Levomethamphetamine is neurotoxic

Danger from methamphetamine


1 Swiss Society for Forensic Medicine SGRM Société Suisse de Médecine Légale SSML Società Svizzera di Medicina Legale SSML Section Forensic Chemistry and Toxicology Dangerousness of methamphetamine Opinion of the Section Forensic Chemistry and Toxicology of the Swiss Society for Forensic Medicine (SGRM) with the participation of Dr. phil. Thomas Briellmann, IRM Basel, coordinator Dr. it. sc. Marc Augsburger, CURML, site Lausanne, head of the group forensic toxicology SGRM Dr. rer. nat. Werner Bernhard, IRM Bern Dr. sc. nat. ETH Michael Bovens, Forensic Institute Zurich Dr. rer. nat. Cornelia Brehmer, IRM Zurich, Section President Dr. sc. nat. Ivo Niederer, St. Gallen Canton Police Nicolas Donzé, ICHV Sion Dr. it. sc. Jean-Luc Dubugnon, ICC Lausanne Dr. phil. Franz Dussy, IRM Basel, head of the group forensic chemistry SGRM Prof. Dr. rer. nat. Thomas Krämer, IRM Zurich Dr. it. sc. Maria Teresa Pinorini, Laboratorio di chimica e di tossicologia, Olivone Dr. it. sc. Olivier Plaut, CURML, site Genève Dr. rer. nat. Frank Sporkert, CURML, site Lausanne Walter Sturm, IRM St. Gallen Prof. Dr. rer. nat. Wolfgang Weinmann, IRM Bern Summary The Forensic Chemistry and Toxicology Section of the Swiss Society for Forensic Medicine recommends using 12 grams as the amount for methamphetamine, which can endanger the health of many people. The information relates to methamphetamine hydrochloride. Reason Introduction In accordance with the mandate of the Zurich Public Prosecutor's Office of March 10, 2009 and the oral remarks by Public Prosecutor Winkler from September 2009, the Forensic Chemistry and Toxicology Section of the SGRM comments below on the dangers of methamphetamine and the difference between methamphetamine and ecstasy (3,4- Methylenedioxymethamphetamine, MDMA). In their daily work, the authors of this statement are regularly confronted with forensic-toxicological and / or forensic-chemical questions in connection with methamphetamine and MDMA. Methamphetamine report SGRM, June 2010 page 1 of 7

2 Chemical basics Methamphetamine (chemical name: N-methyl-1-phenyl-propan-2-amine) is a derivative of amphetamine, which is methylated on nitrogen. It belongs to the phenylethylamine family. This group includes many substances that can have a stimulating, but also entactogenic (more intense perception of one's own emotions) or hallucinogenic effect and are also found in a wide range in the narcotics scene. Molecular formula: C 10 H 15 N Molecular weight: g / mol Methamphetamine exists in two so-called stereoisomeric forms, which are now referred to as R and S stereoisomers. These two stereoisomeric forms are mentioned in Appendix II of the 1971 United Nations Convention on Psychotropic Substances. The Swissmedic Narcotics Ordinance (BetmV-Swissmedic) also contains the racemate (equimolar ratio = 1: 1 ratio of the two stereoisomers) or the R stereoisomer under the name levomethamphetamine. Depending on the synthesis route or the use of starting substances, methamphetamine is produced as a racemate or with a preferred stereoisomer ratio. As far as we know, the production of the racemate from phenyl-2-propanone (P2P or BMK for short, an industrial chemical declared as a precursor) is currently still the most common production method. In the following assessment and the designation methamphetamine, the racemate is therefore assumed, i.e. the R and S stereoisomers are not dealt with individually. Methamphetamine can be present as a base (CAS) or in salt form (mostly as hydrochloride, CAS). 1 gram of methamphetamine base corresponds to 1.24 grams of methamphetamine hydrochloride. Use of methamphetamine Methamphetamine as a base is a colorless, volatile oil that is insoluble in water. The main salt in circulation is the colorless or off-white water-soluble hydrochloride in powder form or in crystalline form as ice. Names for methamphetamine in the scene are also inter alia. Speed, Ice, Crank, Meth, Crystal Meth, Yaba, Thai Pills, Shabu, Pervitin (name of an earlier drug). These products are usually either powder or crystalline. Methamphetamine-containing tablets are almost exclusively imported from Thailand to Switzerland via various routes. Compared to the classic ecstasy tablets, the so-called Thai pills have more uniform logos. The most common coinage is wy, seldom only y. Thai pills can also be easily distinguished from ecstasy tablets from a purely visual point of view. They are 6 mm smaller in diameter - compared to the 8-9 mm diameter of the ecstasy tablets - and at around 90 mg lighter - compared to the mg weight of an ecstasy tablet, mostly red to reddish brown (approx. 1% is green) and mostly stretched with caffeine. This helps the tablet when smoking (the most common form of consumption of Thai pills in contrast to the oral consumption of ecstasy tablets) 1 Chemical Abstracts Service, designation standard for chemical substances Methamphetamine report SGRM, June 2010 page 2 of 7

