Managing Treatment

What a Trip: Mental Health’s Psychedelic Revolution

ADDitude examines the promise, and perils, of psychedelic-assisted therapy in the first of a two-part series exploring and explaining how ketamine, MDMA, and psilocybin are used with therapy for mental health care.

Ecstasy. ‘Shrooms. Special K. These illicit drugs, once relegated to nightclubs and music festivals, have once again become revolutionary medicines with thrilling potential to help people suffering from mental health conditions, including depression, post-traumatic stress disorder (PTSD), opioid and alcohol addiction, eating disorders, and more.

The number of clinics offering infusions of ketamine — the only psychedelic that is legal nationwide — has exploded. Research on the drug known as ecstasy, or MDMA (3,4-methyl-enedioxymethamphetamine), has shown such promise for treating severe PTSD that pharmaceutical companies are preparing to seek FDA approval.1 Experts say psilocybin, the psychoactive ingredient in magic mushrooms that has shown efficacy for treatment-resistant depression,2 may not be far behind.

Used under medical supervision and paired with pre- and post-drug therapy, these psychedelics have been life-changing in alleviating symptoms for many patients. Bob, an ADDitude reader in Arizona, took part in a clinical trial involving psilocybin for obsessive-compulsive disorder (OCD). “I have not had OCD symptoms since I finished the trial over a year ago,” he says.

Bob has also been receiving ketamine treatments for depression, anxiety, ADHD, and complex PTSD. He says the treatments have been more effective than cognitive behavioral therapy and prescription antidepressants, and without the “difficult side effects.”

While many patients like Bob report profound benefits from psychedelics, some psychiatrists and researchers fear that the pharmaceutical industry is moving too quickly toward legalization, while important questions about long-term efficacy and safety remain.

[Read: Real Stories of Using Ketamine for Depression, Anxiety, PTSD]

Psychedelic Therapy: A Blast from the Past

Psychedelics have an ancient history of medicinal use by the Aztecs and other civilizations. In Western culture, the groundbreaking potential of psychedelics to heal disorders of the mind took root around 1950, when the first English-language paper citing their therapeutic benefits was published. By 1960, Sandoz Pharmaceuticals had begun manufacturing psilocybin and LSD, substances later popularized, in part, by iconic Harvard psychologist Timothy Leary, Ph.D.

For years, he and other therapists embraced these experimental drugs for their potential to aid patients. At the same time, LSD played a major role in the counterculture movement of the 1960s. When then-President Richard Nixon outlawed all psychedelics in 1970, the drugs became associated with criminality. That effectively ended most research into psychedelics’ therapeutic value for 30 years.

In 2000, a new era of research began when scientists from Johns Hopkins University secured regulatory approval to study the effect of psychedelics on behavior, brain function, learning and memory, and mood. In 2020, Johns Hopkins opened a psychedelics research center. Since then, most of the country’s elite universities have followed suit. Researchers at Yale, Stanford, Universities of California Berkeley and San Francisco, and New York University have conducted clinical trials investigating the therapeutic benefits of psychedelics on mental health disorders.

[Read: LSD, MDMA, Magic Mushrooms Clinical Trial Guidelines Released by FDA]

“Monumental Results”

For patients diagnosed with depression and in acute distress, waiting six weeks for commonly prescribed antidepressants to begin working may not be feasible, says Gregory Barber, M.D., a psychiatrist in Bethesda, Maryland, and author of “Ethical and Practical Implications of Psychedelics in Psychiatry,” a scientific review that was published recently in the American Psychiatric Association’s Psychiatric Services journal.3 Ketamine, however, has been shown to improve mood sometimes after only one or two infusions.

“With psychedelics, there is some evidence to suggest that even single doses have medium- to long-term effects,” Barber says. “The ability to simplify treatment in this way would be a real paradigm shift.”

Karlyn, an ADDitude reader, knows this first-hand. Diagnosed with bipolar disorder and ADHD, she had been taking antidepressants for 16 years. “My psychiatrist recommended ketamine infusions in 2021 when I was acutely suicidal. It was the best drug that I have ever used for depression. By the fourth infusion, I felt relief,” she says.

Eight percent of Americans suffer from major depressive disorder (MDD). While a majority of individuals seek treatment, about 30 percent find no relief from antidepressants.4 This means that millions of Americans struggle with troubling symptoms like sadness, hopelessness, and suicidality.

