An infamous public health campaign once famously claimed that drugs do nothing but turn users’ brains into fried eggs. However, a growing body of research suggests that psychedelics may in fact help unscramble the mind, resulting in major improvements in mental health. These days, scientists have largely laid the egghead idea to rest, instead attempting to understand how these consciousness-altering drugs bring about their therapeutic effects.

With current evidence, it would appear that psychedelics have the potential to move the dial on conditions like depression and addiction, yet it is unclear whether healing is mediated by the psychedelic experience itself or by an increase in the brain’s ability to rewire itself following a trip.

Summing up this intriguing psychedelic puzzle, Dr Rosalind Watts – clinical lead of the famous Imperial College London study on psilocybin for depression – posed the question to IFLScience: “is it a brain reset or is it a turbo-charged therapeutic experience? If you ask different patients, you get different responses.”

A “Brain Defrag”

Patients enrolled in Watts’s study had all been diagnosed with severe, treatment-resistant depression – yet showed dramatic, lasting improvements after being treated with psilocybin, the psychoactive compound in magic mushrooms. Six months later, Watts and her colleagues interviewed participants about their experiences, noting that several alluded to a mental “defrag”.

“The reset switch had been pressed so everything could run properly,” explained one patient, while another said “I felt my brain was rebooted”. Yet another testified that the effect was “like when you defrag the hard drive on your computer,” and claimed to have visualized their mind being “put into order.”

Fascinatingly, brain scans of patients undergoing psilocybin treatment for depression have revealed that the drug does appear to completely reboot and rearrange certain neurological pathways that are heavily linked to the condition.

In the previous chapter in this series, we explained how psychedelics cause a brain network called the default mode network (DMN) to disintegrate, yet scans taken a day after treatment show an increase in connectivity within the DMN, indicating that it comes back online with renewed vigor once the acute effects of the drug wear off.

Describing this neurological phenomenon, the study authors explained that “this process might be likened to a ‘reset’ mechanism in which acute modular disintegration (e.g. in the DMN) enables a subsequent re-integration and resumption of normal functioning.”

Separate research has revealed that a single dose of ayahuasca causes brain connectivity to become more fluid and flexible for up to several weeks, resulting in prolonged enhancements in mental health parameters. This phenomenon has been dubbed the “psychedelic afterglow” and has been linked to increased mindfulness capacities after drinking the potent Amazonian brew. 

Returning to the question of how psychedelics heal, Watts explains that clinical improvements tend to occur “when there’s a beautiful confluence of afterglow – which is a physiological brain flexibility – combined with having had a deeply therapeutic experience. So it’s working on both levels, it’s neurological and psychological.”

New Brain Cells?

Far from frying the insides of your bonce, research has shown that psychedelics may actually spark the creation of new neurons and synapses, meaning you could end up with more brain cells after dropping acid. While this has yet to be confirmed in live human subjects, a sensational study on mice found that ayahuasca triggered neurogenesis within the hippocampus.

Such a finding could be a game-changer for psychiatry, given the central role of this brain region in learning and memory. By generating new neurons in this key structure, it’s thought that psychedelics could enable people to alter their modes of cognition and thinking, thereby helping recovery from depression, anxiety, addiction, and other mental conditions.

Separate research has indicated that tiny doses of the psychedelic drug DMT are sufficient to trigger a 40 percent increase in neuronal connections when applied to rat neurons in a test tube. In addition to the implications this may have for mental health, this finding led to suggestions that psychedelics could help to prevent or repair brain damage following strokes and other brain injuries.

What About The Psychedelic Experience?

Intriguingly, this massive boost in neuronal connections was achieved using a dose of DMT far too small to produce any alterations of consciousness, fueling the argument that psychedelics might help the brain to rewire itself without the need for mind-bending trips. Known as neuroplasticity, this capacity to reshape connectivity patterns in the brain is strongly linked to mental health improvements.

Researchers at the University of California, Davis, are attempting to create a drug mirroring the healing effects of classic psychedelics without activating the 5-HT2A receptor that mediates the alterations of consciousness these drugs are synonymous with. Their work has already indicated that it is possible to enhance neuroplasticity and attenuate depression and addiction in mice without producing a trip, implying that psychedelic experiences may not be essential for emotional healing.

Psychedelics that lack any psychoactive effects would be considerably more palatable to certain patients who may be a little apprehensive about diving through a mental wormhole. However, it’s also worth remembering that humans tend to be more psychologically complex than both mice and test tubes, and one mustn’t make any assumptions as to the clinical efficacy of psychedelics until they have been tested further on actual people.

In a poignant study involving terminal cancer patients, psilocybin was found to significantly reduce anxiety, depression, and feelings of hopelessness, with these improvements lasting for several years. Importantly, positive outcomes were strongly linked to the content of the psychedelic experience itself, with one participant explaining that their renewed sense of positivity was born from a feeling of “overwhelming love” while under the influence of the drug.

Other studies have highlighted the importance of “ego dissolution” and “mystical experiences” in psychedelic-assisted psychotherapy. For instance, mystical experiences have been correlated with reductions in depression following treatment with the compound 5-MeO-DMT, while several participants in the psilocybin study explained how the disintegration of their ego allowed them to discover a restorative sense of connection to the world.

“This sense of connectedness, we are all interconnected, it’s like a miracle!” exclaimed one patient, while another explained how “before [psilocybin] I enjoyed nature, now I feel part of it.”

Emphasizing the healing potential of this archetypical psychedelic-induced experience, Watts says that “more and more I think that depression and suffering are to do with the ego consciousness of the separate self – the insecure, unsafe, separate safe. But when the ego gets broken down, whether it’s fully or just partially, and [patients] feel that connectedness with everything else, that’s really the thing [that brings about healing].”

Emotional Processing

Another major theme from interviews with participants in the psilocybin study was an increase in emotional intensity. Many revealed how their depression went hand-in-hand with an experience of “numbness”, and that after years of missing the richness of life, they suddenly became filled with emotion during their psychedelic experiences.

This burst of feeling is encapsulated by one patient who revealed that “I was weeping, tears were flowing out of me,” while under the influence of psilocybin, but that “it wasn’t a painful crying, it was like turning on the taps.”

Such a surge of emotion may be explained by the fact that activity within the amygdala was found to increase when participants in this study ingested psilocybin. In contrast, conventional antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are known to dampen activity in the amygdala, which could lead to reducing emotional processing.

By reawakening affective processing in this key limbic brain region, psychedelics appear to help people overcome depression by re-establishing their ability to feel rather than keeping it suppressed.

Integration

While psychedelics appear to activate a number of different mechanisms that may be beneficial for mental health, it’s important to remember that none of these are tantamount to healing per se. Rather, via neurological and psychological effects, these substances help to create conditions that are favorable for wellbeing, opening up a window of opportunity for therapy.

The process of converting these temporary changes and experiences into enduring psychological improvements is known as integration, seen by many experts as the key to psychedelic therapy. “Psychedelics don’t bring about any change without integration, so I think integration is literally everything,” says Watts.

Currently preparing to launch a year-long psychedelics integration program focusing on community-building and contact with the natural world, she explains that the true beauty of these psychoactive compounds lies in their ability to inspire us to seek out connection. “Psychedelics are the way in. They open the door and allow people to be more emotional, more connected to nature, more connected to ourselves” she says.

“They open us up, but what we need to build now are structures for integration.”