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junker-town · 5 years

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Bad officiating could cost the Lions and Browns a playoff spot

Photo by Stacy Revere/Getty Images

The refs aren’t the only ones blowing it this week. Marcus Mariota and Jameis Winston are also costing themselves money.

Everyone knows NFL officiating is a mess right now. Well, anyone with eyes — so, not NFL officials. Amirite?

That’s a big topic of conversation at fall league meeting this week, not that that helps the Browns or Lions. Both teams found themselves on the wrong end of officiating that could, at best, be described as controversial. At worst? Well, it’s probably not safe to print, so we’ll just say the equivalent of watching the Titans-Broncos game this past weekend.

Let’s start with the Browns. Less than a week after getting manhandled in San Francisco, the Browns got to flee to the Cleve to host the Seahawks. The home team led for a majority of the game, but the mistakes started piling up. The most egregious call from the refs was thinking this is an illegal blindside block on Jarvis Landry:

This was not even close to a blindside block by Jarvis Landry. Refs hate the Browns so much pic.twitter.com/AwsseApyfs

— Sir Yacht (@SirYacht) October 13, 2019

That came right after a questionable ineligible man downfield penalty.

A costlier one was a horse collar flag that gave the Seahawks an extra 15 yards on what turned out to be their game-winning drive. But there were several others to choose from, including a possible touchdown for the Browns that never counted, an uncalled facemask penalty on fourth-and-goal that gave Seattle the ball, and an iffy Seahawks catch that sealed the game.

The Browns lost by just four points and fell two games back of the Ravens in the AFC North. A win over a contender could’ve been a turning point for them. Now, they’re tied with the Steelers and have the Patriots waiting for them next time they play.

On Monday night, the Lions never trailed the Packers at Lambeau — until the clock struck zero, that is. The officiating was indefensible enough that the NFL admitted at least one of the many, many bad calls against the Lions was wrong. Trey Flowers’ second (and, on record, an incorrect call) hands to face flag let the Packers sit on the ball until their game-winning field goal:

oh my god the refs bailed out Green Bay with a nonexistent hands-to-the-face penalty on third-and-long FOR THE SECOND TIME THIS QUARTER (both on Trey Flowers, good lord) pic.twitter.com/Hg3k0OxS3L

— Christian D'Andrea (@TrainIsland) October 15, 2019

The Lions had four dubious calls in the fourth quarter alone go against them in the 23-22 loss. They dropped to last place in a tightly contested NFC North, while the Packers improved to 5-1 and were able to remain all alone at the top.

Both the Lions and Browns have serious gripes with the way they lost. And when January rolls around and playoff spots can come down to one game, Week 6 could end up being the deciding factor.

Panic index: The Lions and Browns need to look in the mirror a bit with how they ended up in the L column. The Lions have had fourth-quarter leads in all three of their non-wins and wasted precious red zone opportunities by settling for field goals against the Packers. The Browns are the most penalized team in the league, and only the Giants have given away the ball more. Against Seattle, they turned it over four times, including three interceptions from Baker Mayfield.

That said, these are two of the most hard-luck franchises in the NFL who are trying to overcome their history. They shouldn’t have to beat their opponent and the refs each week. The good news is that there’s still a lot of season left, and the teams usually worthy of a playoff spot are able to get past situations like this and move on to the next game.

Jameis Winston and Marcus Mariota are blowing their contract years

2019 is the most important season for the top two picks of the 2015 NFL Draft. And both Jameis Winston and Marcus Mariota are blowing it.

The former Heisman winners both came into the season with just one year remaining on their rookie contracts. While a valued franchise quarterback would have been locked into long-term extensions by now, each faces an uncertain future thanks to erratic histories of uneven play. Without a track record of consistent performances to bring to the negotiating table, the pressure’s been on each to step up and prove their worth. Another underwhelming season would cast the pair firmly in the Ryan Fitzpatrick tier of unreliable veterans.

Through six weeks, Winston and Mariota are on a path to journeyman-dom.

