Psychedelic Brain Science
How psychedelics work? Where lies their neuroplastic potential? Why do they help to "reset" your brain and help to deal with anxiety, low mood, boost creativity and build better relationships?
Let’s discuss the neuroscience behind psychedelics: how do they produce their unique effects on our brains, alter our state of consciousness, our cognition, and our sense of self.
And what’s happening biologically that makes these substances effective at changing our minds in profound ways, especially when paired with professional therapy, or a trained and experienced sitter?
What are psychedelic drugs?
First, a drug is any substance that is absorbed into the body and changes normal functions. Caffeine, sugar, alcohol, the nicotine in cigarettes…although they’re legal, common, and acceptable for most to consume in everyday life (despite some of them being very harmful) they’re also drugs.
Drugs that impact your brain can organised into a few main categories depending on the effects they have on your body:
Depressants, which can produce effects like euphoria, depression, anxiety, fat gain, hormonal imbalances, brain shrinking, dementia, confusion, drowsiness, and mood swings. This includes drugs like alcohol or heroin.
Stimulants can produce alertness, euphoria, and increased focus or confidence. So drugs like caffeine, cocaine or methamphetamine.
Cannabinoids, which may cause relaxation or stimulation, euphoria or anxiety, and even increase or decrease sensitivity to physical stimulation.
Psychedelics are a class of psychoactive drugs that produce changes in perception, mood, neuroplasticity, emotional regulation, and cognitive processes.
We can also classify popular psychedelics further by looking at their main, signature properties.
The classic psychedelics are characterised by distorted perceptions and thoughts.
Empathogens tend to induce a sense of belonging or connectedness.
Dissociatives, which can induce disconnected, euphoric, floaty experiences.
The way these drugs interact with your body and brain differ depending on the drug. To understand the basic physical mechanisms of drugs, we are going to explore some neuroscience.
Your Brain
The brain consists of a complex network of hyper-connected cells called neurons. Working together, our neurons give us the ability to sense and control our body, make decisions, store and retrieve memories, make plans, imagine, and create.
To do so, neurons must communicate with one another. And one of the ways they do that is by creating and sending chemical messengers called neurotransmitters. These molecules move between neurons and get picked up by specific receptors. Then—like a game of telephone—pass the message along to the next set of neurons.
Neurotransmitters and neuroreceptors have a very specific relationship: the transmitter is like a key, and the receptor is like the lock. When a neurotransmitter key fits into a neuroreceptor lock, the two become connected, and the message is passed along.
Our bodies have many types of neurotransmitters and receptors. Adrenaline, for example, is the neurotransmitter that is released when we are excited. Dopamine, known as the “feel-good” neurotransmitter, plays a role in motivation.
The neurotransmitter we’re most interested in when it comes to psychedelics is called serotonin. Serotonin is related to the flexibility and sensitivity of the brain, and is involved in learning and development. There are many different serotonin molecules and receptors, but the one we are going to review more closely is called 5-HT2A.
5-HT2A Serotonin & Psychedelics
There are 5-HT2A receptors located throughout the body and in many regions of the brain, and they are connected to a wide range of functions: memory, mood, perception, anxiety, cognition, imagination, and learning, just to name a few.
We have strong evidence that LSD, psilocybin, and other psychedelic molecules activate the 5-HT2A receptors. Meaning—from the perspective of the neurons—they act just like serotonin. They bind to and activate these 5HT2A receptors, and the neurons respond as if they’ve received a serotonin message.
Not all psychedelic drugs produce their effects solely through this particular receptor, but most work through a similar mechanism: the drug’s molecules are similar enough to naturally occurring neurotransmitters that they can act as “keys” to certain neural “locks.”
So that’s a quick look at how psychedelic drugs interact with your brain chemistry at the smallest scales: neurons and neuroreceptors.
But there’s more to the story, and that is how the changes at these small scales influence brain function and activity at higher levels. Psychedelics can actually help change your brain—especially in cases where changes are really challenging.
How psychedelics change your brain?
