I'm curious about a docking comparison of the 2 ligands below. I've yet to set-up the appropriate software so wondered if anyone could run a quick comparison? HT2A sure, but any relevant receptor would be interesting.
>The serotonin 1A receptors and serotonin transporter are important biological targets in the treatment of diseases of the central nervous system, especially for depression. In this study, new 3-(1H-indol-3zyl)pyrrolidine-2,5-dione derivatives linked with the 3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole moiety were synthesised and evaluated for their affinity for 5-HT1A receptor and serotonin reuptake inhibition.
>Selected compounds were then tested for their affinity for D2, 5-HT2A, 5-HT6 and 5-HT7 receptors, and also in-vitro metabolic stability assays in human microsomes. Finally, in vivo assays allowed us to evaluate the agonist–antagonist properties of pre- and postsynaptic 5-HT1A receptors. 3-(1-(4-(3-(5-methoxy-1H-indol-3-yl)-2,5-dioxopyrrolidin-1-yl)butyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-carbonitrile (4f) emerged as the most promising compound from the series, due to its favourable receptor binding profile (K:HT1A = 10.0 nM; K:SERT = 2.8 nM), good microsomal stability and 5-HT1A receptor agonistic activity.
A few excerpts from the paper:
>The original amphetamine epidemic was generated by the pharmaceutical industry and medical profession as a byproduct of routine commercial drug development and competition.
>... Fueled by advertising and marketing urging doctors to prescribe the drug for depression...annual sales of Benzedrine tablets grew steadily to about $500000 in 1941. ...by 1962, US production reached an estimated 80,000kg of amphetamine salts. ...amphetamines became 1st-line treatments for emotional distress and psychosomatic complaints in the 1950s.
From the paper titled "Amphetamines: a current epidemic": >There is currently a high volume of regular amphetamine usage within the United States adult population.
>Due to the risk of misdiagnosis and the limited amount of medical research into amphetamine addiction and long-term efficacy, practitioners should consider seeking additional educational resources before diagnosing patients with ADHD and prescribing daily, long-term use of amphetamines.
>In this study, we designed and synthesized novel 5-HT2A partial agonists based on the structures of the antipsychotic drug aripiprazole and our previously reported lead compound IHCH-7086. Two series of new compounds were synthesized, a number of which exhibited potent 5-HT2A partial agonist activity in G protein coupling and β-arrestin2 recruitment assays.
They "rediscovered" a desmethylene-type LSD analog (see 23m) similar to compound 11 from this patent.
>Small-molecule natural products (NPs) have a long and successful track record of providing first-in-class drugs and pharmacophore (scaffolds) in all therapeutic areas, serving as a bridge between modern and traditional medicine. This trajectory has been remarkably successful in three key areas of modern therapeutics: cancers, infections, and CNS diseases. Beginning with the discovery of morphine 200 years ago, natural products have remained the primary source of new drugs/scaffolds for CNS diseases.
>In this perspective, we address the question: why are the majority of active compounds in the CNS domain natural products? Our analysis indicates that ∼84% approved drugs for CNS diseases are NPs or NP-inspired, and interestingly, 20 natural products provided more than 400 clinically approved CNS drugs. We have discussed unique physicochemical properties of NPs and NP-inspired vis-à-vis synthetic drugs, isoform selectivity, and evolutionary relationship, providing a rationale for increasing focus on natural product driven discovery for next-generation drugs for neurodegenerative diseases.
>In this study, we designed and synthesized novel 5-HT2A partial agonists based on the structures of the antipsychotic drug aripiprazole and our previously reported lead compound IHCH-7086. Two series of new compounds were synthesized, a number of which exhibited potent 5-HT2A partial agonist activity in G protein coupling and β-arrestin2 recruitment assays.
DOI: 10.1021/acs.jmedchem.5c02045
URL: https://doi.org/10.1016/j.bioorg.2022.106254
DOI: 10.1016/j.bioorg.2022.106254
Thank you in advance
As the title suggests, here's an index of posts about ADHD. The resolution is, of course, based on Rays work.
Does my stimulant medication make me normal?
Is ADHD under, over or misdiagnosed?
