document_title: AP Poll

question_text: when does new ap poll come out basketball

text: AP Poll

text: College football[edit]

text: The football poll is released Sundays at 2pm Eastern time during the football season, unless ranked teams have not finished their games.

text: History[edit]

text: The AP college football poll has a long history. The news media began running their own polls of sports writers to determine who was, by popular opinion, the best football team in the country at the end of the season. One of the earliest such polls was the AP College Football Poll, first run in 1934.[3] In 1935, AP sports editor Alan J. Gould declared a three way tie for national champion in football between Minnesota, Princeton, and Southern Methodist. Minnesota fans protested, and a number of Gould's colleagues led by Charles "Cy" Sherman suggested he create a poll of sports editors instead of only using his own list, and the next year the poll was born.[4] It has run continuously from 1936.[5]

text: Due to the long-standing historical ties between individual college football conferences and high-paying bowl games like the Rose Bowl and Orange Bowl, the NCAA had not held a tournament or championship game to determine the champion of what is now the highest division, NCAA Division I, Football Bowl Subdivision (the Division I, Football Championship Subdivision and lower divisions do hold championship tournaments). As a result, the public and the media began to acknowledge the leading vote-getter in the final AP Poll as the national champion for that season.

text: While the AP Poll currently lists the Top 25 teams in the nation, from 1936 to 1961 the wire service only ranked 20 teams. From 1962 to 1967 only 10 teams were recognized. From 1968 to 1988, the AP again resumed its Top 20 before expanding to the current 25 teams in 1989.

text: The AP began conducting a preseason poll starting in 1950.[6][7]

text: At the end of the 1947 season the AP released an unofficial post-bowl poll which differed from the regular season final poll.[8] Until the 1968 college football season, the final AP poll of the season was released following the end of the regular season, with the lone exception of the 1965 season. In 1964, Alabama was named the national champion in the final AP Poll following the completion of the regular season, but lost in the Orange Bowl to Texas, leaving Arkansas as the only undefeated, untied team after the Razorbacks defeated Nebraska in the Cotton Bowl Classic. In 1965, the AP's decision to wait to crown its champion paid handsomely, as top-ranked Michigan State lost to UCLA in the Rose Bowl, number two Arkansas lost to LSU in the Cotton Bowl Classic, and fourth-ranked Alabama defeated third-ranked Nebraska in the Orange Bowl, vaulting the Crimson Tide to the top of the AP's final poll (Michigan State was named national champion in the final UPI Coaches Poll, which did not conduct a post-bowl poll).

text: Beginning in the 1968 season, the post bowl game poll became permanent and the AP championship reflected the bowl game results. The UPI did not follow suit with the coaches' poll until the 1974 season.

text: No. 1 vs. No. 2[edit]

text: As of the completion of the 2015 season the number one ranked team has faced the number two ranked team 50 times since the inception of the AP Poll in 1936.[9] The number one team has a record of 28–20–2 against the number two team.[9]

text:
No. 1 vs. No. 2 games

Light blue indicates bowl game

Season
No. 1
Result
No. 2
Site
Event

1943
Notre Dame
35–12
Michigan
Michigan Stadium • Ann Arbor, MI
1943 Michigan–Notre Dame football rivalry game

1943
Notre Dame
14–13
Iowa Pre-Flight
Notre Dame Stadium • Notre Dame, IN

1944
Army
23–7
Navy
Baltimore Stadium • Baltimore, MD
1944 Army–Navy Game

1945
Army
48–0
Notre Dame
Yankee Stadium • New York, NY
1945 Army–Notre Dame football rivalry game

1945
Army
32-13
Navy
Philadelphia Municipal Stadium • Philadelphia, PA
1945 Army–Navy Game

1946
Army
0–0
Notre Dame
Yankee Stadium • New York, NY
1946 Army vs. Notre Dame football game

1962
USC
42–37
Wisconsin
Rose Bowl Stadium • Pasadena, CA
1963 Rose Bowl

1963
Oklahoma
7–28
Texas
Cotton Bowl • Dallas, TX
1963 Red River Shootout game

1963
Texas
28–6
Navy
Cotton Bowl • Dallas, TX
1964 Cotton Bowl Classic

1966
Notre Dame
10–10
Michigan State
Spartan Stadium • East Lansing, MI
1966 Notre Dame vs. Michigan State football game

1968
Purdue
37–22
Notre Dame
Notre Dame Stadium • Notre Dame, IN
1968 Shillelagh Trophy game

1968
Ohio State
27–16
USC
Rose Bowl Stadium • Pasadena, CA
1969 Rose Bowl

1969
Texas
15–14
Arkansas
Razorback Stadium • Fayetteville, AR
1969 Texas vs. Arkansas football game

1971
Nebraska
35–31
Oklahoma
Oklahoma Memorial Stadium • Norman, OK
1971 Nebraska vs. Oklahoma football game

1971
Nebraska
38–6
Alabama
Miami Orange Bowl • Miami, FL
1972 Orange Bowl

1978
Penn State
7–14
Alabama
Louisiana Superdome • New Orleans, LA
1979 Sugar Bowl

1981
USC
28–24
Oklahoma
Los Angeles Coliseum • Los Angeles

1982
Georgia
23–27
Penn State
Louisiana Superdome • New Orleans, LA
1983 Sugar Bowl

1985
Iowa
12–10
Michigan
Kinnick Stadium • Iowa City, IA

1986
Oklahoma
16–28
Miami
Miami Orange Bowl • Miami, FL

1986
Miami
10–14
Penn State
Sun Devil Stadium • Tempe, AZ
1987 Fiesta Bowl

1987
Nebraska
7–17
Oklahoma
Memorial Stadium • Lincoln, NE
1987 Nebraska–Oklahoma football rivalry game

1987
Oklahoma
14–20
Miami
Miami Orange Bowl • Miami, FL
1988 Orange Bowl

1988
Notre Dame
27–10
USC
Los Angeles Coliseum • Los Angeles
1988 Jeweled Shillelagh game

1989
Notre Dame
24–19
Michigan
Michigan Stadium • Ann Arbor, MI
1989 Michigan–Notre Dame football rivalry game

1991
Florida State
16–17
Miami
Doak Campbell Stadium • Tallahassee, FL
1991 Miami vs. Florida State football game

1992
Miami
13–34
Alabama
Louisiana Superdome • New Orleans, LA
1993 Sugar Bowl

1993
Florida State
24–31
Notre Dame
Notre Dame Stadium • Notre Dame, IN
1993 Florida State vs. Notre Dame football game

1993
Florida State
18–16
Nebraska
Miami Orange Bowl • Miami, FL
1994 Orange Bowl

1995
Nebraska
62–24
Florida
Sun Devil Stadium • Tempe, AZ
1996 Fiesta Bowl

1996
Florida
21–24
Florida State
Doak Campbell Stadium • Tallahassee, FL
1996 Florida–Florida State football rivalry game

1998
Tennessee
23–16
Florida State
Sun Devil Stadium • Tempe, AZ
1999 Fiesta Bowl

1999
Florida State
46–29
Virginia Tech
Louisiana Superdome • New Orleans, LA
2000 Sugar Bowl

2002
Miami
24–31 2OT
Ohio State
Sun Devil Stadium • Tempe, AZ
2003 Fiesta Bowl

2004
USC
55–19
Oklahoma
Pro Player Stadium • Miami Gardens, FL
2005 Orange Bowl

2005
USC
38–41
Texas
Rose Bowl Stadium • Pasadena, CA
2006 Rose Bowl

2006
Ohio State
24–7
Texas
Darrell K Royal – Texas Memorial Stadium • Austin, TX

2006
Ohio State
42–39
Michigan
Ohio Stadium • Columbus, OH
2006 Michigan vs. Ohio State football game

2006
Ohio State
14–41
Florida
University of Phoenix Stadium • Glendale, AZ
2007 BCS National Championship Game

2007
Ohio State
24–38
LSU
Louisiana Superdome • New Orleans, LA
2008 BCS National Championship Game

2008
Alabama
20–31
Florida
Georgia Dome • Atlanta, GA
2008 SEC Championship Game

2008
Florida
24–14
Oklahoma
Sun Life Stadium • Miami Gardens, FL
2009 BCS National Championship Game

2009
Florida
13–32
Alabama
Georgia Dome • Atlanta, GA
2009 SEC Championship Game

2009
Alabama
37–21
Texas
Rose Bowl Stadium • Pasadena, CA
2010 BCS National Championship Game

2010
Auburn
22–19
Oregon
University of Phoenix Stadium • Glendale, AZ
2011 BCS National Championship Game

2011
LSU
9–6 OT
Alabama
Bryant–Denny Stadium • Tuscaloosa, AL
2011 LSU vs. Alabama football game

2011
LSU
0–21
Alabama
Mercedes-Benz Superdome • New Orleans, LA
2012 BCS National Championship Game

2012
Notre Dame
14–42
Alabama
Sun Life Stadium • Miami Gardens, FL
2013 BCS National Championship Game

2013
Florida State
34–31
Auburn
Rose Bowl · Pasadena, CA
2014 BCS National Championship Game

2015
Clemson
40–45
Alabama
University of Phoenix Stadium · Glendale, AZ
2016 College Football Playoff National Championship

text: AP Poll inclusion in the BCS[edit]

text: In 1997, the Bowl Championship Series (BCS) was developed to try to unify the poll results by picking two teams for a "real" national championship game. For the first several years the AP Poll factored in the determination of the BCS rankings, along with other factors including the Coaches Poll and computer-based polls. Because of a series of controversies surrounding the BCS, the AP demanded in December, 2004, that its poll no longer be used in the BCS rankings,[10] and so the 2004–2005 season was the last season that the AP Poll was used for this purpose.

