Thursday, January 31, 2013

online sell art

http://hyperallergic.com/64324/online-art-galleries-go-indie/

GAME

Week 2 Report
Order:
1.       C
2.       T
3.       O
To determine the order of the game T and C play Rock, Paper, Scissors.  T wins, placing him in the second spot.  To determine 1st and 3rd players C flips a coin that O calls it in the air.  She loses giving her the third spot, C the first.
Rock, Paper, Scissors is not a communist pastime. Cheaters can only cheat if they know the system.
Eye Contact- 5 Min.
T goes behind a pole and lies down on a mat, C takes the Bogart Street side wall, O takes the far corner. 
C-
1.  O and T are placed face-to-face standing in a spotlight in the center of the room.  They cannot see the light, the light is only for the one who can see, which is C.  The light is to help with anxiety and focus. 
2.  Hands of O and T and bound together.
3.  A triangle is drawn around them on the floor.  Each side of the triangle acknowledges the energies of one of the different players, the energy of C, O and T creating the event.  The enactor brushes against the participants allowing her body to be recognized by the sightless.
4.  C reads to O and T whispering in their ear from ‘Traubenritter’s Maxims’- subjects about religion such as ‘the devil can only tempt us with what is already our own’, ‘Still, that naughtiness is what keeps you from getting old’.  C leaves out the quote that inspired her to read these words to them.  She leaves out ‘The human senses are very peculiar things.  If we sit and listen to the cheerful voices of women chattering, no one even notices that we hear.  If we look over and watch them, enjoy their sprightliness and beauty, perhaps, then people notice we are staring, we are not very civil, it is rude to stare.  But not illegal.  If however we get up from our table and walk over to theirs, and begin to touch them with our hands, then in an instant commotion, managers shouting, the police appear, we are dragged away to the madhouse, guilty of a crime of the senses.  Using the wrong senses to apprehend.  What a civilization we have coaxed ourselves to inhabit.  The physiologists assure us that the eye is just a highly specialized kind of skin.  And our hands must be content with that.’  C has been asked to possibly read on a museum audio guide, reading under anxiety has made her eyes jump I the past, eyes jump in the past, she does this to test herself, there are things that she knows as enactor that the participants don’t, things that help her by being secrets. 
Eye Contact- 5 min.
T-
1.  C is instructed to pet her nose and reach out to the body in front of her and feel a smooth and soft thing.  Turns out to be O’s nose and cheek.  Can C get confused that O’s nose is her own?  It happens slightly when she tries for it.
2.  O and C get led out of Nothing Space, as they are going to the door C tells T that the door will lock and they need the keys from the space.  She is instructed to take off her blindfold.  The two guide O down the stairs, out the door to the subway.  T goes through and comes around to open the door but C mentions that there is a cop, they leave, they go to Brooklyn Natural.  O is given a melon and asked to pay with provided money.  She goes to the street gives the melon to a handsome man smoking a cigarette in a nice jacket with a good haircut.  He takes the melon as though in stride, no big deal, and walks down the street.  T and C take O to the bar, at the door she refuses to enter.  T has decided to push O and she feels that he is a sadist putting her in such vulnerable positions.  The sidewalk is icy.  The strangers are formless and watching, walking up and down the stairs is done with trust.  The cars are watched only by friends, her life is in the arms of others.  T pushes, T plays, T gives.  O is brave, O is trusting, O is concerned.  An exchange of meaning.  We go back up to the room.  O learns that C took off her blindfold. 

5 min.
C on the bench, T under the bench, O in the corner.

O-

1.  O takes C for a five minute dance.  She puts a long strand of pearls around C’s neck.  They sway and C is quizzed on men she is attracted to, Jimmy Hendricks vs. Van Morrison etc. 
2.  O takes T for a five minute dance.  C hears only the music and laughter. 


Thursday, January 24, 2013

Stereo Total - Cannibale

Stereo Total - Touche Moi

stereo total - l amour a trois

GAME

There is a trinity in the room- not like any you have ever known. 
Two next to one is a grand three. 
This is how numbers come to mean.
I have something to say- we always have something worth telling. 
Shhh, words are betrayers.  Actions make a better language, and if you try to speak, I will leave you.
We are always where we are.
I am getting dressed without knowing where I am going.  Should I dress to be destroyed?  Sexed?  Stabbed, muddied, fingered, smelled, do I dress for work, play pretty, play rough?  Am I about to be taken to the ground, tied up, buried?  Am I about to be embraced, whispered, tangled, made gentle?  Will I cry, laugh, punch, feel euphoric?
You can do anything to me, at any time, we create doorways- action is always up to us, instructions are just an excuse, we all need them to act right or act at all.  But I don’t know what will- so I ready myself as priestess and sacrifice.  I clean and cover every inch of me in scent.  I soften, and make my body ready to dislodge other bodies.
Heading to Nothing Space to go outside of life as I live it- ‘This is like Santa’ I think, as expectation resurrects from adulthoods controlled passivity, mystery as phoenix, anticipation, my adrenaline is pumping.  I am running to the door to escape the cold without a jacket, I am running because I can only run and have trouble falling asleep, to do is to be an action.   
The earths skyview is drawn wrong at the Central Station but I can’t tell why because the right and the left of the story is told among anxiety, where the earth spins and it all comes into sight, interior constellations drawn on the mind not matching the pattern of the outside world, night makes vision so, this night, is the time that erases looking into seeing. 
There are three bold and shy players in one room.  No one is in charge, then one is in charge.  
INSTRUCTION
Say beyond saying.
Show rather than tell.
Convey beyond the intentional showing.
What you are projecting vs. what is read. 
We are brave when we don’t feel bravery and have to make it.
The thing you really want to say is only born in electric silence. 
The location spoken in this room is one of the best experiences of your life.  Can you bring yourself to speak yourself, and will someone be there to listen right?
The best location is in you, and born between, in eternity, where time appears irrelevant.

Some play best when they enact prescribed inscriptions, when spontaneity liberates responsibility, when radical force is a gateway to wisdom.  Broken, let loose, by understanding each other.  Liberty, like a bell, is resonance, sharing.  Break free of traps, let go of something to survive better.  Freedom is what every great nation and pop song is written on, and so too are the brilliant hours. 
Honey on the lips can be felt better without the eyes.  What does it mean to have a blind lover, and why are they not regular in prostitution rings and porn?  To be felt, fuck, fuck, to be felt, or better yet known as a feeling. 
Inside a room and outside of a room are two very different spaces. 
The dirty truth can only be learned, no one can teach it, it comes from discovery, feeling an answer.  Slowly conclusions take away the writing of moments and the desperation of living, but real finality is a sensation, that’s the rub, the balm, the action without eyes. 
To fall backwards through void expectation is to awaken on the other side where things are finally understood. 
This is just one story- it is always just one story.  Authority is an illusion, power is action, action is responsibility toward experience- come on, make my day.

for orpheus study

Ryoanji, For Voice, Flute, Oboe, Trombone, Contrabass, Percussion, Chamber Orchestra & 2nd Voice Ad Lib: Ryoanji (1983-85) For Hichiriki, 2 Ryuteki And Percussion

on Internationale Ferienkurse für Neue Musik Darmstadt 1998


The Deserted Churchyards, For Instrumental Ensemble: The Deserted Churchyards

on The New Danes

Chemins II on Sequenza VI, for viola & 9 instruments: Chemins II On Sequenza VI

Iannis Xenakis: Polytope de Cluny (1972)

