Key takeaways.

  • What does the research say about psilocybin and depression?

    Psilocybin has showed positive effects in those with depression, especially those with terminal illnesses who confront the fear and anxiety associated with end-of-life.

  • Why is psilocybin different to conventional therapies?

    Psilocybin has, so far, showed a fantastic safety profile. On top of this, psilocybin works immediately whereas conventional therapies typically take a long time to work.

  • What’s the clinical significance of psilocybin in depression?

    Given how few treatment options there are for depression, many of which are not long lasting, there is a dire need for safe and effective alternatives for the treatment of depression. Psilocybin offers hope.

Depression is one of the most burdensome global health problems, affecting around 4% of the world’s population and 5.4% of Canadians over 15. One of the biggest hurdles of depression is its resistance to treatment, as currently available therapies are only effective for some, or simply only partially effective. 

A lot of people just don’t get to remission. And the instance of relapse is concerningly high.

The need for more effective therapies for depression has necessitated the new-age plight into psychedelic research. What early research began in the 60s came to an abrupt halt but has recently been picked back up again. Now, our new research is showing us that beyond the ability to put depression in remission, psilocybin also keeps it there for the long term.

The research on psilocybin and depression.

A collage of many kinds of mushrooms with human bodies.
@amyo426

What we’re observing in the clinical setting at the moment is very exciting. Although for many it’s “old news” that psychedelics such as psilocybin have the potential to treat depression, it’s nonetheless exciting to watch these revelations take place in the scientific sphere.

A number of preliminary clinical trials have already taken place on the effects of psilocybin and depression, as well as in the context of end of life patients battling anxiety and depression. Let’s check them out and break them down.

Carhart-Harris et al., 2016.

In this study, Carhart-Harris and his research team administered two high doses of psilocybin (10mg and 25mg) 7 days apart. Each of the patients was diagnosed with moderate-to-severe treatment resistant major depression. 

The primary outcome of the study was to measure the subjective effects at different doses, but the research team made secondary findings on the effect of psilocybin on depressive symptoms. Patients showed marked improvement in depression scores 1 week and 3 months after high dose treatment. Anxiety and anhedonia scores improved, too. 

The purpose of Carhart-Harris et al.’s 2016 research was to understand the safety of psilocybin treatment in the context of clinical depression. They reported transient anxiety and confusion, mild and transient nausea, and transient headache. Overall, the team concluded that psilocybin was poised to be a safe and effective treatment for clinical depression, pending more rigorous trials.

Ross et al., 2016

A concept illustration of depression, with the face removed from the head.
@artbylelo

In this double-blind, placebo controlled clinical trial, psilocybin was put to the test for the treatment of anxiety and depression in patients with life threatening cancer. The trial included 29 cancer patients with cancer related anger and depression. They were given a single dose of psilocybin at 0.3mg/kg or niacin, both in conjunction with psychotherapy. The psilocybin and niacin groups were compared at 7 weeks and 6.5 months after treatment.

Between treatment and 7 weeks, the researchers observed immediate, substantial, and sustained antidepressant and anxiolytic effects in the psilocybin group. The participants also reported better spiritual wellbeing and improved quality of life. At 6.5 month follow up, the psilocybin group (60-80%) continued to show clinically significant reduction in depression and anxiety as well as improved attitudes towards death. Interestingly, Ross et al. highlighted that the mystical experience appeared to be the driver of these changes.

The psychological distress caused by terminal illness is a special circumstance, but the findings of Ross et al. support the use of psilocybin for depression alongside psychotherapy.

Griffiths et al., 2016.

The Griffiths et al. study is a lot like the Ross et al. study, investigating the effects of psilocybin on depression in terminal cancer patients. The findings of this study are blaringly supportive of Ross et al.’s findings, showing a marked reduction in feelings of depression and anxiety pretty much immediately, and ongoing for at least 6.5 months.

However, in addition, Griffiths et al. identified that it was a musical-type psilocybin experience that mediated positive changes in depressive symptoms and quality of life.

Carhart-Harris et al., 2017.

In this more recent study from Carhart-Harris, MRI data was collected on patients with depression both pre and post psilocybin treatment to better understand the mechanisms at play. The research team conducted whole-brain analysis on 19 patients  both before and after treatment. The researchers observed decreased depressive symptoms in all 19 patients and their brain scans showed:

  • Decreased cerebral blood flow in the frontal cortex
  • Decreased cerebral blood flow to the amygdala that correlated with reduced symptoms
  • Changes in resting-state functional connectivity depending on the brain site

The researchers put this all together and proposed a “reset” mechanism by which psilocybin exerts long-lasting effects on the brain post treatment. The whole concept of post-treatment brain changes opens up a whole new world of understanding outside of what we typically accept as clinical outcomes.

Safety and swiftness of action vs conventional therapies.

An illustration of a woman whose skull is open, and from out of it grows flowers.
@caitlinhillart

When it comes to comparisons between psilocybin and conventional therapies, there are two standout beneficial aspects of psilocybin: safety and how quickly it works. Conventional therapy for depression includes SSRI’s (a class of antidepressant drugs) and psychotherapy. It’s important to recognize that antidepressant drugs are formulated on conventional theories about depression. 

It can take SSRI’s anywhere between 4 and 6 weeks to work. It’s hypothesized that this is because antidepressants aren’t direct mood enhancers, but that they have effects on emotional processing before they have any effect on mood. 

In every study we explored, psilocybin had effects virtually immediately after treatment, and was long lasting thereafter.

Treatment emergent adverse events aren’t uncommon with SSRI’s, with anything from weight gain to serotonin disorder (which is fatal) as a side effect. Fatal adverse events aren’t a common occurrence with SSRI’s, but compared to placebo, there are significantly more adverse effects reported from SSRI’s.

In the research we mentioned, adverse effects of psilocybin included transient headaches, confusion, and anxiety. They were overall deemed safe to use under clinical guidance. There nonetheless does exist the risk of psychosis, though it’s not clear for whom or under what circumstances. 

Clinical significance of psilocybin.

Why is all of this important? Well, for a lot of reasons. To start with, depression has become so common in the modern world, it’s almost a social disease. The recurrence rate is so high that depression becomes an ongoing challenge to the health system. For example, depression is the most prevalent diagnosis among suicide victims. Lifetime depression can increase the risk of suicide by 20 times compared to the normal population. 

The ongoing burden of depression demands alternative therapy that’s safe and effective, and demands it urgently. Psilocybin poses an unbelievably cheap, safe, and immediately effective treatment potential for those with severe depression, and even those whose depression hasn’t reached severity.

If psilocybin can live up to the expectations it’s setting, it can absolutely change the face of clinical depression forever.  

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