A rational perspective on the safety of amphetamine medications
This article examines the ideological and institutional forces that led to the marginalization of homeopathy in American medicine, despite its popularity among prominent figures, including John D. Rockefeller.
>Even though John D. Rockefeller Sr., America’s richest man and first billionaire, provided substantial financial support to conventional medical schools and institutions, his personal medical care was supervised by doctors specializing in homeopathic medicine, a completely different type and style of treatment.
>According to Kirschmann in A Vital Force, not only did Rockefeller use homeopathic physicians, but all of the Standard Oil families sought homeopathic care, primarily with Dr. Merrick. Merrick was highly respected by both homeopathic and conventional physicians, and it was rumored that various conventional obstetricians secretly consulted with her on their more complex cases.
In the ADHD community this is called a crash / comedown / burnout depending on the context. The 'crash' phenomenon is more accurately understood as a metabolic event —a 'metabolic crash'— which occurs when a stimulant artificially 'pushes' the metabolic system beyond its limits causing over-exhaustion. This manifests as fatigue, sleepiness or brain fog (sometimes irritability). It's most commonly encountered with amphetamine-type medications which is the focus of this post.
In the academic literature a 'crash' is framed as 'metabolic exhaustion'. The following 9 quotes offer some general context for this term and its physiological implications: >Dissociation prevents the ultrarunning athlete from detecting the subtle, early warning signs of dehydration, blistering, or metabolic crash (source)
>[T]he benefit of post-stress glucose comes instead from its ability to prevent metabolic exhaustion. (source)
>...specifically sympathetic overdrive (eg, a faster rate of depletion than replacement of cellular resources, greater energy expenditure, metabolic exhaustion (source)
>It was suggested that the administration of MDMA (amphetamine-type drug) may cause a state of metabolic exhaustion (source)
>The aging process is, however, permissive for the development of several degenerative disorders and infectious diseases, which are strongly influenced by nutritional imbalances, inflammation, metabolic exhaustion (source)
>The modern lifestyle involves over-exposure to processed foods, nutrient imbalance, and contact with environmental toxins, that place a significant metabolic burden on cells. This leads to oxidative stress, endoplasmic reticulum stress and inflammation, that when combined with impaired cellular repair mechanisms, ultimately cause premature cellular fatigue and metabolic exhaustion. (source)
>"Metabolic aging" refers to the gradual decline in cellular metabolic function across various tissues due to defective hormonal signaling [...] While this process usually corresponds with chronological aging, the recent increase in metabolic diseases occurring at younger ages in humans suggests the premature onset of cellular fatigue and metabolic aging. (source)
>From a physiological point of view, fatigue is associated with metabolic fatigue (source)
>The term fatigue or energy-related dysfunction in this context does not refer to muscle or peripheral metabolic fatigue, but rather, to “central fatigue,” which is a subjective lack of physical and/or mental energy that is thought to be related to brain mechanisms. (source)
This 'crash' is distinct from the general comedown which involves (1) the immediate (acute) withdrawal symptoms as the medication wears off and, depending on the person, (2) a 'metabolic crash' (which can be either a minor or major event). There is also (3) PAWS which stands for "post-acute withdrawal syndrome": >PAWS refers to a cluster of withdrawal symptoms that can last for months to years after acute withdrawal from a substance. PAWS symptoms have been anecdotally described after withdrawal from many substances—alcohol, benzodiazepines, opioids, stimulants, nicotine, caffeine, antidepressants, and antipsychotics. (source)
Amphetamine withdrawal is also mentioned in psychiatry’s DSM (Diagnostic and Statistical Manual of Mental Disorders): >The DSM criteria for diagnosing amphetamine withdrawal include dysphoric mood and two or more symptoms: fatigue, vivid or unpleasant dreams, insomnia or hypersomnia, increased appetite and psychomotor agitation or retardation that occur following discontinuation of the drug. (source)
For some people this 'crash' effect can occur fairly quickly after taking their stimulant (within 60 mins). This signifies pre-existing metabolic issues whereby the metabolic system is more susceptible to over-exhaustion (due to the artificial boosting effect from amphetamine). This means someone could easily fall asleep after taking their stimulant, or the effects might appear to stop working too soon; whilst others might feel briefly energised followed by a period of fatigue, sleepiness or lethargy. I outlined other reasons why amphetamine can promote relaxation in this post (second-to-last paragraph).