sublime

http://www.sublimefrequencies.com/

http://lobefood.com/category/downloads/sublime-frequencies/samplers/


http://sublimefrequenciescommunique.blogspot.com/

SFlogo

Iannis XENAKIS | Six Chansons pour Piano

Two Door Cinema Club - What You Know



cheezeeefunn

alam seni-agogo 67

Oh My English! OST Music Video - Liyana Jasmay & Altimet

YouTube A Ramlie Oh Fatimah

A Ramlie - Kasih Tak Sudah

Pop Yeh yeh

Devendra Banhart - Feel just like a child

Wednesday, January 16, 2013

time

Warbling on the borderline of extinction, between salvation and eternal loss, boundaries mark a desire to destroy.  Finish the deed, at hand, with our hands, or by the hands of a clock, as though that which is is too precious to save, so great, miraculous in appearance, that the thought of anything surviving seems unnatural.  Just as easily as it arrived the swan sings a final song, the bird streaks its colorful flight across the sky and vanishes into an enchanted wood, the light, dancing on the floor, disappears by its glimmering.  We expect that the earth will not remain.  We suspect that preservation is a futile vanity, all we know of beauty is its inevitable death, like a child standing on the sidewalk in bare feet waiting for badness to end a jubilant mood, so too do we understand the cycles of life, that the recycling of materials into other materials is a part of energy and change is the only constant.  So does the dawn become the dusk, so does the evening fade to reveal the stars, that which was already there but unable to be seen.  We register only effects and barely the causes, we invent gods to think for us, we take ourselves out of the responsibility of living, Sisyphus shoving the day into the day into the day, the seemingly never ending that we cry out, wail out, that we learn to speak for, unfortunately, one day, like all things, the story, the day, the seemingly immortal, will finalize too, earth time is the master of us all.  And it is the ending, the narrator that stops speaking, the gods that die with men, when there are only fossils of machines to litter a vacant earth, that will make a void without notice.  I dare every human to think of a balanced world once a day.  Humans should not be anti-nature in thought, post-nature, supra-nature, we are nature.  The same way we say ‘my body’, breaking the mind and the body in two with language, the environment is not outside of nature.  We should be speaking of our survival, the longevity of life itself.  The turtle that lived to be twenty-five and crawled onto the shore at Tamarindo will one day die, and the sixty-seven eggs she laid may never live, the finality of nature, the evil of post-nature thinking, the destruction that so many fear humans can’t help but do.  Can’t help but do when we create!  Are we Kali, devouring all that is?  Time is the real destroyer, the creator.  Are we the scoundrel saints burning ourselves alive, heating the earth to death as though at a spit to prove that we have a right?  We did it all because we can’t make the ends meet, while gods litter our minds until we find the energy behind the veil, the eternal light, were material is less knowable, or not there at all like the place that star gazers wonder about tucked inside black holes.  I walk down the streets of Brooklyn, and in that journey are a thousand endings, my own death dormant in my body, the cells dividing fifty times and stopping, the end of the day beyond the end of the block in front of me, the inevitable end of all speech.

Fantasia on a Theme by Thomas Tallis - Ralph Vaughan Williams

Friday, January 11, 2013

No Flowers on the Psych Ward

No Flowers on the Psych Ward

By Amelia Rachel Hokule’a Borofsky
Share18 30
Administration looks at everything as a possible weapon of self or mass destruction. But we need windows and nature. 
BLOOM-by-Anna-Schuleit-Blue-Hallway-main.jpg
The connecting hallway between the historic part of MMHC and the research annex was covered in blue African Violets. (John Gray)
Psychiatric hospitals have a certain smell. Old urine hits the nostrils first and then the sting of bleach. As I unlock the metal doors, the smell lets me know where and what I am: a pre-doctoral intern at a forensic psychiatric hospital in Boston. As I walk down the white hall, I see a white woman in a Harvard sweatshirt, a Boston red-sox cap covering her curly ponytail. She screams, "If you are not crazy when you get in here, you are crazy when you get out!"
Perhaps I was naïve to think that healing was the intention, but on the ward, I find only its absence. The hospital functions as a holding cell for people not safe on the streets and not safe in jail. People rotate through. One of the regulars, an African-American man who whistles loudly tells me, "I was born in a zoo, and I'll die in a zoo." I tell myself otherwise, but it's hard not to feel like a zookeeper.
Boredom fills the ward, too. An African American woman wears the same pink sweatpants all year. She is obese both from the side effects of the her meds and from her never leaving bed. She develops hypertension and then diabetes. I wonder if boredom can classify as an infectious disease. The staff tries to motivate everyone: Exercise classes! Substance abuse chats! Morning meetings!
Some patients feign interest in order to improve their chances of being discharged. It is the staff, and abiding interns, who make all the decisions. Psychiatric hospitals, by definition, disempower patients. Having a crime plus mental illness on your record means a loss of certain rights. But I do not want a doctorate in disempowerment. As the year wears on, I am having a hard time getting out of bed.
* * *
BLOOM-by-Anna-Schuleit-Tiny-Office-with-Tulips-inset.jpgOne of the tiny offices on the third floor, with orange tulips at mid-day. (Anna Schuleit)
Enter the flower shop. After a particularly hard day, I see a glass window reading "New Leaf Flores." I am greeted with vibrant oranges and twigs. I walk in and the owners offer me a glass of red wine. Their shop quickly becomes my mental health salvation. Every Friday, after walking the white walls of the ward, I walk to their flower shop and spend the evening taking thorns off red roses.
Psychiatric hospitals have no flowers. Visitors do not bring them. They usually bring toothpaste, deodorant and underwear. I ask my supervisor if I can bring leftover flowers from the shop. "Glass vases," he shakes his head. I find plastic vases and sneak in de-thorned pink roses. A patient asks, "Can I give one to my girl?" The next day, the flowers and plastic vases vanish.
So many items cannot come onto a locked psychiatric ward. Administration looks at everything as a possible weapon of self or mass destruction. No curtains. No jewelry. No art. No glass. And, I learn, no flowers, no plants, no nature.
Searching for a way to up both my own and the patients' spirits, I find a wealth of research on the intuitive link between nature and mental health. A few studies conclude that office workers perform better with windows and foliage. Another shows that ornamental indoor plants in hospital rooms enhance health outcomes for patients recovering from surgery.
Then I find the solution I'm looking for. In this study, as I remember it, two random groups of psychiatric patients received plants. In one group, the nurses watered the plants for the patients. In the other group, the patients watered their own plants. On measures of depression before and after the experiment, the patients who watered their own plants showed the most improvement.
I ask my supervisor if we can conduct a similar study. "Talk to the infectious diseases control nurse," he says. I give her a copy of the study and an argument about oxygen. Her eyebrows arch. "Ants, cockroaches, all sorts of bugs" she says and walks away to give a lecture on hand washing. I bring it up in the team meeting. Everyone smiles and nods. I try to speak with the director, whom I never see on the ward. Her office sits outside the locked doors. She has plants. The study never happens.
* * *
BLOOM-by-Anna-Schuleit-Red-Mums-inset.jpgRed Regina Mums in the hallway that was the last one to close--it used to be one of the busiest homeless shelters in Boston. (Anna Schuleit)
My supervisor brings me photos from an art exhibit entitled Bloom, commissioned to commemorate the closure of the Massachusetts Mental Health Center. Affectionately known as "Mass Mental," the hospital had been open for 91 years functioning as the premier teaching hospital for Harvard Medical School. It trained thousands of psychiatrists and offered services regardless of ability to pay. In 2003, Mass Mental closed its doors, saying it would soon reopen. The hospital commissioned Anna Schuleit to create art in the emptied space.
To mark the historic closing, Schuleit went through the roster of every patient who had ever walked through those doors. She found 28,000 patients had been served. So she installed 28,000 potted flowers. Former patients, employees, staff, students and the general public came to the opening and walked through the flower-drenched halls. An audio of sounds from the psychiatric hospital played over the old PA system. On the website, Schuleit shares entries from the guestbook. One reads, "Anna saw these corridors as places to be filled with growth. For all the patients who never received flowers, these flowers are for you." After the exhibit ended, 28,000 potted flowers went to people behind bars. The potted plants did not come to our psychiatric hospital.
I still wonder if it might be possible for flowers to enter a psychiatric hospital before all the patients have gone.
BLOOM-by-Anna-Schuleit-orange-Tulips.jpg
Treatment rooms on the first floor, with orange tulips. (Anna Schuleit)
BLOOM-by-Anna-Schuleit-White-Mums.jpg
One of the longest axes of the building: white mums and orange tulips on the first floor. (Anna Schuleit)
BLOOM-by-Anna-Schuleit-Basement-with-Sod.jpg
The basement of the building was covered with 5,600square feet of live sod, which was raked and watered throughout the day, and continued to grow. (John Gray)
BLOOM-by-Anna-Schuleit-orange-begonias.jpg
Orange begonias leading to the doctor's offices. (Anna Schuleit)
2BLOOM-by-Anna-Schuleit-White-Tulips.jpg
The Child Psychiatry unit with white tulips. (John Gray)
BLOOM-by-Anna-Schuleit-Pink-Heather.jpg
Pink Heather in one of the patients' waiting rooms. These flowers had traveled the farthest to be part of 'Bloom' -- from California. (Anna Schuleit

Why Does the World Exist?

