As someone who supports thoughtful use of complementary and alternative medicine, I absolutely believe that compounds like SAMe or St. John’s Wort can offer meaningful benefits—when used appropriately and supported by evidence. But with the rise of anti-aging influencers, we’re seeing a familiar pattern: mechanistically promising compounds getting pushed far ahead of the science.
Methylene Blue is a perfect example.
🧬 Mechanistic appeal:
Enhances mitochondrial respiration
Acts as a redox mediator to reduce oxidative stress
May support autophagy and protein homeostasis
Studied for cognitive enhancement and neuroprotection
Sounds great on paper—and some early research is encouraging. But…
⚠️ Here’s the caution:
Most data is from animal studies or in vitro experiments
Human trials for cognitive or anti-aging outcomes are small, inconsistent, and early-stage
Long-term safety at “biohacker” doses remains largely untested
Many people are understandably drawn to the promise of longer, healthier lives, but often at the cost of embracing interventions before we truly understand their risks, benefits, or limitations.
Even if the science makes theoretical sense, biology doesn’t always behave the way our models predict.
Let’s stay open—but also skeptical. Not everything that sounds too good to be true ends up being true.
A recent 8-week double-blind, randomized, placebo-controlled trial investigated whether oral creatine monohydrate (5g/day) could enhance the effects of cognitive-behavioral therapy (CBT) in treating major depressive disorder (MDD)—especially in under-resourced areas where access to treatment is limited.
🔬 Why Does This Matter? While CBT is a gold-standard therapy for depression, many patients do not achieve full remission. This study explored whether creatine—widely used for muscle and brain energy metabolism—could provide an extra boost to treatment.
🧠 Key Findings: ✅ Participants receiving creatine + CBT had greater reductions in depression symptoms (measured by the Hamilton Depression Rating Scale) compared to those receiving placebo + CBT ✅ Reported improvements in mood, energy levels, and cognitive function ✅ Creatine was well-tolerated, with no significant safety concerns ✅ CBT was delivered once weekly by trained therapists
⚠️ Study Limitations: 🔹 Small sample size—larger studies are needed to confirm these findings 🔹 Short trial duration—long-term effects are still unknown 🔹 Study population—results may not generalize to all individuals with MDD
💡 What’s Next? If larger studies confirm these results, creatine could become an accessible, affordable adjunct to therapy, particularly in communities with limited mental health resources.
What do you think? Could a common fitness supplement help improve mental health? Let’s discuss! ⬇️
If you’re looking for a way to protect and enhance your brain health, regular exercise should be at the top of your list. Decades of randomized controlled trial (RCT) data have consistently shown that moderate to vigorous physical activity is one of the most effective strategies for maintaining cognitive function and reducing the risk of neurological and mental health disorders.
How Exercise Supports Brain Health
Exercise is not just about physical fitness—it has profound effects on brain function and resilience. Research has demonstrated that regular physical activity contributes to:
✅ Reduced Risk of Dementia & Cognitive Decline – Studies indicate that individuals who engage in moderate to vigorous exercise have up to a 30-40% lower risk of developing dementia compared to those with sedentary lifestyles. Physical activity enhances neuroplasticity, promotes new neuron growth (neurogenesis), and improves synaptic function—all crucial factors in preventing cognitive decline.
✅ Improved Stroke Prevention & Recovery – Exercise lowers blood pressure, enhances circulation, and improves endothelial function, significantly reducing the risk of stroke. For stroke survivors, RCTs suggest that physical rehabilitation incorporating aerobic and strength training can improve motor function, cognitive recovery, and quality of life.
✅ Lower Rates of Anxiety & Depression – Multiple RCTs have shown that exercise is as effective as antidepressantsin treating mild to moderate depression, thanks to its ability to regulate neurotransmitters like serotonin, dopamine, and endorphins. Regular physical activity also reduces cortisol (stress hormone) levels, improving resilience to stress and anxiety disorders.
✅ Better Sleep Quality – Exercise plays a crucial role in regulating circadian rhythms and increasing slow-wave (deep) sleep, which is essential for cognitive recovery and emotional processing. RCTs show that individuals with insomnia who engage in aerobic exercise experience significant improvements in sleep latency, duration, and overall sleep quality.
How Much Exercise is Needed for Brain Benefits?
The gold standard for brain health is a combination of aerobic exercise (such as brisk walking, cycling, or swimming) and strength training (such as weightlifting or bodyweight exercises). Research recommends:
📌 150-300 minutes per week of moderate-intensity aerobic exercise OR 75-150 minutes per week of vigorous-intensity exercise 📌 At least two days per week of strength training to preserve muscle mass and support neuroprotective benefits
The Bottom Line
Regular physical activity isn’t just about fitness—it’s one of the most powerful, evidence-based tools for maintaining brain health, preventing cognitive decline, and improving mental well-being. Whether you’re looking to sharpen memory, reduce stress, or protect against neurological disease, making exercise a regular habit is a science-backed investment in your future.
