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For many years, scientists discouraged, downplayed, or outright prohibited research into the use of psychedelics for treatment of mental health disorders like depression and PTSD in the United States and many other nations. Recently, though, renewed interest in this topic has revealed that some mind- and perception-altering substances may have great value when incorporated into treatment for depression, PTSD, and other mental health concerns.

However, while many headlines trumpet astounding advances and potential breakthrough developments, some experts call these results into question. Most critics push for a more cautious approach.

What Are Psychedelics?

Psychedelics are a category of drugs whose effects include altered perception, changes in mood, and disrupted cognition. Psychedelics are also known as hallucinogens, which refers to their ability to cause various types of hallucinations.

Examples of psychedelics include:

  • Lysergic acid diethylamide (LSD)
  • N,N-Dimethyltryptamine (DMT)
  • Psilocybin
  • Peyote
  • Mescaline

Several other drugs, categorized as dissociatives, dissociative anesthetics, or club drugs, can elicit effects similar to psychedelics. Examples of these drugs include:

  • Ketamine
  • 3,4-Methyl​enedioxy​methamphetamine (MDMA)
  • Phencyclidine (PCP)
  • Dextromethorphan (DXM)
  • Methoxetamine (MXE)

According to an April 2016 article in the journal Pharmacological Reviews, English psychiatrist and researcher Humphrey Osmond coined the term psychedelics in 1957. The author of that article, David E. Nichols of the University of North Carolina’s Eschelman School of Pharmacology, noted that although this term has been in widespread use for more than 60 years, it has “generally been frowned upon by the scientific community because it implies that these substances have useful properties.”

History of Psychedelics in Mental Health Treatment

As the quote at the end of the previous section indicates, psychedelics in mental health treatment is a controversial topic.

Evidence indicates that certain psychedelics (such as peyote and psilocybin) have been included in religious or spiritual ceremonies for thousands of years. In the mental health field, most sources point to the late 1940s or early 1950s as the beginning. This date follows Albert Hoffman’s accidental discovery of LSD’s psychedelic properties in 1943.

In 1953, Humphrey Osmond and colleague Albert Hoffer begin experimenting with LSD to help people who with alcohol use problems. An article published in 2014 indicates:

  • Over the next 17 years, they used LSD to treat about 2,000 people
  • Between 40%-45% of patients remained abstinent for at least one year.
  • More than 40,000 patients participated in various forms of LSD therapy for mental health concerns between 1950 and 1965.

However, during the 1960s, the U.S. government began to crack down on the use of LSD. The effort to prevent the recreational use of psychedelics had a negative impact on legitimate efforts to investigate their potential mental health benefits.

Decades passed before researchers began to study psychedelics to treat people with depressive disorders, posttraumatic stress disorder (PTSD), and other mental health disorders.

Renewed Interest in Psychedelics to Treat Depression and PTSD

Australia became the first nation to legalize the use of MDMA and psilocybin for mental health treatment in July 2023. Authorized psychiatrists may now prescribe these psychedelics to treat patients with treatment-resistant depression (TRD) and PTSD.

Mental health experts define a person as having TRD if they have completed two courses of treatment with two different medications with no improvement.

The decision to approve MDMA for PTSD is supported data in a May 2022 article in the journal Cureus.

The team from Nova Southeastern University that wrote the Cureus article noted problems in that research. They noted 50 percent of people with PTSD did not achieve satisfactory improvements. This failure rate underscores the importance of researching new ways to treat PTSD.

After reviewing several studies into the use of psychedelics to treat PTSD, the Nova Southeastern team reported the following.

Potential Benefits of MDMA Treatment for PTSD

  • Veterans and first responders received therapeutic MDMA reported “a lasting significant decrease” in symptoms.
  • Functional magnetic imaging (fMRI) showed increased signaling in the prefrontal limbic system.
    • This indicates MDMA may help regulate fear responses.
  • Studies involving psilocybin report that this drug can decrease the flow of blood to the amygdala (the relatively small area in the brain that is part of the limbic system, and which regulates emotional responses). As with the effects of MDMA, this promotes a diminished fear response among patients who have PTSD.

Although Australia made international news with its recent legalization announcement, it is not the only country where healthcare providers are using psychedelics or similar substances to treat mental health disorders.

For example, in 2019 the U.S. Food and Drug Administration (FDA) approved the use of Spravato, which contains a ketamine variant called esketamine, for people who have treatment-resistant depression. Spravato is administered by nasal spray. It may only be used in a doctor’s office while the patient is being supervised by a qualified professional.

