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Bad Trips Hasith V.

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Bad Trips Hasith V.

  1. 1. Bad Trips Team H·A·T·Z Presents
  2. 2. Blue Velvet - 1986
  3. 3. Overview <ul><li>The presentation will cover four major psychedelic drugs. </li></ul><ul><ul><ul><li>PCP </li></ul></ul></ul><ul><ul><ul><li>MDMA </li></ul></ul></ul><ul><ul><ul><li>Ketamines </li></ul></ul></ul><ul><ul><ul><li>Nitrous oxide </li></ul></ul></ul><ul><li>Two of the four have a common mode of action within the human brain. </li></ul><ul><li>Short overview of NMDA receptors, exploration of the NMDA-antagonist drugs, and finally, a look at MDMA. </li></ul>
  4. 4. NMDA Receptors <ul><li>Ionotropic receptors that allow for the transfer of electrical signals between neurons in the brain and in the spinal column. </li></ul><ul><li>Receptors that bind glutamate molecules, with a co-agonist, usually in the form of glycine </li></ul><ul><li>Voltage sensitive, so both presynaptic and post synaptic neurons must be active. </li></ul><ul><li>Plays critical role in synaptic plasticity. </li></ul>
  5. 5. NMDA Receptors <ul><li>NMDA antagonist psychedelic drugs produce an effect known as dissociative anesthesia. </li></ul><ul><ul><li>- disrupts associative pathways. </li></ul></ul><ul><ul><li>- triggers false sensory inputs. </li></ul></ul><ul><li>Block the ion channel so no ions can flow in/out, deactivating the receptor temporarily. </li></ul>
  6. 6. NMDA Receptors <ul><li>Because of these psycho mimetic effects, NMDA receptor antagonists, especially, are used as recreational drugs. </li></ul><ul><li>At sub anesthetic doses, these drugs have mild stimulant effects, and at higher doses, begin inducing dissociation and hallucinations. </li></ul>
  7. 7. PCP
  8. 8. PCP <ul><li>Phencyclidine, short form of phenylcyclohexylpiperidine. </li></ul><ul><li>Street names: PCP, Angel Dust, Supergrass, Boat, Tic Tac, Zoom, Shermans </li></ul>
  9. 9. PCP <ul><li>Synthesized in 1926, patented in 1952 by Parke-Davis as Sernyl. </li></ul><ul><li>Used during WWII as an anesthetic </li></ul><ul><li>In 1952, PCP was switched to solely veterinary purposes under the brand Semlyan (again marketed by Parke-Davis) but discontinued after more trials. </li></ul>
  10. 10. PCP <ul><li>Current Status: </li></ul><ul><li>Classified as a Schedule II substance in the United States </li></ul><ul><ul><li>has a high potential for abuse and has a currently accepted medical use in treatment with severe restrictions </li></ul></ul>
  11. 11. PCP <ul><li>Current Status: </li></ul><ul><li>Same class of drugs as Ketamine, and DXM </li></ul><ul><li>Often used recreationally and spiritually. </li></ul><ul><li>Very dangerous </li></ul><ul><li>A powerful disassociate hallucinogenic drug. </li></ul><ul><li>Primary effects last about 5 hour </li></ul><ul><li>After effects remain for up to a day. </li></ul>
  12. 12. PCP <ul><li>Current Status: </li></ul><ul><li>Liquid form is used to dip joints or cigarettes, but can also be taken via more conventional means. </li></ul><ul><li>When smoked, the chemical structure breaks down into phenyl cyclohexene and piperidine. </li></ul>PCP Phenylcyclohexene piperidine
  13. 13. PCP <ul><li>Current Status: </li></ul><ul><li>PCP is barely understood, however, and it is thought that PCP works as a dopamine agonist by being a NMDA antagonist </li></ul><ul><ul><ul><li>Uncompetitive channel blocker that shuts down ion channels by binding to a site within it. </li></ul></ul></ul><ul><li>Complex interactions have been observed leading to nicotinic and muscarinic receptor activation as well . </li></ul>
