Is Mainstream Treatment for ADHD in Adults Dangerous?By Kim Crawford, M.D. Last updated: March 24, 2023
The Basics of ADHD in Adults
ADHD is the most common psychiatric disorder of childhood. It is classified as a neurodevelopmental disorder that may persist from childhood into adulthood. In childhood, it is associated with inattention, hyperactivity, and impulsivity. Symptoms often change as a person gets older and are associated with an increased risk of developing depression, anxiety, and substance abuse. However, recent studies have challenged the idea that every adult with ADHD had it as a child. The results of those studies show the following. First of all, ADHD often goes unrecognized throughout childhood. Secondly, families may help children develop good compensation strategies. The conclusions, therefore, remain that, indeed, ADHD in adults is still considered a continuation from childhood.
Attention-Deficit/Hyperactivity Disorder (ADHD) is often a disabling condition in adults. As just noted, a significant portion of patients is not diagnosed during childhood, as diagnosis of the syndrome can be complex, especially when other psychiatric conditions are also associated. As undiagnosed ADHD patients age, they are presenting to memory clinics with attentional and executive disorders. Neuropsychological examinations of these undiagnosed ADHD patients often reveal atypical cognitive profiles that complicate the usual diagnostic procedures for ADHD and increase the risk of misdiagnosis. Therefore, first and foremost, it is recommended that any explorations of cognitive and/or behavioral disorders in adults should systematically screen for ADHD. Let’s now explore adult ADHD symptoms, usual remedies, and then functional alternatives.
- Is it possible for Adults to Develop ADHD out-of-the-blue?
- What are Adult ADHD Symptoms?
- Typical Medical Treatment for ADHD in Adults
- How do the medications work?
- What’s the problem, then?
- Cortisol part deux
- The gut-brain axis
- Fixing the ravages of high cortisol
- Repairing the gut lining
- Repairing the Microbiome
- Behavioral and supplemental interventions
- The cool stuff: peptides
- Miscellaneous “other”
Can Adults Develop ADHD?
Adults can have ADHD, of course. About 4% to 5% of U.S. adults have it. But surprisingly, few adults get diagnosed or treated for it. Instead, they often end up being evaluated at memory care centers, as noted above.
Who develops adult ADHD? Every adult who has ADHD has probably had it as a child. Some may have been diagnosed and known it. However, some adults may not have been diagnosed when they were younger and only find out later in life due to having “life issues” crop up, which will be discussed below.
While many children with ADHD do outgrow it, about 60% still have it as adults. Adult ADHD affects men and women equally. Many questions of late-onset ADHD remain incompletely answered, and further research is necessary to understand better and explain the etiology and development of this late-onset disorder. One very important thing we are noticing, and reporting: CIRS patients all have difficulty concentrating and often come to me on Adderall.
What are Adult ADHD Symptoms?
If you have adult ADHD, you might have difficulty with the following:
- Ability to concentrate and focus on tasks
- Task organization
- Following directions
- Remembering information
- Finishing work on time or deadline
If you have ADHD, you may have trouble with one or more of the following:
- Mood swings
- Poor organization skills
- Low tolerance for frustration
- Trouble concentrating when reading
- Chronic lateness and forgetfulness
- Chronic boredom
- Trouble controlling anger
- Low self-esteem
- Substance abuse or addiction
- Low motivation
What is the Typical Medical Treatment for ADHD in Adults?
In a word: Stimulants! Adults with ADHD have usually been prescribed stimulant medications. As a result, studies demonstrate that about two-thirds of adults with ADHD have big improvements in their symptoms, at least at first.
Typical medications used include:
- Amphetamine/dextroamphetamine (Adderall, Adderall XR)
- Lisdexamfetamine (Vyvanse)
- Methylphenidate (Ritalin, Concerta, Metadate, Daytrana, Quillivant XR, and Methylin)
- Dextroamphetamine (Dexedrine)
- Dexmethylphenidate (Focalin)
Studies suggest that these drugs improve (the happy brain chemical)- dopamine transmission by increasing its levels in the striatal region of the brain. Researchers have found that most amphetamines promote dopamine release, while Ritalin blocks the transporters that remove dopamine, keeping levels up. Ritalin also seems to improve norepinephrine transmission as well. This is all well in good, but amphetamines stimulate the adrenal glands to produce more and more cortisol over the long term. So-what’s wrong with that? Plenty.
Let’s Talk about Cortisol
Cortisol modulates many of the changes that occur in the body in response to stress. These include things like blood sugar levels and blood pressure. Cortisol has firm control over proper immune responses. It has anti-inflammatory activity. It also activates our entire nervous system by being coupled with adrenaline (epinephrine) release. As a result, it has a role in sleep, mood, energy, anxiety levels, and more. Short term, it acts in a beneficial way to help us through stressful situations. However, long-term adrenal stimulation by amphetamines causes persistently elevated cortisol levels, which definitely can become a problem. Here’s why.
