This research briefing is co-published with the excellent Report on Psychedelics.

June 3rd, 2021

In The Research Briefing:

• Reducing negativity bias in depressed patients with psychedelics
• Psychedelic trials focus mainly on MDMA and psilocybin 
• Positive long-term outcomes after bad trips and a more complete picture of such experiences

DEPRESSION

Separating thought patterns to break free from depression

Sometimes we can get stuck in a thought loop. We humans have the great ability to be excited about something that happens in the future. The anticipation before going to a concert (again) can be just as great as the actual experience at the venue. This works the other way around too. If we expect to feel bad when it rains, if we dread going out that day, we sure will feel bad (without even having left the house). Or when we ascribe anxious nerves as a sign that we can’t perform that next business presentation, the chances increase for you not feeling your best.

All this to say that the patterns in our heads have a strong influence on how we feel, even before the actual events in the real world happen. Or when they happen, they can reinforce our patterns, be they negative or positive. And as you may have guessed from the title of this section, psychedelics are a way to separate thought patterns.

The current paper investigated the therapeutic process of psychedelics through a Research Domain Criteria (RDoC) framework. This takes into account the many levels at which psychedelic-assisted therapy works. It tries to combine everything from genes (which influence we spoke of last week) to the self-reported effects.

This is what the study concluded

• Psychedelic stimulate the growth of neuronal cells (in the hippocampus) and specifically lead to the growth and strengthening of dendrites (the ‘receiving antennas’ of a cell)
• This then leads to better resilience in the face of (chronic) stress, both at the level of neurons as subjectively experienced
• This then leads to an increase in cognitive flexibility, less negative bias, and thus fewer depressed symptoms

Within this framework, with the assistance of psychedelics, a depressed person is now better able to form new memories without the older (negative) memories clouding their judgment. And so breaking free from old thought patterns.

When looking at psychedelic-assisted therapy specifically, one could say that psychedelics make one more receptive to the learning of new patterns and storing new (more positive) memories and self-image. What the most effective dose, form of therapy, and substance will be for which situation is a question that many are now working on.

CLINICAL TRIALS

An overview of where we stand with psychedelic trials

We are currently in the ‘third wave’ of psychedelics research. The first wave being the traditional use and/or the research that was done before the second half of the 20th century. The second wave was the research in the 1960s and ’70s. The current, third, wave is the research (and investments) that have started around the turn of the century.

This review article takes a bird-eye view of the current state of research and identifies which clinical trials are ongoing. The study looked at different psychedelics but has chosen to exclude ketamine from the results. Studies were included that were recruiting, active, or already completed. Most studies looked at treatment (of mental health disorders), whilst a smaller percentage conducted basic science.

What the review found

• Most studies are being done with MDMA and psilocybin (together 87%)
• Most studies are investigating psychedelics or psychedelic-assisted therapy for depression (MDD) and PTSD
• Of the 70 studies identified, only 21 had published their results as of March 2021

As expected, most trials were being done last year, and we can expect even more this year. As can be seen on this tracker, the amount of studies that is registered has been increased even further with 36 studies already registered (excluding ketamine studies).

The authors of the study recommend that future trials put more effort into discovering which protocols work best. This is both with regards to dosing and to the forms of therapy used. This way we can put more effort into finding what will be the most cost-effective or efficient way of providing psychedelic-assisted therapy for a whole range of mental health disorders.

BAD TRIPS

Broadening the definition and understanding of bad trips through the use of ayahuasca

Broadening the definition and understanding of bad trips

Psychedelic experiences aren’t all sunshine and unicorns. A small percentage of trips can be classified as ‘bad’ or ‘challenging’. In many studies, it rarely occurs, but one recent study found that 7 out of 40 that used ayahuasca in a traditional environment had negative experiences. Still, for many such an experience is later classified as helping them grow in the long term.

The Challenging Experience Questionnaire finds that grief, fear (of death or going insane), feeling isolated, and a negative experience of ego dissolution are part of such bad trips. Another study finds that those who score high on the personality trait neuroticism, have a higher chance of having challenging experiences.

The current study argues that the definition of bad trips is still too limited. To study this, the researchers conducted interviews with 38 people and did a survey study with 319 more. They found several aspects that were overlooked by other researchers.

The full ‘bad trip’ phenomenology

• The fear of ego dissolution was a smaller part of the experience than previously identified, some interviewees even identified it as a positive aspect of a trip
• Fear was a larger part of the experience, with 69% of participants identifying this as part of their worst trip
• Confusion was identified 62% of the time, a concept not previously included

Gaining new insights into your life is often a large part of a psychedelic trip. It allows a person to take a step back and look at their life from an outsider’s perspective. The current study identified this as an aspect of the bad trips. Or in other words, people didn’t like what they saw from that vantage point.

Still, this study and previous studies find that challenging experiences usually lead to positive outcomes long term. By being confronted with something one rather not sees, a person is able to resolve that problem.

Research Report Readout

Psychedelics can lead to positive health behavior changes. Current trials are using psychedelics for mental health disorders, but future studies could look further to improvements in diet, exercise, nature exposure and other behaviours that promote physical and psychological well-being.

More on the neurobiology of psychedelics. A review examines the psychoplastogenic effects (neural plasticity) of psychedelics and summarizes the current understanding of the cellular and subcellular mechanisms underlying their ability to produce long-term structural changes and reduce inflammation.

Who goes to check their psychedelics? A survey study (n=1530) examined the demographic profiles of people who made use of drug checking services in the Netherlands in 2018 and found that most participants who acquired this service had longstanding experience and a higher lifetime prevalence of using ecstasy/MDMA than the average Dutch citizen.