  14. 14. PCP <ul><li>Current Status: </li></ul><ul><li>“ &quot;Positive” ” effects - energy, euphoria, sense of calm, visuals, shift in reality </li></ul><ul><li>“ ” Negative” ” effects - salivation, body temperaure increase, time perception changes, uncontrolled behavior, hallucinations can turn disturbing, PCP can be very a confusing, anxious, or terrifying experience. </li></ul>
  16. 17. Ketamine
  17. 18. BBC Horizons – Top Ten Recreational Drugs
  18. 19. Ketamine <ul><li>2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone </li></ul><ul><li>Ketamine exists in two forms (enantiomers) </li></ul><ul><ul><ul><li>(S)-Ketamine is the more potent isomer, and is sometimes marketed as a separate drug (Ketanest S) </li></ul></ul></ul><ul><li>Most pharmaceutical preparations of Ketamine are racemic. </li></ul><ul><li>Street names: jet, super acid, Special &quot;K&quot;, green, K, cat Valium, Lady K. </li></ul>
  19. 20. Ketamine <ul><li>Invented and first synthesized by Calvin Stevens at Wayne State University in 1961 (called CL369) </li></ul><ul><li>Bought by Parke-Davis (now Pfizer) and developed in 1962 as an alternative anesthetic to PCP </li></ul><ul><ul><ul><li>It induced fewer hallucinations, had lower neurotoxicity, and caused fewer seizures </li></ul></ul></ul><ul><li>Chosen over PCP due to its nonbarbiturate and bronchodilatory properties. </li></ul>
  20. 21. Ketamine <ul><li>First used in the Vietnam War in 1964, called a “buddy drug” to help soldiers deal with combat-related stress and as a battlefield anesthetic </li></ul><ul><li>In 1970, after extensive testing, the FDA approved it for use in humans as an anesthetic. </li></ul><ul><li>Helped people deal with opioid withdrawal by suppressing certain feedback loops. </li></ul><ul><li>Due to widespread illicit use, the FDA and DEA categorized it as a Schedule III controlled substance in August, 1999. </li></ul>
  21. 22. Ketamine <ul><li>Non-addictive </li></ul><ul><li>Dosage is higher, more controllable </li></ul><ul><li>Does not have permanent effects on neural physiology (unlike PCP, MDMA) </li></ul><ul><li>Is not hallucinogenic (contrary to popular belief) </li></ul><ul><li>Cheaper, per gram, than most hard drugs (PCP, cocaine, LSD, MDMA) </li></ul><ul><li>Aids with withdrawal symptoms. </li></ul>
  22. 23. Ketamine <ul><li>People began to abuse Ketamine when they realized that apart from being just another anesthetic, it served as a dissociative </li></ul><ul><li>Ketamine became a mainstream street drug in the 1970’s-80’s, approximately when the rave scene/genre of music came into popularity </li></ul>
  23. 24. Ketamine <ul><li>Usage: </li></ul><ul><li>Ketamine use continues to this day in the UK and other parts of western Europe </li></ul><ul><li>The act of using Ketamine is refered to as to “being in a “ K-hole ” ” </li></ul>
  24. 25. Ketamine <ul><li>Usage: </li></ul><ul><li>After effects, many of which are not uncommon include nausea, vomitting, trouble with breathing, and sometimes paranoia </li></ul><ul><li>As of now, 23 people in the world have died from Ketamine use, most of which are due to accidental choking and asphyxiation. </li></ul>Crystalline Ketamine
