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References 1. H. Arksey and L. O’Malley, Scoping studies: towards a methodological framework, Int. J. Soc. Res. Method. 8 (2005) 19-32. 2. S. Derry, R. A. Moore and H. McQuay, Single dose oral codeine, as a single agent, for acute postoperative pain in adults, Cochrane Database System Rev. 4 (2010) CD008099; DOI: 10.1002/14651858. CD008099.pub2. 3. European Medicines Agency, Assessment Report for Codeine-containing Medicinal Products Indicated in the Management of Pain in Children. Procedure under Article 31 of Directive 2001/83/EC resulting from

. Stimulatory Effects of opioids on transmitter release and possible cellular mechanisms: overview and original results. Neurochem Res. 1996;21(11):1353-61. 32. Linet MS, Stewart WF, Celentano DD, Ziegler D, Sprecher M. An epidemiologic study of headache among adolescents and young adults. JAMA. 1989;261(15):2211-6. 33. Zhang WY, Po AL. Do codeine and caffeine enhance the analgesic effect of aspirin?–A systematic overview. J Clin Pharm Ther. 1997;22(2):79-97.

. 2015;(9):CD008659. 9. Pfaffenrath V, Diener HC, Pageler L, Peil H, Aicher B. OTC analgesics in headache treatment: open-label phase vs randomized double-blind phase of a large clinical trial. Headache. 2009;49:638-645. 10. Nielsen S, Van Hout MC. Over-the-Counter Codeine-from Therapeutic Use to Dependence, and the Grey Areas in Between. Curr Top Behav Neurosci. 2016. doi: 10.1007/7854_2015_422. 11. Hamer AM, Spark MJ, Wood PJ, Roberts E. The upscheduling of combination analgesics containing codeine: the impact on the practice of pharmacists. Res Social Adm Pharm

Abstract

Objective: the number of alkaloids like morphine and codeine found in poppy seeds used in food industry are monitored by a directive given by European Food Safety Authority. Based on this regulation the aim of the study was to determine the quantity of morphine and codeine from several brands of poppy seeds. Methods: an HPLC-UV method (205 nm) was developed to measure the quantity of morphine and codeine. Sample preparation was made using recipes posted on Drugs Forum by some users. Limits of detection were not determined because the lowest concentration from the reference (0.1 μg/ml) detected morphine concentrations that are far lower than a limit of toxicological concern. Results: The concentrations, which were found, ranged between Below the Level of Toxicological Concern (BLTC) - 243.26 mg/kg for morphine and BLTC - 88.58 mg/kg for codeine using several methods of preparation. Conclusions: one can observe that there are some brands of poppy seeds which do not respect the regulation about the amount of morphine and codeine. The high amount of morphine in some samples suggests that there are different varieties of poppy seeds, which can be used for an illicit purpose and can lead to addiction or even overdose in some cases.

. et al. (2003) High prevalence of 6-acetylmorphine in morphine-positive oral fluid specimens. Forensic Sci Int 133: 22-25. [14] Cone, E.J., Welch, P., Paul, B.D., Mitchell, J.M. (1991) Forensic drug testing for opiates, III. Urinary excretion rates of morphine and codeine following codeine administration. J Anal. Toxicol. 15: 161-166. [15] Dams, R., Choo, R.E., Lambert, W.E., Jones, H., Huestis, M.A. (2007) Oral fluid as an alternative matrix to monitor opiate and cocaine use in substance-abuse treatment patients. Drug and Alcohol Dependence 87: 258-267. [16

ABSTRACT

The present study examined regional distribution of opiate alkaloids from seized heroin in brain regions of experimental animals in order to select parts with the highest content of opiates. Their analysis should contribute to resolve causes of death due to heroin intake. The tests were performed at different time periods (5, 15, 45 and 120 min) after male and female Wistar rats were treated with seized heroin. Opiate alkaloids (codeine, morphine, acetylcodeine, 6-acetylmorphine and 3,6-diacetylmorphine) were quantitatively determined in brain regions known for their high concentration of μ-opiate receptors: cortex, brainstem, amygdala and basal ganglia, by using gas chromatography-mass spectrometry (GC-MS). The highest content of opiate alkaloids in the brain tissue of female animals was found 15 min and in male animals 45 min after treatment. The highest content of opiates was determined in the basal ganglia of the animals of both genders, indicating that this part of brain tissue presents a reliable sample for identifying and assessing contents of opiates after heroin intake.

