With this post, the psychedelic journey of my blog comes to an end – at least for now. After discussing the troubled history and the molecular level effects of LSD and other psychedelics, let’s take one last plunge into the mystical sea of colors. In today’s post I will try (and largely fail, sorry for the spoiler) to understand how psychedelics impact a person’s feeling of self, and how this might help patients with psychiatric disorders.

A personal note to begin with

Diving into the area of brain research usually leaves me with the feeling that I know nothing at all. Once this feeling strikes me, I start wondering if it isn’t an inherently flawed endeavor, for humans to try comprehending their own brains. My cowardice when it comes to brain research was sealed before I turned twenty-one, when I abandoned my idea of becoming a neurobiologist and instead ventured into molecular biology. Studying the brain just seemed too daunting.

To the current day, while researchers gather more and more information, the big questions about the brain, about humanity seem to elude us. Could psychedelics be an ally on our quest to try to understand the brain? Indeed, the word psychedelic, which comes from Greek, means something like ‘mind manifesting’, highlighting the drug’s ability to bring hidden aspects of the mind out of stealth mode and to the forefront of our consciousness.

What do psychedelics do to the higher command center?

In my last post, I introduced the brain as a midsize company, and discussed its molecular interactions, represented as the level of single employees, and different brain areas represented as individual departments. Now we reach the higher command center – the executive level of our brain company that produces our feeling of self. The neural correlates of this self, however, are incompletely understood. It’s like a magic trick that the lump of cells residing in our skulls plays, turning chemical and electrical signals into a feeling of unity comprising all the parallel processes that happen in our brains.

This sense of self-unity can be blurred or even dissolved by LSD and other psychedelics, also described as a mystical-type experience. While this doesn’t necessarily mean that we can extrapolate one-to-one to normal (whatever that means) states of consciousness – psychedelics might allow us to draw some conclusions on how self is created, and how it is disturbed in psychiatric disorders.

But how can we study the disturbance of a process we don’t fully understand?

The fallback method of modern brain science are imaging studies, which highlight areas of activity in the brain. Yet, a number of recent brain imaging studies have yielded diverging results for brain activity during states of self dissolution. Maybe this inconsistency is due to differences in the study setup, but likely there is also the component of individual differences in the creation of self and its dissolution. It seems that there isn’t a one-size fits all explanation – at least not yet.

Nevertheless, even though we don’t understand what exactly is happening during those mystical states, a positively perceived ego dissolution seems to corelate with success of psychedelic-aided therapy for addiction, depression, and other psychiatric diseases.

Something that happens during those few hours of loss of self leaves a lasting imprint on patient’s brains.

One hypothesis brings us back to the reset idea – think switching off and on a computer. Now I admit that I am speculating, but maybe the temporary loss of self could lead to a shortcut in the negative or obsessive thought patterns, which are etched into the brains of patients with depression, addiction, and other diseases - like a break in an electronic circuit in the unplugged computer. When switching the self back on, negative patterns are not reinstated to the same extent and could be fully overcome.

Beyond self

Even our complex brain company does not exist in a vacuum and is only a small part of a big machine that is interconnected with many other entities. There isn’t a lot of business you can do all by your lonesome.

Similar to our company, our feeling of self, created by our brain does not exist is not in a vacuum and depends on interactions with and reactions by others. In many psychiatric diseases, so-called social cognition, thoughts, and emotions that integrate self with others, is altered. This can lead to social withdrawal – which in many cases enhances the pathology in a downwards spiral.

Interestingly, a number of studies report that psychedelics could have a positive effect on the interaction with others. For example, LSD and psilocybin have been shown to increase emotional empathy and reduce feelings of social exclusion. Together those effects might reduce social withdrawal and improve interactions, with long-term benefits for patients. Although there is currently only thin data on the long-term interpersonal effects that psychedelics have in psychiatric patients, a few studies highlighted self-reported improvements in pro-social behavior, which was beneficial for overcoming smoking addiction and for depression.

A way to cure patients with psychiatric diseases

Treating psychiatric patients with drugs that are perceived as so-called “hard” drugs, which induce hallucinations, and which can have severe mental (if not necessarily physical) side-effects is prone to create a public headshake if not a fully-fledged public outcry. I must admit that I myself was extremely skeptical about the idea before diving deeper into the topic.

However, hallucinogenic, ego-dissolving substances still appear benign when contrasted against methods that have been used for treating mentally ill patients in the past. Indeed, the discovery that LSD changes the chemistry of the brain preceded the first approved depression drug (the monoamine oxidase inhibitor Iproniazid)  by some years and might have been instrumental in paving the way for medical intervention for depression. Before the discovery that chemical substances could treat psychological ailments, there was either psychotherapy or sedation, not to forget the host of medieval methods –electroshock therapy, insulin coma, and of course the lobotomy. In this last, Nobel-prizing winning technology the prefrontal lobes of the brain were surgically removed, first by scalpel and later, as popularized in the United states by Walter Freeman, by icepick. Mark you, the prime age of the icepick brain surgery was the 1950s and not some long-gone times. In comparison, the discovery of drugs which alter brain chemistry, even if the compound might make you see some colors, seem like a massive leap.

Indeed, a number of recent studies showed that patients with alcohol and nicotine addiction, as well as terminal cancer patients suffering from anxiety and depression, individuals with treatment resistant depression and post-traumatic stress disorder benefited from psychedelic treatment. Compared to currently used, psychedelics might have some major advantages – fast onset of improvement (which imaginably is of high relevance for patients with acute suicidal ideas), long duration (meaning patients wouldn’t have to take medication constantly), fewer severe side-effects and low addictive potential.

LSD and other psychedelics appear especially suited for inward-looking psychiatric diseases, characterized by ruminating thought patterns, such as depression and anxiety, addiction, and OCD. In contrast, for other diseases, such as schizophrenia, they are likely to cause harm, instead. Importantly for treating depression, psychedelics also appear to change emotions, and in a controlled setting reduce the response to negative stimuli.

While those results are encouraging, caution is warranted, because there are several sources of bias:

A)      Except for very few studies, those tests of psychedelics were uncontrolled meaning, the patients knew they were going to be treated with the drug. Even expecting to get better will make you better, an effect which is especially evident for psychiatric diseases.

B)      In the case of psychedelics, it is difficult to find the right control conditions. A placebo – a compound that does nothing – is not a good comparison for a compound expected to cause hallucinations, meaning a substance that has an effect akin to that of psychedelics is required.

C)      It is difficult to disentangle the effects of the accompanying therapy from the effects of the drug itself. From a patient perspective, this doesn’t matter much, as long as the therapy works. From the researcher’s perspective, however, it makes it difficult to understand the true contribution of the psychedelic. There are reports of psychiatric patients, who benefited from psycholytic therapy (low dose psychedelic + talk therapy), but also those who got better with psychedelic therapy (high dose psychedelic without additional psychotherapy). All modern studies, however, give psychedelics in the context of psychotherapy, which might be important for the proper integration of the experience and subsequent treatment success.

D)      The confirmation bias of researchers and patients contributing to psychedelics trials is likely especially high, given the ostracized status of the field – those who spent their time and energy on psychedelics research will want it to work very badly and patients who are willing to undergo this treatment will likely have a strong belief that they will benefit.

The research field of psychedelics, despite its decade long history, seems at the beginning of a new era, with more controlled studies, allowing researchers to gauge the true benefits for psychiatric patients.  

And maybe, on the long run, the consciousness-altering, ego-dissolving nature of psychedelics could help use curing the organ we can’t quite understand.