Spring 2020

On the Horizon: Psychedelics for PTSD

Renewed interest in drugs such as LSD and psilocybin for emotional trauma is driving research.

Psychedelics are a class of drugs capable of inducing altered states of consciousness or perception as well as heightened awareness and senses. From the ancient Greek words for “soul” or “mind” and “manifesting,” psychedelics are used to expand the mind. Natural psychedelics from plants and fungus have been used for thousands of years for healing, cultural/religious ceremonies, and spiritual exploration. LSD (lysergic acid diethylamide) and psilocybin (magic mushrooms) are the most well known of the psychedelics, having gained a dangerous reputation in the 1950s and 1960s during early research into therapeutic uses and association with the hippie counterculture. Research studies and funding in the United States stalled in the late 1960s, and LSD and psilocybin were outlawed with the 1970 passing of the Controlled Substances Act.1

Now, there’s renewed interest in psychedelics for treating mental health disorders, as side effects and limited effectiveness of mainstream pharmaceuticals have pushed patients and researchers to advocate for new treatments, especially for posttraumatic stress disorder (PTSD). The fifth most prevalent mental health disorder in the United States, PTSD affects approximately 8% of the US population. During any given year, approximately 8 million adults are living with PTSD. One in 10 veterans who seek health care at a VA hospital are diagnosed with PTSD. More than one-third of those with PTSD have serious functional impairments that are not resolved with existing treatments.

Potential Remedies
There are only two medications approved for PTSD treatment; both are antidepressants that only reduce symptoms, and their effectiveness is limited. Therefore, many with PTSD are treated with a combination of off-label medications and some type of psychotherapy or cognitive therapy. Psychedelic drugs are under investigation for use in conjunction with psychotherapies to better treat PTSD; 3,4-methylenedioxy-methamphetamine (MDMA), better known as ecstasy, is the farthest along in the research pipeline, with clinical trials in patients ongoing for the treatment of PTSD. Other psychedelics under investigation for treating PTSD include psilocybin, ketamine, and ayahuasca.

Each psychedelic seems to have a slightly different mechanism of action and effect on the brain. For example, psilocybin induces introspection, new perspectives, and shifts in how relationships are viewed. MDMA has more of an emotional effect in terms of empathy and openness. Ayahuasca may induce retrieval of traumatic memories. Ketamine, considered a dissociative anesthetic with psychedelic/hallucinogenic properties in low doses, acts on brain receptors and circuitry.2-4 Cannabis is also under investigation for treatment of PTSD, but is not generally classified scientifically as a psychedelic; rather, it is considered psychoactive.

A pioneering organization in psychedelics research is the Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit research and education organization founded in 1986 with a mission to study the medical benefits of psychedelics and cannabis and to promote their legalization and safe use. MAPS efforts helped the New Drug Application for MDMA for PTSD treatment to receive Breakthrough Therapy designation from FDA in August 2017, and the organization is conducting Phase 3 clinical trials to support eventual market approval.

Brad Burge, MA, director of strategic communications for MAPS, notes that MDMA will not be used alone as treatment for PTSD. “It will be used to assist with psychotherapy for PTSD, only in therapeutic settings under the guidance of a trained practitioner.”

Phase 2 trials completed by MAPS included about 100 participants with chronic treatment-resistant PTSD for an average of about 18 years. After two to three sessions of MDMA-assisted psychotherapy, 54% no longer had PTSD at one to two months post treatment; at one-year follow-up, 68% no longer had PTSD (based on standard diagnostic criteria).5 “The ability of MDMA to reduce fear and defensiveness, enhance communication and introspection, and increase empathy and compassion may enhance the effectiveness of psychotherapy,” Burge says. MDMA appears to act as a “therapeutic catalyst” that allows patients to imagine a life without PTSD, facilitates the integration of their past traumas into their current lives, and promotes access to psychotherapeutic and cognitive behavioral therapy tools.4

FDA approval for MDMA-assisted psychotherapy for PTSD is anticipated in late 2021 or early 2022.4

In Practice: Ketamine
Ketamine, the only psychedelic that’s FDA approved for use by mental health providers, is also being used in conjunction with other therapies. A nasal spray formulation of ketamine was approved for treatment-resistant depression in March 2019.

Melanie E. Dillon, MA, LCPC, NCC, CADC, certified holistic cannabis practitioner and owner of Entourage Clinical Services, is a trained ketamine-assisted psychotherapist at The Neuroscience Center in Deerfield, Illinois. She uses the intranasal spray, intramuscular injection, and IV forms of ketamine to treat PTSD, as well as severe anxiety, grief, and substance use disorder in her practice.

