Can psychedelics lift the fog of depression?

Just imagine if you could take a psychedelic trip to relieve persistent, severe depression. Or maybe to get rid of it once and for all.

The thought is fascinating and tempting – not least for those who are so severely affected by depression that they are unable to feel the slightest spark of joy or connection to the world around them.

Nowadays, more and more research is being conducted into the use of psychedelic substances – including psilocybin – to treat psychological disorders, particularly depression. Substances such as LSD, mescalin, ayahuasca and ecstasy (MDMA) are also being studied, the latter currently being tested in connection with treatments for post-traumatic stress (PTSD) in American war veterans.

Behind all of these scientific trials, there is hope that psychedelics may help us develop alternatives to existing therapies, enabling us to offer effective treatments to patients who, for a variety of reasons, have proven unable to gain any significant benefit from the drugs already on the market. One of the target groups is patients with moderate to severe depression who are referred to as ‘therapy-resistant’ but who also find that the drugs which have no appreciable effect often have nasty side effects such as apathy, obesity and sexual dysfunction.

Several countries report promising results. For instance, numerous trials using psilocybin to treat depression seem to indicate that the substance gives many patients a feeling of greater connection to the world around them, relieves their anxiety and gives them courage to face issues with an open mind. Healthy subjects who acted as a control group in some trials described their experience with psilocybin – a drug they had never previously come across – as pleasure-enhancing.

Danish psychiatrist David Erritzøe points out that the good results on depression arising in recent years from a range of scientific trials with psilocybin ‘have made an impression on the regulatory authorities in both Europe and the USA’. He has researched in this field for more than ten years and, today, works at Imperial College London with one of the world’s leading experts in neuropsychopharmacology, Professor David Nutt.

Due to the psilocybin results, both the European Medicines Agency (EMA) and its American equivalent, the FDA, have authorised major patient trials, which are currently being conducted in a number of pharmaceutical groups. David Erritzøe explains:

‘This can be taken as an indication that the authorities on both sides of the Atlantic hope to see results in this field very soon. And, understandably, the intention of the pharmaceutical industry is to design new therapies – for instance, for depression. Existing drugs for depression have major issues, often resulting in side effects such as obesity, lack of sex drive and a feeling of living in a bubble. Psilocybin hasn’t shown these side effects.’

How the pharmaceutical industry will go about patenting drugs based on psilocybin is, according to David Erritzøe, quite a different matter, since its chemical composition was mapped long ago and is universally available. ‘But that’s not my concern. I’m a doctor.’

In Danish nature
Research into the treatment potential of psychedelic substances can be described as a multi-faceted field with a wide variety of approaches. It encompasses everything from animal trials to biochemical measurements and brain scans. And then there are the officially approved trials in which drugs are given to humans.

Many of these studies use psilocybin, naturally present in numerous mushrooms. In Denmark, it is found in the liberty cap mushroom (Psilocybe semilanceata) which grows in many locations in the wild, particularly in wet grassland.
Drying and eating the mushroom will take you on an approximately six-hour trip. However, this is not something to be experimented with, and taking a psilocybin trip is strongly discouraged if you have experience of psychedelic hallucinations or if there are cases of psychosis in your close family. These questions are always asked when planning medical trials with people taking psilocybin – whether they are patients or healthy individuals.

Those who are finally given permission to take part do not simply sit and chew on a liberty cap. They are given the active substance in a synthetic form to ensure that the researchers know exactly what and how much the participants take. Furthermore, the trials follow a protocol to ensure that the trip is safe.

Scientific trials with psilocybin are being conducted in a number of countries, including the UK, Denmark, the USA, Brazil and Switzerland. In Denmark, the trials are conducted at the Neurobiology Research Unit at Rigshospitalet, University of Copenhagen, headed by Professor Gitte Moos Knudsen, and are funded by a range of public and private foundations, including the Lundbeck Foundation.

In the UK, much of the research is being conducted at Imperial College London, where David Erritzøe – who also collaborates with Gitte Moos Knudsen’s team at Rigshospitalet – plays a key role.

Hippies and psychedelic history
Today’s psychedelic research will be easy, almost operating on automatic pilot. It is considered a continuation of the hippie movement’s 1960’s project, since many of the substances used by today’s researchers were also used by the hippies in their pursuit of expansion of consciousness and greater harmony.

However, although the hippies are indisputably the authors of psychedelic history in recent times, when it comes to psilocybin, to a certain extent, they merely inherited a tradition that can be traced back to the Aztecs who lived in central Mexico.

The Aztecs had been using psychotropic psilocybin mushrooms in their rituals since time immemorial when the Spanish conquistadors arrived in Middle America at the beginning of the 16th century. Ancient Spanish sources show that the representatives of the Catholic Church who were travelling with the occupying power found this practice diabolically dangerous and they made aggressive attempts to suppress it.

The experiential potential of psychedelics is linked to their influence on central receptors in the brain – receptors associated with mental processing and perception. These non-addictive substances can convey experiences that enable you – on a mental level – to perceive people, places, states, colours, tastes and other impressions and stimuli in hitherto unknown ways.

As if you had bought an unspecified trip to some faraway country and now find yourself in the middle of a multi-coloured foreign land. Or perhaps – because there is no way of knowing this beforehand – the trip will take you back to a very early stage of the life you have already lived and you will relive an experience you had forgotten, or were not even aware of as far as you can remember.

