Amphetamine-induced psychosis - a separate diagnostic entity or primary psychosis triggered in the vulnerable? / Jørgen G. Bramness, Øystein H. Gundersen, Joar Guterstam, Eline B. Rognli, Maija Konstenius, Else-Marie Løberg, Sigrid Medhus, Lars Tanum, Johan Franck. - (BMC Psychiatry (2012), 12:221

• doi:10.1186/1471-244X-12-221

Use of amphetamine and methamphetamine is widespread in the general population and common among patients with psychiatric disorders. Amphetamines may induce symptoms of psychosis very similar to those of acute schizophrenia spectrum psychosis. This has been an argument for using amphetamine-induced psychosis as a model for primary psychotic disorders. To distinguish the two types of psychosis on the basis of acute symptoms is difficult. However, acute psychosis induced by amphetamines seems to have a faster recovery and appears to resolve more completely compared to schizophrenic psychosis. The increased vulnerability for acute amphetamine induced psychosis seen among those with schizophrenia, schizotypal personality and, to a certain degree other psychiatric disorders, is also shared by non-psychiatric individuals who previously have experienced amphetamine-induced psychosis. Schizophrenia spectrum disorder and amphetamine-induced psychosis are further linked together by the finding of several susceptibility genes common to both conditions. These genes probably lower the threshold for becoming psychotic and increase the risk for a poorer clinical course of the disease.

The complex relationship between amphetamine use and psychosis has received much attention but is still not adequately explored. Our paper reviews the literature in this field and proposes a stress-vulnerability model for understanding the relationship between amphetamine use and psychosis.

Psychiatric and medical effects of anabolic-androgenic steroid use. A controlled study of 160 athletes / Harrison G. Pope Jr, David L. Katz. - (Archives of general psychiatry 51 (1994) 5 (May); p. 375-382)

• PMID: 8179461
• DOI: 10.1001/archpsyc.1994.03950050035004

Abstract

Background: We sought to expand on preliminary findings suggesting that anabolic-androgenic steroids produce psychiatric effects in some athletes who use them.

Methods: We compared 88 athletes who were using steroids with 68 nonusers, using the Structured Clinical Interview for DSM-III-R to diagnose psychiatric syndromes occurring in association with steroid use (if applicable) and in the absence of steroid use. Demographic, medical, and laboratory measures were also performed.

Results: Steroid users displayed more frequent gynecomastia, decreased mean testicular length, and higher cholesterol-high-density lipoprotein ratios than nonusers. Most strikingly, 23% of steroid users reported major mood syndromes--mania, hypomania, or major depression--in association with steroid use. Steroid users displayed mood disorders during steroid exposure significantly more frequently than in the absence of steroid exposure (P < .001) and significantly more frequently than nonusers (P < .01). Users rarely abused other drugs simultaneously with steroids.

Conclusion: Major mood disturbances associated with anabolic-androgenic steroids may represent an important public health problem for athletes using steroids and sometimes for the victims of their irritability and aggression.

Clenbuterol residues in pig muscle after repeat administration in a growth-promoting dose / Pleadin J, Vulić A, Persi N, Vahcić N. Meat Sci. 2010 Nov;86(3):733-7.

• doi: 10.1016/j.meatsci.2010.06.013. Epub 2010 Jun 20

Laboratory for Analytical Chemistry, Croatian Veterinary Institute, Savska 143, HR-10 000 Zagreb, Croatia.

The aim of this study was to determine the level of clenbuterol residues in muscle tissue of pigs after repeat administration in a growth-promoting dose. An anabolic dose of clenbuterol (20 μg/kg body mass per day) was administered orally to experimental group (n=12) for 28 days, whereas control animals (n=3) were left untreated. Clenbuterol treated pigs were randomly sacrificed (n=3) on days 0, 3, 7 and 14 of treatment discontinuation and clenbuterol residues determined in muscle tissue. Determination of residual clenbuterol was by enzyme-linked immunosorbent assay (ELISA) as a screening method and liquid chromatography tandem mass spectrometry (LC-MS/MS) as a confirmation method. The highest clenbuterol content in the muscle of treated animals was recorded on day 0 of treatment cessation (4.40±0.37 ng/g) and significantly (p<0.05) exceeded the maximum residue limit (MRL) of 0.1 ng/g. On day 3 of withdrawal, it was 0.49±0.22 ng/g and on day 7 0.10±0.02 ng/g (at MRL); on day 14 of treatment discontinuation, clenbuterol content was below the limit of detection (<0.1 ng/g) in all samples. Administration of clenbuterol as a growth promoter in pig production could lead to residues in meat for human consumption up to 7 days after treatment discontinuation.

Stephany RW. Handb Exp Pharmacol. 2010;(195):355-67. doi: 10.1007/978-3-540-79088-4_16.

