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129-646: Spaced is a British television sitcom created, written by and starring Simon Pegg and Jessica Stevenson , and directed by Edgar Wright , about the comedic, and sometimes surreal and action-packed, misadventures of Daisy Steiner and Tim Bisley, two twenty-something Londoners who, despite only having just met, decide to move in together after she gives up on squatting and he is kicked out by his ex-girlfriend. Supporting roles include Nick Frost as Tim's best friend Mike, Katy Carmichael as Daisy's best friend Twist, Mark Heap as lodger Brian who lives downstairs and Julia Deakin as landlady Marsha. The first series of

258-858: A Before Sunset / Whatever Happened to the Likely Lads? kind of way". However, in April 2007, Wright confirmed that the show no longer had any possibility of returning in any form, as the actors were all now "too old", and he and Pegg feared it would ruin a good thing. In August of that same year, Wright told Rotten Tomatoes that "there's not going to be a third season, it would be silly now" but that they could "do something that sort of like catches our heroes ten years later." During an interview with The Guardian in July 2013 promoting The World's End with Edgar Wright and Nick Frost, Pegg stated: "Whenever we get asked about... another series of Spaced ... one of

387-624: A dopamine dysregulation syndrome which occurs in some patients taking dopaminergic drugs . The effects of amphetamine on gene regulation are both dose- and route-dependent. Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses. The few studies that have used equivalent (weight-adjusted) human therapeutic doses and oral administration show that these changes, if they occur, are relatively minor. This suggests that medical use of amphetamine does not significantly affect gene regulation. As of December 2019, there

516-469: A vasovagal response , Raynaud's phenomenon (reduced blood flow to the hands and feet), and tachycardia (increased heart rate). Sexual side effects in males may include erectile dysfunction , frequent erections, or prolonged erections . Gastrointestinal side effects may include abdominal pain , constipation , diarrhea , and nausea . Other potential physical side effects include appetite loss , blurred vision , dry mouth , excessive grinding of

645-540: A 30-minute time slot. Throughout their history, American sitcoms have often drawn inspiration from British counterparts. Popular shows like All in the Family , Three's Company , and Sanford and Son were adapted from successful British series. More recently, The Office achieved significant popularity in the United States , following the success of its British counterpart. Numerous television networks in

774-544: A core group of characters who interact in a recurring setting, such as a family, workplace, or institution. However, British sitcoms typically consist of shorter series, often six episodes, and are frequently developed by a smaller writing team. The majority of British sitcoms are half-hour comedies recorded in studio settings using a multiple-camera setup. While many adhere to traditional sitcom conventions, some have ventured into more unconventional territory. For example, Blackadder and Yes Minister/Yes Prime Minister shifted

903-604: A cup of tea and decides to take the gang clubbing. Spaced was nominated in 2000 and 2002 for a British Academy Television Award for situation comedy. Jessica Stevenson won the British Comedy Award in 1999 and 2001 for best TV Comedy Actress. Simon Pegg was nominated in 1999 for the British Comedy Award for Best Male Comedy Newcomer, and the series was nominated that same year for the British Comedy Award for Best TV Sitcom. The show's second series

1032-584: A day, which is roughly 100 times the maximum daily therapeutic dose. Symptoms of a moderate and extremely large overdose are listed below; fatal amphetamine poisoning usually also involves convulsions and coma . In 2013, overdose on amphetamine, methamphetamine, and other compounds implicated in an " amphetamine use disorder " resulted in an estimated 3,788 deaths worldwide ( 3,425–4,145  deaths, 95% confidence ). In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic neurotoxicity , or damage to dopamine neurons, which

1161-461: A fuel substrate. Dextroamphetamine also activates TAAR1 in peripheral organs along the gastrointestinal tract that are involved in the regulation of food intake and body weight. Together, these actions confer an anorexigenic effect that promotes satiety in response to feeding and may decrease binge eating as a secondary effect. Medical reviews of randomized controlled trials have demonstrated that lisdexamfetamine, at doses between 50-70 mg,

1290-634: A greater effect on cataplexy, a symptom more sensitive to the effects of norepinephrine and serotonin. Noradrenergic and serotonergic nuclei in the ARAS are involved in the regulation of the REM sleep cycle and function as "REM-off" cells, with amphetamine's effect on norepinephrine and serotonin contributing to the suppression of REM sleep and a possible reduction of cataplexy at high doses. The American Academy of Sleep Medicine (AASM) 2021 clinical practice guideline conditionally recommends dextroamphetamine for

1419-505: A job interview at a classy women's magazine ("Flaps") and Brian has an invitation to a new art show by Vulva ( David Walliams ), his former partner. At the art show, Tim's hallucinations of zombies cause him to punch Vulva in the face before fleeing. The episode concludes with Daisy's idea for performance art, a parody of Bruce Nauman 's work "Clown Torture", which leads Tim to remark that it is obviously harder than it looks. Tim's bicycle courier friend Tyres ( Michael Smiley ) pops round for

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1548-442: A lodger after Marsha's daughter Amber Weary "flies the nest". The series largely concerns the surreal and awkward adventures of Tim and Daisy as they navigate through life, come to terms with affairs of the heart, and try to figure out new and largely unproductive ways of killing time. They repeatedly clarify that they are not a couple to everyone but Marsha, but despite this, romantic tension develops between them, particularly during

1677-491: A more favorable pharmacokinetic profile and easy crushability (especially tablets). Injection into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels. Chronic overuse of dextroamphetamine can lead to severe drug dependence , resulting in withdrawal symptoms when drug use stops. According to the International Programme on Chemical Safety (IPCS) and

1806-461: A nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5  IQ points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity. Another review indicated that, based upon the longest follow-up studies conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces

1935-412: A number of occasions, one episode centring on its use. Tim and Mike take speed on one occasion, and it is implied that Tim, Mike, Daisy, Twist and Brian take ecstasy while clubbing. Individual tracks that were particularly featured in an episode included " Is You Is or Is You Ain't My Baby ?" by Louis Jordan, "Smash It" by Fuzz Townshend , and " The Staunton Lick " by Lemon Jelly . A Guy Pratt remix of

2064-414: A preference for spending time in places where they have previously used amphetamine. Addiction is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses; in fact, lifetime stimulant therapy for ADHD that begins during childhood reduces the risk of developing substance use disorders as an adult. Pathological overactivation of

