How do Psychedelics enhance Brain Health

What is BDNF and how does it impact Neuroplasticity?

BDNF (Brain Derived Neurotrophic Factor) is a key protein that supports neuroplasticity, learning, and memory by promoting synaptic growth, neurogenesis, and synaptic strengthening. It acts like "fertilizer" for brain cells, helping neurons grow, survive, and form stronger connections.

How to Naturally Boost BDNF

✔ Exercise → High-intensity workouts, aerobic activities, and resistance training boost BDNF.

✔ Intermittent Fasting → Mild caloric restriction triggers BDNF production.

✔ Sunlight (Vitamin D) → Increases BDNF expression.

✔ Learning & Mental Stimulation → Reading, problem-solving, and new experiences activate BDNF pathways.

✔ Meditation & Mindfulness → Lowers stress hormones that suppress BDNF.

✔ Healthy Diet (Omega-3, Curcumin, Polyphenols) → Found in fish, turmeric, and berries, these nutrients enhance BDNF signaling.

✔ Cold Exposure (Cryotherapy, Cold Showers) → Activates BDNF via mild stress adaptation.

What is Neuroplasticity?

Neuroplasticity is the brain's ability to change and adapt in response to experience, learning, or injury. It involves the creation of new neural connections, the strengthening or weakening of existing ones, and even the reorganization of entire brain regions.

There are two main types:

• Structural plasticity – changes in the physical structure of the brain, like growing new neurons (neurogenesis) or forming new synapses.
• Functional plasticity – the brain's ability to shift functions from damaged areas to healthy ones, especially after injury or stroke.

How does Metaplasticity differ from Neuroplasticity?  -Metaplasticity is often described as the "plasticity of plasticity." While neuroplasticity refers to the brain's ability to change its structure and function in response to experience, metaplasticity refers to how previous neural activity or experience alters the brain's future ability to undergo plastic changes.

Which Pyschedelics impact BDNF the most and how?

Ketamine:

Strongest and fastest BDNF surge via NMDA receptor antagonism.

Increases BDNF transcription and release within minutes to hours.

Key mechanism behind its rapid antidepressant effects.

LSD & Psilocybin:

Potent BDNF enhancers through 5-HT2A receptor activation.

Stimulate neuroplasticity and synaptic growth, but slower than ketamine.

Effects last longer but may not be as rapid or intense.

DMT & Ayahuasca:

Moderate BDNF enhancement via serotonergic and β-carboline (MAO inhibitor) mechanisms.

Ayahuasca's harmine component may prolong and strengthen neuroplastic effects.

Mescaline, 2C-B, and MDMA:

Lower BDNF impact compared to the above.

Mescaline & 2C-B stimulate 5-HT2A but with less neuroplasticity research available.

MDMA has mixed results, with some studies showing neurotoxicity at high doses.

Much more coming in the book!

Most classic psychedelics (psilocybin, LSD, DMT) act as agonists at the 5-HT2A receptor, a subtype of serotonin receptor densely located in areas related to mood, cognition, and perception. This receptor activation:

• Increases glutamate release in the prefrontal cortex (PFC)
• Triggers downstream cascades that enhance BDNF (brain-derived neurotrophic factor) and mTOR signaling, both crucial for neuroplasticity

Psychedelics decrease DMN activity, which may:

• Quiet the "inner critic"
• Allow for ego-dissolution, reducing self-centered rumination
• Foster interconnectedness and new perspectives

Emerging evidence suggests psychedelics may:

• Reduce neuroinflammation, which is increasingly implicated in depression
• Modulate immune signaling pathways, contributing to mood regulation

Clinical Evidence:

• Psilocybin for Major Depression: Two doses led to rapid, robust, and sustained antidepressant effects in randomized trials (Davis et al., JAMA Psychiatry, 2021)

Psychedelics enhance creativity by disrupting habitual patterns of thought, loosening cognitive filters, and increasing connectivity between normally segregated brain networks—all of which allow for novel associations, divergent thinking, and intuitive insight.

