From: Arno Subject: Re: clonodine patch for H wihdrawl? Date: 1997/10/20 Newsgroups: alt.drugs.hard > > > Oh yeah, clonidine is nothing more than a drug to lower your blood pressure. > > > Apparently, when you kick d. your bp goes up up up, and clons are > > > supposed to take the edge off that tip. > > > > They do more than that. They don't remove the withdrawal completely but > > make it easier to bear. I don't recall at the moment the particular > > mechanism of action by which this happens, but it is not because of the > > blood pressure that clonidine is given. > > Sorry, but Jack is absolutely right. Clonidine is a blood pressure > lowering drug and that is all. I was given it for detox once and had to be > taken off it because I have low pressure to begin with and it lowered mine > to dangerous levels. It does nothing else as far as withdrawls. What Jack > said about when you kick your pressure rises and the theory was that it > would help withdrawl symptoms somewhat if you could lower the pressure back > to normal is exactly correct. I say theory because in my case and almost > every other person I've spoken to with first hand knowledge, it doesn't do > shit for your withdrawls. This was all explained to me the first time I was > given it by the head doctor at the detox I went to. It was experimental at > the time, so he had to give me all the details. I know it for more than 13 years. Then it was used in Vienna and other places for withdrawal management. Already beyond the experimental state. I had discussions with the doctor-therapists there. I am sorry, but the doctor you talked to has incomplete information. Clonidine is mainly a blood pressure lowering drug, but when it is used in withdrawal, the blood pressure aspect is a side effect only, and not necessarily a desired one. It doesn't make sense to give everybody a drug to lower blood pressure, and if that were the reason they should be given only in relevant cases. In Vienna, they checked the blood pressure of the patients, and naturally all had lowered blood pressure. This checking was done solely to be able to give the maximum dosage without lowering the blood pressure to a dangerous level. There is a good deal of scientific literature about it, and I have seen some of that also, but that was more than eight years ago and naturally I don't have the references in my memory any more. I hope someone else is out there who knows what I am talking about and can give some references, because I have no chance to go to a medical library at present. The effect on withdrawal is via the adrenergic system, as far as I remember. I know that it is easy to think Clonidine has no effect on the symptoms. Many cases may not be aware of the difference, but, as they say, they would be if the clonidine was not given. It reduces the observed withdrawal symptoms in addicted laboratory animals also, and to a significant degree, but that is just by the way. Of course, the suppression of withdrawal is by far not complete, but it is one of the only accepted substances know to suppress withdrawal that does not work via the opiate receptor mechanism. Therefore it is preferred to substances working via that route because those basically only prolong the period required to kick off. The clinic in Vienna was the University Clinic and at the cutting edge of withdrawal management, so we are not talking of some backward, small, exotic establishment. The therapists would give a higher dosage in stronger withdrawal cases on request, and again, people did request for it, and not to have their already low blood pressure lowered further. The usual dosage was 150-300 mg, ideally iv., several times a day. This dosage is much higher than a reasonable dosage for lowering withdrawal induced high blood pressure. They had another interesting, though very expensive, technique, that is to give Nootropil (Piracetam, the smart drug) in _very_ huge dosages (60-120 ml solution iv. from a drip). This regimen, as opposed to Clonidine, had no direct impact on the symptoms but somehow refreshed the mind and gave energy to cope. If doctors in your withdrawal clinics say it is only for blood pressure, there are several possible explanations. It might mean they have not properly understood why they are doing what they are doing and have not studied the scientific literature. However, I rather suspect a misunderstanding in the conversation you had with your doctor, specially as in the case of most patients, the prevalent opinion will be that it does nothing to help their symptoms. In conversations held with a preconceived notion already in one's mind, it can happen that the information actually given is misinterpreted. Another explanation would be that the doctors have some reason not to give that information, perhaps in order to prevent people asking for more clonidine. They may not want to have any special cases or additional work or medical problems with people with too low blood pressure. If it was in the experimental phase, as you say, he might have wanted to prevent any placebo effect from happening, that is people imagining effects due to having an information about what the effects are supposed to be. Or, another favourable explanation, it may