Dr Prateep Beed on psychedelics research, and its expanding contribution to medicine

In this interview, Dr. Beed addressed which countries are at the forefront of psychedelic clinical studies, the state of legal and policy frameworks for these substances, and their promise for salutogenesis and preventive medicine. We also covered the main therapeutic areas where psychedelics are showing positive results, the concerns raised by their therapeutic use, and the opportunities and limitations that ongoing and upcoming clinical trials pose to medicine, beyond neurology, psychiatry, and psychology.

About Dr. Prateep Beed: Dr. Beed has a background in cognitive behavioural sciences (Max Planck Institute, Tübingen) and neurosciences (Charité, Berlin). He is currently Senior Scientist and Lecturer at the Faculty of Neurosciences (Neurowissenschaftlichen Forschungszentrum), Charité University Hospital, Berlin. He is also a Programs Associate and the Neuroscience Section Advisor of the Berlin-based MIND Foundation. A strong focus of his research aims to gain deeper understanding of the brain’s physiology and altered states at the cellular and circuit level. For more information about Dr Beed, you can visit his page at the MIND Foundation.

The global “state of affairs” of medical research and laws

esanum: From your perspective, which countries are at the forefront of the medical applications of psychedelics, in terms of legal frameworks and scientific research?

Dr. Beed: Very recently, Australia legalized the use of the psilocybin and MDMA for therapeutic use. They are setting in a way setting standards in the field. Canada has also made progress on the legalisation of psilocybin. In Europe, Germany and Switzerland are doing a substantial amount of research, as is the UK. These countries could pave the way the legalisation of therapeutic use in the near future. I think we still are 5 or 6 years away from the implementation of policies on psychedelics therapeutics that are responsible, transparent, accessible, and cost-effective.

In Germany, the OVID Clinic is currently doing ketamine-assisted therapy, and the EPIsoDE study, which uses psilocybin for treatment-resistant depression (TRD). In Germany, the use of psychedelics is done in clinical studies, as there is no legal framework yet for their application outside of them.

There is also no law in place yet in Germany for psychedelic use in self-development. There is quite a minimal amount of people taking part in the mental health research of psychedelics as patients, compared to those who use them for self-development. The MIND foundation wants to position itself in the future not only address mental health issues, but also examine psychedelics use for self-development. But we need legal frameworks for this.

Do we focus on health or disease? Psychedelics' potential for preventive medicine and salutogenesis

esanum: In some regions across the world, for example the Amazon River basin, psychedelics are used by indigenous¹ communities since centuries. Are there any current examples of legal frameworks that go beyond clinical applications?

Dr. Beed: When it comes to plant-based psychedelics, an increasing number of countries, like Portugal, and some states in the US, have decriminalized the plants. This implies for example that consuming a mushroom that grows in the forest cannot be criminalized. In terms of ritualistic use, there is still a mixed legal map. We heard of an example of an Amazon shaman who took an ayahuasca plants with him. As he was entering the US, he was informed that the plant was classified as a “banned substance”. He was unaware of any wrongdoing, as the plant was for him a medicinal herb. We still have this very different conception on different plants depending on our cultural context.

During the INSIGHT conference, there was a very interesting talk by Dr Gerhard Gründer², in which he addressed the very fine line between health and disease. This is very interesting because we are also talking more about salutogenesis: how do we have a lifestyle that is about being healthy, rather than focusing on cures for when we are ill. This is an important paradigm to focus on, as it is the use of psychedelics for self-development. Aboriginal cultures have been using psychedelics for many applications, and this adds a powerful argument on their contribution to the salutogenesis model of human wellbeing.

esanum: At present the focus of psychedelic research is on clinical trials to tackle for example depressive disorders, or PTSD. Do you foresee that we will reach a phase in which they could also contribute to preventive medicine?