http://www.amazon.com/Why-Does-World-Exist-Existential/dp/0871404095#_

Corridors of the Mind

Corridors of the Mind

Could neuroscientists be the next great architects?
http://www.psmag.com/culture/corridors-of-the-mind-49051/
The design of the Basilica of San Francesco d'Assisi, in Italy, helped prompt the polio vaccine. (PHOTO: GETTY IMAGES)
ARCHITECTS HAVE BEEN talking for years about “biophilic” design, “evidence based” design, design informed by the work of psychologists. But last May, at the profession’s annual convention, John Zeisel and fellow panelists were trying to explain neuroscience to a packed ballroom.
The late-afternoon session pushed well past the end of the day; questions just kept coming. It was a scene, Zeisel marveled—all this interest in neuroscience—that would not have taken place just a few years earlier.
Zeisel is a sociologist and architect who has researched the design of facilities for Alzheimer’s patients. Architects, he explains, “understand about aesthetics; they know about psychology. The next depth to which they can go is understanding the brain and how it works and why do people feel more comfortable in one space than another?”
This is an admittedly abstract concept. To help explain, architects often tell this story: Early in his career, when he was still struggling to find a cure for polio, Jonas Salk retreated to Umbria, Italy, to the monastery at the Basilica of Assisi. The 13th-century Franciscan monastery rises out of the hillside in geometric white stone, with Romanesque arches framing its quiet courtyards. Salk would insist, for the rest of his life, that something about this place—the design and the environment in which he found himself—helped to clear his obstructed mind, inspiring the solution that led to his famous polio vaccine.
“He really thought there was something to this,” says the architect Alison Whitelaw, “that the quality of the built environment could affect the performance of the brain.”
Today, the near 10-year-old Academy of Neuroscience for Architecture believes that neuroscience could make science’s greatest contribution to the field of architecture since physics informed fundamental structural methods, acoustic designs, and lighting calculations in the late 19th century. In September, the academy held its first national conference at, fittingly, the Salk Institute, in La Jolla, California. When the academy solicited proposals from anyone who might have insight or research to contribute, Whitelaw expected a handful of takers. The conference instead received dozens of proposals from all over the world—“from people,” Whitelaw says, “we didn’t even know were working in this field.”
Now, thanks to a $500,000 gift from the estate of solar-energy pioneer Harold Hay, the academy has dedicated resources to fund research at the intersection of these seemingly disparate fields. And its dream to create joint-degree programs in architecture and neuroscience seems not so far off.
If architects understood both fields, they might be able, in designing hospitals, schools, and homes for people with all manner of disabilities, to create places that would support the development of premature babies, the treatment of children with autism, the fostering of learning abilities of students. Imagine hospitals with such intuitive way-finding that no one gets lost (or stressed as a result); imagine an Alzheimer’s facility that could help its residents remember who they are.

Jonas Salk
Jonas Salk—photographed at his eponymous institute in 1975—worked
with Louis Kahn on the design of the nonprofit scientific research center
UNTIL ABOUT 20 YEARS AGO, scientists believed that our adult brains lost neurons during normal aging at a low but steady rate, and that we weren’t able to replace them, as we do skin cells. This suggested that the brain you had in your early 20s was perhaps the best brain you were going to get. But research in the late 1990s by neurobiologist Fred Gage and other scientists confirmed the process of adult “neurogenesis.” New neurons continue to be born throughout life, particularly in the hippocampus, the part of your brain that processes new information on its way to being stored as long-term memories. This means that your capacity to add new memories and learn new skills can continue to expand. And how fast these cells are added seems directly influenced by the richness of our interactions with our environment. When Gage introduced these findings to architects at the American Institute of Architects’ 2003 convention, he pronounced an idea that is still sinking in: “Changes in the environment change the brain, and therefore they change our behavior.”
Neuroscientists are also gaining an increasingly better understanding of how our brains analyze, interpret, and reconstruct place and space. We know the brain adds information to what it receives from the physical environment: in optical illusions, it supplies lines that the eyes don’t actually see, and it can form three-dimensional images where only two exist on paper (architects are particularly adept at this). The brain also brings memory to our environment. When you enter a particularly beautiful cathedral, your experience includes memories and emotions tied to the past experiences of spiritual places you’ve visited throughout your life. Your brain is drawing connections between place and memory, even if you don’t realize it.
With today’s sophisticated brain-imaging techniques, neuroscientists can examine how the brain processes environments, even with the complex limitations of, say, someone who’s blind, or autistic, or has dementia.
“We are now really beginning to understand better how to measure the responses to the built environment,” says Eduardo Macagno, professor of biological sciences at the University of California, San Diego, “without relying on psychology, social science, observational behavior.”
Those studies, he explains, “don’t have the quantitative and objective experimental approach that we believe neuroscience brings to the interface with architecture.”
Macagno has been testing hospital design in a virtual-reality lab, and this work could bring us closer to that elusive hospital where, for example, no one gets lost. Other findings from the kind of research he is talking about may challenge what architects have practiced for years. For instance, hospital rooms for premature babies were long built to accommodate their medical equipment and caregivers, not to promote the development of the newborns’ brains. Neuroscience research tells us that the constant noise and harsh lighting of such environments can interfere with the early development of a baby’s visual and auditory systems.
Enriched environments might enhance the performance of the human brain, and the growth of new brain cells. Whitelaw is cautious about this profound idea, particularly because architects have learned they shouldn’t overpromise, as some did with the energy-saving benefits of green design. “I’m not saying that we’re going to be able to evolve the human brain further,” she says. Using color, lighting, and layout, though, architects may be able to design places to provide the sensory experiences that neuroscience demonstrates produce the best brain response.
When imagining the future, Zeisel says that we “will not be spending our energy coping with an environment that doesn’t fit our developmental and brain needs.” He adds, “We’ll have a lot more energy as human beings to do what we’re supposed to do, which is to be curious and find things out, learn, develop new ideas, create things.”
Jonas Salk’s Assisi experience makes you think: architects could even design environments expressly to foster research breakthroughs. Salk actually tried to achieve this in working with architect Louis Kahn to design the Salk Institute in La Jolla. The campus, with its ample natural light, views of the Pacific Ocean, and vast central plaza, echoes the monastic tranquility of Assisi. The architecture is inspiring; Salk’s successors must now translate that advantage into science.

Thursday, January 10, 2013

Verizon Powerful Answers - "Attendance :60" Commercial

Verizon Powerful Answers - "The Brave :60" Commercial

True Stories (1986) - Dinner with the Culvers

Food Blog

http://www.thelunchbelle.com/nycentric/2011/3/24/mission-impossible-taking-the-e-w-out-of-n-e-w-y-o-r-k.html

Beauty and Essex

http://www.beautyandessex.com/location-hours/

146 Essex St, New York City, 10002
Nightly, 5pm – 1am

Saturday & Sunday 11:30am – 3pm

(212) 614.0146 (212) 614.0140 info@beautyandessex.com

orchids



Psilocybin

Psilocybin

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Psilocybin
Identifiers
CAS number520-52-5 YesY[Pubchem]
PubChem10624
ChemSpider10178 YesY
EC number208-294-4
KEGGC07576 YesY
MeSHPsilocybine
ChEBICHEBI:8614 YesY
ChEMBLCHEMBL194378 YesY
RTECS numberNM3150000
Beilstein Reference273158
Jmol-3D imagesImage 1
Image 2
Pharmacology
Routes of
administration
Oral, intravenous
Elimination
half-life
oral: 163±64 min
intravenous: 74.1±19.6 min[1]
ExcretionRenal
Legal statusProhibited (S9)(AU)
Properties
Molecular formulaC12H17N2O4P
Molar mass284.25 g mol−1
Melting point
220–228 °C (428–442 °F)[2]
Solubility in watersoluble
Solubilitysoluble in methanol
slightly soluble in ethanol
negligible in chloroform, benzene
Hazards
LD50285 mg/kg (mouse, i.v.)
280 mg/kg (rat, i.v.)
12.5 mg/kg (rabbit, i.v.)[2]
 YesY (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references
Psilocybin[nb 1] (pron.: /ˌsɪləˈsbɪn/ SIL-ə-SY-bin) is a naturally occurring psychedelic compound produced by more than 200 species of mushrooms, collectively known as psilocybin mushrooms. The most potent are members of the genus Psilocybe, such as P. azurescens, P. semilanceata, and P. cyanescens, but psilocybin has also been isolated from about a dozen other genera. As a prodrug, psilocybin is quickly converted by the body to psilocin, which has mind-altering effects similar to those of LSD and mescaline. The effects generally include euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and spiritual experiences, and can include possible adverse reactions such as nausea and panic attacks.
Imagery found on prehistoric murals and rock paintings of modern-day Spain and Algeria suggest that human usage of psilocybin mushrooms dates back thousands of years. In Mesoamerica, the mushrooms had long been consumed in spiritual and divinatory ceremonies before Spanish chroniclers first documented their use in the 16th century. In a 1957 Life magazine article, American banker and ethnomycologist R. Gordon Wasson described his experiences ingesting psilocybin-containing mushrooms during a traditional ceremony in Mexico, introducing the drug to popular culture. Shortly afterward, the Swiss chemist Albert Hofmann isolated the active principle psilocybin from the mushroom Psilocybe mexicana. Hofmann's employer Sandoz marketed and sold pure psilocybin to physicians and clinicians worldwide for use in psychedelic psychotherapy. Although increasingly restrictive drug laws of the late 1960s curbed scientific research into the effects of psilocybin and other hallucinogens, its popularity as an entheogen (spirituality-enhancing agent) grew in the next decade, largely owing to the increased availability of information on how to cultivate psilocybin mushrooms.
Some users of the drug consider it an entheogen and a tool to supplement practices for transcendence, including meditation and psychonautics. The intensity and duration of the effects of psilocybin are variable, depending on species or cultivar of mushrooms, dosage, individual physiology, and set and setting, as was shown in experiments led by Timothy Leary at Harvard University in the early 1960s. Once ingested, psilocybin is rapidly metabolized to psilocin, which then acts on serotonin receptors in the brain. The mind-altering effects of psilocybin typically last from two to six hours, although to individuals under the influence of psilocybin, the effects may seem to last much longer, since the drug can distort the perception of time. Psilocybin has a low toxicity and a relatively low harm potential, and reports of lethal doses of the drug are rare. Several modern bioanalytical methods have been adapted to rapidly and accurately screen the levels of psilocybin in mushroom samples and body fluids. Since the 1990s, there has been a renewal of scientific research into the potential medical and psychological therapeutic benefits of psilocybin for treating conditions including obsessive-compulsive disorder, cluster headaches, and anxiety related to terminal cancer. Possession of psilocybin-containing mushrooms has been outlawed in most countries, and it has been classified as a scheduled drug by many national drug laws.

