title: Georgia Guidestones

text: Right-wing activist Mark Dice demanded that the guidestones should "be smashed into a million pieces, and then the rubble should be used for a construction project", claiming that the guidestones are of "a deep Satanic origin", and that R. C. Christian belongs to "a Luciferian secret society" related to the New World Order. At the unveiling of the monument, a local minister proclaimed that he believed that the monument was "for sun worshipers, for cult worship and for devil worship".


title: Georgia Guidestones

text: Conspiracy theorist Jay Weidner has said that the pseudonym of the man who commissioned the stones – "R. C. Christian" – resembles Rose Cross Christian, or Christian Rosenkreuz, the founder of the Rosicrucian Order. Others who agree with Weidner point to the Rosicrucian’s first manifesto written in 1614, which states “The word R.C. should be their seal, mark and character”. They also see similarities between the writing on the capstone, and the title of (Rosicrucian) Thomas Paine’s “The Age of Reason”.


title: Selma Blair

text: Selma Blair Beitner (born June 23, 1972) is an American actress. She played a number of roles in films and on television before obtaining recognition for her leading role in the film "Brown's Requiem" (1998). Her breakthrough came when she starred as Zoe Bean on the WB sitcom "Zoe, Duncan, Jack and Jane" (1999–2000), and as Cecile Caldwell in the cult film "Cruel Intentions" (1999). She continued to find success with the comedies "Legally Blonde" (2001) and "The Sweetest Thing" (2002), and achieved international fame with her portrayal of Liz Sherman in the big-budget fantasy films "Hellboy" (2004) and "" (2008).


title: Selma Blair

text: Her other notable film credits include "Storytelling" (2001), "A Guy Thing" (2003), "A Dirty Shame" (2004), "The Fog" (2005), "WΔZ" (2007), "Feast of Love" (2007), "The Poker House" (2008), "Dark Horse" (2011), "In Their Skin" (2012), "Ordinary World" (2016), "Mothers and Daughters" (2016), "Mom and Dad" (2017), "After" (2019) and "A Dark Foe" (2020).


title: Selma Blair

text: On television, she starred as Kim in the American remake of "Kath & Kim" (2008–2009); as Kate Wales on the sitcom "Anger Management" (2012–2014); and as Kris Jenner in the of the FX drama series "American Crime Story" (2016). In 2010, Blair narrated the audiobook "The Diary of Anne Frank", earning a nomination for the Grammy Award for Best Spoken Word Album for Children.


title: Selma Blair

text: Blair was born on June 23, 1972, in Southfield, Michigan, a suburb of Detroit. She is the youngest of four daughters of Judge Molly Ann ("née" Cooke) and Elliot I. Beitner. Her father was an attorney, active in the U.S. Democratic Party, and labor arbitrator until his death in 2012 at the age of 82. Her parents divorced when Blair was 23; she subsequently legally changed her surname. She has three older sisters, Katherine, Elizabeth, and Marie Beitner.


title: Selma Blair

text: Her father and maternal grandfather were from Jewish families, while her maternal grandmother, who had Scottish ancestry, was Anglican. Blair formally converted to Judaism as a child, and had a Jewish upbringing; her Hebrew name is Bat-Sheva. Blair attended Hillel Day School, a Jewish day school in Farmington Hills and Cranbrook Kingswood in Bloomfield Hills soon after. She spent her freshman year (1990–1991) at Kalamazoo College, where she studied photography and acted in the play "The Little Theater of the Green Goose". At the time, she wanted to be a ballerina and a horse trainer.


title: Selma Blair

text: At the age of 20 she moved to New York City, where she lived at The Salvation Army. She attended New York University (NYU), as well as acting classes at the Stella Adler Conservatory, the Column Theatre, and the Stonestreet Screen Acting Workshop. Later, she returned to Michigan to finish her studies.


title: Selma Blair

text: After transferring from NYU, she graduated "magna cum laude" from the University of Michigan in 1994 with a triple major in photography, psychology, and English.


title: Selma Blair

text: In 1990, during her time at Cranbrook Kingswood, Blair was involved in a production of T.S. Eliot’s "Murder in the Cathedral". She considered it a failure, but her English teacher told her not to give up; that was the first time she thought she could be an actress.


title: Selma Blair

text: In 1993, she began training at acting schools in New York. An agent discovered her in an acting class, and Blair subsequently signed with her. After 75 auditions, Blair got her first advertising contract for a television spot ad for a theater in Virginia,


title: Selma Blair

text: Blair began auditioning in the mid-1990s. Her first audition was for a cereal commercial. She won her first professional role in 1995 in an episode of the children's television sitcom "The Adventures of Pete & Pete", where she portrayed the love interest of the main character, Big Pete.


title: Selma Blair

text: In 1996, she landed her first feature film role in "The Broccoli Theory", an "unromantic comedy" set in NYC. In 1997, she made her first appearance in a mainstream feature film, the Kevin Kline comedy "In & Out". She auditioned six times for the role and remained on-set for several weeks, but most of her scenes were cut from the film's final version. She obtained her first lead role in a feature film in the teen drama "Strong Island Boys", based on true events about a Long Island '80s street gang. Actor Alec Baldwin called Blair "a cross between Debra Winger and Marlene Dietrich".


title: Selma Blair

text: Later, she was selected for the lead in the fantasy film "Amazon High", co-starring with Karl Urban. She played a present-day orphaned high school student who accidentally travels back in time to the mythical days of the Amazons. The film, which also was proposed as a third show set in the Hercules and Xena mythological genre, has never been aired. Portions of the pilot were later adapted and edited into the "" episode "Lifeblood" in 2000.


title: Selma Blair

text: The same year, Blair was cast as Joey Potter on "Dawson's Creek", but was later replaced by Katie Holmes. Soon afterward, she auditioned for the title role in "Buffy the Vampire Slayer", but Sarah Michelle Gellar was chosen. Blair starred opposite Suzanne Somers in the family drama "No Laughing Matter" as a pregnant teenager. She subsequently appeared in several independent and short productions, including "Debutante", opposite Josh Hartnett, which was shot in NYC and won multiple awards after its premiere in September 1998.


title: Selma Blair

text: In 1998, Blair starred opposite Dominique Swain in the teen drama "Girl"; and in the suspense thriller "Brown's Requiem", based on the crime novel of that name.


title: Selma Blair

text: That year, she also appeared in My Friend Steve's music video for the song "Charmed" (which was also the opening theme for the first season of "Zoe, Duncan, Jack and Jane" in 1999); and in the music video for the single "Every You Every Me" by the British alternative rock band Placebo, which was featured on the "Cruel Intentions" soundtrack.


title: Selma Blair

text: Following several auditions, independent film roles, and guest roles in television series, Blair achieved her breakthrough opposite Sarah Michelle Gellar and Ryan Phillippe in the 1999 coming-of-age drama "Cruel Intentions", loosely based on the 18th-century novel "Les Liaisons dangereuses". It received mixed reviews, with "Variety" finding "newcomer" Blair " too broad" and "overdoing [her role]'s clumsiness". Nevertheless, the film made an impressive US$75.9 million internationally, and brought Blair an MTV Movie Award nomination for "Best Breakthrough Performance" and a win for "Best Kiss", shared with Gellar. "Cruel Intentions" has since developed a cult following.


title: Selma Blair

text: Blair went on to star as Zoe Bean on "Zoe, Duncan, Jack and Jane", alongside Azura Skye and Michael Rosenbaum. The first season follows the lives of four high school classmates from Manhattan. The second season was just renamed "Zoe...", which follows the title character a few years later as a psychology student; the show was not renewed for a third season.


title: Selma Blair

text: She was nominated for the Teen Choice Awards for "TV – Breakout Performance" category for her role in "Zoe, Duncan, Jack & Jane".


title: Selma Blair

text: In 2000, Blair won a Movieline's Young Hollywood Award in the "Exciting New Face – Female Category", and portrayed a seductive college student in the teen comedy "Down to You", alongside Freddie Prinze, Jr. and Julia Stiles. A lukewarm critical and commercial response greeted the film upon its release.


title: Selma Blair

text: Her film career continued with the independent drama "Kill Me Later" opposite Max Beesley. She starred as a suicidal bank teller taken hostage during a bank robbery, who tries to persuade her captors to kill her. The film received a limited release in September 2001, in New York and Los Angeles.


title: Selma Blair

text: Blair co-starred opposite Reese Witherspoon in the comedy "Legally Blonde", portraying a preppy, snobby law student and the "rival" for the affections of Witherspoon's ex-boyfriend. "The Hollywood Reporter" found her to be a "strong presence" in her role, "coming on as a bitch initially, then softening into feminine solidarity with [Witherspoon's] heroine". The film was released on July 13, 2001, topping the US box office in its opening weekend; it went on to gross US$96.5 million in North America and a worldwide total of US$141.7 million. She next starred as a college student having an affair with her professor in the controversial independent drama "Storytelling", alongside Leo Fitzpatrick. It premiered at the 2001 Cannes Film Festival, and received a limited release in most international markets. "SPLICEDwire" remarked in its review for the film that both Blair and Fitzpatrick gave "painfully authentic performances as an emotionally insecure coed and her cerebral palsy-stricken dorm neighbor and lover".


title: Selma Blair

text: She starred with Jared Leto and Jake Gyllenhaal in the crime drama "Highway", which was released directly to-DVD in March 2002. The independent film, filmed in locations of Seattle, is set in the mid-'90s grunge music scene and follows a road trip to the 1994 Kurt Cobain vigil. Blair next appeared opposite Cameron Diaz and Christina Applegate in the comedy "The Sweetest Thing", as the roommate of Diaz's character. While the film received mixed reviews, it grossed US$68.6 million worldwide. For her part, she was nominated for the Teen Choice Awards, in the "Best Actress in a Comedy" category.


title: Selma Blair

text: In 2002, Blair appeared on the cover of "Rolling Stone", and in a television commercial for The Sims Online video game. She also had a guest role in the episode "The One with Christmas in Tulsa" on the hit sitcom "Friends". In 2003, Blair co-starred with Jason Lee in the romantic comedy "A Guy Thing", playing the fiancé of a man who wakes up after his bachelor party in bed with another woman (played by Julia Stiles). The film received negative reviews and made a lackluster US$15.5 million at the North American box office.


