Psychedelics, psilocybin and SSRIs – can psychedelic therapy help treat depression?

According to some researchers, psychedelic substances may, in certain controlled medical contexts, offer interesting advantages over conventional antidepressants because of their strong influence on neuroplasticity and emotional processing. At the same time, they remain highly regulated substances and must not be used without medical supervision. For a broader scientific overview of these substances, see psychedelic therapy on Wikipedia.

“Will psychedelics save the world?” is a thought-provoking publication that examines the potential and limitations of psychedelic therapy in a painfully honest, evidence-based way. The key question is not only whether psychedelics can “save the world”, but whether they can safely support modern people – often exhausted by stress, trauma and depression – when used in a structured therapeutic setting.

Depression is a civilisation disease that often develops slowly and silently, until it covers everyday life with a heavy, dark filter. The number of people struggling with depressive disorders grows every year. At the same time health-care resources are limited: psychiatric wards are being closed, waiting times for psychologists and psychiatrists reach several months, and many people still feel shame about seeking help. We are only learning, as a society, that mental health is as important as the spine, stomach or hand – and that a psychologist or psychiatrist is simply a doctor who knows specific methods and medicines.

Why can psychedelics help treat depression?

An accessible overview of what psychedelics are and what types exist can be found, for example, here. In this article we focus mainly on psilocybin mushrooms (magic mushrooms), which belong to the group of psychoactive substances called psychodysleptics.

Psilocybin – the main active compound in these mushrooms – is a natural psychedelic that influences receptors involved in the production and signalling of serotonin, sometimes called the “happiness hormone”. Serotonin receptors are located in the gut (roughly 90%) and in the brain. One of the factors associated with depressive disorders is reduced availability or impaired signalling of serotonin. Diet, lifestyle, chronic stress and sleep deprivation can all contribute to this imbalance.

If you want to read a short scientific introduction, see also psilocybin on Wikipedia.

SSRIs – antidepressant drugs

SSRIs are currently the most commonly prescribed antidepressants. They were developed in the 1980s and are considered relatively safe compared with older drug classes such as TLPDs. The abbreviation SSRI stands for selective serotonin reuptake inhibitor. These medicines improve mood and help treat depression by blocking the reuptake of serotonin in the brain.

Serotonin is a neurotransmitter in the central nervous system – in simple terms, a chemical signal that carries information between nerve cells. It is released into the synaptic gap between neurons. SSRI drugs block its reuptake, increasing the amount of serotonin in this gap and prolonging its action. In summary, SSRIs prevent serotonin from being quickly removed and recycled, which can alleviate depressive symptoms in many patients.

Psilocybin contained in hallucinogenic mushrooms

Psilocybin is a naturally occurring psychedelic found in mushrooms of the genus Psilocybe (Golden Teacher growkit). It changes the way we perceive reality and experience emotions, and it strongly modulates serotonin signalling in the brain. Depending on dose and context, psilocybin can induce euphoria, improve mood, generate deep psychedelic experiences or cause vivid changes in perception (hallucinations).

The recent renaissance of research into psychedelics has highlighted something crucial: psilocybin is being taken seriously as a potential aid in treating depression, especially its most severe, treatment-resistant forms. The effects of psilocybin are linked to serotonin, which is why some commentators metaphorically refer to it as a “natural-origin SSRI” – although pharmacologically it acts quite differently and should not be equated with standard antidepressants.

If you are interested in the medical side of psilocybin therapy, a helpful starting point is the Wikipedia entry on psychedelic therapy, which summarises ongoing clinical trials.

Differences between SSRIs and psilocybin (psychedelics)

Both SSRIs and psilocybin ultimately influence serotonin, but they act on partly different receptors and in a very different experiential way. SSRIs mainly modulate 5-HT1A receptors, while the key target for psilocybin is 5-HT2A receptors in the cortex.

5-HT1A receptors

5-HT1A receptors are associated with stress regulation and are found, among others, in the limbic system. Their stimulation helps us “endure more” – we become less sensitive to everyday stressors and more resilient. The downside can be emotional flattening or a sense of being slightly disconnected from our feelings in some patients.

5-HT2A receptors

5-HT2A receptors work differently. Their strong activation – as in the case of psilocybin – temporarily increases sensitivity to internal and external stimuli and can “shake up” rigid patterns of thinking. In simplified terms, the message is: “you can handle more, but now process the underlying material so you don’t have to come back to it”. This is linked to increased neuroplasticity and changes not only in the limbic system but across large-scale brain networks.

We are not psychiatrists, so we quote a fragment from an interview conducted by Maciej Lorenc (member of the board of the Polish Psychedelic Society) with Dr Justyna Holka-Pokorska (psychiatrist, sexologist and therapist, president of the Warsaw branch of the Polish Psychiatric Association):

“ML: Both classic psychedelics and SSRI drugs affect the serotonergic system, but they work in different ways. What are the differences?

HP: […] The clinical effect of SSRI drugs is to regulate emotional processing and stabilise the function of neuronal pathways that have become dysfunctional as a result of chronic stress or depression. […] Some patients say that antidepressants overly suppress the emotions they experience, causing a ‘dissociation from emotions’ or even ‘emotional anaesthesia’.”

