Nätdroger -Risker och konsekvenser för användaren U-FOLD Storseminarium Uppsala 3 april 2013 Nätdroger -Risker och konsekvenser för användaren Maria Ellgren Med. Dr., Universitetsadjunkt Inst. för Farmaceutisk Biovetenskap Uppsala Universitet

Kommunikation mellan nervceller Signalsubstanser frisätts och binder till specifika receptorer (mottagarstationer) på närliggande nervcell. Slide 3: How a neuron works. Neurons are unique because they can send information from the brain to the rest of the body. Your brain communicates with the rest of your body by sending messages from one neuron to the next and ultimately to the muscles and organs of the body. Neurons can also store information as memories.   Typically, a neuron contains three important parts: a cell body that directs all activities of the neuron; dendrites (the part that looks like tree branches), which are short fibers that receive messages from other neurons and relay those messages to the cell body; and the axon, a long single fiber that transmits messages from the cell body to dendrites of other neurons. Every moment, messages are moving with amazing speed back and forth from neuron to neuron. As a matter of fact, scientists often compare the activity of neurons to the way electricity works. A neuron communicates with other neurons at special places called synapses or synaptic clefts. To send a message, a neuron releases a chemical messenger, or neurotransmitter, into the synaptic cleft. From there, the neurotransmitter crosses the synapse and attaches to key sites called receptors on the next neuron in line. When neurotransmitters attach to these receptors, they cause changes inside the receiving neuron and the message is delivered. Neurons communicate with each other through a network of interconnected cells that scientists are still trying to fully understand. Scientists do know that this complex communication system within the brain can be disrupted by the chemicals in drugs. Did you know that more than 400 chemicals are in a marijuana leaf? And over 4,000 chemicals besides nicotine are in tobacco! Illustration used with permission, courtesy of Lydia V. Kibiuk and the Society for Neuroscience. ____________________ Maria Ellgren från National Institute on Aging, National Institute of Health, USA

= synthetic designer drugs (SDD), research chemicals (RC) Nätdroger = synthetic designer drugs (SDD), research chemicals (RC) Ursprungligen tagits fram som forskningssubstanser Påverkar specifika signalsystem och ger “attraktiva” effekter som eufori och hallucinationer Narkotikaklassas efter hand  ersätts av nya snarlika substanser som ger liknande effekt Slide 6: Impulse flow Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon. ____________________ Maria Ellgren

Nätdroger Syntetiska cannabinoider Katinoner Spice, K2, Aroma,… Substanser: AM-2201, JWH-018, JWH-073, CP-47497, etc. Sprayas på torkade örter och röks Liknar cannabis (hasch, marijuana) Katinoner Badsalt, Cloud 9, Ivory wave, Vanilla sky,… Substanser: Mephedrone, MDPV, methylone, etc. Pulver snortas eller rullas in i papper och sväljs Liknar psykostimulantia (kokain, ecstasy, amfetamin) Slide 6: Impulse flow Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon. ____________________ Maria Ellgren

-Risker och konsekvenser för användaren Nätdroger -Risker och konsekvenser för användaren Risker kopplade till verkningsmekanismen och efterfrågade effekten Ej olagligt –inte heller lagligt!... Slide 6: Impulse flow Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon. ____________________ Maria Ellgren

-verkningsmekanism och effekt Katinoner -verkningsmekanism och effekt Frontal cortex- varseblivning Inget i syn men ____________________ Maria Ellgren

(Mephedrone, MDPV, methylone, etc.) Katinoner (Mephedrone, MDPV, methylone, etc.) Verkningsmekanism liknar psykostimulantia Blockerar och/eller reverserar dopamin-, noradrenalin- och serotonintransportörerna Minskar nedbrytning av dopamin, noradrenalin och serotonin Ökad dopamin-, noradrenalin- och serotoninsignalering Transportör Slide 6: Impulse flow Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon. ____________________ Maria Ellgren

Katinoner Effekter MDPV Dopamin > noradrenalin >> serotonin (block, ej frisättning) Mephedrone / methylone Serotonin > dopamin = noradrenalin Dopamin Eufori, hyperaktivitet Noradrenalin Hjärtklappning, ökad puls och blodtryck, vakenhet Serotonin Förhojd kroppstemp, celldöd, “kärlek”/aggression, hallucinationer Slide 6: Impulse flow Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon. ____________________ Maria Ellgren

Hjärnans belöningssystem (mesokortikolimbiska dopaminsystemet) Aktiveras av mat- och vattenintag sex fysisk aktivitet beroendeframkallande droger Känsla av välbefinnande /eufori Dopamin  Modifierad från NIDA, NIH, USA ____________________ Maria Ellgren

