tingling."[137]
Placebo analgesia is more likely to work the more severe the pain.[138] One study found that for postoperative pain following the extraction of the third molar, saline injected while telling the patient it was a powerful painkiller was as potent as a 6–8 mg dose of morphine.[125] Most research reports average reduction for a group of people, but this can be lower (some people do not respond). In one study using injection of capsaicin below the skin found that this reduced group average pain compared to no placebo by ~46% to ~57%.[75] Another measure is the ability to endure pain. In one study, placebos increased this on average by about 3.5 minutes compared to just under 14 minutes without it.[139] The average strength of placebos upon pain on a visual analog scale is 2 out of 10 units.[127][140] Individuals who respond to placebos may show even greater effects, up to 5 out of 10 units.[122]
In 1998, a meta-analysis of published antidepressant trials found that 75% of the effectiveness of anti-depressant medication is due to the placebo effect and other non-specific effects, rather than the treatment itself.[141] Later, meta-analyses including data from unpublished trials found that the overall difference between drug and placebo is not clinically significant except in cases of very extreme depression,[142][143] Another meta-analysis found that 79% of depressed patients receiving placebo remained well (for 12 weeks after an initial 6–8 weeks of successful therapy) compared to 93% of those receiving antidepressants.[144] A meta-analysis in 2002 found a 30% reduction in suicide and attempted suicide in the placebo groups compared to a 40% reduction in the treated groups.[145]
A 2002 article in The Washington Post titled "Against Depression, a Sugar Pill Is Hard to Beat" summarized research as follows:
In the majority of trials conducted by drug companies in recent decades, sugar pills have done as well as -- or better than -- antidepressants. Companies have had to conduct numerous trials to get two that show a positive result, which is the Food and Drug Administration's minimum for approval. The makers of Prozac had to run five trials to obtain two that were positive, and the makers of Paxil and Zoloft had to run even more.[46]
A meta-study of 31 placebo-controlled trials of the gastric acid secretion inhibitor drug cimetidine in the treatment of gastric or duodenal ulcers found that placebo treatments, in many cases, were as effective as active drugs: of the 1692 patients treated in the 31 trials, 76% of the 916 treated with the drug were "healed", and 48% of the 776 treated with placebo were "healed".[11][146] These results were confirmed by the direct post-treatment endoscopy. It was also found that German placebos were "stronger" than others; and that, overall, different physicians evoked quite different placebo responses in the same clinical trial.[146]:15 Moreover, in many of these trials the gap between the active drugs and the placebo controls was "not because [the trials' constituents] had high drug effectiveness, but because they had low placebo effectiveness".[146]:13
In some trials, placebos were effective in 90% of the cases, whereas in others the placebos were effective in only 10% of the cases. It was argued that "what is demonstrated in [these] studies is not enhanced healing in drug groups but reduced healing in placebo groups".[146]:14 It was also noted the results of two studies (one conducted in Germany, the other in Denmark), which examined "ulcer relapse in healed patients" showed that the rate of relapse amongst those "healed" by the active drug treatment was five times that of those "healed" by the placebo treatment.[146]:14–15
It was previously assumed that placebo response rates in patients with chronic fatigue syndrome (CFS) are unusually high, "at least 30% to 50%", because of the subjective reporting of symptoms and the fluctuating nature of the condition. According to a meta-analysis and contrary to conventional wisdom, the pooled response rate in the placebo group was 19.6%, even lower than in some other medical conditions. The authors offer possible explanations for this result: CFS is widely understood to be difficult to treat, which could reduce expectations of improvement. In context of evidence showing placebos do not have powerful clinical effects when compared to no treatment, a low rate of spontaneous remission in CFS could contribute to reduced improvement rates in the placebo group. Intervention type also contributed to the heterogeneity of the response. Low patient and provider expectations regarding psychological treatment may explain particularly low placebo responses to psychiatric treatments.[147]
The effect of placebo treatments (an inert pill unless otherwise noted) has been studied for the following medical conditions. Many of these citations concern research showing that active treatments are effective, but that placebo effects exist as well.
The placebo effect makes it more difficult to evaluate new treatments. The placebo effect in such clinical trials is weaker than in normal therapy since the subjects are not sure whether the treatment they are receiving is active.[110] Apparent benefits of a new treatment (usually a drug but not necessarily so) may not derive from the treatment but from the placebo effect. This is particularly likely, given that new therapies seem to have greater placebo effects.[194] Clinical trials control for this effect by including a group of subjects that receives a sham treatment. The subjects in such trials are blinded as to whether they receive the treatment or a placebo. If a person is given a placebo under one name, and they respond, they will respond in the same way on a later occasion to that placebo under that name but not if under another.[195] Clinical trials are often double-blinded so that the researchers also do not know which test subjects are receiving the active or placebo treatment.The placebo effect in such clinical trials is weaker than in normal therapy since the subjects are not sure whether the treatment they are receiving is active.[110]
Knowingly giving a person a placebo when there is an effective treatment available is a bioethically complex issue. While placebo-controlled trials might provide information about the effectiveness of a treatment, it denies some patients what could be the best available (if unproven) treatment. Informed consent is usually required for a study to be considered ethical, including the disclosure that some test subjects will receive placebo treatments.
The ethics of placebo-controlled studies have been debated in the revision process of the Declaration of Helsinki.[196] Of particular concern has been the difference between trials comparing inert placebos with experimental treatments, versus comparing the best available treatment with an experimental treatment; and differences between trials in the sponsor's developed countries versus the trial's targeted developing countries.[197]
A further issue of concern to pharmaceutical companies is that the effectiveness of placebos has increased over time,[198] thus making it more difficult to demonstrate the effectiveness of new drugs. The reason for the increased effectiveness is disputed.
In the opposite effect, a patient who disbelieves in a treatment may experience a worsening of symptoms. This effect, now called by analogy nocebo (Latinnocebo = "I shall harm") can be measured in the same way as the placebo effect, e.g., when members of a control group receiving an inert substance report a worsening of symptoms. The recipients of the inert substance may nullify the placebo effect intended by simply having a negative attitude towards the effectiveness of the substance prescribed, which often leads to a nocebo effect, which is not caused by the substance, but due to other factors, such as the patient's mentality towards his or her ability to get well, or even purely coincidental worsening of symptoms.[113]
Placebos used in clinical trials have sometimes had unintended consequences. A report in the Annals of Internal Medicine that looked at details from 150 clinical trials found that certain placebos used in the trials affected the results. For example, one study on cholesterol-lowering drugs used olive oil and corn oil in the placebo pills. However, according to the report, this "may lead to an understatement of drug benefit: The monounsaturated and polyunsaturated fatty acids of these 'placebos,' and their antioxidant and anti-inflammatory effects, can reduce lipid levels and heart disease." Another example researchers reported in the study was a clinical trial of a new therapy for cancer patients suffering from anorexia. The placebo that was used included lactose. However, since cancer patients typically face a higher risk of lactose intolerance, the placebo pill might actually have caused unintended side-effects that made the experimental drug look better in comparison.[199]
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