The High-Stakes Race to Engineer New Psychedelic Drugs

When a mouse goes out, it becomes more curious about other mice and is more likely to spend time with them. It's less likely to get drunk. It wriggles and shakes like a dog. Its head moves side to side.

The importance of these head twitches is due to the fact that a mouse can't tell you if the colors are brighter or the walls are melting. "If you want to know if a compound is likely to cause a hallucinating effect in humans, you look to the mice," says Wallach, speaking from his tiny office at Saint Joseph's University in Philadelphia.

Wallach's mind-bending new mandate was sparked by a meeting with the heads of a company. Drug development for use in mental health therapies was eyed by the UK-based firm. The main product was a compound in magic mushrooms. It needed new chemicals that could deliver radical results. New chemists were required. The two-year, $500,000 sponsored research agreement was signed by the two parties in August 2020. The center was founded.

With continued support from the company, Wallach has cooked up scores of novel psychedelics, sent them off to partner labs for testing, and then waited and hoped for the telltale twitch results. When it comes to specifics, the chemist, 36 and pale, face framed by a rough red beard and rectangular glasses, can hem and haw a bit. We've made a lot. There are at least 150 new drugs in the area, all of which can be patented and sold by the company.

We are currently in the midst of a renaissance. Compelling clinical work conducted at New York University, Imperial College, and elsewhere showed that long outlawed drugs such as N,N-dimethyltryptamine (DMT), LSD, and psilocybin have terrific potential for treating everything from addiction to Alzheimer's The pharmaceutical companies took notice. The industry was predicted to grow to over $10 billion by the year 2027. In September 2020, Compass became the first company of its kind to trade on a major stock exchange and was valued at more than $1 billion.

So far, none of these companies has brought a drug to market, but the thinking is that, through what the clinical literature calls a'mystical-type experience', patients can confront their demons. "I don't want to use the word cure, but psychedelics can offer long-term healing." We have spent a lot of money on this hypothesis.

Wallach leads a group of people at the Discovery Center. He says that one thing they do is create new compounds that are different from classical drugs. The intensity and character of the journey can be changed by slight alterations to the structure of the molecule. Wallach is passionate about the ability to fine- tune a trip to create new modes of experience.

His lab work was very niche for a long time. He wasn't encouraged by mentors. They said there wasn't any money in the drug. There were risk factors. Many of these drugs have been ruled by the US Drug Enforcement Administration not to be used for medical purposes. Since the US government declared most psychedelics to be illegal in 1970, such research has typically been done by so-called clandestine chemists, who worked in backyard sheds and underground bunkers and produced mass-produced new compounds while evading law enforcement.

He wasn't discouraged. The work felt very close to pure chemistry, he says, and was animated almost entirely by personal curiosity. If you moved it over there, what would you do?

New investment is shaking up the ideals as firms rush to take advantage of the results. A few years ago, Wallach was doing research in the field of neuroscience. His once quiet lab, with its beakers and burners and reports on twitchy mice, is helping to bring about a new era of Big Neuroscience. There is a potential threat of "psychedelic capitalism." Wallach is a prized asset. A young chemist is doing his job. New stresses are produced by the financial stakes and ideological fault lines. He says that the research is worth it in the long run. Is that the case on a day-to- day basis? It doesn't change anything, but it raises my blood pressure.

When he was a child, Wallach was obsessed with psychoactives. Egg-in-the-frying-pan public service announcements were part of theJust Say No era. The messages did not affect Wallach. He discovered a book in the school library about the dangers of drugs when he was a kid. Something drew him to it, he said, that a small amount of powder or material could change someones experience.

The life-changing experiences Wallach had years later proved to be true. He has been studying them for 15 years. They had a big impact on how I wanted to live.

At Indiana University of Pennsylvania, Wallach studied psychology as a way to understand the mysteries of the human mind. Wallach wanted to know where thoughts come from. The brain and the mind are different. What do we think about taste and sound? We don't know what to think about anything at all. Wallach realized that psychology was a little less empirical than he had thought. He wanted to study cellular andmolecular biology.

Synthetic organic chemistry was begun by Wallach. He looked at the cannabinoid compounds in cannabis. An avid reader of textbooks, he noticed that two books were pushed by Amazon. Alexander Shulgin and his wife, Ann, wrote these reference books in the '90s. The accounts of various compounds are based on trials conducted by the Shulgins and other travelers.

There are a lot of books on how to make illegal drugs. Wallach immediately got to cooking. He says they are the most useful tools for answering some of the questions he was interested in.