Dr. Beed: Exactly. There is enough data and evidence to show the importance of the salutogenesis paradigm. But the people who are looking into psychedelics need to define the proper ways on how this field can contribute to salutogenesis, to health policy. There have also been shortcomings, pitfalls, and abuse of psychedelics. We don’t want a “1970” happening again.³ That is why it is important that we approach psychedelics worldwide more responsibly, garnering facts, and making this knowledge available to everyone. This is what we are doing in the scientific community: we build the research, disseminate the knowledge, educate people, and spread awareness, so that we can move more towards the self-development applications of psychedelics.

Promising therapeutic applications, and the issue of limited access

esanum: For which mental illnesses or anxiety disorders does the medical use of psychedelics show the best possible effects?

Dr. Beed: We are still finding different applications from psychedelics, and do not have a full picture of benefits. There are classical serotonergic psychedelics, and atypical psychedelics. Typical serotonergic psychedelics include LSD, and psilocybin, found in so called “magic mushrooms”. Atypical psychedelics include MDMA and ketamine. For example, LSD has been found to be effective against cluster headaches, and MDMA for the treatment of PTSD. Psylocibin, as well as ketamine are two strong candidates for fast-acting antidepressive action.

It's still intriguing to know why they are helping different health conditions more effectively. But the positive effects have been shown. In current trials, there are substances that are given priority to address certain mental health disorders. For example, to my knowledge, psilocybin is being used for its antidepressant effects, but not LSD. There's also a logistical reason for this: in assisted therapy, the patient is accompanied by the therapist through the psilocybin effects, which can last three to four hours, and aftercare is also provided. But with LSD, the effects are longer. The health system cannot afford therapy assistants to remain with a patient for 8-12 hours. So, in practice, the current trials are not limited only by the mechanisms of action but also by the practicality of therapeutics.

esanum: Clinical studies are showing that many patients see sustained positive effects, sometimes for months, after only one or two sessions. Current psychedelic therapy costs are an issue, but do they compare to the cumulative and long-term costs of how health systems currently manage (or not) mental health conditions?

Dr. Beed: I'm not an expert on this topic, but I can mention that, as an example, the health system regulatory framework in Germany is very complicated. It is not easy to secure a spot in therapeutic treatment, even if there are many people suffering from mental health disorders. There are limited places available, and this is related to the structures in place, the health system, the insurance providers. Even though the burden of mental health issues is high.

Contraindications, and long-term care issues after therapy successes

esanum: Which contraindications could you identify at present in psychedelics therapy?

Dr. Beed: There have been instances of HPPD, Hallucinogen Persisting Perception Disorder, although it is very rare. In data from the EPIsoDE study, one patient out of fifty reported it. Dr Gerhard Gründer gave a talk at INSIGHT on the issue of withdrawal and antidepressants. He explained that some patients taking antidepressants would stop the medication and face a feeling of dependency and withdrawal from the medication itself, which is very difficult to handle. With the psychedelics, the withdrawal instances are very rare. We are observing that in psilocybin studies, patients report feeling better for up to six months after a dose, but then the study ends, and they cannot get a legal dose after the six-month period of a clinical trial. This is very different. Patients want access to the treatment because it is helping them with their symptoms.

In the phase-three trial of the EPIsoDE study, the aim is to integrate a long-term follow-up for those patients that benefitted from a therapy. We cannot just show these patients the benefits of a treatment, and then not do anything afterwards. This is an ongoing debate, and clinical study design is a tricky process, but we have to address a long-term framework for such treatments. So the issue has not been about withdrawal, but about continued access given the positive results.

Psychedelics: implications for more medical specialties

esanum: Psychedelics research is strongly driven by neurology, psychiatry, and psychology practitioners, but what could colleagues from other medical fields take away from it?

Dr. Beed: A lot of new areas are being looked at. For example, LSD opens a critical plasticity window, as with other psychedelics, as recently shown at the Dolenlab led by Dr. Gül Dölen,⁴ and by many others. For example, Dr. Dölen and her team is comparing many psychedelics to determine for how long they allow a “therapeutic window” to remain open. When this critical “plasticity window” (which we see in young people) reopens, the brain is more malleable, more open to changes.