Mariota has been by far the more disappointing player. Four injury-plagued seasons in Nashville left his status as an offensive cornerstone in the air, and he gave his detractors their strongest argument yet in a complete meltdown in Denver. Mariota put together the worst game of his pro career, going 7-of-18 and throwing a pair of interceptions in a performance so bad it convinced head coach Mike Vrabel to bench him in favor of Ryan Tannehill.

Tannehill, for the record, threw for more than double the yards Mariota had in fewer pass attempts. That left the Titans with a starting quarterback decision to make — and they’re going with Tannehill, sending Mariota to the bench.

Winston had been on a more optimistic course in 2019 due to the presence of QB-whispering head coach Bruce Arians, but any gain he’d made in the previous four weeks (a 10:2 TD:INT ratio and a 111.6 passer rating) was quickly wiped away by an absolute disaster in Week 6. The mercurial QB was responsible for SIX turnovers against the Panthers, throwing five interceptions and losing one of two fumbles.

That derailed an otherwise encouraging start to the season for a player facing free agency. Winston was on pace to set personal highs in passer rating and adjusted yards per pass coming into his meltdown in London. And while he’s still a capable big-armed passer, his ongoing lapses in judgment set a defined ceiling as an “exciting and ultimately heartbreaking” NFL quarterback.

Panic index: Actually, being completely inconsistent and untrustworthy is pretty on brand for Winston and Mariota. We look forward to their training camp QB battles in Washington and Cincinnati next fall.

The Rams’ offensive line has crumbled into a mess

There’s a long history of Super Bowl hangovers. Just a few years ago, the Panthers followed their 15-1 season that ended with a Super Bowl 50 loss by going 6-10 in 2016. By comparison, the Rams’ 3-3 record in 2019 isn’t that bad — or at least not right now. But it’s still surprising.

Los Angeles looked like a team that could easily shake off any kind of Super Bowl loser curse. The Rams have a bevy of young offensive stars with Jared Goff, Todd Gurley, Brandin Cooks, Cooper Kupp, and Robert Woods. The defense has back-to-back Defensive Player of the Year Aaron Donald wreaking havoc in the middle and just traded for an elite cornerback in Jalen Ramsey.

The problem is that all that offensive talent doesn’t matter much when it has no room to work. The Rams’ offensive line — which graded out as one of the best in the NFL in 2018 — didn’t take long to collapse into a heap of garbage.

The Rams are 31st in the NFL in pass blocking, just barely ahead of the tanking Dolphins, according to Pro Football Focus. They’re 27th in run blocking.

Elder statesman Andrew Whitworth hasn’t been a problem at left tackle. He’s allowed just one hit on Jared Goff so far in 2019. That’s where the positivity ends. The interior of the offensive line is getting beat consistently and the Rams can’t run or pass very well as a consequence.

The Rams already took their first step toward fixing the issue by trading for the Browns’ backup center, Austin Corbett. It’ll probably take more than just that, though.

Panic index: The LA offense isn’t horrible. It’s still 10th in points scored and 12th in total yards. But that’s barely above average, and when it’s combined with mediocre defense, the result is a .500 football team. Unless the offensive line picks up the slack now that Corbett’s in the middle, that’s not changing.

The Cowboys’ defense has taken a big step back

Dallas dropped to 3-3 in a surprising 24-22 loss to the New York Jets, and the defense is much to blame. The Cowboys gave up 382 total yards — 332 of those coming from quarterback Sam Darnold alone.

One of the worst defensive breakdowns came in the second quarter, as Darnold found Robby Anderson for a 92-yard touchdown pass — the longest play in the NFL this season.

SAM DARNOLD IS BACK! 92-yard throw to Robby Anderson for SIX! pic.twitter.com/vP34TudMGw

— Entirely Sports (@Entirely_Sports) October 13, 2019

The problem starts with the defensive line — the unit has dealt with injuries (DL Tyrone Crawford headed to the IR most recently), and struggles with stopping the run and creating pressure on the quarterback. The defense has fallen to No. 25 in Football Outsiders’ DVOA metric and is also one of the worst in adjusted sack rate (27th).

