To understand psychedelics — those powerful and cryptic agents of the mind — scientists are exploring uncharted landscapes. “We don’t yet really know why psilocybin or other psychedelic drugs seem to have the effects that they do,” Professor Paul Hutson, director of the University of Wisconsin-Madison Transdisciplinary Center for Research in Psychoactive Substances, told the Wisconsin Examiner. “We don’t know to what extent the magnitude or the type of psychedelic experience, altered state of consciousness, is required to maximize benefit.”

UW-Madison researchers are actively pursuing answers to those questions as they study the effects of psilocybin (the active component of many psychedelic mushrooms) on depression, Post Traumatic Stress Disorder (PTSD) and various addictions, and by seeing how other psychedelics — like 3, 4 Methylenedioxymethamphetamine (MDMA) sometimes called Ecstasy or Molly — stack up in comparison. 

A new executive order signed by President Donald Trump has expedited the review of psychedelics as mental health treatments. The order could open new doors for researchers. Other universities and private companies are exploring the potential of other psychedelics including Lysergic Acid Diethylamide (LSD), derived from the ergot fungus, and 5-MeO-DMT, which is produced by plants and a species of toad. 

The Food and Drug Administration (FDA) has identified certain psychedelics — LSD, Psilocybin, and MDMA — as “breakthrough” substances that can help treat difficult to manage diseases, and has encouraged the development of new treatments. Hutson says a national voucher program is another recent tool used to stimulate the creation of psychedelic medicines. The Usona Institute, a nonprofit in the city of Fitchburg, received one of the vouchers. Another voucher was granted to develop methylone, which is similar to MDMA, to treat PTSD. “It’s a very similar chemical structure, has some similar effects, and it’s done very well in some of the early studies,” said Hutson. 

Hutson said he was surprised when the federal government chose to support methylone over MDMA. 

Yet, Hutson told the Wisconsin Examiner, “it was gratifying to see that they have helped accelerate the evaluation.” He thinks that the new regime will help companies and universities funnel data to the FDA more regularly “as opposed to a package that’s delivered on their doorstep that they then need to go through,” Hutson explained. “So there will be more of a staggered or sequential evaluation of the data as it comes out.”

Until recently, the use of psychedelics had gone underground, after a burst of mainstream optimism about their use in the 1950s and 60s. Researchers and psychologists experimented with the drugs openly, until negative attention led to their prohibition in 1970, five years before the public would also learn about their covert use by the CIA in its infamous and illegal MK-Ultra program.

Building the right treatment programs

As legitimate and ethical treatment programs return today, Hutson feels that one barrier will be finding sites that will be able to provide treatment, “both in terms of the room and also the therapists that the FDA is requiring,” he explained. “Right now, the FDA is requiring two people to be in the room,” he said, both of whom must be college graduates with bachelor’s degrees. State-level credentials and also at least a year of mental health experience are further requirements.

“And if those are the expectations for the people that are sitting in the room for eight hours with these patients that are being dosed, we’re going to have a really hard time addressing the demand that’s going to come when these drugs are approved,” said Hutson. 

“We’re grappling with what kind of training program we might be able to provide, not yet knowing what the FDA is going to require,” he added. He also said that although the FDA would require the primary therapist to be a psychologist or a physician with a mental health background, the federal agency does not require any psychedelic-specific special training.

There’s also the actual space where patients undergo the psychedelic journey to consider. “I think the key for any dosing space is that it be safe and comfortable,” Hutson said. “We’re typically looking for a place that has private bathrooms so you won’t have to go out into the hall. And the different dosing spaces around the country have different levels of extravagance, and ours is one of the nicer in the country. But you can’t afford to spend that kind of money on every dosing. You don’t really need a place as nice as ours.” 

What’s more important, Hutson said, is the care patients receive. “With the psilocybin studies that we are doing and most other scientists are doing, there’s the expectation that the two monitors are there primarily to provide reassurance and if the subject gets anxious, provide reminders that they are in a safe place.” 

Researchers and companies are also beginning to form various camps, creating disagreements over things like the role of psycho-therapy in psychedelic treatment. While some groups argue that psychotherapy needs to follow a protocol — and their treatments rely heavily on that strategy — others have been trying to back away from that model. Hutson pointed to methylone as an example of a psychedelic treatment that doesn’t put an emphasis on psychotherapy. Other companies are using LSD without psychotherapy, arguing that improvements within the patient are brought about by the drug alone. 

This approach allows companies to simplify the treatments and thus the package that would go to the FDA for approval. Meanwhile, Hutson said that donors who once supported research want to switch gears and become investors in psychedelic companies. 

“They want to be putting their money into companies that are now increasingly in the space that they’d like to make some money on it,” explained Hutson. “Which is really disappointing because in our methamphetamine use disorder study, we had enough money to dose three individuals, and those three individuals — adding psilocybin to their therapy — decreased their methamphetamine use by over 90%. So really remarkable. We’re seeing where others are reporting similar results with other substances of abuse such as alcohol, tobacco, cocaine and so on.”  

Research into opioid recovery is ongoing, though Hutson said they’re finding that the impulsive behaviors associated with opioids can be difficult to treat or change. Participants may show up intoxicated and not be able to participate, for example. “So we just have a hard time herding cats,” said Hutson. 