Elizabeth Wolfson, Ph.D., a California psychotherapist who has been in practice for 30 years, says she has integrated ketamine into her therapy with “monumental” results. “It augments and deepens the work that people do in psychotherapy and accelerates the process in a way that I see as transformative,” she says.

Psychedelic Therapy: Investigating Risks

Psychedelics’ powers to heal have been heralded in countless headlines, so it’s no surprise that the drugs have recently enjoyed a surge in popularity. According to the National Survey on Drug Use and Health, 7.1 million Americans used hallucinogens in 2020. Proof of a changing public perception is apparent in Oregon and Colorado, where citizens have voted to legalize psilocybin.

The drugs, however, are not without risk. When psychedelic use takes place outside therapeutic settings, the symptoms people are trying to improve may actually worsen. The “therapy” part of psychedelic-assisted therapy is essential to positive outcomes.

In clinical trials and at carefully selected doses, ecstasy, ketamine, and psilocybin have produced generally mild side effects. When taken at higher doses, these drugs can cause disorientation, paranoia, and panic, which can lead to dangerous behavior, accidents, self-harm, and even suicidality. Other adverse effects include the potential for hallucinogen persisting perception disorder (a rare condition in which patients previously exposed to hallucinogenic drugs continue to experience distorted perceptions of the world around them months or years later), misuse, and abuse.

“The clinical trials have had very exciting results, but those results came in carefully controlled research settings with mental health professionals who have hundreds of hours of training,” Barber says. “It doesn’t mean that you will get similar benefits in other settings.”

Important Questions Remain

Experts agree that large-scale research on the long-term effects of psychedelics is needed. Many aspects of how the drugs work, their long-term outcomes, safety concerns, and patient suitability for treatment are still not known.

“I’ve seen psychedelics transform people positively very quickly, but I’ve also seen it be very challenging for people both in the moment and after the experience,” Barber says. “Psychedelics are not going to be for everyone nor solve every problem.”

Patient Suitability

People who have the following conditions or history are not considered good candidates for psychedelic-assisted therapy:

  • a personal or family history of psychosis
  • unstabilized bipolar disorder
  • high blood pressure
  • heart disease
  • thyroid disease

Psychedelics Research Timeline

1943: LSD’s psychoactive effects are discovered by Swiss chemist Albert Hoffman.

1950: First English-language publication suggests LSD may aid psychotherapy.

1957: The term “psychedelic” is coined. Life magazine publishes “Seeking the Magic Mushroom.”

1960: Harvard psychologist Timothy Leary begins experiments with psilocybin.

1963: LSD is sold on the street in sugar cubes. Timothy Leary is fired by Harvard.

1965: Sandoz stops manufacturing LSD and psilocybin.

1997: Swiss scientists publish new research on the effects of psilocybin on humans.

2000: Johns Hopkins researchers secure regulatory approval to resume psychedelics research.

2017: FDA grants “breakthrough” status to MDMA and psilocybin, putting the drugs on a fast track for approval.

2023: Findings of Phase 3 clinical trials on MDMA for PTSD are published.

Psychedelic Therapy & Mental Health: Next Steps

Nicole C. Kear is Consumer Health Editor at ADDitude.

View Article Sources

1Mitchell, J.M., Bogenschutz, M., Lilienstein, A. et al. MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study. Nat Med. 2021(27),1025–1033.

2Goodwin, G., Aaronson, S., Alvarez, O. et al. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022 Nov 3.; 387:1637-1648. DOI: 10.1056/NEJMoa2206443

3Barber GS, Dike CC. Ethical and Practical Considerations for the Use of Psychedelics in Psychiatry. Psychiatr Serv. 2023 Aug 1;74(8):838-846. doi: 10.1176/appi.ps.20220525. Epub 2023 Mar 29. PMID: 36987705.

4Zhdanava M, Pilon D, Ghelerter I, Chow W, Joshi K, Lefebvre P, Sheehan JJ. The Prevalence and National Burden of Treatment-Resistant Depression and Major Depressive Disorder in the United States. J Clin Psychiatry. 2021 Mar 16;82(2):20m13699. doi: 10.4088/JCP.20m13699. PMID: 33989464.


SUPPORT ADDITUDE
Thank you for reading ADDitude. To support our mission of providing ADHD education and support, please consider subscribing. Your readership and support help make our content and outreach possible. Thank you.