Christian D’Andrea summed up a lot of their issues earlier this week:

The pass rush has regressed as well. Jets QBs had been sacked on 24 of their 144 dropbacks coming into Week 6 — an absurd 16.7 percent of their pass attempts (though 16 of those came with Luke Falk’s behind center). Darnold was sacked just twice over the course of 34 designed pass plays when the Cowboys came to town. That’s not what Dallas had been hoping for when it signed DeMarcus Lawrence to a five-year, $105 million extension last spring.

Just two weeks ago, we had the Cowboys’ offense in the panic index after putting up just 10 points against the New Orleans Saints. But at least the defense kept them in the game. Now, Dallas has let the Packers and Jets to score season-high points against them in back-to-back weeks. As Bill Barnwell points out, an offense regressing with a stout defense isn’t all that concerning, but the Cowboys have fallen off on both sides of the ball recently:

The Cowboys offense has fallen off over the last three weeks. Another prominent offense has similarly declined, but it’s been masked by their defense. pic.twitter.com/qAJLiloBTz

— Bill Barnwell (@billbarnwell) October 15, 2019

Panic index: The biggest concern here is that both the offense and defense have regressed in recent weeks. But there were signs of life with what the Cowboys did in the second halves against both the Jets and Packers, although they ultimately fell short. Dallas was a top-10 defense just a year ago, and if it wants to get back to the playoffs again, the unit has to perform a lot better than how it has been.

The Chiefs (and Frank Clark) can’t get a sack

Deshaun Watson and the Texans went into Kansas City as underdogs to Patrick Mahomes and the Chiefs. But Watson left with the big win because the Chiefs couldn’t take advantage of Houston’s biggest weakness: its offensive line.

Despite Watson being sacked 18 times already this season, the Chiefs couldn’t bring him down. During the offseason, Kansas City let Justin Houston and Dee Ford leave, and the splashy addition of Frank Clark hasn’t resulted in an improved rush. The team is near the bottom of the league in sacks, with 11 on the season, and it’s last in adjusted sack rate.

More concerning than the overall number is the Chiefs’ complete lack of production in consecutive games. They also failed to sack Jacoby Brissett in a loss to the Colts, and only managed one sack on Gardner Minshew in Week 1.

Panic index: The Chiefs have been dealing with injuries — both Chris Jones and Xavier Williams missed the game against the Texans — but this isn’t a one-week issue, and additions like Clark were expected to bring the pressure on their own. Clark hasn’t been that guy so far, and the Chiefs need an answer.

0 notes

aleesblog · 5 years

Text

Speed from Cloud Nine to Brain Gain

Long before the advent of medicinal chemistry, Nature’s Treasure Chest had revealed a diversity of tonics all of which would now be classified as stim- ulants. Ma-huang, the yellow hemp (Ephedra sinica) known to contain ephed- rine and now banned in the United States was revered in Ancient China for its performance enhancement and used by its practitioners to induce perspiration and treat chest complaints. Quids of betel and khat leaves have been chewed for thousands of years in South East Asia and the Horn of Africa as a way to loosen the tongue and enhance gregariousness. Traces of nicotine from tobacco have been found on a Mayan vase dated 700 AD providing support for its early use as an entheogen by the shamen. The chewing of coca leaves mixed with lime can be traced back at least as far as the Moche period (600 AD). Among the Incas, coca was a divine practice and its leaves were revered by the Andean Indians as a means of assuaging hunger. By the fifteenth century AD, the beans of the coffee plant were being brewed in public places on the Arabian Peninsula as a pick me up for the exhausted.

When tea, coffee, and chocolate were brought from the new colonies by the great navigators the elite of Western Europe considered them sacred gifts and profane pleasures.

