With Dr. David Erritzøe and Henri Sant-Cassia
This fireside conversation invited David Erritzoe and Henri Sant-Cassia to help explore the re-emergence of psychedelic research and how these curious compounds can offer insights into the mysteries of the mind. Erritzoe, the Clinical Senior Lecturer and Consultant Psychiatrist of the Centre for Psychedelics Research at Imperial College London, offered a scientific insight into the matter, while Sant-Cassia, the co-founding partner of the Conscious Fund, demonstrated how the commercial potential of these compounds is linked to their therapeutic benefits.
The fireside began with a brief history of psychedelics, which showed that these compounds have been independently discovered in a number of cultures and continents. Sant-Cassia recounted that psychedelics have been used in ancient times in both medical and religious contexts dating back millennia. Sant-Cassia noted that a modern scientific exploration of these compounds began over 100 years ago, followed by a surge in research during the 1950s and 1960s, but were stifled by the 60s counter-culture movement and the Reagan era’s “war on drugs” As such, the research landscape has only re-opened very recently. Sant-Cassia emphasised that psychedelics, ‘if used in the correct medical setting’, can have a positive impact on patients with mental health conditions, and also those with chronic pain where treatment options are currently limited. The potential of these compounds has been recognised by large pharmaceutical companies like Johnson & Johnson, which is already producing a nasal anti-depressant spray based on ketamine. The FDA has fast-tracked some compounds from MDMA and psilocybin and designated them as 'breakthrough therapies' and there are several clinics which administer psychedelic compounds in Europe and North America. Sant-Cassia concluded his opening remarks on a positive note that the focus now is on identifying the real therapeutic benefits in treating mental health, addiction and chronic pain issues.
Erritzoe began by giving examples of typical serotonergic psychedelics, such as psilocybin, ayahuasca (DMT) and LSD. He explained that the typical psychedelics are well-understood compounds that have been used for thousands of years in different cultures worldwide, rather than a new invention by pharmaceutical companies. Erritzoe went on to explain the pharmacological mechanism by which psychedelics affect brain function. He reported that psychedelics impact the serotonin receptors in human brains, a neuromodulator responsible for regulating mood, although this is not fully understood. This, Erritzoe continued, is the same system on which current conventional harmacological drugs act. Serotonin, as a molecule, is similar to the classic psychedelic module, which forms part of the reason why psychedelics successfully bind with this receptor. Erritzoe described this as somewhat similar to the mechanism of Selective Serotonin Reuptake Inhibitors (SSRIs). Additionally, Erritzoe was clear to mention that psychedelics do not cause addiction in the same way that other Class A substances might, citing a study published in The Lancet (Nutt et al. 2010). States such as euphoria, sedation and stimulation were amongst the impacts that Erritzoe clarified were not induced by psychedelics. Rather, he explained, psychedelics create an ‘altered state’ or an ‘expanded state’ of consciousness. This, he identified, fits with the meaning of the word itself, which translates to ‘mind revealing’ or ‘mind manifesting’.
Mitigating the harms of psychedelics was one of the greatest concerns for medical experts, specifically the potential for schizophrenia. Erritzoe provided some nuance on this matter indicating that when Albert Hoffman synthesised LSD in 1943, it was tested to demonstrate what psychotic experiences could look like. Not only have psychedelics shown minimal harmful and addictive effects, they also seem to have the potential to treat alcohol addiction. Furthermore, their downstream negative effects seemed to be much lower even than those of alcohol or drug-abuse. Ultimately the ‘ego-dissolving’ experience could produce some reservations regarding their use in patients at high risk of psychosis; Erritzoe cautioned their use in these individuals. Erritzoe emphasised that harmful effects can be mitigated under closely monitored therapeutic guidance.
Sant-Cassia identified that Health and Social Care in the Netherlands have partially decriminalised the use of psychedelics; similar regulatory schemes have been put in place around the world, such as Oregon, Jamaica, the Bahamas and Peru. Sant-Cassia went on to explain that scrutinising currently illegal compound through clinical trials will result in safe and regulated production of psychedelic compounds, similar to conventional drug development. Sant-Cassia claimed that regulation would allow for safe use of psychedelics after extensive testing, including mixing the compounds with other ingredients in order to change their profiles. This, he explained, is a good starting point for entering the pharmaceutical market, considering that psychedelics are strong compounds which can induce, for example, cardiovascular risks in an addiction-weakened body. Sant-Cassia did highlight that these compounds are extremely effective, if taken correctly and at the appropriate dose. He recognised that every medicine could cause side effects, and it would be pertinent to consider the cost-benefit analysis to evaluate the trade-off between side effects and therapeutic use.