  25. 26. Ketamine <ul><li>Usage: </li></ul><ul><li>Up to 1999, people have been using Ketamine as a “safe” alternative to ecstasy (MDMA), and this gave rise to “dud pills” </li></ul><ul><li>These dud pills often were simply a mixture of Ketamine, caffeine, cocaine, and sometimes baby powder </li></ul><ul><li>With the rise in popularity of Ketamine, governments around the world began cracking down on its use. </li></ul><ul><ul><li>-Hong Kong 2000: Class III </li></ul></ul><ul><ul><li>-UK 2005: Class C substance </li></ul></ul>
  26. 27. Ketamine <ul><li>Current Status </li></ul><ul><li>Ketamine is a non-competitive NMDA receptor antagonist </li></ul><ul><ul><ul><li>Impairs frontal lobe activity. </li></ul></ul></ul><ul><ul><ul><li>Disrupts dopaminergic neurotransmission </li></ul></ul></ul><ul><ul><ul><li>Impedes higher level cognitive functions </li></ul></ul></ul><ul><li>May also increase glutamate release in the prefrontal cortex, increasing glutamatergic at AMPA receptors </li></ul>
  27. 28. Nitrous Oxide
  28. 29. Nitrous Oxide <ul><li>N2O originally synthesized for anesthetic purposes. </li></ul><ul><li>“ Street name: laughing gas. </li></ul>
  29. 30. Nitrous Oxide <ul><li>First synthesized artificially in 1772 by English scientist Joeseph Priestly. </li></ul><ul><ul><li>-heating ammonium nitrate in presence of iron fillings. </li></ul></ul><ul><ul><li>-documented in his paper Experiments and Observations on Different Kinds of Air </li></ul></ul><ul><li>Humphry Davis experimented with the gas in the late 1790s, documenting the effects on the subject. </li></ul><ul><li>- the sense of euphoria led to the naming ' laughing gas ' </li></ul><ul><ul><ul><li>Used mostly for recreational purposes, to achieve what is known today as a high up until the 1840s. </li></ul></ul></ul>
  30. 31. Nitrous Oxide <ul><li>Horace Wells, a British dentist, documented the anesthetic properties of nitrous oxide in 1840. </li></ul><ul><li>Popularity of nitrous oxide as an anesthetic grew rapidly after Samuel Colton introduced the use in dentist practices across the United States. </li></ul>
  31. 32. Nitrous Oxide <ul><li>Current Status </li></ul><ul><li>Not banned or regulated by the DEA </li></ul><ul><li>- legal anesthetic </li></ul><ul><li>Regulation by FDA </li></ul><ul><li>- separation from automotive-grade nitrous oxide </li></ul><ul><li>- recreational use is from the nitrous oxide from aerosol propellant in whipped cream cans. </li></ul><ul><li>- Theft from dental surgeries has also seen a rise. </li></ul>
  32. 33. Effects of Nitrous Oxide
  33. 34. Nitrous Oxide <ul><li>Current Status </li></ul><ul><li>Is a NMDA receptor antagonist </li></ul><ul><li>-binds inside the ion channel, blocking the flow of ions. </li></ul><ul><li>- is independent of N 2 O concentration [Mennerick et. al.]. </li></ul><ul><li>Seems to be an activator of GABA A receptors in the hippocampus, producing postsynaptic current, with research ongoing. </li></ul>
  34. 35. Nitrous Oxide <ul><li>Current Status </li></ul><ul><li>Induces a sense of euphoria </li></ul><ul><li>- dissociative anesthesia effect isn't as strong as that of other NMDA antagonists. </li></ul><ul><li>Majority of deaths from N 2 O inhaling insufficient oxygen, leading to hypoxia. </li></ul><ul><li>Nitrous oxide inactivates Vitamin B-12 via oxidation. Victims of initial Vitamin B-12 deficiencies may experience pernicious anemia. </li></ul>
  35. 36. MDMA / Ecstasy
  36. 37. MDMA <ul><li>Short for 3,4-Methylenedioxymethamphetamine. </li></ul><ul><li>“ Street names: X, E, Molly, rolls, Ecstasy </li></ul>
  37. 38. MDMA <ul><li>First synthesized in 1912 by chemist Anton Kollisch for Merck Corporation </li></ul><ul><li>Intended as a preventative agent for internal bleeding </li></ul><ul><li>Revisited occasionally by Merck, largely forgotten until late 1970s </li></ul>
