Rapid Opiate Detoxification Treatment

Total Detox Friend

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Scenario 2 Drug screening 1 oclock position in Figure

The second approach is to screen through a large database of known molecules and check their binding affinity to the target protein. The advantage of this approach is that, mostly, the compounds that have been accumulated in a database have been investigated before - though mostly in a different context. Their bioaccessibility and toxicity may have been studied and they probably have been synthesized. Screening compounds from a library can been done in the laboratory or in the computer. In the latter case, the process is called virtual screening. Compound databases become large, so a mixture of the two processes may be advisable. Here, a set of compounds is preselected from a large library with virtual screening. These compounds are then tested in the laboratory. Chapter 6 of volume 2 by Matthias Rarey, Martin Stahl, and Gerhard Klebe gives more detail on virtual drug screening.

Evasion of True Positive Results

For obvious reasons, drug users are highly motivated to produce a clean sample. In response to this need, a black market has emerged to provide products with the sole purpose of creating a false-negative test result. These products include pretested and certified drug-free urine substitution kits, and a variety of adulterants. These include the Whizzinator (an artificial penis used to deliver a known drug-free urine under direct observation conditions) and passingpisstest.com, which provides a nontechnical description of how blood and urine drug tests work. Those who interpret test results should be aware that addicts can be highly creative in their efforts to thwart detection and monitoring. As an example, adulterants are substances placed in a sample to alter the results of a drug test. They accomplish this by physically altering the characteristics of the sample, such as temperature, pH, and specific gravity, which disrupts the mechanisms of the assay. Adulterants range from...

Testing Programs in Occupational Settings

There are two types of workplace testing regulated and nonregulated. Regulated testing refers to programs conducted under the Federal Testing Guidelines and includes industries working with the Department of Transportation (DOT), Federal employees, and companies with Federal contracts over 25,000 per year. Nonregulated programs are typically private sector employers who are not federally required to have a DFW program but voluntarily choose to drug-test employees. These programs are not required to have an MRO and are not federally regulated. Drug testing in the workplace has seen dramatic growth since 1988. Former President Ronald Reagan proclaimed the need for a drug-free workplace in America during his years in office. This initiative resulted in the Drug-Free Workplace (DFW) Act signed into law in November 1988. This legislation (HR-5210-124 Section 5152) laid the groundwork for the existing regulations (49-CFR-40) for virtually all of the drug-testing policies and protocols...

Any additional data needed for IND

Figure 1 National Institutes of Health classical cytotoxic preclinical drug screening process. *Cellular screens are usually performed on permanent cell lines using some type of growth inhibition or cytotoxicity assay (e.g., methylthiazolidiphenyl tetrazolium (MTT), sulforhodamine B (SRB)). **In vivo models can include xenografts immuno-suppressed mice, murine tumors mice, other species (e.g., rats) with syngeneic or spontaneous tumors in companion animals (e.g., dogs), hollow fiber assays, etc. w Aspects of mechanism of action, metabolism, PK PD, and toxicology can be addressed at any point or concurrently with earlier testing. (Source http dtp.nci.nih.gov.)

Interventions Aimed at Reducing the Likelihood of Involvement with the Corrections System

As noted earlier, the War on Drugs and the War on Crime have had an enormous impact on increasing rates of incarceration in the United States (Mauer, 1999 Golembeski and Fullilove, 2005). The length of incarceration as a result of violation of drug laws and the likelihood that an offender will go to jail vary significantly by state and municipality. The type of drug, the amount possessed and or sold, and a host of other factors are often weighed in sentencing and parole decisions. Truth in Sentencing laws also determine how much of a mandatory sentence will be served. All of these factors affect how many people are sent to prison and the number who remain there for a given period of time (Sentencing Project, 2006b). Reducing the length of time served for a first offense, using drug courts'' as a means of dealing with first offenders, and repealing laws, such as syringe possession laws, that add people to the jails and years onto their sentenced are appropriate targets for legislative...

In Vitro Surrogate Blood Brain Barrier Models

It shows upregulation of some BBB features, in particular tight junctional organization, generating TEER of typically 100-300 ohm cm _ 2.102 It has been used to screen BBB permeability of flavonoid compounds,103 and performed well in the recent study sponsored by the European Centre for the Validation of Alternative Methods (ECVAM) comparing cell culture models as drug screening tools.96 Although it appears to express P-gp, it does so at lower levels than the BBB in vivo, so should be used with caution.