Contents

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[edit] History

[edit] Early

Mayan "mushroom stones" of Guatemala
There is evidence to suggest that psychoactive mushrooms have been used by humans in religious ceremonies for thousands of years. Murals dated 9000 to 7000 BCE found in the Sahara desert in southeast Algeria depict horned beings dressed as dancers, clothed in garb decorated with geometrical designs, and holding mushroom-like objects. Parallel lines extend from the mushroom shapes to the center of the dancers' heads.[4] 6,000-year-old pictographs discovered near the Spanish town of Villar del Humo illustrate several mushrooms that have been tentatively identified as Psilocybe hispanica, a hallucinogenic species native to the area.[5] Archaeological artifacts from Mexico, as well as the so-called Mayan "mushroom stones" of Guatemala have similarly been interpreted by some scholars as evidence for ritual and ceremonial usage of psychoactive mushrooms in the Mayan and Aztec cultures of Mesoamerica.[6] In Nahuatl, the language of the Aztecs, the mushrooms were called teonanácatl, or "God's flesh". Following the arrival of Spanish explorers to the New World in the 16th century, chroniclers reported the use of mushrooms by the natives for ceremonial and religious purposes. According to the Dominican friar Diego Durán in The History of the Indies of New Spain (published c. 1581), mushrooms were eaten in festivities conducted on the occasion of the accession to the throne of Aztec emperor Moctezuma II in 1502. The Franciscan friar Bernardino de Sahagún wrote of witnessing mushroom usage in his Florentine Codex (published 1545–1590),[7] and described how some merchants would celebrate upon returning from a successful business trip by consuming mushrooms to evoke revelatory visions.[8] After the defeat of the Aztecs, the Spanish forbade traditional religious practices and rituals that they considered "pagan idolatry", including ceremonial mushroom use. For the next four centuries, the Indians of Mesoamerica hid their use of entheogens from the Spanish conquerors.[9]
Although several psychedelic mushrooms are found in Europe, there is little documented usage of these species in Old World history. The few existing historical accounts about psilocybin mushrooms typically lack sufficient information to allow species identification, and usually refer to the nature of their effects. For example, Flemish botanist Carolus Clusius (1526–1609) described the bolond gomba (crazy mushroom), used in rural Hungary to prepare love potions. English botanist John Parkinson included details about a "foolish mushroom" in his 1640 herbal Theatricum Botanicum.[10] The first reliably documented report of intoxication with Psilocybe semilanceata—Europe's most common and widespread psychedelic mushroom—involved a British family in 1799, who prepared a meal with mushrooms they had picked in London's Green Park.[11]

[edit] Modern

American banker and amateur ethnomycologist R. Gordon Wasson and his wife Valentina studied the ritual use of psychoactive mushrooms by the native population in the Mazatec village Huautla de Jiménez. In 1957, Wasson described the psychedelic visions that he experienced during these rituals in "Seeking the Magic Mushroom", an article published in the popular American weekly Life magazine.[12] Later the same year they were accompanied on a follow-up expedition by French mycologist Roger Heim, who identified several of the mushrooms as Psilocybe species.[13] Heim cultivated the mushrooms in France, and sent samples for analysis to Albert Hofmann, a chemist employed by the Swiss multinational pharmaceutical company Sandoz (now Novartis). Hofmann, who had in 1938 created LSD, led a research group that isolated and identified the psychoactive compounds from Psilocybe mexicana.[14][15] Hofmann was aided in the discovery process by his willingness to ingest mushroom extracts to help verify the presence of the active compounds.[8] He and his colleagues later synthesized a number of compounds chemically related to the naturally occurring psilocybin, to see how structural changes would affect psychoactivity. The new molecules differed from psilocybin in the position of the phosphoryl or hydroxyl group at the top of the indole ring, and in the numbers of methyl groups (CH3) and other additional carbon chains.[16]
Albert Hofmann (shown here in 1993) purified psilocybin and psilocin from Psilocybe mexicana in the late 1950s.
Two diethyl analogs (containing two ethyl groups in place of the two methyl groups) of psilocybin and psilocin were synthesized by Hofmann: 4-phosphoryloxy-N,N-diethyltryptamine, called CEY-19, and 4-hydroxy-N,N-diethyltryptamine, called CZ-74. Because their physiological effects last only about three and a half hours (about half as long as psilocybin), they proved more manageable in European clinics using "psycholytic therapy"—a form of psychotherapy involving the controlled use of psychedelic drugs.[16] Sandoz marketed and sold pure psilocybin under the name Indocybin to physicians and clinicians worldwide.[17] There were no reports of serious complications when psilocybin was used in this way.[1]
In the early 1960s, Harvard University became a testing ground for psilocybin, through the efforts of Timothy Leary and his associates Ralph Metzner and Richard Alpert (who later changed his name to Ram Dass). Leary obtained synthesized psilocybin from Hofmann through Sandoz pharmaceutical. Some studies, such as the Concord Prison Experiment, suggested promising results using psilocybin in clinical psychiatry.[18][19] According to a 2008 review of safety guidelines in human hallucinogenic research, however, Leary and Alpert's well-publicized termination from Harvard and later advocacy of hallucinogen use "further undermined an objective scientific approach to studying these compounds".[20] In response to concerns about the increase in unauthorized use of psychedelic drugs by the general public, psilocybin and other hallucinogenic drugs suffered negative press and faced increasingly restrictive laws. In the United States, laws were passed in 1966 that prohibited the production, trade, or ingestion of hallucinogenic drugs; Sandoz stopped producing LSD and psilocybin the same year.[21] Further backlash against LSD usage swept psilocybin along with it into the Schedule I category of illicit drugs in 1970. Subsequent restrictions on the use of these drugs in human research made funding for such projects difficult to obtain, and scientists who worked with psychedelic drugs faced being "professionally marginalized".[22]
The increasing availability of information on growing techniques made it possible for amateurs to grow psilocybin mushrooms (Psilocybe cubensis pictured) without access to laboratory equipment.
Despite the legal restrictions on psilocybin use, the 1970s witnessed the emergence of psilocybin as the "entheogen of choice".[23] This was due in large part to a wide dissemination of information on the topic, which included works such as those by author Carlos Castaneda, and several books that taught the technique of growing psilocybin mushrooms. One of the most popular of this latter group was published in 1976 under the pseudonyms O.T. Oss and O.N. Oeric by Jeremy Bigwood, Dennis J. McKenna, K. Harrison McKenna, and Terence McKenna, entitled Psilocybin: Magic Mushroom Grower's Guide. Over 100,000 copies were sold by 1981.[24] As ethnobiologist Jonathan Ott explains, "These authors adapted San Antonio's technique (for producing edible mushrooms by casing mycelial cultures on a rye grain substrate; San Antonio 1971) to the production of Psilocybe [Stropharia] cubensis. The new technique involved the use of ordinary kitchen implements, and for the first time the layperson was able to produce a potent entheogen in his own home, without access to sophisticated technology, equipment or chemical supplies."[25]
Because of a lack of clarity about laws about psilocybin mushrooms, retailers in the late 1990s and early 2000s (decade) commercialized and marketed them in smartshops in the Netherlands and the UK, and on the internet. Several websites[nb 2] emerged that have contributed to the accessibility of information on description, use, effects and exchange of experiences among users. Since 2001, six EU countries have tightened their legislation on psilocybin mushrooms in response to concerns about their prevalence and increasing usage.[26] In the 1990s, hallucinogens and their effects on human consciousness were again the subject of scientific study, particularly in Europe. Advances in neuropharmacology and neuropsychology, and the availability of brain imaging techniques have provided impetus for using drugs like psilocybin to probe the "neural underpinnings of psychotic symptom formation including ego disorders and hallucinations".[27] Recent studies in the United States have attracted attention from the popular press and thrust psilocybin back into the limelight.[28][29]