text: In the 2003 season the BCS system broke down when the final BCS standings ranked the University of Southern California (USC) at No. 3 while the two human polls in the system had ranked USC at No. 1. As a result, USC did not play in the BCS' designated national championship game. After defeating another highly ranked team, Michigan, in its final game, the AP Poll kept USC at No. 1 while the Coaches Poll was contractually obligated to select the winner of the BCS game, Louisiana State University (LSU), as the No. 1 team. The resulting split national title was the very problem that the BCS was created to solve, and has been widely considered an embarrassment.[11]

text: In 2004, a new controversy erupted at the end of the season when Auburn and Utah, who both finished the regular season 12–0, were left out of the BCS title game in favor of Oklahoma who also was 12–0 and had won decisively over Colorado in the Big 12 Championship game. USC went on to a win easily over Oklahoma in the Orange Bowl while Auburn and Utah both won their bowl games, leaving three undefeated teams at the end of the season. Also, in that same year, Texas made up late ground on California (Cal) in the BCS standings and as a result grabbed a high-payout, at-large spot in the Rose Bowl. Previous to that poll, Cal had been ranked ahead of Texas in both human polls and the BCS poll. Going into their final game, the Golden Bears were made aware that while margin of victory did not affect computer rankings, it did affect human polls and just eight voters changing their vote could affect the final standings.[12] Both teams won their game that week, but the Texas coach, Mack Brown, had made a public effort to lobby for his team to be moved higher in the ranking. When the human polls were released, Texas remained behind Cal, but it had closed the gap enough so that the BCS poll (which determines placement) placed Texas above Cal, angering both Cal and its conference, the Pac-10.[13] The final poll positions had been unchanged with Cal at No. 4 AP, No. 4 coaches, and No. 6 computers polls and Texas at No. 6 AP, No. 5 coaches, and No. 4 computer polls.[13] The AP Poll voters were caught in the middle because their vote changes were automatically made public, while the votes of the Coaches poll were kept confidential. Although there had been a more substantial shift in the votes of the Coaches Poll, the only clear targets for the ire of fanatical fans were the voters in the AP Poll. While officials from both Cal and the Pac-10 called for the coaches' votes to be made public, the overtures were turned down and did little to solve the problem of AP voters. Cal went on to lose to Texas Tech in the Holiday Bowl. Texas defeated Michigan in the Rose Bowl.

text: Many members of the press who voted in the AP Poll were upset by the controversy and, at the behest of its members, the AP asked that its poll no longer be used in the BCS rankings. The 2004 season was the last season that the AP Poll was used in the BCS rankings, it was replaced in the BCS equation by the newly created Harris Interactive College Football Poll.[14]

text: Final AP football polls[edit]

text: Other media football polls[edit]

text: The AP Poll is not the only college football poll. The other major poll is the Coaches Poll, which has been sponsored by several organizations: the United Press (1950–1957), the United Press International (1958–1990), USA Today (1991–present), CNN (1991–1996), and ESPN (1997–2005). Having two major polls has led to numerous "split" national titles, where the two polls disagreed on the No. 1 team. This has occurred on eleven different occasions (1954, 1957, 1965, 1970, 1973, 1974, 1978, 1990, 1991, 1997, 2003).

text: College basketball[edit]

text: In Division I men's and women's college basketball, the AP Poll is largely just a tool to compare schools throughout the season and spark debate, as it has no bearing on postseason play. Generally, all top 25 teams in the poll are invited to the men's and women's NCAA basketball tournament, also known as March Madness. The poll is usually released every Monday and voters' ballots are made public.[15]

text: Men's basketball[edit]

text: The AP began compiling a ranking of the top 20 college men's basketball teams during the 1948–1949 season. It has issued this poll continuously since the 1950–1951 season. As of January 2018, UCLA and Duke are tied for the most appearances atop the rankings at 134 times.[16]

text: Women's basketball[edit]

text: The women's basketball poll began during the 1976–1977 season, and was initially compiled by Mel Greenberg and published by The Philadelphia Inquirer. At first, it was a poll of coaches conducted via telephone, where coaches identified top teams and a list of the Top 20 team was produced. The initial list of coaches did not include Pat Summitt, who asked to join the group, not to improve her rankings, but because of the lack of media coverage, Summitt believed it would be a good way to stay on top of who the top teams were outside of her own schedule.[17] The contributors continued to be coaches until 1994, when the AP took over administration of the poll from Greenberg, and switched to a panel of writers.[18] In 1994, Tennessee started out as No. 1 in the polls with Connecticut at No. 4. After losses by the No. 2 and No. 3 teams, Tennessee and Connecticut were ranked No. 1 and No. 2, headed into a showdown, scheduled as a special event on Martin Luther King day, the only women's basketball game scheduled on that day. Because of the unusual circumstances, the decision was made to hold off the AP voting for one day, to ensure it would be after the game. Connecticut won the game, and moved into first place in the AP poll, published on Tuesday for the only time. (Connecticut went on to complete an undefeated season.)[19] Over the history of the poll, over 255 coaches have had a team represented in polls.[20]

text: NFL football[edit]

text: Beginning in 2012, the AP began issuing a weekly pro football ranking, the AP Pro32 rankings.[21]


document_title: Anger Management (TV series)

question_text: who plays lacey's sister on anger management

question_tokens: who plays lacey 's sister on anger management

root

text: Anger Management (TV series)

text: Premise[edit]

text: The series revolves around Charlie Goodson (Sheen), a one-time minor league baseball player who struggled to take the next step because of his recurring anger issues. Thanks to a therapist, Dr. Kate Wales (Selma Blair), Charlie was able to get his issues under control and finally make it to the major leagues. But he had a relapse during a big league game, breaking a bat over his knee in anger and causing a career-ending injury.

tag: p

text: The incident inspired Charlie to return to school and become an anger management therapist. Charlie is divorced from his one-time wife, Jennifer (Shawnee Smith), on whom he cheated multiple times during his baseball-playing days. The two still see a lot of each other because they share joint custody of their teenage daughter Sam (Daniela Bobadilla), who has obsessive-compulsive disorder.

text: Charlie has a complicated relationship with Kate, who is not only his therapist, but also his best friend and a sex-only love interest. He holds regular group sessions for anger-management patients in his home, and also does anger therapy at an area prison.[7]

text:
Season
Episodes
Originally aired

First aired
Last aired

1
10
June 28, 2012 (2012-06-28)
August 23, 2012 (2012-08-23)

2
90
January 17, 2013 (2013-01-17)
December 22, 2014 (2014-12-22)

tag: table

text: Cast and characters[edit]

text: Main[edit]

text:
Charlie Sheen as Charles "Charlie" Goodson, a former professional baseball player turned anger-management therapist.[8]
Selma Blair as Dr. Kate Wales, Charlie's ex–therapist colleague and casual sex partner. (episodes 1–52, 57 and 63)
Shawnee Smith as Jennifer Goodson, Charlie's ex-wife.[note 1]
Daniela Bobadilla as Sam Goodson, Charlie and Jennifer's teenage daughter. (episodes 1–52, 54, 57 and 63)
Noureen DeWulf as Lacey Patel, Charlie's spoiled, shallow, destructive anger-management patient.
Michael Arden as Patrick, Charlie's homosexual passive-aggressive anger-management patient.
Derek Richardson as Nolan Johnson, Charlie's normally unassertive anger-management patient.
Barry Corbin as Ed, Charlie's elderly redneck anger-management patient.[9] (episodes 3–100; recurring previously)
Brian Austin Green as Sean Healy, Charlie's nemesis, who has also dated Jennifer. After Jennifer leaves him over his infidelity, Sean and Charlie become friends and tomcat around together. (episodes 45–100; recurring previously)
Laura Bell Bundy as Dr. Jordan Denby, a new psychologist and business partner for Charlie. Often Charlie's comic foil, Jordan links up sexually with Sean Healy. (episodes 47–100)[10]

tag: ul

text: Recurring[edit]