Following its extraction from Erythroxylum coca in the middle of the nineteenth century cocaine was soon adopted by the medical profession as a local anesthetic, nasal decongestant, and mistakenly as an effective treatment for morphinism. Sigmund Freud observed that it caused exhilaration and lasting euphoria and in 1885 Parke-Davis marketed it in the United States with the sensational but largely truthful slogan that it could, “supply the place of food, make the coward brave, the silent eloquent and render the sufferer insensitive to pain.” At first, it was considered no more addictive than coffee or tea and was included as a vital ingredient in Coca-Cola. Mounting concerns about its addictive potential eventually led in 1914 to the U.S. Government decreeing that its unauthorized possession for recreational purposes was now a criminal offense.

Amphetamine and methylamphetamine were first synthesized around the same time as cocaine but little interest was shown in them until the 1930s when Smith Kline and French looking for a substitute for ephedrine launched Dexedrine inhalers for the relief of hay fever and asthma. During World War 2, amphetamine was widely used by the Allies to combat fatigue and increase bravado but concerns about the increasingly widespread use of “Mother’s little helpers” in the 1960s led to its “off label” use being outlawed in Europe and North America. It was hardly surprising that a class of drugs reported to give limitless energy, increase vigilance, and improve sexual per- formance might prove attractive to human beings. Stockbrokers were able to stay up all night to play the international markets and be in the office the following morning fresh as daisies. Unscrupulous professional sportsmen got an edge on their adversaries broke records and achieved glory. Long distance truck drivers reached ever more demanding deadlines without falling asleep at the wheel. “Speed” offered a short cut to prosperity and bliss and fuelled the capitalist dream.

Advocates of responsible stimulant use pointed to the many well-known artists and intellectuals who attributed their creativity to amphetamine use. Jack Kerouac wrote On The Road in a “creative groove” working day and night for 3 weeks typing on a long roll of paper, chosen deliberately to avoid interrupting his rhythm.

Benny has made me see a lot. The process of intensifying awareness naturally leads to an overflow of old notions, and voila, new material wells up like water forming its proper level, and makes itself evident at the brim of consciousness.

Amphetamines accelerated his thought processes and allowed him to write in “the now.” He had found a new spontaneous way of writing that banished convention and communicated raw physical and emotional experience. “Speed” has also played a role in some of the youth culture movements of Generations X Y, and Z. First used by the Beats in the jazz scene “Bennies” and “Purple Hearts” helped the Mods gain their teenage rite of passage. Bronchipax (ephedrine) and Durophet black bombers (dexamphetamine) helped Northern Soul boys escape bleak post-industrial landscapes while “Ecstasy” brought a sense of emotional connection on the dance floor, increased appreciation of sound, color and touch, and a feeling of closeness to others.

The risk of physical dependence with cocaine and amphetamine is relatively low but heavy regular usage or overdosage can have serious medical consequences leading to accident and emergency hospital referral. Reckless behavior and feelings of invincibility lead to falls, fights, and road traffic acci- dents, and death can occur from malignant hyperthermia. Profound agita- tion and acute paranoid psychoses with morbid jealousy require urgent psychiatric referral and drug abstinence after long-term use can unmask chronic depression with suicidal risk. Chorea (crack dancing) abnormal ste- reotyped movements of the lips, mouth and tongue, and teeth grinding are underreported neurological complications. Complex stereotyped purpose- less behaviors (punding) first described in Scandinavian and Californian bikers using high doses of intravenous amphetamine are also now recognized to occur with cocaine and are also seen in patients with Parkinson’s disease treated with l-dopa, the natural precursor of dopamine. The sympathomimetic properties of stimulants can also lead to hypertension and an increased risk of stroke and heart failure.

The substituted amphetamines increase brain dopamine, serotonin, and noradrenaline release and inhibit reuptake at axonal synapses. Both cocaine and methamphetamine also act as substrates at vesicular and synaptic storage sites leading to competitive inhibition with monoamine transporters. It would seem reasonable therefore, to expect that they might be useful treat- ments for both depression and Parkinson’s disease but so far the results have been modest at best. The brains of chronic methamphetamine users have been found to have significant (50–60%) reductions in dopamine but in con- trast to the findings in Parkinson’s disease caudate dopamine deficiency which in some cases approached that seen in Parkinson’s disease was always greater than that found in the putamen. None of the methamphetamine addicts had developed Parkinson’s disease during life and in contrast to MPTP the unwanted by product of kitchen chemistry manufacture of the narcotic MPPP there was no evidence to suggest that it caused structural damage to dopamine neurones (Moszczynska et al., 2004). Further, evidence for permanent changes in striatal dopamine signaling, however, comes from functional imaging studies in abstinent methamphetamine addicts where dopamine receptor changes have been found (Volkow et al., 2001).