[edit] Occurrence

The mushroom Psilocybe mexicana
Psilocybin was first isolated from Psilocybe mexicana.
The mushroom Psilocybe semilanceata
P. semilanceata is common in Europe, Canada, and the United States.
Psilocybin is present in varying concentrations in over 200 species of Basidiomycota mushrooms. In a 2000 review on the worldwide distribution of hallucinogenic mushrooms, Gastón Guzmán and colleagues considered these to be distributed amongst the following genera: Psilocybe (116 species), Gymnopilus (14), Panaeolus (13), Copelandia (12), Hypholoma (6), Pluteus (6) Inocybe (6), Conocybe (4), Panaeolina (4), Gerronema (2) and Agrocybe, Galerina and Mycena (1 species each).[30] Guzmán increased his estimate of the number of psilocybin-containing Psilocybe to 144 species in a 2005 review. The majority of these are found in Mexico (53 species), with the remainder distributed in the US and Canada (22), Europe (16), Asia (15), Africa (4), and Australia and associated islands (19).[31] In general, psilocybin-containing species are dark-spored, gilled mushrooms that grow in meadows and woods of the subtropics and tropics, usually in soils rich in humus and plant debris.[32] Psilocybin mushrooms occur on all continents, but the majority of species are found in subtropical humid forests.[30] Psilocybe species commonly found in the tropics include P. cubensis and P. subcubensis. P. semilanceata—considered by Guzmán to be the world's most widely distributed psilocybin mushroom[33]—is found in Europe, North America, Asia, South America, Australia and New Zealand, but is entirely absent from Mexico.[31] Although the presence or absence of psilocybin is not of much use as a chemotaxonomical marker at the familial level or higher, it is used to classify taxa of lower taxonomic groups.[34]
Species % psilocybin
P. azurescens
1.78
P. serbica
1.34
P. semilanceata
0.98
P. baeocystis
0.85
P. cyanescens
0.85
P. tampanensis
0.68
P. cubensis
0.63
P. weilii
0.61
P. hoogshagenii
0.60
P. stuntzii
0.36
P. cyanofibrillosa
0.21
P. liniformans
0.16
Maximum reported psilocybin concentrations (% dry weight) in 12 Psilocybe species[35]
Both the caps and the stems contain the psychoactive compounds, although the caps contain consistently more. The spores of these mushrooms do not contain psilocybin or psilocin.[36][37][38] The total potency varies greatly between species and even between specimens of a species collected or grown from the same strain.[39] Because most psilocybin biosynthesis occurs early in the formation of fruit bodies or sclerotia, younger, smaller mushrooms tend to have a higher concentration of the drug than larger, mature mushrooms.[40] In general, the psilocybin content of mushrooms is quite variable (ranging from almost nothing to 1.5% of the dry weight)[41] and depends on species, strain, growth and drying conditions, and mushroom size.[42] Cultivated mushrooms have less variability in psilocybin content than wild mushrooms.[43] The drug is more stable in dried than fresh mushrooms; dried mushrooms retain their potency for months or even years,[44] while mushrooms stored fresh for four weeks contain only traces of the original psilocybin.[45] The psilocybin contents of dried herbarium specimens of Psilocybe semilanceata in one study were shown to decrease with the increasing age of the sample: collections dated 11, 33, or 118 years old contained 0.84%, 0.67%, and 0.014% (all dry weight), respectively.[46] Mature mycelia contain some psilocybin, while young mycelia (recently germinated from spores) lack appreciable amounts.[47] Many species of mushrooms containing psilocybin also contain lesser amounts of the analog compounds baeocystin and norbaeocystin,[48] chemicals thought to be biogenic precursors.[49] Although most species of psilocybin-containing mushrooms bruise blue when handled or damaged due to the oxidization of phenolic compounds, this reaction is not a definitive method of identification or determining a mushroom's potency.[39][50]

[edit] Chemistry

Psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine or 4-PO-DMT) is a prodrug that is converted into the pharmacologically active compound psilocin in the body by a dephosphorylation reaction. This chemical reaction takes place under strongly acidic conditions, or under physiological conditions in the body, through the action of enzymes called phosphatases.[43]
Psilocybin is a tryptamine compound with a chemical structure containing an indole ring linked to an ethylamine substituent. It is chemically related to the amino acid tryptophan, and is structurally similar to the neurotransmitter serotonin. Psilocybin is a member of the general class of tryptophan-based compounds that originally functioned as antioxidants in earlier life forms before assuming more complex functions in multicellular organisms, including humans.[51] Other related indole-containing psychedelic compounds include dimethyltryptamine, found in many plant species and in trace amounts in some mammals, and bufotenine, found in the skin of psychoactive toads.[52] Biosynthetically, the biochemical transformation from tryptophan to psilocybin involves several enzyme reactions: decarboxylation, methylation at the N9 position, 4-hydroxylation, and O-phosphorylation. Isotopic labeling experiments suggest that tryptophan decarboxylation is the initial biosynthetic step and that O-phosphorylation is the final step.[53][54] The precise sequence of the intermediate enzymatic steps is not known with certainty, and the biosynthetic pathway may differ between species.[55]
A possible biosynthetic route to psilocybin. Although the order of the first (decarboxylation) and last (phosphorylation) steps are known with some certainty, the sequence of the two intermediate steps is speculative.
Psilocybin is a zwitterionic alkaloid that is soluble in water, methanol and aqueous ethanol, but insoluble in organic solvents like chloroform and petroleum ether.[56] Exposure to light is detrimental to the stability of aqueous solutions of psilocybin, and will cause it to rapidly oxidize—an important consideration when using it as an analytical standard.[57] Osamu Shirota and colleagues reported a method for the large-scale synthesis of psilocybin without chromatographic purification in 2003.[58] Starting with 4-hydroxyindole, they generated psilocybin from psilocin in 85% yield, a marked improvement over yields reported from previous syntheses.[59][60][61] Purified psilocybin is a white, needle-like crystalline powder[58] with a melting point between 220–228 °C (428–442 °F),[62] and a slightly ammonia-like taste.[63]

[edit] Analytical methods

Several relatively simple chemical tests—commercially available as reagent testing kits—can be used to assess the presence of psilocybin in extracts prepared from mushrooms. The drug reacts in the Marquis test to produce a yellow color, and a green color in the Mandelin test.[64] Neither of these tests, however, is specific for psilocybin; for example, the Marquis test will react with many classes of controlled drugs, such as those containing primary amino groups and unsubstituted benzene rings, including amphetamine and methamphetamine.[65] Ehrlich's reagent and DMACA reagent are used as chemical sprays to detect the drug after thin layer chromatography.[66] Many modern techniques of analytical chemistry have been used to quantify psilocybin levels in mushroom samples. Although the earliest methods commonly used gas chromatography, the high temperature required to vaporize the psilocybin sample prior to analysis causes it to spontaneously lose its phosphoryl group and become psilocin—making it difficult to chemically discriminate between the two drugs. In forensic toxicology, techniques involving gas chromatography coupled to mass spectrometry (GC–MS) are the most widely used due to their high sensitivity and ability to separate compounds in complex biological mixtures.[67] These techniques include ion mobility spectrometry,[38] capillary zone electrophoresis,[68] ultraviolet spectroscopy,[69] and infrared spectroscopy.[70] High performance liquid chromatography (HPLC) is used with ultraviolet,[57] fluorescence,[71] electrochemical,[72] and electrospray mass spectrometric detection methods.[73]
Various chromatographic methods have been developed to detect psilocin in body fluids: the rapid emergency drug identification system (REMEDi HS), a drug screening method based on HPLC;[74] HPLC with electrochemical detection;[72][75] GC–MS;[74][76] and liquid chromatography coupled to mass spectrometry.[77] Although the determination of psilocin levels in urine can be performed without sample clean-up (i.e., removing potential contaminants that make it difficult to accurately assess concentration), the analysis in plasma or serum requires a preliminary extraction, followed by derivatization of the extracts in the case of GC–MS. A specific immunoassay has also been developed to detect psilocin in whole blood samples.[78] A 2009 publication reported using HPLC to quickly separate forensically important illicit drugs including psilocybin and psilocin, which were identifiable within about half a minute of analysis time.[79] These analytical techniques to determine psilocybin concentrations in body fluids are, however, not routinely available, and not typically used in clinical settings.[80]