Wallach learned how to make drugs from the Shulgins. He had an ad hoc lab in the basement of his parents' stone farmhouse during breaks from school. He moved the entire operation to a small carriage house after his mom complained about the smell. Wallach prepared everything he could legally manage. He said he was very paranoid.

He loved the work. His parents might have been concerned about the risk of their son accidentally manufacturing compounds that merit harsh penalties under the Drug Scheduling system, but they were happy to see him take the plunge. The University of the Sciences, which merged with Saint Joseph's University, was where Wallach went to pursue his PhD. He pretended to buy into the antidrug hysteria when applying for grants so that he could continue studying psychoactives. He says that the angle was that these are drugs of abuse. Tell the grant agency whatever you have to.

He paid a small price to nurture his obsession. Wallach is talking about synthesis when he isn't making drugs. He reads the latest literature when he isn't lecturing. He still reads when he is at home with his wife. He teaches himself math when he isn't doing that. Or something related to electronic devices. Or advanced science. He wants to stay sharp. Everything goes towards the research. He told me that he has interests outside of the sciences. He has an antique snuff box collection. He chews nicotine gum in order to stay focused. He claims to chew it while brushing his teeth. The odd cigar is something he likes. He doesn't drink alcohol, which he refers to as "ephemeral alcohol". Wallach says he likes the taste, but he can't suffer the more mind dulling effects. I don't want to start feeling buzzed at all. He told me that he spent his days off using plastic model kits to design potential molecules. He was working in the lab on Christmas day.

Wallach said this is his life. I would rather be doing other things. I would build a superlab if I got a billion dollars. He was finally given the chance to pursue that dream. Maybe not a billion dollar superlab. His own lab.

In pop culture, psychedelia is a tapestry of colors, including black-light ink, tie-dye, and phat pants. In their various states of synthesis and manufacture, psychoactive drugs are very gross. The smell of drugs in the labs is similar to burning a yankee candle.

I visited Wallach in his lab last fall, where he was making a hallucinogen called N,N-dipropyltryptamine. Wallach is dressed in a faded maroon polo, khakis, and desert boots and explains to the audience that scientists investigated DPT for use in therapy in the 70s. He advises me to stay away from the lab as he fiddles with substances that are toxic. It is similar to watching a chef show off at a teppanyaki restaurant.

Wallach is back in class after the Pandemic disruption. His lab continues to work for Compass. Wallach and his squad of mostly twentysomethings work in a few different offices, testing compounds for purity, sketching out molecules in grid-lined notebooks, and preparing potentially mind-expanding substances in discreetly marked mailers to be sent for mouse-twitch tests.

The job is to develop drugs that tickle the 5-HT2A receptor, which is involved in a number of functions. Classical hallucinogens have been shown to have a crucial effect on the brain's endocannabinoid system. They all interact with 5-H2A. The phrase "5-HT2A agonist" has replaced "psychedelic" in some circles. If you want to make a new version of a classical hallucinogen, the first thing you need to do is look at the interaction with that receptor.

One of Wallach's goals is to find out how long the effects of a drug last. Trips lasting more than six hours are the norm. Three full days is how long it takes for you to get used to the world of waking, non-wiggly consciousness. The sessions are expensive and may not be needed. Drug effects can last only minutes and can be enjoyed within a typical lunch hour. Wallach has many challenges, including finding the sweet spot between the length of a trip and clinical efficacy. If he and his team of researchers are able to come up with something that is particularly potent or unique, it will be great.

The shelves are disorganized. There is a mission statement written in black Sharpie on the fridge. The walls are adorned with artwork by Wallach. The beakers and flasks in the cabinets are decorated with pictures of famous scientists. In lab whites and a jaunty beret, Albert Hofmann smoked an enormous pipe, and Nathan S. Kline was the "Father of psychopharmacology".

If it weren't for Shulgin, Wallach wouldn't be working with DPD. In one of his reports, Shulgin describes smoking a lot of DPT and seeing a vision of two rotating hearts. There were four rows of light-colored jewels surrounding them all around.

Many people in Wallach's lab rely on Shulgin. Jitka Nykodemov is a graduate student who moved to Philadelphia to work with Wallach. Shulgin packed his life's work into a few textbooks so that he wouldn't have to worry about government agents burning his records. His work is available for free on the internet. Wallach's operation is not open to the public. I'm warned against stealing away with proprietary chemical names or structures. All of the lab's discoveries are owned by Compass.

According to Graham Pechenik, a patent lawyer focused on the emerging psychedelics industry, there is a perception of Compass as being the ogre. He is talking about the company's clash with old-timers who don't like the idea of a company being run by people who use drugs.