An article on the Johns Hopkins Medicine website describes both esketamine and ketamine as “highly effective depression treatments.”

Benefits of Eskatamine and Ketamine

  • Patients who receive esketamine or ketamine therapy have reported improvements in their symptoms in a matter of hours. Traditional antidepressants typically take several weeks to begin producing noticeable positive effects.
  • Esketamine, according to Johns Hopkins Medicine, is the only drug other than lithium that has a documented history of decreasing suicidal ideation.
  • Studies indicate that esketamine can reverse cellular damage (such as shrinkage or lost connectivity) within the brains of people who have been struggling with depression.

Esketamine is currently approved in the U.S. only for treatment-related depression. Ketamine is approved only as an anesthetic. However, the effectiveness of these medications has prompted many doctors to prescribe them as off-label treatments for a host of additional mental health concerns.

Psychedelic and psychedelic-adjacent drugs have clearly yielded positive results for many people who have depression, PTSD, and other mental health disorders. But – as we will discuss in the next section – not everyone greets the increased use of these substances to treat mental illnesses with enthusiasm.

Concerns About Using Psychedelics to Treat Depression and PTSD

The FDA’s announcement that it had approved Spravato (esketamine) for treatment-related depression was released March 5, 2019. Nine months later, some experts pushed back on this decision. The journal Epidemiology and Psychiatric Sciences published an article titled “Esketamine for treatment resistant depression: a trick of smoke and mirrors?”

As that title indicates, the authors doubted esketamine could meet the expectations created by the FDA’s approval.

Primary Concerns About Psychedelics

  • The FDA relied on three randomized trials when approving esketamine. However, according to the authors of the Dec. 16 article, only one of these three trials demonstrated that esketamine was more effective than placebo.
  • The authors were concerned that esketamine was evaluated only against a placebo, instead of being compared to another medication.
  • They theorized esketamine temporarily masked depressive symptoms, rather than improved them.
  • They claimed the FDA’s assertions that esketamine is safer than ketamine were undocumented.

Though the authors doubted esketamine’s efficacy, their focus in this article was on the evaluation, approval, and regulation process. Critics of the Australian government’s decision to legalize MDMA and psilocybin for PTSD and depression expressed similar concerns.

A June 2023 Nature article describes this legalization as “a controversial move.”

Here’s why.

MDMA and Psilocybin: Is Approval the Right Choice?

  • Psychiatrist Susan Rossell expressed concern that the Australian government had not clarified who should (and should not) receive psychedelics as part of their treatment. The possibility of a “bad trip,” she noted, could exacerbate patients’ mental health struggles.
  • Psychiatric researcher Steve Kisely criticized the lack of a mandate that psychedelic treatment for depression and PTSD should occur only in a clinical environment and be accompanied by psychotherapeutic support.
  • Alan Davis, the director of Ohio State University’s Center for Psychedelic Drug Research and Education, was one of several experts who felt that the legalization effort was premature, citing a dearth of evidence regarding both efficacy and safety.

Also, Paul Liknaitzky, who leads the clinical psychedelic research program at Monash (Melbourne) University, decried the lack of stringent data collection and reporting requirements for the healthcare providers who prescribe these medications.

“It’s a shame for accountability, and also a shame for us being able to learn collaboratively on the ground,” he said.

Potential Implications for Treatment

Given the momentum that research and legalization efforts have achieved in the U.S., Australia, and elsewhere, it seems likely that psychedelics will continue to play a role in mental health treatment moving forward.

However, considering the concerns that many experts continue to express about using LSD, MDMA, ketamine, and other drugs to treat mental health disorders, it also seems likely that widespread acceptance of these advances may be slow to occur.

From the perspective of a patient or a prospective patient, is important to remember that there is no single “perfect” type of treatment for depression, PTSD, or any other mental health disorder. And even if psychedelics continue to demonstrate their effectiveness for depression and PTSD, they may become a valuable option – but they won’t be a cure-all.

If you are seeking mental healthcare for yourself or someone in your family, you should focus your attention on finding a provider whose services and approach to treatment align with your needs, goals, and expectations (or those of your loved one). If you think psychedelics are an option for you, please discuss your preferences with your healthcare provider.

As researchers discover new techniques and approaches for treating mental illnesses, it will become increasingly important for patients to ask questions, express their concerns, and have open and honest conversations with their caregivers. Regardless of which services or medications a center provides, maintaining this type of collaborative and respectful environment can increase each patient’s ability to achieve improved health and better quality of life.