text:
Brett Butler as Brett, the female bartender at a tavern that Charlie frequents.
Michael Boatman as Michael, Charlie's neighbor and friend, who is in the real estate business. He is always freeloading off Charlie while listening to him talk about his romantic pursuits. He is especially unlucky at love.[11] (episodes 1–55, guest episode 95)
James Black as Cleo/Derek, a "gay" member of Charlie's prison anger-therapy group. In "Charlie's Patient Gets Out of Jail", Cleo is released on parole and reveals to Charlie that his real name is Derek and that he had a wife before going to prison, claiming he's only "prison gay".
Darius McCrary as Donovan, a "prison gay" member of Charlie's prison anger-therapy group; Cleo/Derek's romantic partner. (episodes 1–42)
Stephen Taylor as Wayne, a member of Charlie's prison anger-therapy group. Despite a seemingly pleasant, philosophical demeanor, he's revealed to have been a dangerous serial killer.
Aldo Gonzalez as Ernesto Sylvia, a member of Charlie's prison anger-therapy group.
Martin Sheen as Martin Goodson, Charlie's hypercritical father. (episodes 10–100)
Steve Valentine as Dr. Moore, a rival psychiatrist whom Charlie considers his archenemy. (episodes 13–44)
Anna Hutchison as Sasha, a hooker who is occasionally a real girlfriend for Charlie. She and Charlie are briefly married after a wild night in Las Vegas. (episodes 49–92)
Ajay Mehta as Sanjay Patel, Lacey's father.
Meera Simhan as Mira Patel, Lacey's mother.
Schuyler Helford as Sateen, Lacey's sister, who is frequently competing with her.
Michael Gross as Dr. Randy Warren, a "psychic psychologist" whom Charlie exposes as a fraud. He later appears in Charlie's prison therapy group. (episodes 77–80)
Elaine Hendrix as Warden Hartley, the new warden at the prison where Charlie and Jordan work. (episodes 79–83)

text: Production[edit]

text: On July 18, 2011, it was announced that a show based on the 2003 film of the same name was in development with Charlie Sheen starring in the role originally played by Jack Nicholson from the film. The series was Sheen's first acting role since he was officially fired from the hit CBS sitcom Two and a Half Men.[2]

text: On October 27, 2011, it was announced that FX had picked up the series with an initial ten-episode order which, if successful, FX would then order an additional 90 episodes under a syndication model crafted by Debmar-Mercury. On August 29, 2012 it was announced that the show would be picked up for a further 90 episodes.[12] On January 9, 2013, FX president John Landgraf said that there will essentially be "45 new episodes per year". Landgraf also announced that Martin Sheen, who guest-starred in season one as Charlie's on-screen father, would become a season two regular cast member.[13] While Martin did appear more frequently on the show, it was only in selected episodes and he was ultimately not promoted to regular cast member.

text: FX paid a $600,000-per-episode license fee for the series.[14] To boost its sagging season two ratings, FX announced that four episodes (two of them first-run) would air on FX's parent network Fox on Monday nights in June, starting June 3, 2013.[15]

text: Casting[edit]

text: Casting announcements began in January 2012, with Shawnee Smith and Selma Blair first cast as the two female leads. Smith was cast as Charlie's ex-wife and Blair was cast as Charlie's therapist and possible love interest.[16][17]

text: Several actresses tested for the two female lead roles, including Julie Benz, Jenica Bergere, Elaine Hendrix (who would get a role on the show), Kate Reinders and Nichole Hiltz.[18]

text: Next to be cast was Noureen DeWulf, in the role of Lacey, a spoiled rich girl who is sentenced to join the therapy group after shooting her boyfriend in the testicles when he cheated on her.[19] Michael Arden and Daniela Bobadilla were cast as, respectively, Patrick (an openly gay member of Charlie's therapy group) and Sam (Charlie's teenaged daughter who has obsessive-compulsive disorder).[20] Barry Corbin was cast as Ed, a cranky, bigoted Vietnam veteran and the member of the therapy group who is angry at everyone. Originally billed as a recurring character, the producers decided after just two episodes to make Ed a series regular. Derek Richardson was the last actor cast in the series, in the role of Nolan, a frequently stoned member of the therapy group whose anger issue is that he has no anger.[21]

text: Brian Austin Green, who initially made a guest appearance, was promoted to a starring role following the dismissal of Selma Blair. Denise Richards, Lindsay Lohan, Cee Lo Green, and Kerri Kenney-Silver[22] made guest appearances. Guitarist Slash made a cameo appearance. Sheen's father, Martin Sheen, who made a guest appearance in season one as Charlie's on-screen father, had an expanded role in the second season. FX president John Landgraf said, "I thought it would be a better series if it was also a multi-generational series".[13]

text: Selma Blair's dismissal[edit]

text: On June 17, 2013, TMZ reported that Sheen had told producers that he would refuse to work should Blair turn up to work that day as a result of her being the most vocal among the cast and crew[23] regarding complaints about his being a "menace" to work with – specifically questioning his punctuality and work ethic.[24] The following day, TMZ reported that Sheen had told the producers that, if they refused to fire Blair, then he would quit.[25] Later that day, Lionsgate issued a statement confirming that Blair would not be returning to the show[26] and that a new female lead role would be created to fill the void.[23]

text: The new female lead role was described as a "by-the-book psychiatrist" who joins Charlie to co-author the sex study research he and Kate had been working on before she left and moved to India.[27] On August 5, 2013, FX announced that Laura Bell Bundy would be replacing Blair as Charlie's new colleague, Dr. Jordan Denby, with production on the first episode featuring Bundy's character beginning that same day.[28] It was announced that Brian Austin Green would have an expanded role following Blair's firing. Ironically, Blair's character's final line in the series was that Sheen's Charlie Goodson character was "going to be very excited he and I can keep working together".[citation needed]

text: Potential lawsuit[edit]

text: On September 13, 2013, TMZ reported that Blair was threatening both Sheen and Lionsgate Entertainment for the $1.2 million she would have earned had she not been dismissed from the show but also noted that both sides were talking and attempting to reach a settlement. It was also reported that a decision had already been made prior to her dismissal to write her off the show as "America didn't want to see Charlie with just one girlfriend" – however, the plan was to phase the character out over eight episodes and that, once Sheen heard of Blair's comments, "that process was accelerated" and the character abruptly moved to India.[29]

text: Canceled episode[edit]

text: In June 2013, a press release for an episode titled "Charlie and Kate Have Sex for Science" stated that the episode was set to air on June 27, 2013, as the twenty-sixth episode of the season.[30] Following the aftermath of Blair's dismissal, the planned broadcast was canceled and replaced with "Charlie and the Hot Nerd" – the first episode produced without Blair.[31] The status of "Charlie and Kate Have Sex for Science" is unknown as all episodes with production codes up to, and including, 1040 (Blair's final episode) have aired. An episode with a similar title, but with different storylines, named "Charlie Does It For Science" aired on December 5, 2013.[32]

text: Broadcast[edit]

text: The original broadcast was within the United States of America on the cable channel FX from June 28, 2012, and was later broadcast via free-to-air the Fox network from June 3, 2013.[1] In Canada the series premiered on CTV on August 12, 2012.[33][34] New episodes later aired on M3. In the United Kingdom/Ireland it premiered on Comedy Central on September 12, 2012.[35][36] Anger Management began airing in Australia on the Nine Network on August 14, 2012, and in New Zealand on TVNZ's TV2 from August 15, 2012.[37][38]

text: Critical reception[edit]

text: Anger Management received largely negative reviews. Based on 33 reviews collected by Rotten Tomatoes, the first season of Anger Management received an average 21% overall "Rotten" approval rating; the website's consensus states, "Anger Management is aggressively so-so, with thin characters and a few groan-worthy gags for every good one."[39]

text: Metacritic gave the first season of the show a score of 44 out of 100 based on 33 critics' reviews.[40] Linda Stasi of the New York Post called the series "not so bad", adding "Anger Management is pretty conventional up to and including an idiot laugh track—and a character named Charlie—again. But maybe the familiar is what will keep crazy Charlie [Sheen] from killing himself and others in a blind, drunken, psycho haze on set. Or maybe not."[41] The Wall Street Journal's Nancy DeWolf Smith thought the series was "usually funny, often clever" and added "The accomplishment here is that tight writing and editing, a solid cast with good timing and Mr. Sheen's chops as the ne plus ultra of sitcom performers, make the whole thing feel, if not entirely fresh—then crisp."[42]

text: Alan Sepinwall of HitFix stated: "Anger Management is Charlie Sheen doing what Charlie Sheen does—on-screen. It's not artful, it's not elegant ... It will likely give his fans what they want. And if there are enough of them to trigger the order for the extra 90 episodes, then FX, Helford and everyone else will feel justified in taking another chance on the guy, despite what happened in the past."[43]

text: The Huffington Post's Maureen Ryan stated: "despite the careful attention to image enhancement possibilities, the core ugliness and toxic narcissism of 'Anger Management' are impossible to ignore. ... Whoever 'Anger Management' benefits – and it certainly won't be viewers used to FX's usual scripted fare – whole enterprise is really just image management. Nice work if you can get it."[44] Anger Management was renewed for 90 more episodes, and production started on September 24, 2012.

text: Home media[edit]

text:
Title
DVD release
Notes

Region 1
Region 2
Region 4

Season One
January 8, 2013
January 14, 2013
April 30, 2014

Contains all 10 episodes from Season One
Available in both DVD and Blu-ray format in the United States and Canada
Available only on DVD format in UK
Available only on DVD format in Australia

Volume Two
October 15, 2013
October 21, 2013
TBA

Contains episodes 1–22 from Season Two
Available on both DVD and Blu-ray format in the United States and Canada
Available only on DVD format in the UK

