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Only nine of 185 randomized clinical trials and 23 of 259 non-randomized studies and patient reports of methylphenidate in children and adolescents with ADHD reported assessment of psychotic symptoms.

During the Vietnam War, the U.S. Army Used Drugs to Build Super Soldiers - The Atlantic

“We had the best amphetamines available and they were supplied by the U.S. government,” said Elton Manzione, a member of a long-range reconnaissance platoon (or Lurp). He recalled a description he’d heard from a navy commando, who said that the drugs “gave you a sense of bravado as well as keeping you awake. Every sight and sound was heightened. You were wired into it all and at times you felt really invulnerable.” Soldiers in units infiltrating Laos for a four-day mission received a medical kit that contained, among other items, 12 tablets of Darvon (a mild painkiller), 24 tablets of codeine (an opioid analgesic), and six pills of Dexedrine. Before leaving for a long and demanding expedition, members of special units were also administered steroid injections.

During the Vietnam War, the U.S. Army Used Drugs to Build Super Soldiers - The Atlantic

Since World War II, little research had determined whether amphetamine had a positive impact on soldiers’ performance, yet the American military readily supplied its troops in Vietnam with speed. “Pep pills” were usually distributed to men leaving for long-range reconnaissance missions and ambushes. The standard army instruction (20 milligrams of dextroamphetamine for 48 hours of combat readiness) was rarely followed; doses of amphetamine were issued, as one veteran put it, “like candies,” with no attention given to recommended dose or frequency of administration. In 1971, a report by the House Select Committee on Crime revealed that from 1966 to 1969, the armed forces had used 225 million tablets of stimulants, mostly Dexedrine (dextroamphetamine), an amphetamine derivative that is nearly twice as strong as the Benzedrine used in the Second World War. The annual consumption of Dexedrine per person was 21.1 pills in the navy, 17.5 in the air force, and 13.8 in the army.

Elon Musk, Amid Tesla Furor, Tells of ‘Most Difficult’ Year - The New York Times

He said he had been working up to 120 hours a week recently — echoing the reason he cited in a recent public apology to an analyst whom he had berated. In the interview, Mr. Musk said he had not taken time off of more than a week since 2001, when he was bedridden with malaria. “There were times when I didn’t leave the factory for three or four days — days when I didn’t go outside,” he said. “This has really come at the expense of seeing my kids. And seeing friends.” Mr. Musk stopped talking, seemingly overcome by emotion. He turned 47 on June 28, and he said he spent the full 24 hours of his birthday at work. “All night — no friends, nothing,” he said, struggling to get the words out.

ADHD drugs do not improve cognition in healthy college students -- ScienceDaily

Results of the new study, published last month in the journal Pharmacy, show that the standard 30 mg dose of Adderall did improve attention and focus -- a typical result from a stimulant -- but that effect failed to translate to better performance on a battery of neurocognitive tasks that measured short-term memory, reading comprehension and fluency. Weyandt has a theory about why working memory would be adversely affected by the medication. Brain scan research shows that a person with ADHD often has less neural activity in the regions of the brain that control executive function -- working memory, attention, self-control. For people with ADHD, Adderall and similar medications increase activity in those regions and appear to normalize functioning. "If your brain is functioning normally in those regions, the medication is unlikely to have a positive effect on cognition and my actually impair cognition. In other words, you need to have a deficit to benefit from the medicine," Weyandt said. Participants in the study also reported their perceived effects of the drug and its impact on their emotions, with students reporting significant elevation of their mood when taking Adderall. In contrast to the small, mixed effects on cognition, the drug had much larger effects on mood and bodily responses, increasing positive mood, emotional ratings of the drug effect, heart rate and blood pressure. "These are classic effects of psychostimulants," said White. "The fact that we see these effects on positive emotion and cardiovascular activity, in the same individuals for whom cognitive effects were small or negative in direction, is important. It indicates that the cognitive and the emotional impact of these drugs are separate. How you feel under the drug does not necessarily mean that there is an improvement in cognition; there can be a decrease, as seen here in young adults without ADHD."

