What are the Effects of Psychedelics on the Brain and Body?

Psychedelic-psychiatrist Stanislav Grof proposed that psychedelics are to the study of the mind what the microscope is to biology and the telescope is to astronomy. Let’s explore what’s known thus far.

Neurotransmission and serotonin

When most people think of serotonin, they think of the brain’s ‘happy chemical’, keeping our mood in check. Serotonin also appears to play a critical role in producing the psychedelic experience.

Research into serotonin and LSD shares a close link. In the 1950s, the realization that seemingly tiny doses of LSD were able to exert such dramatic effects was, in fact, a key influence in the advancement of the then-new field of neurochemistry, which led to the invention of SSRI antidepressants.4

Psychedelics’ effects are mainly driven by interactions at a specific serotonin receptor, known as the 5-HT2A receptor. Here, psychedelic molecules bind, unleashing a range of neurochemical processes that are still not fully understood.

LSD’s potential to bind with the 5-HT2A receptor is even stronger than serotonin’s. And the fact that the receptor holds onto the LSD molecule by folding over it may explain the substance’s long and intense duration.4

The default mode network and the self

Psychedelics are known to profoundly alter activity at the Default Mode Network, or DMN – a richly interconnected set of brain structures that play an executive role in cognition and are responsible for complex mental abilities, such as mind-wandering, introspection and our narrative sense of self. 

Through dysregulating activity in the DMN, psychedelics reduce their usual control, allowing new patterns to emerge. These DMN-related changes are thought to play an important role in producing radical shifts in self-conception. At the extreme are subjective reports of ego-dissolution, where people may experience losing their sense of self entirely.

The DMN has also been implicated in depression, where it may encode rigid thinking patterns and distorted self-perception. One way that psychedelics may work therapeutically is by loosening these entrenched negative patterns and allowing people to see and experience themselves in new and healthier ways.

Psychedelics and creativity: spontaneous insights versus task-based solutions

Many famous artists and thinkers have credited psychedelics for provoking creative insights. But do psychedelics really improve creativity? 

Well, yes and no. Research has found that a dose of psilocybin improves experiences of spontaneous creativity, such as having new insights and original thoughts, but decreases performance in deliberate creativity, where people try to generate and find creative solutions regarding a specific task.

These changes were found to be related to activity in a highly interconnected set of brain structures known as the Default Mode Network (DMN). Decreased functional connectivity between these areas led to an impairment in finding task-based solutions, but also to an increase in general spontaneous insights, as well as the long-term generation of novel ideas. 

This suggests that psychedelics may play a nuanced role in creativity: good for brainstorming and new spontaneous ideas but bad for coming up with specific solutions related to a task at hand.

Brain entropy and visiting new brain states

Over the course of our lives, our brain develops predictable patterns of activity by drawing on learned cognitive strategies to meet our everyday needs. While this saves time and energy, it also means that we can become overly reliant on previously established thoughts and behaviors – some of which may perhaps no longer be serving us.

Psychedelics are thought to temporarily disrupt these ingrained patterns of neural activity, bringing the brain into an unpredictable ‘high entropy’ state characterized by potentially beneficial disorder and flexibility. 

The figure below illustrates different functional patterns of brain activity under placebo or psilocybin. The circle on the right suggests that psilocybin opens the brain up to new pathways of activity. New connections are made, allowing different parts of the brain to communicate with one another. 

This disorganization of brain activity and increased neural ‘crosstalk’ provide a fertile ground for new insights, different perspectives, and altered experiences.

Neuroplasticity and the changing brain

For many years, neuroscientists thought that the brain could only grow and change during childhood. Once you hit adulthood, what you have is what you get.

Since then, we have discovered that this is not entirely true: the brain can change, albeit in a limited way. In neuroscience, this capacity of neuronal change is called neuroplasticity – the ability of neurons to change their structure and function in response to a triggered event.

Taking psychedelics represents one such trigger for the brain, as studies have found that even a single dose can produce rapid changes in neuroplasticity, such as affecting how and when neurons fire and causing the growth of new neurons.

Questions remain regarding how much these neuroplastic mechanisms can explain the therapeutic potential of psychedelics. Are they responsible for psychedelics’ healing potential, or are there other processes at play?

The amygdala and your emotions

“I don’t even know what got into my emotions, but I felt so good, and the crying just made me feel even better”, Snoop Dogg recalls of his psilocybin mushroom experience.

A psychedelic trip can take you through a range of emotions, and people often report that it helps them deal with adverse life experiences. This is backed up by research suggesting that psilocybin reduces the emotional processing of negative stimuli and increases overall positive mood. 

These changes appear to be related to psychedelics’ effect on the amygdala – an ancient brain structure involved in processing fear stimuli and memories. Under psilocybin, studies have found reduced amygdala activity when viewing negative stimuli. These changes are still present one week after taking psilocybin, suggesting positive results can continue long after the initial drug effects have worn off.

The Visual System and geometric hallucinations

In 1926, Heinrich Klüver analyzed the subjective reports of hallucinations of subjects under the influence of mescaline. He found that they reported seeing geometric patterns, which could be grouped into four main sub-types: lattices, cobwebs, tunnels, and spirals. 

The shared nature of such experiences suggests that they may be caused by a common mechanism. But how are they generated? 

One leading idea is that the mechanisms generating these geometric hallucinations are closely related to the physical structure of the early visual cortex – a part of the brain with a column-like structure that specializes in detecting lines and edges. 

When these columns are stimulated in a certain way, there is evidence that their symmetrical structure can lead to the kinds of geometric forms described by participants under the influence of mescaline. If this is right, then the geometric hallucinations we see under psychedelics may provide a glimpse into the architecture of our brains.

Synesthesia and blurring the boundaries in perception

Have you ever seen shapes while listening to music? Or do certain words have colors for you?

If so, you may have synesthesia – a phenomenon in which stimulation of one sensory modality leads to the stimulation of another. While some people experience it naturally, it is also a common effect during a psychedelic trip.

Synesthesia comes in many forms, but under the influence of psychedelics, it mostly involves vision and hearing. For example, seeing colors while listening to someone talk. Other sensory combinations may be tasting colors, smelling sounds, or feeling scents.

These experiences may be related to serotonin-driven changes in the excitability and connectedness of sensory brain regions. Put simply: neurons in these areas are more active and likely to communicate with one another.

This hyper-activation can lead to increased crosstalk between the senses. Different brain regions communicate more openly, and neural activity in one sensory modality can more easily influence activity in another. This excitability is particularly strong in the visual cortex, which may explain why visual experiences are the most common.

Boosting the body’s immunity

One of psychedelics’ lesser known effects is their ability to regulate the body’s defense system. 

Normally, when there is tissue damage, or an invading pathogen is detected, the body will generate an inflammatory response. Specialized immune cells are sent to the affected area, healing any damaged tissue and/or attacking the intruder.

While this inflammation can help with recovery, it can become chronic when the body continues to generate the inflammatory response, incorrectly believing that there is still an injury or disease that needs to be fought. This can lead to long-term health problems, like Alzheimer’s disease, diabetes, and cancer.

Research suggests that psychedelics could act as anti-inflammatory agents by modulating the body’s immune response. This is because immune cells in the body also have serotonin receptors, thus responding to substances like psychedelics that can modulate serotonin activity in the brain and body.

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