  38. 39. MDMA <ul><li>1927, Max Oberlin of Merck discovered it operated in a manner similar to ephedrine. </li></ul><ul><li>1953/1954, US Army commissioned studies on the chemical, focusing on toxicity and behavioral effects. </li></ul><ul><li>First scientific paper on MDMA came in 1958, Yutaka Katsuya in Journal of the Pharmaceutical Society of Japan </li></ul>
  39. 40. MDMA <ul><li>Rises to prominence again in 1970s after its analogue, MDA, was scheduled. </li></ul><ul><li>- MDA significantly more neurotoxic than MDMA </li></ul><ul><li>Alexander Shulgin synthesized MDMA at UC Berkeley in 1976; published first study of its psychoactive effects on humans in 1978 </li></ul>MDA MDMA
  40. 41. MDMA <ul><li>Adoption: </li></ul><ul><ul><li>Was adopted by gay club scene in Dallas as “ ' Adam ' ”, spread to nightclubs all over US </li></ul></ul><ul><ul><li>Became commonplace in both European club scene and US drug culture </li></ul></ul><ul><ul><li>Scheduled by DEA on May 31, 1985 </li></ul></ul>
  41. 42. MDMA <ul><li>Legal Therapeutic Uses: </li></ul><ul><ul><li>Used in psychotherapy prior to its scheduling . </li></ul></ul><ul><ul><li>Relaxant to cause patients to “open up”. </li></ul></ul><ul><ul><li>Patients claimed to have shown improvement after usage of MDMA </li></ul></ul><ul><ul><li>Is still used medically, notably in treatment of PTSD. </li></ul></ul>
  42. 43. MDMA <ul><li>Current Research: </li></ul><ul><ul><li>MAPS (Multidisciplinary Association for Psychedelic Studies) is spearheading a rescheduling effort. </li></ul></ul><ul><ul><li>Only organization supporting clinical trials of MDMA. </li></ul></ul><ul><ul><li>Cites use in psychotherapy, especially for PTSD </li></ul></ul>
  43. 44. MDMA <ul><li>Current Status: </li></ul><ul><ul><li>MDMA is DEA Schedule I </li></ul></ul><ul><ul><ul><li>“ Drugs with little to no therapeutic use and high potential for abuse” </li></ul></ul></ul><ul><ul><ul><li>Medical community contends Schedule III </li></ul></ul></ul><ul><ul><ul><li>less potential for abuse, existing therapeutic use </li></ul></ul></ul>
  44. 45. MDMA <ul><li>Usage: </li></ul><ul><ul><li>Sold for roughly $2-$20/tab on street, dependent on purity </li></ul></ul><ul><ul><li>Availability typically coincides with activity of rave scene </li></ul></ul><ul><ul><li>Designer analogs are often sold, as well as facsimiles </li></ul></ul><ul><ul><li>Raises questions about reliability </li></ul></ul>
  45. 46. MDMA <ul><li>Usage: </li></ul><ul><ul><li>To use is to “roll”, the high is “rolling” </li></ul></ul><ul><ul><li>Used commonly in raves, large concerts </li></ul></ul><ul><ul><li>Users appear to be in ecstasy, hence the name </li></ul></ul><ul><ul><li>Increased sensation of tactile stimuli </li></ul></ul><ul><ul><li>Sense of well-being </li></ul></ul>
  46. 47. Alexander Shulgin on the synthesis of MDMA
  47. 48. MDMA <ul><li>Neuropharmacology: </li></ul><ul><ul><li>MDMA interacts with 5-HT receptors </li></ul></ul><ul><ul><li>- unique mode of action. </li></ul></ul><ul><ul><li>Forces the serotonin transporter to release the serotonin in the process of reuptake. </li></ul></ul><ul><ul><li>- independent of the presynaptic neuron actually firing. </li></ul></ul><ul><ul><li>Acts as a serotonin releasing agent and non-selective SRI. </li></ul></ul><ul><ul><li>- same effect on norepinephrine and dopamine. </li></ul></ul>
