A drug developer’s guide to navigating psychedelic trials

As their 300-gram MDMA shipment got to the border, PharmAla Biotech found themselves in a sticky situation. The export and import permits were in place, but the dispatch of the shipment was left by their shipper to the last possible day.

When the shipment was finally sent out, a worker at the airport put the properly prepared and labelled box into another box, resulting in its rejection by the airline. Meanwhile, both the import and export permits expired and the shipment was stuck for an agonising three months, because of a mere box.

Amid the frustration and setbacks, stakeholders navigate the convoluted landscape of permits and regulations, delivering clinical trials successfully. The lessons learnt during these frustrating times are invaluable, and worth sharing for the advancement of the sector. 

The discussion led by Clerkenwell Health at PSYCH Symposium: London 2023 brought together a panel to do just that. Here are some of the key takeaways. 

Stay abreast of regulatory changes

Psychedelics exist within a highly regulated subset of an already highly regulated space.  On top of that, regulatory requirements change constantly. As George McBride, Co-founder and CCO of Clerkenwell Health puts it, “It’s an evolving beast causing uncertainty, hurdles and delays. You might conceive of a trial now, but by the time you’re delivering, it might be in a different environment with different regulations.”

“Compounds that are not controlled today may become controlled tomorrow due to changes in the regulatory framework and following increased activity or awareness on the compound,” adds Peter Mollison, CEO of Eramol, a clinical trial manufacturing organisation. “So, keeping abreast and horizon scanning of the upcoming changes that will impact your study design and drug supply is key.”

Help develop robust frameworks for psychedelic clinical trials

Until very recently, there was no guidance showing what a psychedelic clinical trial should look like. Drug developers have been engaging regulators at a very early stage and working with them as they request information in real-time, further increasing the timelines.

While FDA’s recent guidance is a good starting point for the sector, the nuances between jurisdictions still exist. “It’s challenging to navigate exactly what these nuances might look like and how you might address those in terms of your trial applications and designs,” says Clare Knight, Senior Clinical Trial Manager at Clerkenwell Health. 

There is a need to develop more robust guidelines for each jurisdiction as well as an understanding of key principles that work across areas. This will be essential to make trials more approvable and streamline the whole process.

Plan carefully for drug import and export, and returns

While planning for an early phase single territory trial isn’t too complicated, the minute you start thinking about Phase 2 and 3 trials, you’re looking at multi-site multi-country trials. It’s then no longer feasible to have a drug manufacturer in every territory and you’ll have to move the compounds around. That’s when the delays and unknowns come in. 

Peter from Eramol says that “One of the biggest mistakes is to think that you can just ship a product back without any permits.” For example, an underperforming site might want to return the product but struggle to return it quickly enough. The product then goes out of date and leads to waste.

Panellists noted that drug import and export in the US, UK and Australia are relatively easy; however, Australia uses a paper-based system which slows down timelines. Moreover, although the EU is a single market, import/export permits still exist, and the regulations vary depending on the country.

Work with sites that understand what is required to deliver a protocol

One of the main pain points for drug developers is the lack of highly experienced delivery infrastructure. There is a real shortage of sites that are able to deliver psychedelic clinical trials. 

Knight adds: “I’ve worked in psychiatry research most of my career. In psychiatry. There’s a whole set of considerations that don’t exist in other areas of medicine. We’re just adding another layer on top of that when we work with vulnerable populations and substances that may cause a change in their perception.”

Have early and open communication with your vendors

In other more well-established areas of clinical research, vendors work in silos and you can assume that the different parts will run fairly to plan and join together in the end. On the other hand, the constantly evolving psychedelics sector rely on communicating with each other.

Dr Guy Higgins, CSO of Transpharmation, a preclinical CRO, shares: “We work very closely with Mindset and always have an open dialogue such as how the animal data can translate and help guide the early clinical programme.” Engaging your collaborators at the earliest stage, before working on a protocol, is also crucial to understand each other’s timelines and interdependencies and mitigate these in trial designs.

Improve collaboration in the sector

A $3 million grant to research psilocybin was recently announced by the Canadian government. That was a direct result of the lobbying work carried out by PsyCan, a trade association in Canada. The member companies were organised and went to the government together to engage in sectoral issues.

PharmAla’s Nick is the board chair of PsyCan and he says, “If you want government to stop hindering your progress, you have to tell them so. If you tell them so by yourself, they’re probably not going to listen, but if you act as a group, you might have some success.”

Psychedelics is still a nascent sector where everyone is finding their feet. We need to work together, particularly in this challenging economic climate, to build a supportive network that propels psychedelic research to new heights.

Watch the full panel