What happens with long-term high cortisol?
Cortisol helps us deal with stress by shutting down “unnecessary functions,” like reproduction and the immune system, to allow the body to direct its energy towards dealing with the stressor. These functions are supposed to be short-lived to deal with the stress. However, our modern lives are full of stress, and when stress is chronic or caused by amphetamines, this becomes a problem.
Cortisol partially shuts down the immune system when levels are high. It interferes with T-cell (a type of white cell) production and function, making your body more susceptible to pathogens like viruses, bacteria, and fungi. Ever notice how people who are constantly under stress are also always getting sick? This is why.
Cortisol also affects your muscles and bones. Cortisol is “catabolic.” It inhibits the uptake of amino acids into muscle cells, making it impossible to fuel muscle cells. It also inhibits bone formation and decreases intestinal calcium absorption. So when cortisol is high, there’s minimal to no bone growth and little muscle growth going on. And yes, there’s more when you have long-term high cortisol levels.
Adults with ADHD tend to have BDNF levels on the low side of normal for reasons still unknown. BDNF is “brain cell food,” so it’s important to continue neurogenesis throughout our lifetimes. Add high cortisol to the mix, and first, we see gut hyperpermeability. Why? High cortisol can cause the breakdown of your GI lining. It does this by slowing down both GI motility (peristalsis) and the process of digestion. When this happens, some people experience reflux, or “heartburn,” while others have absolutely no symptoms. Blood flow then decreases to all of the digestive organs. This results in a higher concentration of toxic metabolites, which then whittle away at your gut lining.
We then see a breach in the gut-brain barrier, the slow-down of conversion of neural stem cells into neurons, and the further lowering of BDNF needed for that process to happen. Cortisol has even been shown to be a direct neurotoxin! The result=impaired cognitive performance in terms of memory, executive functioning, speed of thought, and so on. It usually all starts with a little “brain fog.” More about the gut-brain barrier next.
In addition, we see dampened thyroid function, blood sugar imbalances, insomnia, osteoporosis, blood pressure elevations, lowered immune function, and universally- increased abdominal fat.
What happens to the gut-brain axis?
Much recent research shows that changes in gut microbiota could affect the brain’s cognitive, behavioral, and basically- all physiological functions. Although the exact mechanism of the connectivity of the gut-brain axis has not yet been elucidated, the evidence shows that gut microbiota plays an important role by producing immune factors, hormones, and metabolites that influence brain functioning.
Stress, meaning high cortisol, can significantly impact the microbiota-gut-brain axis. Recent studies have implicated the gut microbiota in many brain conditions, including anxiety, autism, Alzheimer’s disease, schizophrenia, and Parkinson’s disease. In addition, ongoing research implicates diseases such as obesity, heart disease, and diabetes.
Fixing the Effects of High Cortisol
When we finally stop someone’s amphetamines, we still have the carnage caused (often) by years of taking them with resultant years of high cortisol levels. We know cortisol is a direct neurotoxin, likely being a risk factor for Alzheimer’s disease. We know all of the things mentioned above. However, when we’re talking about the root cause of Ulcerative colitis, Crohn’s disease, or any autoimmune disease for that matter, we see the direct effect high cortisol has on the gut. As previously mentioned, sustained high cortisol can be the sole reason for having a leaky gut. But for adult ADHD symptoms controlled by the “traditional drugs” discussed previously, it often requires someone to actually experience cognitive changes to bring them to a doctor such as myself. So what do we do?
First, we lower high cortisol levels. Adrenal (herbal) adaptogens, glandulars, liposomal GABA, and certain aromatherapy oils are proven to lower cortisol levels. Stress-reducing techniques such as “vagal breathing,” meditation, and yoga are great practices to maintain overall health as well as lower cortisol levels. Finally, just activating your hypoglossal nerve (the nerve to the tongue and vocal cords) and, therefore, your adjacent vagal nerve to tone down your sympathetic nervous system will help. All you need to do is gargle, sing or do vocal exercises. We also always need to fix the gut lining and the microbiome. Here’s how we do it.
Heal the gut
The pentadecapeptide BPC-157 (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) has been demonstrated to counteract peritonitis, and heal upper intestinal lesions, heal colitis lesions and seal up a hyperpermeable gut lining.
Gastric pentadecapeptide BPC 157, now found to be effective in the upper and lower GI tract, is remarkably free of side effects, as are the other peptides being used in functional medicine. More about peptides to follow.