Erritzoe noted that the main paradox when discussing psychedelics is that there appears to be no relation between harm and regulation of the compound. This raises the question as to why and how drugs are classified under the current system. Class A (Schedule 1) drugs, stated Erritzoe, are deemed to hold no medicinal value; however, he added, psychedelics are proving to have medicinal benefits. Current trials look promising, according to Erritzoe, although he thought that they should now be scaled up to be able to completely make a conclusion on their efficiency. He gave the examples of Imperial College London and Johns Hopkins University (New York), which are paving the way in terms of international multi-centre trials, as well as many companies investing in psychedelics for their therapeutic benefits, such as the use of MDMA as a potential treatment for post-traumatic stress disorder (PTSD). He concluded by stating that psychedelics look ‘promising’, but that it might be too early to assess their efficacy and therefore discuss the issue of regulation.
Erritzoe then offered a careful analysis of the therapeutic potential of these compounds. One study suggested that a single dose intervention can show large improvements relative to SSRIs, which require multiple doses over a period of time. Importantly, the need for an infrastructure to use psychedelics for therapeutic use was deemed as essential by Sant-Cassia. Commenting on the practical experiences of patients, he said, 'the key thing that psychedelics do, is that they give the patient insight'. Both expert witnesses were challenged on why this would offer greater benefits than meditation, which can also enable a patient to gain better insight on the internal workings of their mind. Sant-Cassia indicated the difference is that meditation takes many years of practice, with potentially high attrition in patients, limiting those who are agitated or distressed, and so, these circumstances are fundamentally not conducive to such individuals. It is expected that the experiences of meditating and using psychedelics are similar.
This brought into question the nature of the psychedelic state. Erritzoe claimed that understanding this from a neuroscientific perspective depends heavily on the experimental method of assessment. It is well known that as the brain matures, it becomes more sophisticated and functional networks become more pronounced. Using MRI, a method which can measure these networks, shows that psychedelics seem to break down the separation between these networks. Erritzoe illustrated this by giving the example of this is the “Default Mode Network” which supports the ‘Ego’ in the brain. Separation between this network and others seems to break down during the psychedelic experience, possibly explaining aspects of the experience such as “flowing into something greater than oneself”. Openness has been demonstrated in several studies to be a quality with measurable changes. The impact of these compounds on an individual's openness to new ideas was of great interest among both speakers. The speakers suggested that this could show a correlation between cultures which use psychedelics and the extent of pluralism that they embrace.
This led to a discussion around what can be learnt from ancient traditions with respect to psychedelics. Erritzoe claimed that experience and wisdom from these cultures is highly relevant for the application of psychedelics in Western medicine. In order to approve a licence, he noted that regulatory bodies, such as the FDA, MHRA and EMA, need to abide by models that do not ignore the context of these compounds. Erritzoe admitted that this is where the challenge arises: in applying psychological context to pharmacology. He acknowledged that since psychedelic experiences can be difficult and somewhat traumatising, it is useful to draw on cultural knowledge surrounding psychedelic use along with going through existing regulatory models to create safe contexts. This should, he argued, improve accessibility to a wider population, rather than restrict access to the wealthy.
The sustainable application of psychedelics in the context of dharmic principles were then explored. Henri began by clarifying that the drive to fund psychedelic research is guided by the healthcare challenges, as opposed to capital gains. The field is hopeful in this regard but should consider and acknowledge the ancient origins of psychedelics in a transparent manner. Henri actively avoided short term, “sociopathic” profit-focused approaches and expects companies to use sustainable models to generate profits over 50-100 years. Erritzoe gave a hopeful outlook saying that while human nature has a dark side, heavy market competition could self-regulate exploitation and greed.
The speakers were at odds when questioned on the efficacy of psychedelics in the clinic. Henri touched on trial data but also alluded to an overwhelming number of patient stories with anecdotal evidence of life-changing turnarounds in severe addicts. Contrarily, David suggested that when these studies are scaled up with proper randomised control trials, the effects may not be as prominent as they are in early stages. It is unlikely that psychedelics will be seen in the clinic in any immediate time-frame, with licencing regulations, phase 3 clinical trials and the training of thousands of medical professionals to administer these drugs before any global main-stream access will be seen.
David’s closing remarks provided a sobering view on the future of research in psychedelics. While initial research has shown some promise, there is a significant amount to understand about these compounds and their impact on neuroplasticity. Importantly, to fully understand this, in the first instance, the scientific understanding of the brain requires more research including the creation of tools to understand consciousness, sleeping and dreaming; further, to connect these to diseased states like chronic pain and eating disorders. The application of pharmacology would be secondary to unravelling basic physiology. Psychedelic research could provide a financial model to fund these neuroscientific endeavours.
Henri gave his final thoughts on society’s readiness for psychedelic research and the sustainable uptake of these compounds. Henri advocated open-mindedness towards holistic healthcare on a wider perspective and envisaged a shift in global healthcare patterns. The concept of wellness has already begun to penetrate the healthcare narrative, but there is too much money invested in conventional medicines and psychedelics could be seen as a competitor in this market. Thus, the ultimate question will fall down to competition between human flourishing and profit.