title: Selma Blair

text: She filmed supporting parts for the independent road film "Dallas 362" (2003) and the well-received comedy-drama "In Good Company" (2004), and appeared alongside former NBA star John Salley and Judy Davis in the television movie "Coast to Coast". In 2004, Blair took on the role of Liz Sherman, a depressed pyrokinetic superhero, in Guillermo del Toro's blockbuster fantasy film "Hellboy", co-starring Ron Perlman. Based on Mike Mignola's popular comic book series, the film was favorably received by critics; "The New York Times" remarked: "Blair's heavy-lidded eyes seem to be at half mast from some lovely lewd fantasy. With her sleepy carnality and dry, hesitant timing, she is a superb foil for Mr. Perlman's plain-spoken bravado." "Hellboy" topped the box office in the U.S. and Canada in its opening weekend, and ultimately grossed US$99.3 million around the globe.


title: Selma Blair

text: Also in 2004, Blair played the role of an exhibitionist dancer in John Waters' satirical sex comedy "A Dirty Shame", alongside Tracey Ullman. The film received a limited theatrical run in North America, garnering an overall mixed response; "A.V. Club" described the production as a "proud retreat back into the sandbox of sexual juvenilia" and a "potty-mouthed manifesto from an elder statesman of shock", while positively pointing out that both Blair and Ullman "throw themselves headfirst into the insanity, reveling in the forfeiture of dignity, self-respect, and self-consciousness their roles demand". Blair took part on the social project "The 1 Second Film" as a producer, and was included on the "FHM" list of "The 100 Sexiest Women of 2004".


title: Selma Blair

text: Blair starred as a young Harvard-trained economist involved in an international oil scandal in the political thriller "The Deal" (2005), opposite Christian Slater and Angie Harmon. It received limited release in the United States and the United Arab Emirates. She next played supporting role in the independent black comedy "Pretty Persuasion" (2005), starring Evan Rachel Wood. Her last film release in 2005 was the John Carpenter-produced remake "The Fog", in which she did her own stunts, and spent 12 hours in a water tank over two days to shoot her underwater scenes. The film, co-starring Tom Welling and Maggie Grace, met with overwhelmingly negative reviews, and grossed a modest US$46.2 million worldwide. Blair also starred with Elias Koteas in the fantasy short film "The Big Empty", based on the story "The Specialist" and produced by George Clooney. It revolved around a young woman with a psychosomatic medical condition.


title: Selma Blair

text: Blair starred in the dysfunctional family drama "The Night of the White Pants", with Nick Stahl. The film premiered through a limited theatrical run in NYC in 2006. She also appeared in a small role in the comedy-drama "The Alibi" (2006). In 2007, Blair took on the lead role in Edward Burns' "Purple Violets", a romantic comedy co-starring Burns, Patrick Wilson and Debra Messing. In the film, Blair played a frustrated and lonely writer who falls in love with her childhood sweetheart. It premiered at the Tribeca Film Festival and was the first feature film to debut exclusively on the iTunes Store.


title: Selma Blair

text: She co-starred in Robert Benton's romantic dramedy "Feast of Love" (2007), opposite Greg Kinnear and Morgan Freeman, portraying a woman who begins a lesbian relationship due to her marital frustrations. The film received mixed critical reviews upon its limited theatrical premiere in North America.


title: Selma Blair

text: She next appeared in the British crime thriller "WΔZ" (2007), opposite Stellan Skarsgård, Melissa George and Tom Hardy. Blair starred as a lab assistant who is sexually assaulted by a criminal gang, and becomes a serial killer after watching her mother's death. The film had a limited theatrical run, but was favorably


title: Selma Blair

text: In 2008, she reprised her role of Liz Sherman in "", where her character has a larger role in the storyline than its predecessor. The film garnered largely positive reviews from critics and became a worldwide commercial success, grossing US$160 million. She was nominated for the Scream Awards for Best Actress in a Fantasy Movie or TV Show.


title: Selma Blair

text: In 2008, Blair starred as a drug-addicted and alcoholic mother in Lori Petty's independent drama "The Poker House", opposite Jennifer Lawrence (in her breakthrough role) and Chloë Grace Moretz, who starred as her daughters. The film is set in 1976 and was based on Petty's real story, in which she and her two little sisters were abused by their mother and a violent pimp. The production initially had a 2008 limited release in theaters only, but was later re-released in 2015 in the UK as "Behind Closed Doors"; it received generally favorable reviews from critics, with "The Hollywood Reporter" considering her performance one of the best of her film career. Blair worked with Antonio Banderas and Meg Ryan in the comedy "My Mom's New Boyfriend" (2008), where she played a young FBI agent. The movie was screened only in Latin American cinemas and went straight-to-DVD in Anglo America.


title: Selma Blair

text: Blair accepted the titular role on the NBC sitcom "Kath & Kim", opposite Molly Shannon. The sitcom was based on the Australian television series of the same name about a mother and daughter who are obsessed with celebrity culture. Blair had to gain weight and use hair extensions to play her role as Kim, a self-absorbed suburban young princess who is forced to reassess her relationship with her mother. The series was canceled after one season. Blair also appeared with Rainn Wilson singing "Baby, It's Cold Outside" for the 2008 Gap winter ad campaign, and was included in "Glamour's" list of the 50 Most Glamorous Women of 2008.


title: Selma Blair

text: In 2009, Blair returned to the stage, when she took on the lead role of Kayleen in Rajiv Joseph's "Gruesome Playground Injuries", opposite stage actor Brad Fleischer. The drama made its world premiere at Houston's Alley Theatre on October 16, 2009, to largely positive reviews. In 2010, Blair lent her voice to narrate "The Diary of a Young Girl: The Definitive Edition", originally written by Holocaust victim Anne Frank. The audiobook received generally positive reviews from critics and readers. Her performance received a 2011 Grammy Award for Best Spoken Word Album for Children nomination.


title: Selma Blair

text: Blair starred in the music video for Danko Jones' "Full of Regret"; the video also featured Elijah Wood and Lemmy Kilmister. She next had a guest role in three episodes of the online series "Web Therapy" starring Lisa Kudrow, and appeared as a guest judge in Heidi Klum's fashion reality show "Project Runway". She appeared in a supporting role as a lesbian teacher in the small-scale black comedy "The Family Tree" (2011), with Madeline Zima, and starred in the psychological thriller "Columbus Circle", with Amy Smart and Giovanni Ribisi, playing an agoraphobic heiress who has to face her fears after she killed a man in her apartment. Filming for "Columbus Circle" took place in 2009, but the movie received a straight-to-DVD release in March 2012.


title: Selma Blair

text: In 2011, Blair appeared as guest-star in the "Portlandia" episode "Blunderbuss", appeared in "Animal Love", a short college film about life in the post global warming world premiered at the Los Angeles Film Festival, and also starred in the comedic short film "The Break-In", directed by Jaime King. In the independent comedy-drama "Dark Horse" (2011), Blair starred with Christopher Walken, Mia Farrow and Jordan Gelber, reprising her role of "Storytelling" (2001), who has become an "overmedicated depressive" woman. "Dark Horse" received a limited theatrical release and garnered a positive response from critics. "A.V. Club" felt that "the scenes between Gelber and Blair are the strongest in [in the film], because they form a bond not out of shared interests or passion, but a weary kind of compromise".


title: Selma Blair

text: In 2012, Blair starred in the short film "Slideshow of Wieners: A Love Story", a satirical love story about the Internet. Shortly after, she returned to the small screen as the female lead with the premiere of FX's "Anger Management" co-starring Charlie Sheen. She starred in 53 episodes as Dr. Kate Wales, Sheen's neurotic therapist and love interest.


title: Selma Blair

text: The series premiered to mixed critical reviews, but broke ratings records with 5.74 million viewers in its debut and ranks as the most-watched sitcom premiere in cable history. Blair left the show in June 2013, during the shooting of the second season due to disagreements with Sheen.


title: Selma Blair

text: In 2012, Blair narrated Xfinity TV commercials, including the London 2012 Olympics ads, and reprised her role as a woman who pretends she is pregnant in two episodes of the reformatted television version of "Web Therapy". She starred opposite Rachel Miner and James D'Arcy in the thriller "In Their Skin" (2012), about a woman and her family who suffer a brutal home invasion by their psychopathic neighbors after the death of their daughter. It received a mixed critical response after its world premiere at the Tribeca Film Festival, and had a limited theatrical release in North America.


title: Selma Blair

text: In 2013, Blair was the voice of Destiny in the IFC's animated series "Out There". She also had a guest role on the season two of the TV series "Comedy Bang! Bang!". In August 2014, she obtained her first small-screen role since she left "Anger Management" when she was cast as Joanna in the Amazon's comedy pilot "Really" alongside Sarah Chalke. The comedy, about the complicated life of a group of friends in their 30s is, as of May 2015, available only in the US and the UK.


title: Selma Blair

text: Blair starred in the drama "Sex, Death And Bowling" (2015), alongside Adrian Grenier and Bailey Chase. The film is about the marriage of an American soldier who fought in the American intervention in Iraq and who has terminal pancreatic cancer. The film began shooting in October 2013, and was released in selected American theaters in October 2015. Blair also starred with Green Day punk rock frontman Billie Joe Armstrong in the musical drama "Ordinary World" (2016), as the hard-working lawyer wife of Armstrong's aging rock star character. The production premiered at the Tribeca Film Festival in April 2016.


title: Selma Blair

text: In February 2016, Blair returned to television in the FX miniseries "American Crime Story: The People vs. O. J. Simpson", where she appeared with Cuba Gooding Jr., John Travolta, and David Schwimmer, portraying Kris Jenner, the former wife of Simpson's attorney Robert Kardashian. The project recreated the 1995 publicized O. J. Simpson murder case, and aired to critical and popular acclaim. Also in 2016, Blair starred as a "single, unfulfilled rock photographer" in the independent drama "Mothers and Daughters", as part of a large ensemble cast, consisting of Susan Sarandon, Sharon Stone, Mira Sorvino and Courteney Cox. The film was released on 6 May 2016 for digital markets and received largely mixed reviews. "The Hollywood Reporter" found the "talented actresses" involved to be "hamstrung" by the film's "unsubtle script that piles on far too many melodramatic plot contrivances for a 90-minute [production]", and remarked that while Blair's "voiceover narration promises to be a connective thread, [her] device is quickly abandoned, with the profusion of barely interconnected characters".


title: Selma Blair

text: In June 2016, Blair was cast alongside Nicolas Cage and Anne Winters in Brian Taylor's horror comedy film, "Mom and Dad", which was released in theaters on January 19, 2018. The film received positive reviews from critics.


title: Selma Blair

text: On August 21, 2018, it was announced that Blair was cast in a recurring role on the Netflix science-fiction drama series, "Another Life". It ran for two seasons from 2019 to 2021 before being canceled.


title: Selma Blair

text: On September 8, 2022, Blair was announced as a contestant on season 31 of "Dancing with the Stars". She is partnered with Sasha Farber. In the fifth week of the competition, at the advice of her doctors, Blair departed the competition because of her deteriorating health.