Treatment And Management Of Substance Use Disorders

Methadone detoxification is the preferred method of managing opioid withdrawal. Schedules using bu-prenorphine and or clonidine for opioid detoxification are also available (NIH Consensus Development Conference, 1998). Detoxification from cocaine and stimulants is not done pharmacologically.

Psychosocial Treatments

Safety, efficacy, and long-term results of a modified version of rapid opiate detoxification under general anesthesia A prospective study in methadone, heroin, codeine, and morphine addicts. Acta Anaesthsiol Scand, 44(3), 326-333. O'Connor, P. G., Waugh, M. E., Carroll, K. M., Rounsaville, B. J., Diagkogiannis, I. A., & Schottenfeld, R. S. (1995). Primary care-based ambulatory opioid detoxification The results of a clinical trial. J Gen Intern Med, 10, 255-260. Rabinowitz, J., Cohen, H., & Atias, S. (2002). Outcome of naltrexone maintenance following ultra rapid opiate detoxification versus intensive inpatient detoxification. AmJ Addict, 11(1), 52-56.

Medical Use And Abuse

Workplace drug testing is usually limited to identification of marijuana, cocaine, morphine-codeine, amphetamine-methamphetamine, and phencycli-dine (PCP). However, benzodiazepines and barbiturates may be added to the test panel. Laboratory positive test results for patients with legitimate prescriptions for benzodiazepines and barbiturates are reported to employers by medical review officers (MROs) as negative, as are other laboratory results that reflect appropriate medical treatment with other controlled substances (MacDonald, DuPont, & Ferguson, 2003).

Introduction Analysis Of Urinary Drugs In Clinical And Forensic Toxicology

Clinical and forensic toxicology is concerned with the detection, identification, and measurement of toxic compounds and their metabolites in human body fluids and tissues. Most often the toxic compounds are drugs taken either accidentally or intentionally in quantities sufficient to cause an adverse reaction or death. Analysis and identification of a possible drug or drug combinations, toxicological drug screening and confirmation should encompass as many different classes of drugs as possible. The most important classes being salicylate, paracetamol, antiepileptics, antidepressants, neuroleptics, hypnotics (benzodiazepines, barbiturates, diphenhydramine), digoxin, and theophylline, as well as many illicit drugs, such as opiates, methadone, D-lysergic acid diethylamide (LSD), cocaine, and or its major metabolite benzoylecgonine, cannabinoids and amphetamines. Currently, urinary drug monitoring has established itself as the basis of clinical and forensic toxicology. It is also the...

Analysis And Confirmation Of Urinary Drugs And Metabolytes By Cems

Tural information of compounds, and to use the MS as a CE detector (70,71). Currently there are few published articles discussing CE-MS monitoring of drugs in urine. The best examples are CE-MS determination of urinary N-1-hydroxyethylflurazepam (the major metabolite of flurazepam) (72), halo-peridol (48), anti-inflammatory drugs (ibuprofen, flurbiprofen) and their metabolites (73), paracetamol and metabolites (24,25,74), nonopioid analgesics (24), methadone (30,36), and methylphenidate (75). In addition, the feasibility of using MS as the detector for the enantiomers of terbutaline spiked into a urine blank has been demonstrated (76). In this instance the use of the chiral selector (heptakis (2,6-di-0-methyl)-p-cyclodextrin) in addition to the use of MS gave the selectively needed to verify the chiral composition in complex matrices.

Specimen Not Suitable

The reason I am speaking to you personally is because the results of your urine drug test have been received and it is a positive test. The purpose of this interview is to provide you with an opportunity to voluntarily share information with me that might explain a positive result, such as anything from your medical history, prescriptions, recent treatment or something in your diet. Before I ask you any further questions, I want to tell you that any information that you may disclose will be TREATED CONFIDENTIALLY and not be released unless a U.S. Department of Transportation regulation requires or permits such a disclosure. You have the option of not discussing the matter with me, if you choose. Do you have any questions at this point Non-contact positive test donor declines interview refuses medical interview report as positive drug test.