[edit] Pharmacology

The neurotransmitter serotonin is structurally similar to psilocybin.
Psilocybin is rapidly dephosphorylated in the body to psilocin, which is a partial agonist for several serotonergic receptors. Psilocin has a high affinity for the 5-HT2A serotonin receptor in the brain, where it mimics the effects of serotonin (5-hydroxytryptamine, or 5-HT). Psilocin binds less tightly to other serotonergic receptors 5-HT1A, 5-HT1D, and 5-HT2C.[1] Serotonin receptors are located in numerous parts of the brain, including the cerebral cortex, and are involved in a wide range of functions, including regulation of mood and motivation.[81] The psychotomimetic (psychosis-mimicking) effects of psilocin can be blocked in a dose-dependent fashion by the 5-HT2A antagonist drugs ketanserin and risperidone.[82] Although the 5-HT2A receptor is responsible for most of the effects of psilocin, various lines of evidence have shown that interactions with non-5-HT2A receptors also contribute to the subjective and behavioral effects of the drug.[83][nb 3] For example, psilocin indirectly increases the concentration of the neurotransmitter dopamine in the basal ganglia, and some psychotomimetic symptoms of psilocin are reduced by haloperidol, a non-selective dopamine receptor antagonist. Taken together, these suggest that there may be an indirect dopaminergic contribution to psilocin's psychotomimetic effects.[85] In contrast to LSD, which binds to all dopamine receptor subtypes, psilocybin and psilocin have no affinity for the dopamine receptors.[1]
The chemical structures of psilocybin and related analogs have been used in computational biology to help model the structure, function, and ligand-binding properties of the 5-HT2C G-protein-coupled receptor.[86][87]

[edit] Toxicity and harm potential

Chart of dependence potential and effective dose/lethal dose ratio of several psychoactive drugs. Source:[88]
The toxicity of psilocybin is low. In rats, the median lethal dose (LD50) when administered orally is 280 milligrams per kilogram (mg/kg), approximately one and a half times that of caffeine. When administered intravenously in rabbits, psilocybin's LD50 is approximately 12.5 mg/kg.[62] Psilocybin comprises approximately 1% of the weight of Psilocybe cubensis mushrooms, and so nearly 1.7 kilograms (3.7 lb) of dried mushrooms, or 17 kilograms (37 lb) of fresh mushrooms, would be required for a 60-kilogram (130 lb) person to reach the 280 mg/kg LD50 value of rats.[45] Based on the results of animal studies, the lethal dose of psilocybin has been extrapolated to be 6 grams, 1000 times greater than the effective dose of 6 milligrams.[89] The Registry of Toxic Effects of Chemical Substances assigns psilocybin a relatively high therapeutic index of 641 (higher values correspond to a better safety profile); for comparison, the therapeutic indices of aspirin and nicotine are 199 and 21, respectively.[90] The lethal dose from psilocybin toxicity alone is unknown at recreational or medicinal levels, and has rarely been documented—as of 2011, only two cases attributed to overdosing on hallucinogenic mushrooms (without concurrent use of other drugs) have been reported in the scientific literature.[45][nb 4] Most of the comparatively few fatal incidents reported in the literature that are associated with psychedelic mushroom usage involve the simultaneous use of other drugs, especially alcohol. Probably the most common cause of hospital admissions resulting from magic mushroom usage involve "bad trips" or panic reactions, in which affected individuals become extremely anxious, confused, agitated, or disoriented. Accidents, self-injury, or suicide attempts can result from serious cases of acute psychotic episodes.[45]
Repeated use of psilocybin does not lead to physical dependence.[1] A 2008 study concluded that, based on US data from the period 2000–2002, adolescent-onset (defined here as ages 11–17) usage of hallucinogenic drugs (including psilocybin) did not increase the risk of drug dependence in adulthood; this was in contrast to adolescent usage of cannabis, cocaine, inhalants, anxiolytic medicines, and stimulants, all of which were associated with "an excess risk of developing clinical features associated with drug dependence".[93] Similarly, a 2010 Dutch study ranked the relative harm of psilocybin mushrooms compared to a selection of 19 recreational drugs, including alcohol, cannabis, cocaine, ecstasy, heroin, and tobacco. Magic mushrooms were ranked as the illicit drug with the lowest harm,[94] corroborating conclusions reached earlier by expert groups in the United Kingdom.[95][96] Although no studies have linked psilocybin with birth defects,[97] it is recommended that pregnant women avoid its usage.[98]

[edit] Physiology

Although psilocybin may be prepared synthetically, outside of the research setting, it is not typically used in this form. The psilocybin present in certain species of mushrooms can be ingested in several ways: by consuming fresh or dried fruit bodies, by preparing a tisane, or by combining with other foods to mask the bitter taste.[26] Less frequently, mushroom extracts are injected intravenously.[45] The effects of the drug begin 10–40 minutes after ingestion, and last 2–6 hours depending on dose, species, and individual metabolism.[99] The half life of psilocybin is 163 ± 64 minutes when taken orally, or 74.1 ± 19.6 minutes when injected intravenously.[1] A dosage of 4–10 mg, corresponding roughly to 50–300 micrograms per kilogram (µg/kg) of body weight, is required to induce psychedelic effects. A typical recreational dosage is 10–50 mg psilocybin, which is roughly equivalent to 10–50 grams of fresh mushrooms, or 1–5 grams of dried mushrooms.[45] A small number of people are unusually sensitive to psilocybin, such that a normally threshold-level dose of about 2 mg can result in effects usually associated with medium or high doses. In contrast, there are some who require relatively high doses to experience noticeable effects. Individual brain chemistry and metabolism play a large role in determining a person's response to psilocybin.[99]
Psilocybin is converted in the liver to the pharmacologically active psilocin, which is then either glucuronated to be excreted in the urine, or further converted to various psilocin metabolites.
Psilocybin is metabolized mostly in the liver. As it becomes converted to psilocin, it undergoes a first-pass effect, whereby its concentration is greatly reduced before it reaches the systemic circulation. Psilocin is broken down by the enzyme monoamine oxidase to produce several metabolites that can circulate in the blood plasma, including 4-hydroxyindole-3-acetaldehyde, 4-hydroxytryptophol, and 4-hydroxyindole-3-acetic acid.[1] Some psilocin is not broken down by enzymes, and instead forms a glucuronide; this is a biochemical mechanism animals use to eliminate toxic substances by linking them with glucuronic acid, which can then be excreted in the urine.[76][100] Psilocin is glucuronated by the glucuronosyltransferase enzymes UGT1A9 in the liver, and by UGT1A10 in the small intestine.[101] Based on studies using animals, about 50% of ingested psilocybin is absorbed through the stomach and intestine. Within 24 hours, about 65% of the absorbed psilocybin is excreted into the urine, and a further 15–20% is excreted in the bile and feces. Although most of the remaining drug is eliminated in this way within 8 hours, it is still detectable in the urine after 7 days.[21] Clinical studies show that psilocin concentrations in the plasma of adults average about 8 µg/liter within 2 hours after ingestion of a single 15 mg oral psilocybin dose;[102] psychological effects occur with a blood plasma concentration of 4–6 µg/liter.[1] Psilocybin is about 100 times less potent than LSD on a weight per weight basis, and the physiological effects last about half as long.[103]
Tolerance to psilocybin builds and dissipates quickly; ingesting psilocybin more than about once a week can lead to diminished effects. Tolerance dissipates after a few days, so doses can be spaced several days apart to avoid the effect.[104] A cross-tolerance can develop between psilocybin and the pharmacologically similar LSD,[105] and between psilocybin and phenethylamines such as mescaline and DOM.[83] Monoamine oxidase inhibitors (MAOI) have been known to prolong and enhance the effects of psilocybin.[106] Alcohol consumption may enhance the effects of psilocybin, because acetaldehyde, one of the primary breakdown metabolites of consumed alcohol, reacts with biogenic amines present in the body to produce MAOIs related to tetrahydroisoquinoline and β-carboline. Tobacco smokers can also experience more powerful effects with psilocybin,[45] because tobacco smoke exposure decreases levels of MAO in the brain and peripheral organs.[107]

[edit] Effects

American psychologist and counterculture figure Timothy Leary conducted early experiments into the effects of psychedelic drugs, including psilocybin.
The effects of psilocybin are highly variable and depend on the mindset and environment in which the user has the experience, factors commonly referred to as set and setting. In the early 1960s, Timothy Leary and colleagues at Harvard University investigated the role of set and setting on the effects of psilocybin. They administered the drug to 175 volunteers from various backgrounds in an environment intended to be similar to a comfortable living room. Ninety-eight of the subjects were given questionnaires to assess their experiences and the contribution of background and situational factors. Individuals who had experience with psilocybin prior to the study reported more pleasant experiences than those for whom the drug was novel. Group size, dosage, preparation, and expectancy were important determinants of the drug response. Those placed in groups of more than eight individuals generally felt that the groups were less supportive, and their experiences were less pleasant. Conversely, smaller groups (fewer than six individuals) were seen as more supportive. Participants also reported having more positive reactions to the drug in those groups. Leary and colleagues proposed that psilocybin heightens suggestibility, making an individual more receptive to interpersonal interactions and environmental stimuli.[18] These findings were affirmed in a later review by Jos ten Berge (1999), who concluded that dosage, set, and setting were fundamental factors in determining the outcome of experiments that tested the effects of psychedelic drugs on artists' creativity.[108]
After ingesting psilocybin, a wide range of subjective effects may be experienced: feelings of disorientation, lethargy, giddiness, euphoria, joy, and depression. About a third of users report feelings of anxiety or paranoia.[45] Low doses of the drug can induce hallucinatory effects. Closed-eye hallucinations may occur, in which the affected individual sees multicolored geometric shapes and vivid imaginative sequences.[109] Some individuals report experiencing synesthesia, such as tactile sensations when viewing colors.[110] At higher doses, psilocybin can lead to "Intensification of affective responses, enhanced ability for introspection, regression to primitive and childlike thinking, and activation of vivid memory traces with pronounced emotional undertones".[27] Open-eye visual hallucinations are common, and may be very detailed although rarely confused with reality.[109]
A 2011 prospective study by Roland R. Griffiths and colleagues suggests that a single high dosage of psilocybin can cause long-term changes in the personality of its users. About half of the study participants—described as healthy, "spiritually active", and many possessing postgraduate degrees—showed an increase in the personality dimension of openness (assessed using the Revised NEO Personality Inventory), and this positive effect was apparent more than a year after the psilocybin session. According to the study authors, the finding is significant because "no study has prospectively demonstrated personality change in healthy adults after an experimentally manipulated discrete event."[111] Although other researchers have described instances of psychedelic drug usage leading to new psychological understandings and personal insights,[112] it is not known whether these experimental results can be generalized to larger populations.[111]