3 for a better release (sublimation) of the methamphetamine hydrochloride salt. In addition, Thai pills often have a typical scent of vanilla. Methamphetamine can be swallowed and snorted, but also injected or smoked as a Thai pill, as mentioned above. Methamphetamine hydrochloride in crystalline form is sufficiently volatile to be smoked. When taken orally, a dose can be a few tens to several hundred milligrams. The methamphetamine content of powders is usually below 10%. Compared to tablets containing MDMA, tablets contain a rather narrowly limited active ingredient content of approx. 15 mg methamphetamine (calculated as base) or approx. 19 mg (as hydrochloride salt). In rare cases, slightly higher levels of up to approx. 20 mg methamphetamine (calculated as base) or approx. 24 mg (as hydrochloride salt) occur. Caffeine and sugar are often used as extenders. Methamphetamine in Switzerland According to a recommendation of the Conference of the Swiss Law Enforcement Authorities (KSBS) on the serious case in the trade in Thai amphetamines on November 22, 2007, the increasing trade in Thai amphetamines (or Thai pills) concerns the Swiss police , Criminal and health authorities since the end of the 90s. The conference also stated that trading in Thai amphetamines now has much higher profit margins than selling cocaine. According to many addiction medicine specialists, Thai amphetamine (Yaba) is the most dangerous drug on the market today. In 2009, just under methamphetamine tablets were seized in Switzerland. Effects of methamphetamine If amphetamines are sniffed, the effect occurs after a few minutes, with smoking and injections after a few seconds (“rush”). The absorption takes place here via the nasal mucous membrane or via the lungs; when injected, the drug gets directly into the blood. With methamphetamine, intoxication can last up to 70 hours. When amphetamines are taken in tablet form, the active ingredient is released in the gastrointestinal tract and then absorbed in the course of the intestine. The effect takes about 30 to 60 minutes and lasts for several hours. As with other narcotics, the risks associated with the consumption of methamphetamine are influenced by consumption behavior (frequency, duration, dosages, form of consumption, individual state of health, etc.). Both the current condition of the individual (also called set) and the respective environmental conditions (setting) play a role. Methamphetamine, especially when smoked, can quickly lead to psychological dependence. After repeated consumption, the body can get used to methamphetamine, so that the dose has to be increased for the desired effect to be repeated. This leads to what is known as a tolerance towards the consumption of amphetamines. Repeated and high-dose use of methamphetamine is linked to violent behavior and paranoid psychosis. Psychosis caused by ice (smoked methamphetamine) can last for days or weeks. Many users suffer from severe insomnia. After consuming methamphetamine, psychoactive substances such as cannabis or benzodiazepines are therefore often consumed for relaxation, which can lead to polytoxicomania. After the effects have subsided, depressive moods can occur. As little as 3 mg of methamphetamine should be enough to have a stimulating effect on most people. In the context of therapeutic measures, the recommended single dose was therefore 3 to 6 mg methamphetamine-expert report SGRM, June 2010 page 3 of 7