In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters ("anabolics") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters ("hormones") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of "legal natural levels" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone preparations or the site of application of "pour on" preparations - the hormone concentrations observed in meat samples of illegally treated animals are typically in the range of a few micrograms per kilogram (ppb) down to a few tenths of a microgram per kilogram. In the EU dozens of illegal hormones are used and the number of active compounds is still expanding. Besides estrogenic, androgenic and progestagenic compounds also thyreostatic, corticosteroidal and beta-adrenergic compounds are used alone or in "smart" combinations.An overview is given of the compounds identified on the EU black market. An estimate is also given of the probability of consumption in the EU of "highly" contaminated meat from the application sites in cattle. Finally some data are presented on the concentration of estradiol in bovine meat from animals treated and not treated with hormone implants. These data are compared with the recent findings for estradiol concentrations in hen's eggs. From this comparison, the preliminary conclusion is that hen's eggs are the major source of 17alpha- and 17beta-estradiol in the consumer's daily "normal" diet.

Determination of 76 pharmaceutical drugs by liquid chromatography-tandem mass spectrometry in slaughterhouse wastewater / Shao B, Chen D, Zhang J, Wu Y, Sun C. J. - (Chromatogr A. 2009 Nov 20;1216(47):8312-8318

• doi: 10.1016/j.chroma.2009.08.038. Epub 2009 Aug 21.

Central Laboratory, Beijing Center for Disease Control and Prevention, Beijing 100013, China

A multi-residue method for the analysis of 76 pharmaceutical agents of nine classes of drugs (tetracyclines, macrolides, fluoroquinolones, beta-agonists, beta-blockers, diuretics, sedatives, sulfonamides and chloramphenicol) in slaughterhouse wastewater and a receiving river is presented. After simultaneous extraction with an Oasis HLB solid-phase extraction (SPE) cartridge and further purification using an amino SPE cartridge, analytes were detected by liquid chromatography-electrospray ionization-tandem mass spectrometry in positive or negative ion mode. Standard addition was used for quantification to overcome unavoidable matrix effects during ESI-MS analysis. Recoveries for most analytes based on matrix-matched calibration in different test matrices were >60%. The method quantification limits of 76 pharmaceuticals were in the range 0.2-30 ng/L. Nineteen compounds of 76 drugs were found in raw and treated slaughterhouse wastewater from four main slaughterhouses in Beijing. Sulfanamides (sulfanilamide, sulfameter), fluoroquenones (ofloxacin, pefloxacin, norfloxacin, ciprofloxacin, enrofloxacin), tetracyclines (tetracycline, oxytetracycline) and macrolides (kitasamycin, tylosin, erythromycin) were most frequently detected, with the highest levels up to approximately 3 microg/L in slaughterhouse wastewater and approximately 1 microg/L in treated wastewater. Illicit drugs for animal feeding such as clenbuterol and diazepam were commonly detected in slaughterhouse wastewater. These analytes were also observed in a river receiving slaughterhouse wastewater, with a highest level of up to 0.2 microg/L.

Meat products as potential doping traps? / Hans Braun, Hans Geyer, Karsten Koehler. - (International Journal of Sport Nutrition and Exercise Metabolism 18 (2009) 5 (October); p. 539-542).
- PMID: 19051433.
- DOI: https://doi.org/10.1123/ijsnem.18.5.539

Abstract:

Recently published news regarding food safety in China caused some worldwide disturbance and uncertainty among top athletes and their supporting staff. According to an article in The New York Times, a member of the U.S. Olympic team discovered oversized chicken breast when visiting a supermarket in Beijing, China. More interesting, the chicken contained considerable amounts of anabolic steroids, which were reported to be large enough to cause a failed doping test after ingesting the meat (Shpigel, 2008). Based on this case report it appears necessary to assess the danger posed to our (Olympic) athletes by foods and especially meat products on a more general basis. More important, our athletes are involved in worldwide travel during the competitive season. Therefore we must consider not only our athletes’ local food choices but also the wide variety of foods and regional delicacies our athletes might be confronted with in foreign countries.

Barbosa J, Cruz C, Martins J, Silva JM, Neves C, Alves C, Ramos F, Da Silveira MI. Food Addit Contam. 2005 Jun;22(6):563-6.
Laboratório Nacional de Investigação Veterinária, Lisboa, Portugal.
Abstract

This paper describes the occurrence of four cases of acute food poisoning, involving a total of 50 people, due to the ingestion of lamb and bovine meat containing residues of clenbuterol. Symptoms shown by the intoxicated people may be generally described as gross tremors of the extremities, tachycardia, nausea, headaches and dizziness. Analytical methodology developed for the determination of clenbuterol in meat, liver and blood samples is described. Procedures are described which should be followed when the described symptoms are evident in a group of people who have ingested contaminated meat, and particularly liver of ruminants.