2193-729: A pronounced gene-related phenotype ) in the D1-type medium spiny neurons in the nucleus accumbens is necessary and sufficient for many of the neural adaptations and regulates multiple behavioral effects (e.g., reward sensitization and escalating drug self-administration ) involved in addiction. Once ΔFosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in ΔFosB expression. It has been implicated in addictions to alcohol , cannabinoids , cocaine , methylphenidate , nicotine , opioids , phencyclidine , propofol , and substituted amphetamines , among others. ΔJunD ,

2322-410: A reserve capacity that is normally off-limits. At therapeutic doses, the adverse effects of amphetamine do not impede athletic performance; however, at much higher doses, amphetamine can induce effects that severely impair performance, such as rapid muscle breakdown and elevated body temperature . Amphetamine, specifically the more dopaminergic dextrorotatory enantiomer ( dextroamphetamine ),

2451-515: A reward and motivation), positive reinforcement and positively-valenced emotions, particularly ones involving pleasure . Large recreational doses of dextroamphetamine may produce symptoms of dextroamphetamine overdose . Recreational users sometimes open dexedrine capsules and crush the contents in order to insufflate (snort) it or subsequently dissolve it in water and inject it. Immediate-release formulations have higher potential for abuse via insufflation (snorting) or intravenous injection due to

2580-605: A stimulant psychosis that may involve a variety of symptoms, such as delusions and paranoia. A Cochrane review on treatment for amphetamine, dextroamphetamine, and methamphetamine psychosis states that about 5–15% of users fail to recover completely. According to the same review, there is at least one trial that shows antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis. Psychosis rarely arises from therapeutic use. Many types of substances are known to interact with amphetamine, resulting in altered drug action or metabolism of amphetamine,

2709-509: A task) and increase arousal (wakefulness), in turn promoting goal-directed behavior. Stimulants such as amphetamine can improve performance on difficult and boring tasks and are used by some students as a study and test-taking aid. Based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs. However, high amphetamine doses that are above

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2838-564: A time-limited withdrawal syndrome that occurs within 24 hours of their last dose." This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in roughly 88% of cases, and persist for 3–4  weeks with a marked "crash" phase occurring during the first week. Amphetamine withdrawal symptoms can include anxiety, drug craving , depressed mood , fatigue , increased appetite , increased movement or decreased movement , lack of motivation, sleeplessness or sleepiness, and lucid dreams . The review indicated that

2967-510: A transcription factor, and G9a , a histone methyltransferase enzyme, both oppose the function of ΔFosB and inhibit increases in its expression. Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB). Similarly, accumbal G9a hyperexpression results in markedly increased histone 3 lysine residue 9 dimethylation ( H3K9me2 ) and blocks

3096-464: A young professional couple in order to meet the requisites of an advertisement for a relatively cheap flat in the distinctive building at 23 Meteor Street, Tufnell Park , owned by resident landlady Marsha Klein. Also in the building is Brian Topp, an eccentric conceptual artist who lives and works on his various pieces in the ground-floor flat. Frequent visitors are Daisy's best friend Twist Morgan and Tim's best friend Mike Watt. The latter ends up becoming

3225-454: Is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses. Very high doses can result in psychosis (e.g., hallucinations , delusions and paranoia ) which rarely occurs at therapeutic doses even during long-term use. Recreational doses are generally much larger than prescribed therapeutic doses and carry a far greater risk of serious side effects. Amphetamine belongs to

3354-424: Is also used recreationally as a euphoriant and aphrodisiac, and like other amphetamines ; is used as a club drug for its energetic and euphoric high. Dextroamphetamine (d-amphetamine) is considered to have a high potential for misuse in a recreational manner since individuals typically report feeling euphoric , more alert, and more energetic after taking the drug. A notable part of the 1960s mod subculture in

3483-450: Is also used to treat binge eating disorder in the form of its inactive prodrug lisdexamfetamine . Amphetamine was discovered as a chemical in 1887 by Lazăr Edeleanu , and then as a drug in the late 1920s. It exists as two enantiomers : levoamphetamine and dextroamphetamine . Amphetamine properly refers to a specific chemical, the racemic free base , which is equal parts of the two enantiomers in their pure amine forms. The term

3612-472: Is characterized by dopamine terminal degeneration and reduced transporter and receptor function. There is no evidence that amphetamine is directly neurotoxic in humans. However, large doses of amphetamine may indirectly cause dopaminergic neurotoxicity as a result of hyperpyrexia , the excessive formation of reactive oxygen species , and increased autoxidation of dopamine. Animal models of neurotoxicity from high-dose amphetamine exposure indicate that

3741-402: Is characterized by recurrent and persistent episodes of compulsive binge eating. These episodes are often accompanied by marked distress and a feeling of loss of control over eating. The pathophysiology of BED is not fully understood, but it is believed to involve dysfunctional dopaminergic reward circuitry along the cortico-striatal-thalamic-cortical loop . As of July 2024, lisdexamfetamine

3870-412: Is dangerous. Amphetamine modulates the activity of most psychoactive drugs. In particular, amphetamine may decrease the effects of sedatives and depressants and increase the effects of stimulants and antidepressants . Amphetamine may also decrease the effects of antihypertensives and antipsychotics due to its effects on blood pressure and dopamine respectively. Zinc supplementation may reduce

3999-507: Is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), enhancing quality of life and academic achievement, and producing improvements in a large number of functional outcomes across 9 categories of outcomes related to academics, antisocial behavior , driving, non-medicinal drug use, obesity, occupation, self-esteem , service use (i.e., academic, occupational, health, financial, and legal services), and social function. One review highlighted

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4128-467: Is frequently used informally to refer to any combination of the enantiomers, or to either of them alone. Historically, it has been used to treat nasal congestion and depression. Amphetamine is also used as an athletic performance enhancer and cognitive enhancer , and recreationally as an aphrodisiac and euphoriant . It is a prescription drug in many countries, and unauthorized possession and distribution of amphetamine are often tightly controlled due to

4257-421: Is high, amphetamine may reduce gastrointestinal motility (the rate at which content moves through the digestive system); however, amphetamine may increase motility when the smooth muscle of the tract is relaxed. Amphetamine also has a slight analgesic effect and can enhance the pain relieving effects of opioids . FDA-commissioned studies from 2011 indicate that in children, young adults, and adults there

4386-458: Is known to produce abnormal dopamine system development or nerve damage, but, in humans with ADHD, long-term use of pharmaceutical amphetamines at therapeutic doses appears to improve brain development and nerve growth. Reviews of magnetic resonance imaging (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of

4515-601: Is known to strongly induce cocaine- and amphetamine-regulated transcript (CART) gene expression , a neuropeptide involved in feeding behavior, stress, and reward, which induces observable increases in neuronal development and survival in vitro . The CART receptor has yet to be identified, but there is significant evidence that CART binds to a unique G i /G o -coupled GPCR . Amphetamine also inhibits monoamine oxidases at very high doses, resulting in less monoamine and trace amine metabolism and consequently higher concentrations of synaptic monoamines. In humans,

