Talk:Opioid/Archive 1

message: I have merged the previous text for opiate into this expanded entry for opioid, and created a redirect from opiate.
As the article says, the word "opioid" is now the preferred general medical and scientific term for any drug, natural or synthetic, that behaves like opium on the central nervous system. "Opiate" is a more restrictive term that applies only to natural and semi-synthetic opioids, so I thought it made sense to perform this restructuring.
User: karn
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I have now also merged in the contents of opioid analgesic, added some text, and created a redirect. The list of opioids is not complete, and the various classifications need checking.
User: karn
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I am not particularly happy with the opening sentence referring to opium. 
I think this is a little unfortunate to imply all drugs listed below
are opium derivates or opioid receptors are in any way sensitive to opium.
It'd be better to mention opium later on in the article.
Kpjas
----
How would you reword it? The definition of "opioid" *is* in fact any drug that mimics the effects of opium in the body, whether or not the drug is actually made from opium. Perhaps it would be better to say that an opioid is any drug that mimics the effects of *morphine*, the primary alkaloid in natural opium? User:Karn
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Okay, I've reworded the opening to drop the first reference to opium, and to then refer to it as a source of morphine. I also added brief references to the three subtypes of opioid receptors. How does that look? User:Karn
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Two questions:
1) Should I create a redirect from pentazocine (on this page) to Talwin? (I know Talwin is not the best entry for the subject - but I don't have the knowledge to improve on it)
:::I think Talwin>>>pentazocine is better, best to have the article under the chemical name, since the patent on Talwin will eventually expire, but the chemical name will not.  'think long term'.  cheers.Pedant 22:49, 2004 Nov 11 (UTC)
::::Thanks. [for doing it and for educating me] (I'm learning as I go.) CJewell 14:51, 26 Nov 2004 (UTC)
replies: text: I remember the two pages mismatching to the point of being contradictory. They're clearer (and they match) now. CJewell 14:51, 26 Nov 2004 (UTC)

text: See your talk. JFW | T@lk 11:42, 11 Nov 2004 (UTC)
thread_title:  No title 

message: Another future use of opioids might be to protect against ischemia/reperfusion injuries, particularly in the heart. The proposed mechanisms involve actions on potassium pumps, protein kinase C, or potentially nitric oxide synthase. I'm doing a literature review on this aspect at the moment, but if someone who's already up to speed on the issue (and who knows that they want to jump in and include this in the current article) wants to put a line or two in, go right ahead :)
While this is still relatively cutting-edge stuff, it might also give readers an idea of how opioid receptors act in non-neural tissue.
For a review on opioids & cardioprotection, I'd recommend Schultz & Gross, 2001. Pharmacology & Therapeutics 89:123-137.
Cheers; Potatophysics 09:48, 9 September 2005 (UTC)
thread_title:  Future Uses of Opioids 

message: I was reading the discussion of the definition of 'opioid' and what I was thinking is that in the age of pharmacogenomics, an opioid is any ligand that binds an opioid receptor (is that tautological?). To that end, I added some brief info on receptor types and subtypes to give a summary of info that is presented in greater detail on the pharmacology page. One other thing: in the reading I have done, the sigma opioid receptor mediates some properties of dysphoria and hallucinations and is listed as having specific agonists such as pentazocine, yet on the pharmacology page, it says that the sigma receptor has been found not to be a true opioid receptor. Am I behind the times? Thanks!
Awolf1 16:46, 22 November 2005 (UTC)
thread_title:  receptor types 

message: Come on, no one really uses this term "ludibund". Someone (Jonathan Ott?) made it up by pseudo-back-translating to Latin, to avoid the word "recreational", right? But it never caught on, so why is wikipedia using an unknown dodge-word as a topic heading? 
TH 00:36, 2 December 2005 (UTC)
replies: text: It is because "abuse" is insulting to the "recreational" community, and "recreational" is an understatement to the medical community. JFW | T@lk 01:00, 2 December 2005 (UTC)
thread_title:  ludibund 

message: Tramadol, mentioned above, seems to be US FDA-approved for pain, not for depression; and it's on Public Citizen's list at WorstPills.org, so I'm not inclined to cite it.
TH 00:41, 2 December 2005 (UTC)
replies: text: What does WorstPills base itself on? JFW | T@lk 01:00, 2 December 2005 (UTC)
thread_title:  Tramadol 

message: The old version was fatally flawed, I believe --
starting with the fact that the two headers
"Opioid Abuse" and "Ludibund use" implied
that some recreational use is not abuse --
and right there in the headers you have a POV that many would
disagree with.
:During alcohol prohibition you could say the same about alcohol — that any non-medical use of alcohol was abuse.  Today, one can drink wine with dinner without being called an alcohol abuser.  Also during prohibition, a considerable number of teetotallers used opioids (opium, morphine and heroin) as an alternative to alcohol.  Now things are the opposite way around.  Does that negate opposing POV?  I think not.  --Thoric 22:20, 5 December 2005 (UTC)
replies: text: Obviously you don't understand how POV works.  The article is a collection of information and points of view, and what makes the article have a neutral point of view, is by presenting all points of view without trying to favor one over another.  I suggest you actually read Wikipedia:Neutral point of view.  Thanks.  --Thoric 23:40, 5 December 2005 (UTC)