Differences in perspective

The influence of profit motives on psychedelic medicine has also led some to explore ways of using fast-acting psychedelics like 5-MeO-DMT (produced by many plants and at least one species of toad) to treat more patients and make more money. “Perhaps those drugs don’t give the patient time to deal with it or to get over the shock of the experience and to get a therapeutic benefit out of it,” Hutson cautioned. “We don’t know yet. We don’t know if you need the psychedelic experience at all, [or] can you just use the biochemical reaction of the drug to the receptors. Is there something critical to the consciousness effect, not just the psychedelics, you know, the hallucinations?…We’re trying to figure that out.” 

There is also the question of how future patients will pay for care, and whether insurance companies will cover treatments. 

Hutson thinks that once the FDA approves methylone for mental healthcare there will be pressure on insurance companies to cover the costs. Yet, Hutson mused, “anti-depressants are fairly cheap, they’re a lot less expensive than a dose of psilocybin, but psilocybin may have more durable and more impressive results.” 

Getting insurance companies to commit to covering addiction treatment is another hurdle. “I think it’s going to be a tough job to get the insurance companies to cover those off-label prescribing efforts,” Hutson said. Right now, psychedelic treatment can range anywhere from $3,000-$10,000 out of pocket, depending on who’s in the room and what they charge, he added.

There are also people questioning whether the visionary part of the psychedelic experience is even necessary for treatment. One man who participated in UW-Madison’s study using psilocybin to treat opioid addiction described being in the presence of what he called a “god” or “higher power” that manifested as a sort of “energy that was in front of me.” He also called the dosing space the “sacred room in there,” where he took “the medicine.”

Such encounters are common in the world of psychedelic research. Yet so-called “non-psychedelic psychedelics” are being developed that produce no visionary effect at all. Hutson also highlighted a study at UW-Madison where people are given a drug to make them forget their psilocybin visions, and another where people are given psilocybin while they are asleep to test whether you need to be awake to receive a benefit. 

Visionary plant medicines have been used by humankind for millennia. Some users say the spiritual aspect is important to the experience and that therapists and researchers can benefit from personal experience with psychedelics. 

“That is an opinion that many hold that in order to understand what the subject is going through you need to have had that experience,” said Hutson. “And so I disagree with that. You know, my background is in cancer therapy and I don’t feel like I need to take a cancer drug just to know how miserable a lot of them can make people feel. So I can have a sense of what they are likely to experience, and appreciate that and try to deal with that. The other thing, though, is that right now it’s illegal for people to be taking these drugs. So for these therapists to be taking it exposes them to some risk.” 

There are also concerns about therapists imposing their own expectations on patients’ experiences. Questions like “Did you see god in your experience like I did?” could make patients feel they didn’t have the experience they should have had, Hutson cautioned.

Nevertheless, a therapist should also never disregard the reported experience, however incredible, he said. Hutson recalled Bill Richards, a psychologist from Johns Hopkins University, who talked about encountering a monster during a psychedelic journey. “And you don’t run away from the monster, ” said Hutson, recounting what Richards said. “You approach it, and perhaps jump into its mouth and look out through its eyes to see what it sees, which is you. What does the monster see in you? Who’s the monster?” 

Hutson said that therapists and researchers at UW-Madison try to keep an open mind when asking patients to reflect on their experiences. “Reassure, kind of redirect sometimes,” he said. “If there was some kind of intention that was set beforehand, maybe we could return to that.”

Confronting the future

Questions about dosing concern researchers, such as whether boosters are needed, how far apart, and whether there are people or conditions that should not be treated with psychedelics.  While dosing people with schizophrenia isn’t recommended, Hutson said there may be potential benefits from the drugs for people with bipolar disorders, neurological degenerative diseases, end-of-life distress and eating disorders. 

“We haven’t looked at all the possible other chemical effects that these drugs have.  They’re very potent compounds and they have very potent effects on the mind,” Hutson said. “Can we dose these individuals? Is there any benefit to these individuals? Is there any harm to these individuals?”

Hutson worries that it’s too soon for widespread acceptance that psychedelics are safe. While there is not a risk of fatal overdose or addiction for LSD, psilocybin or DMT,  there is the potential for harmful accidents when people are on the drugs. Hutson also mentioned research into Ibogane — a visionary psychedelic used by African tribal cults for ancestor–based ceremonies — which shows that the plant-derived compound could be damaging to the cardiac system. 

The professor is also skeptical of “micro-dosing,”  taking small non-psychoactive amounts of psychedelics in order to improve mood or cognition. He said there’s little evidence to suggest it works better than a placebo, and that it can also be damaging to the heart. Recreational users also cannot determine whether their mushrooms or drugs are contaminated with something, Hutson cautioned. When sold on the black market, drugs like MDMA could be adulterated with fentanyl or other dangerous substances, and something sold as LSD may actually contain risky research chemicals or designer drugs. 

After each psychedelic experience, it’s also crucial for the patient to have  a period of integration or debriefing in order to process their journey and integrate any lessons learned or improved symptoms into their daily life.

“It’s a mind-altering drug,” Hutson said. “And it produces suggestibility and flexibility, and the experiences during the dose may not be as important as the experiences afterward. So if somebody leaves a psychedelic dosing environment and goes into an unsafe or threatening environment, there may actually be harm from that reenforcement that occurs, that negative reenforcement. And so I’m concerned that people will think that these are safe by its FDA approval.”

Caution and trepidation, however, are accompanied by enthusiasm and curiosity in the psychedelic research world.  UW-Madison has several ongoing research projects Hutson said have had “remarkable results.” Methylone is being studied for use treating PTSD, and more. “Very active,” Hutson said. “A lot going on.”

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