Amphetamine type stimulants comprise the second most widely used class of illicit drugs in the world. According to a national survey of recreational drug use in the United States carried out seventeen years ago 1 in 20 adults aged 35 years or older had used non-prescribed amphetamines at least once (mainly “crystal meths”) (Office of Applied Studies, 1998). At least 4 million people (1.5% of the population) in the United States aged 12 and older have used methylphenidate at least once off label. Increasingly widespread use of “crystal meths” (methylamphetamine) has led to public health concerns that dopamine and serotonergic neurones could be “excited to death” in chronic high-dose users increasing the risk of depression and delayed Parkinson’s disease (Guilarte, 2001).

Several retrospective case-control and population studies have provided backing for this notion. A 16-year follow-up cohort study involving California inpatient hospital episodes and death records in patients at least 30 years of age found an increased risk of Parkinson’s disease in amphetamine users in an active comparator group of cocaine users and another control group with appendicitis. For every 10,000 meth/amphetamine users over 30 followed up for 10 years 21 cases of Parkinson’s disease would be expected to occur compared with only 12 cases in the two control groups (Callaghan, Cunningham, Sykes, & Kish, 2012). In a telephone survey from three faculty practice clinics in San Francisco, there was an increase in Parkinson’s disease but not peripheral neuropathy or amyotrophic lateral sclerosis in adult methamphetamine users with an Odds Ratio of 8.27. In the cases with Parkinson’s disease, there was an average of 27 years between amphetamine exposure and the onset of bradykinesia and rigidity (Garwood, Bekele, McCulloch, & Christine, 2006).

Individuals with low-novelty-seeking personality traits, nonsmokers, and men who drink no caffeinated beverages are at greater risk of developing Parkinson’s disease (Ascherio et al., 2004; Menza, Golbe, Cody, & Forman, 1993). These individuals are less likely to experiment with recreational drugs including cocaine and stimulants. Nevertheless, these findings provide sup- port for the notion that there may be some individuals who would otherwise be considered at lower risk of developing Parkinson’s disease who increase their chances of developing the disease from chronic use of high-dose meth- amphetamine (Guilarte, 2001). Although the mechanisms are completely different some the patients now in their sixties who were identified to have been exposed to subtoxic levels of MPTP have not yet gone on to develop Parkinsonism (Tetrud, Langston, Garbe, & Ruttenber, 1989).

Each new stimulant craze seems to last 30 or 40 years (cocaine, amphet- amine, methylamphetamine, freebase cocaine, and MDMA). In the last few years, mephedrone (known on the street as “Meouw Meouw,” “Bubble,” “Vanilla Sky,” “White Rush,” “Impact,” “White Dove,” or “Drone”) sometimes mixed with another stimulant methylone (Explosion) has started to replace Ecstasy as the favored party drug in the United Kingdom. It is a synthetic cathinone identical to one of the alkaloids present in khat and is sold on the Internet as crystals disguised as “bath salts” (internet names include “Purple Wave,” “Zoom,” and “Cloud Nine”). In the United Kingdom, substituted cathinones were made illegal in 2010 and khat widely used by Somali and Ethiopian immigrants and bought in markets has also been banned.

Although there is as yet no convincing evidence that methcathinone can lead to irreversible brain damage in humans, significant numbers of drug users in Russia, Estonia, Latvia, Ukraine, and Georgia who synthesizes methcathinone from pseudoepehedrine (Sudafed) nasal decongestants mixed with potassium permanganate and vinegar have developed a severe irreversible neurological syndrome (Sikk et al., 2007). Whether toxic levels of methcathinone in these “ephedrone” addicts compound the toxic damage of manganese related to the method of preparation remains to be determined.

