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Bryce Hanna

@photobiogenesis

Jun 19

One of the hallmarks of intelligence is a well-balanced GABA/glutamate ratio

Interestingly neurogenesis significantly improves this, for example via activation of the TrkB receptor by BDNF

TrkB activation:
- upregulates GABA-A receptor expression
- increases glutamate -> GABA conversion by upregulating the GAD pathway
- upregulates KCC2 which maintains low chloride concentration within neurons, maintaining susceptibility to GABA-induced chloride influx

Exercise, as well as various foods/herbs, increase BDNF expression

Several flavonoids also activate TrkB directly including:
- tropoflavin
- eutropoflavin
- norwogonin (Skullcap)
- apigenin (chamomile)
- chrysin

Psychedelics including LSD and psilocin also potently activate TrkB, which likely mediates many of their antidepressant effects

Partial TrkB receptor activation suppresses cortical epileptogenesis through actions on parvalbumin interneurons
sciencedirect.com/science/articl…

BDNF-trkB-KCC2-GABA pathway may be related to chronic stress-induced hyperalgesia at both the spinal and supraspinal level
sciencedirect.com/science/articl…

TrkB agonism: new tools from nature's pharmacopeia
patreon.com/photobiogenesi…

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Bryce Hanna

@photobiogenesis

Jun 16

"X, Y, and Z increase neurogenesis"

The unifying mechanism of herbs, foods, and practices like exercise that promote neurogenesis is that they help increase the three main requirements of neurons

Energetic substrate, oxygen, and stimulation

A huge amount of herbs that increase BDNF do so via the latter two mechanisms, they stimulate neurons and increase blood flow

Bacopa, gotu kola, and gingko biloba are good examples, they stimulated neurons by raising acetylcholine/serotonin/dopamine and increase circulation via mechanisms like PDE inhibition

While the brain's preferred fuel is glucose, hyperglycemia inactivates neurogenesis

Many herbs and foods, like ginseng and cacao, promote insulin sensitivity and glucose uptake and utilization by the brain

Alternative fuels that signal energy depletion also drive neurogenesis in a hormetic fashion, specifically ketones and lactate

This is why high cognitive activity and exercise are so beneficial, they are extremely stimulating to neurons, enhance stimulation, and create a shift from glucose -> lactate/ketones

There are other specific mechanisms of certain compounds, such as directly binding nerve growth factor receptors like TrkB and TrkA

This is one of the reasons why psychedelics are so remarkable, they bind to these neurogenesis-activating receptors with high affinity

Agonism of certain serotonin receptors like 5HT2A can also cross-activate TrkB through the formation of dimers between the two receptors

I believe dopamine can have a similar effect, though these neurotransmitters also play a role in stimulation

Other key substrates like magnesium, zinc, and B-vitamins also have research suggesting they can promote neurogenesis

Omega-3 fats are particularly interesting as they are required as building blocks for neurons, are depleted by oxidative stress, and reduce neuroinflammation

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Bryce Hanna

@photobiogenesis

Jun 13

Blue lotus is the serotonin antagonist cyproheptadine wishes it could be

Cyproheptadine = antihistamine with some additional serotonin antagonism

Blue lotus = mixed dopamine agonism, serotonin antagonism, and some additional histamine antagonism

This is why blue lotus is so potent in tuning every system in the body ranging from gut health to circulation to blood brain barrier integrity and brain protection

Revered for centuries for good reason

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Bryce Hanna

@photobiogenesis

Jun 12

Small amounts of DMT are actually synthesized in the lungs from serotonin to protect against hypoxia

Psychedelics have the same effect in the brain

This means DMT-induced near-death experiences may serve as the brain's final attempt to protect itself when major hypoxia occurs

"Results showed that DMT robustly increases the survival of these cell types in severe hypoxia"

"We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain"
pmc.ncbi.nlm.nih.gov/articles/PMC50…

It seems that psychedelics in general "flex" the brain's hypoxia response and this is how they promote neurogenesis and synaptic plasticity

This creates an adaptive hormetic response

During the trip: psychedelics similate hypoxia by restricting blood flow serotonin receptor activation, vasoconstriction, and increased neural stimulation

After the trip: they upregulate antioxidant and anti-inflammatory pathways, downregulate serotonin receptors, and promote healing and release of growth factors like BDNF

This has powerful antidepressant effects

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Bryce Hanna

@photobiogenesis

Jun 11

Serotonin, hypoxia, and the blood-brain axis

Serotonin is one of the most complex and misunderstood transmitters in biology

It traces a connection between the gut, blood, lungs, and brain that coordinates stress responses throughout the body

THREAD //

We can "frame" serotonin in different ways

The mainstream view is that serotonin is a neurotransmitter that regulates happiness, anxiety, and sociability

While there is some truth to this, it exist within a spectrum, excessive serotonin is analgesic and emotionally blunting

If we dig deeper we also find that serotonin has different roles in localized tissue

One of the simplest ways we can tie this together is that serotonin regulates response to hypoxia in various systems

Let's look at the lungs as a good example

Read 20 tweets

Bryce Hanna

@photobiogenesis

Jun 5

Let's talk about flavonoids

THREAD //

Flavonoids are one of the most medicinal classes of active compounds found in food and herbs

If you've seen discussion of "polyphenols" or "antioxidants" in fruits and vegetables this essentially always refers to flavonoids

Similarly most plant pigments are actually flavonoids

While the term flavonoid is derived from the Latin root word "flavus" meaning yellow, these compounds actually come in a wide variety of colors and structures

Most people don't realize it but the blue/purple anthocyanin pigments found in blueberries are also flavonoids

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