title: Selma Blair

text: During the early 2000s, Blair appeared twice on the cover of the "Vanity Fair Hollywood Issue"; as one of "Hollywood's Next Wave of Stars." In early 2002, she appeared in a Pirelli Calendar alongside Rachael Leigh Cook.


title: Selma Blair

text: Blair is known to follow new style and fashion trends in addition to her radical hairstyle changes, lending her image to the Marc Jacobs-Brian Bowen Smith clothing line. She has worked with other fashion designers, including Karen Zambos, Martin Margiela, Isaac Mizrahi, Reinaldo Herrera, and Stella McCartney. She has been a frequent guest at New York Fashion Week, and other fashion events.


title: Selma Blair

text: On October 30, 2005, she appeared in "The New York Times Magazine" award-winning photography gallery, "The Selma Blair Witch Project: Fall’s Dark Silhouettes Have a Way of Creeping Up on You" by the art photographer Roger Ballen, at the Palau Robert in Barcelona in 2012.


title: Selma Blair

text: In 2010, Blair posed with Demi Moore and Amanda De Cadenet for a spread in "Harper's Bazaar" magazine. In 2012, she became the spokesperson for, and first actress to appear on, the "Get Real For Kids" campaign. In the spring of that year, she released "SB," a line of handbags and wallets which she designed.


title: Selma Blair

text: She has appeared on the covers and photo sessions of other magazines. In 1999, she appeared in "Seventeen", and in subsequent years, in magazines including "Vanity Fair", "Marie Claire", "Vogue", "Glamour", "Rolling Stone", "The Lab Magazine", "Interview", "Dazed & Confused", "Hunger", and "Elle". She has been the face of fashion houses Chanel, Miu Miu and GAP.


title: Selma Blair

text: In February 2018, she presented parts of the collection of Christian Siriano celebrating his 10th stage anniversary in Masonic Hall during New York Fashion Week 2018.


title: Selma Blair

text: In 1990, Blair's childhood sweetheart died in an accident at the age of 18. Recalling the event, she said, "It made me realize I have to live. Having the boy I loved not anymore on this planet, I'd better live, I'd better do something."


title: Selma Blair

text: On January 24, 2004, after six months of dating, Blair married writer and producer Ahmet Zappa (son of musician Frank Zappa) at Carrie Fisher's mansion in Beverly Hills, California. They lived in Los Angeles in a 1920s-era home they bought for $1.35 million in 2004. She filed for divorce from Zappa on June 21, 2006, citing "irreconcilable differences." In a statement to "People" magazine, a spokesperson for the couple said, "Selma and Ahmet have decided to divorce, but love each other very much and will continue to be close friends." The divorce became final in December 2006.


title: Selma Blair

text: In 2010, Blair began dating fashion designer Jason Bleick. In January 2011, her representative announced that she was pregnant with her first child, and their son was born that July. In September 2012, they announced that they had separated after two years.


title: Selma Blair

text: In October 2018, Blair revealed that she had been diagnosed with multiple sclerosis in August of that year. For years she had thought that she was suffering from minor illnesses, or even a pinched nerve, but the diagnosis finally explained her disabilities, including her occasional falling, dropping things, foggy memory, and her left side "acting like it was asking for directions from a broken GPS." She was inspired to reveal the news as a way to thank Allisa Swanson, her costume designer, who had become her unofficial "dresser" for her role in the Netflix series "Another Life", saying that Swanson "gets my legs in my pants, pulls my tops over my head, (and) buttons my coats." Blair wrote about her experiences with multiple sclerosis in her memoir, "Mean Baby: A Memoir of Growing Up", which was published in May 2022.


title: Selma Blair

text: On May 27, 2012, Blair was a special guest at the National Memorial Day Concert at the U.S. Capitol in Washington, DC. She presented the story of Brigette Cain, a war widow who lost her husband (Pfc. Norman L. Cain III) in Afghanistan.


title: Selma Blair

text: In October 2012, Blair starred in the political satire sketch "The Woman for Romney", about the campaign proposals of Mitt Romney, former Republican Party nominee for the 2012 United States presidential election. She also supported Marianne Williamson for the 2014 congressional elections.


title: Selma Blair

text: Blair enjoys child and animal care. She has practiced horseback riding since age 17. Wink, her dog since early in her acting career, died in February 2011. She collects black-and-white photographs and practices ice skating.


title: Selma Blair

text: Blair's charity work and philanthropic causes include Marc Jacobs' Skin Cancer Awareness Campaign, H&M's Fashion Against AIDS 2011 Campaign, Children's Action Network, AmFAR AIDS Research 2011, Lange Foundation (dedicated to saving homeless and abandoned animals), Bulgari-Save the Children 2012 Ad Campaign, No Kid Hungry, Staying Alive Foundation and the National Multiple Sclerosis Society. On October 2, 2015, she received the Universal Smile Award during THE SMILE GALA LA 2015 to benefit children with cleft lip and palate. She was included as one of the Silence Breakers selected as the 2017 "Time" Person of the Year. In December 2021, Michelle Pfeiffer presented Blair with the Equity in Entertainment Award at the Power 100 Women ceremony. In December 2022 she was chosen as one of the BBC's 100 women.


title: Benzodiazepine

text: Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, insomnia, and seizures. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955 and was made available in 1960 by Hoffmann–La Roche, who soon followed with diazepam (Valium) in 1963. By 1977, benzodiazepines were the most prescribed medications globally; the introduction of selective serotonin reuptake inhibitors (SSRIs), among other factors, decreased rates of prescription, but they remain frequently used worldwide.


title: Benzodiazepine

text: Benzodiazepines are depressants that enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABA receptor, resulting in sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties. High doses of many shorter-acting benzodiazepines may also cause anterograde amnesia and dissociation. These properties make benzodiazepines useful in treating anxiety, panic disorder, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal and as a premedication for medical or dental procedures. Benzodiazepines are categorized as short, intermediate, or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia; longer-acting benzodiazepines are recommended for the treatment of anxiety.


title: Benzodiazepine

text: Benzodiazepines are generally viewed as safe and effective for short-term use—about two to four weeks—although cognitive impairment and paradoxical effects such as aggression or behavioral disinhibition can occur. A minority of people have reactions such as worsened agitation or panic when they stop taking benzodiazepines. Benzodiazepines are associated with an increased risk of suicide due to aggression, impulsivity, and negative withdrawal effects. Long-term use is controversial because of concerns about decreasing effectiveness, physical dependence, benzodiazepine withdrawal syndrome, and an increased risk of dementia and cancer. In the long term, stopping benzodiazepines often leads to improved physical and mental health. The elderly are at an increased risk of both short- and long-term adverse effects, and as a result, all benzodiazepines are listed in the Beers List of inappropriate medications for older adults. There is controversy concerning the safety of benzodiazepines in pregnancy. While they are not major teratogens, uncertainty remains as to whether they cause cleft palate in a small number of babies and whether neurobehavioural effects occur as a result of prenatal exposure; they are known to cause withdrawal symptoms in the newborn.


title: Benzodiazepine

text: Taken in overdose, benzodiazepines can cause dangerous deep unconsciousness, but they are less toxic than their predecessors, the barbiturates, and death rarely results when a benzodiazepine is the only drug taken. Combined with other central nervous system (CNS) depressants such as alcohol and opioids, the potential for toxicity and fatal overdose increases significantly. Benzodiazepines are commonly used recreationally and also often taken in combination with other addictive substances, and are controlled in most countries.


title: Benzodiazepine

text: Benzodiazepines possess psycholeptic, sedative, hypnotic, anxiolytic, anticonvulsant, muscle relaxant, and amnesic actions, which are useful in a variety of indications such as alcohol dependence, seizures, anxiety disorders, panic, agitation, and insomnia. Most are administered orally; however, they can also be given intravenously, intramuscularly, or rectally. In general, benzodiazepines are well tolerated and are safe and effective drugs in the short term for a wide range of conditions. Tolerance can develop to their effects and there is also a risk of dependence, and upon discontinuation a withdrawal syndrome may occur. These factors, combined with other possible secondary effects after prolonged use such as psychomotor, cognitive, or memory impairments, limit their long-term applicability. The effects of long-term use or misuse include the tendency to cause or worsen cognitive deficits, depression, and anxiety. The College of Physicians and Surgeons of British Columbia recommends discontinuing the usage of benzodiazepines in those on opioids and those who have used them long term. Benzodiazepines can have serious adverse health outcomes, and these findings support clinical and regulatory efforts to reduce usage, especially in combination with non-benzodiazepine receptor agonists.


title: Benzodiazepine

text: Because of their effectiveness, tolerability, and rapid onset of anxiolytic action, benzodiazepines are frequently used for the treatment of anxiety associated with panic disorder. However, there is disagreement among expert bodies regarding the long-term use of benzodiazepines for panic disorder. The views range from those holding benzodiazepines are not effective long-term and should be reserved for treatment-resistant cases to those holding they are as effective in the long term as selective serotonin reuptake inhibitors (SSRIs).


title: Benzodiazepine

text: The American Psychiatric Association (APA) guidelines note that, in general, benzodiazepines are well tolerated, and their use for the initial treatment for panic disorder is strongly supported by numerous controlled trials. APA states that there is insufficient evidence to recommend any of the established panic disorder treatments over another. The choice of treatment between benzodiazepines, SSRIs, serotonin–norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and psychotherapy should be based on the patient's history, preference, and other individual characteristics. Selective serotonin reuptake inhibitors are likely to be the best choice of pharmacotherapy for many patients with panic disorder, but benzodiazepines are also often used, and some studies suggest that these medications are still used with greater frequency than the SSRIs. One advantage of benzodiazepines is that they alleviate the anxiety symptoms much faster than antidepressants, and therefore may be preferred in patients for whom rapid symptom control is critical. However, this advantage is offset by the possibility of developing benzodiazepine dependence. APA does not recommend benzodiazepines for persons with depressive symptoms or a recent history of substance use disorder. The APA guidelines state that, in general, pharmacotherapy of panic disorder should be continued for at least a year, and that clinical experience supports continuing benzodiazepine treatment to prevent recurrence. Although major concerns about benzodiazepine tolerance and withdrawal have been raised, there is no evidence for significant dose escalation in patients using benzodiazepines long-term. For many such patients, stable doses of benzodiazepines retain their efficacy over several years.