text: WP:CITE. Please. JFW | T@lk 04:25, 4 December 2005 (UTC)
thread_title:  nonclinical use -- major reorg 

message: No offense intended toward Australian readers and writers, but I clarified and added info by switching from Rossi to Drug Facts and Comparisons, widely available in the US (unlike Rossi) and therefore more meaningful to and verifiable by a larger fragment of the world population. 
Drug Facts and Comparisons was indicated to me by a medical university librarian as the most authoritative and independent source of drug information. I think she said that DF&C got its information from Medex, but I'm not sure about that. DF&C is at factsandcomparisons.com. 
Note added info: "sole", not "main"; anesthesia; methadone for detox; and the four "only" restrictions. 
TH 17:27, 8 December 2005 (UTC)
thread_title:  Citation switched from Rossi to Drug Facts and Comparisons 

message: TH 17:53, 8 December 2005 (UTC)
replies: text: Put ~~~~ after your posts. JFW | T@lk 05:29, 9 December 2005 (UTC)

text: Hmmm. Probably because the Wiki wouldn't know where to automatically put your signature. It would have to run a diff after saving the edit, putting more strain on the server than a simple transinclusion. 07:28, 9 December 2005 (UTC)
thread_title:  Why doesn't Wikipedia automatically sign my Talk for me? 

message: The more I read, the less I see evidence that "most opioids produce euphoria in most people". For example, Reynolds et al., Morphine and Allied Drugs, says codeine does not generally produce euphoria. Lacking evidence, I think we have to go with the weaker statement. 
Also, I haven't found evidence that the rate of developing tolerance is the same across all effects. I've found hints to the contrary. Lacking evidence, I think we have to go with the weaker statement. I cite Weil for the exception of constipation.
TH 07:09, 9 December 2005 (UTC)
thread_title:  less euphoria; unequal tolerance 

message: Controlled Substances Act: 
Way, E. Leong (Department of Pharmacology, School of
Medicine, Universtiy of California, San Francisco, San Francisco,
California, USA), "History of Opiate Use in the Orient and the United
States", in Opioids in Mental Illness: Theories, Clinical
Observations, and Treatment Possibilities, edited by Karl Verebey,
The New York Academy of Sciences, New York, New York, 1982, p. 22. 
British system:
Berridge, Virginia (Institute of Historical Research,
University of London, London, England), "Opiate Use in England,
1800-1926", in Opioids in Mental Illness: Theories, Clinical
Observations, and Treatment Possibilities, edited by Karl Verebey,
The New York Academy of Sciences, New York, New York, 1982, p. 9.
TH 22:08, 18 December 2005 (UTC)
thread_title:  Controlled Substances Act; British system 

message: The table from Drug Facts and Comparisons has gotten bounced around a bit and damaged. I have just fixed it and double-checked every line against my photocopy from DF&C 4.0. The photocopy that the university medical librarian made for me after recommending DF&C as the most authoritative and impartial source. 
I know nothing about indications in countries other than the US.
TH 04:22, 19 December 2005 (UTC)
replies: text: http://www.bnf.org.uk for the British system. JFW | T@lk 08:40, 19 December 2005 (UTC)
thread_title:  The DF&C table is correct now 