Re-Balancing your Disturbed Microbiome
By definition, when you have gut hyperpermeability, you have more “toxic bacteria” than “healthy bacteria” populating your GI tract. Use prebiotic fiber to feed the good bacteria and (if you are not in a “mold and mycotoxin situation” a little bit of “good yeast” (Saccharomyces boulardii) to begin to re-create a healthy gut microbiome. If you like un-ripe bananas, they make great prebiotic fiber. Other foods include asparagus, Jerusalem artichokes, red onions, and naturally fermented (not pickled) foods such as sauerkraut.
When your gut lining is coming together-usually the 2 to 3-week mark, add probiotics. Historically, we have recommended 50 to 100 billion probiotic CFU’s per day. A mixture (in your main probiotic) of Lactobacillus species and Bifidobacterium species is probably fine. Still, even more evidence supports the use of sporulating probiotics for an even better microbiome. These probiotics are species of Bacillus with b. subtilis and b. coagulans being the most studied. Start as low as 5 billion and increasing to as many as 25 billion CFU’s daily (best done under a doctor’s supervision if you have GI symptoms). But now that you’re weaning from ADHD stimulants, what do you do?
Food, Exercise, Sleep, Therapy, and Supplements
Studies have associated poor attention and worsened ADHD symptoms with diets full of the unhealthy things we tell you not to eat, such as refined sugar and fried foods. In addition, artificial food colorings and the preservative-sodium-benzoate may worsen ADHD-hyperactivity in children but otherwise hasn’t been studied for other effects or in adults.
According to some good clinical evidence, regular exercise may reduce adult ADHD symptoms. And I don’t believe I need to tell you that poor sleep quality impairs attention and other cognitive functions, worsening ADHD symptoms.
Cognitive-behavioral therapy has been shown to improve ADHD symptoms in adults. In addition, mindfulness-based therapies improved ADHD symptoms in multiple studies, mostly in adults as well.
Supplements that might be useful: ADHD patients tend to have lower magnesium levels than average, with the caveat that most of us not on MG supplementation are a bit deficient. At any rate, in two clinical trials, magnesium supplementation did indeed improve adult ADHD symptoms. Similarly, there is a higher prevalence of vitamin D deficiency in ADHD patients, and studies suggest that supplementation is helpful. Finally, fish oil supplementation appears to be quite promising, is anti-inflammatory, and is usually a good “health practice” anyway.
L-Tyrosine: This amino acid is being discussed separately because the data supports its use in adults with ADHD. A review of 15 clinical trials concluded that L-tyrosine (a dopamine precursor) boosts attention and cognitive performance in stressful and demanding situations in normal adults. These were not trials done with adult ADHD symptoms, but the extrapolation of that data to patients with ADHD has resulted in numerous clinical reports of the same benefits. There is less data on SAMe (S-adenosyl-L-methionine), but one study indeed suggested that it might be a useful way to increase dopamine and norepinephrine.
Peptides are small chains of amino acids that make up proteins and are available in every part of your body. Because peptides can be found in any part of the body, they each have particular functions. They act as messengers, signaling specific glands and proteins into performing specific tasks. These; essentially bioidentical substances have been isolated and replicated for use by Functional Medicine doctors. Since they are bioidentical, there are no side effects. They are an amazing addition to our arsenal of treatments, and there happen to be three that are quite useful for adult ADHD symptoms.
Heptapeptide Semax: (Met-Glu-His-Phe-Pro-Gly-Pro)
Semax is considered a brain-enhancing or “nootropic” peptide due to its ability to increase BDNF:brain-derived neurotrophic factor, nick-named “brain fertilizer,” since it is the largest (neurotrophic) stimulator of neurogenesis. In addition, Semax has also been found to be a potent enkephalinase inhibitor. In other words, the enzyme that destroys the natural painkillers and anti-anxiety brain chemicals called enkephalins is blocked by Semax, which has been independently proven to reduce anxiety and, therefore, likely decrease cortisol. In addition, several studies demonstrate its ability to cause the brain to release both serotonin and dopamine, enhancing feelings of well-being and, more-than-likely (due to the dopamine boost) attentiveness.
The heptapeptide Semax is an analog of the N-terminal fragment (4-10) of ACTH (adrenocorticotropic hormone) but is absent any hormonal activity. However, it has been found to stimulate memory and attention in rodents and humans after intranasal application. In addition, evidence from animal studies reveals that Semax augments the effects of psychostimulants on central dopamine release.
As noted above, it stimulates central brain-derived neurotrophic factor (BDNF) synthesis. In addition, Semax is thought to improve selective attention and modulate brain development. Since ADHD is likely to be a neurodevelopmental disorder with disturbance in both dopamine and BDNF function production, it is proposed by many neuroscientists that Semax may have excellent therapeutic potential in ADHD. In Russia, this peptide is used as a common alternative for drug therapy for children with ADHD. In addition, functional doctors in the U.S. prescribe it for mood issues, adult ADHD symptoms, cognitive and pain issues.