4644-424: Is much more glamorous. It doesn't make any sense. I remember that the producer at the time said, 'Yeah, we'd have to change a few things. We'd have to take out the drugs and the swearing, and obviously, Mike can't have guns.'" Neither Wright, Pegg, nor Stevenson were at any point approached regarding the proposed American remake, which Wright had dubbed "McSpaced", due to the involvement of film director McG . Wright

4773-779: Is no association between serious adverse cardiovascular events ( sudden death , heart attack , and stroke ) and the medical use of amphetamine or other ADHD stimulants. However, amphetamine pharmaceuticals are contraindicated in individuals with cardiovascular disease . At normal therapeutic doses, the most common psychological side effects of amphetamine include increased alertness , apprehension, concentration , initiative, self-confidence and sociability, mood swings ( elated mood followed by mildly depressed mood ), insomnia or wakefulness , and decreased sense of fatigue. Less common side effects include anxiety , change in libido , grandiosity , irritability , repetitive or obsessive behaviors, and restlessness; these effects depend on

4902-491: Is no effective pharmacotherapy for amphetamine addiction. Reviews from 2015 and 2016 indicated that TAAR1 -selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions; however, as of February 2016, the only compounds which are known to function as TAAR1-selective agonists are experimental drugs . Amphetamine addiction is largely mediated through increased activation of dopamine receptors and co-localized NMDA receptors in

5031-455: Is not an effective monotherapy for amphetamine addiction. A systematic review and meta-analysis from 2019 assessed the efficacy of 17 different pharmacotherapies used in randomized controlled trials (RCTs) for amphetamine and methamphetamine addiction; it found only low-strength evidence that methylphenidate might reduce amphetamine or methamphetamine self-administration. There was low- to moderate-strength evidence of no benefit for most of

5160-564: Is one of the leading channels in India, dedicated entirely to Sitcoms. Taarak Mehta Ka Ooltah Chashmah is the longest-running sitcom of Indian television and is also known as the flagship show of SAB TV . On Tiptoes and Shabhaye Barareh were among the first and most important sitcoms that led to the growth of this type of comedy in Iran, both receiving wide critical and audience acclaim. El Chavo del Ocho , which ran from 1971 to 1980,

5289-466: Is safe and effective for the treatment of moderate-to-severe BED in adults. These reviews suggest that lisdexamfetamine is persistently effective at treating BED and is associated with significant reductions in the number of binge eating days and binge eating episodes per week. Furthermore, a meta-analytic systematic review highlighted an open-label, 12-month extension safety and tolerability study that reported lisdexamfetamine remained effective at reducing

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5418-586: Is sufficiently overexpressed, it begins to increase the severity of addictive behavior (i.e., compulsive drug-seeking) with further increases in its expression. While there are currently no effective drugs for treating amphetamine addiction, regularly engaging in sustained aerobic exercise appears to reduce the risk of developing such an addiction. Exercise therapy improves clinical treatment outcomes and may be used as an adjunct therapy with behavioral therapies for addiction. Chronic use of amphetamine at excessive doses causes alterations in gene expression in

5547-481: Is the only USFDA - and TGA -approved pharmacotherapy for BED. Evidence suggests that lisdexamfetamine's treatment efficacy in BED is underpinned at least in part by a psychopathological overlap between BED and ADHD, with the latter conceptualized as a cognitive control disorder that also benefits from treatment with lisdexamfetamine. Lisdexamfetamine's therapeutic effects for BED primarily involve direct action in

5676-405: Is thought to phosphorylate SERT via TAAR1 . Like dopamine, amphetamine has low, micromolar affinity at the human 5-HT1A receptor . Acute amphetamine administration in humans increases endogenous opioid release in several brain structures in the reward system . Extracellular levels of glutamate , the primary excitatory neurotransmitter in the brain, have been shown to increase in

5805-430: Is usually not noticeable, but when respiration is already compromised, it may be evident. Amphetamine also induces contraction in the urinary bladder sphincter , the muscle which controls urination, which can result in difficulty urinating. This effect can be useful in treating bed wetting and loss of bladder control . The effects of amphetamine on the gastrointestinal tract are unpredictable. If intestinal activity

5934-603: The A-Team theme song, featured at the conclusion of " Epiphanies ", was a fan favourite, but was never made commercially available. In 2001, a soundtrack to the first series was released in tandem with the first series' release on DVD and videotape. A second soundtrack was not released, although the series' official fan website has an episode-by-episode list of music featured in the second series. After taking some speed , Tim has spent all night playing Resident Evil 2 and Mike has accidentally travelled to Sheffield . Daisy has

6063-725: The Canadian Screen Award for Best Comedy Series . In 2020, the sixth and final season of Schitt's Creek was nominated for 15 Primetime Emmy Awards . This broke the record for the most Emmy nominations given to a comedy series in its final season. During the 72nd Primetime Emmy Awards , the show became the first ever comedy or drama series to sweep the four acting categories ( Outstanding Lead Actor , Outstanding Lead Actress , Outstanding Supporting Actor , Outstanding Supporting Actress for Eugene Levy , Catherine O'Hara , Dan Levy , and Annie Murphy respectively) and one of only four live action shows, along with All in

6192-753: The RTR channel. The "boom" of Russian sitcoms began only in the 2000s, when in 2004, the STS started the highly successful sitcom " My Fair Nanny " (an adaptation of the American sitcom " The Nanny "). Since that time, sitcoms in Russia have been produced by the two largest entertainment channels in the country — STS and TNT . In 2007, the STS released the first original domestic sitcom — " Daddy's Daughters " (there were only adaptations before), and in 2010, TNT released " Interns " —

6321-425: The United States feature sitcoms in their programming. CBS , TBS, Nickelodeon , and Disney Channel are just a few examples of networks that air sitcoms. Amphetamine Amphetamine (contracted from a lpha - m ethyl ph en et hyl amine ) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy , and obesity ; it

6450-483: The central nervous system after conversion to its pharmacologically active metabolite, dextroamphetamine. Centrally, dextroamphetamine increases neurotransmitter activity of dopamine and norepinephrine in prefrontal cortical regions that regulate cognitive control of behavior. Similar to its therapeutic effect in ADHD, dextroamphetamine enhances cognitive control and may reduce impulsivity in patients with BED by enhancing