Volume Three
April 15, 2014
TBA
TBA

Contains episodes 23–46 from Season Two
Available on both DVD and Blu-ray format in the United States and Canada

text: Notes[edit]

text: Jump up ^ While still credited among the main cast every episode, Smith's role in the series was greatly reduced and from late 2013 she only appeared in a small number of episodes.

tag: ol


document_title: Nathan Riggs

question_text: how do owen and riggs know each other

question_tokens: how do owen and riggs know each other

text: Nathan Riggs

text: Storylines[edit]

text: Nathan Riggs is introduced in the sixth episode of the show's twelfth season as a new cardio attending at Grey-Sloan Memorial. It is quickly learned that he and Owen Hunt (Kevin McKidd) had been friends, but that their friendship ended acrimoniously. It is later revealed that Nathan and Owen's feud was caused by the disappearance of Owen's sister, Megan. Megan, who had been engaged to Nathan at the time of her abduction, had discovered Nathan's infidelity before running off and ultimately getting kidnapped. Owen has long blamed Riggs for the fate of his sister, who has been presumed dead for 10 years now. However, as time goes on, Nathan and Owen learn to work together and eventually tentatively reinstate their friendship.

text: Towards the end of Season 12, Nathan sleeps with Meredith Grey (Ellen Pompeo) in the back of her car. After the incident, they both agree that it was a one-time thing, as Meredith still has trouble moving on from her late husband, Derek Shepherd (Patrick Dempsey). Meredith also learns that her half-sister, Maggie Pierce (Kelly McCreary), has developed a crush on Nathan, further separating Nathan and Meredith. Still, Nathan continues to pursue Meredith, and although she resists, they eventually begin a relationship after sleeping together again. The two stay together for some time, but just when things are on the verge of getting serious, Megan is found in the Season 13 finale. Meredith sends Nathan off to Megan, insisting that she would have done the same thing had it been Derek. Nathan and Megan initially have trouble resuming their relationship, as she believes that he is still in love with Meredith, but they finally get back together when he brings her son, Farouk, to her from Iraq, proving his loyalty to her. In "Danger Zone", Nathan moves to Los Angeles with Megan and Farouk to start their lives together.

text: Departure[edit]

text: Nathan made his last appearance in the season 14 episode "Danger Zone". The episode was designed as the departure for series regular Martin Henderson,[1] having joined the cast in 2015 and conceived originally as the love interest for Meredith.

text: Shonda Rhimes announced the exit of Martin Henderson as Nathan Riggs via Twitter: "I loved that we were able to give Riggs a happy ending worthy of his character and talent. As for Martin, this is not an ending for our relationship. He has been  part of the Shondaland family since the pilot of Inside the Box and he will always be family. I can’t wait to find a new project to work with him on in the future." Henderson indicated in an interview with Deadline that his departure was a storytelling based decision, as he was given a "short-term contract", adding, "This [was] my final year so I was expecting Nathan’s storyline to be wrapped up."[2]

text: Henderson shared his thoughts on his relationships with both Megan and Meredith

text: I think there was clearly something for Nathan in those relationships. Feelings like that, I don’t think they go away. The nature of his previous commitment to Megan and his feelings around that put him in a horrible state of having to choose between two people he cares about, but honoring his commitment to Megan and following through on that is the right thing to do. It doesn’t negate his feelings for Meredith. The complications of Meredith’s emotions, the loss of Derek and moving on from that still plagues her. And there’s as much ambiguity around all those feelings. The two of them found each other and that provided good drama. I feel bad for fans who were keen on Meredith and Nathan making it, and not being privy to where each character would go. It’s hard to hear those outpourings from those who didn’t know it was going to end up like this. But it makes for nice drama and it’s something that Shonda does brilliantly: Dashing people’s hopes and expectations. That’s why the show continues to be successful. You can’t predict what will happen to people at any time.[3]


document_title: MDMA

question_text: where did the name molly come from for the drug

question_tokens: where did the name molly come from for the drug

text: MDMA

text: Effects

text: In general, MDMA users report feeling the onset of subjective effects within 30–60 minutes of MDMA consumption and reaching the peak effect at 75–120 minutes, which then plateaus for about 3.5 hours.[28] The desired short-term psychoactive effects of MDMA have been reported to include:

text:
Euphoria – a sense of general well-being and happiness[13][14]
Increased self-confidence, sociability and feelings of communication being easy or simple[4][13][14]
Entactogenic effects – increased empathy or feelings of closeness with others[13][14] and oneself[4]
Relaxation and reduced anxiety[4]
Increased emotionality[4]
A sense of inner peace[14]
Mild hallucination[14]
Enhanced sensation, perception, or sexuality[4][13][14]
Altered sense of time[16]

text: The experience elicited by MDMA depends on the dose, setting, and user.[4] The variability of the induced altered state by MDMA is lower compared to other psychedelics. For example, MDMA used at parties is associated with high motor activity, reduced sense of self-identity as well as poor awareness of the background surroundings. Use of MDMA individually or in a small groups in a quiet environment and when concentrating, is associated with increased lucidity, capability of concentration, sensitivity of aesthetic aspects of the background and emotions, as well as greater capability of communication with others.[10][29] In psychotherapeutic settings MDMA effects have been described by infantile ideas, alternating phases of mood, sometimes memories and moods connected with childhood experiences.[29][30]

text: Sometimes MDMA is labelled as an “empathogenic” drug, because of its empathy-producing effects.[31][32] Results of different studies show its effects of powerful empathy with others.[31] When testing the MDMA for medium and high dosage ranges it showed increase on hedonic as well as arousal continuum.[33][34] The effect of MDMA increasing sociability is consistent, however effects on empathy have been more mixed.[35]

text: Use

text: Recreational

text: MDMA is often considered the drug of choice within the rave culture and is also used at clubs, festivals and house parties.[10] In the rave environment, the sensory effects from the music and lighting are often highly synergistic with the drug. The psychedelic amphetamine quality of MDMA offers multiple reasons for its appeal to users in the rave setting. Some users enjoy the feeling of mass communion from the inhibition-reducing effects of the drug, while others use it as party fuel because of the drug's stimulatory effects.[36] MDMA is used less frequently than other stimulants, typically less than once per week.[37]

text: MDMA is sometimes taken in conjunction with other psychoactive drugs known as such as LSD, psilocybin mushrooms, and ketamine, an act called "candy-flipping".[38]

text: Medical

text: As of 2017[update], MDMA has no accepted medical indications.[6][39][40] Before it was widely banned, it saw limited use in therapy.[4][6][41]

text: Other

text: A small number of therapists continue to use MDMA in therapy despite its illegal status.[42][43]

text: Small doses of MDMA are used as an entheogen to enhance prayer or meditation by some religious practitioners.[44] MDMA has been used as an adjunct to New Age spiritual practices.[45]

text: Forms

text: MDMA has become widely known as ecstasy (shortened "E", "X", or "XTC"), usually referring to its tablet form, although this term may also include the presence of possible adulterants or dilutants. The UK term "mandy" and the US term "molly" colloquially refer to MDMA in a crystalline powder form that is thought to be free of adulterants.[8][9][46] MDMA is also sold in the form of the hydrochloride salt, either as loose crystals or in gelcaps.[47][48]

text: In part due to the global supply shortage of sassafras oil, substances that are sold as molly frequently contain no MDMA and instead contain methylone, ethylone, MDPV, mephedrone, or any other of the group of compounds commonly known as bath salts.[9][46][47][48] Powdered MDMA ranges from pure MDMA to crushed tablets with 30–40% purity.[6] MDMA tablets typically have low purity due to bulking agents that are added to dilute the drug and increase profits (e.g., lactose) and binding agents.[6] Tablets sold as ecstasy sometimes contain 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxyethylamphetamine (MDEA), other amphetamine derivatives, caffeine, opiates, or painkillers.[4] Some tablets contain little or no MDMA.[4][6][12] The proportion of seized ecstasy tablets with MDMA-like impurities has varied annually and by country.[6] The average content of MDMA in a preparation is 70 to 120 mg with the purity having increased since the 1990s.[4]

text: MDMA is usually consumed by mouth. It is also sometimes snorted.[15]

text: Adverse effects

text: Short-term

text: The most serious short-term physical health risks of MDMA are hyperthermia and dehydration.[14][49] Cases of life-threatening or fatal hyponatremia (excessively low sodium concentration in the blood) have developed in MDMA users attempting to prevent dehydration by consuming excessive amounts of water without replenishing electrolytes.[14][49][50]

text: The immediate adverse effects of MDMA use can include:

text:
Dehydration[10][14][49]
Hyperthermia[4][10][49]
Bruxism (grinding and clenching of the teeth)[4][10][13]
Increased wakefulness or insomnia[4][14]
Increased perspiration and sweating[14][49]
Increased heart rate and blood pressure[4][10][49]
Increased psychomotor activity[4]
Loss of appetite[4][12]
Nausea and vomiting[13]
Diarrhea[14]
Erectile dysfunction[4][51]
Visual and auditory hallucinations (rarely)[4]
Mydriasis[4]

text: The adverse effects that last up to a week[13][52] following cessation of moderate MDMA use include:

