Psychedelic Research Roundup — pandemic edition

In short: a roundup of some of the psychedelic research that caught my eye over the past couple years.

Preachy intro:

Psychedelics, for those leading the underground cultural revolution, were always something anti-establishment. Something that could challenge the current system rather than hybridise with it.

But for those fronting the above-ground, news-report, investor-friendly psychedelic movement, its survival depends on appeasement, on being inoffensive, and on maintaining the status-quo.

The most visible part of the mainstream psychedelic scene is propelled by a heaving mass of well-funded clinical psychedelic research.These players are driven by an urge to see psychedelics administered in clean therapeutic offices by extremely qualified psychotherapists (who would of course never touch the stuff in their spare time) for fees that will make shareholders salivate.

Obviously, research that challenges capitalism, racism, colonialism, homophobia, transphobia, jingoism, and of course the current Western medical/scientific paradigm, is not going to be welcome in this mainstream world. This means that the biggest psychedelic news outlets and organisations will be pretty selective about the kinds of research they cover.

That’s why in this roundup I’m going to highlight some of the research that has stood out to me, and criticise places where I feel the influence of mainstream culture has twisted scientific endeavour.

Research roundup:

‘Impartiality’ in psychedelic research

For something as subjective as the psychedelic experience, you’d think that logically, a scientist would much better understand the topic if they had encountered the experience in question.

Research by Matthias Forstmann and Christina Sagioglou at the University of Zurich, published this year, shows that the public perception of how close a psychedelic researcher is to their topic of interest can affect how the results of such research is perceived.

Hundreds of members of the US public were recruited to complete online surveys regarding their perception of psychedelic researchers. The study found that the public would consider a psychedelic researcher as being slightly less honest, professional, and unbiased if the researcher admitted to taking psychedelics in their personal life. However, those surveyed seemed to have a powerful trust in the unscrupulousness of data, because they would not worry about the significance and validity of the scientific output of said researcher. What does negatively impact the sense of validity of the research, in the eyes of the public, is whether the researcher has presented at conferences where psychedelic social activities are also taking place.

Perhaps unsurprisingly, participants in the study who had taken psychedelics were much less likely to judge a researcher’s output differently based on personal psychedelic use.

This study highlighted how restricted psychedelic researchers must feel about disclosing personal use of psychedelics, or even about attending certain conferences or social gatherings. This doesn’t really sound like an age of scientific enlightenment.

The willingness of the public to negatively judge scientific conferences that deviate even slightly from the norm is terrifying, but proves how determined the mainstream psychedelic movement is to marry itself to normativity. One of the scenarios that Forstmann and Sagioglou devised was a conference where the attendees ate dinner on floor seating rather than traditional seating… it doesn’t take much to freak people out.

On the flip side, we also see here how powerful psychedelic bias can be. People who’ve taken psychedelics are more likely to be enthusiastic about psychedelic research — potentially to the point of overlooking areas of bias or corruption.

Interestingly, the authors suggest that the reason the public judge psychedelic researchers who’ve taken psychedelics to be untrustworthy, but their research valid, is because they are suspicious of researchers who may have had a transformative experience on psychedelics which gives them a personal agenda. This amuses me because scientists always have a personal agenda — we’ve just come to accept certain kinds of agenda over others. Example: Scientist A wants to prove that psychedelics can treat war veterans so we don’t have to feel quite so guilty about slaughtering brown children (acceptable personal agenda). Scientist B wants to show that psychedelics can help shift us towards more climate-conscious, justice-oriented and empathetic states of mind (unacceptable personal agenda).

Non-hallucinogenic analogues

Many would consider this a naive endeavour, and it not only conflicts with our intuition about how psychedelics work, but also previous research which has shown that the strength of the mystical qualities of a psychedelic experience correlates positively with the strength of its therapeutic effects.

I’ve chosen one example of a study investigating a non-hallucinogenic analogue, although there are many out there. A large team led by Lindsay Cameron and David Olson at the University of California have developed an analogue of the natural psychedelic ibogaine, and reported that it can have antidepressant and anti-addictive effects in rats.