title: Benzodiazepine

text: Guidelines issued by the UK-based National Institute for Health and Clinical Excellence (NICE), carried out a systematic review using different methodology and came to a different conclusion. They questioned the accuracy of studies that were not placebo-controlled. And, based on the findings of placebo-controlled studies, they do not recommend use of benzodiazepines beyond two to four weeks, as tolerance and physical dependence develop rapidly, with withdrawal symptoms including rebound anxiety occurring after six weeks or more of use. Nevertheless, benzodiazepines are still prescribed for long-term treatment of anxiety disorders, although specific antidepressants and psychological therapies are recommended as the first-line treatment options with the anticonvulsant drug pregabalin indicated as a second- or third-line treatment and suitable for long-term use. NICE stated that long-term use of benzodiazepines for panic disorder with or without agoraphobia is an unlicensed indication, does not have long-term efficacy, and is, therefore, not recommended by clinical guidelines. Psychological therapies such as cognitive behavioural therapy are recommended as a first-line therapy for panic disorder; benzodiazepine use has been found to interfere with therapeutic gains from these therapies.


title: Benzodiazepine

text: Benzodiazepines are usually administered orally; however, very occasionally lorazepam or diazepam may be given intravenously for the treatment of panic attacks.


title: Benzodiazepine

text: Benzodiazepines have robust efficacy in the short-term management of generalized anxiety disorder (GAD), but were not shown effective in producing long-term improvement overall. According to National Institute for Health and Clinical Excellence (NICE), benzodiazepines can be used in the immediate management of GAD, if necessary. However, they should not usually be given for longer than 2–4 weeks. The only medications NICE recommends for the longer term management of GAD are antidepressants.


title: Benzodiazepine

text: Likewise, Canadian Psychiatric Association (CPA) recommends benzodiazepines alprazolam, bromazepam, lorazepam, and diazepam only as a second-line choice, if the treatment with two different antidepressants was unsuccessful. Although they are second-line agents, benzodiazepines can be used for a limited time to relieve severe anxiety and agitation. CPA guidelines note that after 4–6 weeks the effect of benzodiazepines may decrease to the level of placebo, and that benzodiazepines are less effective than antidepressants in alleviating ruminative worry, the core symptom of GAD. However, in some cases, a prolonged treatment with benzodiazepines as the add-on to an antidepressant may be justified.


title: Benzodiazepine

text: A 2015 review found a larger effect with medications than talk therapy. Medications with benefit include serotonin-noradrenaline reuptake inhibitors, benzodiazepines, and selective serotonin reuptake inhibitors.


title: Benzodiazepine

text: Benzodiazepines are sometimes used in the treatment of acute anxiety, as they bring about rapid and marked relief of symptoms in most individuals; however, they are not recommended beyond 2–4 weeks of use due to risks of tolerance and dependence and a lack of long-term effectiveness. As for insomnia, they may also be used on an irregular/"as-needed" basis, such as in cases where said anxiety is at its worst. Compared to other pharmacological treatments, benzodiazepines are twice as likely to lead to a relapse of the underlying condition upon discontinuation. Psychological therapies and other pharmacological therapies are recommended for the long-term treatment of generalized anxiety disorder. Antidepressants have higher remission rates and are, in general, safe and effective in the short and long term.


title: Benzodiazepine

text: Benzodiazepines can be useful for short-term treatment of insomnia. Their use beyond 2 to 4 weeks is not recommended due to the risk of dependence. The Committee on Safety of Medicines report recommended that where long-term use of benzodiazepines for insomnia is indicated then treatment should be intermittent wherever possible. It is preferred that benzodiazepines be taken intermittently and at the lowest effective dose. They improve sleep-related problems by shortening the time spent in bed before falling asleep, prolonging the sleep time, and, in general, reducing wakefulness. However, they worsen sleep quality by increasing light sleep and decreasing deep sleep. Other drawbacks of hypnotics, including benzodiazepines, are possible tolerance to their effects, rebound insomnia, and reduced slow-wave sleep and a withdrawal period typified by rebound insomnia and a prolonged period of anxiety and agitation.


title: Benzodiazepine

text: The list of benzodiazepines approved for the treatment of insomnia is fairly similar among most countries, but which benzodiazepines are officially designated as first-line hypnotics prescribed for the treatment of insomnia varies between countries. Longer-acting benzodiazepines such as nitrazepam and diazepam have residual effects that may persist into the next day and are, in general, not recommended.


title: Benzodiazepine

text: Since the release of non benzodiazepines in 1992 in response to safety concerns, individuals with insomnia and other sleep disorders have increasingly been prescribed nonbenzodiazepines (2.3% in 1993 to 13.7% of Americans in 2010), less often prescribed benzodiazepines (23.5% in 1993 to 10.8% in 2010). It is not clear as to whether the new non benzodiazepine hypnotics (Z-drugs) are better than the short-acting benzodiazepines. The efficacy of these two groups of medications is similar. According to the US Agency for Healthcare Research and Quality, indirect comparison indicates that side-effects from benzodiazepines may be about twice as frequent as from nonbenzodiazepines. Some experts suggest using nonbenzodiazepines preferentially as a first-line long-term treatment of insomnia. However, the UK National Institute for Health and Clinical Excellence did not find any convincing evidence in favor of Z-drugs. NICE review pointed out that short-acting Z-drugs were inappropriately compared in clinical trials with long-acting benzodiazepines. There have been no trials comparing short-acting Z-drugs with appropriate doses of short-acting benzodiazepines. Based on this, NICE recommended choosing the hypnotic based on cost and the patient's preference.


title: Benzodiazepine

text: Older adults should not use benzodiazepines to treat insomnia unless other treatments have failed. When benzodiazepines are used, patients, their caretakers, and their physician should discuss the increased risk of harms, including evidence that shows twice the incidence of traffic collisions among driving patients, and falls and hip fracture for older patients.


title: Benzodiazepine

text: Prolonged convulsive epileptic seizures are a medical emergency that can usually be dealt with effectively by administering fast-acting benzodiazepines, which are potent anticonvulsants. In a hospital environment, intravenous clonazepam, lorazepam, and diazepam are first-line choices. In the community, intravenous administration is not practical and so rectal diazepam or buccal midazolam are used, with a preference for midazolam as its administration is easier and more socially acceptable.


title: Benzodiazepine

text: When benzodiazepines were first introduced, they were enthusiastically adopted for treating all forms of epilepsy. However, drowsiness and tolerance become problems with continued use and none are now considered first-line choices for long-term epilepsy therapy. Clobazam is widely used by specialist epilepsy clinics worldwide and clonazepam is popular in the Netherlands, Belgium and France. Clobazam was approved for use in the United States in 2011. In the UK, both clobazam and clonazepam are second-line choices for treating many forms of epilepsy. Clobazam also has a useful role for very short-term seizure prophylaxis and in catamenial epilepsy. Discontinuation after long-term use in epilepsy requires additional caution because of the risks of rebound seizures. Therefore, the dose is slowly tapered over a period of up to six months or longer.


title: Benzodiazepine

text: Chlordiazepoxide is the most commonly used benzodiazepine for alcohol detoxification, but diazepam may be used as an alternative. Both are used in the detoxification of individuals who are motivated to stop drinking, and are prescribed for a short period of time to reduce the risks of developing tolerance and dependence to the benzodiazepine medication itself. The benzodiazepines with a longer half-life make detoxification more tolerable, and dangerous (and potentially lethal) alcohol withdrawal effects are less likely to occur. On the other hand, short-acting benzodiazepines may lead to breakthrough seizures, and are, therefore, not recommended for detoxification in an outpatient setting. Oxazepam and lorazepam are often used in patients at risk of drug accumulation, in particular, the elderly and those with cirrhosis, because they are metabolized differently from other benzodiazepines, through conjugation.


title: Benzodiazepine

text: Benzodiazepines are the preferred choice in the management of alcohol withdrawal syndrome, in particular, for the prevention and treatment of the dangerous complication of seizures and in subduing severe delirium. Lorazepam is the only benzodiazepine with predictable intramuscular absorption and it is the most effective in preventing and controlling acute seizures.


title: Benzodiazepine

text: Because of their muscle relaxant action, benzodiazepines may cause respiratory depression in susceptible individuals. For that reason, they are contraindicated in people with myasthenia gravis, sleep apnea, bronchitis, and COPD. Caution is required when benzodiazepines are used in people with personality disorders or intellectual disability because of frequent paradoxical reactions. In major depression, they may precipitate suicidal tendencies and are sometimes used for suicidal overdoses. Individuals with a history of excessive alcohol use or non-medical use of opioids or barbiturates should avoid benzodiazepines, as there is a risk of life-threatening interactions with these drugs.


title: Benzodiazepine

text: In the United States, the Food and Drug Administration has categorized benzodiazepines into either category D or X meaning potential for harm in the unborn has been demonstrated.


title: Benzodiazepine

text: Exposure to benzodiazepines during pregnancy has been associated with a slightly increased (from 0.06 to 0.07%) risk of cleft palate in newborns, a controversial conclusion as some studies find no association between benzodiazepines and cleft palate. Their use by expectant mothers shortly before the delivery may result in a floppy infant syndrome. Newborns with this condition tend to have hypotonia, hypothermia, lethargy, and breathing and feeding difficulties. Cases of neonatal withdrawal syndrome have been described in infants chronically exposed to benzodiazepines in utero. This syndrome may be hard to recognize, as it starts several days after delivery, for example, as late as 21 days for chlordiazepoxide. The symptoms include tremors, hypertonia, hyperreflexia, hyperactivity, and vomiting and may last for up to three to six months. Tapering down the dose during pregnancy may lessen its severity. If used in pregnancy, those benzodiazepines with a better and longer safety record, such as diazepam or chlordiazepoxide, are recommended over potentially more harmful benzodiazepines, such as temazepam or triazolam. Using the lowest effective dose for the shortest period of time minimizes the risks to the unborn child.


title: Benzodiazepine

text: The benefits of benzodiazepines are least and the risks are greatest in the elderly. They are listed as a potentially inappropriate medication for older adults by the American Geriatrics Society. The elderly are at an increased risk of dependence and are more sensitive to the adverse effects such as memory problems, daytime sedation, impaired motor coordination, and increased risk of motor vehicle accidents and falls, and an increased risk of hip fractures. The long-term effects of benzodiazepines and benzodiazepine dependence in the elderly can resemble dementia, depression, or anxiety syndromes, and progressively worsens over time. Adverse effects on cognition can be mistaken for the effects of old age. The benefits of withdrawal include improved cognition, alertness, mobility, reduced risk incontinence, and a reduced risk of falls and fractures. The success of gradual-tapering benzodiazepines is as great in the elderly as in younger people. Benzodiazepines should be prescribed to the elderly only with caution and only for a short period at low doses. Short to intermediate-acting benzodiazepines are preferred in the elderly such as oxazepam and temazepam. The high potency benzodiazepines alprazolam and triazolam and long-acting benzodiazepines are not recommended in the elderly due to increased adverse effects. Nonbenzodiazepines such as zaleplon and zolpidem and low doses of sedating antidepressants are sometimes used as alternatives to benzodiazepines.


