Jukka Karjalainen, Cybin Corp Interview on Psilocybin Clinical trials

Psilocybin Clinical Trials and Drug Development

A Conversation with Dr. Jukka Karjalainen of Cybin Corp.

You won’t have to look very long or very far to find research suggesting that psychedelics are the future of effective mental health treatment. Major institutions around the globe are conducting new studies, and international scientific conferences are being held to discuss the developments. The potential for compounds like psilocybin is being shouted from the rooftops, and the pharmaceutical world is responding. It’s why we’re here. There’s a great deal riding on the success of the compounds now being adapted and synthesized for medical purposes, both in terms of the outlook for patients, and the companies and investors seeking a piece of what’s already being called the psychedelic renaissance. Truffle Report decided to speak with Dr. Jukka Karjalainen, chief medical officer of Cybin Corp., a life sciences company based in Toronto, about how this much-touted potential is being turned into a reality with the current wave of psilocybin clinical trials.

Dr. Karjalainen: Background and History with Psychedelic Research

Dr. Karjalainen is the Chief Medical Officer of  Cybin’s drug development strategy for using psilocybin to treat major depressive disorder, or MDD. Before we got too deeply involved, I asked for some information on his background. “I’m a medical doctor and a pediatrician,” he says, “also a specialist in pharmaceutical medicine and general practice. I’ve been in research since the early 1980s, and a practicing physician for twenty-two years. I’ve written ninety peer-reviewed scientific articles, chapters in books, and articles for various publications over the last forty years.” He began consulting with pharmaceutical companies in the late ’80s and early ’90s, becoming a research manager and later medical director. “My interest in psychedelics goes back about twenty years now. In 2001, I was reviewing the existing psilocybin literature for a couple of pharmaceutical companies. It was interesting, but because it’s a Schedule I drug, it ended up not going ahead at the time,” he adds.

Dr. Karjalainen clarifies that he knew of a great deal of research into psilocybin, some of which went back decades, but “everyone was afraid of taking that step forward. It hasn’t been until the past less than ten years that we’ve been able to really re-start clinical trials with psychedelics, particularly psilocybin.” He also mentions that, unsurprisingly, he considers psilocybin’s classification to be unjustified. “Schedule I is considered to have a high potential for abuse, increased suicide risk, and no known medical potential. Psilocybin is just the opposite. It’s the other way around.”

Psilocybin as a Treatment for Major Depressive Disorder: ‘The Only Compound I Know’ 

With background out of the way, I wanted to know more about his work with Cybin, and asked about the choice they’d made, in contrast with other psychedelic drug developers, to focus specifically on treating MDD with psilocybin. “Major depressive disorder is the second largest treatment market in the world, after cardiac diseases,” he answers. “It’s huge. And the current antidepressants are not optimal. There’s not a good treatment. There’s a lot of side effects, a lot of issues with antidepressants. The patients are not happy, the doctors are not happy, nobody is happy. You have to take them every day, multiple times a day. The risk of suicide for people under the age of twenty-five taking antidepressants is significantly elevated with black-box warning in each product.”

Broadening the scope of his answer to psilocybin research, Dr. Karjalainen explains, “This is the first targeted medication in development, that has already shown in the early phases of research and trials to be clinically efficacious for so many indications.”

He went on to list:

–        Major depressive disorder

–        Treatment resistant depression

–        Anxiety

–        Obsessive compulsive disorder

–        Cancer-related anxiety and depression

–        PTSD

–        A wide range of eating disorders

–        Different types of headaches

–        Alzheimer’s disease

–        And in particular, promising results in treating substance abuse, including alcohol, opioids, smoking, and cocaine

“This is the only compound I know, in the lifespan of the entire pharmaceutical industry, that can potentially treat such a vast number of indications, so many diseases. The next closest are some oncology compounds, drugs that affect three, four, maybe five different types of cancers. That’s it,” Dr. Karjalainen tells Truffle.

It’s reason enough for any doctor.

Sublingual Films as a Delivery System

Carrying on with our conversation, I wanted to bring us back to Cybin’s focus. At this point, they’re developing sublingual strips to act as a synthetic psilocybin delivery system. I asked about that choice. “They aren’t exactly strips,” Dr. Karjalainen says, “more of a thin film. And there are a few different reasons for us going that way. In the clinical trials, what’s been used is a 25 mg oral capsule, and this has to go through the stomach and intestinal tract before being absorbed into the liver.” He goes on to explain that when compared to sublingual delivery directly to the bloodstream, between fifty and sixty percent of the active ingredient is metabolized through first-pass liver metabolism.

“There have been studies that have shown the effects of delivering psilocybin intravenously, in which a 1 mg dose can be equivalent to a 10-20 mg dose delivered orally. This will lead to many benefits. Synthetic psilocybin at the moment is quite expensive to manufacture. The actual cost of the treatment per dose will be reduced very significantly with oral film dosing. The absorption rate and ultimate bioavailability for oral capsules are also quite variable, with some having thirty percent bioavailability, some as high as sixty percent. Patients could get a higher or lower dose than intended, and the treatment could be ineffective. Circulation of the active ingredient with the sublingual film is much more stable. It’s the best option for consistency of dose and control of side effects. Then there are the patients. Patients who have these conditions may not want to take the capsules or tablets in public. The film requires no water to ingest, and is very discreet.”