not be disclosed in an attempt to move people away from the mentality to always look out for a pharmaceutical fix - so that they may start to become psychologically more self-reliant. ==================================================================== From: (Arno) Subject: Re: clonodine patch for H wihdrawl? Date: 1997/10/25 Newsgroups: alt.drugs.hard On Fri, 24 Oct 1997 18:13:24 +0100, news@petermc.demon.co.uk (Peter McDermott) wrote: >>> But I think all the reasons you give for the weaknesses of a Clonidine >>> detox *also* apply to Methadone detoxes as well. While methadone works >>> admirably in maintenance, as a tool for short term detox, I'm not at >>> all sure that it offers any significant advantages over Clonidine. >> >>I'm just talking about fighting withdrawal. And mostly out of my ass at that. > >Ah, well in *that* context I vote Methadone every time. > >But I do have growing concerns about it's value in detoxification. >It seems to me that it just puts off the fateful day until the >methadone actually stops and the withdrawals start for real. That is also the conclusion of a scientific study I read on this topic several years ago. It was comparing clonidine and methadone detoxification, and the conclusion was that the overall level of discomfort is rather similar, only with clonidine it is at the beginning of the withdrawal, with methadone towards the end. Also, with clonidine the whole process takes less time whereas with methadone the discomfort is spread over a longer period. > >People do tell me that it's possible to avoid any discomfort >by going for a very slow, very long-term detox that cuts down >by tiny, tiny amounts extremely gradually, but I've never actually >met anyone who has managed to complete such a course, so I >don't know. A related method that I know to work is go down to a low dose first and then shift over to a less dependence creating substance like buprenorphine or dextropropoxyphen. There may be a little discomfort when that shift is done, but at that stage it is minimal. It is then possible to downdose further rather quickly with the new drug and finish off in 1-3 weeks. With this method there is surprisingly little discomfort. ==================================================================== From: Arno Subject: Re: clonodine patch for H wihdrawl? Date: 1997/10/20 Newsgroups: alt.drugs.hard [...] HealthGate Documents: Title Clonidine in opiate withdrawal: review and appraisal of clinical findings. Author Washton AM; Resnick RB Source Pharmacotherapy, 1981 Sep-Oct, 1:2, 140-6 Abstract Studies in animals and humans have demonstrated that clonidine hydrochloride, an alpha-2-noradrenergic agonist, significantly attenuates the opiate withdrawal syndrome. Inpatient and outpatient clinical studies have shown that clonidine is a reasonably safe, specific, and effective agent for detoxifying opiate addicts. Clonidine seems best suited for use as a transitional treatment between opiate dependence and induction onto the opiate antagonist naltrexone. Dosage regimens of clonidine must be individualized according to symptoms and side effects and closely supervised because of varying sensitivity to clonidine's sedative, hypotensive, and withdrawal-suppressing effects. Clonidine is an important new treatment option for selected opiate addicts and may be the treatment of choice when detoxification using methadone is inappropriate, unsuccessful, or unavailable. Lofexidine, a structural analogue of clonidine, may be safer and more effective as an opiate detoxification treatment. It has similar withdrawal-suppressing actions but causes little hypotension and sedation. Although clonidine and lofexidine may be highly effective in helping opiate addicts achieve initial abstinence, a multi-modality aftercare treatment approach including naltrexone and psychotherapy may be necessary to maintain an abstinent state. Language of Publication English Unique Identifier 86313119 Title Clonidine: inpatient studies from 1978 to 1981. Author Gold MS; Pottash AL; Extein I Source J Clin Psychiatry, 1982 Jun, 43:6 Pt 2, 35-8 Abstract We have studied and reviewed data reported by others, which support a norepinephrine (NE) hyperactivity hypothesis for opiate withdrawal. Other hypotheses explained parts of the opiate withdrawal syndrome but the NE hypothesis had the potential to explain most of the clinical manifestations of abrupt opiate discontinuation in addicted persons. Clonidine's ability to almost completely reverse the opiate withdrawal syndrome in acute withdrawal studies supported the NE hypothesis and suggested a new use of clonidine. Lofexidine's efficacy was additional support for the NE hypothesis. Clonidine is an effective emergency treatment for acute opiate withdrawal and in the detoxification of methadone, heroin, and other opiate addictions. Clonidine reverses the cognitive, affective, and physiological signs and symptoms and continues to suppress their re-emergence when given for 10-14 days in a detoxification protocol. NE hyperactivity in withdrawal may result from endorphin system dysfunction at the level of the locus coeruleus (LC), the mismatch between needed NE, opiate and other inhibition at the LC in the person addicted to high doses