So, lace up your sneakers, get moving, and give your brain the boost it deserves! 🧠💪
📢 Update on Schizophrenia Research #MentalHealth #Schizophrenia
🧠 Iclepertin (BI 425809), initially showing promise in Phase II trials, unfortunately did not meet the primary and key secondary endpoints in the Phase III CONNEX program. Despite this, it was well tolerated, and the safety profile remained consistent.
🔬 Phase III Results:
No statistically significant improvements in cognition or functioning were observed compared to placebo over six months.
Context: Iclepertin is a glycine transporter 1 (GlyT1) inhibitor, a class of drugs aimed at enhancing the function of the NMDA receptor by increasing glycine levels. This receptor plays a crucial role in cognitive processes, and improving its function was hypothesized to alleviate cognitive impairments in schizophrenia.
📊 Visual Insights: Below are graphs illustrating the trial data, showing the comparison between Iclepertin and placebo groups across various cognitive assessments.
🔍 Implications and Next Steps: Although these results are disappointing, they provide valuable insights for future research. The findings highlight the complexity of treating cognitive impairment in schizophrenia and underscore the need for continued exploration of new therapeutic targets and strategies.
What’s next? Researchers will analyze the data further to identify any subgroups that may have benefited and explore other potential mechanisms to address this unmet medical need.
💬 Join the Discussion: Have you or someone you know experienced cognitive challenges related to schizophrenia? What are your thoughts on current treatment options? Share your experiences or questions below—let’s foster a supportive community!
🔔 Stay Updated: Follow us for more updates on ongoing research and join our forums for in-depth discussions on mental health innovations. Together, we can stay informed and connected. #ClinicalTrials #Neuroscience #Breakthrough
Today’s issue of JAMA Psychiatry highlights an important breakthrough study titled: “Slowing cognitive decline in major depressive disorder and mild cognitive impairment: A randomized controlled trial.”
This publication reveals the primary findings from the PACt-MD study (Prevention of Alzheimer’s dementia with Cognitive remediation plus transcranial direct current stimulation in Mild cognitive impairment and Depression). This large-scale RCT examined whether combining cognitive remediation therapy (CRT) with transcranial direct current stimulation (tDCS) could effectively slow cognitive decline in individuals with both mild cognitive impairment (MCI) and major depressive disorder (MDD).
Key Findings:
The combination of CRT and tDCS showed promising effects in decelerating cognitive decline in patients with MCI and MDD.
Improved cognitive outcomes were observed in specific areas such as memory, executive function, and attention compared to control groups.
Why This Matters: Cognitive impairment is a critical concern in both MCI and MDD, often leading to functional decline and increased dementia risk. This study provides valuable insights into non-pharmacological approaches to mitigate cognitive deterioration in high-risk populations.
🔍 Stay tuned for more on the methodology and detailed results. This could open doors to novel, accessible interventions for those at risk of Alzheimer’s and cognitive impairment.
The ketogenic diet, primarily known for its benefits in weight loss and managing conditions like epilepsy, has been increasingly explored for its potential impact on mental health, including psychiatry. While research in this area is still emerging, some studies suggest that the ketogenic diet may offer benefits for certain psychiatric conditions.
Mood Disorders: Some research indicates that the ketogenic diet might have a positive impact on mood disorders such as depression and bipolar disorder. The diet’s ability to stabilize blood sugar levels and regulate neurotransmitters like serotonin and dopamine could contribute to mood improvement.
Anxiety: The ketogenic diet’s effects on GABA (gamma-aminobutyric acid), a neurotransmitter that helps regulate anxiety, have been of interest to researchers. By increasing GABA levels, the diet may have an anxiolytic effect, potentially reducing symptoms of anxiety.
Cognitive Function: Ketones produced during ketosis are an alternative fuel source for the brain. Some studies suggest that ketones may provide more efficient energy for brain cells, leading to improved cognitive function and clarity of thought. This could have implications for conditions such as ADHD and cognitive impairment.
Neuroprotective Effects: Ketones have been shown to have neuroprotective properties, which could be beneficial in neurodegenerative disorders like Alzheimer’s disease and Parkinson’s disease. By providing an alternative energy source for the brain, the ketogenic diet may help protect against neuronal damage and promote brain health.