text:
Trismus[13]
Loss of appetite[52]
Insomnia[52]
Tiredness or lethargy[53][54]

text:
Anxiety or paranoia[52]
Depression[13][52]
Irritability[52]
Impulsiveness[52]
Restlessness[52]
Memory impairment[13]
Anhedonia[52]

text: Long-term

text: As of 2015[update], the long-term effects of MDMA on human brain structure and function have not been fully determined.[55] However, there is consistent evidence of structural and functional deficits in MDMA users with a high lifetime exposure.[55][56] In contrast, there is no evidence of structural or functional changes in MDMA users with only a moderate (<50 doses used and <100 tablets consumed) lifetime exposure.[56] MDMA use at high doses has been shown to produce brain lesions, a form of brain damage, in the serotonergic neural pathways of humans and animals.[3][12] It is unclear if typical MDMA users may develop neurotoxic brain lesions.[57] Long-term exposure to MDMA in humans has been shown to produce marked neurodegeneration in striatal, hippocampal, prefrontal, and occipital serotonergic axon terminals.[55][58] Neurotoxic damage to serotonergic axon terminals has been shown to persist for more than two years.[58] Elevations in brain temperature from MDMA use are positively correlated with MDMA-induced neurotoxicity.[10][55] Adverse neuroplastic changes to brain microvasculature and white matter also occur in humans using low doses of MDMA.[10][55] Reduced gray matter density in certain brain structures has also been noted in human MDMA users.[10][55] Global reductions in gray matter volume, thinning of the parietal and orbitofrontal cortices, and decreased hippocampal activity have been observed in long term users.[4] The effects established so far for recreational use of ecstasy lie in the range of moderate to large effects for SERT reduction.[59]

text: Impairments in multiple aspects of cognition, including attention, learning, memory, visual processing, and sleep have been found in regular MDMA users.[4][13][60][55] The magnitude of these impairments is correlated with lifetime MDMA usage[13][60][55] and are partially reversible with abstinence.[4] Several forms of memory are impaired by chronic ecstasy use;[13][60] however, the effect sizes for memory impairments in ecstasy users are generally small overall.[61][62] MDMA use is also associated with increased impulsivity and depression.[4]

text: Serotonin depletion following MDMA use can cause depression in subsequent days. In some cases depressive symptoms persist for longer.[4] Some studies indicate repeated recreational users of ecstasy have increased rates of depression and anxiety, even after quitting the drug.[63] Depression is one of the main factors for cessation of use.[4]

text: At high doses, MDMA induces a neuroimmune response which, through several mechanisms, increases the permeability of the blood-brain barrier, thereby making the brain more susceptible to environmental toxins and pathogens.[64][65][page needed] In addition, MDMA has immunosuppressive effects in the peripheral nervous system and pro-inflammatory effects in the central nervous system.[66]

text: During pregnancy

text: MDMA is a moderately teratogenic drug (i.e., it is toxic to the fetus).[68][69] In utero exposure to MDMA is associated with a neuro- and cardiotoxicity[69] and impaired motor functioning. Motor delays may be temporary during infancy or long-term. The severity of these developmental delays increases with heavier MDMA use.[60][70]

text: Reinforcement disorders

text: Approximately 60% of MDMA users experience withdrawal symptoms when they stop taking MDMA.[12] Some of these symptoms include fatigue, loss of appetite, depression, and trouble concentrating.[12] Tolerance to some of the desired and adverse effects of MDMA is expected to occur with consistent MDMA use.[12] A 2007 analysis estimated MDMA to have a psychological dependence and physical dependence potential roughly three fourths and four fifths that of cannabis.[67]

text: MDMA has been shown to induce ΔFosB in the nucleus accumbens.[71] Because MDMA releases dopamine in the striatum, the mechanisms by which it induces ΔFosB in the nucleus accumbens are analogous to other dopaminergic psychostimulants.[71][72] Therefore, chronic use of MDMA at high doses can result in altered brain structure and drug addiction, which occur as a consequence of ΔFosB overexpression in the nucleus accumbens.[72] MDMA is less addictive than other stimulants such as methamphetamine and cocaine.[73][74] Compared with amphetamine, MDMA and its metabolite MDA are less reinforcing.[75]

text: One study found approximately 15% of chronic MDMA users met the DSM-IV diagnostic criteria for substance dependence.[76] However, there is little evidence for a specific diagnosable MDMA dependence syndrome because MDMA is typically used relatively infrequently.[37]

text: There are currently no medications to treat MDMA addiction.[77]

text: Harm assessment

text: A 2007 UK study ranked MDMA 18th in harmfulness out of 20 recreational drugs. Rankings for each drug were based on the risk for acute physical harm, the propensity for physical and psychological dependency on the drug, and the negative familial and societal impacts of the drug. The authors did not evaluate or rate the negative impact of ecstasy on the cognitive health of ecstasy users (e.g. impaired memory and concentration).[67]

text: Overdose

text: MDMA overdose symptoms vary widely due to the involvement of multiple organ systems. Some of the more overt overdose symptoms are listed in the table below. The number of instances of fatal MDMA intoxication is low relative to its usage rates. In most fatalities MDMA was not the only drug involved. Acute toxicity is mainly caused by serotonin syndrome and sympathomimetic effects.[76] MDMA's toxicity in overdose may be exacerbated by caffeine, with which it is frequently cut (mixed with to increase volume).[78] A scheme for management of acute MDMA toxicity has been published focusing on treatment of hyperthermia, hyponatraemia, seratonin syndrome, and multiple organ failure.[79]

text:
Symptoms of overdose

System
Minor or moderate overdose[80]
Severe overdose[80]

Cardiovascular

Disseminated intravascular coagulation[14]
Intracranial hemorrhage[14]
Severe hypertension[14][81] or hypotension[14]
Hypotensive bleeding[4]

Central nervous
system

Abnormally fast reflexes[82]
Agitation[14][81]
Mental confusion[14]
Paranoia[14][81]
Stimulant psychosis[4][10]

Cognitive and memory impairment[14] potentially to the point of retrograde or anterograde amnesia[83]
Coma[10][81]
Convulsions[14][81]
Hallucinations[14][81]
Loss of consciousness[10]
Serotonin syndrome[10][14][50]

Musculoskeletal

Muscle rigidity[14]
Rhabdomyolysis (i.e., rapid muscle breakdown)[14][50]

Respiratory

Acute respiratory distress syndrome[14]

Urinary

Acute kidney injury[14][84]

Other

Cerebral edema[10]
Hepatitis[14][50]
Hyperpyrexia (a life-threatening elevation of body temperature)[14][50]
Hyponatremia (Syndrome of inappropriate antidiuretic hormone)[14][49][50]

text: Interactions

text: A number of drug interactions can occur between MDMA and other drugs, including serotonergic drugs.[12][85] MDMA also interacts with drugs which inhibit CYP450 enzymes, like ritonavir (Norvir), particularly CYP2D6 inhibitors.[12] Concurrent use of MDMA high dosages with another serotonergic drug can result in a life-threatening condition called serotonin syndrome.[4][12] Severe overdose resulting in death has also been reported in people who took MDMA in combination with certain monoamine oxidase inhibitors,[4][12] such as phenelzine (Nardil), tranylcypromine (Parnate), or moclobemide (Aurorix, Manerix).[86]

text: Pharmacology

text: Pharmacodynamics

text: MDMA acts primarily as a presynaptic releasing agent of serotonin, norepinephrine, and dopamine, which arises from its activity at trace amine-associated receptor 1 (TAAR1) and vesicular monoamine transporter 2 (VMAT2).[12][87][88] MDMA is a monoamine transporter substrate (i.e., a substrate for DAT, NET, and SERT), so it enters monoamine neurons via these neuronal membrane transport proteins;[87] by acting as a monoamine transporter substrate, MDMA produces competitive reuptake inhibition at the neuronal membrane transporters (i.e., it competes with endogenous monoamines for reuptake).[87][89] MDMA inhibits both vesicular monoamine transporters (VMATs), the second of which (VMAT2) is highly expressed within monoamine neurons at vesicular membranes.[88] Once inside a monoamine neuron, MDMA acts as a VMAT2 inhibitor and a TAAR1 agonist.[87][88]

text: Inhibition of VMAT2 by MDMA results in increased concentrations of the associated neurotransmitter (serotonin, norepinephrine, or dopamine) in the cytosol of a monoamine neuron.[88][90] Activation of TAAR1 by MDMA triggers protein kinase A and protein kinase C signaling events which then phosphorylates the associated monoamine transporters – DAT, NET, or SERT – of the neuron.[87] In turn, these phosphorylated monoamine transporters either reverse transport direction – i.e., move neurotransmitters from the cytosol to the synaptic cleft – or withdraw into the neuron, respectively producing neurotransmitter efflux and noncompetitive reuptake inhibition at the neuronal membrane transporters.[87] MDMA has ten times more affinity for uptake at serotonin transporters compared to dopamine and norepinephrine transporters and consequently has mainly serotonergic effects.[91]:1080

text: In summary, MDMA enters monoamine neurons by acting as a monoamine transporter substrate.[87] MDMA activity at VMAT2 moves neurotransmitters out from synaptic vesicles and into the cytosol;[88] MDMA activity at TAAR1 moves neurotransmitters out of the cytosol and into the synaptic cleft.[87]