title: Benzodiazepine

text: Long-term use of benzodiazepines is associated with increased risk of cognitive impairment and dementia, and reduction in prescribing levels is likely to reduce dementia risk. The association of a history of benzodiazepine use and cognitive decline is unclear, with some studies reporting a lower risk of cognitive decline in former users, some finding no association and some indicating an increased risk of cognitive decline.


title: Benzodiazepine

text: Benzodiazepines are sometimes prescribed to treat behavioral symptoms of dementia. However, like antidepressants, they have little evidence of effectiveness, although antipsychotics have shown some benefit. Cognitive impairing effects of benzodiazepines that occur frequently in the elderly can also worsen dementia.


title: Benzodiazepine

text: The most common side-effects of benzodiazepines are related to their sedating and muscle-relaxing action. They include drowsiness, dizziness, and decreased alertness and concentration. Lack of coordination may result in falls and injuries, in particular, in the elderly. Another result is impairment of driving skills and increased likelihood of road traffic accidents. Decreased libido and erection problems are a common side effect. Depression and disinhibition may emerge. Hypotension and suppressed breathing (hypoventilation) may be encountered with intravenous use. Less common side effects include nausea and changes in appetite, blurred vision, confusion, euphoria, depersonalization and nightmares. Cases of liver toxicity have been described but are very rare.


title: Benzodiazepine

text: The long-term effects of benzodiazepine use can include cognitive impairment as well as affective and behavioural problems. Feelings of turmoil, difficulty in thinking constructively, loss of sex-drive, agoraphobia and social phobia, increasing anxiety and depression, loss of interest in leisure pursuits and interests, and an inability to experience or express feelings can also occur. Not everyone, however, experiences problems with long-term use. Additionally, an altered perception of self, environment and relationships may occur.


title: Benzodiazepine

text: Compared to other sedative-hypnotics, visits to the hospital involving benzodiazepines had a 66% greater odds of a serious adverse health outcome. This included hospitalization, patient transfer, or death, and visits involving a combination of benzodiazepines and non-benzodiapine receptor agonists had almost four-times increased odds of a serious health outcome.


title: Benzodiazepine

text: In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.


title: Benzodiazepine

text: The short-term use of benzodiazepines adversely affects multiple areas of cognition, the most notable one being that it interferes with the formation and consolidation of memories of new material and may induce complete anterograde amnesia. However, researchers hold contrary opinions regarding the effects of long-term administration. One view is that many of the short-term effects continue into the long-term and may even worsen, and are not resolved after stopping benzodiazepine usage. Another view maintains that cognitive deficits in chronic benzodiazepine users occur only for a short period after the dose, or that the anxiety disorder is the cause of these deficits.


title: Benzodiazepine

text: While the definitive studies are lacking, the former view received support from a 2004 meta-analysis of 13 small studies. This meta-analysis found that long-term use of benzodiazepines was associated with moderate to large adverse effects on all areas of cognition, with visuospatial memory being the most commonly detected impairment. Some of the other impairments reported were decreased IQ, visiomotor coordination, information processing, verbal learning and concentration. The authors of the meta-analysis and a later reviewer noted that the applicability of this meta-analysis is limited because the subjects were taken mostly from withdrawal clinics; the coexisting drug, alcohol use, and psychiatric disorders were not defined; and several of the included studies conducted the cognitive measurements during the withdrawal period.


title: Benzodiazepine

text: Paradoxical reactions, such as increased seizures in epileptics, aggression, violence, impulsivity, irritability and suicidal behavior sometimes occur. These reactions have been explained as consequences of disinhibition and the subsequent loss of control over socially unacceptable behavior. Paradoxical reactions are rare in the general population, with an incidence rate below 1% and similar to placebo. However, they occur with greater frequency in recreational abusers, individuals with borderline personality disorder, children, and patients on high-dosage regimes. In these groups, impulse control problems are perhaps the most important risk factor for disinhibition; learning disabilities and neurological disorders are also significant risks. Most reports of disinhibition involve high doses of high-potency benzodiazepines. Paradoxical effects may also appear after chronic use of benzodiazepines.


title: Benzodiazepine

text: While benzodiazepines may have short-term benefits for anxiety, sleep and agitation in some patients, long-term (i.e., greater than 2–4 weeks) use can result in a worsening of the very symptoms the medications are meant to treat. Potential explanations include exacerbating cognitive problems that are already common in anxiety disorders, causing or worsening depression and suicidality, disrupting sleep architecture by inhibiting deep stage sleep, withdrawal symptoms or rebound symptoms in between doses mimicking or exacerbating underlying anxiety or sleep disorders, inhibiting the benefits of psychotherapy by inhibiting memory consolidation and reducing fear extinction, and reducing coping with trauma/stress and increasing vulnerability to future stress. The latter two explanations may be why benzodiazepines are ineffective and/or potentially harmful in PTSD and phobias. Anxiety, insomnia and irritability may be temporarily exacerbated during withdrawal, but psychiatric symptoms after discontinuation are usually less than even while taking benzodiazepines. Functioning significantly improves within 1 year of discontinuation.


title: Benzodiazepine

text: The main problem of the chronic use of benzodiazepines is the development of tolerance and dependence. Tolerance manifests itself as diminished pharmacological effect and develops relatively quickly to the sedative, hypnotic, anticonvulsant, and muscle relaxant actions of benzodiazepines. Tolerance to anti-anxiety effects develops more slowly with little evidence of continued effectiveness beyond four to six months of continued use. In general, tolerance to the amnesic effects does not occur. However, controversy exists as to tolerance to the anxiolytic effects with some evidence that benzodiazepines retain efficacy and opposing evidence from a systematic review of the literature that tolerance frequently occurs and some evidence that anxiety may worsen with long-term use. The question of tolerance to the amnesic effects of benzodiazepines is, likewise, unclear. Some evidence suggests that partial tolerance does develop, and that, "memory impairment is limited to a narrow window within 90 minutes after each dose".


title: Benzodiazepine

text: A major disadvantage of benzodiazepines is that tolerance to therapeutic effects develops relatively quickly while many adverse effects persist. Tolerance develops to hypnotic and myorelaxant effects within days to weeks, and to anticonvulsant and anxiolytic effects within weeks to months. Therefore, benzodiazepines are unlikely to be effective long-term treatments for sleep and anxiety. While BZD therapeutic effects disappear with tolerance, depression and impulsivity with high suicidal risk commonly persist. Several studies have confirmed that long-term benzodiazepines are not significantly different from placebo for sleep or anxiety. This may explain why patients commonly increase doses over time and many eventually take more than one type of benzodiazepine after the first loses effectiveness. Additionally, because tolerance to benzodiazepine sedating effects develops more quickly than does tolerance to brainstem depressant effects, those taking more benzodiazepines to achieve desired effects may experience sudden respiratory depression, hypotension or death. Most patients with anxiety disorders and PTSD have symptoms that persist for at least several months, making tolerance to therapeutic effects a distinct problem for them and necessitating the need for more effective long-term treatment (e.g., psychotherapy, serotonergic antidepressants).


title: Benzodiazepine

text: Discontinuation of benzodiazepines or abrupt reduction of the dose, even after a relatively short course of treatment (two to four weeks), may result in two groups of symptoms—rebound and withdrawal. Rebound symptoms are the return of the symptoms for which the patient was treated but worse than before. Withdrawal symptoms are the new symptoms that occur when the benzodiazepine is stopped. They are the main sign of physical dependence.


title: Benzodiazepine

text: The most frequent symptoms of withdrawal from benzodiazepines are insomnia, gastric problems, tremors, agitation, fearfulness, and muscle spasms. The less frequent effects are irritability, sweating, depersonalization, derealization, hypersensitivity to stimuli, depression, suicidal behavior, psychosis, seizures, and delirium tremens. Severe symptoms usually occur as a result of abrupt or over-rapid withdrawal. Abrupt withdrawal can be dangerous and lead to excitotoxicity, causing damage and even death to nerve cells as a result of excessive levels of the excitatory neurotransmitter glutamate. Increased glutamatergic activity is thought to be part of a compensatory mechanism to chronic GABAergic inhibition from benzodiazepines. Therefore, a gradual reduction regimen is recommended.


title: Benzodiazepine

text: Symptoms may also occur during a gradual dosage reduction, but are typically less severe and may persist as part of a protracted withdrawal syndrome for months after cessation of benzodiazepines. Approximately 10% of patients experience a notable protracted withdrawal syndrome, which can persist for many months or in some cases a year or longer. Protracted symptoms tend to resemble those seen during the first couple of months of withdrawal but usually are of a sub-acute level of severity. Such symptoms do gradually lessen over time, eventually disappearing altogether.


title: Benzodiazepine

text: Benzodiazepines have a reputation with patients and doctors for causing a severe and traumatic withdrawal; however, this is in large part due to the withdrawal process being poorly managed. Over-rapid withdrawal from benzodiazepines increases the severity of the withdrawal syndrome and increases the failure rate. A slow and gradual withdrawal customised to the individual and, if indicated, psychological support is the most effective way of managing the withdrawal. Opinion as to the time needed to complete withdrawal ranges from four weeks to several years. A goal of less than six months has been suggested, but due to factors such as dosage and type of benzodiazepine, reasons for prescription, lifestyle, personality, environmental stresses, and amount of available support, a year or more may be needed to withdraw.


title: Benzodiazepine

text: Withdrawal is best managed by transferring the physically dependent patient to an equivalent dose of diazepam because it has the longest half-life of all of the benzodiazepines, is metabolised into long-acting active metabolites and is available in low-potency tablets, which can be quartered for smaller doses. A further benefit is that it is available in liquid form, which allows for even smaller reductions. Chlordiazepoxide, which also has a long half-life and long-acting active metabolites, can be used as an alternative.


title: Benzodiazepine

text: Nonbenzodiazepines are contraindicated during benzodiazepine withdrawal as they are cross tolerant with benzodiazepines and can induce dependence. Alcohol is also cross tolerant with benzodiazepines and more toxic and thus caution is needed to avoid replacing one dependence with another. During withdrawal, fluoroquinolone-based antibiotics are best avoided if possible; they displace benzodiazepines from their binding site and reduce GABA function and, thus, may aggravate withdrawal symptoms. Antipsychotics are not recommended for benzodiazepine withdrawal (or other CNS depressant withdrawal states) especially clozapine, olanzapine or low potency phenothiazines e.g. chlorpromazine as they lower the seizure threshold and can worsen withdrawal effects; if used extreme caution is required.


