This article originally appeared on VICE India.
Learning about carbon molecules and atomic bonds may not be everyone’s preferred dose. Yet, that’s exactly what it takes to mould the Walter Whites of the world. But contrary to what Breaking Bad will have you believe, the realm of making mind-altering substances isn’t all about dodging bullets, entering into dangerous liaisons, and warding off junkies. Yes, making drugs could involve explosion-prone conical flasks and a shitload of money, but out in the real world, a drug designer is often one chained to long hours in a laboratory, calculatively toying with toxic chemicals to figure out which of its curative properties will stick. Dr Alan P Kozikowski is one of them.
Kozikowski, a US-based veteran drug designer with over 500 publications and 100 patents on his portfolio, is the co-founder of pharmaceutical research companies Actuate Therapeutics as well as HNF-Pharma. An organic chemist who trained himself to become a drug designer under the guidance of skilled scientists like Nobel prize winner EJ Corey, Kozikowski has previously established himself through drugs like Huperzine-A, a medication derived from memory-restoring Chinese herbs that is now used to treat Alzheimer’s patients. He was also part of a American government-funded research team that patented Nocaine, a safer and less addictive analog of cocaine to treat the illegal drug’s withdrawal symptoms. He currently serves as the lead scientist at a lab called Bright Minds Biosciences, where he is leading a team creating a compound similar to a psychedelic, but without the bad trip or downer.
The therapeutic potential of psilocybin, the hallucinogenic compound found in magic mushrooms, has been explored in treating anxiety, depression and post traumatic stress disorder for a few years now. However, while shrooms and LSD continue to be illegal in most places around the world, Kozikowski is currently leading a team of organic chemists and scientists to create the ultimate psychedelic cure for therapeutic purposes. His team at Bright Minds has managed to manufacture a compound that mirrors the hallucinogenic effects of psychedelics, but is relatively less harmful. While this compound is still in its testing phase, and is unlikely to be available for use for the next few years, we decided to catch up with Kozikowski on what it was like working on the new-and-apparently-improved psychedelic, how they managed to eliminate the bad trip, and how he feels about microdosing.
Dr Alan Kozikowski is a trained organic chemist from the University of Berkeley and Harvard who taught himself to become a drug designer under the guidance of skilled scientists including Nobel Prize winner EJ Corey. Photo: Alan Kozikowski
VICE: What gave you the idea to design a psychedelic without the bad trip?
Dr Alan Kozikowski: It’s because of the lore that surrounds magic mushrooms as well as my long-time interest in how chemicals work on the brain. With any drug, you have to first identify an unmet medical need, a demand in the marketplace for a new drug to cure a disease or condition, in order to be able to get the funding required to create and test it. Large pharmaceutical companies have more or less abandoned research on drugs to treat central nervous system (CNS) disorders simply because they failed to achieve a return on their investment. One of the last blockbuster CNS drugs was Prozac, which was discovered about 48 years ago. Since psychedelics already existed and have been proven to help anxiety and depression when used therapeutically, we felt they had a promising future and wanted to be the ones to design new CNS drugs based largely on psilocybin.
A team of scientists including pharmacologists, organic chemists, behavioural biologists, clinicians and business managers have thus come together with an objective to improve and update a pre-existing drug. Psychedelics have the ability to impact a person’s brain in a positive way, but they also have the disadvantage of targeting certain receptor subtypes that have been linked to heart disease, thus making them potentially dangerous for anyone who takes them habitually.
The active ingredient found in magic mushrooms is psilocybin, which has proven to be an invaluable compound as it has the potential to rewire the brain and improve mental health conditions like anxiety, depression and post-traumatic stress disorder (PTSD) when taken in moderate doses in a controlled setting.
