MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. Appeared originally in Nat Med 2021; 27:1025-1033.

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study.

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.

A Holistic Self-learning Approach for Young Adult Depression and Anxiety Compared to Medication-Based Treatment-As-Usual.

A package of biopsychosocial services for young adults experiencing psychological distress was evaluated and compared to usual outpatient psychiatric care. Young adults (18-25) with moderate-to-severe symptoms of depression and/or anxiety (n = 26) were enrolled in a 13-week intervention consisting of nutritional coaching and multi-vitamin supplements, weekly educational and peer support groups, and a modest financial stipend to engage with physical or expressive activities. A comparison group (n = 13) continued with their usual medication-based outpatient care. Program participants reported significantly improved depression, anxiety, severity of distress, overall quality of life, and empowerment over 4 months, with progress maintained or further improved at 2-month follow-up. No evidence of change on any outcome was observed for comparison group participants. Although long-term impacts on mental health trajectories and reliance on psychotropic medications remain unknown, a holistic self-learning approach is a viable alternative to standard outpatient psychiatric care for young adults.

Cannabidiol in Anxiety and Sleep: A Large Case Series.

CONTEXT: Cannabidiol (CBD) is one of many cannabinoid compounds found in cannabis. It does not appear to alter consciousness or trigger a "high." A recent surge in scientific publications has found preclinical and clinical evidence documenting value for CBD in some neuropsychiatric disorders, including epilepsy, anxiety, and schizophrenia. Evidence points toward a calming effect for CBD in the central nervous system. Interest in CBD as a treatment of a wide range of disorders has exploded, yet few clinical studies of CBD exist in the psychiatric literature. OBJECTIVE: To determine whether CBD helps improve sleep and/or anxiety in a clinical population. DESIGN: A large retrospective case series at a psychiatric clinic involving clinical application of CBD for anxiety and sleep complaints as an adjunct to usual treatment. The retrospective chart review included monthly documentation of anxiety and sleep quality in 103 adult patients. MAIN OUTCOME MEASURES: Sleep and anxiety scores, using validated instruments, at baseline and after CBD treatment. RESULTS: The final sample consisted of 72 adults presenting with primary concerns of anxiety (n = 47) or poor sleep (n = 25). Anxiety scores decreased within the first month in 57 patients (79.2%) and remained decreased during the study duration. Sleep scores improved within the first month in 48 patients (66.7%) but fluctuated over time. In this chart review, CBD was well tolerated in all but 3 patients. CONCLUSION: Cannabidiol may hold benefit for anxiety-related disorders. Controlled clinical studies are needed.

Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series.

OBJECTIVES: Cannabidiol (CBD) is a non-psychotomimetic cannabinoid compound that is found in plants of the genus Cannabis. Preclinical research has suggested that CBD may have a beneficial effect in rodent models of post-traumatic stress disorder (PTSD). This effect is believed to be due to the action of CBD on the endocannabinoid system. CBD has seen a recent surge in research regarding its potential value in a number of neuro-psychiatric conditions. This is the first study to date examining the clinical benefit of CBD for patients with PTSD. METHODS: This retrospective case series examines the effect of oral CBD administration on symptoms of PTSD in a series of 11 adult patients at an outpatient psychiatry clinic. CBD was given on an open-label, flexible dosing regimen to patients diagnosed with PTSD by a mental health professional. Patients also received routine psychiatric care, including concurrent treatment with psychiatric medications and psychotherapy. The length of the study was 8 weeks. PTSD symptom severity was assessed every 4 weeks by patient-completed PTSD Checklist for the DSM-5 (PCL-5) questionnaires. RESULTS: From the total sample of 11 patients, 91% (n = 10) experienced a decrease in PTSD symptom severity, as evidenced by a lower PCL-5 score at 8 weeks than at their initial baseline. The mean total PCL-5 score decreased 28%, from a mean baseline score of 51.82 down to 37.14, after eight consecutive weeks of treatment with CBD. CBD was generally well tolerated, and no patients discontinued treatment due to side effects. CONCLUSIONS: Administration of oral CBD in addition to routine psychiatric care was associated with PTSD symptom reduction in adults with PTSD. CBD also appeared to offer relief in a subset of patients who reported frequent nightmares as a symptom of their PTSD. Additional clinical investigation, including double-blind, placebo-controlled trials, would be necessary to further substantiate the response to CBD that was observed in this study.

Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report.