[edit] Physical effects

Common responses include: pupil dilation (93%); changes in heart rate (100%), including increases (56%), decreases (13%), and variable responses (31%); changes in blood pressure (84%), including hypotension (34%), hypertension (28%), and general instability (22%); changes in stretch reflex (86%), including increases (80%) and decreases (6%); nausea (44%); tremor (25%); and dysmetria (16%) (inability to properly direct or limit motions).[nb 5] The temporary increases in blood pressure caused by the drug can be a risk factor for users with pre-existing hypertension.[109] These qualitative somatic effects caused by psilocybin have been corroborated by several early clinical studies.[114] A 2005 magazine survey of club goers in the UK found that nausea or vomiting was experienced by over a quarter of those who had used hallucinogenic mushrooms in the last year, although this effect is caused by the mushroom rather than psilocybin itself.[45] In one study, administration of gradually-increasing dosages of psilocybin daily for 21 days had no measurable effect on electrolyte levels, blood sugar levels, or liver toxicity tests.[1]

[edit] Perceptual distortions

The ability of psilocybin to cause perceptual distortions is linked to its influence on the activity of the prefrontal cortex.
Psilocybin is known to strongly influence the subjective experience of the passage of time.[115] Users often feel as if time is slowed down, resulting in the perception that "minutes appear to be hours" or "time is standing still".[116] Studies have demonstrated that psilocybin significantly impairs subjects' ability to gauge time intervals longer than 2.5 seconds, impairs their ability to synchronize to inter-beat intervals longer than 2 seconds, and reduces their preferred tapping rate.[116][117] These results are consistent with the drug's role in affecting prefrontal cortex activity,[118] and the role that the prefrontal cortex is known to play in time perception.[119] However, the neurochemical basis of psilocybin's effects on the perception of time are not known with certainty.[85]
Users having a pleasant experience can feel an ecstatic sense of connection to others, nature, and the universe; other perceptions and emotions are also often intensified. Users having an unpleasant experience (a "bad trip") describe a reaction accompanied by fear, other unpleasant feelings, and occasionally by dangerous behavior. In general, the phrase "bad trip" is used to describe a reaction that is characterized primarily by fear or other unpleasant emotions, not just transitory experience of such feelings. A variety of factors may contribute to a psilocybin user experiencing a bad trip, including "tripping" during an emotional or physical low or in a non-supportive environment (see: set and setting). Ingesting psilocybin in combination with other drugs, including alcohol, can also increase the likelihood of a bad trip.[45][80] Other than the duration of the experience, the effects of psilocybin are similar to comparable dosages of LSD or mescaline. However, in the Psychedelics Encyclopedia, author Peter Stafford noted, "The psilocybin experience seems to be warmer, not as forceful and less isolating. It tends to build connections between people, who are generally much more in communication than when they use LSD."[120]

[edit] Possible adverse psychiatric effects

Panic reactions can occur after consumption of psilocybin-containing mushrooms, especially if the ingestion is accidental or otherwise unexpected. Reactions characterized by violence, aggression, homicidal and suicidal attempts,[121] prolonged schizophrenia-like psychosis,[82][122] and convulsions[123] have been reported in the literature. A 2005 survey conducted in the United Kingdom found that almost a quarter of those who had used psilocybin mushrooms in the past year had experienced a panic attack.[45] Other adverse effects less frequently reported include paranoia, confusion, derealization, disconnection from reality, and mania.[124] Psilocybin usage can temporarily induce a state of depersonalization disorder.[125] Usage by those with schizophrenia can induce acute psychotic states requiring hospitalization.[45]
The similarity of psilocybin-induced symptoms to those of schizophrenia has made the drug a useful research tool in behavioral and neuroimaging studies of this psychotic disorder.[126][127][128] In both cases, psychotic symptoms are thought to arise from a "deficient gating of sensory and cognitive information" in the brain that ultimately lead to "cognitive fragmentation and psychosis".[127] Flashbacks (spontaneous recurrences of a previous psilocybin experience) can occur long after having used psilocybin mushrooms. Hallucinogen persisting perception disorder (HPPD) is characterized by a continual presence of visual disturbances similar to those generated by psychedelic substances. Neither flashbacks nor HPPD are commonly associated with psilocybin usage,[45] and correlations between HPPD and psychedelics are further obscured by polydrug use and other variables.[129]

[edit] Mystical experiences

Psilocybin mushrooms have been and continue to be used in indigenous New World cultures in religious, divinatory, or spiritual contexts. Reflecting the meaning of the word entheogen ("the god within"), the mushrooms are revered as powerful spiritual sacraments that provide access to sacred worlds. Typically used in small group community settings, they enhance group cohesion and reaffirm traditional values.[130] American philosopher Terence McKenna documented the worldwide practices of psilocybin mushroom usage as part of a cultural ethos relating to the Earth and mysteries of nature, and suggested that mushrooms enhanced self-awareness and a sense of contact with a "Transcendent Other"—reflecting a deeper understanding of our connectedness with nature.[131]
Psychedelic drugs can induce states of consciousness that have lasting personal meaning and spiritual significance in individuals who are religious or spiritually inclined; these states are called mystical experiences. Some scholars have proposed that many of the qualities of a drug-induced mystical experience are indistinguishable from mystical experiences achieved through non-drug techniques, such as meditation or holotropic breathwork.[132][133] In the 1960s, Walter Pahnke and colleagues systematically evaluated mystical experiences (which they called "mystical consciousness") by categorizing their common features. These categories, according to Pahnke, "describe the core of a universal psychological experience, free from culturally determined philosophical or theological interpretations", and allow researchers to assess mystical experiences on a qualitative, numerical scale.[134]
In the 1962 Marsh Chapel Experiment, which was run by Pahnke at the Harvard Divinity School under the supervision of Timothy Leary,[135] almost all of the graduate degree divinity student volunteers who received psilocybin reported profound religious experiences.[136] One of the participants was religious scholar Huston Smith, author of several textbooks on comparative religion; he later described his experience as "the most powerful cosmic homecoming I have ever experienced."[137] In a 25-year followup to the experiment, all of the subjects given psilocybin described their experience as having elements of "a genuine mystical nature and characterized it as one of the high points of their spiritual life".[138] Psychedelic researcher Rick Doblin considered the study partially flawed due to incorrect implementation of the double-blind procedure, and several imprecise questions in the mystical experience questionnaire. Nevertheless, he said that the study cast "a considerable doubt on the assertion that mystical experiences catalyzed by drugs are in any way inferior to non-drug mystical experiences in both their immediate content and long-term effects".[139] This sentiment was echoed by psychiatrist William A. Richards, who in a 2007 review stated "[psychedelic] mushroom use may constitute one technology for evoking revelatory experiences that are similar, if not identical, to those that occur through so-called spontaneous alterations of brain chemistry."[140]
In their studies on the psilocybin experience, Johns Hopkins researchers use peaceful music and a comfortable room to help ensure a comfortable setting, and experienced guides to monitor and reassure the volunteers.
A group of researchers from Johns Hopkins School of Medicine led by Griffiths conducted a study to assess the immediate and long-term psychological effects of the psilocybin experience, using a modified version of the mystical experience questionnaire and a rigorous double-blind procedure.[141] When asked in an interview about the similarity of his work with Leary's, Griffiths explained the difference: "We are conducting rigorous, systematic research with psilocybin under carefully monitored conditions, a route which Dr. Leary abandoned in the early 1960s."[142] The National Institute of Drug Abuse-funded study, published in 2006, has been praised by experts for the soundness of its experimental design.[nb 6] In the experiment, 36 volunteers without prior experience with hallucinogens were given psilocybin and methylphenidate (Ritalin) in separate sessions; the methylphenidate sessions served as a control and psychoactive placebo. The degree of mystical experience was measured using a questionnaire developed by Ralph W. Hood;[143] 61% of subjects reported a "complete mystical experience" after their psilocybin session, while only 13% reported such an outcome after their experience with methylphenidate. Two months after taking psilocybin, 79% of the participants reported moderately to greatly increased life satisfaction and sense of well-being. About 36% of participants also had a strong to extreme "experience of fear" or dysphoria (i.e., a "bad trip") at some point during the psilocybin session (which was not reported by any subject during the methylphenidate session); about one-third of these (13% of the total) reported that this dysphoria dominated the entire session. These negative effects were reported to be easily managed by the researchers and did not have a lasting negative effect on the subject's sense of well-being.[144]
A followup study conducted 14 months after the original psilocybin session confirmed that participants continued to attribute deep personal meaning to the experience. Almost one-third of the subjects reported that the experience was the single most meaningful or spiritually significant event of their lives, and over two-thirds reported it among their five most spiritually significant events. About two-thirds indicated that the experience increased their sense of well-being or life satisfaction.[136] Similarly, in a recent (2010) web-based questionnaire study designed to investigate user perceptions of the benefits and harms of hallucinogenic drug use, 60% of the 503 psilocybin users reported that their use of psilocybin had a long-term positive impact on their sense of well-being.[45][124]
In 2011, Griffiths and colleagues published the results of further studies designed to learn more about the optimum psilocybin doses needed for positive life-changing experiences, while minimizing the chance of negative reactions. In a 14-month followup, the researchers found that 94% of the volunteers rated their experiences with the drug as one of the top five most spiritually significant of their lives (44% said it was the single most significant). None of the 90 sessions that took place throughout the study were rated as decreasing well-being or life satisfaction. Moreover, 89% reported positive changes in their behaviors as a result of the experiences. The conditions of the experimental design included a single drug experience a month, on a couch, in a living-room-like setting, with eye shades and carefully chosen music (classical and world music). As an additional precaution to guide the experience, as with the 2006 study, the 2011 study included a "monitor" or "guide" whom the volunteers supposedly trusted. The monitors provided gentle reassurance when the volunteers experienced anxiety. The volunteers and monitors all remained blind to the exact dosages for the sake of the experiment.[145]

