Psychedelics represent a fascinating class of compounds, ranging from naturally occurring molecules such as psilocybin and mescaline to synthetic analogues like LSD. For decades, these substances were constrained by regulatory and societal stigma, leaving their therapeutic potential largely unexplored, and a scientific moratorium on research. Today, however, renewed scientific interest, driven by promising data in psychiatry, has opened the door to rigorous research aimed at understanding their mechanisms and translating them into viable treatments.

As a CDMO with a facility designed to work with highly potent compounds, we see the promise of psychedelic medicines up close, alongside the practical challenges that determine whether a program advances on time and on budget. From controlled substance licensing to formulation strategy, the road from API to clinic (and eventually market) is navigable, but it demands deep technical rigor, robust quality systems, and early, transparent collaboration. Here’s an overview of some of the key challenges facing psychedelics, as well as their possibilities in psychiatry.

The Challenges for UK Biotechs

Beyond clinical considerations, formulation science plays a critical role in the success of psychedelic programs. Many psychedelic compounds exhibit poor aqueous solubility, chemical instability, and extreme potency, which complicates dosage form development. Oral solid dosage forms remain the most common route, but they require precise micro-dosing capabilities and protective excipients to prevent oxidative degradation. Controlled-release technologies are also under investigation to modulate onset and duration of effect, ensuring both safety and therapeutic consistency.

• Intranasal Spravato (Esketamine): Spravato, an FDA-approved intranasal esketamine, represents a breakthrough in outpatient psychedelic delivery. Patients self-administer under medical supervision using a refined nasal spray system, ensuring reliable dosing and maintaining safety monitoring protocols.

• Oral Tablet and Capsule Delivery: Whilst still seeking regulatory approval, MDMA and psilocybin aim to be administered orally during guided therapy sessions. Tablets or capsules, which is typically 120–125 mg of MDMA, are ingested under watchful clinical supervision. A supplemental half‑dose may follow 2 hours later to extend therapeutic effects, all tracked and titrated by therapists.

Manufacturing these compounds introduces additional challenges. HPAPI containment strategies must be integrated into facility design to protect operators and prevent cross-contamination. Occupational exposure limits (OELs) for psychedelics are often extremely low, necessitating advanced engineering controls and validated cleaning protocols. For biotechs, partnering with a CDMO experienced in these containment and compliance requirements is essential to avoid costly delays.

There remains a wide remit of challenges for biotechs looking to develop psychedelic therapies, both logistically and operationally.

• Clinical trial implications: Psychedelics are powerful substances, which makes them almost impossible to run the traditional clinical trial method of comparing the active with the placebo response.
• Timelines for identifying potential study participants are extensive: The criteria for including and excluding participants from studies is a long process. An individual’s history and psychological profile must be considered, and then the clinical trial process of drug development can take years.

The Possibilities of Psychedelic Therapy

The specifics of what psychedelics might entail are still in development. However, it would likely involve a certified practitioner guiding patients through a few hours of a psychedelic experience. For those suffering with mental health issues, there is a suggestion that psychedelics can deal with the source of pain rather than simply numbing it as antidepressants tend to.

Currently, 80% of patients on antidepressants relapse after stopping their antidepressant treatment. The initial studies of psychedelics suggest that the results of a single treatment can be sustained for several weeks or even months, without a need to taper off. However, long term results are still being fully researched.

Mechanistically, psychedelics act primarily through 5-HT2A receptor agonism, disrupting the brain’s default mode network (DMN) a system associated with rigid thought patterns and rumination. This disruption, often described as the “snow globe effect,” temporarily relaxes entrenched neural pathways, enabling new patterns of connectivity and cognitive flexibility. Preclinical studies suggest enhanced synaptogenesis and dendritic spine growth, pointing to a surge in neuroplasticity that may underpin their therapeutic benefits.

For patients with depression or anxiety, this represents a paradigm shift. Current antidepressant therapies often require chronic administration and still result in relapse rates exceeding 80% after discontinuation. In contrast, early data on psychedelics indicate that a limited number of guided sessions may produce sustained improvements without the need for ongoing pharmacotherapy. While these findings remain preliminary, they highlight the potential for psychedelics to address the root causes of mental health disorders rather than simply managing symptoms.

Current Psychedelic Approvals

Currently, the only psychedelic treatment with approval from the FDA is Johnson & Johnsons Spravato which can be prescribed to individuals with treatment resistant depression (TRD). It is a derivative of ketamine which is already approved as an anaesthetic. Spravato is administered through a nasal spray device, taken twice a week for the first four weeks, and then delivered weekly.

In terms of other psychedelics reaching regulatory approval status, Lykos Therapeutics were investigating MDMA as a treatment option for post-traumatic stress disorder, but received a negative outcome in August 2024. They continue to work with the FDA to address concerns. Meanwhile, Compass Pathways are currently looking at using Psilocybin as a treatment for TRD, and hope to launch in 2027.  Finally, LSD was granted ‘Breakthrough Therapy’ designation back in 2024, which will allow its development for Generalized Anxiety Disorder.

Conclusion

The interest in psychedelics is creating exciting opportunities in addition to significant technical and regulatory hurdles. From containment strategies and controlled substance licensing to innovative formulation approaches, our expertise ensures that promising molecules can be translated into safe, scalable therapies. For biotechs, success in this space requires a partner who can anticipate challenges and deliver solutions with precision.

To learn more about the facilities we have at Upperton for developing psychedelic treatments, take a look around the laboratories on our website, or download our capability brochure.