of powerful exogenous opiate LC inhibitors and available endogenous inhibitory substances or other mechanisms. Language of Publication English Unique Identifier 82213759 Title Efficacy of clonidine in opiate withdrawal: a study of thirty patients. Author Gold MS; Pottash AL; Sweeney DR; Kleber HD Source Drug Alcohol Depend, 1980 Oct, 6:4, 201-8 Abstract In a placebo-controlled, double-blind crossover trial, clonidine caused a marked and significant reduction of objective signs and subjective symptoms of opiate withdrawal in thirty hospitalized opiate addicts. In an open trial of clonidine in opiate withdrawal, clonidine was found to suppress opiate withdrawal signs and symptoms, allowing all of the patients to detoxify successfully from chronic opiate addiction. Clonidine was demonstrated to reverse and suppress the signs, symptoms, and effects associated with opiate withdrawal. These data support a release from chronic opiate-induced noradrenergic inhibition producing noradrenergic hyperactivity as the pathophysiological substrate for opiate withdrawal. Clonidine replaces opiate-mediated inhibition with alpha-2 mediated inhibition of noradrenergic nuclei. Language of Publication English Unique Identifier 82003787 Title Outpatient opiate detoxification with clonidine. Author Washton AM; Resnick RB Source J Clin Psychiatry, 1982 Jun, 43:6 Pt 2, 39-41 Abstract The finding that clonidine has significant withdrawal-suppressing effects in opiate addicts has led to clinical testing of its utility as a non-opiate treatment for opiate detoxification. Our outpatient studies have shown that clonidine can be used safely and effectively to detoxify opiate-dependent patients without hospitalization. Because of sedative and hypotensive side effects as well as varying sensitivity to the drug, clonidine doses must be individualized according to each patient's blood pressure and symptoms. Clonidine seems best suited for clinical use as a transitional treatment between opiate dependence and naltrexone. Our 10-day outpatient clonidine detoxification procedure has been extremely effective in allowing patients abruptly to discontinue the use of opiates and stay opiate-free long enough to initiate naltrexone treatment. Clonidine's side effects of sedation and hypotension have limited its clinical usefulness, particularly with outpatients, suggesting that other alpha-2 noradrenergic agonists might be found to have similar antiwithdrawal efficacy but without clonidine's undesirable side effects. Initial outpatient testing of lofexidine, a structural analog of clonidine, indicates that this drug may be as effective as clonidine for opiate detoxification and might be more suitable for outpatient treatment if it is found to lack the sedative and hypotensive side effects sometimes found with clonidine. Language of Publication English Unique Identifier 82213760 Title Clonidine versus long- and short-term methadone-aided withdrawal from opiates. An uncontrolled comparison. Author Kasvikis Y; Bradley B; Gossop M; Griffiths P; Marks I Address Institute of Psychiatry, De Crespigny Park, London. Source Int J Addict, 1990 Oct, 25:10, 1169-78 Abstract Twelve heroin addicts and one methadone addicts began withdrawal from street opiates, under clonidine cover, in a general psychiatric ward. Ten (80%) of them completed it within 6 days. Clonidine doses used were lower than in similar studies and all patients were alert and mobile throughout withdrawal. Two other groups of opiate addicts, of similar age and sex, were withdrawn on standard methadone regimens. Clonidine and methadone withdrawal had similar acceptability and attrition rates. Self-reports of subjective discomfort were higher in the clonidine group without affecting compliance with treatment. Withdrawal under clonidine cover deserves further study, in view of the need for postwithdrawal treatment to prevent relapse to opiate use. Language of Publication English Unique Identifier 91216677 Title Clonidine. Author Roehrich H; Gold MS Address Fair Oaks Hospital, Summit, NJ 07901. Source Adv Alcohol Subst Abuse, 1987, 7:1, 1-16 Abstract Clonidine has provided a nonaddicting solution to an ancient problem, opiate withdrawal without opiates. Gold and colleagues' initial demonstration that this alpha 2 adrenergic agonist could be used to detoxify opiate addicts provided the first nonaddicting treatment for opiate dependency. This discovery has also led to research investigating the utility of clonidine for a number of other neuropsychiatric conditions as well. Clonidine has been studied for use in neonatal narcotic addiction, alcohol detoxification, akathisia, mania, narcolepsy, attention deficit disorder, panic disorder, and alcohol amnestic disorder. Additionally, the clinical application of clonidine was based upon a large body of preclinical research and has opened up other avenues of investigation for non-addictive treatment of opiate dependency. Language of Publication English Unique Identifier 88160791 Title Double-blind study of lofexidine and clonidine in the detoxification of opiate addicts in hospital. Author Kahn A; Mumford JP; Rogers GA; Beckford H Address All Saints Hospital, Addictive Behaviour Centre, Birmingham, UK. Source Drug