In the last decade, there’s been a surge of scientific interest in the healing power of psychedelics—mind-altering drugs like psilocybin, LSD, mescaline, ayahuasca, ketamine, and MDMA (3,4-methylenedioxy-methamphetamine). Currently, there are more than 300 government-approved clinical trials testing the use of these drugs in many disorders and diseases—disorders for which they can provide relief even when no other treatment has worked.  

Some of the strongest scientific evidence supports the use of psilocybin for depression, anxiety, alcoholism, and tobacco addiction, the use of ketamine for depression, and the use of MDMA for post-
traumatic stress disorder (PTSD).

But researchers are also looking at psychedelics for a wide variety of other conditions, including obsessive-
compulsive disorder, burnout, suicidality, eating disorders, opioid addiction, ADHD, mild cognitive impairment and Alzheimer’s disease, Parkinson’s disease, diabetes, liver disease, migraine, and cluster headaches, phantom limb pain, and even the symptoms of COVID-19.

But don’t expect your doctor to be prescribing a psychedelic anytime soon. None of these drugs are approved for use by the United States Food and Drug Administration (FDA), except for esketamine (Spravato), a ketamine-derived nasal spray for treatment-resistant depression. And under federal law, the use of psychedelics is illegal, except in government-approved clinical trials. (Several cities in the United States have decriminalized psilocybin, like Washington, D.C., Denver, Seattle, and Oakland. The state of Oregon has legalized it for both personal and therapeutic use. These local laws do not nullify federal law.) However, in the context of the hundreds of government-
approved clinical trials being conducted around the United States, these drugs present a future option you should know about.

How psychedelics work

So-called “classic” psychedelics like psilocybin, LSD, mescaline, and ayahuasca work by binding to the 2A receptor for serotonin, a brain chemical (neurotransmitter) that regulates fundamental brain activities like mood, emotions, sleep, and sex drive. This receptor is only the first “domino” in a lengthy series of falling dominoes that produce a wide range of psychological and biological effects. (One of those dominoes is the neurotransmitter glutamate, which is the first receptor for “non-classic” psychedelics like ketamine.)

The result is that many parts of the brain are activated that are not normally activated, and some parts of the brain—like the prefrontal cortex, which regulates cognitive control—are far less active. Additionally, when you take a psychedelic, the way the brain communicates with itself is radically changed. There is a massive increase in what scientists call “global connectivity”—parts of the brain that don’t normally communicate with each other now do so.

Think of it this way: Normally, “local networks” in the brain mostly communicate with their next-door neighbors. When you take a psychedelic, those same networks communicate less with the neighbors and more with the people across town.

Mystical experience

This increase in connectivity may be the reason why a psychedelic often has a profound effect on your sense of reality, including your sense of self. In studies at the Center for Psychedelic Research and Consciousness at Johns Hopkins University School of Medicine, this subjective experience is called a “mystical experience.” Such experience is characterized by a positive mood, a sense of wholeness and connection within oneself and with the outside world, a sense of direct knowledge of the nature of reality, a sense of everything being sacred or holy, transcendence of time and space, and a sense of ineffability, or the fact that reality is beyond definition and language.

Research shows that those who have a mystical experience while taking a psychedelic are more likely to experience positive therapeutic effects. Their depression and anxiety are often relieved—even depression and anxiety after a terminal diagnosis, like cancer. Their desire for an addictive substance, such as alcohol, cigarettes, or opioids, subsides. Bottom line: A mystical experience while taking a psychedelic can grant a new perspective on life and self that allows a person to have a fundamental psychological resolution of their condition or disorder.

In many cases, the result is more like a cure than a reduction in symptoms. You might take a psychedelic one, two, or three times, rather than taking a drug every day for the rest of your life, as an antidepressant. That’s one of the key advantages of these remarkable drugs. Many scientific studies and papers present the power and potential of psychedelics to heal.