Testing Methodologies

A multitude of methods are available to aid in the detection of drug use in humans. The most common drug testing technologies are listed in Table 4.1. The most popular initial test screen is an enzyme immunoassay (EIA) analysis of a urine sample. If this is positive, a confirmatory gas chromatography-mass spectroscopy (GC-MS) test is performed on the split sample. Given the greater sensitivity of GC-MS over EIA, the cutoff levels are reduced. The most commonly used analytic technique for a comprehensive drug screen, thin-layer chromatography (TLC), is the least expensive test available. TLC utilizes the differences in polarity and chemical interaction with developing solvents to produce different visualizations on a thin-layer coating. The visualizations are highlighted using ultraviolet (UV) or fluorescent lighting, or by color reactions created after being sprayed with chemical dyes. Identical molecules cluster in the same area, yielding specific color reactions. Unfortunately, TLC...


Representative Goldenseal is an herb frequently used as an astringent and to reputedly mask the presence of illicit drugs, especially marijuana, on urine screens. Goldenseal is, however, ineffective as an undetected adulterant and is easily detected by GC MS ( + drug test). Latin Hydrastis canadensis. Toxin Hydrastine. Antidote None.

Molecular Sorting

Other recent reports of note include the use of flow cytometers to screen for G-protein-coupled receptors 77 , to decipher immunologic signaling networks with phosphospecific flow cytometry 78 and other enzymatic activity 79 , high-throughput drug screening and signaling through the use of bar-coding 80 , and the cell sorter as a DNA sequencing and transcriptional profiling tool 81 . A recent study used a dual fluorescent protein reporter to select for plasmids containing DNA inserts as templates for sequencing as a method for bacterial clone selection without plating. By designing the insertion site between the genes encoding for two different fluorescent proteins, insertion of genetic material resulted in loss of expression of the downstream fluorescent protein (Fig. 6) 82 . Several recent reviews outline other ingenious applications for flow cytometry and cell sorting in the arena of biotechnology as well as discuss changes in the technology behind these instruments 1,3,83-91 .


Despite the legitimate concern with false-positive and false-negative test results, the weakest link in the chain of drug testing is chain-of-custody violations. Regardless of the sophistication of laboratory technology, human error in completing the requisite paperwork at the drug-testing site remains the single most important inconsistent aspect of the testing process. Given the variety of available methods to cheat, it is likely that drug testing will not catch all drug users. As is the case in all aspects of clinical medicine, an accurate diagnosis of substance abuse is based on a comprehensive clinical workup drug testing is only one, albeit important, component of the process. Workplace drug testing hopefully will not only deter drug use by employees while on the job (eliminating costly accidents and errors) but may also assist in initially identifying individuals with drug use disorders. In the world of sports, drug testing is intended to create a level playing field for all...

Cebased Immunoassay

Isotachophoresis system that became commercially available in the mid-1970s. Subsequently, Jorgen and coworkers demonstrated the analytical potential of CE using 75- m fused silica capillaries (3-5) leading to the adaptation and modification of CE for specific applications. The main advantage of CE when used as a separation technique is the small sample-size requirement, minimal sample preparation, rapid TAT, and the potential for automation (6). Currently, nonimmunological CE-based assays are increasingly being used in toxicological drug screening and confirmation for drugs of abuse in urine (7-10). Preliminary confirmation is by on-col-umn, multiwave length UV detection of the solutes with comparison to normalized standard spectra with final confirmation by gas chromatography-mass spectrometery (GC-MS). These CE-based methods rely mainly on capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC). Separation of enantiomers can also be achieved...


With flavopridol (1) as a reference, a COMPARE search of compounds evaluated by the NCI as part of the Anti-tumor Drug Screen program (ADS) uncovered kenpaullone (14a) as a potential CDK1 cyclin B inhibitor (IC5o 0.4 M). Subsequent testing confirmed this activity 64 . From a model of 14a docked in the ATP binding site of CDK2, it was suggested that substitution at the 9-position with a hydrogen bond acceptor might increase affinity by forming a H-bond with a conserved water molecule found in the crystal structure of CDK2 65 . This hypothesis was confirmed by comparing the unsubstituted paullone scaffold 14b, with poor CDK1 activity (IC50 7.0 M), to 9-CN paullone 14c, a 300-fold improvement (IC50 0.024 M). Substitution with a nitro group at the 9-position gave alster-paullone (14d, IC50 0.03 5 M), a compound with submicromolar antiproliferative activity against the HCT-116 tumor cell line (GI50 0.83 M). Further analysis of the model of 14a docked in CDK2, suggested that substitution on...