What does 'metabolic exhaustion' mean practically?
The core metabolic system (thyroid, mitochondria) governs energy levels, mood, brain function, hormones – so when it 'crashes' so do these aformentioned things (within reason) which provokes various negative symptoms. Many of these symptoms overlap with ADHD making it incredibly difficult to distinguish one from the other.
This implies that the treatment itself can provoke/exacerbate ADHD symptoms (in both the short & long-term). This is due to amphetamine-induced metabolic & hormonal dysregulation which causes cumulative issues, including on brain function: >Brain neurons are highly vulnerable to even transient challenges to energy homeostasis and neural metabolic failure is a critical component of excitotoxic and neuro-degenerative cascades. (source)
Ideally when a 'crash' occurs the patient should ensure appropriate rest & recovery in order to mitigate (repair & heal from) any harm, particularly "HPA axis dysfunction" and the consequences thereof. The HPA axis is a key contributor to amphetamines effects and its disruption implies a negative physiological (and psychological) impact, including on hormonal regulation (source) and the circadian rhythm (source).
>Amphetamine induces activation of the HPA axis, with the subsequent release of ACTH and glucocorticoids (eg cortisol). (source)
>The novel d-amphetamine prodrug lisdexamfetamine is applied to treat ADHD. d-Amphetamine releases dopamine and noradrenaline and stimulates the HPA axis (source)
>The HPA axis is the main part of the hormonal system that controls reactions to stress. It also regulates many other processes (e.g. digestion, immune system, mood and emotions, sexuality, energy storage and utilization). (source)
...
To overlook the nature of the 'crash' and its implications would be unwise and arguably foolish. Medical practitioners overlook the severity of this issue and usually prescribe a larger dose (of amphetamine), additional booster/top-up doses (of amphetamine), or a new separate drug (eg SSRI, SNRI, NDRI, NRI) which can further complicate the situation.
This can successfully mask & conceal the 'crash' (giving a false sense of security) but at what cost? — and how sustainable is this over the span of several years? The drugs life changing benefits conceal a cumulative deterioration which ought to be taken seriously. For most people it's a trade-off since being able to navigate day-to-day life is the priority (understandably so).
>Over time, the isolation of psychiatry from other medical specialties has diminished the value of diagnosis and treatment, reducing psychiatry to a specialty that provides non-specialized psychological support.
>According to Nancy Andreasen, “Validity of psychiatric diagnosis has been sacrificed to achieve reliability. DSM diagnoses have given researchers a common nomenclature - but probably the wrong one. Although creating standardized diagnoses that would facilitate research was a major goal, DSM diagnoses are not useful for research because of their lack of validity”. (source)
The Making of Modern Psychiatry >...which he outlined his vision of a scientific psychiatry based on psychology and clinical observation, he settled into his work. (source)
Dated 2026: >Scientists at Freie Universität Berlin recently published a hypothesis-generating framework called Energy Deficit Hyperactivity Disorder (EDHD).
>This model moves away from the idea that people with ADHD have “broken” parts of their brain. Instead, it suggests that executive functions are conditionally available rather than permanently missing.
Here's an article on EDHD directly from the researchers themselves (link).
(study reference: 10.1016/j.neubiorev.2026.106616)
The issue of undiagnosed ADHD is a growing concern. Appointment waiting times in UK can reach up to 12 months whilst in America, supplier shortages leaves patients unable to access their medication, and ineffective/defective generics are a common problem. In Europe, doctors are misinformed about diagnostic procedures and have trouble taking patients' concerns seriously. Several studies show the risks & dangers of undiagnosed ADHD so patients often resort to telehealth prescribers or private options which can be expensive.