message: I added this paragraph:
"Opioids are prohibited for psychological relief (with the narrow exception of anxiety due to shortness of breath), despite their extensively reported psychological benefits. The prohibition has no therapeutic basis; its basis is fear of addiction and of diversion. The prohibition allows no exceptions, even when opioids might be especially effective and when the possibility of addiction or diversion is very low – for example, in the treatment of senile dementia, geriatric depression, and psychological distress due to chemotherapy or terminal diagnosis".
---
CITATIONS regarding the idea that opioids can relieve psychological distress and can act as antidepressants: 
“In the middle nineteenth and well into the twentieth century”, morphine “was used as a tranquilizer and sedative. . . . It was used in mood disorders . . . until such applications were discouraged by enforcement” (note that Dr. Way says “discouraged by enforcement”, not "discouraged by results of clinical trials"). 
- Way, E. Leong (Department of Pharmacology, School of Medicine, University of California, San Francisco, San Francisco, California, USA), "History of Opiate Use in the Orient and the United States", in Opioids in Mental Illness: Theories, Clinical Observations, and Treatment Possibilities, edited by Karl Verebey, The New York Academy of Sciences, New York, New York (1982), p. 18.
“From being in a state of agony and apprehension the patient is calm and at ease. . . . Closely allied to the pain-relieving effect of opiates is their ability to influence mood. This effect is again a property of great value to medicine and very much the therapeutic ally of the pain-relieving effect; even when the pain of a spreading cancer is not fully abolished by the drug injection, the mood effect can make the residual pain more tolerable and generally produce a lessening of emotional distress. The patient is in a way emotionally distanced from what is happening, and floats as it were on the surface of his experience”.
- Berridge, Virgina, Opium and the People: Opiate Use in Nineteenth-Century England, 1987, pp. xxf.
“Exogenous opiates . . . have analgesic, anxiolytic, euphoric, and calming effects”.
- Gold, Mark S., A. Carter Pottash, Donald Sweeney, David Martin, and Irl Extein (Fair Oaks Hospital, Summit, New Jersey, USA): "Antimanic, Antidepressant, and Antipanic Effects of Opiates: Clinical, Neuroanatomical, and Biochemical Evidence", in Opioids in Mental Illness: Theories, Clinical Observations, and Treatment Possibilities, edited by Karl Verebey, The New York Academy of Sciences, New York, New York, 1982, p. 145.
“Morphine . . . allays . . . apprehension”. 
- Reynolds, A. K., PhD, and Lowell O. Randall, PhD, Morphine and Allied Drugs (1959), p. 145.
“It may be anticipated that opioids could be highly effective, therapeutically, in depressive illness". 
- Emrich, H. M., P. Vogt, and A. Herz (Max-Planck Institute for Psychiatry, Munich, Germany), "Possible Antidepressive Effects of Opioids: Action of Buprenorphine", in Opioids in Mental Illness: Theories, Clinical Observations, and Treatment Possibilities, edited by Karl Verebey, The New York Academy of Sciences, New York, New York, 1982, p. 108.
In a study of depressed patients, buprenorphine provided “clinically striking improvement in both subjective and objective measures of depression”.
- Bodkin JA, Zornberg GL, Lukas SE, Cole JO (McLean Hospital, Consolidated Department of Psychiatry, Harvard Medical School), “Buprenorphine Treatment of Refractory Depression”, Journal of Clinical Psychopharmacology, February, 1995, 15(1):49-57.
In another study of buprenorphine in the treatment of psychiatric patients (mostly Vietnam veterans), “most [patients] commented on how much better they felt after BPN [buprenorphine], using words like ‘relaxed’, ‘peaceful’, ‘more friendly’. . . . Some went into a discussion group after BPN and for the first time spoke about painful experiences. . . . The only responder who did not like BPN was the normal subject”. 
- Mongan, Lou and Enoch Callaway, Letter to the Editor, Biological Psychiatry, 1990, Volume 28, Issue 12, pp. 1078ff.
In cases of terminal disease, “the analgesia, tranquility, and even euphoria afforded by the use of opioids can make the final days far less distressing for the patient and family”. 
- Gutstein, Howard B. and Huda Akil, “Opioid Analgesics: Clinical Summary”, in Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 11th Edition, 2006, edited by Brunton, Laurence L., John S. Lazo, Keith L. Parker, Iain L. O. Buxton, and Donald Blumenthal.
(The authors make no comment on the plight of those who might appreciate the “tranquility, and even euphoria” but have no need for analgesia.)
“Then Helen, daughter of Zeus, turned to new thoughts. Presently she cast a drug into the wine whereof they drank, a drug to lull all pain and anger, and bring forgetfulness of every sorrow. Whoso should drink a draught thereof, when it is mingled in the bowl, on that day he would let no tear fall down his cheeks, not though his mother and his father died, not though men slew his brother or dear son with the sword before his face, and his own eyes beheld it". 
- Homer, The Odyssey, Book IV, lines 219-222, translation by Samuel Butcher & Andrew Lang. It is not certain that the drug is opium, but no other reasonable candidate has been proposed. The effect of opium may be exaggerated in this report, but the scene is a good proxy for the psychotherapeutic use of opium by early physicians such as Hippocrates, Dioscorides, and Galen. 
---
CITATIONS regarding the idea that thymoleptics (SSRIs, MAOIs, etc.) are always superior to opioids as antidepressants: 
Thymoleptics are unreliable and slow: “patients must be aware that antidepressants take at least four to six weeks to have a full therapeutic effect and that only about half of patients respond to the first medication prescribed”.
-  Whooley, Mary A., MD and Gregory E. Simon, MD, MPH, "Managing Depression in Medical Outpatients", The New England Journal of Medicine, December 28, 2000, p. 1948.
The study called “Sequenced Treatment Alternatives to Relieve Depression” (STAR*D), sponsored by the National Institute of Mental Health, found that only half of the 1500 patients in the study “achieved remission – virtually the complete absence of symptoms. . . . About half the patients in the study who improved did not show benefits until eight to 10 weeks into the study".
- Maugh, Thomas M. II, “New Hope amid Depression”, San Francisco Chronicle, March 23, 2006, p. A3.
Opioids, on the other hand, act quickly: “We have found that most patients experience benefits of an adequate dose within three hours”. 
- Callaway, Enoch, Editorial, Biological Psychiatry, June 15, 1996.
And opioids act surely: I have found no reports of opioids failing to have a positive effect, except in the case of "normal" people (see above and below) and the case of negative side effects such as nausea. 
Marcia Angell, MD, former editor-in-chief of the New England Journal of Medicine, reports on a survey (enabled by the Freedom of Information Act) of FDA reviews of drug-company submissions that found placebos to differ from the six top-selling antidepressants by only two points on the sixty-two-point Hamilton Depression Scale – a difference that she says is “unlikely to be of any clinical significance”. 
- Angell, Marcia, MD, The Truth About the Drug Companies: How They Deceive Us and What to Do About It (2004), p. 113. 
Pharmaceutical companies can hide their failures: they are not required to make public “all clinical trials, even the ones where the drugs failed to work”. 
- Lamb, Gregory M., “A New Corporate Villain – Drugmakers?”, The Christian Science Monitor, September 20, 2004, http://www.csmonitor.com/2004/0920/p11s02-ussc.html.
Pharmaceutical companies surreptitiously magnify their positive results: they “publish positive results more than once, in slightly different forms in different journals. The FDA has no control over this selected publishing. The practice leads doctors to believe that drugs are much better than they are. . . . There is a general inflation in the notion of the good that drugs can do (and a deflation in concern about side effects)”. 
- Angell, The Truth About the Drug Companies, p. 112.
Pharmaceutical companies can apply suspicious selectivity when recruiting for clinical studies. A survey and a study of 803 outpatients at Brown University showed that from one-sixth to 95 percent of “depressed patients treated in an outpatient setting would be excluded from the typical study approved by the federal Food and Drug Administration to determine whether a new antidepressant medication works”. The study concludes that "subjects treated in antidepressant trials represent a minority of patients treated for major depression in routine clinical practice”. 
- Zimmerman, Mark, MD, Jill I. Mattia, PhD, and Michael A. Posternak, MD, “Are Subjects in Pharmacological Treatment Trials of Depression Representative of Patients in Routine Clinical Practice?”, American Journal of Psychiatry, March, 2002, 159:469-473. 
“The current practice . . . may actually skew the findings of the drug trials”, according to Zimmerman. 
- Rosack, Jim, “Clinical-Trial Criteria Leave Limited Study Population”, Psychiatric News, V folume 37 Number 10, May 17, 2002, p. 28. 
Opiates can be superior to thymoleptics for psychological relief: “As shown in the present investigation, the mixed opiate agonist/antagonist buprenorphine exhibits antidepressant properties in cases not responding to conventional thymoleptic therapy. This is a remarkable finding, since for this type of patient, an inevitable consequence would be the application of electroconvulsion, . . . which . . . is not a desirable choice in the treatment of psychiatric patients”.