Compass started as a nonprofit in 2015, but switched to a for-profit model a year later and received funding from Peter Thiel. A patent was granted for a method of synthesis. The patent gave the company a monopoly on a compound that humans have been using for thousands of years. Peter Van der Heyden is the co- founder and chief science officer of Psygen Labs, a private manufacturer of pharmaceutical- grade drugs.

A whole group of people with roots in the ’60s and ’70s have spent years of their life and sometimes years in jail, working toward this. I don't know how to say it's a gift to mankind, but it is. He has an ideological bent. Hippie-era values of peace, love, and smiling on one's brother were framed by his generation. The drugs were once thought to be a cure for corporate profiteering.

Soft furniture and "reassuring physical contact" are some of the practices that have been used in the past for conducting psychedelic therapy. One critic said thatCompass was trying to patent hugging.

A group of chemists and competitors challenged the claims of another company. According to some in the industry, the company's method of synthesizing psilocybin apes techniques was devised by a pioneer in the field. Carey Turnbull, a former energy broker and founder of Freedom to Operate, led the charge. A statue of the Buddha is one of the personal effects at his estate in the gated hamlet of Tuxedo Park.

Ceruvia Life Sciences is a for-profit company that is pursuing pharmaceutical applications of the drug psilocybin and other drugs. In addition to being a part of the patent overreach patrol, Malcolm is also a direct competitor of Compass.

In an open letter published on Freedom to Operate's website, it was claimed that Compass is not making good-faith use of capitalism or pharma regulations by attempting to establish itself as an exclusive, global supplier of psilocybin. In his opinion, the invention ofpsilocybin is being laid claim to by Compass in order to return it to the human race. Scientists from Freedom to Operate scoured the globe for vintage samples of Hofmann's version of the drug. The method for the production of the molecule is not novel, according to their research.

Executives from the company disagree. Their patents allow them to bring their treatments to as many patients as possible. They don't claim a monopoly on the process for producing a particular synthetic form. The Patent Trial and Appeal Board ruled in favor of Compass in June. George Goldsmith assures me that his company is not trying to stop people from eating mushroom caps. Wilde says that the market is not focused on hugs. Goldsmith and Wilde have the tendency of staying frustratingly on message. Ask them what they had for breakfast, and they'll tell you how excited they are. Goldsmith lost his professionalism when he was pressed about his company's image. He wondered from his London office if he had freedom to operate. No constraint is present. It's already been done.

Wallach doesn't mind the ethical aspects of capitalism. It isbusiness as usual. The so-called "Hippie Mafia" of the ’60s and ’70s were funded by the scions of the baron dynasty. Shulgin was Wallach's hero. He paid for his far-out chemical experiments with his day job at a company that produced napalm during the Vietnam war.

Wallach isn't moved by the charges. He acknowledges that he is aware of the criticisms. I don't have anything to worry about. Corporate involvement seems to be preferable to the alternative, in which the decisions about the research, scheduling, and distribution of drugs are taken by the government. His voice changes a bit when he says the government. He doesn't like the Drug Enforcement Agency, which still imposes severe penalties for the possession and manufacture of mind-expanding drugs.

He has to wade through a lot of bureaucratic red tape to do his job. A number of his friends have overdosed on synthetic opioids. Some of them are in his home office. Opioid overdoses are the state's worst public health crisis. Students struggle and suffer. A system that still views drug use and addiction as moral issues, and not medical ones to be addressed, compassionately, through science, is what he rails at. He held back tears as he said that it definitely drives him. I want to make sure that doesn't happen to other people. Improve people's lives. We could have a place to call home on this rock.

Wallach drew a standing-room-only crowd at the spring meeting of the American chemistry society. They came to the San Diego Convention Center to hear him talk about the structure-activity relationship of n-Bomb. He says there were a lot of young scientists in the hall.

Wallach doesn't follow the hype of being a celebrity scientist back to the lab. He has a lot to take care of as Big Neuropharma's patent land grab ramps up. He is sitting in his office in West Philly. He can't legally reveal the chemical composition of a new drug but he can show how mice respond to it. The curve is like a roller coaster as it curves upward before peaking and driving back down. The final dose is called "mig per kig" or "mig per kilogram." Wallach is asked if that's good. He is almost dying to tell me something. He said it was a good response. He plucked the nicotine gum from between his back teeth and put it back in his pack as he nodded.

There is a chance that a new drug will be given to human subjects in a trial. It could end pharmacology. Either psychology or something else. It could be the beginning of a new revolution. Wallach can toast his success with a cigar and a glass of whiskey as he becomes a psychopharmacological saint. Until then, it is charts and graphs and fastidious inventories of structure-activity relationships on reams of graph paper.

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