Bad Trips

Team H·A·T·Z Presents

Blue Velvet - 1986

Overview

The presentation will cover four major psychedelic drugs.

PCP MDMA Ketamines Nitrous oxide

Two of the four have a common mode of action within the human brain.

Short overview of NMDA receptors, exploration of the NMDA-antagonist drugs, and finally, a look at MDMA.

NMDA Receptors

Ionotropic receptors that allow for the transfer of electrical signals between neurons in the brain and in the spinal column.

Receptors that bind glutamate molecules, with a co-agonist, usually in the form of glycine

Voltage sensitive, so both presynaptic and post synaptic neurons must be active.

Plays critical role in synaptic plasticity.

NMDA Receptors

NMDA antagonist psychedelic drugs produce an effect known as dissociative anesthesia.

- disrupts associative pathways.

- triggers false sensory inputs. Block the ion channel so no ions can flow in/out,

deactivating the receptor temporarily.

NMDA Receptors

Because of these psycho mimetic effects, NMDA receptor antagonists, especially, are used as recreational drugs.

At sub anesthetic doses, these drugs have mild stimulant effects, and at higher doses, begin inducing dissociation and hallucinations.

PCP

PCP

Phencyclidine, short form of phenylcyclohexylpiperidine.

Street names: PCP, Angel Dust, Supergrass, Boat, Tic Tac, Zoom, Shermans

PCP

Synthesized in 1926, patented in 1952 by Parke-Davis as Sernyl.

Used during WWII as an anesthetic

In 1952, PCP was switched to solely veterinary purposes under the brand Semlyan (again marketed by Parke-Davis) but discontinued after more trials.

PCP

Current Status:

Classified as a Schedule II substance in the United States

has a high potential for abuse and has a currently accepted medical use in treatment with severe restrictions

PCP

Current Status:

Same class of drugs as Ketamine, and DXM Often used recreationally and spiritually. Very dangerous

A powerful disassociate hallucinogenic drug. Primary effects last about 5 hour After effects remain for up to a day.

PCP

Current Status:

Liquid form is used to dip joints or cigarettes, but can also be taken via more conventional means.

When smoked, the chemical structure breaks down into phenyl cyclohexene and piperidine.

PCP Phenylcyclohexene piperidine

PCP

Current Status:

PCP is barely understood, however, and it is thought that PCP works as a dopamine agonist by being a NMDA antagonist

Uncompetitive channel blocker that shuts down ion channels by binding to a site within it.

Complex interactions have been observed leading to nicotinic and muscarinic receptor activation as well.

PCP

Current Status:

“"Positive”” effects - energy, euphoria, sense of calm, visuals, shift in reality

“”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.

TITLE: THE CASE OF 'BIG LURCH'

Ketamine

BBC Horizons – Top Ten Recreational Drugs

Ketamine

2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone Ketamine exists in two forms (enantiomers)

(S)-Ketamine is the more potent isomer, and is sometimes marketed as a separate drug (Ketanest S)

Most pharmaceutical preparations of Ketamine are racemic.

Street names: jet, super acid, Special "K", green, K, cat Valium, Lady K.

Ketamine

Invented and first synthesized by Calvin Stevens at Wayne State University in 1961 (called CL369)

Bought by Parke-Davis (now Pfizer) and developed in 1962 as an alternative anesthetic to PCP

It induced fewer hallucinations, had lower neurotoxicity, and caused fewer seizures

Chosen over PCP due to its nonbarbiturate and bronchodilatory properties.

Ketamine

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

In 1970, after extensive testing, the FDA approved it for use in humans as an anesthetic.

Helped people deal with opioid withdrawal by suppressing certain feedback loops.

Due to widespread illicit use, the FDA and DEA categorized it as a Schedule III controlled substance in August, 1999.

Ketamine Non-addictive Dosage is higher, more

controllable Does not have permanent

effects on neural physiology (unlike PCP, MDMA)

Is not hallucinogenic (contrary to popular belief)

Cheaper, per gram, than most hard drugs (PCP, cocaine, LSD, MDMA)

Aids with withdrawal symptoms.