Nonprescription use of Ritalin linked to adverse side effects, UB study finds - University at Buffalo

“We saw changes in the brain chemistry in ways that are known to have an impact on the reward pathway, locomotor activity, and other behaviors, as well as effects on body weight,” Thanos says. “These changes in brain chemistry were associated with serious concerns such as risk-taking behaviors, disruptions in the sleep/wake cycle and problematic weight loss, as well as resulting in increased activity and anti-anxiety and antidepressive effects.” Further research indicated that female subjects were more sensitive to the behavioral effects of methylphenidate than the males. Thanos hopes that studying the effects of methylphenidate on those without ADHD may lead to a greater understanding of how the drug works on the brain and behavior, and can help researchers understand the impact of the drug on young people throughout development. “Understanding more about the effects of methylphenidate is also important as people with ADHD show greater risk to be diagnosed with a drug dependency problem,” Thanos says. “In addition, this study highlights the potential long-range risks college students take in using Ritalin for a quick study boost.”

10 SEALs Set to be Separated from the Service for failing Drug Tests; Investigation Underway - USNI News

“We have a zero-tolerance policy for the use of illicit drugs and as such these individuals will be held accountable for their actions. We are confident in our drug testing procedures and will continue to impress on all members of the command that illicit drugs are incompatible with the SEAL ethos and Naval service.” It’s unclear if the incidents are related. The failure of the drug tests has sparked a Naval Special Warfare Command investigation into the circumstances around the failures. Since he took command of Naval Special Warfare Command in 2016, commander Rear Adm. Tim Szymanski has been vocal inside the community that bad behavior would not be tolerated in the SEAL community. In late 2016, East Coast SEALs took an operational pause to address the drug problem in special warfare after several investigations found a spike in usage “I feel like I’m watching our foundation, our culture erode in front of our eyes,” commander of Naval Special Warfare Group 2 Capt. Jamie Sands said in a closed-door meeting as part of the standdown, according to video obtained by CBS.

A.D.H.D. Study Suggests Medication May Reduce Crime - The New York Times

“The study adds a lot,” said Dr. Gabrielle Carlson, director of child and adolescent psychiatry at Stony Brook University medical school, who was not involved in the study. “Cutting the crime rate, that’s not trivial. Maybe it will get some help for people in jail. It gives people who were on the fence maybe a little more confidence in this treatment.”

The Selling of Attention Deficit Disorder - The New York Times

In an interview last month, Dr. Dodson said he makes a new diagnosis in about 300 patients a year and, because he disagrees with studies showing that many A.D.H.D. children are not impaired as adults, always recommends their taking stimulants for the rest of their lives. He said that concern about abuse and side effects is “incredibly overblown,” and that his longtime work for drug companies does not influence his opinions. He said he received about $2,000 for the 2002 talk for Shire. He earned $45,500 in speaking fees from pharmaceutical companies in 2010 to 2011, according to ProPublica, which tracks such payments. “If people want help, my job is to make sure they get it,” Dr. Dodson said. Regarding people concerned about prescribing physicians being paid by drug companies, he added: “They like a good conspiracy theory. I don’t let it slow me down.”

Psychotic and Manic-like Symptoms During Stimulant Treatment of Attention Deficit Hyperactivity Disorder | American Journal of Psychiatry

Combining across stimulant medications, during double-blind, placebo-controlled trials, placebo was not associated with any toxicosis events in 3,990 subjects with a combined duration of treatment of over 425 years. For therapeutic doses of active medication, there were 13 reports of toxicosis in 5,717 subjects with a combined treatment duration of over 800 years. In open-label trials, stimulants were associated with 45 reports of toxicosis in 15,999 subjects with a combined treatment duration of almost 9,400 years. Although there are methodological problems in summing across stimulant medications and across studies that may have different sensitivities for identifying psychotic-like and manic-like symptoms, these numbers suggest as a preliminary estimate that toxicosis will occur in approximately 0.25% of children treated with stimulants, or about 1 in 400—a proportion suggesting an infrequent but not rare effect of therapeutic dosing.