“It is worth noting that in the vast majority of cases, the benefits of antidepressants against symptoms of depression and anxiety significantly outweigh the side effects. […] Thus, the introduction of SSRI drugs was a major progress in psychiatry, but it can also be said that in some ways it helped cement the foundations of the lifestyle of an era of rampant consumerism, reinforcing the hyper-productivity demands placed on employees.”

“ML: And what is the therapeutic effect of psilocybin?”

HP: “Psilocybin and psilocin are natural tryptamine alkaloids and structural analogues of serotonin. […] Their action mimics that of serotonin, which is missing from the synaptic gap during a depressive episode. The clinical effect of psilocybin is different from SSRIs: instead of extinguishing sensitivity to stimuli, reactivity may temporarily increase. The new methodology assumes that the psychedelic experience itself can become therapeutic, by allowing people to gain a new perspective. There is also evidence that these substances stimulate neuroplasticity in the brain and can interrupt the ‘depressive triad’ of automatic negative thoughts about the past, present and future.”

NOTE!

The content on the psychodelicroom.pl website is educational, research-based, and expresses many opinions that should be treated with caution. We advise against using any substances that affect consciousness, as all of these substances can both help and be very harmful. In particular, we advise against cultivating mushrooms from growkits in countries where it is illegal – including Poland – because it involves criminal liability. We recommend that you dispose of the growkits purchased from us within 72 hours of receiving them.

Is psilocybin better than an SSRI?

There is no clear, universal answer. Psilocybin is an extremely promising agent in psychiatric research, but the body of evidence is still not large enough for it to replace standard treatments. SSRIs have played an important role in treating depression and have helped many people return to everyday functioning. They are invaluable in many contexts.

SSRIs can be seen as a tool that helps patients cope with daily life – work, childcare, basic tasks – when symptoms are overwhelming. They may reduce insomnia and protect the mind from crisis, although they do not directly “remove” the deeper causes of depression or anxiety. The article compares SSRIs to crutches: when we break a leg, we get support that allows us to move while the bone heals. Later we add rehabilitation. Similarly, SSRIs can stabilise a patient, while psychotherapy and lifestyle changes help address underlying issues.

There are many opinions about the pros and cons of SSRIs, and we are not trying to claim that psilocybin is “better”. For some people, classic antidepressants will remain the safest and most appropriate choice; for others, in the future, supervised psychedelic-assisted therapy might become an additional option – always under the care of medical professionals.

DISCONTINUATION OR WITHDRAWAL OF ANTIDEPRESSANT THERAPY SHOULD ALWAYS BE CONSULTED WITH YOUR DOCTOR. STOPPING MEDICATION ON YOUR OWN MAY SERIOUSLY HARM YOUR HEALTH AND INCREASE THE RISK OF RELAPSE.

Research on psychedelics – the beginnings

We talk about a “renaissance” of psychedelics because research into their therapeutic potential started decades ago. From the 1950s onward, numerous studies explored LSD and other substances in the treatment of various psychiatric conditions. This work was largely halted after 1971, when regulatory changes banned many psychedelics. A key figure here was US president Richard Nixon, whose “war on drugs” also targeted the counterculture and anti-war movement.

Among pioneers we can mention Albert Hofmann, the Swiss chemist who first synthesised LSD, and Czech psychiatrist Stanislav Grof. Hofmann worked for the Sandoz pharmaceutical company, which invested millions of dollars to distribute LSD samples to psychiatric hospitals and universities around the world, hoping someone would find a therapeutic use. Grof used psychedelics intensively in clinical research for almost 20 years, in Prague and later in the US, working with severe cases and achieving remarkable treatment progress under strict protocols.

Less well known is Marina Boyadjieva, who worked at the Department of Psychiatry at Sofia Medical University and developed experimental models of psychosis using LSD. For a historical overview of psychedelics, see also history of LSD on Wikipedia.

If you want to learn more about these early experiments:

https://www.rp.pl/nauka/art13151351-lsd-ma-70-lat
https://www.stangrof.com/
https://www.biblionetka.pl/art.aspx?id=878504
https://hyperreal.info/info/wczesne-badania-nad-lsd-w-komunistycznej-bulgarii
https://www.atlasobscura.com/articles/the-early-state-sanctioned-lsd-experiments-in-communist-bulgaria

Contemporary research on psychedelics

Psychedelics have only recently returned to mainstream scientific research. In 2000, a team at the Center for Psychedelic & Consciousness Research at Johns Hopkins Medicine in Baltimore received one of the first modern approvals in the US to resume studies with psychedelic substances.

The centre – and other teams worldwide – investigates the properties of psilocybin and related compounds in a controlled clinical setting. A foundational 2006 study on the safety and lasting effects of a single dose of psilocybin opened the door for further trials at other universities and hospitals. You can find more details at: https://hopkinspsychedelic.org/.