Alcohol Depend, 1997 Jan 10, 44:1, 57-61 Abstract Twenty eight opiate addicted inpatients who had been stabilised on methadone took part in a double-blind randomised trial of clonidine and lofexidine (14 on each treatment) for opiate detoxification: clonidine or lofexidine dosage was titrated according to symptoms. The course of withdrawal symptoms was very similar with both treatments, representing an appreciable suppression of symptoms when compared with experiences of sudden methadone withdrawal, but lofexidine resulted in significantly less hypotension and adverse events. These results suggest that lofexidine is a valuable drug for opiate detoxification and may be more acceptable to patients wishing to withdraw from opiates. Language of Publication English Unique Identifier 97183861 Title Clonidine blocks acute opiate-withdrawal symptoms. Author Gold MS; Redmond DE Jr; Kleber HD Source Lancet, 1978 Sep 16, 2:8090, 599-602 Abstract In a double-blind, placebo-controlled, cross-over trial, clonidine eliminated objective signs and subjective symptoms of opiate withdrawal for 240--360 min in eleven addicts in a hospital setting. In an open pilot study of the effects of clonidine on longer-term opiate abstinence and symptoms, the same patients did well while taking clonidine for one week. There was only one documented instance of heroin use, in a patient who did not take clonidine after hospital discharge. 6 weeks or more after the study, four patients were back on reduced doses of methadone, one was on tricyclic antidepressants, and seven were off of all opiates. All eleven patients were doing well. These data suggest that opiate withdrawal is due to increased neuronal activity in areas such as the locus coeruleus which are regulated by both alpha-2 adrenergic and opiate receptors. Language of Publication English Unique Identifier 79009448 Title [Effects of clonidine on opiate withdrawal symptoms. Results - biochemical mechanisms (author's transl)] Author Girard M; Escande M; Granier F; Gardes JP Source Encephale, 1982, 8:1, 37-48 Abstract Clonidine was administered to nineteen patients in an inpatient setting after abrupt discontinuation of chronic opiate addiction (morphine, héroin, dextromoramide). Clonidine produces a decrease sometimes very rapid in opiate withdrawal signs but does not suppress the whole affects associated with. These data support the hypothesis that clonidine has antiwithdrawal effect by replacing opiate-mediated inhibition with alpha 2 mediated inhibition of brain noradrenergic activity. Language of Publication French Unique Identifier 82235593 Title Clonidine transdermal patches for use in outpatient opiate withdrawal. Author Spencer L; Gregory M Address Adult Outpatient Chemical Dependency Center, Mills-Peninsula Hospital, Burlingame, CA 94010. Source J Subst Abuse Treat, 1989, 6:2, 113-7 Abstract We conducted a study to assess the clinical usefulness of transdermal clonidine for heroin detoxification in an outpatient drug treatment clinic. Twenty-two young otherwise healthy heroin addicts participated. Outcome was assessed on the basis of (a) hypotension and other side effects of clonidine; (b) patient retention; (c) concomitant drug use; (d) subjective symptoms of withdrawal; and (e) objective signs of withdrawal. Side effects were present but in no case necessitated discontinuation of treatment. Drop-out rates were equal to conventional treatment offered at the clinic. The availability of clonidine broadens the therapeutic options available to patients and clinicians in treating the opiate-addicted patient. Transdermal clonidine offers several advantages over the oral form: patches can be applied weekly, fewer supplemental medications are required, and patches supply an even blood level of medication. A protocol for use is recommended. Language of Publication English Unique Identifier 89311567 Title [Comparative effectiveness of alpha-2 adrenergic agonists (clonidine-guanfacine) in the hospital detoxification of opiate addicts] Author Muga R; Tor J; Forteza-Rei J; Jacas C; Altés J; Mestre L Address Unidad Hospitalaria de Desintoxicación, Servicio de Medicina Interna, Hospital de Badalona Germans Trias i Pujol, Universitat Autònoma de Barcelona. Source Med Clin (Barc), 1990 Feb 10, 94:5, 169-72 Abstract The usefulness of two alpha-2 adrenergic agonists (clonidine and guanfacine) and their comparative effectiveness were evaluated regarding the control of the opiates abstinence syndrome and the secondary effects, including development of cardiovascular abnormalities, in 88 parenteral heroin abusers admitted to two hospital units for the treatment of addiction. The patients were treated in a random, double blind fashion, with clonidine or guanfacine. In the study dosages, both drugs proved to be useful to control the abstinence syndrome. Nearly 70% of those treated with any of the two agonists were able to complete the treatment. When both drugs were compared, a higher degree of restlessness (p less than 0.01) was found among those treated with clonidine, although there were no differences in any other evaluated parameters to compare the degree of abstinence in each drug. The most commonly found side effects were orthostatism, lassitude, mental