Psychedelics have been under investigation by academics, clinicians and pharmaceutical companies for some time and the momentum and interest in this area show no sign of slowing down. In this article we take a look at the latest initiative in the US and the current state of play in a number of other countries, including the UK.
Psychedelics are defined as “drugs which cause effects on the mind, such as feelings of deep understanding, or unusually strong experiences of colour, sound, taste and touch” (Cambridge Dictionary), or alternately, “a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states and/or an apparent expansion of consciousness” (Wikipedia).
As of 1 July 2023, Australia’s decision to legalise MDMA (A “non-classic” psychedelic that is more correctly described as an entactogen or empathogen) and psilocybin (the active compounds in ecstasy and magic mushrooms respectively) for the treatment of PTSD and treatment-resistant depression has come into effect (Australian Government, 2023), meaning that these treatments can now be prescribed by physicians.
In the EU, a number of clinical trials for psilocybin, MDMA and LSD are either ongoing or have taken place. Regulatory progress has been a little slower than Australia, with no approvals given to date, although the EMA – the EU’s medical regulator – is alive to the promise of this area of research and is closely following developments (European Medicine Agency, 2023)
The UK is also making progress, with similar trials for MDMA, psilocybin, DMT and other compounds having taken place – although as in the EU, no regulatory approval has been given yet. Most recently, the MHRA (the UK’s regulator) has approved a trial to investigate MSP-1014, a novel compound that is closely related to psilocybin for the treatment of depression (European Pharmaceutical Review, 2023)
The US appears to be some way ahead of the UK and the EU. The Biden administration has confirmed that it anticipates regulators will approve MDMA and psilocybin as therapies sometime in 2024 (The Intercept, 2022)
With MDMA and psilocybin seemingly well on the way to gaining regulatory approval in many key jurisdictions, researchers and companies will no doubt be looking to develop improved or even entirely different psychedelic therapeutic compounds. Perhaps with this in mind, the FDA has now released draft guidance (U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) ,2023) that outlines some of the challenges associated with psychedelic drug development programs and aims to help researchers design studies whose results will be capable of supporting future drug applications – or should at the very least codify the approach that researchers have already been taking to date.
Here are a few of the key topics for psychedelic drug development programs addressed by the guidance.
CMC includes manufacturing of bulk drug substance and final drug product, setting specifications, release criteria, stability programs, and analytical methods. Among other points, the guidance notes:
Nonclinical studies are typically carried out before a compound is used to treat humans. Here the guidance suggests:
These studies look at the action and behaviour of drugs in humans. Here the guidance notes:
Most psychedelics are controlled substances regarded by regulators to have high abuse potential. The guidance notes that these drugs need to be evaluated for abuse potential during development and new drug applications should contain relevant data and proposals in relation to drug scheduling under the Controlled Substances Act.
Clinical studies evaluate the effect of a compound on particular health outcomes. Here, the guidance points out the following:
The FDA has invited comments on its draft guidance by 25 August 2023. Stay tuned for further news.