4 Methamphetamine hydrochloride, the maximum daily dose stated was 15 mg methamphetamine hydrochloride. Oral doses of more than 20 mg can cause considerable psychological and vegetative side effects in those who are not used to it. Seized methamphetamine tablets in Switzerland usually contain between 15 to 20 mg methamphetamine base per tablet. While only a part of the ingested dose reaches the brain with oral ingestion, venous injection and even more with inhalation / smoking lead to the rapid absorption of a high proportion of the anesthetic in the brain, so that a stronger intoxicating effect is achieved with this form of consumption. In contrast to the sulfate salt of amphetamine, methamphetamine hydrochloride, especially in crystalline form (ice), is sufficiently volatile to be smoked. In contrast to smoking crack (cocaine base), methamphetamine passes into the gas phase without decomposition when heated slightly, so that the bioavailability is higher than with crack. When smoking amphetamine, which is usually sold as a sulfate salt, on the other hand, the molecules decompose when heated, so that amphetamine is not suitable for this form of consumption. Methamphetamine causes the increased release of noradrenaline and dopamine (compared to amphetamine to a higher degree), which on the one hand (due to noradrenaline) leads to an increase in performance and on the other hand to increased dopamine concentrations in brain regions, which are responsible for the mood . This triggers the intense feeling of happiness after consumption. Methamphetamine reaches the brain more quickly than amphetamine, which means that the stimulating effect is stronger and a higher state of intoxication occurs. Because of this, methamphetamine is more addictive than amphetamine. Other effects are the rise in body temperature, the acceleration of pulse and breathing, rise in blood pressure and the suppression of hunger and the need for sleep. Undesirable side effects of methamphetamine include: a central excitement with panic attacks, hallucinations, psychoses or depressive episodes. Overdosing can lead to cerebral seizures or stroke. Occurring hyperthermia (strong increase in body temperature to values ​​above 40 C), combined with desiccosis (dehydration), can have life-threatening consequences. These can occur particularly at high room temperatures and / or during intense physical exertion, as is the case, for example, when dancing in discos. Other side effects are tachycardia (rapid heartbeat), which can lead to cardiac arrhythmias and heart attacks, increased blood pressure, kidney failure or liver damage. The inhaled and nasal form of methamphetamine can increase the psychological side effects. Recent studies have shown that methamphetamine is neurotoxic and, if used long-term, leads to nerve damage, which manifests itself in a deterioration in cognitive abilities such as deficits in attention and memory. As already mentioned, methamphetamine-induced psychoses have also been described. According to the US National Institute on Drug Abuse (NIDA), methamphetamine is said to have a negative impact on the course of HIV / AIDS due to its neurotoxicity. For example, more neurological and cognitive deficits were observed in HIV patients who used methamphetamine. Deaths after consuming methamphetamine have been reported. Compared to amphetamine, methamphetamine has about twice as strong an effect on the cardiovascular system. Chronic methamphetamine abuse shows changes in the activity of the dopamine system, which affects brain functions. Structural and functional changes have been noted in some areas of the brain that control emotional behavior and memory. Long-term use of methamphetamine can also lead to deterioration in physical and mental health. Weight loss, organ damage, fever, diarrhea, dental problems or a weakened immune system can occur. Psychological consequences are methamphetamine report SGRM, June 2010 page 4 of 7

5 et al. Depressive moods with states of exhaustion and anxiety, restlessness, irritability and increased aggressiveness, lack of inhibition and lack of critical ability as well as psychoses, hallucinations or delusions. Difference between methamphetamine and ecstasy On the one hand, the substance methylenedioxymethamphetamine (MDMA), on the other hand, the entirety of the group of designer drugs is called ecstasy. Methamphetamine and ecstasy (methylenedioxymethamphetamine, MDMA) are both amphetamine derivatives; methylenedioxyethylamphetamine (MDEA) and methylenedioxyamphetamine (MDA) are also included. The structure of methamphetamine differs from that of MDMA, MDEA and MDA, however, in that a differentiated view is imperative. In MDMA, MDEA and MDA, the molecular structure contains a second ring system. This results in a significant change