torpor and oral xerosis. These were independent of the drug used. There were no differences between both drugs regarding heart rate or blood pressure, although both parameters were significantly modified with the doses used in the study. Language of Publication Spanish Unique Identifier 90220032 Title Evaluation of clonidine suppression of opiate withdrawal reactions: a multidisciplinary approach. Author Cuthill JD; Beroniade V; Salvatori VA; Viguié F Address Department of Psychiatry, Hôpital Hôtel-Dieu de Montréal, Québec. Source Can J Psychiatry, 1990 Jun, 35:5, 377-82 Abstract The purpose of this open, uncontrolled study in a group of confirmed heroin addicts of both sexes was to determine whether clonidine by itself suppresses opiate withdrawal reactions, its maximal effective dosage range, the time of maximal effect, duration of its effectiveness and the extent of cardiovascular side effects. After a washout phase of opium residues, clonidine was administered for eight days and its effects were closely monitored and recorded. Even during the first 24 hour period, when clonidine was administered alone in a high dosage, it suppressed the signs and symptoms of opiate withdrawal reactions. The maximum effect was attained within three days. Thereafter, it maintained improvement until natural resolution of the reactions. Side effects were limited to some small but statistically significant cardiovascular changes. Illicit drug use during the treatment period indicated that drug related behaviour is only slightly affected by clonidine. The drug is thus effective in the acute withdrawal phase but does not replace the important psychosocial management needed to achieve long term drug abstinence. Language of Publication English Unique Identifier 90322279 Title Dapiprazole compared with clonidine and a placebo in detoxification of opiate addicts. Author Pini LA; Sternieri E; Ferretti C Address Clinical Pharmacology Department, University of Modena, Italy. Source Int J Clin Pharmacol Res, 1991, 11:2, 99-105 Abstract The activity of dapiprazole, clonidine and a placebo were studied to reduce abstinence symptoms and modify the psychological outline during a withdrawal period in heroin addicts. Forty heroin addicts were treated in a double-blind design and, within two weeks, relapse in heroin use was higher in the placebo group (8/10) in comparison with the dapiprazole (1/20) and clonidine (0/10) groups. During treatment clonidine was able to reduce depression and paranoid-ideas scores, whereas dapiprazole reduced depression, anxiety, hostility, phobic anxiety, obsessiveness and psychoticism. Side-effects were mild and it may be concluded that both dapiprazole and clonidine are effective and safe drugs for the treatment of opiate withdrawal syndrome. Language of Publication English Unique Identifier 91348968 Title The sequential use of clonidine and naltrexone in the treatment of opiate addicts. Author Gold MS; Dackis CA; Washton AM Source Adv Alcohol Subst Abuse, 1984 Spring, 3:3, 19-39 Abstract The efficacy of clonidine in the management of opiate withdrawal states has improved and refined the medical approach to this condition. In addition, the use of clonidine for opiate detoxification paves the way for naltrexone maintenance. Naltrexone, by providing chronic opiate receptor blockade, prevents opiate intoxication and subsequent readdiction in recovered addicts. The sequential use of clonidine and naltrexone, in conjunction with drug rehabilitation, appears to represent a viable and effective treatment for opiate addiction in motivated patients. The development of clonidine and naltrexone as treatment agents for opiate addiction also demonstrates that neurobiological advances can be translated into new and effective clinical approaches. This paper summarizes some of our experiences with the clonidine/naltrexone approach in motivated opiate addicts. Language of Publication English Unique Identifier 85043336 Title Effect of clonidine on the chronic morphine tolerance and on the sensitivity of the smooth muscles in mice. Author Ramaswamy S; Pillai NP; Gopalakrishnan V; Ghosh MN Source Life Sci, 1983 Sep 19, 33:12, 1167-72 Abstract Clonidine, when administered for prolonged period showed no tolerance to its analgesic activity. Prior exposure to clonidine attenuated the tolerance development to morphine-induced analgesia and the supersensitivity to acetylcholine (ACh) in ileum during chronic morphine treatment. Further, acute administration of lower doses of clonidine (upto 1 mg) produced supersensitivity in ileum to Ach while the higher dose (10 mg) induced subsensitivity. In vas deferens, clonidine in all the concentrations tested induced dose and time dependent supersensitivity to norepinephrine (NE) similar to that produced by morphine. Chronic clonidine treatment failed to alter the ACh responses in ileum while it produced supersensitivity to NE in vas deferens. The results suggest that clonidine and morphine possess comparable properties and the antagonism of chronic morphine tolerance by clonidine may be the therapeutic basis for its clinical application in the treatment of opiate addicts. Language of Publication English Unique Identifier 83296639 " [...]