- Emrich, H. M., "Possible Antidepressive Effects of Opioids: Action of Buprenorphine", in Opioids in Mental Illness: Theories, Clinical Observations, and Treatment Possibilities, edited by Karl Verebey, The New York Academy of Sciences, New York, New York, 1982, p. 111.
Opiates can be superior to thymoleptics for psychological relief: “We have personally treated five patients with BPN in whom the results were impressive. Three were more or less typical cases of depression who had failed adequate trials with various treatments, including, in one case, a thorough course of ECT [electro-convulsive therapy]. Of the two less typical patients, one was a case of panic disorder with onset in childhood and what could better be called dysthymia rather than typical depression.... All five patients were followed for several years while good results were maintained”.
- Callaway, Enoch, Editorial, Biological Psychiatry, June 15, 1996.
Opiates can be superior to thymoleptics for psychological relief: “Through advances in medicine, the human life span has lengthened with a consequent increase in the population of geriatric patients with dementia and depression. The choice of psychotropic medication for these patients poses special problems owing to their increased susceptibility to adverse drug reactions [here the authors quote three sources]. The side effects of major tranquilizers, e.g. extra-pyramidal restlessness, parkinsonism, and hypertensive episodes, may complicate the clinical picture of an elderly, agitated patient. However, the main clinical problem with these drugs is that there is often mental hebetude even though target symptoms have abated. The patients appear overdrugged, and relatives often refer to them as “zombies” and are discomforted in their presence. Many of these patients display rapid clinical improvement following discontinuation of maintenance doses of psychotropic drugs, calling in question the advisability of long-term medication for psycho-geriatric patients. . . . As for tricyclic medication for the depressed aged patient, there is a lowered threshold for toxic confusion, glaucoma, urinary retention, cardiovascular embarrassment, and parkinsonism. This may at time[s] seriously limit their use in the elderly. . . . During the past 27 years, the senior author has treated many cases of senile dementia with suitably adjusted dosage of opium-related compounds [mostly deodorized tincture of opium]. The results have often been superior to those obtained previously in the same patients with other medications, including phenothiazines and tricyclic antidepressants. Not only the target symptoms (depression, confusion, paranoid ideation, etc.) abated, but a cheerful and cooperative mood appeared, rendering the patient amenable to rehabilitative measures”. 
- Abse, D. Wilfred, William J. Rheuban, and Salman Akhtar, “The Poppy: Therapeutic Potential in Cases of Dementia with Depression”, in Opioids in Mental Illness: Theories, Clinical Observations, and Treatment Possibilities, edited by Karl Verebey, The New York Academy of Sciences, New York, New York, 1982, pp. 79ff.
---
CITATIONS regarding the idea (voiced above, months ago, without citation) that opioids would just make a person sleepy: 
Opiates may produce “excitation” and “stimulation”. 
- Reynolds, A. K., PhD, and Lowell O. Randall, PhD, Morphine and Allied Drugs (1959), p. 19. 
Berridge provides considerable discussion of opioids as stimulants, and shows that they were not uncommonly viewed as such. 
- Berridge, Opium and the People: Opiate Use in Nineteenth-Century England, 1987.
Takano discusses farmers who take opium to help them work a long, hard day in the fields. 
- Takano, Hideyuki, The Shore Beyond Good and Evil: A Report from Inside Burma's Opium Kingdom (2002). 
Way discusses the use of opium as an aid to work. 
- Way, E. Leong (Department of Pharmacology, School of Medicine, University of California, San Francisco, San Francisco, California, USA), "History of Opiate Use in the Orient and the United States", in Opioids in Mental Illness: Theories, Clinical Observations, and Treatment Possibilities, edited by Karl Verebey, The New York Academy of Sciences, New York, New York (1982).
---
CITATIONS regarding the idea (voiced above, months ago, without citation) that constipation and nausea might be major obstacles to the use of opioids for mood therapy:
“Constipation . . . is treated [with laxatives and stool-softeners]. . . . Opium-related nausea might occur after an increase in dosage or initiation of opium therapy".
- Burton, Allen W., "Acute, Chronic, and Cancer Pain: Clinical Management", in Opioid Research: Methods and Protocols, edited by Pan, Zhizhang Z., 2004, p. 277.
(The implication is that easing in to the target dosage will greatly reduce constipation and nausea. Since opioids act so quickly, easing in is not necessarily a long process.)
"It is very important to watch out for constipation, which can be severe” and “can be a very considerable complication”.
- Abse, D. Wilfred, quoted in “Opiate Antagonists in the Treatment of Mental Diseases: General Discussion”, in Opioids in Mental Illness: Theories, Clinical Observations, and Treatment Possibilities, edited by Karl Verebey, The New York Academy of Sciences, New York, New York, 1982, p. 129.
“Nausea and vomiting are relatively uncommon in recumbent patients given therapeutic doses of morphine”.
- Gutstein, Howard B. and Huda Akil, “Opioid Analgesics: Effects”, in Goodman and Gilman’s.
(The implication is that nausea is manageable, given that just lying down can make it a relatively uncommon symptom.) 
---
CITATIONS regarding the idea that addiction, triggered by euphoria, is a speedy and frequent result of therapeutic use of opioids: 
The dosage required to produce euphoria is significantly greater than the dosage required to relieve distress, and tolerance appears to develop much more rapidly for euphoria than for other effects of opioids. For example, Hideyuki Takano says of his second use of opium: “On the one hand, the opium worked on the symptoms unbelievably well and quickly. On the other, that blissful pleasure of floating in air, experienced the first time, disappointingly never recurred. However, the milder euphoria that came instead was pleasant”.
- Takano, Hideyuki, The Shore Beyond Good and Evil: A Report from Inside Burma's Opium Kingdom (2002), pp. 188f. 
While anodyne effects are common, perhaps universal, euphoria seems to be unavailable to many: “Euphoria is not a universal accompaniment of opiate administration. Indeed, to the well-adjusted individual, morphine effects may be anything but pleasant. It is in the emotionally unstable person who is liable to be abnormally excited or depressed, that is to say, the individual who is removed from normal psychological equilibrium in relation to the immediate environment and circumstances, that euphoria is most marked. . . . Opiates afford an escape mechanism from reality and the burdens and disappointments of everyday life”. 
- Reynolds, A. K., PhD, and Lowell O. Randall, PhD, Morphine and Allied Drugs (1959), p. 125.
“When therapeutic doses of morphine are given to patients with pain, they report that the pain is less intense, less discomforting, or entirely gone; drowsiness commonly occurs. In addition to relief of distress, some patients experience euphoria”.
- Gutstein, Howard B. and Huda Akil, “Opioid Analgesics: Effects”, in Goodman and Gilman’s.
“Although tolerance does develop to oral opioids, many patients obtain relief from the same dosage for weeks or months”.
- Gutstein, Howard B. and Huda Akil, “Opioid Analgesics: Clinical Summary”, in Goodman and Gilman’s.
“Tolerance and dependence are physiological responses seen in all patients and are not predictors of addiction. . . . These processes appear to be quite distinct. For example, cancer pain often requires prolonged treatment with high doses of opioids, leading to tolerance and dependence. Yet abuse in this setting is very unusual (Foley, 1993)”.
- Gutstein, Howard B. and Huda Akil, “Opioid Analgesics: Effects”, in Goodman and Gilman’s.
“The importance of the issues of tolerance, dependence, and respiratory depression have been exaggerated”.  
- Walsh, T. Declan, MSc, “Prevention of Opioid Side Effects”, Journal of Pain and Symptom Management, December, 1990, p. 362.
“The existence of so-called chippers, individuals who use heroin recreationally on a periodic basis, indicates that exposure to an opioid alone does not reliably lead to escalating use or addictive behaviors, even in those who consume these drugs for purposes other than pain control”. 
- Portenoy, Russell K., MD, “Chronic Opioid Therapy in Nonmalignant Pain”, Journal of Pain and Symptom Management, February, 1990, p. S54. 
“An early concern that self-administration of opioids would increase the probability of addiction has not materialized”. 
- Gutstein, Howard B. and Huda Akil, “Opioid Analgesics: Therapeutic Use”, in Goodman and Gilman’s.
“Interestingly, according to reports of that [Kraepelin’s] time, although a standardized evaluation of the therapeutic efficacy was, and is, lacking, this treatment was effective and did not result in opiate addiction, possibly since the doses applied were comparatively low”.
- Emrich, H. M., P. Vogt, and A. Herz (Max-Plack Institute for Psychiatry, Munich, Germany, "Possible Antidepressive Effects of Opioids: Action of Buprenorphine", in Opioids in Mental Illness: Theories, Clinical Observations, and Treatment Possibilities, edited by Karl Verebey, The New York Academy of Sciences, New York, New York, 1982, p. 108.
“[J. H.] Jaffe many years ago [in 1968] opined that the fear of addiction is out of proportion to the actual frequency of its occurrence. In the cases of opium-treated dementias with which we are concerned, this fear seems especially misplaced. In our experience, [the patient] does not require increasing doses . . . over time”.
 