in effect. With the amphetamine derivatives known as designer drugs, the stimulating effect - as with methamphetamine and amphetamine - is not in the foreground, but an affective change of state in the sense of a stimulating, contact-promoting (entactogenic), disinhibiting mood with a simultaneous increase in motor activity. These designer drugs are therefore also known as entactogens. After consuming these entactogens, high doses - in contrast to amphetamine and methamphetamine - lead to a hallucinogenic effect. The effective single dose of these designer drugs is significantly higher than that of methamphetamine, for example between 80 and 150 mg for MDMA. This roughly corresponds to the range of MDMA content of a tablet observed in recent years, whereby MDMA contents of mg per tablet are not uncommon. Even if MDMA contains the term ... methamphethamine in its name, this designer drug has little in common with methamphetamine in terms of its effects. Due to the different basic structure, MDMA cannot be produced (synthesized) from methamphetamine. This also applies in the opposite case. Amount of substance methamphetamine that can put the health of many people at risk The Swiss Federal Supreme Court has only ruled on the serious case of amphetamine and ecstasy (MDMA) to date. In the BGE 113 IV 32 of January 16, 1987 it stipulated that 36 grams of amphetamine can endanger the health of many people. The 36 grams stem from the consideration that, in the opinion of the experts and based on the knowledge at the time, the assumption of a ratio of 1: 2 between cocaine and amphetamine was justifiable. According to BGE 125 IV 90 of April 21, 1999, it cannot be said that ecstasy is suitable for bringing physical or mental health into an obvious and serious danger, so that no substance quantity has been specified for MDMA for severe cases. However, the Federal Supreme Court specified that this ruling should be reviewed if significant new knowledge - in particular on neurotoxicity - were obtained. In a report dated November 15, 1999, Dr. Ch. Giroud from the Institut universitaire de médecine légale (IUML) Lausanne believes that Thai amphetamines should be regarded as at least as dangerous as cocaine, and postulated a serious case from an amount of 18 grams of methamphetamine base. On August 22, 2006, the Court of Cassation of the Canton of Neuchâtel took the view that the literature published between 1999 and the date of the judgment still supported the IUML Lausanne report and that there was no reason to deviate from it. Methamphetamine report SGRM, June 2010 page 5 of 7

6 In an expert opinion dated June 25, 2001, Dr. W. Bernhard (Institute for Forensic Medicine Bern) commented on the assessment of Thai pills as a serious drug case. He came to the conclusion that if the drug was taken by sniffing or swallowing, a limit of 16.6 grams of methamphetamine could be used for severe cases. While smoking methamphetamine, he postulated a severe case of 700 pills, i. H. the equivalent of 13.5 grams of methamphetamine. The Conference of the Swiss Law Enforcement Authorities (KSBS) recommended in 2007 that a serious case of 16 grams or more of pure active substance be accepted in all proceedings relating to the trade in Thai amphetamines. Since a yaba pill contains an average of 0.022-0.026 grams of methamphetamine (the composition being quite similar from one case to the other, as the product cannot be stretched from manufacture to retail), the trade would be 700 to 825 pieces among the Art. 19 No. 2 lit. a BetmG fall. The law enforcement authorities in Switzerland should ensure uniform practice in this area. In Germany, on December 3, 2008, the Federal Court of Justice (BGH) set the not insignificant amount of methamphetamine base at 5 grams.The BGH relied on two experts who both stated that when ingested orally methamphetamine is about one and a half to twice as strong as amphetamine. In the consumption form of smoking - which is not possible with amphetamine - methamphetamine has at least twice as strong an effect as amphetamine and, above all, considerably faster, because the blood-brain barrier is overcome more quickly due to the higher lipophilicity (fat solubility) of methamphetamine. The explanatory memorandum also states that, based on the 200 units of consumption on which the limit value of the not small amount of amphetamine is based, a very high single dose of 25 mg