When we look at the academic literature on ADHD we see spurious activity; researchers are avidly searching for an explanation which would provide an empirical biological basis. At present, the label ADHD merely signifies "a group of behaviours" which is loosely termed as a "complex neurobehavioral problem" (ref¹, ref², ref³). This hampers efforts to make accurate diagnoses since the criteria are ambiguous, often overlapping with dozens of psychiatric conditions. A diagnosis involves arbitrariness which further hinders objectivity, and those involved in the diagnosis (clinicians, parents, teachers) form their own interpretations and judgements about the criteria, making the assessment biased toward subjective perceptions and cultural context.
>Although DSM-5 gives a [diagnostic] framework to the labels of mild, moderate, and severe by attempting to quantify the number of symptoms required, it does not help with defining the subjectivity of impairment. For example, what is meant by “no more than minor impairment in social or occupational functioning” and how many are “few, if any symptoms” when attempting to quantify impairment? — there is no consistent way to assess severity of ADHD symptoms (source)
As with many psychiatric classifications, ADHD is premised on an arbitrary consensus among a small psychiatric community. In other words: >“psychiatrists do not prove things but decide things: they decide what is disordered and what is not, decide where to draw the threshold between normality and abnormality, decide that biological causes and treatments are most critical in understanding and managing emotional distress” (source)
Scholars play a crucial role in creating & strengthening the facets of ADHD by communicating about this phenomenon as if it was an objective natural state — despite the ineptitude surrounding its diagnosis, causes, and treatment. Although the label allows patients to understand themselves —and be understood by others— it simultaneously distances them from "normalcy" and imposes stigma. Thus we can observe popularisation of the "neurodivergent" identity and by definition, the "neurotypical".
In essence, a positive diagnosis does not represent having ADHD but becoming and performing ADHD through deploying psycho-medical discourse (ref⁴). ADHD is, arguably, this century's prototypical sociocultural label which provides a convenient way of communicating about one's experiences and reacting to them within the societal, institutional, social, and individual levels. For example:
ADHD is better understood as a social category that eliminates human diversity and enforces a standard model of what an individual should behave and be like in order to navigate within the cultural boundaries of normalcy (being a productive citizen ref⁵). As bizarre as it may sound, ADHD is an inherently ambiguous concept which only exists in an abstract space of text and spoken word. The assumption that it represents a mental health or neurodevelopmental issue only serves to obfuscate practical resolution.
>ADHD is listed in DSM-5 under “Neurodevelopmental Disorders” in spite of reviews showing that (a) genetic evidence on ADHD is inadequate and diffused with ambiguous interpretations, (b) that no biological marker is diagnostic for ADHD something that even DSM-5 authors themselves explicitly admit, (c) the so-called “underlying mechanisms” remain unknown, and (d) no biological tests are available for its diagnosis. (source)
By accepting the label ADHD a person promptly shelves their symptoms as innate attributes. Any future issues are framed in this context which —as far as the patient is concerned— is "just part of who they are". They officially adopt a neurodevelopmental disorder which validates their lived experience and subconsciously moulds their perceptions of themselves & their place in society. Their hypothesised natural state becomes legitimised by the medical authorities. Thus, the label ADHD detracts from investigating & identifying the root biological issues responsible for the physical & mental discordance which constituets symptoms recognised as ADHD.
By rejecting the label ADHD a person is free to discover more realistic & pragmatic ways to move forward. The re-contextualisation of ADHD as a catch-all term for behaviors (symptoms) of diverse origin implies that myriad things will produce so-called ADHD. This bypasses all limiting presuppositions about a purely neurodevelopmental disorder which would otherwise cripple the search for a resolution. If we consider that ADHD has multiple causes then each person could require a tailored treatment. >Treatment approaches may similarly need to expand from symptomatic management toward more personalized interventions that account for neurobiological profiles and life-course adversity. (source)
This frees them to proactively search for solutions. An overwhelmingly reasonable approach involves repairing the bodys "metabolic system" since this governs & regulates everything, this type of strategy is well-known. On this basis we rename ADHD to EDHD (Energy Deficit Hyperactivity Disorder) as per this recent academic paper. This is futher outlined in this post (see last paragraph).