Dillon says that ketamine integrates very well with psychotherapy and other therapies, such as transcranial magnetic stimulation (TMS), because patients are able to process information that would otherwise be too painful and triggering without the assistance of psychedelics. “Ketamine has a calming, numbing, and, for some, dissociative effect that allows them to break the mind/body connection—to be able to ‘view’ and process painful events and situations without ‘feeling’ them—in order to break through barriers,” she explains. At higher doses administered with TMS, IV ketamine can “reset” the default mode network in the brain, allowing a break from intrusive thoughts, thought patterns, and memories. Ketamine can also act as an antianxiety agent, allowing patients to release feelings and emotions without a heightened awareness of doing so.

“Disrupting the memories and feelings associated with past trauma allows patients to move through the trauma and on to healing,” Dillon notes. Some patients with PTSD have had breakthroughs in a shorter number of sessions than with traditional therapies, she’s observed. Other therapists refer patients to Dillon and her colleagues for intensive work. “The synergistic effect of combining TMS with IV ketamine has created long-lasting benefits—we’ve followed some patients for two years post treatment, and they have continued to do well,” Dillon says.

Proceeding With Caution
In contrast to cannabis, which is generally used daily, psychedelics are not used on a frequent, daily, or self-administered basis. Psychedelics require a safe setting with trusted and trained professionals, skilled in handling whatever therapeutic needs or side effects (eg, nausea, vomiting) might come up during a session, Dillon cautions. As a mental health professional, she’s concerned that recent decriminalization of psilocybin in some locales could lead to abuse. “I do have concern for the misuse or overuse of substances that have previously only been used in ceremonies or for healing. A certain amount of mental stability is essential to derive positive benefits from a psychedelic experience, since it can be very unpredictable and destabilizing.” Mental health professionals who can evaluate the appropriateness of treatment and provide a safe experience are essential for good outcomes, Dillon emphasizes.

Dillon is excited about recent clinical studies on psychedelics, such as MDMA, psilocybin, and ketamine, that have demonstrated some remarkable results. “Words such as ‘cure’ and ‘remission’ are being used, which is very promising.” While acceptance from the medical and legal communities has been slow, standards of care for use of psychedelics for mental health disorders are being developed to establish guidelines for patient selection and screening, treatment protocols, and follow-up therapy/monitoring for application when additional psychedelics are approved for therapeutic use. “The time has come for the medical community to recognize that methods that have been employed for the last 50-plus years are not effective for a majority of patients. I have patients every day for whom medications are doing little and their dysfunction continues to increase. Alternative methods like psychedelics can have a more immediate, gentle, and long-lasting effect when provided appropriately,” she says.

Numerous studies of psychedelics for treatment of PTSD and other mental health disorders are ongoing there and at other centers in the United States, Europe, Canada, and Israel. Initial results from scientific studies of psychedelic-assisted therapy for those with PTSD show significant clinical improvements with few serious adverse effects. Several researchers in the field of psychedelic medicine have referred to these positive outcomes as “revolutionizing mental health care.”1,4 Research into therapeutic uses of psychedelics received a further huge boost in September 2019 when Johns Hopkins University—the oldest and one of the most highly esteemed research institutions in the United States—established the Johns Hopkins Center for Psychedelic & Consciousness Research—the first dedicated research center for psychedelics ( “We are at the beginning of a new age in health care,” Dillon asserts.

— Jennifer Van Pelt, MA, is a health care researcher and freelance writer in the Lancaster, Pennsylvania, area.


1. Belouin SJ, Henningfield JE. Psychedelics: where we are now, why we got here, what we must do. Neuropharmacology. 2018;142:7-19.

2. Byock I. Taking psychedelics seriously. J Palliat Med. 2018;21(4):417-421.

3. Inserra A. Hypothesis: the psychedelic ayahuasca heals traumatic memories via a sigma 1 receptor-mediated epigenetic-mnemonic process. Front Pharmacol. 2018;9:330.

4. Doblin RE, Christiansen M, Jerome L, Burge B. The past and future of psychedelic science: an introduction to this issue. J Psychoactive Drugs. 2019;51(2):93-97.

5. Mithoefer MC, Feduccia AA, Jerome L, et al. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology (Berl). 2019;236(9):2735-2745.


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