“Designer psychostimulants” are also disguised as “plant food,” “room deodorants,” “fish food,” or “computer screen cleaner.” Some of these sub- stances are relatively easily made without specific laboratory equipment and instructions for their manufacture are readily available on the web. Other “designer” cathinones include butylone (bk-MBDB), napthylpyrovalerone (NRG-1), and methylenedioxypyrovalerone (MPDV). A group of entactogens sometimes called 2C drugs similar in structure to Ecstasy, Benzo-fury (5and 6-APB) DMBA (Frenzy) and 4,40-DMAR (Serotoni), and some piperazines are other stimulants currently in use. A methamphetamine-caffeine tablet known in Thailand as “yaba” (literal translation madness drug) is now beginning to be exported and used as a party drug by speed freaks in other countries. Some batches are adulterated with small amounts of heroin to boost the effect. These compounds are promoted as “legal highs” leading to the misapprehension that they are without risk.

The “uppers” epidemics have totally overshadowed the potential of substituted amphetamines for good and their use in medicine is now restricted to the treatment of sleep disorders including narcolepsy and hypersomnolence (amphetamine and modafinil), attention deficit hyperactivity disorder in children (amphetamines and methylphenidate) and as second line treatment for orthostatic hypotension due to autonomic failure (ephedrine). They are also sometimes used to counteract the sedative effects of opioids in palliative care and for legitimate non-medical uses such as to combat potentially fatal tiredness in military aviation and space flight.

Man’s craving for excitement and exhilaration has resulted in an insatiable and so far unsatisfied quest for the perfect pick me up. Even though the regions of the brain now linked with pleasure are more clearly delineated Aldous Huxley’s Brave New World “State prescribed happy pill” remains a pipe dream.

Although there is still considerable interest in the potential of stimulants to relieve chronic mental fatigue, suppress appetite and treat depression recent focus has been less on their powers of reinvigoration and more on their potential to improve vigilance and lay down long-term memories. On American university campuses some white males have replaced caffeine with methylphenidate, modafinil, and amphetamines as a way of helping them compensate for activities that are detrimental to their ability to pass competitive examinations. An online survey conducted by the Journal Nature on 1600 academics in 60 countries revealed that one in five had used pep pills for nonmedical reasons (Sahakian & Morein-Zamir, 2007).

Despite the substantial risks and hazards involved in nootropic research, it is to be hoped that neuroscientists and Pharma’s psychiatric drug research departments will not give up on a group of drugs with the potential to improve society. If science can develop new stimulants that would safely allow human beings to repeat a whole conversation verbatim or increase their digit span from seven to twelve then smart drugs might no longer just be a privileged “Students little helper” but be used to enhance concentration and cognition in those from deprived socioeconomic backgrounds who “have been dealt a poor deck of cards.”

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aleesblog · 6 years

Text

The Story of “Speed” from “Cloud Nine” to Brain Gain

Andrew Lees*,1, Katrin Sikk†, Pille Taba

Abstract

The substituted amphetamines have had a checkered medical history intertwined with a sensational cultural history. Mankind's insatiable fascination with speed has led to widespread misuse sometimes with disastrous neurological and psychiatric conse- quences that may cause a permanent harm but their potential to enhance cognition should not be dismissed or forgotten. Further, smarter research could perhaps still lead to an expanded beneficial role for stimulant use in modern society.

Long before the advent of medicinal chemistry, Nature’s Treasure Chest had revealed a diversity of tonics all of which would now be classified as stim- ulants. Ma-huang, the yellow hemp (Ephedra sinica) known to contain ephed- rine and now banned in the United States was revered in Ancient China for its performance enhancement and used by its practitioners to induce perspi- ration and treat chest complaints. Quids of betel and khat leaves have been chewed for thousands of years in South East Asia and the Horn of Africa as a way to loosen the tongue and enhance gregariousness. Traces of nicotine from tobacco have been found on a Mayan vase dated 700 AD providing support for its early use as an entheogen by the shamen. The chewing of coca leaves mixed with lime can be traced back at least as far as the Moche period (600 AD). Among the Incas, coca was a divine practice and its leaves were revered by the Andean Indians as a means of assuaging hunger. By the fifteenth century AD, the beans of the coffee plant were being brewed in public places on the Arabian Peninsula as a pick me up for the exhausted.