As mentioned here, current treatments are purely symptomatic. Their miraculous short-term benefits conceal a cumulative deterioration which only becomes apparent at a later date (months or years). Concerningly, some treatments (atomoxetine, methylphenidate, modafinil, bupropion, viloxazine, amphetamine) provoke short & long-term issues that overlap with and exacerbate ADHD. A psychiatrist can't realistically distinguish between them and thus can't accurately keep track of their patients progress. This leads to invalid analyses, erroneous assessments and subsequent blunderous clinical decisions (iatrogenic harm*).
When there are clear signs that something is wrong (symptoms), it is sensible to investigate & address the root cause. The alternative is to misconstrue ADHD as a neurodevelopmental disorder and mask symptoms using medications.
* note:
The issue of undiagnosed ADHD is a growing concern. Appointment waiting times in UK can reach up to 12 months whilst in America, supplier shortages leaves patients unable to access their medication, and ineffective/defective generics are a common problem. In Europe, doctors are misinformed about diagnostic procedures and have trouble taking patients' concerns seriously. Several studies show the risks & dangers of undiagnosed ADHD so patients often resort to telehealth prescribers or private options which can be expensive.
When we look at the academic literature on ADHD we see spurious activity; researchers are avidly searching for an explanation which would provide an empirical biological basis. At present, the label ADHD merely signifies "a group of behaviours" which is loosely termed as a "complex neurobehavioral problem" (ref¹, ref², ref³). This hampers efforts to make accurate diagnoses since the criteria are ambiguous, often overlapping with dozens of psychiatric conditions. A diagnosis involves arbitrariness which further hinders objectivity, and those involved in the diagnosis (clinicians, parents, teachers) form their own interpretations and judgements about the criteria, making the assessment biased toward subjective perceptions and cultural context.
>Although DSM-5 gives a [diagnostic] framework to the labels of mild, moderate, and severe by attempting to quantify the number of symptoms required, it does not help with defining the subjectivity of impairment. For example, what is meant by “no more than minor impairment in social or occupational functioning” and how many are “few, if any symptoms” when attempting to quantify impairment? — there is no consistent way to assess severity of ADHD symptoms (source)
As with many psychiatric classifications, ADHD is premised on an arbitrary consensus among a small psychiatric community. In other words: >“psychiatrists do not prove things but decide things: they decide what is disordered and what is not, decide where to draw the threshold between normality and abnormality, decide that biological causes and treatments are most critical in understanding and managing emotional distress” (source)
Scholars play a crucial role in creating & strengthening the facets of ADHD by communicating about this phenomenon as if it was an objective natural state — despite the ineptitude surrounding its diagnosis, causes, and treatment. Although the label allows patients to understand themselves —and be understood by others— it simultaneously distances them from "normalcy" and imposes stigma. Thus we can observe popularisation of the "neurodivergent" identity and by definition, the "neurotypical".
In essence, a positive diagnosis does not represent having ADHD but becoming and performing ADHD through deploying psycho-medical discourse (ref⁴). ADHD is, arguably, this century's prototypical sociocultural label which provides a convenient way of communicating about one's experiences and reacting to them within the societal, institutional, social, and individual levels. For example:
ADHD is better understood as a social category that eliminates human diversity and enforces a standard model of what an individual should behave and be like in order to navigate within the cultural boundaries of normalcy (being a productive citizen ref⁵). As bizarre as it may sound, ADHD is an inherently ambiguous concept which only exists in an abstract space of text and spoken word. The assumption that it represents a mental health or neurodevelopmental issue only serves to obfuscate practical resolution.
>ADHD is listed in DSM-5 under “Neurodevelopmental Disorders” in spite of reviews showing that (a) genetic evidence on ADHD is inadequate and diffused with ambiguous interpretations, (b) that no biological marker is diagnostic for ADHD something that even DSM-5 authors themselves explicitly admit, (c) the so-called “underlying mechanisms” remain unknown, and (d) no biological tests are available for its diagnosis. (source)
By accepting the label ADHD a person promptly shelves their symptoms as innate attributes. Any future issues are framed in this context which —as far as the patient is concerned— is "just part of who they are". They officially adopt a neurodevelopmental disorder which validates their lived experience and subconsciously moulds their perceptions of themselves & their place in society. Their hypothesised natural state becomes legitimised by the medical authorities. Thus, the label ADHD detracts from investigating & identifying the root biological issues responsible for the physical & mental discordance which constituets symptoms recognised as ADHD.