6579-664: The comedy-dramas of the 1980s and 1990s. Although there have been few long-running Australian-made sitcoms, many American and British sitcoms have been successful in Australia, since sitcoms are considered a staple of the government broadcaster Australian Broadcasting Corporation (ABC). In the 1970s and 1980s many British sitcoms also screened on the Seven Network . By 1986, UK comedies Bless This House and Are You Being Served? had been re-screened several times by ABC Television ; they were then acquired and screened by

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6708-428: The firing rate of dopamine neurons, preventing a hyper-dopaminergic state. Amphetamine is also a substrate for the presynaptic vesicular monoamine transporter , VMAT2 . Following amphetamine uptake at VMAT2, amphetamine induces the collapse of the vesicular pH gradient, which results in the release of dopamine molecules from synaptic vesicles into the cytosol via dopamine efflux through VMAT2. Subsequently,

6837-531: The hypothalamic–pituitary–adrenal axis . In December 2017, the first study assessing the interaction between amphetamine and human carbonic anhydrase enzymes was published; of the eleven carbonic anhydrase enzymes it examined, it found that amphetamine potently activates seven, four of which are highly expressed in the human brain , with low nanomolar through low micromolar activating effects. Based upon preclinical research, cerebral carbonic anhydrase activation has cognition-enhancing effects; but, based upon

6966-523: The indirect activation of both dopamine D 1 receptor and α 2 -adrenergic receptor in the prefrontal cortex . A systematic review from 2014 found that low doses of amphetamine also improve memory consolidation , in turn leading to improved recall of information . Therapeutic doses of amphetamine also enhance cortical network efficiency, an effect which mediates improvements in working memory in all individuals. Amphetamine and other ADHD stimulants also improve task saliency (motivation to perform

7095-528: The lateral hypothalamus , leading to significantly reduced cerebrospinal orexin levels; this reduction is a diagnostic biomarker for type 1 narcolepsy. Lateral hypothalamic orexin neurons innervate every component of the ascending reticular activating system (ARAS), which includes noradrenergic , dopaminergic , histaminergic , and serotonergic nuclei that promote wakefulness . Amphetamine’s therapeutic mode of action in narcolepsy primarily involves increasing monoamine neurotransmitter activity in

7224-508: The mesocorticolimbic projection , which arise through transcriptional and epigenetic mechanisms. The most important transcription factors that produce these alterations are Delta FBJ murine osteosarcoma viral oncogene homolog B ( ΔFosB ), cAMP response element binding protein ( CREB ), and nuclear factor-kappa B ( NF-κB ). ΔFosB is the most significant biomolecular mechanism in addiction because ΔFosB overexpression (i.e., an abnormally high level of gene expression which produces

7353-476: The mesolimbic pathway , a dopamine pathway that connects the ventral tegmental area to the nucleus accumbens , plays a central role in amphetamine addiction. Individuals who frequently self-administer high doses of amphetamine have a high risk of developing an amphetamine addiction, since chronic use at high doses gradually increases the level of accumbal ΔFosB , a "molecular switch" and "master control protein" for addiction. Once nucleus accumbens ΔFosB

7482-413: The minimum effective dose of amphetamine when it is used for the treatment of ADHD. In general, there is no significant interaction when consuming amphetamine with food, but the pH of gastrointestinal content and urine affects the absorption and excretion of amphetamine, respectively. Acidic substances reduce the absorption of amphetamine and increase urinary excretion, and alkaline substances do

7611-504: The neurobiological effects of physical exercise suggests that daily aerobic exercise, especially endurance exercise (e.g., marathon running ), prevents the development of drug addiction and is an effective adjunct therapy (i.e., a supplemental treatment) for amphetamine addiction. Exercise leads to better treatment outcomes when used as an adjunct treatment, particularly for psychostimulant addictions. In particular, aerobic exercise decreases psychostimulant self-administration, reduces

7740-457: The phenethylamine class . It is also the parent compound of its own structural class, the substituted amphetamines , which includes prominent substances such as bupropion , cathinone , MDMA , and methamphetamine . As a member of the phenethylamine class, amphetamine is also chemically related to the naturally occurring trace amine neuromodulators, specifically phenethylamine and N -methylphenethylamine , both of which are produced within

7869-504: The prefrontal cortex . Stimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems. Approximately 80% of those who use these stimulants see improvements in ADHD symptoms. Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans. The Cochrane reviews on

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7998-606: The presynaptic neuron either through DAT or by diffusing across the neuronal membrane directly. As a consequence of DAT uptake, amphetamine produces competitive reuptake inhibition at the transporter. Upon entering the presynaptic neuron, amphetamine activates TAAR1 which, through protein kinase A (PKA) and protein kinase C (PKC) signaling, causes DAT phosphorylation . Phosphorylation by either protein kinase can result in DAT internalization ( non-competitive reuptake inhibition), but PKC-mediated phosphorylation alone induces

8127-405: The reinstatement (i.e., relapse) of drug-seeking, and induces increased dopamine receptor D 2 (DRD2) density in the striatum . This is the opposite of pathological stimulant use, which induces decreased striatal DRD2 density. One review noted that exercise may also prevent the development of a drug addiction by altering ΔFosB or c-Fos immunoreactivity in the striatum or other parts of

8256-432: The reversal of dopamine transport through DAT (i.e., dopamine efflux ). Amphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through an unidentified Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent pathway, in turn producing dopamine efflux. Through direct activation of G protein-coupled inwardly-rectifying potassium channels , TAAR1 reduces

8385-422: The reward system . Drug tolerance develops rapidly in amphetamine abuse (i.e., recreational amphetamine use), so periods of extended abuse require increasingly larger doses of the drug in order to achieve the same effect. According to a Cochrane review on withdrawal in individuals who compulsively use amphetamine and methamphetamine, "when chronic heavy users abruptly discontinue amphetamine use, many report

8514-500: The "Definitive Collectors Edition" boxed set introduced a similar subtitle track for Series 1. 2000 AD artists Jim Murray and Jason Brashill provided the artwork for Tim's comic The Bear , as well as other incidental artwork for the show. Tim's boss Bilbo wears a 2000 AD comic T-shirt whilst lecturing Tim about Star Wars: Episode I – The Phantom Menace . The series is also noted for its regular recreational drug use references, from its title onwards. Tim and Daisy smoke cannabis on

8643-431: The 1990s these included: Dekh Bhai Dekh (1993), Zabaan Sambhalke (1993), Shrimaan Shrimati (1995), Office Office (2001), Ramani Vs Ramani (Tamil 2001), Amrutham (Telugu 2001–2007), Khichdi (2002), Sarabhai vs Sarabhai (2005) F.I.R. (2006–2015), Taarak Mehta Ka Ooltah Chashmah (2008–present), Uppum Mulakum (Malayalam 2015–present), and Bhabiji Ghar Par Hain (2015–present). SAB TV