When tea, coffee, and chocolate were brought from the new colonies by the great navigators the elite of Western Europe considered them sacred gifts and profane pleasures.

Following its extraction from Erythroxylum coca in the middle of the nineteenth century cocaine was soon adopted by the medical profession as a local anesthetic, nasal decongestant, and mistakenly as an effective treat- ment for morphinism. Sigmund Freud observed that it caused exhilaration and lasting euphoria and in 1885 Parke-Davis marketed it in the United States with the sensational but largely truthful slogan that it could, “supply the place of food, make the coward brave, the silent eloquent and render the sufferer insensitive to pain.” At first, it was considered no more addictive than coffee or tea and was included as a vital ingredient in Coca-Cola. Mounting concerns about its addictive potential eventually led in 1914 to the U.S. Government decreeing that its unauthorized posses- sion for recreational purposes was now a criminal offense.

The risk of physical dependence with cocaine and amphetamine is rel- atively low but heavy regular usage or overdosage can have serious medical consequences leading to accident and emergency hospital referral. Reckless behavior and feelings of invincibility lead to falls, fights, and road traffic acci- dents, and death can occur from malignant hyperthermia. Profound agita- tion and acute paranoid psychoses with morbid jealousy require urgent psychiatric referral and drug abstinence after long-term use can unmask chronic depression with suicidal risk. Chorea (crack dancing) abnormal ste- reotyped movements of the lips, mouth and tongue, and teeth grinding are underreported neurological complications. Complex stereotyped purpose- less behaviors (punding) first described in Scandinavian and Californian bikers using high doses of intravenous amphetamine are also now recognized to occur with cocaine and are also seen in patients with Parkinson’s disease treated with l-dopa, the natural precursor of dopamine. The sympathomi- metic properties of stimulants can also lead to hypertension and an increased risk of stroke and heart failure.

MPTP the unwanted by product of kitchen chemistry manufacture of the narcotic MPPP there was no evidence to suggest that it caused structural damage to dopamine neurones (Moszczynska et al., 2004). Further, evi- dence for permanent changes in striatal dopamine signaling, however, comes from functional imaging studies in abstinent methamphetamine addicts where dopamine receptor changes have been found (Volkow et al., 2001).

Amphetamine type stimulants comprise the second most widely used class of illicit drugs in the world. According to a national survey of recrea- tional drug use in the United States carried out seventeen years ago 1 in 20 adults aged 35 years or older had used non-prescribed amphetamines at least once (mainly “crystal meths”) (Office of Applied Studies, 1998). At least 4 million people (1.5% of the population) in the United States aged 12 and older have used methylphenidate at least once off label. Increasingly widespread use of “crystal meths” (methylamphetamine) has led to public health concerns that dopamine and serotonergic neurones could be “excited to death” in chronic high-dose users increasing the risk of depres- sion and delayed Parkinson’s disease (Guilarte, 2001).

Each new stimulant craze seems to last 30 or 40 years (cocaine, amphet- amine, methylamphetamine, freebase cocaine, and MDMA). In the last few years, mephedrone (known on the street as “Meouw Meouw,” “Bubble,” “Vanilla Sky,” “White Rush,” “Impact,” “White Dove,” or “Drone”) some- times mixed with another stimulant methylone (Explosion) has started to replace Ecstasy as the favored party drug in the United Kingdom. It is a syn- thetic cathinone identical to one of the alkaloids present in khat and is sold on the Internet as crystals disguised as “bath salts” (internet names include “Purple Wave,” “Zoom,” and “Cloud Nine”). In the United Kingdom, substituted cathinones were made illegal in 2010 and khat widely used by Somali and Ethiopian immigrants and bought in markets has also been banned.