Katinoner Effekter MDPV Dopamin > noradrenalin >> serotonin (block, ej frisättning) Mephedrone / methylone Serotonin > dopamin = noradrenalin Dopamin Eufori, hyperaktivitet Noradrenalin Hjärtklappning, ökad puls och blodtryck, vakenhet Serotonin “kärlek”/aggression, hallucinationer, förhöjd kroppstemp, celldöd, Slide 6: Impulse flow Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon. ____________________ Maria Ellgren

(Mephedrone, MDPV, methylone, etc.) Katinoner (Mephedrone, MDPV, methylone, etc.) Akuta kliniska effekter hjärtklappning, puls- och bt-ökning, kärlsammandragning extrem oro/rastlöshet/aggression (agitation) kroppstempökning hallucinationer kraftig eufori Fallbeskrivningar eller studier med få subjekt, självrapporter på internetforum, giftinformationscentraler Eufori själva syftet, hög beroendepotential! Slide 6: Impulse flow Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon. ____________________ Maria Ellgren Watterson et al Addiction Biol 2012

Syntetiska cannabinoider -verkningsmekanism och effekt Frontal cortex- varseblivning Inget i syn men ____________________ Maria Ellgren

Cannabinoider -verkningsmekanism Nervcell kroppseget cannabis Cannabisreceptor (CB1) Nervcell ____________________ Maria Ellgren

Cannabinoider -verkningsmekanism Nervcell kroppseget cannabis Cannabisreceptor (CB1) Nervcell ____________________ Maria Ellgren

Cannabinoider -verkningsmekanism THC Nervcell syntetiskt cannabis kroppseget cannabis Cannabisreceptor (CB1) Nervcell ____________________ Maria Ellgren

Effekter av cannabisrökning Bindning till cannabisreceptorer orsakar: Förstärkta syn, ljud och känselintryck Försämrad kognition (minne, koncentration, problemlösning, etc.) Ångest, paranoida tankar, psykos Hunger Eufori Frontal cortex- varseblivning Inget i syn men ____________________ Maria Ellgren

Syntetiska cannabinoider Hasch & marijuana/ THC Binder ofta mycket starkare till cannabisreceptorn Större risk för överdosering (hur mkt har sprayats på?) Innehåller inte cannabidiol (CBD) som har viss skyddande effekt ____________________ Maria Ellgren

Cannabidiol (CBD)  Skyddar mot cannbisinducerad psykos (schizofreni?) Akuta psykosrelaterade THC-effekter minskade av CBD Zuardi A.W. et al. Psychopharmacology 1987, Morgan C.J.A. et al. BJP 2008 Psykospatienter oftare rökt cannabis med hög TCH-halt och låg CBD-halt Di Forti M. et al. BJP 2009  Skyddar mot cannbisinducerad psykos (schizofreni?) Cannbisberedning med hög CBD-halt gav lägre eufori och merbegär Morgan C.J. et al Neuropsychopharm. 2010. 35(9):1879-85  Skyddar mot beroendeutveckling? Cannabis förädlas att innehålla mer THC/mindre CBD Spice innehåller inget CBD! ____________________ Maria Ellgren

Kliniska effekter av syntestiska cannabinoider stark eufori ångest/oro psykos, hallucinationer epilepsianfall hjärtklappning och höjt blodtryck muskelspasmer minnesförsämring Stor risk för överdosering Fallbeskrivningar eller studier med få subjekt, självrapporter på internetforum, giftinformationscentraler ____________________ Maria Ellgren

Konsekvenser av långtidsanvändning av syntetiska cannabinoider eller katinoner vet vi ingenting om! Slide 6: Impulse flow Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon. ____________________ Maria Ellgren

Inte narkotikaklassat, “naturliga örter”, ingen åldersgräns = säkert?... Inte heller godkänt läkemedel! Slide 6: Impulse flow Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon. ____________________ Maria Ellgren

Inte olagligt = ofarligt? Läkemedel Rigorös testning vad gäller hälsorisker/säkerhet Höga krav på dokumentation, kvalitetstester och renlighet under tillverkningen Olagliga/ “icke-godkända” substanser: Gick tillverkningen som den skulle? Renhet/dos? Biverkningar? Renlighet? Hela tiden nya substanser nya styrkor, nya bieffekter Ingen åldersgräns  Potentiellt farligt att sätta i sig! Slide 6: Impulse flow Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon. ____________________ Maria Ellgren

-Risker och konsekvenser för användaren Nätdroger -Risker och konsekvenser för användaren Mer forskning behövs för att vetenskapligt fastställa skadeverkningar av specifika substanser Men, substanserna tas fram för att de påverkar specifika signalsystem där påverkan har väl dokumenterade skadeverkningar, bara oklart hur farligt det är! Slide 6: Impulse flow Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon. ____________________ Maria Ellgren

Nätdroger och den unga hjärnan Riktar sig till unga Hjärnan ej färdigutvecklad förrän uppemot 25 års ålder  mer känslig, större risk för bestående skador Ingen åldersgräns som för tobak och alkohol! Slide 6: Impulse flow Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon. ____________________ Maria Ellgren