The Dark Side of Psychedelic Trials

Interest in psychedelic medicine has never been higher. Possession and use of psychedelic drugs have been decriminalized in Oregon and Colorado, and the latest research appears to support the effectiveness of psychedelic-assisted psychotherapy in treating severe depression. Most American psychiatrists view psilocybin and ketamine as safer than alcohol or Xanax, too, according to a recent study.

But among the celebrations for this historic progress, some psychedelic experts are whispering a word of caution.

“We will soon be able to be all treated with psychedelics, and we will all be healed and everyone is happy, right? Not so fast,” says Dr. Markus Roggen, president and chief science officer of Vancouver-based Delic Labs.

Speaking to audiences at the recent Analytical Cannabis webinar, “Advances in Psilocybin Research”, Roggen warned that while the rapid progress in psychedelic science is encouraging in many ways, there is a clear need to improve the ways in which some of these trials are handled.

Additionally, as some in the sector look to patent their inventions, Roggen offered a short introduction to the psilocybin crystals and how these are relevant to the intellectual property debates that are sure to come as the sector expands.

Patient safety and flawed trials

“Everyone is looking at psychedelics. With that attention comes scrutiny, and it’s not all rosy,” Roggen said. “There is some bad news.”

Earlier this year, Health Canada announced the suspension of a clinical trial for MDMA-assisted psychotherapy following “concerns for participant safety.” These concerns were raised after video footage emerged showing two of the trials’ therapists physically restraining a distressed PTSD patient during the trial.

“This patient came to the MDMA trial because of PTSD, as a result of sexual abuse in her youth. And during therapy, she was blindfolded, she was inappropriately touched, she was pinned down, and the therapist started a sexual relationship with her outside of that trial,” Roggen summarized.

“There are so many no-nos in this aspect. And it was all filmed, and no actions were taken by the trial organizers while this happened, and it was only reviewed years later.”

After reviewing both of the trials for MDMA-assisted psychotherapy, Health Canada suspended the aforementioned study and asked the second trial, run by the Multidisciplinary Association for Psychedelic Studies (MAPS), to correct several issues related to record-keeping and staff training.

“These various entities are often not pharmaceutical companies who have been running clinical trials for decades or centuries. It is more [often] interest groups, and they might not bring the expertise and [knowledge of] how to run and organize a clinical trial. And with this comes risk,” Roggen said.

Improving the study of psychedelics

One of the main ways in which a clinical trial can demonstrate its credibility is to pre-register. Pre-registered trials disclose their methods and outcomes in advance before any of the research is actually completed.

“If you go onto a trial saying, ‘This is what I’m planning to do and this is how I’m going to analyze the data, and that’s what I’m going to analyze for,’ and then you follow your protocol that you pre-registered… It’s a better approach because it keeps you honest,” Roggen said.

Rather than running an experiment, seeing the results, and retroactively using the data to generate a hypothesis – a form of selective reporting also known as “p-hacking” – pre-registered trials force the organizers to reveal their hypothesis in advance. This gives additional credibility to the study’s interpretation.

There are also some improvements that can be made that are more specific to the psychedelic science sector. For example, Alberta recently moved to impose stricter regulations on who can provide psychedelic-assisted therapy sessions.

Under the new rules, “only a psychiatrist or a physician in consultation with a psychiatrist can prescribe a psychedelic drug for the purposes of treating a psychiatric disorder, unless the drug is ketamine provided outside of psychedelic-assisted psychotherapy.”

Apart from this exception for ketamine, psychiatrists who conduct psychedelic therapy must apply for a license under the Mental Health Services Protection Act. Staff at psychedelic therapy clinics will also be required to report any injuries or deaths immediately to the government. As clinical trials on psychedelics continue around the world, many may wish to consider implementing similar policies on counselor qualifications or incident reporting.

The emerging world of psilocybin patents

The word “crystal” probably has more connotations with the world of rocks and gemstones, but organic compounds such as psilocybin can also inhabit crystalline structures. Very pure psilocybin naturally exists as a white, crystalline powder. And although psilocybin is largely converted to the active metabolite psilocin in the body, psilocybin is normally the focus of much psychedelics research as psilocybin is very unstable in environmental conditions.

“Chocolate comes in various different crystal forms. And then it melts in your car and then it doesn’t taste well anymore,” Roggen gave as an example. “Polymorphs are important. Different [crystal] polymorphs will have different absorption in the body, and different medical effects.”

If a psychedelic company has the correct polymorph for a certain application, with all of its favorable absorption and therapeutic properties, then the company can treat a patient with it. Importantly, the company can also patent it.

This is already happening; Compass Pathways was granted a US patent for a psilocybin structure named Polymorph A in October 2021. This patent was subsequently challenged by a group arguing that this sort of discovery should not be patentable. However, Patent Trial and Appeal Board (PTAB), a group of administrative judges within the United States Patent and Trademark Office, recently decided that this petition would not move forward to trial.

As research continues within the psychedelics sector, this issue of patenting crystalline structures is certainly likely to raise its head again. Roggen’s own lab, Delic Labs, has recently began working with a crystallization expert to further explore cannabinoid and psilocybin crystallization, with a view to better understanding the chemistry which controls these processes.

“Crystals are not just the boring end product. It has a lot of influence on biological uptake, patentability, medical effects, and the value foundation of this industry,” Roggen said.