OCD after three weeks on ADHD drugs – henry copeland – Medium

One boy spent 36 hours playing with legos. Another had a similar experience with video games. Another child spent seven straight hours raking leaves, “after which he still felt compelled to rake individual leaves as they fell.”

1 in 6 adults getting Adderall experience acute anxiety in 4 months

Acute anxiety symptoms occurred in 4 of 7 patients with a comorbid anxiety diagnosis. CONCLUSION:

Chapter 5—Medical Aspects of Stimulant Use Disorders - Treatment for Stimulant Use Disorders - NCBI Bookshelf

Some researchers and clinicians describe the development of stimulant-induced psychosis as an evolving process. Panel members depicted MA users as having brief and transient psychotic episodes before a full-blown psychosis emerges after more extensive chronic use. MA users often recognize these early psychotic effects and try to stave them off by self-medicating with alcohol or decreasing drug use. In several articles, Ellinwood and colleagues describe the evolution of MA-induced psychosis as progressively abnormal behaviors--beginning at moderately high doses--with intense feelings of curiosity about the environment and patterns of exploration that result, for example, in examining the punctuation periods in a magazine text for evidence of a secret code (Ellinwood et al., 1973).

Department of Health | The amphetamine withdrawal syndrome

Animal and human studies have confirmed that the methamphetamine withdrawal syndrome may be protracted (the mood disturbance may last up to a year in some cases) and tends to be more severe than cocaine withdrawal (see Cho & Melega, 2002 for a thorough review; Davidson et al., 2001; Volkow, Chang, Wang, Fowler, Franceschi et al., 2001). Similarly, there is some evidence to suggest that individuals who have experienced a methamphetamine-related psychosis are at risk of further psychotic episodes, even in the absence of further psychostimulant use (Yui, Ikemoto, Ishiguro & Goto, 2000).

Engineering euphoria

Isomers of the same molecule, although very similar, often have different effects. For instance, the right-handed isomer of methamphetamine, dextromethamphetamine, is the most potent human stimulant known: This is the “meth” that tweakers crave. But the left-handed isomer of methamphetamine, levomethamphetamine, is a vasoconstrictor with little to no psychoactive effect and is used in nasal decongestants and inhalers. In contrast, both isomers of amphetamine are psychostimulants, so Shire combines both the l- and d- isomers in Adderall, each packaged in two different types of salt carriers. By creating a custom racemic mix of l- and d- isomers, and by using a custom blend of salt carriers for each molecule, Adderall meets the definition of an amphetamine formulation that can be patented for prescription use. In a word: genius. Formulating the perfect blend of speed for children sounds like a task more suited to a crime syndicate than a pharmaceutical company, but Shire put some serious thought into packaging amphetamine into pills for kids with short attention spans. The l- isomer of amphetamine, levoamphetamine, packs a euphoric rush of norepinephrine for a quick and speedy high, with a small release of dopamine for a short period of increased alertness and focus. Levoamphetamine (a.k.a. benzedrine) is a favorite of tweakers who want the most bang for their buck. The d- isomer of amphetamine, dextroamphetamine, produces less of an initial rush but increases the supply of dopamine and norepinephrine in the brain’s synaptic clefts for many hours. Dextroamphetamine (a.k.a. dexedrine) is considered by many to be the first “smart drug,” used experimentally to increase focus, memory, and intelligence.

Drug-Induced Psychosis: How to Avoid Star Gazing in Schizophrenia Research by Looking at More Obvious Sources of Light

They administered dextroamphetamine by mouth on days 1, 3, and 5 to 10 healthy volunteers, and measured the effect on striatal dopamine release before exposure, then the day of first exposure, then 2 weeks later after the third dose, using the PET/[11C] raclopride technique. Each dose of amphetamine caused greater dopamine release in the ventral striatum together with greater behavioral responses. Indeed, 1 year later there was a greater psychomotor response and greater increase dopamine release compared to the initial dose, in the ventral striatum, progressively extending to the dorsal caudate and putamen (Boileau et al., 2006). Such findings have led to the “dopamine sensitization” hypothesis of schizophrenia which postulates that a sensitized dopamine system is responsible for the genesis of psychotic symptoms (Peleg-Raibstein et al., 2009).