  48. 49. MDMA <ul><li>Neuropharmacology: </li></ul><ul><ul><li>The reuptake inhibition and release agent properties stem from MDMA triggering release of oxytocin. </li></ul></ul>
  49. 50. MDMA <ul><li>Effects: </li></ul><ul><ul><li>Research shows decreased cognitive and memory function In long term users. </li></ul></ul><ul><ul><li>Neurotoxic effects </li></ul></ul><ul><ul><ul><li>reduces 5-HT terminal counts in laboratory experiments. </li></ul></ul></ul><ul><ul><ul><li>Reduces serotonin transporter count with long term use. </li></ul></ul></ul>
  50. 51. Bibliography <ul><li>Shimizu et. al. NMDA Receptor-Dependent Synaptic Reinforcement as a Crucial Process for Memory Consolidation. Vol. 290 Science. 10 Nov. 2000. </li></ul><ul><li>Wang et. al. Blockade of N-Methyl-D-Aspartate (NMDA) Receptors by Ketamine Produces Loss of Postnatal Day 3 (PND-3) Monkey Frontalcortical Neurons in Culture. Oxford University Press 2006 </li></ul><ul><li>Gorelick, David. A. Phencyclidine (PCP). Neuropharmacology : The Fifth Generation of Progress. American College of Neuropsychopharmacology http://www.acnp.org/G4/GN401000171/CH167.html </li></ul><ul><li>Waterhouse, Rikki N.Imaging the PCP site of the NMDA ion channel.Nuclear Medicine and Biology, Volume 30, Issue 8, November 2003 </li></ul><ul><li>Nitrous Oxide. Erowid.ORG. Retrieved Oct 17th. http://www.erowid.org/chemicals/nitrous/nitrous.shtml </li></ul><ul><li>BBC Horizons: Top Ten Recreational Drugs. http://www.youtube.com/watch?v=o9tQ-h5_8P8&feature=related </li></ul><ul><li>http://en.wikipedia.org/wiki/File:Oxytocin.svg </li></ul><ul><li>FOX News. The Dangers of PCP http://www.youtube.com/watch?v=jkzdam289V8] </li></ul><ul><li>Young, Emma. Ecstasy really does unleash the love hormone. New Scientist. April 2007 </li></ul><ul><li>Laws, Keith R. Joy Kokkalis. Ecstasy (MDMA) and memory function: a meta-analytic update. Human Psychopharmacology: Clinical and Experimental. Vol. 22. pp. 381-388. 2007 </li></ul><ul><li>Malberg, Jessica E. Lewis S. Seiden. Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat. Journal of Neuroscience. Vol. 18 </li></ul><ul><li>DEA.gov. Inhalants. http://www.usdoj.gov/dea/concern/inhalants.html </li></ul><ul><li>DEA.gov. PCP. http://www.usdoj.gov/dea/concern/pcp.html </li></ul><ul><li>http://en.wikipedia.org/wiki/File:Nitrous-oxide-dimensions-3D-balls.png </li></ul><ul><li>http://en.wikipedia.org/wiki/File:Ketamine_Structural_Formulae.png </li></ul><ul><li>http://en.wikipedia.org/wiki/File:R-ketamine-3D-balls.png </li></ul><ul><li>Ketamine. http://www.nlm.nih.gov/cgi/mesh/2009/MB_cgi?term=6740-88-1&rn=1 </li></ul><ul><li>Science Friday. Ketamine and Depression. http://media.libsyn.com/media/sciencefriday/scifri-2007072724.mp3 </li></ul>
  51. 52. Bibliography <ul><li>DEA. MDMA. http://www.usdoj.gov/dea/concern/mdma.html </li></ul><ul><li>http://www.usdoj.gov/dea/images_ecstasy.html </li></ul><ul><li>Effects of Laughing Gas. http://www.youtube.com/watch?v=iudTMHRePFA&feature=related </li></ul><ul><li>MDMA. Erowid.ORG. Retrieved Oct 17th. http://www.erowid.org/chemicals/mdma/mdma.shtml </li></ul><ul><li>Shroder, Tom. The Peace Drug. Washington Post. Nov. 25 2007. http://www.washingtonpost.com/wp-dyn/content/article/2007/11/20/AR2007112001777_pf.html </li></ul><ul><li>BKChem. http://bkchem.zirael.org/ </li></ul><ul><li>Alexander Shulgin on the discovery of MDMA. http://www.youtube.com/watch?v=u9FuI4MNtxI&feature=related </li></ul><ul><li>http://commons.wikimedia.org/wiki/File:NMDA_receptor.jpg </li></ul><ul><li>http://www.websters-online-dictionary.org/RE/RECEPTOR.html </li></ul>