Ketamine

People began to abuse Ketamine when they realized that apart from being just another anesthetic, it served as a dissociative

Ketamine became a mainstream street drug in the 1970’s-80’s, approximately when the rave scene/genre of music came into popularity

Ketamine

Usage: Ketamine use continues to this day in the UK and other parts

of western Europe

The act of using Ketamine is refered to as to “being in a “K-hole””

Ketamine

Usage: After effects, many of which are not uncommon include

nausea, vomitting, trouble with breathing, and sometimes paranoia

As of now, 23 people in the world have died from Ketamine use, most of which are due to accidental choking and asphyxiation.

Crystalline Ketamine

Ketamine

Usage: Up to 1999, people have been using Ketamine as a “safe”

alternative to ecstasy (MDMA), and this gave rise to “dud pills” These dud pills often were simply a mixture of Ketamine, caffeine,

cocaine, and sometimes baby powder With the rise in popularity of Ketamine, governments around the

world began cracking down on its use.-Hong Kong 2000: Class III

-UK 2005: Class C substance

Ketamine

Current Status Ketamine is a non-competitive NMDA receptor antagonist

Impairs frontal lobe activity. Disrupts dopaminergic neurotransmission Impedes higher level cognitive functions

May also increase glutamate release in the prefrontal cortex, increasing glutamatergic at AMPA receptors

Nitrous Oxide

Nitrous Oxide

N2O originally synthesized for anesthetic purposes.

“Street name: laughing gas.

Nitrous Oxide

First synthesized artificially in 1772 by English scientist Joeseph Priestly.-heating ammonium nitrate in presence of iron fillings.

-documented in his paper Experiments and Observations on Different Kinds of Air

Humphry Davis experimented with the gas in the late 1790s, documenting the effects on the subject.

- the sense of euphoria led to the naming 'laughing gas'

Used mostly for recreational purposes, to achieve what is known today as a high up until the 1840s.

Nitrous Oxide

Horace Wells, a British dentist, documented the anesthetic properties of nitrous oxide in 1840.

Popularity of nitrous oxide as an anesthetic grew rapidly after Samuel Colton introduced the use in dentist practices across the United States.

Nitrous Oxide

Current StatusNot banned or regulated by

the DEA- legal anesthetic Regulation by FDA- separation from

automotive-grade nitrous oxide

- recreational use is from the nitrous oxide from aerosol propellant in whipped cream cans.

- Theft from dental surgeries has also seen a rise.

Effects of Nitrous Oxide

Nitrous Oxide

Current Status Is a NMDA receptor antagonist-binds inside the ion channel, blocking the flow of ions.

- is independent of N2O concentration [Mennerick et. al.].

Seems to be an activator of GABAA receptors in the hippocampus, producing postsynaptic current, with research ongoing.

Nitrous Oxide

Current Status Induces a sense of euphoria- dissociative anesthesia effect isn't as strong as that of

other NMDA antagonists. Majority of deaths from N2O inhaling insufficient

oxygen, leading to hypoxia. Nitrous oxide inactivates Vitamin B-12 via oxidation.

Victims of initial Vitamin B-12 deficiencies may experience pernicious anemia.

MDMA / Ecstasy

MDMA

Short for 3,4-Methylenedioxymethamphetamine.

“Street names: X, E, Molly, rolls, Ecstasy

MDMA

First synthesized in 1912 by chemist Anton Kollisch for Merck Corporation

Intended as a preventative agent for internal bleeding

Revisited occasionally by Merck, largely forgotten until late 1970s

MDMA

1927, Max Oberlin of Merck discovered it operated in a manner similar to ephedrine.

1953/1954, US Army commissioned studies on the chemical, focusing on toxicity and behavioral effects.

First scientific paper on MDMA came in 1958, Yutaka Katsuya in Journal of the Pharmaceutical Society of Japan

MDMA

Rises to prominence again in 1970s after its analogue, MDA, was scheduled.

- MDA significantly more neurotoxic than MDMA

Alexander Shulgin synthesized MDMA at UC Berkeley in 1976; published first study of its psychoactive effects on humans in 1978

MDA MDMA

MDMA

Adoption:

Was adopted by gay club scene in Dallas as “'Adam'”, spread to nightclubs all over US

Became commonplace in both European club scene and US drug culture

Scheduled by DEA on May 31, 1985

MDMA

Legal Therapeutic Uses:

Used in psychotherapy prior to its scheduling. Relaxant to cause patients to “open up”. Patients claimed to have shown improvement after

usage of MDMA Is still used medically, notably in treatment of PTSD.

