How Do Psychedelics Clinical Trials Work?

How psychedelics companies get to the clinical trial stage

“It begins with our discovery phase,” Reichelt explained. Companies like Cybin develop novel molecules using psychedelic compounds and then begin reviewing their capabilities. At a molecular level, according to the neuroscientist, these substances are examined for their properties, and that leads into the next stage ⁠— preclinical research.

What follows tends to be the animal testing portion of the drug development pipeline. At that time, researchers look for reactions, such as head twitches, in mice in order to gauge hallucinogenic effects.

“That's a quantifiable behavioral response that you can then apply to whether or not this drug is having a psychedelic-like effect in mice,” Reichelt said. “We can't ask them what's going on in their brains.”

Another part of preclinical trial screening requires looking at toxicology from the molecules. “We need to make sure that they're safe and they're not going to cause any adverse effects in these animal models before we then move into a human,” Reichelt said.

All of this research helps companies to create an investigational new drug (IND) package. According to Reichelt, these packages contain all sorts molecule information, such as how the drug is absorbed by the test subject, how it distributes around the system, how it gets into the brain and how it gets cleared; any adverse physiological effects are also examined.

Reichelt said that in the pharma world, the preclinical trial process can take up to seven years on average.

Once the data backs up the procedures put forward in the preclinical stage, Reichelt said, the fun begins — that's when researchers can launch a Phase 1 trial, which involves healthy human volunteers. Essentially the drug is tested in a clinical setting with various investigation formats for the substance with the healthy patients. “This is a clinical trial,” Reichelt told INN.

In order to reach that stage, though, the IND package has to get approval from the appropriate drug regulator.

“What's really important with clinical trials is that it is transparent and well controlled. These are being run by really skilled individuals,” Reichelt said. The expert added these trials require a significant amount of time and cannot rely on anecdotal data. Instead, specific readouts and consistent results are a must in this setting.

“Everything needs to be pre-screened, everything needs to be approved. Ethically, it's really important that this is all supported by the organizations in the sites that are getting the studies,” Reichelt said.

“Everything has to be very transparent, and aligning to Good Clinical Practice.”

Regulators like the FDA play a key role in psychedelics clinical trials

While stigma still exists when it comes to psychedelic substances in the medical space, the top regulators in the drug development industry have already shown a willingness to engage with these drugs.

Notably, back in 2018, the US Food and Drug Administration (FDA) approved a trial for psilocybin in treatment-resistant depression from COMPASS Pathways (NASDAQ:CMPS).

“It paved the way for second generation and third generation molecules,” Reichelt said, noting that the psychedelic drug development business has evolved to include publicly traded companies. “We need to get the FDA approval through the clinical trials to be able to allow people to access these therapeutically via their physicians."

The expert is keenly aware of the rules and standards imposed by the FDA, as Cybin is going through its own dealings with the top drug regulator. The company has a variety of trials in its pipeline with psilocybin analogues and DMT.

Reichelt told INN that Cybin has also built out a therapeutic program to accompany the use of drugs on patients.

The placebo problem for psychedelics clinical trials

During a panel at the Wonderland event, Reichelt engaged in a deep conversation about the role of placebos in clinical trials.

When conducting clinical trials, researchers have to test the effectiveness of their drug candidate. Accomplishing that requires some volunteer patients to be assigned a placebo substance — this is standard practice for the pharma world, with patients not knowing which group they are in. But in psychedelics clinical trials it becomes a real challenge, according to Reichelt.

The neuroscientist told INN that in the preclinical trial stage, rats can easily be given a saline solution instead of the actual psychedelic compound. “But people aren't rats, and they are much more difficult in terms of working with them,” Reichelt said.

A patient in a trial may immediately suspect they are in the placebo group if they don’t feel any hallucinogenic effects. “With the placebos there's no consensus as of yet regarding what is the gold standard placebo for a psychedelic clinical trial,” Reichelt said.

When it comes to the type of volunteers seen in these trials, Reichelt said there’s an added pressure for patients who are facing mental health conditions that they haven't yet been able to resolve.

“There's a lot of hype and expectation around these treatments. And I think that it can be very difficult for individuals who are experiencing mental health conditions, who potentially do feel like this is their last chance,” Reichelt.

The scientist explained that, while there’s no straight answer when it comes to the placebo conundrum with psychedelics clinical trials, she has seen a variety of clever efforts on how to tackle it.

Investor takeaway

When asked about the enthusiasm of her medical peers outside of the psychedelics industry, Reichelt said she sees excitement across the board. “What's been really exciting with psychedelics is that it's shaking up the field, because these molecules are really powerful, and they have a lot of promise to be able to treat people really effectively,” the expert said.