8772-482: The 1990s, sitcoms have since expanded to animated sitcoms , with successful shows of the genre including The Simpsons , King of the Hill , and Family Guy . Critics have debated the exact definition of a sitcom, mostly regarding productions created at the turn of the 21st century. Many contemporary American sitcoms use a single-camera setup and do not feature a laugh track, instead more resembling documentaries or

8901-482: The 2010s, resulting in a decline in sitcom popularity. Nevertheless, there have been recent efforts to revive the sitcom genre. For instance, Netflix released So Not Worth It in 2021, featuring many creators from popular South Korean sitcoms. Popular South Korean sitcoms include the High Kick series, which has spawned several spin-offs. British sitcoms , like their American counterparts, often revolve around

9030-529: The ARAS. This includes noradrenergic neurons in the locus coeruleus , dopaminergic neurons in the ventral tegmental area , histaminergic neurons in the tuberomammillary nucleus , and serotonergic neurons in the dorsal raphe nucleus . Dextroamphetamine, the more dopaminergic enantiomer of amphetamine, is particularly effective at promoting wakefulness because dopamine release has the greatest influence on cortical activation and cognitive arousal, relative to other monoamines. In contrast, levoamphetamine may have

9159-417: The Family , The Golden Girls , and Will & Grace where all the principal actors have won at least one Emmy Award. Sitcoms started appearing on Indian television in the 1980s, with serials like Yeh Jo Hai Zindagi (1984), Nukkad (1986), and Wagle Ki Duniya (1988) on the state-run Doordarshan channel. Gradually, as private channels were permitted to operate, many more sitcoms followed. In

9288-728: The Seven Network. In 1981, Daily at Dawn was the first Australian comedy series to feature a regular gay character (Terry Bader as journalist Leslie). In 1987, Mother and Son won the Television Drama Award for portraying a woman suffering from senile dementia and her interaction with her family, presented by the Australian Human Rights Commission . In 2007, Kath & Kim ' s first episode of series 4 attracted an Australian audience of 2.521 million nationally. This

9417-1140: The U.S. Food and Drug Administration (FDA), amphetamine is contraindicated in people with a history of drug abuse , cardiovascular disease , severe agitation , or severe anxiety. It is also contraindicated in individuals with advanced arteriosclerosis (hardening of the arteries), glaucoma (increased eye pressure), hyperthyroidism (excessive production of thyroid hormone), or moderate to severe hypertension . These agencies indicate that people who have experienced allergic reactions to other stimulants or who are taking monoamine oxidase inhibitors (MAOIs) should not take amphetamine, although safe concurrent use of amphetamine and monoamine oxidase inhibitors has been documented. These agencies also state that anyone with anorexia nervosa , bipolar disorder , depression, hypertension, liver or kidney problems, mania , psychosis , Raynaud's phenomenon , seizures , thyroid problems, tics , or Tourette syndrome should monitor their symptoms while taking amphetamine. Evidence from human studies indicates that therapeutic amphetamine use does not cause developmental abnormalities in

9546-488: The UK was recreational amphetamine use, which was used to fuel all-night dances at clubs like Manchester's Twisted Wheel . Newspaper reports described dancers emerging from clubs at 5 a.m. with dilated pupils. Mods used the drug for stimulation and alertness , which they viewed as different from the intoxication caused by alcohol and other drugs. Dr. Andrew Wilson argues that for a significant minority, "amphetamines symbolised

9675-588: The United States in 1926 with the radio show Sam 'n' Henry . The subsequent success of Amos 'n' Andy , also created by Freeman Gosden and Charles Correll , solidified the sitcom's place in American radio programming. The transition to television brought about significant changes in the sitcom format. Mary Kay and Johnny , which premiered in 1947, became the first American television sitcom. Today, American sitcoms typically run for 22 minutes, allowing for approximately eight minutes of advertising within

9804-527: The amount of amphetamine used is the primary factor in determining the likelihood and severity of adverse effects. Amphetamine products such as Adderall , Dexedrine, and their generic equivalents are currently approved by the U.S. FDA for long-term therapeutic use. Recreational use of amphetamine generally involves much larger doses, which have a greater risk of serious adverse drug effects than dosages used for therapeutic purposes. Cardiovascular side effects can include hypertension or hypotension from

9933-477: The brain, such as the right caudate nucleus of the basal ganglia . Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD. Randomized controlled trials of continuous stimulant therapy for the treatment of ADHD spanning 2 years have demonstrated treatment effectiveness and safety. Two reviews have indicated that long-term continuous stimulant therapy for ADHD

10062-560: The brain, with its most pronounced effects targeting the norepinephrine and dopamine neurotransmitter systems . At therapeutic doses, amphetamine causes emotional and cognitive effects such as euphoria , change in desire for sex , increased wakefulness , and improved cognitive control . It induces physical effects such as improved reaction time, fatigue resistance, decreased appetite , elevated heart rate, and increased muscle strength. Larger doses of amphetamine may impair cognitive function and induce rapid muscle breakdown . Addiction

10191-506: The brain. The concentrations of the main neurotransmitters involved in reward circuitry and executive functioning, dopamine and norepinephrine, increase dramatically in a dose-dependent manner by amphetamine because of its effects on monoamine transporters . The reinforcing and motivational salience -promoting effects of amphetamine are due mostly to enhanced dopaminergic activity in the mesolimbic pathway . The euphoric and locomotor-stimulating effects of amphetamine are dependent upon

10320-438: The cognitive processes responsible for overriding prepotent feeding responses that precede binge eating episodes. In addition, dextroamphetamine's actions outside of the central nervous system may also contribute to its treatment effects in BED. Peripherally, dextroamphetamine triggers lipolysis through noradrenergic signaling in adipose fat cells, leading to the release of triglycerides into blood plasma to be utilized as

10449-792: The cytosolic dopamine molecules are released from the presynaptic neuron into the synaptic cleft via reverse transport at DAT . Similar to dopamine, amphetamine dose-dependently increases the level of synaptic norepinephrine, the direct precursor of epinephrine . Based upon neuronal TAAR1 mRNA expression, amphetamine is thought to affect norepinephrine analogously to dopamine. In other words, amphetamine induces TAAR1-mediated efflux and non-competitive reuptake inhibition at phosphorylated NET , competitive NET reuptake inhibition, and norepinephrine release from VMAT2 . Amphetamine exerts analogous, yet less pronounced, effects on serotonin as on dopamine and norepinephrine. Amphetamine affects serotonin via VMAT2 and, like norepinephrine,