Abstract

There are a number of compounds that can modify the activity of ABC (ATP-binding cassette) and SLC (solute carrier) transporters in the blood-brain barrier (BBB). The aim of this study was to investigate the effect of natural and synthetic substances on the expression level of genes encoding transporters present in the BBB (mdr1a, mdr1b, mrp1, mrp2, oatp1a4, oatp1a5 and oatp1c1). Our results showed that verapamil caused the greatest reduction in the mRNA level while other synthetic (piracetam, phenobarbital) and natural (codeine, cyclosporine A, quercetin) substances showed a selective inhibitory effect. Further, the extract from the roots of Panax ginseng C. A. Meyer exhibited a decrease of transcription against selected transporters whereas the extract from Ginkgo biloba L. leaves resulted in an increase of the expression level of tested genes, except for mrp2. Extract from the aerial parts of Hypericum perforatum L. was the only one to cause an increased mRNA level for mdr1 and oatp1c1. These findings suggest that herbs can play an important role in overcoming the BBB and multidrug resistance to pharmacotherapy of brain cancer and mental disorders, based on the activity of selected drug-metabolizing enzymes and transporters located in the BBB

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Retraction By the request of corresponding author Fogarasi Erzsébet, the article „Could Codeine Containing OTC Analgesics Sold in Romania be Used as Recreational Drugs?” published in Acta Medica Marisiensis, 2016;62(3):309-312 (DOI 10.1515/amma-2016-0031) was retracted, due to identified Conflicts of Interest. As an immediate consequence of the aforementioned retraction, the accompanying editorial “The Culprit Coffee Filter and Freezer?” published in Acta Medica Marisiensis, 2016;62(3) had to be retracted for lack of object. This does not mean that we deny or

Fatal Poisoning By Alcohol and Heroin

Drug abuse with alcohol consumption have been on the rise in Split-Dalmatian County for a while now. This article reports two separate cases with three deaths due to fatal combinations of heroin and alcohol. The first case of poisoning is related to a young couple, a 30-year-old man and a 28-year-old woman, who were found dead in a car, surrounded by cans of a variety alcoholic drinks. Two needles were found beside the bodies as well. The victims were registered drug abusers who had been in withdrawal programs. The second case was a 29-year-old man who was found dead in a house. Three fresh injection marks were visible on his right arm, and two needles were near his body. He was not known as a drug addict, but he had tried to commit suicide recently.

Carboxyhaemoglobin was found in blood samples of both victims from the first case. The concentration was 25 % and that could contribute to their death. In both described cases blood alcohol concentration was higher then 1.60 g kg-1. Toxicology tests were positive for heroin, meconin, acetaminophen, 6-acetylmorphine, codeine, noscapine and papaverine. Ethanol, being a respiratory depressant, combined with morphine drastically increases the risk of rapid death due to respiration failure.

and morphine for transitional analgesia after remifentanil-based anesthesia in neurosurgery. Anesth Analg. 2006; 103: 1237-40. 17. De Gray LC, Matta BF. Acute and chronic pain following craniotomy: a review. Anaesthesia. 2005; 60: 693-704. 18. Goldsak C, Scuplak M, Smith M. A double-blind comparison of codeine and morphine for postoperative analgesia following intracranial surgery. Anaesthesia. 1996; 51:1029-32. 19. Stoneham MD, Cooper R, Quiney NF, Walter FJM. Pain following craniotomy: a preliminary study comparing PCA morphine with intramuscular codeine