Psilocybin Depression Treatment: Are Magic Mushrooms Safe?

Affecting an estimated 21 million U.S. adults each year, depression is becoming a national crisis. Finding the right treatment can be challenging. Just look at the statistics showing that about 30% of people with the mental health condition have what’s called treatment-resistant depression, meaning they haven’t gotten better after trying at least two antidepressants.

With the rise in treatment-resistant depression, it’s no wonder scientists are searching for more effective ways to treat the mental disorder. In recent years, psychedelics have been making waves as potential therapies for a range of mental health disorders.

The hallucinogen ketamine made headline news in 2019 when it earned FDA approval as a new drug therapy for major depressive disorder. Another hallucinogen, psilocybin (the psychoactive compound in magic mushrooms), has also been gaining favor as a new approach for treatment-resistant depression and other mental health conditions.

But is taking a psychedelic trip on magic mushrooms safe for people looking for mental health treatment?

WHAT IS PSILOCYBIN?

Psilocybin is a natural hallucinogen that distorts perception and can cause profound visual and auditory hallucinations. People can have very different experiences form ingesting magic mushrooms.

Psychedelic effects can include:

• Seeing colors more vividly
• Feeling like time has slowed down
• Thinking unusual thoughts
• Seeing objects that appear to be moving
• Feelings of euphoria

Not everybody has such a magical experience. Some people have decidedly unpleasant reactions to the substance, including:

• Nausea
• Numbness
• Anxiety
• Paranoia
• Panic attacks
• Fear
• Feelings of depression

These positive or negative effects emerge about a half hour after ingesting the substance and can last approximately four to six hours.

HISTORY OF PSILOCYBIN

People have been using psychoactive mushrooms for medicinal and religious purposes for thousands of years. In the 1950s, Swiss chemist Albert Hofmann, the man who gained notoriety for discovering LSD, synthesized the substance. This opened the door to clinical research using the drug as a potential therapy for a variety of mental health issues.

In 1970, the U.S. designated it as a Schedule I drug of the Controlled Substances Act, effectively criminalizing it and indicating that it has a high risk of abuse. This put an end to most clinical research until it resurfaced more recently.

The Food and Drug Administration has since given psilocybin a breakthrough therapy designation for both treatment-resistant depression (2018) and major depressive disorder (2019), meaning it has been fast-tracked for review as a potential medication.

PSILOCYBIN AS A MENTAL HEALTH TREATMENT

A small but growing body of research suggests psilocybin may be helpful for mental health conditions, such as:

• Treatment-resistant depression
• Obsessive-compulsive disorder (OCD)
• Substance use disorders
• Cancer-related anxiety and depression
• Anorexia nervosa

For example, a 2024 study compared the effects of psilocybin therapy versus escitalopram (Lexapro) on people with moderate to severe depression. For this trial, the psilocybin group received two 25mg doses of the psychedelic drug along with psychological support. The other group took the selective serotonin reuptake inhibitor (SSRI) escitalopram for six weeks while also receiving psychological support.

After six months of treatment, both groups showed improvements in the severity of their depression symptoms. However, the psilocybin depression treatment group experienced greater sustained improvements in psychological connectedness, functioning, and sense of meaning in life.

However, it’s critical to note that the body of scientific literature about psilocybin as a mental health treatment remains very small—involving only about 600 patients total as of 2024.

HOW DOES PSILOCYBIN AFFECT THE BRAIN?

Scientists have long believed that psilocybin works by binding to serotonin receptors in the brain. This prevents the reuptake of serotonin, a neurotransmitter that’s involved with mood control, shifting attention, and cognitive flexibility. Antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs) work in the same way to enhance serotonin.

A 2012 brain imaging study found that psilocybin also decreases activity in certain brain regions, including the thalamus, which is involved in the transfer of information.

“‘Knocking out’ these key hubs with psilocybin appears to allow information to travel more freely in the brain, probably explaining why people’s imaginations become more vivid and animated and the world is experienced as unusual,” study author Robin Carhart-Harris told LiveScience.

Newer brain-imaging research published Nature in 2024 indicates that the drug desynchronizes the brain. Typical pathways disconnect then reconnect to other pathways in the brain. The brain scans in this study show how the brain becomes more malleable while using the psychedelic, making it possible for people to overcome maladaptive thinking and behavioral patterns.

TAKE CAUTION WITH PSILOCYBIN FOR MENTAL HEALTH

It’s important to understand that treatment with psilocybin typically takes place in a medical setting with the guidance of a trained mental health professional. A psychiatrist or psychotherapist helps lead patients through the experience and helps integrate insights for the psychedelic trip.

Self-medication with the drug is never recommended. However, the media attention on psilocybin may be contributing to an increase in recreational usage of magic mushrooms.

Statistics show that from 2017 to 2022, law enforcement seizures of magic mushrooms more than tripled. And from 2018 to 2022, the National Poison Data System reported a three-fold increase in calls to U.S. poison control centers involving psilocybin use by adolescents and young adults.

The hype surrounding magic mushrooms as a mental health treatment may have outpaced the scientific evidence. In spite of the promising findings, a 2018 review concludes that our understanding of psilocybin’s effects is still in its infancy and suggests caution.

“Progress needs to be made in explicitly understanding the cognitive and neural mechanistic process by which psilocybin works,” the authors say.

In addition, scientists have yet to determine if the use of psilocybin could have detrimental effects in the long run.

On the Change Your Brain Every Day podcast, psychiatrist and brain health expert Dr. Daniel Amen and his wife, bestselling author Tana Amen, discuss the risks associated with psilocybin. After 40-plus years in the field, Dr. Amen says he has seen this happen before in psychiatry where a new drug hits the scene with great promise only to have major consequences emerge later.

“When I was a resident at Walter Reed in 1987 when Xanax came on the market, everybody was so excited about ‘mommy’s little helper,’—another benzo but non-addictive,” he says.  “That was a lie. It increases the risk for addiction and dementia.”

Brain SPECT imaging studies at Amen Clinics have shown that some anti-anxiety drugs, such as benzodiazepines, have negative impacts on blood flow and activity in the brain. “They’re harmful to the brain,” says Dr. Amen.

He thinks it could be the same with psychedelics. “I feel like the street drugs of the ’60s—marijuana, ketamine, and magic mushrooms—are the big innovations in psychiatry as opposed to get your brain healthy and your mind will follow,” says Dr. Amen on the podcast.

Like many others in the scientific community, Dr. Amen cautions that more research on psilocybin is needed to know the lasting impacts on the brain and to establish whether it is safe on a long-term basis. In the meantime, enhancing brain health can be a powerful step in the healing process.

Reviewed by Amen Clinics Inc. Clinicians