10578-456: The expression of ΔFosB (i.e., they cause the brain to produce more of it), chronic acquisition of these rewards can result in a similar pathological state of addiction. Consequently, ΔFosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced sexual addictions , which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use. These sexual addictions are associated with

10707-596: The fetus or newborns (i.e., it is not a human teratogen ), but amphetamine abuse does pose risks to the fetus. Amphetamine has also been shown to pass into breast milk, so the IPCS and the FDA advise mothers to avoid breastfeeding when using it. Due to the potential for reversible growth impairments, the FDA advises monitoring the height and weight of children and adolescents prescribed an amphetamine pharmaceutical. The adverse side effects of amphetamine are many and varied, and

10836-647: The first sitcom, filmed as a comedy (unlike dominated "conveyor" sitcoms). Sitcoms, or "시트콤" in Korean, gained significant popularity in South Korea during the 1990s. This popularity was fueled by the success of shows like Dr. Oh's People , LA Arirang , and Men and Women . The use of computer graphics (CG) in sitcoms began to increase in the late 1990s as more broadcasters adopted CG technology. This led to more visually dynamic and creative sitcoms. However, viewer preferences shifted towards dramas and thrillers in

10965-496: The focus from domestic or workplace settings to the world of politics. A more recent development in British comedy is the mockumentary , a style that blends documentary and comedic elements. Shows like The Office , Come Fly with Me , W1A , People Just Do Nothing , and This Country have successfully employed this format to explore a variety of topics and characters. Sitcoms, or situation comedies, made their debut in

11094-426: The highest efficacy (i.e., abstinence rate) and acceptability (i.e., lowest dropout rate). Other treatment modalities examined in the analysis included monotherapy with contingency management or community reinforcement approach, cognitive behavioral therapy , 12-step programs , non-contingent reward-based therapies, psychodynamic therapy , and other combination therapies involving these. Additionally, research on

11223-607: The human body. Phenethylamine is the parent compound of amphetamine, while N -methylphenethylamine is a positional isomer of amphetamine that differs only in the placement of the methyl group . Amphetamine is used to treat attention deficit hyperactivity disorder (ADHD), narcolepsy (a sleep disorder), obesity , and, in the form of lisdexamfetamine , binge eating disorder . It is sometimes prescribed off-label for its past medical indications , particularly for depression and chronic pain . Long-term amphetamine exposure at sufficiently high doses in some animal species

11352-434: The human brain. Dextroamphetamine is a more potent agonist of TAAR1 than levoamphetamine. Consequently, dextroamphetamine produces greater CNS stimulation than levoamphetamine, roughly three to four times more, but levoamphetamine has slightly stronger cardiovascular and peripheral effects. In certain brain regions, amphetamine increases the concentration of dopamine in the synaptic cleft . Amphetamine can enter

11481-461: The induction of ΔFosB-mediated neural and behavioral plasticity by chronic drug use, which occurs via H3K9me2 -mediated repression of transcription factors for ΔFosB and H3K9me2-mediated repression of various ΔFosB transcriptional targets (e.g., CDK5 ). ΔFosB also plays an important role in regulating behavioral responses to natural rewards , such as palatable food, sex, and exercise. Since both natural rewards and addictive drugs induce

11610-431: The interacting substance, or both. Inhibitors of enzymes that metabolize amphetamine (e.g., CYP2D6 and FMO3 ) will prolong its elimination half-life , meaning that its effects will last longer. Amphetamine also interacts with MAOIs , particularly monoamine oxidase A inhibitors, since both MAOIs and amphetamine increase plasma catecholamines (i.e., norepinephrine and dopamine); therefore, concurrent use of both

11739-668: The magnitude and speed by which it increases synaptic dopamine and norepinephrine concentrations in the striatum . Amphetamine has been identified as a potent full agonist of trace amine-associated receptor 1 (TAAR1), a G s -coupled and G q -coupled G protein-coupled receptor (GPCR) discovered in 2001, which is important for regulation of brain monoamines. Activation of TAAR1 increases cAMP Tooltip cyclic adenosine monophosphate production via adenylyl cyclase activation and inhibits monoamine transporter function. Monoamine autoreceptors (e.g., D 2 short , presynaptic α 2 , and presynaptic 5-HT 1A ) have

11868-427: The neuronal monoamine transporters , amphetamine also inhibits both vesicular monoamine transporters , VMAT1 and VMAT2 , as well as SLC1A1 , SLC22A3 , and SLC22A5 . SLC1A1 is excitatory amino acid transporter 3 (EAAT3), a glutamate transporter located in neurons, SLC22A3 is an extraneuronal monoamine transporter that is present in astrocytes , and SLC22A5 is a high-affinity carnitine transporter. Amphetamine

11997-443: The nucleus accumbens; magnesium ions inhibit NMDA receptors by blocking the receptor calcium channel . One review suggested that, based upon animal testing, pathological (addiction-inducing) psychostimulant use significantly reduces the level of intracellular magnesium throughout the brain. Supplemental magnesium treatment has been shown to reduce amphetamine self-administration (i.e., doses given to oneself) in humans, but it

12126-795: The number of binge eating days for the duration of the study. In addition, both a review and a meta-analytic systematic review found lisdexamfetamine to be superior to placebo in several secondary outcome measures, including persistent binge eating cessation, reduction of obsessive-compulsive related binge eating symptoms, reduction of body-weight, and reduction of triglycerides. Lisdexamfetamine, like all pharmaceutical amphetamines, has direct appetite suppressant effects that may be therapeutically useful in both BED and its comorbidities. Based on reviews of neuroimaging studies involving BED-diagnosed participants, therapeautic neuroplasticity in dopaminergic and noradrenergic pathways from long-term use of lisdexamfetamine may be implicated in lasting improvements in

12255-507: The occurrence of hyperpyrexia (i.e., core body temperature  ≥ 40 °C) is necessary for the development of amphetamine-induced neurotoxicity. Prolonged elevations of brain temperature above 40 °C likely promote the development of amphetamine-induced neurotoxicity in laboratory animals by facilitating the production of reactive oxygen species, disrupting cellular protein function, and transiently increasing blood–brain barrier permeability. An amphetamine overdose can result in