title: Benzodiazepine

text: Withdrawal from long term benzodiazepines is beneficial for most individuals. Withdrawal of benzodiazepines from long-term users, in general, leads to improved physical and mental health particularly in the elderly; although some long term users report continued benefit from taking benzodiazepines, this may be the result of suppression of withdrawal effects.


title: Benzodiazepine

text: Beyond the well established link between benzodiazepines and psychomotor impairment resulting in motor vehicle accidents and falls leading to fracture; research in the 2000s and 2010s has raised the association between benzodiazepines (and Z-drugs) and other, as of yet unproven, adverse effects including dementia, cancer, infections, pancreatitis and respiratory disease exacerbations.


title: Benzodiazepine

text: A number of studies have drawn an association between long-term benzodiazepine use and neuro-degenerative disease, particularly Alzheimer's disease. It has been determined that long-term use of benzodiazepines is associated with increased dementia risk, even after controlling for protopathic bias.


title: Benzodiazepine

text: Some observational studies have detected significant associations between benzodiazepines and respiratory infections such as pneumonia where others have not. A large meta-analysis of pre-marketing randomized controlled trials on the pharmacologically related Z-Drugs suggest a small increase in infection risk as well. An immunodeficiency effect from the action of benzodiazepines on GABA-A receptors has been postulated from animal studies.


title: Benzodiazepine

text: A Meta-analysis of observational studies has determined an association between benzodiazepine use and cancer, though the risk across different agents and different cancers varied significantly. In terms of experimental basic science evidence, an analysis of carcinogenetic and genotoxicity data for various benzodiazepines has suggested a small possibility of carcinogenesis for a small number of benzodiazepines.


title: Benzodiazepine

text: The evidence suggesting a link between benzodiazepines (and Z-Drugs) and pancreatic inflammation is very sparse and limited to a few observational studies from Taiwan. A criticism of confounding can be applied to these findings as with the other controversial associations above. Further well-designed research from other populations as well as a biologically plausible mechanism is required to confirm this association.


title: Benzodiazepine

text: Although benzodiazepines are much safer in overdose than their predecessors, the barbiturates, they can still cause problems in overdose. Taken alone, they rarely cause severe complications in overdose; statistics in England showed that benzodiazepines were responsible for 3.8% of all deaths by poisoning from a single drug. However, combining these drugs with alcohol, opiates or tricyclic antidepressants markedly raises the toxicity. The elderly are more sensitive to the side effects of benzodiazepines, and poisoning may even occur from their long-term use. The various benzodiazepines differ in their toxicity; temazepam appears most toxic in overdose and when used with other drugs. The symptoms of a benzodiazepine overdose may include; drowsiness, slurred speech, nystagmus, hypotension, ataxia, coma, respiratory depression, and cardiorespiratory arrest.


title: Benzodiazepine

text: A reversal agent for benzodiazepines exists, flumazenil (Anexate). Its use as an antidote is not routinely recommended because of the high risk of resedation and seizures. In a double-blind, placebo-controlled trial of 326 people, 4 people had serious adverse events and 61% became resedated following the use of flumazenil. Numerous contraindications to its use exist. It is contraindicated in people with a history of long-term use of benzodiazepines, those having ingested a substance that lowers the seizure threshold or may cause an arrhythmia, and in those with abnormal vital signs. One study found that only 10% of the people presenting with a benzodiazepine overdose are suitable candidates for treatment with flumazenil.


title: Benzodiazepine

text: Individual benzodiazepines may have different interactions with certain drugs. Depending on their metabolism pathway, benzodiazepines can be divided roughly into two groups. The largest group consists of those that are metabolized by cytochrome P450 (CYP450) enzymes and possess significant potential for interactions with other drugs. The other group comprises those that are metabolized through glucuronidation, such as lorazepam, oxazepam, and temazepam, and, in general, have few drug interactions.


title: Benzodiazepine

text: Many drugs, including oral contraceptives, some antibiotics, antidepressants, and antifungal agents, inhibit cytochrome enzymes in the liver. They reduce the rate of elimination of the benzodiazepines that are metabolized by CYP450, leading to possibly excessive drug accumulation and increased side-effects. In contrast, drugs that induce cytochrome P450 enzymes, such as St John's wort, the antibiotic rifampicin, and the anticonvulsants carbamazepine and phenytoin, accelerate elimination of many benzodiazepines and decrease their action. Taking benzodiazepines with alcohol, opioids and other central nervous system depressants potentiates their action. This often results in increased sedation, impaired motor coordination, suppressed breathing, and other adverse effects that have potential to be lethal. Antacids can slow down absorption of some benzodiazepines; however, this effect is marginal and inconsistent.


title: Benzodiazepine

text: Benzodiazepines work by increasing the effectiveness of the endogenous chemical, GABA, to decrease the excitability of neurons. This reduces the communication between neurons and, therefore, has a calming effect on many of the functions of the brain.


title: Benzodiazepine

text: GABA controls the excitability of neurons by binding to the GABA receptor. The GABA receptor is a protein complex located in the synapses between neurons. All GABA receptors contain an ion channel that conducts chloride ions across neuronal cell membranes and two binding sites for the neurotransmitter gamma-aminobutyric acid (GABA), while a subset of GABA receptor complexes also contain a single binding site for benzodiazepines. Binding of benzodiazepines to this receptor complex does not alter binding of GABA. Unlike other positive allosteric modulators that increase ligand binding, benzodiazepine binding acts as a positive allosteric modulator by increasing the total conduction of chloride ions across the neuronal cell membrane when GABA is already bound to its receptor. This increased chloride ion influx hyperpolarizes the neuron's membrane potential. As a result, the difference between resting potential and threshold potential is increased and firing is less likely.


title: Benzodiazepine

text: Different GABA receptor subtypes have varying distributions within different regions of the brain and, therefore, control distinct neuronal circuits. Hence, activation of different GABA receptor subtypes by benzodiazepines may result in distinct pharmacological actions. In terms of the mechanism of action of benzodiazepines, their similarities are too great to separate them into individual categories such as anxiolytic or hypnotic. For example, a hypnotic administered in low doses produces anxiety-relieving effects, whereas a benzodiazepine marketed as an anti-anxiety drug at higher doses induces sleep.


title: Benzodiazepine

text: The subset of GABA receptors that also bind benzodiazepines are referred to as benzodiazepine receptors (BzR). The GABA receptor is a heteromer composed of five subunits, the most common ones being two "α"s, two "β"s, and one "γ" (αβγ1). For each subunit, many subtypes exist (α, β, and γ). GABA receptors that are made up of different combinations of subunit subtypes have different properties, different distributions in the brain and different activities relative to pharmacological and clinical effects. Benzodiazepines bind at the interface of the α and γ subunits on the GABA receptor. Binding also requires that alpha subunits contain a histidine amino acid residue, ("i.e.", α, α, α, and α containing GABA receptors). For this reason, benzodiazepines show no affinity for GABA receptors containing α and α subunits with an arginine instead of a histidine residue. Once bound to the benzodiazepine receptor, the benzodiazepine ligand locks the benzodiazepine receptor into a conformation in which it has a greater affinity for the GABA neurotransmitter. This increases the frequency of the opening of the associated chloride ion channel and hyperpolarizes the membrane of the associated neuron. The inhibitory effect of the available GABA is potentiated, leading to sedative and anxiolytic effects. For instance, those ligands with high activity at the α are associated with stronger hypnotic effects, whereas those with higher affinity for GABA receptors containing α and/or α subunits have good anti-anxiety activity.


title: Benzodiazepine

text: The benzodiazepine class of drugs also interact with peripheral benzodiazepine receptors. Peripheral benzodiazepine receptors are present in peripheral nervous system tissues, glial cells, and to a lesser extent the central nervous system. These peripheral receptors are not structurally related or coupled to GABA receptors. They modulate the immune system and are involved in the body response to injury. Benzodiazepines also function as weak adenosine reuptake inhibitors. It has been suggested that some of their anticonvulsant, anxiolytic, and muscle relaxant effects may be in part mediated by this action. Benzodiazepines have binding sites in the periphery, however their effects on muscle tone is not mediated through these peripheral receptors. The peripheral binding sites for benzodiazepines are present in immune cells and gastrointestinal tract.


title: Benzodiazepine

text: A benzodiazepine can be placed into one of three groups by its elimination half-life, or time it takes for the body to eliminate half of the dose. Some benzodiazepines have long-acting active metabolites, such as diazepam and chlordiazepoxide, which are metabolised into desmethyldiazepam. Desmethyldiazepam has a half-life of 36–200 hours, and flurazepam, with the main active metabolite of desalkylflurazepam, with a half-life of 40–250 hours. These long-acting metabolites are partial agonists.


title: Benzodiazepine

text: Benzodiazepines share a similar chemical structure, and their effects in humans are mainly produced by the allosteric modification of a specific kind of neurotransmitter receptor, the GABA receptor, which increases the overall conductance of these inhibitory channels; this results in the various therapeutic effects as well as adverse effects of benzodiazepines. Other less important modes of action are also known.


title: Benzodiazepine

text: The term "benzodiazepine" is the chemical name for the heterocyclic ring system (see figure to the right), which is a fusion between the benzene and diazepine ring systems. Under Hantzsch–Widman nomenclature, a diazepine is a heterocycle with two nitrogen atoms, five carbon atom and the maximum possible number of cumulative double bonds. The "benzo" prefix indicates the benzene ring fused onto the diazepine ring.


title: Benzodiazepine

text: Benzodiazepine drugs are substituted 1,4-benzodiazepines, although the chemical term can refer to many other compounds that do not have useful pharmacological properties. Different benzodiazepine drugs have different side groups attached to this central structure. The different side groups affect the binding of the molecule to the GABA receptor and so modulate the pharmacological properties. Many of the pharmacologically active "classical" benzodiazepine drugs contain the 5-phenyl-1"H"-benzo["e"] [1,4]diazepin-2(3"H")-one substructure (see figure to the right). Benzodiazepines have been found to mimic protein reverse turns structurally, which enable them with their biological activity in many cases.


title: Benzodiazepine

text: Nonbenzodiazepines also bind to the benzodiazepine binding site on the GABA receptor and possess similar pharmacological properties. While the nonbenzodiazepines are by definition structurally unrelated to the benzodiazepines, both classes of drugs possess a common pharmacophore (see figure to the lower-right), which explains their binding to a common receptor site.