- Abse, D. Wilfred, William J. Rheuban, and Salman Akhtar, “The Poppy: Therapeutic Potential in Cases of Dementia with Depression”, in Opioids in Mental Illness: Theories, Clinical Observations, and Treatment Possibilities, edited by Karl Verebey, The New York Academy of Sciences, New York, New York, 1982, pp. 79ff.
"Some 20 years ago at the University of North Carolina where I was working, people were interested in some of the opiate effects on elderly people at the psychiatric unit for whom the drug was euphoric. Also, these researchers investigated cheerful, young adults who were being given various drugs and opiates to see their reactions. Healthy, cheerful students who received opiates became depressed after they had a dose, which was the opposite of what was happening with the older people with impaired nervous systems."
- Abse, D. Wilfred, quoted in “Opiate Antagonists in the Treatment of Mental Diseases: General Discussion”, in Opioids in Mental Illness: Theories, Clinical Observations, and Treatment Possibilities, edited by Karl Verebey, The New York Academy of Sciences, New York, New York, 1982, p. 129.
TH 01:09, 18 February 2006 (UTC)
thread_title:  senile dementia, geriatric depression, chemotherapy, terminal diagnosis 

message: Further research with respect to the last paragraph of "Clinical use" produced additional citations and the addition of "geriatric depression" to the list - formerly "senile dementia, chemotherapy, terminal diagnosis", now "senile dementia, geriatric depression, chemotherapy, terminal diagnosis". 
To keep all the citations in support of the paragraph in one place, I went back up in this Discussion page and inserted them into the original list. The new citations are:
1. Regarding thymoleptics: "Through advances in medicine, . . . limit their use in the elderly". 
2. Regarding constipation: "It is very important . . . considerable complication". 
3. Regarding addiction: "Some 20 years ago . . . impaired nervous systems". 
TH 01:25, 3 March 2006 (UTC)
thread_title:  geriatric depression 