12384-762: The only post-synaptic receptor at which amphetamine is known to bind is the 5-HT1A receptor , where it acts as an agonist with low micromolar affinity. The full profile of amphetamine's short-term drug effects in humans is mostly derived through increased cellular communication or neurotransmission of dopamine , serotonin , norepinephrine , epinephrine , histamine , CART peptides , endogenous opioids , adrenocorticotropic hormone , corticosteroids , and glutamate , which it affects through interactions with CART , 5-HT1A , EAAT3 , TAAR1 , VMAT1 , VMAT2 , and possibly other biological targets . Amphetamine also activates seven human carbonic anhydrase enzymes, several of which are expressed in

12513-419: The onset of fatigue ), while improving reaction time . Amphetamine improves endurance and reaction time primarily through reuptake inhibition and release of dopamine in the central nervous system. Amphetamine and other dopaminergic drugs also increase power output at fixed levels of perceived exertion by overriding a "safety switch", allowing the core temperature limit to increase in order to access

12642-447: The opposite effect of TAAR1, and together these receptors provide a regulatory system for monoamines. Notably, amphetamine and trace amines possess high binding affinities for TAAR1, but not for monoamine autoreceptors. Imaging studies indicate that monoamine reuptake inhibition by amphetamine and trace amines is site specific and depends upon the presence of TAAR1 co-localization in the associated monoamine neurons. In addition to

12771-435: The opposite. Due to the effect pH has on absorption, amphetamine also interacts with gastric acid reducers such as proton pump inhibitors and H 2 antihistamines , which increase gastrointestinal pH (i.e., make it less acidic). Amphetamine exerts its behavioral effects by altering the use of monoamines as neuronal signals in the brain, primarily in catecholamine neurons in the reward and executive function pathways of

12900-667: The other medications used in RCTs, which included antidepressants (bupropion, mirtazapine , sertraline ), antipsychotics ( aripiprazole ), anticonvulsants ( topiramate , baclofen , gabapentin ), naltrexone , varenicline , citicoline , ondansetron , prometa , riluzole , atomoxetine , dextroamphetamine, and modafinil . A 2018 systematic review and network meta-analysis of 50 trials involving 12 different psychosocial interventions for amphetamine, methamphetamine, or cocaine addiction found that combination therapy with both contingency management and community reinforcement approach had

13029-674: The quality of evidence for these findings is low and is consequently reflected in the AASM's conditional recommendation for dextroamphetamine as a treatment option for narcolepsy. In 2015, a systematic review and a meta-analysis of high quality clinical trials found that, when used at low (therapeutic) doses, amphetamine produces modest yet unambiguous improvements in cognition, including working memory , long-term episodic memory , inhibitory control , and some aspects of attention , in normal healthy adults; these cognition-enhancing effects of amphetamine are known to be partially mediated through

13158-470: The reasons we're not going to do it is because we couldn't possibly write it with any degree of truth now, because that's not where we are or who we are any more. I always find it's better to write from a perspective of truth." Fox announced on 29 October 2007 that it would commission a pilot for an American version of Spaced , a project they then scuttled in May 2008 following a generally negative reaction from

13287-443: The regulation of eating behaviors that are observed even after the drug is discontinued. Narcolepsy is a chronic sleep-wake disorder that is associated with excessive daytime sleepiness, cataplexy , and sleep paralysis . Patients with narcolepsy are diagnosed as either type 1 or type 2, with only the former presenting cataplexy symptoms. Type 1 narcolepsy results from the loss of approximately 70,000 orexin -releasing neurons in

13416-514: The release of Spaced in Region 1 (U.S. and Canada). Despite the raised profile resulting from Shaun of the Dead and Hot Fuzz (film collaborations between Pegg and Wright that performed well in the Region 1 countries), no DVDs surfaced between 2004 and 2007. In an interview, it was suggested a deal with Anchor Bay Entertainment failed to come to fruition over the music rights. Wright announced

13545-611: The release of a Region 1 Spaced DVD release on 22 July 2008, which included an all-new commentary with Wright, Pegg, and Stevenson, as well as special guests Quentin Tarantino , Kevin Smith , Bill Hader , Diablo Cody , Matt Stone and Patton Oswalt . Supplemental features included the original commentaries, the Skip to the End documentary, outtakes, deleted scenes, and raw footage. Since

13674-413: The risk of developing a substance use disorder as an adult. Current models of ADHD suggest that it is associated with functional impairments in some of the brain's neurotransmitter systems ; these functional impairments involve impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the noradrenergic projections from the locus coeruleus to

13803-486: The second series. The show has a distinctive cinematic style set by Wright and is shot with a single camera . In addition to borrowing liberally from the visual language of film it has particular stylistic mannerisms, such as the recurring device of scene changes occurring in the middle of a pan. The series' atmosphere is also established by the use of a particular flavour of contemporary dance music on its soundtrack. Northern Exposure 's frequent use of fantasy sequences

13932-448: The series' creators and fans of the original show. Wright was initially approached about an American version after the first series was broadcast in 1999, and felt an American remake was impossible due to the series' fundamental theme. "Same reason it couldn't be a film," Wright said. "Part of the charm of 'Spaced' is, it's people in north London acting out stuff from American films... you know, Hollywood in, kind of, suburbia... American TV

14061-568: The severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence. Mild withdrawal symptoms from the discontinuation of amphetamine treatment at therapeutic doses can be avoided by tapering the dose. An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care. The severity of overdose symptoms increases with dosage and decreases with drug tolerance to amphetamine. Tolerant individuals have been known to take as much as 5 grams of amphetamine in

14190-532: The show has earned an estimated $ 1 billion in syndication fees alone for Televisa . Gliding On , a popular sitcom in New Zealand in the early 1980s, won multiple awards during its run including Best Comedy, Best Drama and Best Direction at the Feltex Awards . The first Russian sitcom series was "Strawberry", which resembled "Duty Pharmacy" in a Spanish format. It was aired from 1996 to 1997 on

14319-411: The show's end, cast and crew associated with Spaced have been quoted with differing opinions as to whether a third series would be produced, with their most recent statements reflecting a consensus that the show has concluded and will not see a third series. Edgar Wright initially was "torn" about making more Spaced , saying "we have genuinely talked about it and have some neat ideas that could work in

14448-548: The show, comprising seven episodes, premiered in the UK on Channel 4 on 24 September 1999, and the second and final series, also consisting of seven episodes, started on 23 February 2001 and concluded on 13 April. Both series were nominated for the BAFTA TV Award for Best Situation Comedy . Daisy Steiner and Tim Bisley are two London based twenty-somethings who meet by chance in a café while both are flat-hunting. Despite barely knowing each other, they conspire to pose as