title: Benzodiazepine

text: The first benzodiazepine, chlordiazepoxide ("Librium"), was synthesized in 1955 by Leo Sternbach while working at Hoffmann–La Roche on the development of tranquilizers. The pharmacological properties of the compounds prepared initially were disappointing, and Sternbach abandoned the project. Two years later, in April 1957, co-worker Earl Reeder noticed a "nicely crystalline" compound left over from the discontinued project while spring-cleaning in the lab. This compound, later named chlordiazepoxide, had not been tested in 1955 because of Sternbach's focus on other issues. Expecting pharmacology results to be negative, and hoping to publish the chemistry-related findings, researchers submitted it for a standard battery of animal tests. The compound showed very strong sedative, anticonvulsant, and muscle relaxant effects. These impressive clinical findings led to its speedy introduction throughout the world in 1960 under the brand name "Librium". Following chlordiazepoxide, diazepam marketed by Hoffmann–La Roche under the brand name "Valium" in 1963, and for a while the two were the most commercially successful drugs. The introduction of benzodiazepines led to a decrease in the prescription of barbiturates, and by the 1970s they had largely replaced the older drugs for sedative and hypnotic uses.


title: Benzodiazepine

text: The new group of drugs was initially greeted with optimism by the medical profession, but gradually concerns arose; in particular, the risk of dependence became evident in the 1980s. Benzodiazepines have a unique history in that they were responsible for the largest-ever class-action lawsuit against drug manufacturers in the United Kingdom, involving 14,000 patients and 1,800 law firms that alleged the manufacturers knew of the dependence potential but intentionally withheld this information from doctors. At the same time, 117 general practitioners and 50 health authorities were sued by patients to recover damages for the harmful effects of dependence and withdrawal. This led some doctors to require a signed consent form from their patients and to recommend that all patients be adequately warned of the risks of dependence and withdrawal before starting treatment with benzodiazepines. The court case against the drug manufacturers never reached a verdict; legal aid had been withdrawn and there were allegations that the consultant psychiatrists, the expert witnesses, had a conflict of interest. The court case fell through, at a cost of £30 million, and led to more cautious funding through legal aid for future cases. This made future class action lawsuits less likely to succeed, due to the high cost from financing a smaller number of cases, and increasing charges for losing the case for each person involved.


title: Benzodiazepine

text: Although antidepressants with anxiolytic properties have been introduced, and there is increasing awareness of the adverse effects of benzodiazepines, prescriptions for short-term anxiety relief have not significantly dropped. For treatment of insomnia, benzodiazepines are now less popular than nonbenzodiazepines, which include zolpidem, zaleplon and eszopiclone. Nonbenzodiazepines are molecularly distinct, but nonetheless, they work on the same benzodiazepine receptors and produce similar sedative effects.


title: Benzodiazepine

text: Benzodiazepines have been detected in plant specimens and brain samples of animals not exposed to synthetic sources, including a human brain from the 1940s. However, it is unclear whether these compounds are biosynthesized by microbes or by plants and animals themselves. A microbial biosynthetic pathway has been proposed.


title: Benzodiazepine

text: In the United States, benzodiazepines are Schedule IV drugs under the Federal Controlled Substances Act, even when not on the market (for example, nitrazepam and bromazepam). Flunitrazepam is subject to more stringent regulations in certain states and temazepam prescriptions require specially coded pads in certain states.


title: Benzodiazepine

text: In Canada, possession of benzodiazepines is legal for personal use. All benzodiazepines are categorized as Schedule IV substances under the Controlled Drugs and Substances Act.


title: Benzodiazepine

text: In the United Kingdom, the benzodiazepines are Class C controlled drugs, carrying the maximum penalty of 7 years imprisonment, an unlimited fine or both for possession and a maximum penalty of 14 years imprisonment an unlimited fine or both for supplying benzodiazepines to others.


title: Benzodiazepine

text: In the Netherlands, since October 1993, benzodiazepines, including formulations containing less than 20 mg of temazepam, are all placed on List 2 of the Opium Law. A prescription is needed for possession of all benzodiazepines. Temazepam formulations containing 20 mg or greater of the drug are placed on List 1, thus requiring doctors to write prescriptions in the List 1 format.


title: Benzodiazepine

text: In East Asia and Southeast Asia, temazepam and nimetazepam are often heavily controlled and restricted. In certain countries, triazolam, flunitrazepam, flutoprazepam and midazolam are also restricted or controlled to certain degrees. In Hong Kong, all benzodiazepines are regulated under Schedule 1 of Hong Kong's Chapter 134 "Dangerous Drugs Ordinance". Previously only brotizolam, flunitrazepam and triazolam were classed as dangerous drugs.


title: Benzodiazepine

text: Internationally, benzodiazepines are categorized as Schedule IV controlled drugs, apart from flunitrazepam, which is a Schedule III drug under the Convention on Psychotropic Substances.


title: Benzodiazepine

text: Benzodiazepines are considered major addictive substances. Non-medical benzodiazepine use is mostly limited to individuals who use other substances, i.e., people who engage in polysubstance use. On the international scene, benzodiazepines are categorized as Schedule IV controlled drugs by the INCB, apart from flunitrazepam, which is a Schedule III drug under the Convention on Psychotropic Substances. Some variation in drug scheduling exists in individual countries; for example, in the United Kingdom, midazolam and temazepam are Schedule III controlled drugs.


title: Benzodiazepine

text: British law requires that temazepam (but "not" midazolam) be stored in safe custody. Safe custody requirements ensures that pharmacists and doctors holding stock of temazepam must store it in securely fixed double-locked steel safety cabinets and maintain a written register, which must be bound and contain separate entries for temazepam and must be written in ink with no use of correction fluid (although a written register is not required for temazepam in the United Kingdom). Disposal of expired stock must be witnessed by a designated inspector (either a local drug-enforcement police officer or official from health authority). Benzodiazepine use ranges from occasional binges on large doses, to chronic and compulsive drug use of high doses.


title: Benzodiazepine

text: Benzodiazepines are commonly used recreationally by poly-drug users. Mortality is higher among poly-drug users that also use benzodiazepines. Heavy alcohol use also increases mortality among poly-drug users. Dependence and tolerance, often coupled with dosage escalation, to benzodiazepines can develop rapidly among drug misusers; withdrawal syndrome may appear after as little as three weeks of continuous use. Long-term use has the potential to cause both physical and psychological dependence and severe withdrawal symptoms such as depression, anxiety (often to the point of panic attacks), and agoraphobia. Benzodiazepines and, in particular, temazepam are sometimes used intravenously, which, if done incorrectly or in an unsterile manner, can lead to medical complications including abscesses, cellulitis, thrombophlebitis, arterial puncture, deep vein thrombosis, and gangrene. Sharing syringes and needles for this purpose also brings up the possibility of transmission of hepatitis, HIV, and other diseases. Benzodiazepines are also misused intranasally, which may have additional health consequences. Once benzodiazepine dependence has been established, a clinician usually converts the patient to an equivalent dose of diazepam before beginning a gradual reduction program.


title: Benzodiazepine

text: A 1999–2005 Australian police survey of detainees reported preliminary findings that self-reported users of benzodiazepines were less likely than non-user detainees to work full-time and more likely to receive government benefits, use methamphetamine or heroin, and be arrested or imprisoned. Benzodiazepines are sometimes used for criminal purposes; they serve to incapacitate a victim in cases of drug assisted rape or robbery.


title: Benzodiazepine

text: Overall, anecdotal evidence suggests that temazepam may be the most psychologically habit-forming (addictive) benzodiazepine. Non-medical temazepam use reached epidemic proportions in some parts of the world, in particular, in Europe and Australia, and is a major addictive substance in many Southeast Asian countries. This led authorities of various countries to place temazepam under a more restrictive legal status. Some countries, such as Sweden, banned the drug outright. Temazepam also has certain pharmacokinetic properties of absorption, distribution, elimination, and clearance that make it more apt to non-medical use compared to many other benzodiazepines.


title: Benzodiazepine

text: Benzodiazepines are used in veterinary practice in the treatment of various disorders and conditions. As in humans, they are used in the first-line management of seizures, status epilepticus, and tetanus, and as maintenance therapy in epilepsy (in particular, in cats). They are widely used in small and large animals (including horses, swine, cattle and exotic and wild animals) for their anxiolytic and sedative effects, as pre-medication before surgery, for induction of anesthesia and as adjuncts to anesthesia.


title: Pitbull (rapper)

text: Armando Christian Pérez (born January 15, 1981), known professionally by his stage name Pitbull, is an American rapper and businessman. He began his career in the early 2000s, recording reggaeton, Latin hip hop, and crunk music under a multitude of labels. In 2004, he released his debut album "M.I.A.M.I." under TVT Records and the executive production of Lil Jon. Pitbull later released his second album, "El Mariel", in 2006 and his third, "The Boatlift", in 2007. His fourth album, "Rebelution" (2009), included his breakthrough hit single "I Know You Want Me (Calle Ocho)", which peaked at number two on the US "Billboard" Hot 100 and number four on the UK Singles Chart.


title: Pitbull (rapper)

text: After rebranding himself as a pop artist, Pitbull's next English-language album, "Planet Pit" (2011), featured his first US number one single "Give Me Everything" (featuring Ne-Yo, Afrojack and Nayer). The single from his EP "Meltdown" (also included in a version of his album, "Global Warming"), titled "Timber" (featuring Kesha), hit No.1 in eighteen countries, including the United States and the United Kingdom. The next single from the album, "Feel This Moment" (featuring Christina Aguilera), was a Top 10 hit in the United States, Canada, Australia and the United Kingdom. He performed the song "We Are One (Ole Ola)" (with Jennifer Lopez and Claudia Leitte), which served as the official theme of the 2014 FIFA World Cup. Pitbull released his latest album "Libertad 548" on September 27, 2019. The new album includes the RIAA Latin 9× Platinum hit single "No Lo Trates" (featuring Daddy Yankee and Natti Natasha). The album spawned RIAA Latin Platinum single "Me Quedaré Contigo" (also featuring Ne-Yo), and was certified RIAA Latin Platinum on January 28, 2021.


title: Pitbull (rapper)

text: Pitbull has sold over 25 million studio albums and over 100 million singles worldwide. He has over 15 billion views on YouTube as of May 2020. He was ranked by "Billboard" as the 45th Top Artist of the 2010s and the 24th Top Latin Artist of the 2010s. Pitbull's other ventures include brand ambassadorship and for various entities, activism and philanthropy in the Latino American community, a radio station (Pitbull's Globalization) on Sirius XM Radio and ownership of the Trackhouse Racing NASCAR team. As of May 2019, Pitbull has won 35 "Billboard" Latin Music Awards.