The Link Between Psychotic Disorders and Substance Use | Psychiatric Times

The most robust body of evidence for the relationship between the onset of psychotic disorders and drug use comes from the Swedish conscript studies.12,13 Baseline drug use information was taken at intake to the army for these studies. The authors found that cannabis use, and to a lesser extent amphetamine use, predicted onset of psychotic disorder later in adulthood. The explanatory variable was age at use, with younger age predicting psychotic disorders. This relationship did not exist for other drugs used, such as cocaine. A more recent cohort study in New Zealand confirmed the relationship between cannabis use and the onset of psychotic disorders.14 This study demonstrated that younger age of first cannabis use predicted younger age of psychotic disorder onset in individuals with the Val/Val genotype for COMT on the Val158Met polymorphism (a gene that codes for the activity level of an enzyme involved in the breakdown of dopamine).

Adderall for ADHD / ADD: Uses, Dosages, Side Effects, and Benefits of Treatment

There have been 11 reported cases of psychotic reaction from among 7,000,000 prescriptions for Adderall written since 1996.

Ritalin Use in Childhood Has Long-Term Effects on the Brain

The initial scans revealed that the brains of subjects who began taking Ritalin before the age of 16 (the “early treatment” group) had lower levels of GABA — a neurotransmitter linked to inhibition control and often implicated in the neurological makeup of ADHD — than did those who started stimulants later or never took them all. After Ritalin was administered, however, and the patients re-scanned, only the early treatment group saw any increase in GABA levels.

ADHD drugs increase brain glutamate, predict positive emotion in healthy people -- ScienceDaily

In this new study, subjects were first screened for mental and physical health and then underwent MRI spectroscopy scans designed to detect the concentration of neural compounds in specific regions of their brain. From the medical literature on psychostimulants, White and her team wanted to look in the anterior cingulate cortex, which is a "hub" brain region that connects multiple brain networks involved in emotion, decision-making and behavior. They found that two ADHD medications, d-amphetamine and Desoxyn, significantly increased the overall amount of glutamate in the right dorsal anterior cingulate cortex, even after controlling for possible confounding factors, such as volume of gray matter in the region. The rise in brain glutamate predicted both the duration and the intensity of positive emotion, measured by participant ratings about whether they liked the drug or felt high after consuming it.

Crappy studies

Unfortunately, the extant studies on side effect risk of the stimulants used for ADHD treatment have many limitations. All have been restricted to relatively short durations of exposure; and most are based on an assumption that a dose of methylphenidate is equivalent to half of an equal dose of amphetamine. Therefore, amphetamine is administered at 50% of the methylphenidate dose using fixed-dose designs, rather than titrating to a pre-determined efficacy endpoint before comparing adverse events. Most studies have not incorporated measurement of plasma drug level achieved although few relationships between these common adverse events and plasma levels have been noted 15. Nevertheless, it is potentially important that treatment within approved dose ranges with amphetamines, especially newer extended-release formulations, have produced residual low, but detectable, steady-state blood levels up to 24 h after administration. Thus many individuals experience some degree of continuous drug exposure. Although not tested, this finding suggests that cardiovascular complications, which have been associated with both normal aging and amphetamine abuse in young addicts, may appear earlier in older adults receiving maintenance amphetamine treatment 26. Regarding the detection of risk for uncommon or rare severe psychological or behavioral reactions to stimulants, controlled studies have not been large enough to pinpoint risk factors or determine differential risk by treatment assignment. Finally, a common observation across studies of the pharmacokinetics, pharmacodynamics, and safety profiles of amphetamine is the high degree of interindividual variability across most measures and endpoints. This variability calls for additional caution in application of the increasingly common practice of prescribing stimulants concurrent with use of other psychotropic medications 27, 28.