Ibogaine is an interesting compound to attempt to develop a non-hallucinogenic analogue of, as almost every single human report of its profound anti-addictive effects references the experience itself as being crucial in motivating behaviour change. Most reports describe encounters with ancestors, or stern deities, who offer unpleasant re-living of shameful memories and witnessing the harm that dependent behaviours have caused loved ones. To imagine that subsequent anti-addictive behaviour changes are the result merely of biochemical processes — and therefore that the experience itself is practically a meaningless epiphenomenon — has profound philosophical implications. This is why I’m particularly interested in the results of this research topic.

In Cameron and Olson’s study, the antidepressant and anti-addictive effects of their analogue are tested using the forced-swim test and extinction-reinstatement training, respectively, in rodents. There are, of course, severe limitations in these techniques and how relevant they are to human depression and addiction. Additionally, the non-hallucinogenic property of the ibogaine analogue is only shown using a basic head-twitch assay, and this by no means suggests that this compound wouldn’t have some kind of psychoactive effect in humans.

Ultimately the only kind of research that will answer the question of the role of the psychedelic experience in psychedelic-assisted therapy is double-blind research involving humans taking both the psychedelic compound and its non-psychedelic analogue. These studies, when they come along, could be a make-or-break moment for the psychedelic therapy industry that hopes to sterilise, patent, and reduce the psychedelic experience.

Microdosing

But there have been some really interesting studies into microdosing over the past couple of years.

A team led by Nadia Hutten and Kim Kuypers at the Maastricht University tested 24 participants with three different microdoses of LSD — 5ug, 10ug, and 20ug. They found that the microdoses had a range of effects, both positive (improved mood, amicability, focus and attention) and negative (confusion and anxiety). This study confirmed the common-sense understanding that higher doses (above 10ug) are not desirable for microdosing, as psychedelic effects start to become apparent, and negative reactions will be more amplified.

Another paper produced from this same study showed that the 20ug dose significantly improved pain tolerance – although this is not groundbreaking. We already knew that psychedelics alter pain perception and it’s not surprising that the higher dose had a stronger effect.

Yet another paper from this same study reported on BDNF levels in these patients. BDNF (Brain-Derived Neurotrophic Factor) is a protein that boosts the growth and health of neurons, and is strongly linked to memory and cognitive function. They found that BDNF levels tended to increase by around 10–20% following microdosing, although we can’t yet make any sweeping generalisations about microdosing and cognitive health.

Moving on to a different group, Rotem Petranker and colleagues at York University, Toronto, put together an interesting survey that shows a mix in response to microdosing — some people are amazed at the results, others are underwhelmed from minimal effects. Many of the people who were disappointed by microdosing felt that their expectations were too high: a nice reminder to avoid sensationalism when talking about microdosing.

I want to also mention a study from a couple years ago led by Steliana Yanakieva and Devin Terhune at Goldsmith’s, University of London, which found that microdosing with LSD affected time perception. 36 participants received a dose of LSD in the study, with 12 participants taking a placebo. Using a task that required participants to memorise small lengths of time, the researchers found that those who had microdosed were more likely to falsely remember time intervals as being longer than they actually were. This effect was only found when participants had to memorise lengths of time longer than two seconds — and at that point the microdosers mistakenly reported that lengths of time were about 25% longer than they actually were. Interestingly, in this study the participants were given an extended microdosing regime, dosing once every three days for 18 days, and the test to determine changes in time perception was given 12 days into the microdosing regime. Obviously it’s nothing new that LSD changes time perception, but it’s interesting that a microdosing regime can consistently alter it.

Finally a study from this year which got a bit of attention, as it suggested that the benefits of microdosing are all placebo. Led by Balázs Szigeti and David Erritzoe at Imperial College London, they attempted to use a “citizen science” method whereby participants self-blinded their microdosing routine at home with the guidance of the researchers. Although the method of self-blinding was functional, it lacked any assurance that participants weren’t “cheating” — they could at any point find out whether they were taking real doses or placebo. Additionally, there was no control over the type or dose of substance that participants chose to microdose with. The study reports that both microdosers and those taking placebo had similarly positive effects from four weeks of ‘microdosing,’ which some might take to mean that microdosing is no better than placebo. I don’t think this is something we can yet conclude, especially not from this weak study. Anyway, this takes us nicely onto the next section…

Placebo

One study led by Jay Olson and Samuel Veissière at McGill University shows both how powerful the placebo effect can be, and how much of the subjective psychedelic experience is influenced by context and mindset.