message: If you want to alter my paragraph, you must, per Wikipedia policy, provide citations. And make sure your citations have more authority than the 38 citations that I provided, on the discussion page, in support of my paragraph.
TH 05:05, 11 March 2006 (UTC)
thread_title:  Note to the person who changed Clinical Use: 

message: In support of the last paragraph of the "United States" section of the article, I added a citation regarding the STAR*D study of 1500 patients. I also added the paragraph regarding "opioids act surely".  
I made these two additions above here on the Discussion page, so that all the citations would stay together.
TH 05:38, 1 April 2006 (UTC)
thread_title:  added citation on STAR*D and clarification on "act surely" 

message: Just started a page on Etonitazene, but don't know/can't find very much information. Anybody want to help me?
http://en.wikipedia.org/wiki/Etonitazene
Miserlou 20:09, 7 April 2006 (UTC)
thread_title:  Etonitazene 

message: I have been to and worked in detox facilities and methadone clinics, was a junkie for over five years, my dad has been on opiates for chronic pain for half my life.  I've known hundred of junkies, and never once heard of recurring abdominal pain and nasuea due to taking painkillers...that section (it's under withdrawl and dependence) is just bizarre to me...can anyone provide a source for this?
—The preceding unsigned comment was added by Azrayl (talk • contribs) 21:09, May 22, 2006  (UTC)
:Since that paragraph discusses "when the pain medication runs out," I think it's talking about nausea and abdominal pain as withdrawal symptoms. They are, of course, very common withdrawal symptoms. However, nausea is also a very common side effect of all opiate based drugs. Abdominal pain is also a common side effect and in some cases can be a manifestation of the chronic constipation (and even bowel obstructions) opiate based drugs can cause. One reference which states this is The Drug Guide by Dr Jonathan Upfall, , p.471, which lists "constipation, dry mouth, stomach ache, nausea, vomiting" as side effects of morphine, for example. Sarah Ewart (Talk) 10:16, 2 July 2006 (UTC)
replies: text: Okay, yeah I'm not sure why I said naseau wasn't a side-effect, because it is.  and abdominal pain can present itself due to constipation or withdrawal. --Azrayl 09:11, 15 July 2006 (UTC)
thread_title:  Recurring Abdominal pain and nasuea 

message: The terminology section has definitions that differ from the standard used in psychiatry. To avoid confusion by readers who may have received diagnoses from their healthcare professional, I added a note explaining the variation. With any luck, the addictive disease workgroup at the APA will address nomenclature as part of the DSM-V development. At this time, that's still in the plan. Drgitlow 02:11, 7 July 2006 (UTC)
thread_title:  Added DSM-IV terminology note 

message: Someone deleted (probably just an accident) all the explanations I gave for the changes I made, along with all of the peer reviewed professional references that I gave to substantiate them. Well, here they are again. 
I took out:  
 
"it rarely develops in persons who are taking opioids under medical supervision for legitimate therapeutic purposes (such as pain management), particularly when the dosage used is too low to produce any feeling of euphoria." 
   
and also "the emerging medical consensus is that most chronic pain patients can safely use opioids for years with a minimal risk of addiction or toxicity and that the overall increase in quality of life outweighs any adverse effects of opioid use." 
   
and "Typically, persons taking opioids under medical supervision for the usual clinical purposes (such as pain management) are less likely to develop addictions or patterns of abuse than those who begin using the drug specifically for its other effects such as euphoria. However it is very likely that many addicts began using because they experienced the great relief from some types of "psychological pain" that only opiates can provide." 
   
and "Although physical dependence is nearly universal among those who use opioids regularly, true addiction is quite rare even when large amounts of opioids are used over long periods of time to treat chronic pain under the close supervision of a doctor. This is thought to be because of the rapid development of tolerance to the euphorigenic properties of opioids; without euphoria, only the unpleasant side effects (such as bowel dysfunction) remain, so there is no motivation to take more than is needed to manage pain. 
   