text: MDMA also has weak agonist activity at postsynaptic serotonin receptors 5-HT1 and 5-HT2 receptors, and its more efficacious metabolite MDA likely augments this action.[92][93][94][95] Cortisol, prolactin, and oxytocin quantities in serum are increased by MDMA.[4] A placebo-controlled study in 15 human volunteers found 100 mg MDMA increased blood levels of oxytocin, and the amount of oxytocin increase was correlated with the subjective prosocial effects of MDMA.[96](S)-MDMA is more effective in eliciting 5-HT, NE, and DA release, while (D)-MDMA is overall less effective, and more selective for 5-HT and NE release (having only a very faint efficacy on DA release).[97]

text: MDMA is a ligand at both sigma receptor subtypes, though its efficacies at the receptors have not yet been elucidated.[98]

text: Pharmacokinetics

text: MDMA reaches maximal concentrations in the blood stream between 1.5 and 3 hours after ingestion.[99] It is then slowly metabolized and excreted, with levels of MDMA and its metabolites decreasing to half their peak concentration over the next several hours.[100] The duration of action of MDMA is usually four to six hours, after which serotonin levels in the brain are depleted.[4] Serotonin levels typically return to normal within 24–48 hours.[4]

text: Metabolites of MDMA that have been identified in humans include 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 4-hydroxy-3-methoxyamphetamine (HMA), 3,4-dihydroxyamphetamine (DHA) (also called alpha-methyldopamine (α-Me-DA)), 3,4-methylenedioxyphenylacetone (MDP2P), and 3,4-Methylenedioxy-N-hydroxyamphetamine (MDOH). The contributions of these metabolites to the psychoactive and toxic effects of MDMA are an area of active research. 80% of MDMA is metabolised in the liver, and about 20% is excreted unchanged in the urine.[10]

text: MDMA is known to be metabolized by two main metabolic pathways: (1) O-demethylenation followed by catechol-O-methyltransferase (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) N-dealkylation, deamination, and oxidation to the corresponding benzoic acid derivatives conjugated with glycine.[80] The metabolism may be primarily by cytochrome P450 (CYP450) enzymes CYP2D6 and CYP3A4 and COMT. Complex, nonlinear pharmacokinetics arise via autoinhibition of CYP2D6 and CYP2D8, resulting in zeroth order kinetics at higher doses. It is thought that this can result in sustained and higher concentrations of MDMA if the user takes consecutive doses of the drug.[101][non-primary source needed]

text: MDMA and metabolites are primarily excreted as conjugates, such as sulfates and glucuronides.[102] MDMA is a chiral compound and has been almost exclusively administered as a racemate. However, the two enantiomers have been shown to exhibit different kinetics. The disposition of MDMA may also be stereoselective, with the S-enantiomer having a shorter elimination half-life and greater excretion than the R-enantiomer. Evidence suggests[103] that the area under the blood plasma concentration versus time curve (AUC) was two to four times higher for the (R)-enantiomer than the (S)-enantiomer after a 40 mg oral dose in human volunteers. Likewise, the plasma half-life of (R)-MDMA was significantly longer than that of the (S)-enantiomer (5.8 ± 2.2 hours vs 3.6 ± 0.9 hours).[12] However, because MDMA excretion and metabolism have nonlinear kinetics,[104] the half-lives would be higher at more typical doses (100 mg is sometimes considered a typical dose[99]).

text: Chemistry

text:
(R)-MDMA
(S)-MDMA

MDMA is a racemic mixture and exists as two enantiomers: (R)- and (S)-MDMA.

A powdered salt of MDMA

Reactors used to synthesize MDMA on an industrial scale in a clandestine chemical factory in Cikande, Indonesia

text: MDMA is in the substituted methylenedioxyphenethylamine and substituted amphetamine classes of chemicals. As a free base, MDMA is a colorless oil insoluble in water.[6] The most common salt of MDMA is the hydrochloride salt;[6] pure MDMA hydrochloride is water-soluble and appears as a white or off-white powder or crystal.[6]

text: Synthesis

text: There are numerous methods available to synthesize MDMA via different intermediates.[105][106][107][108] The original MDMA synthesis described in Merck's patent involves brominating safrole to 1-(3,4-methylenedioxyphenyl)-2-bromopropane and then reacting this adduct with methylamine.[109][110] Most illicit MDMA is synthesized using MDP2P (3,4-methylenedioxyphenyl-2-propanone) as a precursor. MDP2P in turn is generally synthesized from piperonal, safrole or isosafrole.[111] One method is to isomerize safrole to isosafrole in the presence of a strong base, and then oxidize isosafrole to MDP2P. Another method uses the Wacker process to oxidize safrole directly to the MDP2P intermediate with a palladium catalyst. Once the MDP2P intermediate has been prepared, a reductive amination leads to racemic MDMA (an equal parts mixture of (R)-MDMA and (S)-MDMA).[citation needed] Relatively small quantities of essential oil are required to make large amounts of MDMA. The essential oil of Ocotea cymbarum, for example, typically contains between 80 and 94% safrole. This allows 500 ml of the oil to produce between 150 and 340 grams of MDMA.[112]

text: Detection in body fluids

text: MDMA and MDA may be quantitated in blood, plasma or urine to monitor for use, confirm a diagnosis of poisoning or assist in the forensic investigation of a traffic or other criminal violation or a sudden death. Some drug abuse screening programs rely on hair, saliva, or sweat as specimens. Most commercial amphetamine immunoassay screening tests cross-react significantly with MDMA or its major metabolites, but chromatographic techniques can easily distinguish and separately measure each of these substances. The concentrations of MDA in the blood or urine of a person who has taken only MDMA are, in general, less than 10% those of the parent drug.[113][114][115]

text: History

text: Early research and use

text: MDMA was first synthesized in 1912 by Merck chemist Anton Köllisch. At the time, Merck was interested in developing substances that stopped abnormal bleeding. Merck wanted to avoid an existing patent held by Bayer for one such compound: hydrastinine. Köllisch developed a preparation of a hydrastinine analogue, methylhydrastinine, at the request of fellow lab members, Walther Beckh and Otto Wolfes. MDMA (called methylsafrylamin, safrylmethylamin or N-Methyl-a-Methylhomopiperonylamin in Merck laboratory reports) was an intermediate compound in the synthesis of methylhydrastinine. Merck was not interested in MDMA itself at the time.[116] On 24 December 1912, Merck filed two patent applications that described the synthesis and some chemical properties of MDMA[117] and its subsequent conversion to methylhydrastinine.[118]

text: Merck records indicate its researchers returned to the compound sporadically. A 1920 Merck patent describes a chemical modification to MDMA.[119] In 1927, Max Oberlin studied the pharmacology of MDMA while searching for substances with effects similar to adrenaline or ephedrine, the latter being structurally similar to MDMA. Compared to ephedrine, Oberlin observed that it had similar effects on vascular smooth muscle tissue, stronger effects at the uterus, and no "local effect at the eye". MDMA was also found to have effects on blood sugar levels comparable to high doses of ephedrine. Oberlin concluded that the effects of MDMA were not limited to the sympathetic nervous system. Research was stopped "particularly due to a strong price increase of safrylmethylamine", which was still used as an intermediate in methylhydrastinine synthesis. Albert van Schoor performed simple toxicological tests with the drug in 1952, most likely while researching new stimulants or circulatory medications. After pharmacological studies, research on MDMA was not continued. In 1959, Wolfgang Fruhstorfer synthesized MDMA for pharmacological testing while researching stimulants. It is unclear if Fruhstorfer investigated the effects of MDMA in humans.[116]

text: Outside of Merck, other researchers began to investigate MDMA. In 1953 and 1954, the United States Army commissioned a study of toxicity and behavioral effects in animals injected with mescaline and several analogues, including MDMA. Conducted at the University of Michigan in Ann Arbor, these investigations were declassified in October 1969 and published in 1973.[120][121] A 1960 Polish paper by Biniecki and Krajewski describing the synthesis of MDMA as an intermediate was the first published scientific paper on the substance.[116][121][122]

text: MDMA may have been in non-medical use in the western United States in 1968.[123] An August 1970 report at a meeting of crime laboratory chemists indicates MDMA was being used recreationally in the Chicago area by 1970.[121][124] MDMA likely emerged as a substitute for its analog methylenedioxyamphetamine (MDA),[125] a drug at the time popular among users of psychedelics[126] which was made a Schedule 1 substance in the United States in 1970.[127][128]

text: Shulgin's research and early use in therapy

text: American chemist and psychopharmacologist Alexander Shulgin reported he synthesized MDMA in 1965 while researching methylenedioxy compounds at Dow Chemical Company, but did not test the psychoactivity of the compound at this time. Around 1970, Shulgin sent instructions for N-methylated MDA (MDMA) synthesis to the founder of a Los Angeles chemical company who had requested them. This individual later provided these instructions to a client in the Midwest. Shulgin may have suspected he played a role in the emergence of MDMA in Chicago.[121]

