Image by Gerd Altmann from Pixabay

Section I

Literature Review

1) Psilocybin is showing further signs of great promise in the fight against depression and PTSD.

Psychedelic assisted psychotherapy has gained a foothold in the mainstream of treatment interventions for treatment resistant depression and PTSD. Psilocybin comes from a mushroom that has serotonergic effects on the receptor 5HT2A in the human brain. The results of the studies were net positives in reducing major mood disorder symptoms that are known to be long term in effect. (Haikazian et. al. 2023) I am very excited to see this therapeutic space expand into traumatized teens and other subsets to see outcome benefits.

2) Nanoplastics in the research in the Journal PNAS. The researchers analyzed bottled water for the presence of nanoplastics and found them to be at 10 to the 5th in volume or 100000 particles per bottle. Now these particles are 10 to the minus 9th in size (-0.000000001 meters) which is insanely small and capable of getting pretty much everywhere in the body. (Qian et. al. 2023)

Bioaccumulation is now the word that describes low levels of persistent plastic exposure ingestion/inhalation and subsequent body tissue accumulation. From ....."Moreover, nanoplastics can cross the blood–brain barrier after intravascular injection and accumulate in the brain. A study on nanoplastics obtained through the food chain showed that nanoplastics cross the blood–brain barrier, inducing brain damage in fish. Furthermore, a study using an ex vivo human placental perfusion model of nanoplastics reported that nanoplastics can cross the placental barrier through passive diffusion. These findings indicate that nanoplastics can penetrate important biological barriers (such as the intestinal barrier, blood–air barrier, blood–brain barrier, and placental barrier) and pose potential adverse effects to people." (Lai et. al. 2022)

Nanoplastics destroy cell membranes inducing apoptosis and macrophage activation to clean up the debris field leading to localized inflammation. There is further evidence that nanoparticles are taken in by mitochondria and increase ROS while decreasing energy production and mitochondrial function. This is a 100% bad pattern of biological effect. (Lai et. al. 2022)

THESE STUDIES ARE REALLY FASCINATING WHILE ALSO INSANELY FRUSTRATING. The end result of these cellular affecting nanoparticles will be inflammation and cellular senescence. We are truly fighting a losing battle between our immune solvency and the external environmental onslaught known as chemicals and toxins. Our epigenetic system will struggle to match this exposome change in volume and speed of onset leaving us genetically at risk for toxin mediated disease.

3) More on nanoplastics (NP) - It turns out that the nanoplastics can activate the innate immune system via the NLRP3 inflammasome. This leads to localized inflammation and resolution of the NP in that area. the problem arises in my mind when the NP's are persistent and found in a human with high NLRP3 activity at baseline due to fructose ingestion and processed foods. (Alijagic et. al. 2023) I am struck by the beauty of the NLRP3 inflammasome system during baseline historical exposome surveillance, inflammation and resolution. It is an elegant system that seems to be at the center of much that we look at including covid, preeclampsia, ASD and much more. Now usher in the emerging research on nano plastics infiltrating all biological tissues at such tiny sizes leading to bioaccumulation and chronic innate immune activation, apoptosis and cellular senescence. I am continually intrigued by the fructose ( or starch via polyol pathway) to uric acid to NLRP3 activation globally as a gasoline source for reducing cellular/mitochondrial resistance to these disparate toxicities as they are emerging and increasing over time. Almost like a Patrice Cani style low level (NLRP3 induced) endotoxemia via refined carbohydrates and toxins working in concert to overwhelm the system over time. This recent PNAS paper above is quite disturbing as they found 100000 nanoparticles per liter of drinking water in the context of this frontiers paper is a solid mess. 

4) Post exertion muscle fatigue is a common finding in a subgroup of patients with long Covid. A paper in Nature Communications notes the muscles of these individuals: "We show that skeletal muscle structure is associated with a lower exercise capacity in patients and that local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise." (Appleman et. al. 2024) Amyloid is a protein deposited in response to inflammation that is ongoing, i.e. not resolving. This begs the question as to why these specific people cannot resolve the SARS2 illness. This remains the unanswered question. I lean towards a dysregulated immune system in the face of chronic stress pre-illness with COVID.

5) Sleep timing or one's chronotype is now associated with cardiovascular risk for coronary changes. "Self-assessed chronotype was classified as extreme morning, moderate morning, intermediate, moderate evening, or extreme evening. 10-year risk of first-onset cardiovascular disease was estimated by the Systemic Coronary Risk Evaluation 2. Significant Coronary Artery Calcification CAC was present in 29 % of the cohort. CAC prevalence increased from extreme morning to extreme evening type (22 %, 28 %, 29 %, 27 %, 41 % respectively)". (Frisk et. al. 2024)

This is likely all related to the epigenetic and biological changes that occur when one is awake at night when we are supposed to sleep. People are more prone to metabolic and immune dysregulation when they are awake at night.

6) Gut microbes linked to dementia. From the journal Brain: "To understand the involvement of Alzheimer’s patient gut microbiota in host physiology and behaviour, we transplanted faecal microbiota from Alzheimer’s patients and age-matched healthy controls into microbiota-depleted young adult rats.

We found impairments in behaviours reliant on adult hippocampal neurogenesis, an essential process for certain memory functions and mood, resulting from Alzheimer’s patient transplants. Notably, the severity of impairments correlated with clinical cognitive scores in donor patients. Discrete changes in the rat caecal and hippocampal metabolome were also evident. As hippocampal neurogenesis cannot be measured in living humans but is modulated by the circulatory systemic environment, we assessed the impact of the Alzheimer’s systemic environment on proxy neurogenesis readouts. Serum from Alzheimer’s patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera.

Our findings reveal for the first time, that Alzheimer’s symptoms can be transferred to a healthy young organism via the gut microbiota, confirming a causal role of gut microbiota in Alzheimer’s disease, and highlight hippocampal neurogenesis as a converging central cellular process regulating systemic circulatory and gut-mediated factors in Alzheimer’s." (Grabrucker et. al. 2023)

This is another study to give us pause in using fecal microbial transplants without thinking through the downstream risks. If you get transplanted with a gut microbiome that is heading down this path, i.e. dementia phenotype, that could go sideways for you in that direction. The other take-home remains that the microbiome is intimately tied to our mental health now and over time so take care of yours.

Have a great week,

Dr. M

Haikazian Psych Res


Lai Nanoparticles

Wolff Journal Haz Mater

Alijagic Frontiers Immun

Appleman Nature Commun

Frisk Sleep Med

Grabrucker Brain