Because these statements are untrue and no evidence or citation is given, while evidence to the contrary is well known in the peer reviewed medical community, addictionj rates are higher among those who use opiates for medical use do to exposure. Please cite a peer reviewed source if you with to replace it. My sources are listed below thank you.  76.20.176.60 12:52, 5 October 2006 (UTC)
replies: text: 76.20.etc's assertions above are false.  most of the above quotes that he opposes are consistent with accepted practice in the pain-specialist community -- although it's understandable that you *CAN* find sources that are opposed, especially if you quote only from the anti-addiction literature and choose articles all from the same source.  as for his assertion about upper limits, there are documented cases of late-stage cancer patients receiving a few grams of intravenous morphine each hour without strong negative effects.  granted, this is an extreme case but it clearly shows that his assertions are untrue. Benwing 05:04, 8 January 2007 (UTC)

text: some sources:     —The preceding unsigned comment was added by Benwing (talk • contribs) 05:18, 8 January 2007 (UTC)
thread_title:  Uncited Statements-again 

message: This research you cite as "new developments" showing that chronic opiate users can take these drugs without dependance is flawed. It is nothing more than a case report, it does npt meet the criteria of being evidence based clinical research. RCT are the gold standard, and even a cohort study would have some credibility, but a case report is not evidence based to proove causality or lack of association. It proves nothing and is not a "development." {{76.20.176.60 20:04, 29 October 2006 (UTC)
replies: text: You seem to have missed the second cite which contains results of various clinical trials (including Phase III) and controlled animal studies, alongwith in vitro experiments. - daksya 06:41, 30 October 2006 (UTC)
thread_title:  Last reversion by Daksya 

message: What has been bothering me is that when I read the opioid article I see a great deal of clinical information and though some is pretty biased, a lot is quite irrefutably factual and informative.  Then, I read the opium article and am wildly disappointed.  Is it the social-acceptance syndrome that causes this?  Papaver Somniferum is one of (and perhaps the highest-importance of) the five most important plants humankind has ever discovered.  The plant and its active derivatives are still the most effective and safe analgesics, cough suppressants, anti-diarrhoeals known.  I wish the vast majority of you would stop bashing the plant and hypocritically lauding all its derivatives.  DrMorelos 00:44, 25 November 2006 (UTC)
thread_title:  Compare and Contrast 

message: I just changed the size of the heading "Piperanilides" to match the other headings.  Due to the fact that "Morphinan derivatives", "Others", etc. were subheadings of it, and they don't seem to be related to piperidines, I think it was just a mistake made by the anon who added the subhead a couple months ago.  If possible, I'd like someone who knows more about the chemistry to confirm this for me, as I can't find anything on Google for "piperanilide" but WP mirrors.  What relation do piperanilides have with phenylpiperidines (as fentanyl is definitely also classed as the latter... I believe)?  Oy.  Thanks in advance... --Galaxiaad 08:17, 19 January 2007 (UTC)
replies: text: They are actually called "anilidopiperidines" or "anilinopiperidines". Fentanyl is no way a phenylpiperidine derivative, since it is an 4-anilidopiperidine (so N-phenylamino-piperidine) derivative.
The relation between 4-phenylpiperidines (e.g. meperidine/pethidine) and 4-anilidopiperidines (e.g. fentanyl) is that, both groups have certain structural similarity, namely the base of their molecular sceleton is the 1-alkylated, 4- substitued-piperidine. In the case of 4-phenylpiperidines, the 4-substituent is a phenyl or substitued phenyl cycle (e.g. 3-hydroxyphenyl in ketobemidone), whereas 4-anilidopiperidines have a N-phenylN-acylamido group as their 4-substituent (Ph-N(-CO-R)-), mostly N-phenyl-N-propionamido group (Ph-N(-CO-CH2-CH3)-).
In general, anilidopiperidines are more potent opioids than phenylpiperidines.--84.163.87.92 21:27, 19 January 2007 (UTC)
thread_title:  Categorization of synthetics 

message: I have removed the link to ketobemidone from the sub-category "Piperoanilidines (or anilidopiperidines), because it is chemically a phenylpiperidine derivative (4-(3-hydroxyphenyl-1-methyl-4-(1-oxopropyl)-piperidine).
I further suggest to fuse the sub-categories of "Phenylheptylamines" and "Diphenylpropylamine derivatives", under "Diphenylpropylamine derivatives", since both methadone and LAAM are chemically derivatives of 3,3-dipheylpropylamine (methadone can be described as (R,S)-1-methyl-3,3-diphenyl-3-(1-oxopropyl-)propyl-N,N-dimethylamine, however it is an homologue of diphenylpropylamine, namely (R,S)-2-N,N-dimethylamino-4,4,-diphenylheptan-5-one; same can be applied for levacetylmethadol/LAAM).
Discussion is wellcomed, if nobody has objections, I will do so in few days.--84.163.87.92 21:19, 19 January 2007 (UTC)
thread_title:  Chemical categorisation of fully synthetic opioids. 

