Pharmacy hours interviewed David Olson, PhD, chief innovation officer, head of the scientific advisory board and co-founder of delix Therapy and associate professor in the Department of Biochemistry and Molecular Medicine at the University of California at Davis, about a recent article qu ‘he co-wrote on psychedelics and other psychoplastogens for the treatment of mental disorders.
Alana Hippensteele: What is a psychoplastogen and why is understanding this class of compounds important for psychedelic research?
David Olson: A psychoplastogen is a small molecule that is very effective in promoting neuronal plasticity and allowing the brain to actually heal the physical damage associated with many brain disorders. The reason understanding this class of compounds is really important to psychedelic research is that psychedelics are some of the most potent psychoplastogens that we know of.
Alana Hippensteele: How do psychoplastogens work differently from other compounds used to treat brain disorders?
David Olson: So, many compounds traditionally used to treat brain disorders simply alleviate the symptoms of the disease, but they don’t really address the underlying problem of the disease. In the case of psychoplastogens, they physically rewire the brain to tackle the root cause of these illnesses.
An analogy I like to do is if your light goes out in your living room you can use a flashlight to move around, and that would be like a traditional treatment, but what a psychoplastogen looks like is like an electrician would come in and fix the broken wiring so you could actually turn that light back on.
Alana Hippensteele: Are the origins of all psychoplastogens natural?
David Olson: Not necessarily. One of the most well-known psychoplastogens is a molecule called ketamine which is a completely synthetic compound and not produced in nature.
Alana Hippensteele: Just to follow up on this point, I understand that ketamine is not always placed in the same category as some other psychedelic drugs. Would you say that under the psychoplastogenic category it would line up with others even though it doesn’t have the same psychedelic effects, is it?
David Olson: Yes, that’s right, and that’s one of the reasons we’ve defined this new psychoplastogenic term, really describing the ability of these molecules to alter neuronal structure and function.
If you get 10 neuropharmacologists in the room and ask them to define different classes of molecules, you get 10 different answers. Thus, defining compounds has always been a challenge for neuropharmacology.
Some people will classify ketamine in the psychedelic class, some will not, but ketamine and traditional classic serotonergic psychedelics, like LSD and psylocibine, are all psychoplastogens.
Alana hippensteele: What are other examples of psychoplastogenic compounds that do not belong to the psychedelic space or the ketamine space?
David Olson: Sure. So one of the first that comes to mind is a molecule called scopolamine. It’s delusional, so it has some of these psychoactive effects, but it’s not traditionally lumped into the same class as something like LSD or ketamine.
Some other examples would be something like this molecule called GLYX-13, it is also known as rapastinel. There is a lot of preclinical work showing that it appeared to produce lasting changes in neuronal structure and function after a single administration.
Next, probably one of the fastest growing classes are the molecules that Delix acts on, and these are so-called non-hallucinogenic psychoplastogens. They don’t have the same kinds of hallucinogenic effects that compounds like LSD do, but they still produce very long-lasting behavioral effects after just one administration.
Alana hippensteele: How does the elimination of the hallucinogenic effect impact the therapeutic benefit? Does it increase it, does it allow it to be more supported, how does it work exactly?
David Olson: So, at the moment, there are no human data on these non-hallucinogenic psychoplastogens. So time will tell, we’ll really have to look at the human data to be sure.
But on the preclinical side, what I can say is that non-hallucinogenic psychoplastogens produce comparable efficacy to their hallucinogenic counterparts. So what we can do is use benchmark compounds that have been used clinically, things like SSRIs, as traditional antidepressants, which act quite slowly and don’t work after just one administration. And then we can use things like ketamine and psilocybin as examples of these new generation psychoplastogenic drugs, and the non-hallucinogenic psychoplastogen seems to be a lot more like ketamine and psilocybin and less like traditional antidepressants.
Alana Hippensteele: How could the introduction of psychedelics into the treatment paradigm, or more specifically psychoplastogens into the treatment paradigm, change the way we think about brain disorders and mental illnesses and their root causes?
David Olson: Yes, this is a really important question that is really at the heart of modern neuroscience in our understanding of the brain.
So, for many years, we thought that brain disorders were simply the result of chemical imbalances in the brain. Now we think of them as neural circuit disorders. So, there are faulty neural circuits that need to be fixed. The paradigm shift with psychoplastogens lies in their ability to physically rewire neural circuits to heal damaged circuits.
Alana Hippensteele: What are some of the challenges of psychedelic medicine in relation to clinical scalability?
David Olson: So currently the way psychedelic psychotherapy works is to go to the clinic to get ready for the session, and then you come in for the drug administration, which can take a while. In the case of psilocybin, we are talking about 6 to 8 hours.
During this time, you’re usually in the room with a few medical professionals who can walk you through this experience to make sure everything is safe and then come back for an onboarding session as well.
So in total there is a lot to be done, and it can be incredibly expensive, and it really hinders the throughput, or the number of patients who can actually benefit from this kind of treatment paradigm. So if you want a scalable drug, what you really want is something safe enough that you can take it home, put it in your medicine cabinet, and you don’t have to. going to the clinic to get everything on time, and that’s really what I think these non-hallucinogenic cycle pathogens really do – they dramatically expand the patient population that can receive psychoplastogenic drugs.
Alana Hippensteele: What are the main takeaways from your recently published article, maybe just a little more detail in the study?
David Olson: So this document really has 3 key points to remember. The first is the idea of using structural neuroplasticity to our advantage so that we can actually physically rewire the brain and heal damaged neural circuits. I think this is a completely new approach in neuropsychiatry.
The second really has to do with the idea that psychoplastogens work in all indications of the disease. So, now I think it’s really important to remember that cortical atrophy, or the physical withering of neurons in a key region of the brain, is really at the heart of a wide variety of brain diseases, such as depression, PTSD, substance use disorders. , and many more. So the reason psychoplastogens seem to work for multiple indications is because they attack the root cause of all of these disorders.
Then, the third key point to remember is the idea of using non-hallucinogenic psychoplastogens as more evolutionary approaches compared to first-generation hallucinogenic molecules like psilocybin. By using these on-the-go drugs we hope to be able to treat a large number of patients, and it is very important to remember that approximately 1 in 5 people will suffer from a brain disorder in their lifetime, so if we really want to to face the magnitude of this problem, we need safe and effective medicines that you can take at home.
Alana Hippensteele: What are the next steps you see on the horizon as a result of this research?
David Olson: I think some of the obvious next steps are to continue to evaluate the indications for which psychoplastogens can be used, and as I mentioned before, cortical atrophy is at the heart of many brain diseases, thus determining whether psychoplastogens can be used in areas beyond neuropsychiatry, get into neurodegenerative diseases, get into neurological disorders like stroke and traumatic brain injury, these are really interesting questions that we haven’t fully addressed for the moment.
Alana Hippensteele: Closing thoughts?
David Olson: While I definitely think first-generation hallucinogenic psychoplastogens like psilocybin are going to help some patients, they just aren’t as progressive as some of the other options. Even though we have enough therapists to deliver these treatments, we are building a psychedelic assisted psychotherapy center next to every Starbucks, the insurance companies decide they will reimburse this in full, the bottom line is that ‘There is still a large percentage of populations who will never be able to take these drugs because of their co-morbidities, their family history of psychotic illnesses such as schizophrenia and bipolar disorder.