A study in the Journal of Pharmacology, published in February 2022, tested psilocybin on 27 people with major depressive disorder. Each person received two doses of psilocybin with supportive psychotherapy. After a year, three out of four patients had more than a 50 percent reduction in depression, and 58 percent had complete remission. The experience of “personal meaning, spiritual experience, and mystical experience” during the psychedelic session predicted the subsequent level of well-being.

In a meta-analysis of nine studies on ketamine and depression, researchers found that adding ketamine more than doubled the response, compared with placebo, with a 63 percent improvement in symptoms and a 64 percent improvement in remission. In the March 9, 2022, issue of Expert Opinion on Drug Safety, the researchers wrote that the treatment is “effective, safe, and acceptable.”

Life-threatening cancer

In a study in the December 2016 issue of the Journal of Pharmacology, 51 cancer patients with a life-threatening diagnosis and symptoms of depression and anxiety took either a therapeutic dose of psilocybin or a very low dose. Those who took the higher dose had large decreases in depression and anxiety, an increase in the quality of life, life meaning, and optimism, and a decrease in anxiety about death.

Substance abuse

Researchers from Johns Hopkins University School of Medicine studied more than 400 people with an average of 4.5 years of substance use disorder (SUD). The abused substances included opioids, cannabis, and stimulants. After taking a psychedelic, 73 percent of participants no longer had SUD. The results were published in the January 2020 issue of Frontiers in Psychiatry.

Post-traumatic stress disorder

There are more than a dozen studies on the use of MDMA for PTSD. In a major study authored by 38 researchers in the United States, Canada, and Israel, 90 people with severe PTSD were given either MDMA or a placebo. Those taking MDMA had a 42 percent greater reduction in symptoms. In the June 2021 issue of Nature Medicine, researchers describe it as a “potential breakthrough treatment.”

Important: As a street drug, MDMA is called “Ecstasy”—but research shows illegally purchased Ecstasy may not contain MDMA, and may contain other illegal drugs.

Health behavioral change

In a scientific paper published in the January 2022 issue of the Journal of Psychopharmacology, an international team of researchers theorized that the next frontier for research into psychedelic therapy might be health behavioral change—using the therapy to improve diet, exercise, and stress­reduction practices, all of which can contribute to physical and psychological well-being.

Safety and legality

Many people use psychedelics on their own—with a study estimating more than 30 million Americans have used a psychedelic during their lifetime. But there are many risks from taking a psychedelic outside the context of an FDA-approved clinical trial.

  •  Legality. Except for ketamine for depression—if you take a psychedelic outside the context of a clinical trial, you’re breaking the law.
  •  Improper compound. If you’re taking a psychedelic, you want confidence in the purity and dose of the compound you’re taking. Having that kind of confidence is nearly impossible outside the setting of a clinical trial.
  •  Health safety. The safest way to protect your health when you take a psychedelic is to receive a real medical screening before the event, in which you’re checked for physical risk factors such as elevated liver enzymes and psychological risk factors such as a family history of schizophrenia.
  •  Cardiovascular. People have died taking psilocybin. If you have severe heart disease, you shouldn’t be taking the drug, which can modestly raise blood pressure.
  •  Lack of support. Psychedelics can cause a “bad trip,” in which you are overcome by delusion and paranoia. Such an outcome is far more likely if you take a psychedelic by yourself rather than in a controlled and supportive setting. Also, a setting outside of a clinical trial may not provide any support during or after taking the psychedelic—when a person may have trouble integrating experiences that come up, like those related to trauma.
  •  Abuse. Taking a psychedelic puts you in one of the most vulnerable situations you’ve ever been in, and some people have been the victims of sexual or psychological abuse.

If you’re determined to take a psychedelic outside the safe and legal bounds of a federally approved clinical trial, there are “psychedelic retreats” in countries like Mexico, Costa Rica, and Jamaica. The “Multidisciplinary Association for Psychedelic Studies,” lists more than 300 therapists and a mission that includes helping “people to benefit from the careful uses of psychedelics.” (Please note: It is technically illegal to travel overseas to engage in an activity that is illegal in the United States.)

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