message: I think this article is quite good, but at present somewhat inaccessible for an untrained person. I will try to rewrite the point-wise sections as prose, and begin improving citations (as per WP:CITE and WP:CITET template). I will try not to change the content and meaning, but as always, criticism from others is important, especially as I am not a pro writer. I will post sections as I complete them. --Seejyb 23:50, 19 January 2007 (UTC)
replies: text: Should all the long paper or book citation details within the text not be converted into footnotes ? If people agree, I can help markup as footnotes and use the relevant citation template to standardise the styling. :-) The information in the article is detailsed and good but overall it reads like lecture-notes points rather than flowing prose. David Ruben  Talk  01:57, 23 January 2007 (UTC)
thread_title:  I will begin to try to improve the style of writing. 

message: The sub-categories "Diphenylheptylamines" (Methadone and LAAM) and "Diphenylpropylamine der." were fused under "Diphenylpropylamine derivatives"; for reason see my argumentation of January 19th. Further, "Piperoanilines" were renamed to "Anilidopiperidines", since this is the mostly used name for this subcategory of synthetic opioids in english literature (fentanyl derivatives); the opioid Etorphine was moved into subcategory "Oripavines", since it is an oripavine derivative. Opioids Loperamide and Diphenoxylate were moved into subcategory "Diphenylpropylamine derivatives", because they are both derivatives of this class (structurally akin to the opioid Piritramide). Spelling of the titles of subcategories "Benzomorphan derivatives" and "Morphinan derivatives" were corrected to "Benzomorphane" and "Morphinane" derivatives, respectivelly (see IUPAC organic nomenclature, english).
For every change, a standard source cited is:  ; Buschmann et al.: Analgesics. From Chemistry and Pharmacology to Clinical Apllication. Wiley-VCH, 2002.--84.163.91.142 03:12, 24 January 2007 (UTC)
thread_title:  Summary of changes of January 24th, 2007; Section: synthetic opioids 

message: Over the past two months I have been working steadily to add the clinical use of opioids for people with palliative care needs.  I realise that opioids are used and abused for many other reasons, but feel that some of these are subjects for other sections, particularly the recreational use of the naturally occuring agents.
There is so much misinformation about this group of chemicals that many people who need opioids for the relief of symptoms such as pain or breathlessness, are frightened by the fear of addiction, tolerance or intolerable adverse effects. Ocasionally patients will believe pain is preferable. 
I realise that some will find these changes more 'clinical', but I have tried to make the academic aspects readable. As far as possible I have tried to reference the experience of palliative care and attempted to make clear the diference between safe and unsafe use of opioids.
Being relatively new to Wikipedia, I am still learning the rules, and apologise that I have not previously written a comment to explain my actions and encourage debate. I am happy to do so now.
--Claud Regnard 23:22, 4 February 2007 (UTC)
thread_title:  Summary of changes to opioids Jan 2007 

message: A citation is DEFINITELY needed for the claim that people taking opioids for medicinal purposes rarely get addicted.
-Jessica
71.246.71.26 12:30, 3 May 2007 (UTC)
thread_title:  Citation needed about addiction 

message: The moderator was not happy with the style of the 'dangerous opioids or dangerous prescribers section, so I have changed this into a more suitable style (I hope).
--Claud regnard 23:48, 9 May 2007 (UTC)
thread_title:  Dangerous opioids 

message: The mention of Harold Shipman is quite bizarre, almost suggesting that he was a victim of juducial anti-opioid prejudice. He was convicted of fifteen counts of murder, not simply of knowingly administering overdoses. It was decided by an inquest that Shipman had murdered at least two hundred and fifteen of his patients, having caused them to include him as a beneficiary in his will. There were two hundred more suspicious deaths associated with him. On that basis, I deleted it. — Preceding unsigned comment added by 86.152.5.95 (talk) 13:44, 16 May 2007 (UTC)
thread_title:  Harold Shipman 

message: There definitley needs to be something done about the article stating that people using opiates for painkillers rarely get addicted, as this is completely wrong.  people taking prescription opiates are at a huge risk for addiction and many of them are addicted. by having their doctors up their dose and being on a lifelong regime, this defines addiction, particularly due to the fact that they cannot stop taking said opiates without withdrawal symptoms, and require more of said opiates for the pain relief and allevation from the withdrawal.
--User:kmac20 23:34, 23 May 2007 (UTC)
thread_title:  Rarely get addicted? 

message: The "dangerous opioids or dangerous prescribers" section still seems biased, written inappropriately, and possibly off-topic.68.127.88.58 01:57, 10 July 2007 (UTC)
thread_title:  Dangerous opioids (continued) 

message: I have added references where asked to do so by the moderator. However, in some sections (eg. adverse effects) there are so many references that could be added and I have taken the short cut of referencing to larger texts and online resources, and I'll wait to see if this is acceptable. --Claud Regnard 01:02, 6 June 2007 (UTC)
thread_title:  Updating references