14577-409: The significant health risks associated with recreational use. The first amphetamine pharmaceutical was Benzedrine , a brand which was used to treat a variety of conditions. Currently, pharmaceutical amphetamine is prescribed as racemic amphetamine, Adderall , dextroamphetamine , or the inactive prodrug lisdexamfetamine . Amphetamine increases monoamine and excitatory neurotransmission in

14706-425: The smart, on-the-ball, cool image" and that they sought "stimulation not intoxication [...] greater awareness, not escape" and " confidence and articulacy" rather than the " drunken rowdiness of previous generations." Dextroamphetamine's dopaminergic (rewarding) properties affect the mesocorticolimbic circuit ; a group of neural structures responsible for incentive salience (i.e., "wanting"; desire or craving for

14835-502: The striatum following exposure to amphetamine. This increase in extracellular glutamate presumably occurs via the amphetamine-induced internalization of EAAT3 , a glutamate reuptake transporter, in dopamine neurons. Amphetamine also induces the selective release of histamine from mast cells and efflux from histaminergic neurons through VMAT2 . Acute amphetamine administration can also increase adrenocorticotropic hormone and corticosteroid levels in blood plasma by stimulating

14964-413: The teeth , nosebleed, profuse sweating, rhinitis medicamentosa (drug-induced nasal congestion), reduced seizure threshold , tics (a type of movement disorder), and weight loss . Dangerous physical side effects are rare at typical pharmaceutical doses. Amphetamine stimulates the medullary respiratory centers , producing faster and deeper breaths. In a normal person at therapeutic doses, this effect

15093-434: The term "sitcom" emerged as radio and TV adapted these principles into a new medium. The word was not commonly used until the 1950s. Early television sitcoms were often filmed in front of a live studio audience using a multiple-camera setup , the latter of which continues in some modern productions such as The Big Bang Theory and Fuller House . Other formats make use of a laugh track or "canned laughter". Since

15222-603: The therapeutic range can interfere with working memory and other aspects of cognitive control. Amphetamine is used by some athletes for its psychological and athletic performance-enhancing effects , such as increased endurance and alertness; however, non-medical amphetamine use is prohibited at sporting events that are regulated by collegiate, national, and international anti-doping agencies. In healthy people at oral therapeutic doses, amphetamine has been shown to increase muscle strength , acceleration, athletic performance in anaerobic conditions , and endurance (i.e., it delays

15351-656: The treatment of both type 1 and type 2 narcolepsy. Treatment with pharmaceutical amphetamines is generally less preferred relative to other stimulants (e.g., modafinil ) and is considered a third-line treatment option. Medical reviews indicate that amphetamine is safe and effective for the treatment of narcolepsy. Amphetamine appears to be most effective at improving symptoms associated with hypersomnolence , with three reviews finding clinically significant reductions in daytime sleepiness in patients with narcolepsy. Additionally, these reviews suggest that amphetamine may dose-dependently improve cataplexy symptoms. However,

15480-591: The treatment of ADHD in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse side effects . A Cochrane review on the treatment of ADHD in children with tic disorders such as Tourette syndrome indicated that stimulants in general do not make tics worse, but high doses of dextroamphetamine could exacerbate tics in some individuals.   Binge eating disorder (BED)

15609-501: The user's personality and current mental state. Amphetamine psychosis (e.g., delusions and paranoia ) can occur in heavy users. Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy. According to the FDA, "there is no systematic evidence" that stimulants produce aggressive behavior or hostility. Amphetamine has also been shown to produce a conditioned place preference in humans taking therapeutic doses, meaning that individuals acquire

15738-466: Was "one of the key influences" in the creation of the show, and Pegg and Stevenson pitched the show to LWT as "a cross between The Simpsons , The X-Files and Northern Exposure ." The series is dense with references to popular culture, including but not limited to science fiction and horror films, comic books, and video games. The Series 2 DVD release introduced the "Homage-o-meter", an alternative set of subtitles listing every reference and homage;

15867-402: Was also angry at the media for what he felt was their overlooking of Stevenson's role in the creation of Spaced by connecting the series to Shaun of the Dead and Hot Fuzz in news articles. Sitcom The structure and concept of a sitcom have roots in earlier forms of comedic theater, such as farces and comedy of manners . These forms relied on running gags to generate humor, but

15996-927: Was criticized by several social commentators as inappropriately disrespectful to the office of the Prime Minister. The show nevertheless proved very popular with both television audiences and critics, becoming the most-watched Australian scripted comedy series of 2011. It was nominated at the 2012 Australian Academy of Cinema and Television Arts Awards for Best Television Comedy Series. Although there have been several notable exceptions, relatively few Canadian sitcoms attained notable success in Canada or internationally. Canadian television has had much greater success with sketch comedy and dramedy series. The popular show King of Kensington aired from 1975 to 1980, at its peak garnering an average of 1.5 to 1.8 million viewers weekly. The 1999 movie Trailer Park Boys

16125-530: Was followed up by a television series of the same name that ran from 2001 to 2018, airing in Canada, the U.S., and the U.K. Corner Gas , which ran for six seasons from 2004 to 2009, became an instant hit, averaging one million viewers per episode. It has been the recipient of six Gemini Awards and has been nominated almost 70 times for various awards. Other noteworthy recent sitcoms have included: Call Me Fitz , Schitt's Creek , Letterkenny , and Kim's Convenience , all of which have been winners of

16254-487: Was nominated for an International Emmy Award in 2001 for Popular Arts. Spaced Series 1 and 2 were both released on DVD in the United Kingdom. These were followed by a boxed set which collects the previously released single-series DVDs, adding a bonus disc with a feature-length documentary, Skip to the End , behind the scenes of the show, as well as a music video by Osymyso . Music rights issues long prevented

16383-559: Was the highest rating for a first episode in the history of Australian television, until the series premiere of Underbelly: A Tale of Two Cities in 2009, which garnered 2.58 million viewers. In 2013, Please Like Me received an invitation to screen at the Series Mania Television Festival in Paris, was praised by critics, and earned numerous awards and nominations. Also in 2013, At Home with Julia

16512-546: Was the most-watched show on Mexican television and had a Latin-American audience of 350 million viewers per episode at its popularity peak during the mid-1970s. The show continues to be popular in Central America as well as in Colombia, Venezuela, Brazil, Spain, the United States, and other countries. Syndicated episodes average 91 million daily viewers in all its American markets. Since it ceased production in 1992,

16641-419: Was upset that "they would a) never bother to get in touch but still b) splash my and Simon's names all over the trade announcements and imply that we're involved in the same way Ricky [Gervais] and Steve [Merchant] were with The Office ". Pegg and Stevenson also complained of the "lack of respect" demonstrated by the creators of the proposed American series, who left them out of discussions as well. Wright

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