Scientists have discovered that psychedelics can affect brain activity in several important ways. The most well-studied are:
The effects on the default mode network (DMN)
Their effects on mental flexibility
and their effects on neuroplasticity
Default Mode Network
The default mode network (DMN) connects areas of the brain responsible for a range of functions including remembering the past, envisioning the future, thinking about others, and thinking about yourself. When the default mode network is in overdrive, it can result in repetitive focus on negative thoughts—the preoccupation or rumination typical of a major depressive episode.
And that’s where psychedelics come in as potential therapeutic tools.
We know from brain scans that activity across the Default Mode Network decreases while under the influence of psychedelics. This temporary decrease in default mode network activity is thought to explain the common “ego-dissolution” experience.
Studies have shown that during psychedelic-assisted therapy an ego-dissolution experience can be positively associated with therapeutic outcomes.
Scientists think that turning down the default mode network with the help of psychedelics might help repetitive, negative brain patterns become unstuck, providing a fresh slate on which to build new and healthy mental habits.
Mental flexibility
Next up is mental flexibility. A key feature of mental health is mental flexibility, or the ability to adapt and shift our thought patterns.
There are two types of mental flexibility:
There is psychological flexibility, which is the ability to feel and think with openness, to voluntarily focus on the present moment, and to build habits based on values and aspirations.
Then there is cognitive flexibility, the ability to move your attention from one thing to another— basically not getting stuck in repeating or ruminating thoughts. People with high cognitive inflexibility tend to get stuck in negative thought patterns.
Psychedelics have been shown to increase both psychological and cognitive flexibility by temporarily increasing the entropy or “disorder” of brain activity.
During a psychedelic experience, regions of the brain that normally don’t communicate with each other are communicating, and doing so in patterns that are very different from a normal waking state. This temporary change in brain activity, allows for the relaxation of prior beliefs, and increases the potential for new ideas and insights.
And the really amazing part: even though this drug-induced brain pattern change is temporary, the new pathways established during a psychedelic experience can persist after the experience, and their effects can be long-lasting.
Neuroplasticity
Neuroplasticity is the brain’s ability to reorganise its structure, function, and connections in response to a changing environment or a shifting set of demands. Psychedelics can enhance neuroplasticity, increasing the brain’s ability to form new connections. In other words, during a psychedelic experience, your brain’s ability to change how it’s wired goes way up.
Neuroplasticity just means the capacity to change: it doesn’t indicate what type of change.
Research has shown a supportive environment and a positive mindset going into the psychedelic experience can result in better outcomes or higher chances of those changes being productive and sustainable.
That’s another reason why working with professional therapists and trained sitters is recommended to achieve those long-lasting therapeutic benefits.
There’s still a lot we’ve yet to discover about how our infinitely complex brain works—and what we can do to help in times when it’s not working as well as it can.
Researchers are studying the properties of psychedelics to address some of the most challenging mental health conditions. These include depression, anxiety, substance use disorder, PTSD, chronic pain, and eating disorders.
Results have been promising—so much so that interest in psychedelics has boomed in recent years, and their therapeutic value increasingly accepted and embraced by the scientific and mental health communities.
Further Reading
Does Psychedelic Therapy Have a Transdiagnostic Action and Prophylactic Potential? by Rita Kočárová, Jiri Horacek, Robin Carhart-Harris
Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents
The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future by Robin Carhart-Harris and Guy M Goodwin
Good Chemistry #26 (Podcast): Dr. Berra Yazar-Klosinski: MDMA, PTSD, Psychotherapy & MAPS
The Tim Ferriss Show #440 (Podcast): Rick Doblin- The Psychedelic Domino That Tips All Others
Making Sense #177 (Podcast): Psychedelic Science, A Conversation with Roland Griffiths
Focus on Clinical Research, Episode 1 (video): The Johns Hopkins Story by Horizons PBC
Focus on Clinical Research, Episode 2 (video): Death, Dying, & Psychedelics by Horizons PBC
NPR Fresh Air (Podcast): Psychiatrist Explores Possible Benefits Of Treating PTSD With Ecstasy Or Cannabis
The Microdose – A newsletter from the U.C. Berkeley Center for the Science of Psychedelics
Psychedelic Scientists Should Honor Indigenous Plants and Traditions By Bia Labate, Ph.D.