Psychedelics are having a renaissance. Since the early 2000s, researchers at Johns Hopkins have been reviving the once-promising research from the 1950s and ’60s, which largely studied the therapeutic benefits of psychedelics on alcohol and heroin addictions. Now clinical trials are showing that the sustained positive effects of psilocybin go far beyond the outcomes of current psychiatric treatments.

“There are no psychiatric illnesses that we have under control,” explained Dr. Josh Woolley, the director of the Translational Psychedelic Research Program at UCSF, when he spoke at Private Medical’s Grand Rounds webinar in March. The “treatments are really inadequate – slow to work, don’t work for everybody, and have a lot of side effects.”

The earliest known depiction of psychoactive mushrooms, from Tassili n’Ajjer, Algeria.

Hallucinogens have a long history in cultural ceremonies, with the earliest known depictions dating back to Algerian cave art from 7000 – 5000 BCE. But since the 1970 Controlled Substances Act classified psilocybin and other psychedelics as Schedule 1 drugs (meaning they pose a high risk for addiction with no medical benefits), much of the emerging research at the time came to a halt.

This new era for psychedelics began when Johns Hopkins released their 2006 study of synthetic psilocybin treatments in healthy, middle-aged people. Volunteers received two eight-hour sessions two months apart. The main outcome marked a significant difference in positive attitudes about their life, positive mood changes, altruistic social effects, and a sense of well-being. “Seventy-six percent of people said that the psychedelic experience was among the top five most meaningful experiences of their entire life,” noted Dr. Woolley.

In a study nearly a decade later, the Hopkins group studied psilocybin’s effect on anxiety and depression in patients with life-threatening cancer. In a video put out by the group, one patient describes how the death of his daughter came up during a session, a moment he feels finally allowed him to process the trauma. “The result of those trips and the ability for me to experience more of myself and more of what life is – to become fully alive, as in ecstatic – very much enables me to go forward,” explained the patient.

Some of the experiences study participants had.

The outcome of neuroplasticity – the ability for the brain to change – is why Private Medical is moving towards a new term for these drugs: neurotherapeutics.

Clinical trials – which, more recently, study the effects of psilocybin on ailments including headache, stroke, traumatic brain injury, eating disorders, bipolar disorder, and loneliness – are focused on mindset and setting. First, the patient undergoes preparatory psychotherapy, meeting with two facilitators for six to eight hours over two weeks. These facilitators are present at the psilocybin session where patients are given a pill, which has a controlled amount of psilocybin (the amount of psilocybin varies in naturally-occuring mushrooms), and wear eye shades and headphones that play music while laying on a couch. After the session, the patients come back over the next two weeks to talk about the experience and integrate it into their lives.

There are “vanishingly small adverse outcomes,” explains Dr. Woolley. And in the case where these drugs are being used to treat substance-use disorders, it’s very rare that someone would become dependent on them, especially when compared to heroin or morphine.

While LSD and psilocybin are classified as Schedule 1 drugs, the reality is that there is a very low risk of dependency and overdose.

Beyond these clinical trials, companies like Dr. Jonathan Sporn’s Gilgamesh Pharmaceuticals are developing novel compounds (what Dr. Sporn calls “close structural cousins” to the illegal substances) to treat depression, anxiety, and substance abuse. Down the line, he anticipates these treatments expanding to neurodegenerative disorders, PTSD, eating disorders, and obsessive compulsive disorder.

Derived from a Central African plant, ibogaine is currently used in offshore addiction treatment (“After one treatment, people are much better, which is remarkable,” notes Dr. Sporn). Gilgamesh is developing a similar compound that will treat substance- use disorders – a treatment he expects you might take only a few times and then never again.

DMT, which is derived from ayahuasca, offers a similar “afterglow effect” that you would experience with mushrooms but in a much shorter period of time (about 10 minutes). The six-hour experience on mushrooms “is too long for our health care system to handle,” explains Dr. Sporn. “So we’re trying to make something that is long enough that it will work, but not so long that it’s not practical for mass markets.”

Another new treatment in development comes from Perception Neuroscience, founded, but no longer run by Dr. Sporn. The company is working with a novel version of ketamine for treatment-resistant depression, which would be used more like a micro-dose, a few days on, a few days off.

At these lower doses, it “will feel a little bit like doing psychotherapy on steroids,” says Dr. Sporn. “The principle is that after you take these [drugs], people are able to think a little bit differently about themselves, about their relationships, [and] have more degrees of freedom.”

We’re still working towards a full understanding of how the brain works. But researchers believe that these drugs affect the brain at the circuit level. Taking depression as an example, “you can’t get something out of your mind – that you’re a bad person and that you’re no good… people can’t get out of that brain circuit, they’re locked into it,” explains Dr. Sporn. With neurotherapeutics, “all of a sudden the person has more access to different brain circuits. It’s almost like rebooting your computer.”

Even with just one high dose, study participants showed early signs of the lasting effects of the psilocybin treatment.

While these treatments won’t be FDA-approved for another two to five years, the research is promising. As Dr. Woolley has seen in trials, one treatment leads to six to eight months where patients’ anxiety and depression are much improved from before the treatment. One study shows a 71 percent reduction in depression symptoms, where over 50 percent of participants were considered in remission. These effects are four times larger than what trials have shown for traditional antidepressants on the market1.

“That’s why people get excited,” Dr. Woolley said. “In regular psychotherapy, people can change dramatically, but it takes years. [With psilocybin], a lot of these [changes] are happening in weeks.”