In the study, 33 participants were told they were going to be given a moderate dose of a new psychedelic substance, and were then given a sugar pill. Everything about their situation was set up to maximise suggestion. The environment was colourful and stimulating, with murals, music, lights, projections, and comfy seating. A number of conspirators posed as co-participants, and acted as if the ‘psychedelic’ was having an affect on them. The conspirators were instructed to mimic and amplify the behaviours of the participant — i.e., if the participant felt that they were seeing colours more brightly, and mentioned this, the conspirators would provide validation and encouragement by also saying that they were seeing bright colours. Even the pill itself was designed to boost the psychedelic context — it was coloured pink, which has been shown to amplify the placebo effect.

61% of the participants reported at least some effect from the placebo, which is not at all surprising considering the monumental amount of suggestion taking place in the research environment. As would be expected, about half of the participants who had prior experience with psychedelics did not report any effects of the placebo, compared to about 30% of drug-naive participants.

Despite 61% of people reporting some psychoactive changes during the experience, only 12% were certain that they had taken a real psychedelic. The rest were unsure (53%) or were sure they had taken a placebo (35%).

Although the experimenters report that some of the participants experienced effects of the magnitude seen in full-dose psychedelic studies, I don’t think this is really a surprise. We already know that context and suggestion can heavily influence anyone’s mental state, and it’s possible to manipulate highly sensitive individuals into full psychedelic states while sober (using a variety of methods!). However, we see here that most people can detect even the most well-designed psychedelic placebo, which I think shows that attempts at using true placebos in clinical psychedelic trials are futile.

Racial justice

Psychedelic research and therapy are deeply, troublingly white. There are all sorts of reasons for this — but it is fundamentally because we live in a white supremacist society that values white bodies over brown bodies. Psychedelic therapy, in its current form, is designed for white people, designed to uphold the current capitalistic system (including the racism embedded in it), and designed to make sure that the colonialism that supplies us with indigenous wisdom about plant medicines is not burdened by reciprocity.

It should be a primary concern of the psychedelic renaissance to make psychedelics equally accessible for all, to be informed by both white and BIPOC knowledge and wisdom, to ensure the fair compensation and protection of indigenous peoples, and to make reparations towards those most harmed by the war on drugs. The reality is that these concerns are nowhere near the forefront, mainly because the leaders of the psychedelic renaissance are threatened by giving up their privilege and handing over a slice of their power. It’s all about maintaining the status quo.

The past two years have seen a rise in the visibility of anti-racist campaigns, mainly due to the public execution of George Floyd. In the psychedelic space, this has been met with the usual storm of white fragility, heralded by cries of “not all white people” and “stop trying to divide us.”

Some amazing research and editorials have been published on this topic recently, just a few of which I have highlighted above. Again, I recommend reading them in full, and I am not claiming that my (white) interpretation is accurate. Some of the take-home message from these papers, for me, are:

  • White people are massively over-represented in psychedelic research (roughly >80% of participants)
  • BIPOC experience higher levels of mental health difficulties than white people (and this is also often underreported)
  • BIPOC experience a much larger amount of prejudice and professional negligence (or openly racist malice) when accessing mental health treatment
  • BIPOC suffer racial and colonial trauma that white people don’t
  • BIPOC suffer the effects of the war on drugs significantly more than white people
  • Psychedelic research is hugely skewed by the overtly-white participant base, and is therefore bad science
  • There are clear solutions for researchers looking to expand their participant diversity (see papers above)
  • There are simple options for psychedelic therapists and facilitators to learn anti-racist awareness
  • There is a need for more BIPOC psychedelic therapists, and practitioners trained in treating racial trauma

I think this is where we’re going to be seeing one of the major fracturings of the psychedelic movement in coming years. The mainstream, corporate, white-led and white-centric medicalisation of psychedelics will continue to conflict with intersectional, queer, anti-racist and anti-colonialist interests, and the mainstream won’t accept the changes it is being asked to make.