methamphetamine base for people who are not used to methamphetamine results in a total amount of active ingredient of 200 x 25 mg = 5 grams, i.e. H. 6.2 grams of methamphetamine hydrochloride is the limit of the not small amount. In view of the more recent findings about the high addiction potential of methamphetamine and the health consequences of improper consumption, this reduction is not only justified, but necessary. Furthermore, the BGH pointed out that by setting the not insignificant amount of 5 grams of methamphetamine base a realistic classification of methamphetamine compared to amphetamine, cocaine and heroin, but not to the 3,4-methylenedioxy derivatives ( MDA, MDMA, MDEA), in which the not small amount is 30 grams of MDA / MDMA / MDEA-Base, has been reached. For the BGH, an equation in the effect with crack (cocaine base) is justified for the form of consumption of smoking methamphetamine. Furthermore, this most dangerous form of consumption plays a major role in determining the limit value, because drug users naturally want to achieve the fastest and most powerful effect possible. For this reason, smoking is the most common method of methamphetamine consumption today. If these considerations are to be taken into account in Switzerland too, the limit value must not be set higher than that for cocaine (18 grams according to BGE 109 IV 143 of September 21, 1983). Taking into account the opinion of the experts in the BGH ruling that methamphetamine is at least twice as effective as amphetamine when smoking, an even lower limit value can be justified. For the Forensic Chemistry and Toxicology Section of the SGRM it is important that the severe case (or the amount of substance that can endanger the health of many people) for methamphetamine differs significantly from amphetamine and shows the dangerousness of this narcotic. A lower limit value is also justified in comparison to cocaine, since methamphetamine hydrochloride has a higher bioavailability than crack. However, for reasons of comparability, the methamphetamine limit value should not be set lower than the current limit value for heroin hydrochloride. For the reasons mentioned above, we therefore recommend setting the amount of substance for methamphetamine, which can put the health of many people at risk, to 12 grams of methamphetamine hydrochloride. Methamphetamine report SGRM, June 2010 page 6 of 7

7 Literature Ordinance of the Swiss Agency for Therapeutic Products of December 12, 1996 on Narcotics and Psychotropic Substances (Narcotics Ordinance Swissmedic, BetmV-Swissmedic), Police Criminal Statistics (PKS), Annual Report 2009, Federal Statistical Office (FSO) Th , 6th edition, Springer-Verlag 2007 Hammer, MR (2006), A Key to Methamphetamine-Related Literature, New York State Department of Health, New York (as of April 16, 2010) Recommendations of the Conference of Law Enforcement Authorities in Switzerland (KSBS) concerning the serious case in the trade in Thai amphetamines dated November 22, 2007 Moffat, AC, Osselton, M, D. and Widdop, B, (eds.) (2004), Clarke's Analysis of Drugs and Poisons, 3rd edition, volume 2, Pharmaceutical Press, London. R.M. Julien, Drogen und Psychopharmaka, Spektrum Akademischer Verlag, 1997 AM Barr et al, The need for speed: an update on methamphetamine addiction, J Psychiatry Neurosci 31 (5): 301-13, 2006 RC Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, California, 2008 EMCDDA-Europol Joint Publications, Methamphetamine a European Union perspective in the global context, Lisbon 2009 National Institute on Drug Abuse, USA (as of April 16, 2010) Swiss Toxicological Information Center (As of April 16, 2010) M. Bovens, expert opinion on the composition of ecstasy tablets, amphetamine and methamphetamine seizures and assessment of the quantitatively serious case of psilocin, WD of September 1, 1999 Swiss Federal Supreme Court, BGE 113 IV 32 of January 16, 1987 Swiss Federal Supreme Court , BGE 125 IV 90 of April 21, 1999 Ch. Giroud, Expertise concernant le cas grave pour methamphétamine, Institut de médecine légale Lausanne, November 15, 1999 W. Bernhard, Recommendations for the assessment of Thai pills as a serious drug case, June 25, 2001 Federal Court of Karlsruhe, Judgment 2 StR 86/08 of December 3, 2008 on the significant amount of methamphetamine Swiss Federal Court, BGE 109 IV 143 of September 21, 1983 methamphetamine report SGRM, June 2010 page 7 of 7