text: Shulgin first heard of the psychoactive effects of N-methylated MDA around 1975 from a young student who reported "amphetamine-like content".[121] Around 30 May 1976, Shulgin again heard about the effects of N-methylated MDA,[121] this time from a graduate student in a medicinal chemistry group he advised at San Francisco State University[126][129] who directed him to the University of Michigan study.[130] She and two close friends had consumed 100 mg of MDMA and reported positive emotional experiences.[121] Following the self-trials of a colleague at the University of San Francisco, Shulgin synthesized MDMA and tried it himself in September and October 1976.[121][126] Shulgin first reported on MDMA in a presentation at a conference in Bethesda, Maryland in December 1976.[121] In 1978, he and David E. Nichols published a report on the drug's psychoactive effect in humans. They described MDMA as inducing "an easily controlled altered state of consciousness with emotional and sensual overtones" comparable "to marijuana, to psilocybin devoid of the hallucinatory component, or to low levels of MDA".[131]

text: While not finding his own experiences with MDMA particularly powerful,[130][132] Shulgin was impressed with the drug's disinhibiting effects and thought it could be useful in therapy.[132] Believing MDMA allowed users to strip away habits and perceive the world clearly, Shulgin called the drug "window".[130][133] Shulgin occasionally used MDMA for relaxation, referring to it as "my low-calorie martini", and gave the drug to friends, researchers, and others who he thought could benefit from it.[130] One such person was Leo Zeff, a psychotherapist who had been known to use psychedelic substances in his practice. When he tried the drug in 1977, Zeff was impressed with the effects of MDMA and came out of his semi-retirement to promote its use in therapy. Over the following years, Zeff traveled around the US and occasionally to Europe, eventually training an estimated four thousand psychotherapists in the therapeutic use of MDMA.[132][134] Zeff named the drug "Adam", believing it put users in a state of primordial innocence.[126]

text: Psychotherapists who used MDMA believed the drug eliminated the typical fear response and increased communication. Sessions were usually held in the home of the patient or the therapist. The role therapist was minimized in favor of patient self-discovery accompanied by MDMA induced feelings of empathy. Depression, substance abuse, relationship problems, premenstrual syndrome, and autism were among several psychiatric disorders MDMA assisted therapy was reported to treat.[128] According to psychiatrist George Greer, therapists who used MDMA in their practice were impressed by the results. Anecdotally, MDMA was said to greatly accelerate therapy.[132]

text: Rising recreational use

text: In the late 1970s and early 1980s, "Adam" spread through personal networks of psychotherapists, psychiatrists, users of psychedelics, and yuppies. Hoping MDMA could avoid criminalization like LSD and mescaline, psychotherapists and experimenters attempted to limit the spread of MDMA and information about it while conducting informal research.[128][135] Early MDMA distributors were deterred from large scale operations by the threat of possible legislation.[136] Between the 1970s and the mid-1980s, this network of MDMA users consumed an estimated 500,000 doses.[13][137]

text: A small recreational market for MDMA developed by the late 1970s,[138] consuming perhaps 10,000 doses in 1976.[127] By the early 1980s MDMA was being used in Boston and New York City nightclubs such as Studio 54 and Paradise Garage.[139][140] Into the early 1980s, as the recreational market slowly expanded, production of MDMA was dominated by a small group of therapeutically minded Boston chemists. Having commenced production in 1976, this "Boston Group" did not keep up with growing demand and shortages frequently occurred.[136]

text: Perceiving a business opportunity, Michael Clegg, the Southwest distributor for the Boston Group, started his own "Texas Group" backed financially by Texas friends.[136][141] In 1981,[136] Clegg had coined "Ecstasy" as a slang term for MDMA to increase its marketability.[133][135] Starting in 1983,[136] the Texas Group mass-produced MDMA in a Texas lab[135] or imported it from California[133] and marketed tablets using pyramid sales structures and toll-free numbers.[137] MDMA could be purchased via credit card and taxes were paid on sales.[136] Under the brand name "Sassyfras", MDMA tablets were sold in brown bottles.[135] The Texas Group advertised "Ecstasy parties" at bars and discos, describing MDMA as a "fun drug" and "good to dance to".[136] MDMA was openly distributed in Austin and Dallas-Fort Worth area bars and nightclubs, becoming popular with yuppies, college students, and gays.[125][136][137]

text: Recreational use also increased after several cocaine dealers switched to distributing MDMA following experiences with the drug.[137] A California laboratory that analyzed confidentially submitted drug samples first detected MDMA in 1975. Over the following years the number of MDMA samples increased, eventually exceeding the number of MDA samples in the early 1980s.[142][143] By the mid-1980s, MDMA use had spread to colleges around the United States.[136]:33

text: Media attention and scheduling

text: United States

text: In an early media report on MDMA published in 1982, a Drug Enforcement Administration (DEA) spokesman stated the agency would ban the drug if enough evidence for abuse could be found.[136] By mid-1984, MDMA use was becoming more noticed. Bill Mandel reported on "Adam" in a 10 June San Francisco Chronicle article, but misidentified the drug as methyloxymethylenedioxyamphetamine (MMDA). In the next month, the World Health Organization identified MDMA as the only substance out of twenty phenethylamines to be seized a significant number of times.[135]

text: After a year of planning and data collection, MDMA was proposed for scheduling by the DEA on 27 July 1984 with a request for comments and objections.[135][144] The DEA was surprised when a number of psychiatrists, psychotherapists, and researchers objected to the proposed scheduling and requested a hearing.[128] In a Newsweek article published the next year, a DEA pharmacologist stated that the agency had been unaware of its use among psychiatrists.[145] An initial hearing was held on 1 February 1985 at the DEA offices in Washington, D.C. with administrative law judge Francis L. Young presiding.[135] It was decided there to hold three more hearings that year: Los Angeles on 10 June, Kansas City, Missouri on 10–11 July, and Washington, D.C. on 8–11 October.[128][135]

text: Sensational media attention was given to the proposed criminalization and the reaction of MDMA proponents, effectively advertising the drug.[128] In response to the proposed scheduling, the Texas Group increased production from 1985 estimates of 30,000 tablets a month to as many as 8,000 per day, potentially making two million ecstasy tablets in the months before MDMA was made illegal.[146] By some estimates the Texas Group distributed 500,000 tablets per month in Dallas alone.[133] According to one participant in an ethnographic study, the Texas Group produced more MDMA in eighteen months than all other distribution networks combined across their entire histories.[136] By May 1985, MDMA use was widespread in California, Texas, southern Florida, and the northeastern United States.[123][147] According to the DEA there was evidence of use in twenty-eight states[148] and Canada.[123] Urged by Senator Lloyd Bentsen, the DEA announced an emergency Schedule I classification of MDMA on 31 May 1985. The agency cited increased distribution in Texas, escalating street use, and new evidence of MDA (an analog of MDMA) neurotoxicity as reasons for the emergency measure.[147][149][150] The ban took effect one month later on 1 July 1985[146] in the midst of Nancy Reagan's "Just Say No" campaign.[151][152]

text: As a result of several expert witnesses testifying that MDMA had an accepted medical usage, the administrative law judge presiding over the hearings recommended that MDMA be classified as a Schedule III substance. Despite this, DEA administrator John C. Lawn overruled and classified the drug as Schedule I.[128][153] Later Harvard psychiatrist Lester Grinspoon sued the DEA, claiming that the DEA had ignored the medical uses of MDMA, and the federal court sided with Grinspoon, calling Lawn's argument "strained" and "unpersuasive", and vacated MDMA's Schedule I status. Despite this, less than a month later Lawn reviewed the evidence and reclassified MDMA as Schedule I again, claiming that the expert testimony of several psychiatrists claiming over 200 cases where MDMA had been used in a therapeutic context with positive results could be dismissed because they weren't published in medical journals.[128][citation needed] No double blind studies had yet been conducted as to the efficacy of MDMA for therapy.[citation needed]

text: United Nations

text: While engaged in scheduling debates in the United States, the DEA also pushed for international scheduling.[146] In 1985 the World Health Organization's Expert Committee on Drug Dependence recommended that MDMA be placed in Schedule I of the 1971 United Nations Convention on Psychotropic Substances. The committee made this recommendation on the basis of the pharmacological similarity of MDMA to previously scheduled drugs, reports of illicit trafficking in Canada, drug seizures in the United States, and lack of well-defined therapeutic use. While intrigued by reports of psychotherapeutic uses for the drug, the committee viewed the studies as lacking appropriate methodological design and encouraged further research. Committee chairman Paul Grof dissented, believing international control was not warranted at the time and a recommendation should await further therapeutic data.[154] The Commission on Narcotic Drugs added MDMA to Schedule I of the convention on 11 February 1986.[155]

text: Post-scheduling

text: The use of MDMA in Texas clubs declined rapidly after criminalization, although by 1991 the drug remained popular among young middle-class whites and in nightclubs.[136]:46 In 1985, MDMA use became associated with Acid House on the Spanish island of Ibiza.[136]:50[156] Thereafter in the late 1980s, the drug spread alongside rave culture to the UK and then to other European and American cities.[136]:50 Illicit MDMA use became increasingly widespread among young adults in universities and later, in high schools. Since the mid-1990s, MDMA has become the most widely used amphetamine-type drug by college students and teenagers.[91]:1080 MDMA became one of the four most widely used illicit drugs in the US, along with cocaine, heroin, and cannabis.[133] According to some estimates as of 2004, only marijuana attracts more first time users in the US.[133]

