5-HT2A: From Psychedelics to Psychiatry

By: burgundy bug

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A yellow smiley face on a pink backdrop

Source: Adobe Stock

“Serotonin” (5-HT) is more than just a buzzword tossed around by Gen Z and Millennials when something benign boosts their mood.

The beloved hormone has an array of functions throughout the body, with seven types of receptors nestled in your brain and peripheral organs. Each of these receptors has subtypes with labels A through D, as well.

But there’s one serotonin receptor that’s often shrouded in mystery and intrigue — the 5-HT2A receptor. This is the serotonin receptor infamous for its role in the psychedelic experience.

But there’s hardly any discussion of its functions beyond its role in tripping your face off and how that’s tied to your mental health.

Serotonin Science

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Serotonin is a hormone that plays a central role in regulating your mood, sleep, digestion, motor skills, libido, blood clotting, and bone health, as explained by Healthline.

Roughly 90 percent of your body’s serotonin is produced by enterochromaffin cells in your intestines, according to a 2018 PNAS Journal study.

Gut bacteria can trigger serotonin secretion, and it’s part of the communication that takes place along the gut-brain axis.

Serotonin then interacts with the various receptors throughout your brain and body. This can have excitatory or inhibitory effects — i.e. it can trigger or put a stop to a series of complex biological processes.

The Role of the 5-HT2A Receptor

First, let’s address the vibrant, mystic, three-eyed elephant in the room: psychedelics.

Shrooms, acid, and a variety of other psychedelic drugs are serotonin agonists. This means they mimic serotonin in your brain, specifically by activating the 5-HT2A receptor, according to a 2016 Pharmacological Reviews publication.

It was first discovered that psychedelics increase serotonin levels throughout the brain in the mid-1950s. But it wasn’t until 1998 that researchers demonstrated the 5-HT2A receptor is central to the effects of tripping in humans.

Later, it was discovered that 5-HT2A is central to mood regulation and emotional face recognition, as well.

And when you take a look at where these receptors are located in the brain, it makes sense. 5-HT2A receptors are in the thalamus, reticular nucleus, amygdala, primary visual cortex, and ventral tegmental area.

Neuroanatomy: 5-HT2A Receptor Expression

5-HT2A in the Thalamus

2-Minute Neuroscience: The Thalamus

Source: 2-Minute Neuroscience: The Thalamus | Neuroscientifically Challenged

The thalamus is implicated in sensory processing, says a Neuroscientifically Challenged article. It receives various inputs and filters out the clutter so only the important information reaches the cortex.

But its communication with the cortex is a two-way street. It also takes information from the cortex, processes it, and sends it back.

The reticular nucleus is among one of the 50 distinct nuclei in the thalamus. It’s the blanket over the thalamus that influences the activity of all other thalamic nuclei — sort of like a mother or a father, so to speak.

According to the Pharmacological Reviews article, the reticular nucleus regulates the flow of information between the thalamus and cortex.

And just to be clear, the cortex (which is short for cerebral cortex), is the outermost layer of your brain. It forms connections between other subcortical (inner layers) of your brain.

5-HT2A in the Amygdala

2-Minute Neuroscience: Amygdala

Source: 2-Minute Neuroscience: Amygdala | Neuroscientifically Challenged

The amygdala is a member of the limbic system, which are the parts of your brain that handle emotions and memories.

Specifically, the amygdala’s involved in generating emotional behavior, the formation of emotional memories, and the consolidation of emotionally arousing memories.

Serotonin regulates activity in the amygdala through various 5-HT2 receptors. 5-HT2A is thought to play a vital role in the formation of emotional memories and emotional responses.

However, the Pharmacological Reviews article makes it quite clear there’s still much to learn about 5-HT2A receptor activity in the amygdala.

5-HT2A in the Primary Visual Cortex

The primary visual cortex is a necessary component of conscious visual processing. It also has an abundant amount of 5-HT2A receptors.

This very well could explain the visual illusions — such as seeing patterns, ultra-vibrant colors, and “breathing walls” — described by those who take psychedelics.

5-HT2A in the Ventral Tegmental Area

2-Minute Neuroscience: Ventral Tegmental Area

Source: 2-Minute Neuroscience: Ventral Tegmental Area | Neuroscientifically Challenged

The VTA is one of the two major dopamine centers in your brain. Dopamine is the “feel good” hormone released by drugs, food, sex, and other rewarding activities — which explains its addictive nature.

Serotonin can directly or indirectly modulate dopamine transmission in the VTA.

And what receptor is involved in the serotonergic modulation of dopamine? You guessed it — 5-HT2A.

5-HT2A and Neuroanatomy: Piecing it All Together

It’s difficult to dive too deep into what all of this means, as each of these systems interacts with other complex regions of the brain. In essence, activation of 5-HT2A receptors has a domino effect.

But when you break it down to simple terms, 5-HT2A exists in regions of the brain that primarily handle processing sensory input, emotions, and visual stimuli.

And psychedelics affect your sensory processing, emotions, and visual processing. It changes how you perceive the world around you and your own emotions in a way that can help break rigid, pessimistic thought patterns.

5-HT2A and Mental Health

Anxiety, mood, trauma, and substance-use disorders have strong effects on your perception and emotions. That’s no secret.

So, is it reasonable to conclude 5-HT2A also plays a role in mental health?

Both the Pharmacological Reviews article and an International Journal of Neuropsychopharmacology study describe how psychedelics can reduce the symptoms of OCD.

Interestingly, however, the International Journal of Neuropsychopharmacology study found 5-HT2A and 5-HT2C agonists (blocking/inhibiting those receptors) were successful in reducing compulsive behavior.

But there are many studies and surveys that demonstrate how full-doses and microdoses of LSD and psilocybin can significantly improve symptoms of depression, anxiety, OCD, PTSD, and other mental health conditions.

A Harm Reduction Journal survey found that respondents felt microdosing psychedelics improved their:

• Mood (26.6 percent)
• Focus (14.8 percent)
• Creativity (12.9 percent)
• Self-efficacy (11.3 percent)
• Energy (10.5 percent)
• Sociality (7.6 percent)
• Cognition (5.8 percent)
• Anxiety (4.2 percent)

Respondents said the biggest “con” to microdosing was its illegality (29.5 percent). However, some said that microdosing negatively impacted their mood (6.9) or increased their anxiety (6.7), causing a bit of conflict among the survey results.

A Frontiers in Psychiatry survey found respondents felt microdosing was more effective than traditional treatment options for anxiety and neurodevelopmental disorders.

A multitude of studies have documented the extreme therapeutic potential of psychedelics in treatment-resistant depression, substance-use disorders, and PTSD, as well.

In Conclusion

While these studies teach us a lot about the therapeutic potential of psychedelics, they simultaneously increase our understanding of mental health on a more structural and chemical level.

The brain is an enigma. There will always be more to learn about its structure along with the chemical and electrical interactions that occur in between.

Serotonin is “trendy” right now, but it’s always been a staple of physiological and psychological functioning.

5-HT2A in particular is vital to understanding the indescribable and captivating experiences described by those who dabble a bit of acid and shrooms.

But it appears to be far more important than just a vehicle for ego transcendence and other hippy-babble.

There’s a lot of evidence to suggest 5-HT2A is tied to mental wellbeing. Increasing our understanding of serotonin and its functions at various receptors opens the floodgates for developing more advanced and effective treatment options for mental health conditions.

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