[edit] Medical research

Psilocybin has been a subject of medical research since the 1960s, when Leary and Alpert ran the Harvard Psilocybin Project, in which they carried out a number of experiments to evaluate the therapeutic value of psilocybin in the treatment of personality disorders, or to augment psychological counseling.[146] In the 2000s (decade), there was a renewal of research concerning the use of psychedelic drugs for potential clinical applications, such as to address anxiety disorders, major depression, and various addictions.[147][148] In 2008, the Johns Hopkins research team published guidelines for responsibly conducting medical research trials with psilocybin and other hallucinogens in humans. These included recommendations on how to screen potential study volunteers to exclude those with personal or family psychiatric histories that suggest a risk of averse reactions to hallucinogens.[20] A 2010 study on the short- and long-term subjective effects of psilocybin administration in clinical settings concluded that despite a small risk of acute reactions such as dysphoria, anxiety, or panic, "the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk"; the authors note, however, that the safety of the drug "cannot be generalized to situations in which psilocybin is used recreationally or administered under less controlled conditions."[27]
The first FDA-approved clinical study of psilocybin since 1970[149]—led by Francisco Moreno at the University of Arizona and supported by the Multidisciplinary Association for Psychedelic Studies—studied the effects of psilocybin on nine patients with obsessive-compulsive disorder (OCD).[150][151] The pilot study found that, when administered by trained professionals in a medical setting, the use of psilocybin was associated with substantial reductions in OCD symptoms in several of the patients.[152] This effect may be caused by psilocybin's ability to reduce the levels of the serotonin-2A receptor, resulting in decreased responsiveness to serotonin.[153] Psilocybin has additionally shown promise to ease the pain caused by cluster headaches, often considered not only the most painful of all types of headaches[154] but "one of the worst pain syndromes known to mankind."[155] In a 2006 study,[156] half of cluster headache patients reported that psilocybin aborted the attacks, and most reported extended remission periods; similar results were reported for LSD.[152] A 2011 review of alternative headache treatments concluded that, despite flaws in the study design, these results suggest that LSD and psilocybin may warrant further study for use in the prevention of cluster headaches—only subhallucinogenic doses of the drugs are required for effective treatment, and no other medications have been reported to stop a cluster headache cycle.[157]
Several modern studies have investigated the possibility that psilocybin can ease the psychological suffering associated with end-stage cancer. Preliminary results indicate that low doses of psilocybin can improve the mood and reduce the anxiety of patients with advanced cancer, and that the effects last from two weeks to six months.[152] These results are comparable to those obtained from early studies that explored the use of LSD to improve the psychological well-being of terminally ill patients, but without the experimental rigor employed in modern clinical psychopharmacology research.[20][152]

[edit] Social and legal aspects

A 2009 national survey of drug use by the US Department of Health and Human Services concluded that the number of first-time psilocybin mushroom users in the United States was roughly equivalent to the number of first-time users of marijuana.[158] In European countries, the lifetime prevalence estimates of psychedelic mushroom usage among young adults (15–34 years) range from 0.3% to 14.1%.[159] In modern Mexico, traditional ceremonial use survives among several indigenous groups, including the Nahuatls, the Matlazinca, the Totonacs, the Mazatecs, Mixes, Zapotecs, and the Chatino. Although hallucinogenic Psilocybe species are abundant in low-lying areas of Mexico, most ceremonial use takes places in mountainous areas of elevations greater than 1,500 meters (4,900 ft). Guzmán suggests this is a vestige of Spanish colonial influence from several hundred years earlier, when mushroom use was persecuted by the Catholic Church.[160]
In the United States, psilocybin (and psilocin) were first subjected to federal regulation by the Drug Abuse Control Amendments of 1965, a product of a bill sponsored by Senator Thomas J. Dodd. The law—passed in July 1965 and effected on February 1, 1966—was an amendment to the federal Food, Drug and Cosmetic Act and was intended to regulate the unlicensed "possession, manufacture, or sale of depressant, stimulant and hallucinogenic drugs".[161] The statutes themselves, however, did not list the "hallucinogenic drugs" that were being regulated.[161] Instead, the term "hallucinogenic drugs" was meant to refer to those substances believed to have a "hallucinogenic effect on the central nervous system".[161]
Dried Psilocybe mushrooms showing the characteristic blue bruising on the stems
Despite the seemingly strict provisions of the law, many people were exempt from prosecution. The statutes "permit[ted] … people to possess such drugs so long as they were for the personal use of the possessor, [for] a member of his household, or for administration to an animal".[161] The federal law that specifically banned psilocybin and psilocin was enacted on October 24, 1968. The substances were said to have "a high potential for abuse", "no currently accepted medical use," and "a lack of accepted safety".[162] On October 27, 1970, both psilocybin and psilocin became classified as Schedule I drugs and were simultaneously labeled "hallucinogens" under a section of the Comprehensive Drug Abuse Prevention and Control Act known as the Controlled Substances Act.[163] Schedule I drugs are illicit drugs that are claimed to have no known therapeutic benefit. The United Nations Convention on Psychotropic Substances (adopted in 1971) requires its members to prohibit psilocybin, and parties to the treaty are required to restrict use of the drug to medical and scientific research under strictly controlled conditions. However, the mushrooms containing the drug were not specifically included in the convention, due largely to pressure from the Mexican government.[158] Most national drug laws have been amended to reflect the terms of the convention; examples include the UK Misuse of Drugs Act 1971, the US Psychotropic Substances Act of 1978,[163] the Canadian Controlled Drugs and Substances Act of 1996,[164] and the Japanese Narcotics and Psychotropics Control Law of 2002.[165] The possession and use of psilocybin is prohibited under almost all circumstances, and often carries severe legal penalties.[158]
Possession and use of psilocybin mushrooms, including the bluing species of Psilocybe, is therefore prohibited by extension. However, in many national, state, and provincial drug laws, there has been a great deal of ambiguity about the legal status of psilocybin mushrooms, as well as a strong element of selective enforcement in some places.[43][166] Most US state courts have considered the mushroom a 'container' of the illicit drugs, and therefore illegal. A loophole further complicates the legal situation—the spores of psilocybin mushrooms do not contain the drugs, and are legal to possess in many areas. Jurisdictions that have specifically enacted or amended laws to criminalize the possession of psilocybin mushroom spores include Germany (since 1998),[165] and California, Georgia, and Idaho in the United States. There is consequently an active underground economy involved in the sale of spores and cultivation materials, and an internet-based social network to support the illicit activity.[167] After a long interruption in the use of psilocybin in research, there has been a general shift in attitudes regarding research with hallucinogenic agents. Many countries are revising their positions and have started to approve studies to test the physiological and therapeutic effects of hallucinogens.[112]

[edit] See also