Understanding the Relationship Between Amphetamines and Psychosis | SpringerLink

Most people with psychosis, who use stimulants, also use cannabis, and cannabis is the most commonly used illicit drug among first-episode schizophrenia cases [40, 44, 45, 46, 48, 49, 50]. A recent review of stimulant-use disorders in people with psychosis found that cannabis use was the variable that most strongly correlated with stimulant use [51•]. Cannabis and methamphetamine have been suggested as the two most important drugs involved in the pathogenesis of psychosis and schizophrenia [34]. As the effect of cannabis, to a certain extent, counters that of amphetamines, users often take it to end amphetamine binges. Studies on psychosis in users of amphetamines seldom report on concurrent cannabis use. Given that cannabis often accompanies the use of amphetamines, it is uncertain to what extent the effect of cannabis might have influenced the evidence on the association between amphetamines and psychosis.

How Meth Destroys The Body | The Meth Epidemic | FRONTLINE | PBS

"There [are] a whole variety of reasons to try methamphetamine," explains Dr. Richard Rawson, associate director of UCLA's Integrated Substance Abuse Programs. "[H]owever, once they take the drug … their reasons are pretty much the same: They like how it affects their brain[s]." Meth users have described this feeling as a sudden rush of pleasure lasting for several minutes, followed by a euphoric high that lasts between six and 12 hours, and it is the result of drug causing the brain to release excessive amounts of the chemical dopamine, a neurotransmitter that controls pleasure. All drugs of abuse cause the release of dopamine, even alcohol and nicotine, explains Rawson, "[But] methamphetamine produces the mother of all dopamine releases." For example, in lab experiments done on animals, sex causes dopamine levels to jump from 100 to 200 units, and cocaine causes them to spike to 350 units. "[With] methamphetamine you get a release from the base level to about 1,250 units, something that's about 12 times as much of a release of dopamine as you get from food and sex and other pleasurable activities," Rawson says. "This really doesn't occur from any normally rewarding activity. That's one of the reasons why people, when they take methamphetamine, report having this euphoric [feeling] that's unlike anything they've ever experienced." Then, when the drug wears off, users experience profound depression and feel the need to keep taking the drug to avoid the crash.

12 of 14

A large dose of intravenous methamphetamine hydrochloride reproduced the amphetamine psychosis in 12 of 14 patients dependent on amphetamine sulfate and failed to produce a psychosis in two patients who were eventually found to have not used amphetamine regularly above the therapeutic dose range. The psychosis was the facsimile of the disorder observed during drug abuse—a schizophrenic-like state of paranoia in a setting of clear consciousness accompanied by auditory or visual hallucinations, or both, but without thought disorder. Since in some cases the onset of the psychosis was sudden and occurred within one hour of commencing the intravenous injection, hypotheses about depletion of catecholamines and long term metabolites may need to be reconsidered.

The Last All-Nighter - NYTimes.com

I wish it had ended that easily. In the months that followed, I was exhausted all the time. I slept through appointments and was unable to stay up to meet deadlines. The drug had curbed my appetite, and helped me to drop from a size 8 to a 4. Without it now I was ravenous and neurotic about what I was eating and how I looked. I was sensitive and emotional from the new chemical imbalance, which gaining weight and falling behind at work exacerbated. It was hard to understand that I was experiencing withdrawal, because I was never warned of possible side effects. Without the drug I felt stupid, unable to focus or follow a thought through to completion. I was shy, and unwilling to initiate conversation. The witty, articulate woman I once was seemed to no longer exist. I felt dumb, out of it. I spoke slowly because it took immense effort to gather and express coherent thoughts. I didn’t understand what I was going through, and that made it more difficult to stay healthy. It felt like another phase of the depression I had become so used to. But once I made it through the hardest part, weeks where my body was literally recalibrating itself to function without the stimulant, I felt like my old self again — relaxed, yet motivated to take care of my mind and body; interested in engaging with the world around me. The person I was so eager to shed in lieu of a new, accomplished, adult me, actually ended up being the one most capable of handling the tumult of living in the hectic life of a 20-something starting out in New York.

Effects of exercise with or without light exposure on sleep quality and hormone reponses

Cycling adenosine monophosphate (cAMP) gets released by the stimulus of adrenocortical hormones due to intake of coffee, tea, chocolate, or stress. Excessive cAMP release accelerates energy release to reach excitement condition that leads us to be nervous and unsettled. However, sunlight exposure decreases cAMP, leading to peaceful and settled conditions [53].