MDMA

Current Research:

MAPS (Multidisciplinary Association for Psychedelic Studies) is spearheading a rescheduling effort.

Only organization supporting clinical trials of MDMA. Cites use in psychotherapy, especially for PTSD

MDMA

Current Status:

MDMA is DEA Schedule I “Drugs with little to no therapeutic use and high

potential for abuse”Medical community contends Schedule IIIless potential for abuse, existing therapeutic use

MDMA

Usage:

Sold for roughly $2-$20/tab on street, dependent on purity

Availability typically coincides with activity of rave scene

Designer analogs are often sold, as well as facsimiles Raises questions about reliability

MDMA

Usage:

To use is to “roll”, the high is “rolling”

Used commonly in raves, large concerts

Users appear to be in ecstasy, hence the name

Increased sensation of tactile stimuli

Sense of well-being

Alexander Shulgin on the synthesis of MDMA

MDMA

Neuropharmacology:

MDMA interacts with 5-HT receptors- unique mode of action. Forces the serotonin transporter to release the

serotonin in the process of reuptake.- independent of the presynaptic neuron actually firing.

Acts as a serotonin releasing agent and non-selective SRI.

- same effect on norepinephrine and dopamine.

MDMA

Neuropharmacology:

The reuptake inhibition and release agent properties stem from MDMA triggering release of oxytocin.

MDMA

Effects:

Research shows decreased cognitive and memory function In long term users.

Neurotoxic effects reduces 5-HT terminal counts in laboratory

experiments. Reduces serotonin transporter count with long

term use.

Bibliography Shimizu et. al. NMDA Receptor-Dependent Synaptic Reinforcement as a Crucial Process for Memory Consolidation. Vol. 290

Science. 10 Nov. 2000.

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

Gorelick, David. A. Phencyclidine (PCP). Neuropharmacology : The Fifth Generation of Progress. American College of Neuropsychopharmacology http://www.acnp.org/G4/GN401000171/CH167.html

Waterhouse, Rikki N.Imaging the PCP site of the NMDA ion channel.Nuclear Medicine and Biology, Volume 30, Issue 8, November 2003

Nitrous Oxide. Erowid.ORG. Retrieved Oct 17th. http://www.erowid.org/chemicals/nitrous/nitrous.shtml

BBC Horizons: Top Ten Recreational Drugs. http://www.youtube.com/watch?v=o9tQ-h5_8P8&feature=related

http://en.wikipedia.org/wiki/File:Oxytocin.svg

FOX News. The Dangers of PCP http://www.youtube.com/watch?v=jkzdam289V8]

Young, Emma. Ecstasy really does unleash the love hormone. New Scientist. April 2007

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

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

DEA.gov. Inhalants. http://www.usdoj.gov/dea/concern/inhalants.html

DEA.gov. PCP. http://www.usdoj.gov/dea/concern/pcp.html

http://en.wikipedia.org/wiki/File:Nitrous-oxide-dimensions-3D-balls.png

http://en.wikipedia.org/wiki/File:Ketamine_Structural_Formulae.png

http://en.wikipedia.org/wiki/File:R-ketamine-3D-balls.png

Ketamine. http://www.nlm.nih.gov/cgi/mesh/2009/MB_cgi?term=6740-88-1&rn=1

Science Friday. Ketamine and Depression. http://media.libsyn.com/media/sciencefriday/scifri-2007072724.mp3

Bibliography DEA. MDMA. http://www.usdoj.gov/dea/concern/mdma.html

http://www.usdoj.gov/dea/images_ecstasy.html

Effects of Laughing Gas. http://www.youtube.com/watch?v=iudTMHRePFA&feature=related

MDMA. Erowid.ORG. Retrieved Oct 17th. http://www.erowid.org/chemicals/mdma/mdma.shtml

Shroder, Tom. The Peace Drug. Washington Post. Nov. 25 2007. http://www.washingtonpost.com/wp-dyn/content/article/2007/11/20/AR2007112001777_pf.html

BKChem. http://bkchem.zirael.org/

Alexander Shulgin on the discovery of MDMA. http://www.youtube.com/watch?v=u9FuI4MNtxI&feature=related

http://commons.wikimedia.org/wiki/File:NMDA_receptor.jpg

http://www.websters-online-dictionary.org/RE/RECEPTOR.html