This is hinting at the use of substances like LSD in stroke events. After a stroke, there is a small timeframe of intervention, of about four hours, where some options can stop the injury spreading further, or allow clot removal, which gives more chances of recovery. That is why it is crucial to receive hospital care as soon as possible. Studies are showing LSD’s effect on the brain’s plasticity and malleability, and hypothetically, LSD could expand this timeframe after a stroke. It is still a wild idea but there is a scientific basis behind it.

There is also a lot of research going is in the field of inflammation. Many psychedelics are showing anti-inflammatory properties. Inflammation is at the base of many of our problems, ranging from autoimmune diseases like Crohn's or ulcerative colitis. At present we use antibody therapy for inflammation. You can suppress the TNF alpha, but when inflammation goes out of control, it results in a lot of autoimmune disorders and other complications. Even depression can be a result of too many inflammatory molecules going around unregulated. If psychedelics could just suppress the TNF-alpha with the antibody against it, as it has been shown in lab settings, that would allow more systemic applications.

esanum: More research is being done on the gut-brain axis. Is this a field where psychedelics could also have an impact, with implications for gastroenterology?

Dr. Beed: Researchers are looking into it. We are still in infancy of this research, but it looks promising because there is this connection. But also, there are serotonin-2A receptors not only in our brain, but also in the gut. 90% of our serotonin receptors are in the gut, so the majority. They are also in the heart valves. When there is an oral administration of a psychedelic, it first goes into the stomach, which is why people feel a bit nauseous after eating “magic mushrooms”. The psychedelic substance enters the digestive system, then the bloodstream, the heart, and the brain. If there are receptors all along, the effects are seen in many parts and systems of the human body.

The complexities of patient insights, and their challenge to therapists

esanum: Can a scientific distinction be made between the insights patients claim to have from psychedelic research and objectively verifiable findings?

Dr. Beed: The insights that patients gain during therapy are very heterogeneous. The challenge is to understand what is behind them. We do not have yet an identifiable common structure on how people think during their therapy sessions. Even for the same individual, no two “trips” are the same. Also, some people can identify their insights after a session, others may not perceive there were any takeaways, while others need to communicate the experience with another person to be able to understand the insights. Some of these insights are so personal that the patient may have to understand them in their own terms first.

Therapies may have a framework for understanding a person’s life, what is important to them, their belief systems, cultural background, where they are in life. These inputs are useful for therapists, but still, the session insights open many questions and interpretation challenges for therapists. Overall, we are at a point where we need to remain self-reflective, sensitive, and open to the insights patients are providing.

esanum: Psychedelics therapy research is mostly focusing on the effects of one single substance. But are there any studies on the use and benefits of more than one psychedelic in a medical setting?

Dr. Beed: Not in clinical trials, or medical settings. There are however cases reporting on polysubstance use, but these are incredibly difficult to interpret [scientifically]. In recreational or self-development settings, a substance like MDMA is known to be used frequently in conjunction with other psychedelics, so users may have insights into effects, but which cannot be attributed to substance A or B. In poly-use, one substance may magnify another, or support it, complement it, and even antagonise with it. For now, we still have many questions on the medical potentials of each individual psychedelic.

This interview took place on 1 September 2023, at the Langenbeck-Virchow-Haus, Berlin, during the INSIGHT Conference 2023 (31 August - 3 September 2023). For more information about the conference, you can access the INSIGHT 2023 site here.

Author's note: We use this term to include native, first nations, and aboriginal communities.
INSIGHT Conference 2023. 31 August 2023. Lecturer: Prof. Dr. med. Gerhard Gründer. Session: “Psychedelics in Psychiatry – an Incremental Step Forward or a Paradigm Shift?”.
Author's note: This refers to the psychedelic era from the mid-1960s to mid-1970s which saw extensive use and misuses of psychedelics in recreational, cultural and research settings.
INSIGHT Conference 2023. 2 September 2023. Lecturer: Prof. Dr. Gül Dölen. Session: “Re-Opening Critical Periods with Psychedelics: Basic Mechanisms and Therapeutic Opportunities”.