The clinician is confronted with a wider range of marijuana users. At one end is the individual who uses the drug only rarely, but whose use is detected on a routine drug screen and brought to the clinician's attention, perhaps for an evaluation. Brief assessment, to make sure the problem is not more serious than it appears, is always necessary in this case. Subsequent follow-up, to ensure that the initial impression was correct, is part of a thorough assessment. In this instance, the user is usually embarrassed and repentant, and has no objection to future monitoring. Users who do not have a problem with marijuana do not have a problem giving it up. They may be able to use it in the future, once they have demonstrated the capacity for voluntary nonuse.


In terms of deaths in custody, all drug use, whether social, abusive, or therapeutic, is relevant (13), and the possibility that a detainee may have abused just one drug or a combination of drugs with or without alcohol before death must be positively excluded. A full drug screen on blood and, if available, urine is imperative. Some laboratories will also examine samples of bile and or liver to detect evidence of previous drug abuse.

The Ce System

For us, the decision to use CE for drug screening was dictated primarily by the need for simplicity. Lurie (7) reported separation and detection of drugs of forensic interest in a micellar electrokinetic capillary chromatography (MECC) system. Thormann et al. (10,17,18), Renou-Gonnord and David (19), and Hyotylainen et al. (20) have also used MECC successfully for drug detection. Gonzales and Laserna (21), used capillary zone electrophoresis (CZE) to screen for banned drugs in sport. Chee and Wan (22) also showed the feasibility of using CZE to screen for 17 basic drugs in urine and plasma. Since our major interest initially was on basic drugs, it seemed reasonable to evaluate CZE, the simplest possible CE configuration. Using the procedure of Chee and Wan, 60 cm (to detector) x 50 m id at 25 kV or 50 cm (to detector) x 75 m at 18 kV id uncoated fused silica capillaries were used. The run buffer was 100 mmol L sodium phosphate at pH 2.38 along with electrokinetic injection, typically...


One study compared the effects of alcohol, diazepam, and methadone on clients commencing or stabilized on a methadone program. The battery of tests showed no evidence for an effect of the acute dose of methadone thus, clients on a methadone program should not be considered impaired in their ability to perform complex tasks, such as driving a motor vehicle. Thus, in the United Kingdom, persons on a stable methadone program who have not abused other drugs for 1 yr and who have clear urine drug screening tests regularly are allowed a driving license subject to annual review. However, it should be remembered that users of heroin are also prone to heavy use of other psycho-active drugs, such as cocaine, alcohol, and tranquilizers, which are all dangerous when it comes to driving.


Carbohydrate microarrays have proven to be powerful tools for basic science and diagnostics. The microarray format enables high-throughput screening and minimizes the amount of sugar compounds as well as the quantity of binding samples, lowering cost for experiments and leading to high efficiency. Carbohydrate microarrays bear a broad application range. Various binding partners can be tested, including proteins, RNA, enzymes, viruses, and whole cells. Many aspects of binding can be addressed binding preferences can be determined, competition studies enable drug screening, and whole cell binding is of high diagnostic value.


In our laboratory, a validated CZE method was reported for the determination of amphetamines and related derivatives sold on the black market in the form of tablets of various compositions (65). However, because of the relatively low sensitivity afforded by the short optical path-length of the capillary, UV detection (UV) of these drugs in biological matrices (e.g., urine or serum) was a challenge. To overcome the limitation of sensitivity, CZE was interfaced with ESI-MS for the analysis of ecstasy and its derivatives. Considering the large number of parameters involved in CE-ESI-MS coupling, a chemometric approach was carried out to optimize such factors as nebulization pressure, drying gas temperature and flow rate, electrospray voltage, skimmer voltage, sheath liquid composition, and its flow rate (66). After optimization of the CE-ESI-MS parameters and using a liquid-liquid extraction procedure, SIM was used to monitor only (M+H)+ signals, which allowed a...