In 1966, Harvard psychologist Timothy Leary, who was exploring the impact of psychedelics on the mind, famously encouraged Americans to “tune in, turn on, and drop out.” More than 50 years later, Americans are listening.

The use of lysergic acid diethylamide (LSD), ecstasy, and other hallucinogens has increased since 2015, and the latest data shows that 5.5 million people have taken psychedelic drugs in 2021.

Psychedelics have a long history of use in healing rituals and religious ceremonies across the globe. Both peyote and psilocybin are native to North America and central to the some of the spiritual practices of Indigenous peoples.

But “it’s become a big fad among certain demographics like the intelligentsia who have been reading books [like This is Your Mind on Plants] by Michael Pollan,” says Albert Garcia-Romeu PhD, assistant professor of psychiatry and behavioral sciences at Johns Hopkins Medicine.”Research into the therapeutic effects of psychedelics started in the 1950s and initial results showed that the hallucinogenics showed promise as treatments for alcoholism and mental disorders, but an uptick in recreational use triggered pushback and stigma.

“[The research] came to a crashing halt, mostly due to the counterculture associations of psychedelics and widespread misuse,” says Dr. Michael P. Bogenschutz, psychiatrist and director of the NYU Langone Center for Psychedelic Medicine. “With the passage of time … research resumed and we’ve started to take a look at what the clinical potential of these drugs might be.”

The current interest in psychedelics has exploded with the global market expected to reach $8 billion by 2029—up from $2.9 billion in 2021. There are numerous different psychedelics but current research targets three classic drugs:

• LSD: The lab-made drug was first synthesized in 1938. At doses of 200 micrograms, considered a high psychoactive dose, according to Garcia-Romeu, the oral hallucinogen has been found to have a therapeutic benefit for reducing anxiety.

• Ayahuasca: The hallucinogenic contains a mix of different plants found in the Amazon and has strong psychoactive effects that have been shown to have antidepressant and anti-addictive effects. “Dosing is more complicated because there are multiple substances involved … and there is no standard formulation,” says Garcia-Romeu.

• Psilocybin: The hallucinogenic compound found in more than 200 species of “magic” mushrooms is a natural psychedelic. In the lab, researchers administer 20 to 30 milligrams of pure psilocybin for antidepressant, anti-anxiety, and anti-addictive properties.

NYU Langone and Johns Hopkins are among several universities, including University of Texas at Austin, Washington University in St. Louis and the University of California San Francisco, that have established psychedelics research centers to conduct clinical trials on the impact of the drugs on alcoholism, smoking cessation, depression and post-traumatic stress disorder (PTSD). The results have been so promising that Garcia-Romeu believes Food and Drug Administration approval to use the hallucinogen MDMA, or ecstasy, to treat PTSD could come as soon as 2023.

“Smaller studies started to show that perhaps [psychedelics] weren’t quite so risky,” says Garcia-Romeu. “[T]here are also some real therapeutic benefits.”

What happens to your brain on psychedelics

Psychedelics have hallucinogenic effects. The so-called “trip” is due to the way the drugs affect the brain: classic psychedelics like psilocybin and LSD bind to the serotonin receptors, changing how the neurotransmitter experiences mood, cognition and perception.

Bogenschutz notes that the networks in the brain become more connected and less organized, causing profound changes in consciousness and perception, sense of space, time and reality; the drugs also appear to promote neuroplasticity or the ability of neurons to remodel and form new pathways of communication in the brain。“The drugs make it possible for the brain to change more than it ordinarily would,” he adds.

“In the context of therapy, enhanced neuroplasticity may lead to enhanced capacity for learning and changes in thought patterns, emotional responses and, ultimately, changes in behavior.”

Based on the effects, current research is exploring the potential for psychedelics to help with conditions like opioid addiction, Alzheimer’s disease, anorexia, and Lyme disease.

Despite their therapeutic potential, psychedelics were added to the Controlled Substances Act in 1970 and remain illegal on the federal level. Their classification as Schedule I narcotics means that researchers require licenses to possess and administer the drugs during clinical trials and strict protocols are in place for their use.

High doses—20 to 30 milligrams of pure psilocybin—are administered in specialized clinics and patients are monitored for up to eight hours to ensure there are no ill effects; aftercare sessions with mental health professionals to talk about the experience and how to capture the therapeutic effects are also part of the treatment.

“It’s not a ‘take two and call me in the morning’ drug or like a cannabis dispensary where you walk in with a [prescription] and take it home,” Garcia-Romeu explains. “It’s all done in a special clinic under supervision.”

Balancing benefits and harms

In some cities and states, the mainstream use of psilocybin and other psychedelics is gaining momentum.

In 2020, Oregon passed a ballot measure that made it the first state to legalize the therapeutic, supervised use of psilocybin; Texas and Connecticut followed suit and Colorado has the issue on the ballot this fall. Several cities, including Santa Cruz, Ann Arbor, and Seattle, have passed measures decriminalizing psilocybin and other plant-based psychedelics.

As research on the potential healing impacts of psychedelics makes headlines, researchers are forced to confront the potential downside of their resurgence. A 2022 JAMA Psychiatry article referred to the issue as “keeping the renaissance from going off the rails” and warns that without optimal clinical management and additional studies to understand the impacts and risks, the new psychedelic research could grind to a halt as it did decades ago. Researchers warned, “adding psychedelics to fringe or unproven psychotherapeutic paradigms may increase the risk of … harm.”

Psychedelics are not without risks, including:

• increased heart rate

• Nausea

• intensified sensory experiences

• sleep problems

• panic that can last up to 12 hours.

Moreover, purchasing Ayahuasca, LSD or magic mushrooms on the street is illegal in most states, and comes with no guarantee of purity.

“It’s something the field has to grapple with because there is the risk—and it may already be happening—that people read about the promising scientific results and somewhat hyped up reports in the press … and get the impression that it’s safe and can be used on their own to feel better,” says Bogenschutz. “We could [be] setting ourselves up for trouble.”