Consequence of boar edible tissue consumption on urinary profiles of nandrolone metabolites : II. Identification and quantification of 19-norsteroids responsible for 19-norandrosterone and 19-noretiocholanolone excretion in human urine / De Wasch K, Le Bizec B, De Brabander H, André F, Impens S. Rapid Commun Mass Spectrom. 2001;15(16):1442-7.
Laboratory of Chemical Analysis, Ghent University, Faculty of Veterinary Medicine, Salisburylaan 133, B-9820 Merelbeke, Belgium.

In previous work (Le Bizec et al., Rapid Commun. Mass Spectrom. 2000; 14: 1058), it was demonstrated that a boar meal intake could lead to possible false accusations of abuse of 17beta-nortestosterone in antidoping control. The aim of the present study was to identify and quantify endogenous 19-norsteroids in boar edible tissue at concentrations that can alter the steroid urinary profile in humans, and lead to excretion of 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE). The samples were analysed in two laboratories. The methodologies used for extraction and detection (GC/MS(EI) and LC/MS/MS(APCI+)) are compared and discussed. 19-Norandrostenedione (NAED), 17beta- and 17alpha-nortestosterone (bNT, aNT), and 17beta- and 17alpha-testosterone (bT, aT) were quantified. The largest concentrations of NAED and bNT were observed in testicles (83 and 172 microg/kg), liver (17 and 63 microg/kg) and kidney (45 and 38 microg/kg). A correlation between the bNT and NAED content of a typical meal prepared with boar parts and the excreted concentrations of 19-NA and 19-NE in human urine was demonstrated.

Consequence of boar edible tissue consumption on urinary profiles of nandrolone metabolites. I. Mass spectrometric detection and quantification of 19-norandrosterone and 19-noretiocholanolone in human urine / B. Le Bizec, I. Gaudin, F. Monteau, F. Andre, S. Impens, K. De Wasch, H. De Brabander

• Rapid Communications in Mass Spectrometry 14 (2000) 12 (30 June), p. 1058-1065
• PMID: 10861987
• DOI: 10.1002/1097-0231(20000630)14:12<1058::AID-RCM991>3.0.CO;2-7

Abstract

For the first time in the field of steroid residues in humans, demonstration of 19-norandrosterone (19-NA: 3alpha-hydroxy-5alpha-estran-17-one) and 19-noretiocholanolone (19-NE: 3alpha-hydroxy-5beta-estran-17-one) excretion in urine subsequent to boar consumption is reported. Three male volunteers agreed to consume 310 g of tissues from the edible parts (meat, liver, heart and kidney) of a boar. The three individuals delivered urine samples before and during 24 h after meal intake. After deconjugation of phase II metabolites, purification and specific derivatisation of target metabolites, the urinary extracts were analysed by mass spectrometry. Identification was carried out using measurements obtained by gas chromatography/high resolution mass spectrometry (GC/HRMS) (R = 7000) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) (positive electrospray ionisation (ESI+)). Quantification was realised using a quadrupole mass filter. 19-NA and 19-NE concentrations in urine reached 3.1 to 7.5 microg/L nearby 10 hours after boar tissue consumption. Levels returned to endogenous values 24 hours after. These two steroids are usually exploited to confirm the exogenous administration of 19-nortestosterone (19-NT: 17beta-hydroxyestr-4-en-3-one), especially in the antidoping field. We have thus proved that eating tissues of non-castrated male pork (in which 17beta-nandrolone is present) might induce some false accusations of the abuse of nandrolone in antidoping.

Segura J, Monfort N, Ventura R. Drug Test Anal. 2012 Nov;4(11):876-81. doi: 10.1002/dta.405. Epub 2012 Mar 9.
Bioanalysis Research Group, IMIM Hospital del Mar Research Institute, Barcelona, Spain.

The use of blood doping is forbidden by the World Anti-Doping Agency. Several practices, such as blood transfusions are used to increase oxygen delivery to muscles and all of them are highly pursued. In this regard, the development of accurate methodologies for detecting these prohibited practices is one of the current aims of the anti-doping control laboratories. Flow cytometry methods are able to detect allogeneic blood transfusions but there is no official methodology available to detect autologous blood transfusions. This paper reviews protocols, including the Athlete Biological Passport, that use indirect markers to detect misuse of blood transfusions, especially autologous blood transfusions. The methods of total haemoglobin mass measurements and the detection of metabolites of blood bags plasticizers in urine are reviewed. The latter seems to be an important step forward because it is a fast screening method and it is based on urine, a fluid widely available for doping control. Other innovative approaches to blood transfusion detection are also mentioned. A combination of the reported methodologies and the implementation of the Athlete Biological Passport is becoming a promising approach.