Core mechanisms include:

• The DMN is involved in self-referential thinking and mental rigidity.
• Psychedelics decrease DMN activity, freeing the mind from entrenched narratives and allowing spontaneous, unconstrained thinking—essential for creativity.
   

• Studies using fMRI (e.g., by Carhart-Harris et al.) show that psychedelics increase communication between brain regions that don’t usually interact.
• This enhances cross-modal thinking—like linking sounds with visuals or merging abstract ideas—key for artistic, musical, and problem-solving creativity. 

• Psychedelics promote growth factors like BDNF, facilitating new neural connections.
   
• This supports adaptability and the formation of fresh ideas or solutions.
   

• Psychedelics reduce filtering of sensory and cognitive input, allowing more information to enter conscious awareness.
• This flood of perception contributes to rich imagination, synesthesia, and unusual associations, which can fuel artistic or visionary experiences.
   

• Divergent thinking = generating many possible solutions or ideas.
• Studies (e.g., Kuypers et al., 2016) found that psychedelics like ayahuasca improve divergent thinking performance, especially in flexible ideation and perspective-shifting.
   

• Psychedelics can induce states of ego-dissolution, awe, or spiritual insight. 
• These shifts often catalyze creative breakthroughs, not just artistically but in personal worldview and innovation.
  
   

Psilocybin, LSD, and DMT, are being explored for their potential neuroprotective effects and ability to prevent or slow Alzheimer's disease. I am hopeful to see trials looking for reversal of Alzheimers in the future as well.

Through the mechanisms of neuroplasticity and brain repair, reduction of brain inflammation, enhanced clearance of Amyloid and Tau Proteins, improved cerebral blood flow, improved mood (reduced anxiety and depression), stress reduction, and enhanced cognitive flexibility, I am hopeful to see trials in the near future demonstrating benefits in prevention and reversal of Alzheimers with psychedelics.

Two clinical trials are ongoing currently.  They include:

1.Johns Hopkins University Study on Psilocybin for Depression in Early Alzheimer's Disease

Researchers at Johns Hopkins University are conducting a study to assess the efficacy of psilocybin-assisted therapy in treating depression among individuals with early-stage Alzheimer's disease or mild cognitive impairment (MCI). The study involves administering psilocybin in a controlled setting, accompanied by counseling sessions, to evaluate its impact on mood and cognitive function. ​hopkinspsychedelic.org

2. Eleusis Ltd.'s Research on LSD Microdosing

Eleusis Ltd., a pharmaceutical company, is exploring the potential of microdosing lysergic acid diethylamide (LSD) as a treatment for Alzheimer's disease. Their research focuses on the anti-inflammatory properties of psychedelics, aiming to develop therapies that could mitigate neuroinflammation associated with AD. 

I devote an entire chapter to important synergies to brain health that can further amplify the benefits from psychedelic therapy.

An overview of important synergies include:

• Diet and exercise
• Mindfulness and Meditation
• Mitochondrial Health via NAD+, Methylene Blue supplementation.
• Reduction in inflammation via natural strategies such as tumeric
• Application of mTOR therapies such as Rapamycin (Sirolimis) to reduce inflammation and enhance health span.
• Bioidentical Hormone Balancing
• Transcranial Near Infrared light therapy.
• Much more in the book!!

Benefits towards treatement of other Brain Conditions will include:

• The potential to augment the treatment neurodegenerative conditions such as Parkinson's and Multiple Sclerosis.
• The potential to stimulate more rapid Neural regeneration and re-wiring following traumatic brain injury (TBI) or Stroke with psychedelic microdosing.
• Treatment of PTSD with MDMA
• Much more in the book!!

This it my favorite chapter, where I'll discuss my personal journeys in this world and of others who have experienced profound enlightenment, healing, deepened connections to nature, enhanced empathy and travels to oneness.