INTRODUCTION: Anxiety and sleep disorders are often the result of posttraumatic stress disorder and can contribute to an impaired ability to focus and to demonstration of oppositional behaviors. CASE PRESENTATION: These symptoms were present in our patient, a ten-year-old girl who was sexually abused and had minimal parental supervision as a young child under the age of five. Pharmaceutical medications provided partial relief, but results were not long-lasting, and there were major side effects. A trial of cannabidiol oil resulted in a maintained decrease in anxiety and a steady improvement in the quality and quantity of the patient's sleep. DISCUSSION: Cannabidiol oil, an increasingly popular treatment of anxiety and sleep issues, has been documented as being an effective alternative to pharmaceutical medications. This case study provides clinical data that support the use of cannabidiol oil as a safe treatment for reducing anxiety and improving sleep in a young girl with posttraumatic stress disorder.

Paradigm shift: stages of physicians' entry into integrative practice.

Integrative medicine and psychiatry are more than areas of interest; they represent a clear philosophic paradigm with a wide range of beliefs that separate it from conventional care. A child psychiatrist will typically pass through a developmental trajectory as he or she begins to embrace this approach to patient care, which can be broken down into common stages that represent the incorporation and expression of a new philosophy. This article outlines those common stages of development, and also walks through the process of opening an integrative mental health clinic.

Integrative approaches to pediatric mood disorders.

Mood disorders represent an increasingly common clinical challenge in pediatric care. The movement to an integrative approach provides many benefits. First, the emphasis is on the holistic assessment of the whole child or teen. As we embrace the ecological nature of human existence, this broad perspective enables us to see the child more comprehensively and thus to treat him or her more effectively. This allows us to grasp the barriers, triggers, strengths, and challenges for each young person. The integrative practitioner focuses more on symptom pattern than on DSM diagnosis. A whole-child approach naturally de-emphasizes labels and limitations of our diagnostic system. We can fully support the self-healing capacity of the child's ecosystem as it relates to body, mind, and spirit. The integrative practitioner actively seeks to avoid risky and unproven pharmacological interventions if possible..,This more cautious and natural approach is desired by many parents who embrace the holistic-integrative philosophy. This can be thought of as a significant and growing American subculture. As culturally sensitive practitioners, it is crucial that we work with children, teens, families, and parents within their belief systems. The last 2 decades have seen a dramatic rise in the number of children given psychiatric medications. If current rates persist, within a generation, half of American children will be taking psychiatric medication. Many reasons for this pattern exist. Integrative practitioners can offer a variety of safe and effective alternatives for the child or teen struggling with a mood disorder. The greatest benefit comes from seeing a child fulfill his or her true potential.

Treating the whole child: An interview with Scott Shannon, MD. Interview by Nancy Nachman-Hunt.

Scott Shannon, MD, is an assistant clinical professor of psychiatry in the Integrative Health Clinic at the University of Colorado Children's Hospital in Denver. He is board certified in general and child/adolescent psychiatry and is a founding member of the American Holistic Medical Association, where he served as president from 2001 to 2002. He is a graduate of the University of Arizona Medical School, where he was influenced by renowned holistic medicine practitioner Andrew Weil, MD, who became a mentor. Dr Shannon also is a graduate of the UCLA College of Medicine's Medical Acupuncture Course and has practiced general medicine in a rural setting. He is editor of Handbook of Complementary and Alternative Treatments in Mental Health (Academic Press, 2002), the first textbook on alternative therapies in this field, and Please Don't Label My Child (Rodale Press, 2007). Dr Shannon maintains a private practice in Fort Collins, Colorado.

Complementary and alternative medicine therapies to promote healthy moods.

Pediatric mood disorders (unipolar depression and bipolar disorder) are serious, common, persistent, and recurrent medical conditions. Depression is the second leading cause of illness and disability among young people worldwide. A healthy lifestyle and healthy environment are the cornerstones for promoting positive moods. In addition, several complementary therapies, including nutritional supplements, herbs, mind-body therapies, massage, and acupuncture can be helpful. The focus of this article is the fundamental lifestyle approaches and complementary therapies that enhance mental health in young people. Various resources are available to clinicians to help patients and families promote mental health.

Spirituality and end-of-life care.

As dying patients adjust to the irreversible nature of their illness, their needs and focus of care changes. Spiritual issues may become a central concern for them, and addressing these issues can be key to relieving suffering. Physicians, unfortunately, have little training in this area and are often uncomfortable discussing spirituality. In this article, we address the role of spirituality in end-of-life care, and discuss a format for spiritual assessment. We hope this will encourage more comprehensive patient-centered, end-of-life care.