Psychedelic Clinical Trials vs. Conventional, and Early Results

At this point, we’d spoken quite a bit about Cybin’s clinical trials. I wanted to hear more from Dr. Karjalainen about how psychedelic clinical trials functioned compared to the rest of the pharmaceutical industry. “It’s been very smooth,” he tells me. “This research has actually been going on since the 1960s, and we understand the effects very well with an oral dose, we understand that the lower sublingual dose is more stable. In the oral capsule, we see some hallucinatory side effects, minor headaches lasting a few hours, all very manageable. We’ve had rarely serious adverse effects. It’s a big difference from testing many other drugs. Other than that, effects on blood have not shown any real safety concerns, and patients are followed up observing how the patient is doing, how the treatment is working.”

“At the present,” he tells me, “we have many different internationally recognized efficacy scales, and safety scales as well.” He references the commonly used MADRS, which is physician-recorded, and BDE-II, which is patient-recorded, among others. “They are all showing us something quite remarkable. With antidepressants, you have to take them every day. Even when successful, it usually takes between five to eight weeks for the clinically targeted effect to appear. The other problem being that over six months, most patients lack efficacy and must switch from one product to another and in fact, more than seventy-five percent of patients stop taking antidepressants. The negative side effects also make use of antidepressants very unsatisfactory. Whereas with psilocybin patients, in clinical trials, we’ve seen the treatment have a positive effect on depression, anxiety, all kinds of other symptoms, with one single dose. It’s very exceptional. There are certain types of genetic treatments, therapies, that you only have to do once, but for any regular therapeutic it’s usually dosed every day. It’s very rare for it to last so long from one dose given at the clinic.”

The Patients/Psilocybin Treatment

It sounds promising, but it’s not a surprise. Psychedelic therapies and pharmaceuticals have gained impressive momentum in recent years precisely because of results such as these. With that in mind, I wanted to understand more about how Dr. Karjalainen decides whether or not a patient is eligible for treatment, and goes about administering the psilocybin. “Obviously the clinical trials are different from the real world,” he says. It’s a fair point to begin on. None of us know yet exactly what legally administered psilocybin therapy might look like in its eventual form. At best, we have educated guesses based on similarities in trial models.

“We recruit patients with a certain scale of major depressive disorder. They must, of course, consent to the study, and they cannot use antidepressants. The dose is given, and the patient is observed in the clinic for six to eight hours. That may change when we have more clinical data available. For now, we keep them in a quiet environment, accompanied by a nurse, and we monitor for hallucinogenic effects. Many patients do not have any, but for those that do it’s usually transitory, lasting an hour or two. There could also be a headache lasting an hour or so, a slight increase in blood pressure. All mild, and expected. I consider this therapy very justifiable for treating someone for four, five, six months with a single administration, as opposed to daily antidepressants.”

Outlook for Psilocybin Clinical Trials and Parting Thoughts

As we began to wind down, I asked Dr. Karjalainen how he envisioned the first wave of legal psilocybin pharmaceuticals being rolled out to patients and consumers. “For me, quite understandably, the first wave would be in the countries where psilocybin has been around for ages, not criminalized. Jamaica, Portugal, the Netherlands, Brazil, we have fourteen countries that we’re looking at. However, it looks like the FDA and Health Canada are moving forward. More so the FDA. They’ve issued Breakthrough Therapy designation to COMPASS Pathways and the Usona Research Institute. Cybin will also be seeking breakthrough status for the sublingual film delivery system.”

It’s not surprising that the regulatory hurdles for medicalized psilocybin, once so daunting, are beginning to come down. I suspect most of us can think of someone in our lives who suffers from one or more of the conditions listed earlier. Comparing the described side effects of psilocybin trial patients with the average side effects of antidepressants, or many other medications currently on the market, should leave little doubt in anyone’s mind that this work is worth pursuing. 

While I’m not sure what precisely my expectations were going into this interview, I can say that the biggest surprises for me, going into a talk about psychedelic drug development, turned out to be that there weren’t any. In clinical trials at least, synthetic psilocybin is performing as expected, living up to its described potential, and, if I understand Dr. Karjalainen correctly, going better and more smoothly than most drug trials in the ordinary pharmaceutical world. Truffle Report is looking forward to speaking with other drug developers, academic institutions, legal scholars and thought leaders in the psychedelic space about what exactly the end result could look like.

In the interest of complete transparency, we’d like to disclose here that Cybin is a client of Truffle Report’s parent company, Puff Digital. Cybin did not pay for, sponsor, or solicit this interview in any way. It’s our intention in the future to ask the same sort of questions to as many other psychedelic drug developers as are willing to speak with us, and to give our readers as complete a picture as possible of the multifaceted field of drug development within the medical psychedelic space.

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