Inflammation: Chronic inflammation has been linked to various psychiatric disorders. The ketogenic diet has anti-inflammatory effects, which could potentially reduce inflammation in the brain and mitigate symptoms of conditions like schizophrenia and PTSD.
Gut-Brain Axis: Emerging research suggests that the gut microbiota plays a crucial role in mental health. The ketogenic diet can influence the gut microbiome, potentially improving gut health and modulating brain function through the gut-brain axis.
While these findings are promising, it’s essential to approach the use of the ketogenic diet in psychiatry with caution. More research, including large-scale clinical trials, is needed to fully understand its efficacy, safety, and long-term effects on mental health conditions. Additionally, the ketogenic diet may not be suitable for everyone and should be implemented under the guidance of healthcare professionals, especially for individuals with pre-existing health conditions or those taking medications.
There has been a lot of news recently about Sam Bankman, the onetime billionaire turned supervillain. At its peak, his company FTX had an in-house performance coach and psychiatrist named George K. Lerner. It’s unclear how many FTX employees Dr. Lerner treated but he did admit to treating some for ADHD and stated “the rate of ADHD at FTX was in line with most tech companies” whatever that means. I’m not here to debate the practices of the good doctor, but Bankman was known to talk publicly about experimenting with focus-enhancing medications. The main medications he allegedly used to become limitless were stimulants such as Adderall and the more interesting one to me and the topic of this week’s video the selegiline patch.
We are going to discuss selegiline in depth and try to understand why a medication primarily used to treat Parkinson’s may be useful for enhancing focus, creativity, and productivity in the fast-paced world of cryptocurrency.
What is Selegiline?
Although many may not have heard of this medication, it’s actually a very old concept in psychiatry. A common “pimping” question in psychiatry residency is what was the first antidepressant medication? Most residents will say it was the tricyclic antidepressants which isn’t a bad guess but it’s not correct. The correct answer is the monoamine oxidase inhibitors (MAOIs) specifically iproniazid a failed treatment for tuberculosis. In 1952 researcher noted that patients receiving this medication became unusually happy, this was shocking considering the medication did nothing for their tuberculosis.
Transdermal selegiline is a tissue selective MAOI (MAO-A and MAO-B inhibitor in the brain) and a relatively selective MAO-B inhibitor in the gut. This is an important point, and I will explain more about it as we move through this topic.
How Do MAOIs Work?
We are speaking about the transdermal selegiline patch here but there is also an oral version that is not approved for major depressive disorder and is a selective MAO-B inhibitor.
The transdermal patch acts in the brain as an irreversible inhibitor of both MAO-A and MAO-B which are enzymes responsible for breaking down norepinephrine, serotonin, and dopamine which in turn will boost the noradrenergic, serotonergic, and dopaminergic neurotransmission.
In lay terms this medication increases the availability of all three major neurotransmitters so that more serotonin, norepinephrine, and dopamine is available to act on post synaptic receptors affecting changes in cells and circuits involved in depression.
FDA Approvals for Selegiline
This is a little complicated because news outlets have stated the medication is only used for Parkinson’s disease which is true if we are talking about the oral tablets. The transdermal patch is FDA approved for major depressive disorder.
Off label use includes the treatment of treatment resistant depression, panic disorder, social anxiety (which MAOIs are usually superior at treating), treatment resistant anxiety, and Alzheimer’s disease.
How to Dose Selegiline
The transdermal patch comes in various doses:
6 mg/24 hours
9 mg/24 hours
12 mg/24 hours
The initial dose for depression is 6 mg/24 hours and it can be increased by 3 mg/24 hours every 2 weeks to a maximum dose of 12 mg/24 hours. Dietary modification to restrict tyramine from food sources is not required for the 6 mg/24hr patch but at higher doses the same food restrictions are required as other oral MAOIs such as phenelzine. This will be important for our next discussion on side effects.
Side Effects of Selegiline
Before starting the medication, the patient should be aware of the potential for increased blood pressure.
Notable Side effects include
Skin reactions at the site of application (the location of the patch should be rotated daily)
Headaches
Dry mouth
Diarrhea
Insomnia
Sedation
Possible weight gain
Serious side effects include:
Hypertensive Crisis
Seizure
Induction of manic episodes in bipolar disorder
Contraindications when combined with:
Meperidine
Another MAOI
SSRIs, SNRIs, TCAs, tramadol
Dextromethorphan
St. John’s wort
Methadone
History of Pheochromocytoma
Elective surgery
Proven allergy to selegiline
The Dreaded Tyramine Reaction
I believe that MAOIs might be the most effective of the antidepressants because of their ability to affect all three major neurotransmitter circuits, but they are rarely used clinically. In most residency training programs, we are not taught to use these medications. The main barrier is the dietary restrictions and risk for hypertensive crisis if the diet is not followed.