This peptide is widely used in Europe and Russia but not approved in the U.S. However, it has been studied for many years and is a go-to for adult ADHD in other countries. Numerous studies show that this peptide increases cognitive functioning and attention with decreased impulsivity in children and adults with ADHD.
Dihexa is a peptide derived from angiotensin IV-a metabolite of the potent, naturally occurring vasoconstrictor angiotensin II. Angiotensin IV has been shown to enhance acquisition, consolidation, and recall of memory and learning in animal models. What’s more, the peptide Dihexa has been determined to be seven orders of magnitude more potent than BDNF. Thus, you first read about BDNF as the potent neurogenesis stimulant, but there’s more to it than simply being a cognitive enhancer.
Brain-derived neurotrophic factor is the most dominant neurotrophin in the CNS (central nervous system). It plays a crucial role in physiological brain functions via its two independent receptors: tropomyosin-related kinase B (TrkB) and p75. These two activities are critical during neurodevelopment. In addition, the disrupting of BDNF signaling has been documented in many neuropsychological diseases, including ADHD.
Dihexa is a first-in-class compound that is orally active, penetrates the blood-brain barrier, increases BDNF, improves memory consolidation and retrieval as well as concentration and neural processing speed.
Miscellaneous Functional Medicine tools
Deserving of more than an honorable mention is functional medication likely to be helpful with adult ADHD symptoms. While definitive research is pending, the logic is compelling for the following.
Oral nicotinamide mononucleotide supplementation increases intracellular NAD+ concentrations, improving mitochondrial biogenesis and ATP (mitochondrial energy) output. It is well known that the brain has an enormous supply of mitochondria, so mitochondrial enhancement should, in theory, benefit all brain functions.
The peptide selank increases BDNF and decreases levels of anxiety by increasing concentrations of GABA in the brain. Due to the importance of BDNF enhancement and, in some cases, lowering anxiety to ameliorate adult ADHD symptoms, it makes sense to utilize this peptide. But, again, data is pending on these two measures.
The Microbiota-Gut-Brain Axis
Gut Microbiota-brain Axis
Annu Rev Pharmacol Toxicol
Microbiota-Gut-Brain Axis: New Therapeutic Opportunities
The Physiology of BDNF and Its Relationship with ADHD
Review: J Alzheimers Dis
Cerebrolysin peptides as mood stabilizers
Zh Nevrol Psikhiatr Im SS Korsakova
An analysis of the peptide composition of a ‘light’ peptide fraction of cerebrolysin
Living “in the zone”: hyperfocus in adult ADHD
Can ADHD have an adulthood onset?
Semax, an analogue of adrenocorticotropin (4-10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome
Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behavior problems associated with child ADHD
Exercise Holds Immediate Benefits for Affect and Cognition in Younger and Older Adults
Candice L. Hogan, Jutta Mata, and Laura L. Carstensen
Efficacy of Meta-Cognitive Therapy (MCT) for Adult ADHD
Mary V. Solanto, Ph.D., David J. Marks, Ph.D., Jeanette Wasserstein, Ph.D., Katherine Mitchell, Psy.D., Howard Abikoff, Ph.D., Jose Ma. J. Alvir, Dr.P.H., and Michele D. Kofman, Ph.D.
Internet-Based Cognitive Behavioral Therapy for Adults With ADHD in Outpatient Psychiatric Care
Cognitive–behavioural therapy in medication-treated adults with attention-deficit/hyperactivity disorder and co-morbid psychopathology: a randomized controlled trial using multi-level analysis
Magnesium status and attention deficit hyperactivity disorder (ADHD): A meta-analysis
Does mindfulness meditation improve attention in attention deficit hyperactivity disorder?
A Trial by Trial Analysis Reveals More Intense Physical Activity is Associated with Better Cognitive Control Performance in Attention-Deficit/Hyperactivity Disorder
Behavioral and cognitive effects of tyrosine intake in healthy human adults
Effect of vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms: A randomized, double blind, placebo-controlled trial
Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents
PMID: 16362768 DOI: 10.1007/s11064-005-8826-8
An update on the pharmacotherapy of attention-deficit/hyperactivity disorder in adults
doi: 10.1016/j.npep.2020.102114. Epub 2020 Dec 28.
Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats
PMID: 33418449 DOI: 10.1016/j.npep.2020.102114
Ross Fiziol Zh Im M Sechenova
Nootropic and analgesic effects of Semax following different routes of administration
Stress in Gastrointestinal Tract and Stable Gastric Pentadecapeptide BPC 157. Finally, do we have a Solution?
Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights
Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157
Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response