‘The experiences psychedelics are able to produce can be rather intense,’ says David Erritzøe, psychiatrist at Imperial College London. ‘So, it’s necessary to work with the substances according to specific methods, following recommendations, to prevent trial subjects from coming to harm.’

According to these internationally recognised guidelines, patient trials with substances such as psilocybin begin with a thorough screening of potential participants. Those who have either had a psychotic experience themselves or have a close relative with psychosis are filtered out at this stage.

Then follow numerous interviews where each participant is told what to expect from the psychedelic trip – at an experiential level. The final stage is the actual session where the subject takes a carefully controlled dose of synthetic psilocybin, in capsule form. This is currently produced in both the UK and the US.

‘The trial subject is not alone at any time while under the influence of the psychedelic substance,’ David Erritzøe emphasises. ‘There’s always a treatment provider in the room, the lights are dimmed and there’s background music – and if you follow the guidelines for organising and performing these trials, it can all be done extremely safely. As far as I know, no-one has come to any harm when taking psychedelics under these controlled conditions,’ says David Erritzøe.

Conducting medical trials without harming participants has top priority, but the safety aspect of psychedelics research is also influenced by some of the hippies’ less positive experiences. There are certainly lots of – true – reports of bad trips: of people who should never have taken a psychedelic substance because they were at risk of developing a psychosis; and of people who in a blissful state thought they could fly and gave it a try, with disastrous consequences because there was no-one to stop them.

So, there’s every good reason to follow the guidelines. However, David Erritzøe points out: ‘That said, we mustn’t forget that most people who use psychedelics unattended actually do respect these guidelines, which were largely developed based on user experiences gathered over the years.’ For instance, someone who is not taking the substance should always be present; someone who can intervene if necessary to take care of those on the drug.

So far, at the Neurobiology Research Unit at Rigshospitalet, University of Copenhagen, they have given 30 healthy trial subjects a single dose of psilocybin, and the trial was conducted in full compliance with the internationally recognised guidelines in the field. Professor Knudsen, head of the research unit, says that the effect was unmistakable: ‘We can see that a single dose changes people’s personality.’

To measure this, the researchers at Rigshospitalet – who also use brain scans in their trials with psychedelics – gave the participants a personality test before and after the psilocybin programme. Subjects were given a NEO PI-R test with 240 questions and asked to assess themselves in relation to five so-called personality dimensions.

These personality dimensions are also known as ‘The Big Five’ and deal with topics such as introversion-extroversion and degree of open-mindedness. The researchers at Rigshospitalet noted that, in some cases, psilocybin reduced participants’ self-perceived anxiety and gave them more courage to address issues with an open mind.

These results confirm data from similar trials on subjects with moderate to severe, treatment-resistant depression conducted in 2018 by David Erritzøe together with British and American colleagues.

The Neurobiology Research Unit at Rigshospitalet is now running a new psilocybin project, also funded by the Lundbeck Foundation. Professor Knudsen explains that the project focuses on headaches:

‘Horton’s headache to be exact. It’s a dreadful burden for those afflicted, and there have been various reports over the years that psilocybin could alleviate Horton’s. It’s just never been investigated scientifically, so we decided to do this in collaboration with the Danish Headache Center, which is also part of Rigshospitalet. And the study is now in progress.’

…and then there’s all the amateurs
The medically controlled and statutorily sanctioned trials with psychedelics for therapeutic purposes are the scientific forum in which new forms of prescription drugs can be generated; based, for example, on psilocybin or DMT, which is the active substance in the South American herbal tea ayahuasca.

While doctors, psychologists, chemists and pharmacists are working on investigating psychedelics for therapeutic purposes, there is also hectic trial activity on an amateur level, among users all over the world.

David Erritzøe explains that people are intensely curious about psychedelic experiences. It does not usually have anything to do with feeling ill. On the contrary, people are interested in discovering whether psychedelics can help them improve their intellectual performance and general well-being. He continues:

‘It’s big business and there’s money to be made from retreats where people can come and try out the drugs in allegedly safe surroundings. These retreats are found in countries whose legislation allows them; for instance in Peru, where they offer ayahuasca, and in the Netherlands, where they use truffles containing psilocybin. And people pour in from far and wide.’

And then there is micro-dosing, a phenomenon many amateurs like to experiment with. The idea is to take tiny doses of a psychedelic substance – often psilocybin or LSD – over a lengthy period. It is believed that this ensures intellectual acuity and physical well-being.

The phenomenon is huge, also on the internet, and many users claim the effect is spectacular. However, could this form of self-medication pose a health risk, even though psychedelics are not addictive?

This question is addressed in a research article published earlier this year in the scientific Journal of Psychopharmacology. Its authors include Gitte Moos Knudsen, David Nutt and David Erritzøe, and the report concludes that, for the present, micro-dosing must be regarded as a field and a practice about which science has insufficient knowledge.

‘Quite simply, we need studies that indicate whether repeated doses of a psychedelic substance have a negative impact on the heart,’ says David Erritzøe. Dr Erritzøe has recently received research funding from the National Institute for Health Research in the UK to investigate the micro-dosing craze.