text: After MDMA was criminalized, most medical use stopped, although some therapists continued to prescribe the drug illegally. Later,[when?] Charles Grob initiated an ascending-dose safety study in healthy volunteers. Subsequent legally-approved MDMA studies in humans have taken place in the US. in Detroit (Wayne State University), Chicago (University of Chicago), San Francisco (UCSF and California Pacific Medical Center), Baltimore (NIDA–NIH Intramural Program), and South Carolina, as well as in Switzerland (University Hospital of Psychiatry, Zürich), the Netherlands (Maastricht University), and Spain (Universitat Autònoma de Barcelona).[157]

text: "Molly", short for 'molecule', was recognized as a slang term for crystalline or powder MDMA in the 2000s.[158][159]

text: In 2010, the BBC reported that use of MDMA had decreased in the UK in previous years. This may be due to increased seizures during use and decreased production of the precursor chemicals used to manufacture MDMA. Unwitting substitution with other drugs, such as mephedrone and methamphetamine,[160] as well as legal alternatives to MDMA, such as BZP, MDPV, and methylone, are also thought to have contributed to its decrease in popularity.[161]

text: Society and culture

text:
Global estimates of illegal drug users in 2014
(in millions of users)[162]

Substance
Best
estimate
Low
estimate
High
estimate

Amphetamine-
type stimulants
35.65
15.34
55.90

Cannabis
182.50
127.54
233.65

Cocaine
18.26
14.88
22.08

Ecstasy
19.40
9.89
29.01

Opiates
17.44
13.74
21.59

Opioids
33.12
28.57
38.52

text: Legal status

text: MDMA is legally controlled in most of the world under the UN Convention on Psychotropic Substances and other international agreements, although exceptions exist for research and limited medical use. In general, the unlicensed use, sale or manufacture of MDMA are all criminal offences.

text: Australia

text: In Australia, MDMA was declared an illegal substance in 1986 because of its harmful effects and potential for abuse. It is classed as a Schedule 9 Prohibited Substance in the country, meaning it is available for scientific research purposes only. Any other type of sale, use or manufacture is strictly prohibited by law. Permits for research uses on humans must be approved by a recognized ethics committee on human research.

text: In Western Australia under the Misuse of Drugs Act 1981 4.0g of MDMA is the amount required determining a court of trial, 2.0g is considered a presumption with intent to sell or supply and 28.0g is considered trafficking under Australian law.[163]

text: United Kingdom

text: In the United Kingdom, MDMA was made illegal in 1977 by a modification order to the existing Misuse of Drugs Act 1971. Although MDMA was not named explicitly in this legislation, the order extended the definition of Class A drugs to include various ring-substituted phenethylamines.[164][165] The drug is therefore illegal to sell, buy, or possess the drug without a licence in the UK. Penalties include a maximum of seven years and/or unlimited fine for possession; life and/or unlimited fine for production or trafficking.

text: Some researchers such as David Nutt have criticized the current scheduling of MDMA, what he determined to be a relatively harmless drug.[166][167] An editorial he wrote in the Journal of Psychopharmacology, where he compared the risk of harm for horse riding (1 adverse event in 350) to that of ecstasy (1 in 10,000) resulted in his dismissal as well as the resignation of his colleagues from the ACMD.[168]

text: United States

text: In the United States, MDMA is currently placed in Schedule I of the Controlled Substances Act.[169] In a 2011 federal court hearing the American Civil Liberties Union successfully argued that the sentencing guideline for MDMA/ecstasy is based on outdated science, leading to excessive prison sentences.[170] Other courts have upheld the sentencing guidelines. The United States District Court for the Eastern District of Tennessee explained its ruling by noting that "an individual federal district court judge simply cannot marshal resources akin to those available to the Commission for tackling the manifold issues involved with determining a proper drug equivalency."[171]

text: Netherlands

text: In the Netherlands, the Expert Committee on the List (Expertcommissie Lijstensystematiek Opiumwet) issued a report in June 2011 which discussed the evidence for harm and the legal status of MDMA, arguing in favor of maintaining it on List I.[171][172][173]

text: Canada

text: In Canada, MDMA is listed as a Schedule 1[174] as it is an analogue of amphetamine.[175] The CDSA was updated as a result of the Safe Streets Act changing amphetamines from Schedule III to Schedule I in March 2012.

text: Demographics

text: In 2014, 3.5% of 18 to 25 year-olds had used MDMA in the United States.[4] In Europe, an estimated 37% of regular club-goers aged 14 to 35 used MDMA in the past year according to the 2015 European Drug report.[4] The highest one-year prevalence of MDMA use in Germany in 2012 was 1.7% among people aged 25 to 29 compared with a population average of 0.4%.[4] Among adolescent users in the United States between 1999 and 2008, girls were more likely to use MDMA than boys.[176]

text: Economics

text: Europe

text: In 2008 the European Monitoring Centre for Drugs and Drug Addiction noted that although there were some reports of tablets being sold for as little as €1, most countries in Europe then reported typical retail prices in the range of €3 to €9 per tablet, typically containing 25–65 mg of MDMA.[177] By 2014 the EMCDDA reported that the range was more usually between €5 and €10 per tablet, typically containing 57–102 mg of MDMA, although MDMA in powder form was becoming more common.[178]

text: North America

text: The United Nations Office on Drugs and Crime stated in its 2014 World Drug Report that US ecstasy retail prices range from US$1 to $70 per pill, or from $15,000 to $32,000 per kilogram.[179] A new research area named Drug Intelligence aims to automatically monitor distribution networks based on image processing and machine learning techniques, in which an Ecstasy pill picture is analyzed to detect correlations among different production batches.[180] These novel techniques allow police scientists to facilitate the monitoring of illicit distribution networks.

text: As of October 2015[update], most of the MDMA in the United States is produced in British Columbia, Canada and imported by Canada-based Asian transnational criminal organizations.[46] The market for MDMA in the United States is relatively small compared to methamphetamine, cocaine, and heroin.[46] In the United States, about 0.9 million people used ecstasy in 2010.[15]

text: Australia

text: MDMA is particularly expensive in Australia, costing A$15–A$30 per tablet. In terms of purity data for Australian MDMA, the average is around 34%, ranging from less than 1% to about 85%. The majority of tablets contain 70–85 mg of MDMA. Most MDMA enters Australia from the Netherlands, the UK, Asia, and the US.[181]

text: Corporate logos on pills

text: A number of ecstasy manufacturers brand their pills with a logo, often being a corporate logo,[182] to help distinguish between suppliers; one of the most notable logos that appears on pills is the Mitsubishi logo.[183] Some pills depict logos of products or shows popular with children, such as Shaun the Sheep.[184]

text: Research

text: The Multidisciplinary Association for Psychedelic Studies (MAPS) is funding pilot studies and clinical trials investigating the use of MDMA in psychotherapy to treat posttraumatic stress disorder (PTSD),[43] social anxiety in autistic adults,[4][185][186][187][188] and anxiety in terminal illness.[189][190] In November 2016, the United States Food and Drug Administration (FDA) approved large-scale phase 3 clinical trials involving the use of MDMA for the treatment of PTSD in individuals who do not respond to traditional prescription drugs or psychotherapy.[23] MDMA has also been proposed as an adjunct to substance abuse treatment.[5] In 2017, doctors in the UK began the first clinical study of MDMA in alcohol addiction.[191]

text: The potential for MDMA to be used as a rapid-acting antidepressant has been studied in clinical trials, but as of 2017 the evidence on efficacy and safety were insufficient to reach a conclusion.[192] A 2014 review of the safety and efficacy of MDMA as a treatment for various disorders, particularly PTSD, indicated that MDMA has therapeutic efficacy in some patients;[60] however, it emphasized that issues regarding the control-ability of MDMA-induced experiences and neurochemical recovery must be addressed.[60] The author noted that oxytocin and D-cycloserine are potentially safer co-drugs in PTSD treatment, albeit with limited evidence of efficacy.[60] This review and a second corroborating review by a different author both concluded that, because of MDMA's demonstrated potential to cause lasting harm in humans (e.g., serotonergic neurotoxicity and persistent memory impairment), "considerably more research must be performed" on its efficacy in PTSD treatment to determine if the potential treatment benefits outweigh its potential to harm to a patient.[13][60]

text: Notes

text:
Jump up ^ The term MDMA is a contraction of 3,4-methylenedioxy-methamphetamine; it is also known as ecstasy (shortened to "E", "X", or "XTC"), mandy, and molly.[8][9] The international nonproprietary name is midomafetamine.[1]
Jump up ^ The FDA's "breakthrough therapy" designation is not intended to imply that a drug is actually a "breakthrough" or that there is high-quality evidence of treatment efficacy for a particular condition;[24][25] rather, it allows the FDA to grant priority review to drug candidates if preliminary clinical trials indicate that the therapy may offer substantial treatment advantages over existing options for patients with serious or life-threatening diseases.[25][26]