By rejecting the label ADHD a person is free to discover more realistic & pragmatic ways to move forward. The re-contextualisation of ADHD as a catch-all term for behaviors (symptoms) of diverse origin implies that myriad things will produce so-called ADHD. This bypasses all limiting presuppositions about a purely neurodevelopmental disorder which would otherwise cripple the search for a resolution. If we consider that ADHD has multiple causes then each person could require a tailored treatment. >Treatment approaches may similarly need to expand from symptomatic management toward more personalized interventions that account for neurobiological profiles and life-course adversity. (source)
This frees them to proactively search for solutions. An overwhelmingly reasonable approach involves repairing the bodys "metabolic system" since this governs & regulates everything, this type of strategy is well-known. On this basis we rename ADHD to EDHD (Energy Deficit Hyperactivity Disorder) as per this recent academic paper. This is futher outlined in this post (see last paragraph).
As mentioned here, current treatments are purely symptomatic. Their miraculous short-term benefits conceal a cumulative deterioration which only becomes apparent at a later date (months or years). Concerningly, some treatments (atomoxetine, methylphenidate, modafinil, bupropion, viloxazine, amphetamine) provoke short & long-term issues that mimic and exacerbate ADHD. A psychiatrist can't realistically distinguish between them and thus can't accurately keep track of their patients progress. This leads to invalid analyses, erroneous assessments and subsequent blunderous clinical decisions (iatrogenic harm*).
When there are clear signs that something is wrong (symptoms), it is sensible to investigate & address the root cause. The alternative is to misconstrue ADHD as a neurodevelopmental disorder and mask symptoms using medications.
* note:
Here's the original comment: >I was diagnosed ADHD in 1993 as an 8 year old. The first medication I was on was Ritalin... things were quiet, I could sit still, and in some ways I blossomed.
>So with the Ritalin I could work on my challenges in relative peace. Some things have gotten better over the years, I transitioned from the hyperactive to the inattentive type and can cope much of the time.
>...
>Medication is a tool and nothing more. And just like any tool if it's not used properly you get hurt. Same as if you use the wrong tool. The need for antidepressants, anxiolytics, and amphetamines are the cost of living under the crushing weight of an uncaring world, one which values "progress" and production over human dignity.
This is from a comment on another post. Reading their words got me pondering on the current paradigm of ADHD. The label of ADHD indicates a group of behaviours which are often found together. Many of these are real symptoms of real biological issues, but the label remains an intangible signpost for "something" which is currently unknown in terms of it's biological origins / cause etc (there are vague theories about this or that but nothing concrete). For something which they do not understand, treatments are approved and assumed safe, but how genuine are these assertions (assumptions) of safety? How can it be claimed that a treatment is safe when the condition it targets isn't understood at all? (no known cause or rational biological explanation)
A key question is: can the treatments make the underlying issue worse? The experts can't genuinely answer this question since they know not the underlying issue(s).
Certainly we know that these medications "work" and have profound life-changing benefits for millions of people, but accepting this without further genuine consideration of the aformentioned question marks doesn't seem sensible. Currently it's a risk/benefit ratio which "leads the way" and the priority for patients is the ability to go about their day-to-day activities.
Here's the original comment: >I was diagnosed ADHD in 1993 as an 8 year old. I was quickly put on medication and while I hated how I felt it did help.
>The first medication I was on was Ritalin. It was a terrible drug for me but the only one available. It quite literally made me sick to my stomach but when it wasn't, things were quiet, I could sit still, and in some ways I blossomed.
>So with the Ritalin I could work on those challenges in relative peace. Some things have gotten better over the years, I transitioned from the hyperactive to the inattentive type and can cope much of the time.
>...
>The need for antidepressants, anxiolytics, and amphetamines are the cost of living under the crushing weight of an uncaring world, one which values "progress" and production over human dignity.