Although there is as yet no convincing evidence that methcathinone can lead to irreversible brain damage in humans, significant numbers of drug users in Russia, Estonia, Latvia, Ukraine, and Georgia who synthesizes methcathinone from pseudoepehedrine (Sudafed) nasal decongestants mixed with potassium permanganate and vinegar have developed a severe irrevers- ible neurological syndrome (Sikk et al., 2007). Whether toxic levels of methcathinone in these “ephedrone” addicts compound the toxic damage of manganese related to the method of preparation remains to be determined.

The “uppers” epidemics have totally overshadowed the potential of substituted amphetamines for good and their use in medicine is now restricted to the treatment of sleep disorders including narcolepsy and hyp- ersomnolence (amphetamine and modafinil), attention deficit hyperactivity disorder in children (amphetamines and methylphenidate) and as second line treatment for orthostatic hypotension due to autonomic failure (ephedrine). They are also sometimes used to counteract the sedative effects of opioids in palliative care and for legitimate non-medical uses such as to combat poten- tially fatal tiredness in military aviation and space flight.

Man’s craving for excitement and exhilaration has resulted in an insatia- ble and so far unsatisfied quest for the perfect pick me up. Even though the regions of the brain now linked with pleasure are more clearly delineated Aldous Huxley’s Brave New World “State prescribed happy pill” remains a pipe dream.

REFERENCES

Ascherio, A., Weisskopf, M. G., O’Reilly, E. J., McCullough, M. L., Calle, E. E., Rodriguez, C., et al. (2004). Coffee consumption, gender, and Parkinson’s disease mortality in the cancer prevention study II cohort: The modifying effects of estrogen. American Journal of Epidemiology, 160(10), 977–984.

The Story of “Speed” from “Cloud Nine” to Brain Gain 7

Callaghan, R. C., Cunningham, J. K., Sykes, J., & Kish, S. J. (2012). Increased risk of Parkinson’s disease in individuals hospitalized with conditions related to the use of meth- amphetamine or other amphetamine-type drugs. Drug and Alcohol Dependence, 120(1–3), 35–40.

Garwood, E. R., Bekele, W., McCulloch, C. E., & Christine, C. W. (2006). Amphetamine exposure is elevated in Parkinson’s disease. Neurotoxicology, 27(6), 1003–1006.

Guilarte, T. R. (2001). Is methamphetamine abuse a risk factor in parkinsonism? Neurotoxicology, 22(6), 725–731.

Menza, M. A., Golbe, L. I., Cody, R. A., & Forman, N. E. (1993). Dopamine-related per- sonality traits in Parkinson’s disease. Neurology, 43(3 Pt 1), 505–508.

Moszczynska, A., Fitzmaurice, P., Ang, L., Kalasinsky, K. S., Schmunk, G. A., Peretti, F. J., et al. (2004). Why is parkinsonism not a feature of human methamphetamine users? Brain, 127(Pt 2), 363–370.

Office of Applied Studies. (1998). National household survey on drug abuse, Main findings. DHSS publication No SMA 00-381 Rockville, MD 2000. Substance abuse and mental health services administration, 32.

Sahakian, B., & Morein-Zamir, S. (2007). Professor’s little helper. Nature, 450(7173), 1157–1159.

Sikk, K., Taba, P., Haldre, S., Bergquist, J., Nyholm, D., Zjablov, G., et al. (2007). Irrevers- ible motor impairment in young addicts—Ephedrone, manganism or both? Acta Neuro- logica Scandinavica, 115(6), 385–389.

Tetrud, J. W., Langston, J. W., Garbe, P. L., & Ruttenber, A. J. (1989). Mild parkinsonism in persons exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neurology, 39(11), 1483–1487.

Volkow, N. D., Chang, L., Wang, G. J., Fowler, J. S., Ding, Y. S., Sedler, M., et al. (2001). Low level of brain dopamine D2 receptors in methamphetamine abusers: Association with metabolism in the orbitofrontal cortex. The American Journal of Psychiatry, 158(12), 2015–2021.

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