This diet should be started a week or so before staring the medication. It allows the patient time to get accustomed to the dietary recommendations before being on the medication when the stakes are higher. The diet must be followed for 2 weeks after stopping the MAOI as it can take time for the MAO enzymes to regenerate due to irreversible inhibition.
Tyramine is an amino acid that is found in some foods, and it helps to regulate blood pressure. MAOIs are responsible for breaking this amino acid down so it’s inactive and unable to causes an increase in blood pressure. When you block MAO excess tyramine will be available to affect blood pressure.
Ingestion of a high tyramine meal is generally considered to be any meal with 40 mg or more in the fasted state. For the low dose transdermal patch 6 mg/24 hours studies show that 200-400 mg of tyramine in the fasted state is required for a hypertensive response. In general, at low doses dietary modification is not required. If the dose is increased to 12 mg/24 hours than 70-100 mg of tyramine is required for a hypertensive response. Although dietary modification may not be required at higher doses, it’s safer to avoid tyramine rich foods once the selegiline dose is increased and to be cautious at lower doses as well.
Low Tyramine Diet Principles
When a patient is on an MAOI diet they should only eat things that are fresh. This goes for food that are stored as well as the storage process may affect the tyramine content. The patient should avoid foods that are beyond their expiration date and avoid fruits and vegetables that are overly ripe. Some cheeses are allowed in the diet, but all aged cheese should be avoided. The same can be said for meat products, fresh meats are fine, but aged or spoiled meats should be avoided.
Fermented products need to be avoided when MAOIs are being used. This goes for all fermented products without exception.
Chinese food and some other eastern foods should be avoided because they contain soy, shrimp paste, tofu, and soy sauces all of which are high in tyramine.
Fava and other broad beans should be avoided this includes Italian green beans.
Foods to Avoid
Matured or aged cheeses (cheddar, and blue examples)
Cheeses: cream cheese, ricotta, fresh cottage cheese, mozzarella, processed cheese slices like American cheese
Milk Products: yogurt, sour cream, and ice cream
Meat: fresh packaged or processed meat e.g. hot dogs
Beverages: coffee, tea, soda, up to a maximum of 2 drinks either 12 oz of canned or bottled beer or 4 oz of red/white wine.
Soy products: soy milk
Other foods: chocolate in moderation and monosodium glutamate in moderation
Onset of Action
The therapeutic effect is usually not immediate and still requires 2-4 weeks or longer once an adequate dose is reached.
Augmentation
For expert psychopharmacologist Only:
You may consider a stimulant such as d-amphetamine, or methylphenidate while watching for increased blood pressure, suicidal ideation, and activation of bipolar disorder)
Lithium
Seconded generation dopamine blocking medication
Mood stabilizing anticonvulsant
Advantages to using MAOIs
May be effective in treatment resistant depression
May improve atypical depressive symptoms such as hypersomnia and hyperphagia
Lower risk for weight gain and sexual side effects
Why Would Selegiline Improve Cognitive function?
Selegiline will increase dopamine and more dopamine in the prefrontal cortex theoretically will enhance cognitive function. A lot of the research on MAOIs and cognitive enhancement come from studies in neurodegenerative disorders such as Alzheimer’s disease. While promising as reported in several articles it does not appear that proper randomized controlled trials were ever conducted. If you watch my videos than you should know the risk of assuming that something that should theoretically work will also work clinically. This is the story of many medications in psychiatry. We also cannot extrapolate that to healthy individuals who do not have neurodegenerative disorders.
Selegiline is metabolized to l-amphetamine, and l-methamphetamine which are well known stimulants that may improve symptoms of attention deficit hyperactivity disorder (ADHD). Again, this is theoretical and has never been proven but based on the metabolism of the medication it makes sense that it may enhance cognition in those with ADHD or even healthy individuals.
People often forget that depression itself is a major reason for cognitive problems. Depression in elderly patients is sometimes referred to as pseudodementia because it can look like the individuals has substantial cognitive deficits in severe cases. It’s possible that the improvement in depressive symptoms is responsible for the enhanced cognitive function.
Conclusion
I think this is a good discussion because it highlights an often-forgotten class of medication in modern psychiatry that can be utilized for patients who have failed other medication options. Many psychiatrists are untrained or too scared to use these medications clinically. As far as cognitive enhancement and finding that limitless pill, I do not think this is it. While it may theoretically improve cognitive function it’s never been proven in randomized controlled trials. I would say the evidence supporting this idea is weak and may even be dangerous given the risk for hypertensive crisis.