Reading this, I consider the condition of modern medicines paradigm of ADHD. The label of ADHD indicates a group of behaviours which are often found together. Many of these are real symptoms of real biological issues, but the label remains an intangible signpost for "something" which is currently unknown in terms of it's biological origins / cause etc (there are vague theories about this or that but nothing concrete). For something which they do not understand, treatments are approved and assumed safe, but how genuine are these assertions (assumptions) of safety? How can it be claimed that a treatment is safe when the condition it targets isn't understood at all? (no known cause or rational biological explanation)
A key question is: can the treatments make the underlying issue worse? The experts can't genuinely answer this question since they know not the underlying issue(s).
Certainly we know that these medications "work" and have profound life-changing benefits for millions of people, but accepting this without further genuine consideration of the aformentioned question marks doesn't seem sensible. Currently it's a risk/benefit ratio which "leads the way" and the priority for patients is the ability to go about their day-to-day activities.
America’s first amphetamine epidemic 1929–1971: >The original amphetamine epidemic was generated by the pharmaceutical industry and medical profession as a byproduct of routine commercial drug development and competition. I review the causes and course of the first, mainly iatrogenic amphetamine epidemic in the United States from the 1940s through the 1960s.
>Assisted by such trends in medical thought, along with pharmaceutical marketing that reinforced them, amphetamines became first-line treatments for emotional distress and psychosomatic complaints in the 1950s. (source)
America’s Workforce Runs on Uppers: >ADHD wasn’t even considered a diagnosis for the adult population until after 2006, when the American Journal of Psychiatry published a study claiming that 4.4% of the U.S. adult population had ADHD. That opened the floodgates for adult use of ADHD drugs. More ADHD diagnoses translated to more ADHD prescriptions, causing a 53% increase in those prescriptions from 2008 to 2012.
>Synthesized in 1929, amphetamine quickly became America’s first choice to put some pep in its step and add some creativity to its coffee. Lovingly referred to by users as “bennies,” Benzedrine abuse skyrocketed in post-WWI America. By the late 1960s, Benzedrine sulfate production ranged from 8 to 10 billion tablets a year. Benzedrine consumption was driven by American perceptions of amphetamines as something of a panacea, a “one-stop shop” for their ailments. (source)
The current amphetamine epidemic: >The U.S. alone accounts for less than 5% of the world’s population, however, it represents 83.1% of the global volume of ADHD medications.
>The CDC explains that there is no singular test that can diagnose ADHD, and that there are many overlapping symptoms between ADHD and other disorders. Due to the risk of misdiagnosis and the limited amount of medical research into amphetamine addiction and long-term efficacy, practitioners should consider seeking additional educational resources before diagnosing patients with ADHD and prescribing daily, long-term use of amphetamines.
>Jeffrey A. Lieberman, former president of the American Psychiatric Association, highlighted this issue, noting that “the problem is not so much that we have a shortage of medication, but instead an overdiagnosis of the condition. There is no way that ADHD, as reflected by prescriptions for psychostimulants, can be multiples in frequency to what they are in western Europe and in other parts of the world.”
>The pharmaceutical companies behind amphetamines then began spending millions of dollars in advertisements. Profit-based pharmaceutical companies clearly recognize the financial potential behind addictive drugs, as first demonstrated by the opioid epidemic as well as the tobacco industry, and now appearing again with the rise in amphetamine use. (source)
...
>[A] diagnosis does not represent having or being ADHD but becoming and performing ADHD through deploying psycho-medical discourse provided in the DSM. (source)
>In other words, there is no scientific evidence to support the claim that ADHD is as a condition within an individual—something individuals have (source)
>ADHD is listed in DSM-5 under “Neurodevelopmental Disorders” in spite of reviews showing that (a) genetic evidence on ADHD is inadequate and diffused with ambiguous interpretations, (b) that no biological marker is diagnostic for ADHD something that even DSM-5 authors themselves explicitly admit, (c) the so-called “underlying mechanisms” remain unknown, and (d) no biological tests are available for its diagnosis. (source)
>...like most psychiatric classifications, ADHD is premised on an arbitrary consensus among a small psychiatric community behind the DSM manual rather than on any new scientific breakthroughs. In other words, “psychiatrists do not prove things but decide things: they decide what is disordered and what is not, decide where to draw the threshold between normality and abnormality, decide that biological causes and treatments are most critical in understanding and managing emotional distress” (source)