title: Pitbull (rapper)

text: Armando Christian Pérez was born on January 15, 1981, in Miami, Florida, to Cuban immigrant parents. While growing up, he was strongly encouraged by his family to "take advantage" of the privilege of living in America, and the opportunities it came with. His family has a history of fighting against the Castro regime in Cuba. When he was three, he could recite the works of Cuban national hero and poet, José Martí, in Spanish. He learned English by watching "Sesame Street" as a child. His father was largely absent from his childhood; his parents separated when he was young, and he was raised mostly by his mother, later stating: "my mom is my father and my mother." He briefly stayed with a foster family in Roswell, Georgia. His parents struggled with substance abuse; as a teenager, he was also involved with drug use and dealing, which eventually led to him getting kicked out of the family house. He attended South Miami Senior High School and Miami Coral Park High School. While growing up, he was influenced by the Miami bass genre of pop music and has cited Celia Cruz and Willy Chirino as sources of inspiration, in addition to rappers such as Nas, Jay-Z, and Snoop Dogg. He credits the "melting pot" of a city that Miami is with introducing him to many different cultures and teaching him important life lessons, implying that he wouldn't be the person he is nowadays if it wasn't for growing up in Miami.


title: Pitbull (rapper)

text: He said he chose his stage name of Pitbull because the dogs "bite to lock. The dog is too stupid to lose. And they're outlawed in Dade County. They're basically everything that I am. It's been a constant fight". After meeting Lil Jon in Miami, Pitbull was featured on Lil Jon and the East Side Boyz' album "Kings of Crunk" in 2002. Pitbull's song "Oye" was featured on the soundtrack to the film "2 Fast 2 Furious" the following year. In addition, Pitbull released several mixtapes, composed of freestyles and remixes of popular rap music. Pitbull also worked with Uncle Luke during his early career, being featured on Luke's 2001 album Somethin' Nasty, including the single "Lollipop" along with Lil' Zane.


title: Pitbull (rapper)

text: In 2001, Pitbull was signed to Luther Campbell's Luke Records by Jullian Boothe, then the label's vice-president of A&R. In 2001, Pitbull was introduced to Robert Fernandez of Famous Artist Music & Management, an independent label and management company specializing in developing artists, by the Diaz Brothers, a producer duo signed to the company. Fernandez "saw the eagerness and hunger he had" and, with the Luke Records deal ending, began working to develop Pitbull. Together they focused on creating a more radio-friendly sound. Fernandez later told HitQuarters: "At that time his music had a lot of verses and took a long time to get into the hook, and so we took time in getting the songs catchier and less on the rap side."


title: Pitbull (rapper)

text: Fernandez introduced Pitbull to Lil Jon, hoping to secure the rapper a small guest intro spot on Lil Jon's upcoming album "Kings of Crunk." According to Fernandez, Jon took a liking to Pérez and offered him a track on the album; it is called "Pitbull's Cuban Ride Out". This track helped raise the young rapper's profile.


title: Pitbull (rapper)

text: In 2004, Pitbull released his debut album "M.I.A.M.I.", with the lead single being "Culo" produced by Lil Jon and the Diaz Brothers. It peaked at No. 32 on the "Billboard" Hot 100 chart and No. 11 on the Hot Rap Tracks chart. Other singles included "Dammit Man", "Back Up", "Toma", and "That's Nasty" (both featuring Lil Jon). He joined the Anger Management Tour, the 2000 hip-hop concert tour headlined by Eminem and 50 Cent. Pitbull also appeared on the Ying Yang Twins' single "Shake", which peaked at No.41 on the Hot 100 and No.12 on the rap chart, Adassa's chart topping single "Kamasutra" & Twista's "Hit the Floor" (#94 Hot 100, No. 20 Rap). Remix album "Money Is Still a Major Issue" was released in November 2005; it included new track "Everybody Get Up", a duet with hip-hop/R&B group Pretty Ricky.


title: Pitbull (rapper)

text: TVT Records, Pitbull's label at the time, and Slip-n-Slide Records disputed over the release of "Welcome to the 305", an unreleased album by Slip-n-Slide that Pitbull recorded in 2001. A Miami judge ruled that Slip-n-Slide had a legal right to release the album as it was recorded when Pitbull was a Slip-N-Slide artist, and prior to him signing with TVT Records. A US District Court judge affirmed the decision further. TVT was then ordered in March 2007 to pay Slip-n-Slide $9.1 million for attempting to block the album's release to record stores and digital download entities.


title: Pitbull (rapper)

text: In 2005, Pitbull and rapper Sean 'Diddy' Combs co-founded Bad Boy Latino, a subsidiary of Combs' Bad Boy Records label. It primarily focuses on Latin hip hop, Latin soul, Latin pop and other tropical music and has offices in New York and Miami, Florida. Along with co-founding it, Pérez currently heads the A&R division of the label.


title: Pitbull (rapper)

text: In January 2006, Pitbull guest-starred in UPN's "South Beach". Pitbull recorded "Nuestro Himno" in collaboration with Wyclef Jean, Carlos Ponce, and Olga Tañón. On "Listennn... the Album", the debut album by Terror Squad member and Miami radio personality DJ Khaled, Pitbull performed on three singles: "Holla at Me" and "Born-N-Raised" alongside other Southern-based rappers.


title: Pitbull (rapper)

text: He dedicated the album to his father, who died in May that year. Along with the usual party-oriented tracks, Pitbull also included politically themed tracks in "El Mariel". The album was released on October 31, 2006, and included singles "Bojangles", "Ay Chico (Lengua Afuera)", "Fuego", and duet with Puerto Rican singer Ken-Y, "Dime (Remix)". "El Mariel" topped the "Billboard" independent albums chart and peaked at No. 17 on the "Billboard" 200 and No. 2 on the rap chart.


title: Pitbull (rapper)

text: Pitbull's third album, titled "The Boatlift", was released on November 27, 2007, spawned by the single "Secret Admirer" featuring Lloyd on the chorus. Earlier, Pitbull announced that this album would have a more gangsta rap edge than his earlier albums. Subsequent singles included "Go Girl" featuring Trina, and "The Anthem" featuring and produced Lil Jon, that song sampling the hook from the song "El Africano" by Wilfrido Vargas and the beat from the song "Calabria" by Rune RK. "Go Girl" peaked at No. 80 on the "Billboard" Hot 100 and No. 36 on the Hot Rap Tracks chart; "The Anthem" No. 36 on the Hot 100 and No.11 on the Hot Rap Tracks.


title: Pitbull (rapper)

text: His variety show, "Pitbull's La Esquina", debuted May 2007 and ran through 2009 on the mun2 cable network.


title: Pitbull (rapper)

text: For his fourth studio album "Pitbull Starring in Rebelution", Pitbull released "I Know You Want Me (Calle Ocho)" through Ultra Records after his former label TVT Records went out of business. "Krazy" peaked at No. 30 on the Hot 100 and No. 11 on the Hot Rap Tracks charts. "I Know You Want Me" peaked at No. 2 on the Hot 100 and peaked within the top ten spots of charts in the United Kingdom, Canada, Italy, and the Netherlands. The song reached No. 1 in France and the European Hot 100 in the week ending August 29, 2009 according to "Billboard" magazine. "I Know You Want Me" ended at position 17 on the Billboard Year-End Hot 100 singles of 2009. He later signed with Polo Grounds Music through Sony Music and created his own label Mr. 305 Inc. The single "Hotel Room Service", which samples "Push the Feeling On", peaked at No. 9 on the Hot 100. The album went on to sell over 7.5 million worldwide digital singles and albums combined.


title: Pitbull (rapper)

text: On their second collaboration since "Go Girl", Pitbull appeared on the debut single of rapper David Rush (formerly Young Bo$$), "Shooting Star", also with Kevin Rudolf and LMFAO. An amateur video of Pitbull punching a disruptive audience member at a Colorado concert leaked onto the Internet in late May 2009. Pitbull explained to MTV News that it was because the fan kept throwing cash around the stage, and after Pitbull pulled him up to the stage, he threw a stash of money right in Pitbull's face. He was tapped by the Miami Dolphins to work alongside T-Pain and Jimmy Buffett to release a new fight song for the Dolphins. The city of Miami granted Pitbull a "Key to the City" honor on August 19, 2009. Another popular single from 2009 was "Blanco", featuring Pharrell Williams of The Neptunes from the soundtrack to the movie Fast & Furious. Pitbull recorded a remix with Mexican pop diva Paulina Rubio for her single "Ni Rosas Ni Juguetes" in November 2009.


title: Pitbull (rapper)

text: In 2010, Pitbull performed the rap section in the Haiti benefit song "Somos El Mundo", a Spanish version of "We Are the World", that included a huge group of Latin artists led by Emilio and Gloria Estefan. He was also a featured guest on Janet Jackson's "Heart, Beat, Love" in addition to "Armada Latina", the fourth single off the album "Rise Up" by Latin rap legends, Cypress Hill. The song was produced by Jim Jonsin and also features Marc Anthony. Pitbull then collaborated with Alexandra Burke on the single "All Night Long". He was also featured on "DJ Got Us Fallin' in Love" by Usher.


title: Pitbull (rapper)

text: Pitbull released his full-length debut Spanish-language album titled "Armando" on November 2, 2010. He was also one of the most nominated artists of the 2011 Billboard Latin Music Awards. He garnered seven nominations for "Latin Rhythm Airplay, Song of the Year" for "Bon, Bon"; "Latin Rhythm Airplay, Artist of the Year, Solo Artist"; "Latin Rhythm Albums, Album of the Year" for Armando; "Latin Rhythm Albums, Artist of the Year, Solo Artist"; "Social 50, Latin Artist of the Year"; "Latin Digital Download of the Year" for "Bon, Bon" and "Hot Latin Song of the Year, Vocal Event" for the song "I Like It" alongside Enrique Iglesias. He also won Telehit's award for "Most Popular Artist".


title: Pitbull (rapper)

text: In April 2011, Jennifer Lopez released "Love?", which featured Pitbull on two singles. "Fresh Out the Oven" did not meet with critical or popular success, but the second cut, "On the Floor", was a certified hit. The single went on to make its "Billboard" Hot 100 debut at number nine, becoming the highest debuting Hot 100 single of Lopez's career.


title: Pitbull (rapper)

text: Pitbull released "Planet Pit" on June 17, 2011. Pitbull collaborated with T-Pain on its first single, which became a moderate hit; "Hey Baby (Drop It to the Floor)", which peaked at No. 7 on the Hot 100.


title: Pitbull (rapper)

text: On March 22, 2011, Pitbull released his second single, "Give Me Everything", which features American R&B singer Ne-Yo, American singer Nayer and Dutch DJ Afrojack, who also produced the song and co-wrote it with Matt Howard, Pitbull and Ne-Yo.; three months later, the song became Pitbull's first single to top the "Billboard" Hot 100. It was ranked No. 5 on the 2011 "Billboard" Year-End Chart.