Current research programmes look at the potential impact of psychedelic-assisted therapy in:

• depression (including treatment-resistant depression),
• addictions (alcohol, nicotine, other substances),
• Alzheimer’s disease,
• Parkinson’s disease,
• post-traumatic stress disorder (PTSD),
• anxiety disorders,
• Lyme disease syndrome,
• eating disorders such as anorexia,
• existential distress in terminally ill patients (e.g. with cancer) – helping them come to terms with dying .

Institutions conducting research on psychedelics

A convenient overview map of centres involved in psychedelic research can be found here: https://www.datawrapper.de/_/AAhCw/.

Some of the better-known institutions include:

• Johns Hopkins University
• Imperial College London
• Vancouver Island University
• Oregon Health & Science University
• Washington State University
• University of California

Will psychedelics save the world? Will psychedelics save us?

In his book “Will psychedelics save the world?” Maciej Lorenc collects interviews with experts who cautiously explore whether these substances can help in treating PTSD, depression and other conditions. The experiences brought by psychedelic sessions are sometimes compared to states achieved in deep meditation – but they are more intense, less predictable and absolutely not suitable for recreational experimentation without proper preparation and supervision.

Many people place great hope in psychedelic therapy or psilocybin microdosing as tools for improving creativity and mental health. At the same time, clinical reality is more complex: not everyone benefits, some people experience difficult or frightening states, and research protocols require careful screening and integration with psychotherapy.

At the University of California, Davis, Prof. David Olson and his team are searching for so-called “non-hallucinogenic psychedelics” – compounds that might enhance neuroplasticity and relieve symptoms without strong visuals that can be distracting or overwhelming for some patients. If successful, such molecules could become an important bridge between classic antidepressants and psychedelic-assisted therapy.

One thing is certain: any therapeutic use of psychedelics must be closely monitored by doctors and trained therapists. Self-experimentation, especially in people with a history of mental illness, can be dangerous and is strongly discouraged.

The pharmaceutical industry and nature

Research on psilocybin still needs to gain momentum and pass through strict regulatory procedures. Some critics worry that commercial interests will favour synthetic, patentable molecules over natural compounds that are harder to monetise. Others point out that without pharmaceutical-grade production and clinical standards, it is impossible to guarantee safety and quality.

We will see in the coming years whether psilocybin – the compound present in psilocybin mushrooms – follows a path similar to that of medical cannabis and becomes a regulated therapeutic tool in some countries. For now, in Poland and many other jurisdictions, it remains an illegal substance outside of approved clinical trials.

* What is a psychedelic experience?

https://pl.wikipedia.org/wiki/Do%C5%9Bwiadczenie_psychodeliczne

https://www.youtube.com/watch?v=d006xwEQK9c&t=2s

The content on the psychodelicroom.pl website is educational, research-based, and expresses many opinions that should be treated with caution. We advise against using any substances that affect consciousness, as all of these substances can both heal and be very harmful. In particular, we advise against cultivating mushrooms from growkits in countries where it is illegal – including Poland – because it involves criminal liability. We recommend that you dispose of the growkits purchased from us within 72 hours of receiving them.

Footnotes:

https://neuroexpert.org/wiki/serotonina/
https://www.doz.pl/czytelnia/a16257-Serotonina__jakie_problemy_zdrowotne_sa_zwiazane_z_nieprawidlowym_poziomem_hormonu_szczescia
https://www.depresjaza.pl/leki/ssri
https://wylecz.to/leki-i-suplementy/selektywne-inhibitory-zwrotnego-wychwytu-serotoniny/
https://kobieta.onet.pl/czesc-psychiatrow-chce-legalizacji-substancji-psychodelicznych/b17m06b
http://www.psychiatria.com.pl/index.php/wydawnictwa/2016-vol-16-no-3/psylocybina-jako-alternatywny-lek-dla-osob-cierpiacych-na-depresje
https://psychodeliki.org/czy-psylocybina-leczy-depresje/
https://psychodeliki.org/czy-psychiatria-potrzebuje-psychodelikow/
https://mind-foundation.org/psychedelic-antidepressant-interactions/?lang=pl
https://depot.ceon.pl/bitstream/handle/123456789/13483/Terapia_szokowa_czyli_zastosowanie_agonist%C3%B3w_receptora_5HT2A_w%20_leczeniu_depresji.pdf?sequence=1
https://psychedelic.support/resources/psilocybin-and-ssris/
https://psychologia.edu.pl/obserwatorium-psychologiczne/1156-piec-powodow-by-nie-brac-lekow-ssri.html
https://www.termedia.pl/mz/Zastosowanie-substancji-psychoaktywnych-w-leczeniu,47703.html
https://www.datawrapper.de/_/AAhCw/
https://www.focus.pl/artykul/czy-psychodeliki-sa-przyszloscia-leczenia-depresji-jeden-taki-lek-jest-juz-dostepny-w-polsce-wywiad
https://web.swps.pl/strefa-psyche/blog/relacje/22619-cala-nadzieja-w-psychodelikach-substancje-psychoaktywne-w-leczeniu-zaburzen-psychicznych