A synthetic version of psilocybin was actually sold by the drug company Sandoz up until 1966, at which point the cultural tide against these psychedelic drugs changed, and the Drug Enforcement Agency listed this as a highly controlled Schedule I drug. Nonetheless, nature has provided us with a very valuable substance, one that structurally resembles the neurotransmitter serotonin itself. The medicinal chemist can thus use this as an inspiration to create something perhaps even better. Like my business head Ian puts it: the first-generation iPhone made in 2007 was a cool creation, but it has been constantly tweaked over the years to give us the seamless experience we’re hooked on to today. This is our attempt to update magic mushrooms psilocybin or LSD so we can work out all their kinks and improve the experience of using them for a good cause.
An illustrated model of the 5-HT2A receptor found in our brain (in red, green, white), binding with a psilocybin analog (in grey).
So how does one actually design a drug like this?
What I do first is actually look at what is known about psilocybin, how it is made, and what analogues of it have been made previously. We then use a computer and online programs as well as various patent search engines, to find all the pertinent literature, both chemistry and biology, on psilocybin and its analogs. This knowledge is then put into effect by the chemist.
Next, using all of the existing literature data plus molecular modelling studies (in which we see how psilocybin fits into the receptors in the brain it targets), we can begin to “design” newer analogs, or structures that are similar to another compound. The aim is to retain the effects of the activity caused by the desired receptor, while having little or no interactions with those receptors.
Once our design plans are in place, we can proceed to build or synthesise these molecules in the laboratory. From there, they go through various phases of clinical trials, starting with animal tests and eventually progressing to human trials.
So how is it different from a regular psychedelic?
Since we are interested in creating new compounds that can reboot the brain, we want to retain some of the psychedelic effects of psilocybin in our new compound. We anticipate being able to create compounds that may have a shorter duration of action, and that would induce a less intense trip than psilocybin itself. Of course, the key point is with the new drugs we will have removed the heart issues associated with psilocybin itself, as we will have reduced or eliminated activity at the serotonin receptor that triggers it. Defining the appropriate dose of the drug to use for various disease states will also be important. Toxicity is of course always related to the amount of the drug you take, and any drug can prove to be toxic if given at very high concentrations.
So what are the side-effects? Can you have a downer with this drug?
The chances of having a downer are highly unlikely. Generally, we see the downer happen because of the effects of serotonin releasing agents in drugs like MDMA, which trigger an overpower of emotions and a consequent comedown. But by eliminating any triggering of these receptors we also reduce the risk of the downer.
One of the side-effects that we have seen so far is that it could trigger heart attacks, and we’re working on ways to eliminate that risk. But we’re still in the testing phase and are currently doing trials, so we’re still about four years away from the FDA approving this drug for therapeutic use.
How do you envision these bad trip-proof psychedelics can be used?
We imagine that these special psychedelics will be administered in a comfortable setting like a therapist's office. The user would be sitting with eye shades on, listening to calming music while taking these drugs. We believe that once they’ve been perfected, you could go into a psychedelic session that can help your brain be reset in the sense that its receptors are altered or rewired to make you feel less clinically depressed or anxious and instead replace these feelings with positive associations. What we’re hoping is that after one to three sessions, you’re good for the next few months, unlike with current antidepressants like Prozac which have side-effects and make you develop a dependency on them, so that you can only feel normal or happy when you’re taking them. It has been said that antidepressants cause an emotional blunting or a dulling of emotions in many people that use them, whereas in contrast, psilocybin acts by enhancing emotional responsiveness in the brain. It is probably for this reason that psilocybin has proven helpful for many individuals in dealing with and healing repressed emotional trauma.
What are your thoughts on microdosing and how would this drug’s effects be different from it?
While I don’t personally take this drug, psilocybin is one of the safest and least addictive drugs out there, and has known therapeutic effects for anxiety and depression. However, with microdosing, your brain starts developing a tolerance to its positive effects, thus reducing its potential. Our drug reduces the amount of hallucinogenic effects in the compound, thus preventing the brain from developing resistance to its effects, which makes it better to use over sustained psychotherapy sessions.
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