Ketamine and depression

Studies have shown that regular doses seem to have a significant antidepressant action, and this has led to the development of an analogue called esketamine that has been approved as a treatment for depression by the FDA, and is available as a nasal spray.

Unlike most psychedelics, ketamine (and also potentially esketamine) has significant physiological risk with regular usage (liver and kidney damage being the most frequently seen). Ketamine also has a high potential for addiction.

Clinics worldwide provide off-label ketamine and prescribed esketamine treatment programs. It’s an attractive prospect to investors, as patients are required to return to clinics for multiple treatments (the positive antidepressant effects tend to wear off after a few days), and clinics are able to treat multiple people at the same time without requiring the same kind of infrastructure or expense as most psychedelic-assisted therapy would require; this is because the ketamine experience is relatively short, and is currently not offered in conjunction with therapy in most clinics.

We don’t really understand how ketamine works to have an antidepressant effect. It seems to function differently from most other psychedelics, in that stronger psychedelic effects don’t usually match up with higher levels of therapeutic benefits. There’s also a delay of a couple of days between the dose and when the most powerful antidepressant effects appear.

The current medical opinion is that ketamine is working on a pharmacological level to address neurotransmitter imbalance or overactive brain regions, rather than producing a profound transformational subjective experience in the same way as other psychedelics. I think that’s a bit of a physicalist trap, and a false duality; psychological changes are happening in both cases, which we should be focusing on. There just happen to be different pharmacological features.

Psychologically, ketamine seems to be providing a brief break from typical depressive symptoms, whereas other psychedelics (in conjunction with guided therapy) allow for a more permanent shift away from harmful thought patterns.

So my trepidation about ketamine and depression is two-fold: firstly, the relatively high physiological risk of repeated use that we don’t really see with other psychedelics, and secondly the potential for ketamine being abused by investors to churn out money without really solving the depression epidemic. As posited in the bipartite model of depression, ketamine may be an effective treatment of immediate symptoms, but may not be able to promote lasting healing in the way that other psychedelics can. That’s why I think it’s useful to differentiate ketamine treatment from most other forms of psychedelic therapy.

Several reviews have been released in the past two years about the antidepressant effects of ketamine, the potential pharmacological actions related to these effects, and the challenges of bringing it into a treatment paradigm. Here I’ll highlight this thesis by Jakob Broström at the University of Skövde, which was published last year.

LSD and social adaptation

The experimenters found that compared to control, when people were given LSD, they were very slightly more likely to change their answer and move it closer to the group’s ‘opinion,’ as long as the group didn’t have a glaringly different opinion.

It may be tempting to consider this result a surprising one, as LSD is stereotypically associated with changing people’s opinions to go against mainstream social trends, not conform to them. However this is a mistake; the current study shows that LSD can increase conformity when exposed to social pressure, not that the LSD experience on its own can produce social conformity. Indeed, when most people take LSD, their internal experiences often lead them to fresh perspectives and ways of understanding that contradict Western paradigms.

The study here highlights just one dimension of the vulnerable state that LSD users find themselves within. Hopefully as this understanding grows, psychedelic practitioners and therapists can take note of the myriad ways they must care for and protect their patients. Additionally, we must all be wary of how easy it is to manipulate people under the influence of psychedelics.

For me, this research shows that while psychedelics may be useful for building social rapport between a therapist and a patient, they have limited use in dramatically changing personal ideologies in a vacuum. For example, people who think that our world leaders would stop imprisoning and killing children if only someone could get close enough to drop some LSD in their coffee may be overly optimistic.

The Psychedelic Future: develop your communities

Psychedelics are powerful, complicated, and versatile.

I think that the way we bring them into our lives can do great harm as well as good. Making assumptions about how they work, and drawing boxes around the ways in which they can be used, comes with great risk.

I think the future will see the true heart of the psychedelic spirit maintained within grassroots communities and collectives. So I hope we see more people fostering and developing their close communities; building intersectionality, queerness and justice into their psychedelic practice; and challenging the mainstream that is becoming more and more divorced from principles of equality and humility.

Now is the time to consider what psychedelics really mean to you, and what kind of society you’d like to see them be a part of.

Biologist, writer