What is needed for the roll-out of psychedelic treatments?

PURPOSE OF REVIEW: The pace of psychedelic treatments continues to increase. Regulation and coherent clinical guidance have not been established. A philosophical divide limits effective resolution of a practice delivery quandary: is this primarily a pharmacological or psychotherapeutic intervention? RECENT FINDINGS: Lykos (formerly MAPS) has submitted its new drug application (NDA) request to the FDA for 3-4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for PTSD and is expecting a response by the summer of 2024. Australia endorsed psilocybin and MDMA for regulated use in 2023. Multiple phase II and III clinical trials are also being conducted in the United States and Europe to study the use of psilocybin. Currently, Colorado and Oregon have legalized psilocybin in different manners. In Colorado, plants containing psilocybin, ibogaine, dimethyltryptamine (DMT) and mescaline (other than peyote) are now legal to possess, share and cultivate. Guidelines for regulated treatment with psilocybin containing mushrooms are in process with service delivery to begin early in 2025. In Oregon, clients must complete a preparation session with a licensed facilitator before consuming psilocybin products at a licensed service center. A prescription is not required. It is expected that other states will follow suit with a ballot measure likely in Massachusetts this year. Additionally, in the United States, the DEA, state boards, pharmaceutical distributors, and professional liability carriers all share mounting concerns about the in-home use of compounded ketamine used as a psychedelic therapeutic via remote prescribing. SUMMARY: Psychedelic treatments are rapidly entering the mainstream of medical care delivery in the United States. Clinical guidelines are urgently needed to ensure well tolerated practice and coherent regulation. The delivery of this guidance is limited by a core philosophical disagreement. Resolution of this conflict will be needed to deliver coherent clinical guidelines. Current research and clinical experience provide a solid foundation for practical clinical guidance and the introduction of psychedelics into healthcare.

Ketamine-Assisted Group Psychotherapy for Frontline Healthcare Workers with COVID-19-Related Burnout and PTSD: A Case Series of Effectiveness/Safety for 10 Participants.

This study reports on 10 frontline healthcare workers, employed during the COVID-19 pandemic and experiencing symptoms of burnout and PTSD, treated with group ketamine-assisted psychotherapy (KAP) in a private outpatient clinic setting. Participants attended 6 sessions once weekly. These included 1 preparation session, 3 ketamine sessions (2 sublingual, 1 intramuscular), 2 integration sessions. Measures of PTSD (PCL-5), depression (PHQ-9), and anxiety (GAD-7) were administered at baseline and post-treatment. During ketamine sessions, the Emotional Breakthrough Inventory (EBI) and the 30-item Mystical Experience Questionnaire (MEQ-30) were recorded. Participant feedback was gathered 1-month post-treatment. We observed improvements in participants' average PCL-5 (59% reduction), PHQ-9 (58% reduction), and GAD-7 (36% reduction) scores from pre- to post-treatment. At post-treatment, 100% of participants screened negative for PTSD, 90% had minimal/mild depression or clinically significant improvement, and 60% had minimal/mild anxiety or clinically significant improvement. MEQ and EBI scores had large variations among participants at each ketamine session. Ketamine was well tolerated, and no significant adverse events were reported. Participant feedback corroborated findings of improvements observed in mental health symptoms. We found immediate improvements treating 10 frontline healthcare workers experiencing burnout, PTSD, depression, and anxiety using weekly group KAP and integration.

MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial.

This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51). Overall, 26.9% (28/104) of participants had moderate PTSD, and 73.1% (76/104) of participants had severe PTSD. Participants were ethnoracially diverse: 28 of 104 (26.9%) identified as Hispanic/Latino, and 35 of 104 (33.7%) identified as other than White. Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was -23.7 (-26.94, -20.44) for MDMA-AT versus -14.8 (-18.28, -11.28) for placebo with therapy (P < 0.001, d = 0.7). LS mean change in SDS score (95% CI) was -3.3 (-4.03, -2.60) for MDMA-AT versus -2.1 (-2.89, -1.33) for placebo with therapy (P = 0.03, d = 0.4). Seven participants had a severe treatment emergent adverse event (TEAE) (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 2 (3.9%)). There were no deaths or serious TEAEs. These data suggest that MDMA-AT reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD and was generally well tolerated. ClinicalTrials.gov identifier: NCT04077437 .

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.

Resting State EEG Correlates of Suicide Ideation and Suicide Attempt.

Suicide is a global phenomenon that impacts individuals, families, and communities from all income groups and all regions worldwide. While it can be prevented if personalized interventions are implemented, more objective and reliable diagnostic methods are needed to complement interview-based risk assessments. In this context, electroencephalography (EEG) might play a key role. We systematically reviewed EEG resting state studies of adults with suicide ideation (SI) or with a history of suicide attempts (SAs). After searching for relevant studies using the PubMed and Web of Science databases, we applied the PRISMA method to exclude duplicates and studies that did not match our inclusion criteria. The selection process yielded seven studies, which suggest that imbalances in frontal and left temporal brain regions might reflect abnormal activation and correlate with psychological distress. Furthermore, asymmetrical activation in frontal and posterior cortical regions was detected in high-risk depressed persons, although the pattern in the frontal region was inverted in non-depressed persons. The literature reviewed suggests that SI and SA may be driven by separate neural circuits and that high-risk persons can be found within non-depressed populations. More research is needed to develop intelligent algorithms for the automated detection of high-risk EEG anomalies in the general population.

Far migration of an intrauterine contraceptive device from the uterus to the small bowel.

A sexually active, asymptomatic 44-year-old presented for Intrauterine device (IUD) removal that had been in place for 13 years. IUD removal was unsuccessful as the strings could not be located. Imaging revealed an extrauterine IUD and at surgical removal of the abdominal IUD a small bowel perforation requiring bowel resection was required. Uterine perforation is a rare complication of IUD use occurring in approximately 1-1.3 in 1000. Risk factors for perforation include provider inexperience, retroverted uterus, immobile uterus, and myometrial defect from a previous cesarean delivery or myomectomy.

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.

Initiating NTD programs targeting schistosomiasis and soil-transmitted helminthiasis in two provinces of the Democratic Republic of the Congo: Establishment of baseline prevalence for mass drug administration.

BACKGROUND: Schistosomiasis (SCH) and soil-transmitted helminthiasis (STH) are widely distributed in the Democratic Republic of the Congo (DRC) and constitute a serious public health problem. As recommended by the World Health Organization (WHO), before launching mass chemotherapy to control these diseases, parasitological surveys were conducted in sentinel sites in six health zones (HZs) in Bandundu and Maniema provinces. Baseline prevalence and intensity of infection for SCH and STH were determined to establish the appropriate treatment plan using Praziquantel (PZQ) and Albendazole (ALB). METHODS: Parasitological surveys were conducted from April to May 2015 in twenty-six selected sampling units (schools) for baseline mapping in six HZs: Fifty school children (25 females and 25 males) aged 9-15 years were randomly selected per sampling unit. A total of 1300 samples (urine and stool) were examined using haematuria dipsticks, parasite-egg filtration and the point-of-care Circulating Cathodic Antigen (POC-CCA) assay for urine samples and the Kato-Katz technique for stool specimens. RESULTS: Three species of schistosomes (S. mansoni, S. haematobium and S. intercalatum) and three groups of STH (hookworm, Ascaris and Trichuris) were detected at variable prevalence and intensity among the schools, the HZs and the provinces. In Bandundu, no SCH was detected by either Kato-Katz or the POC-CCA technique, despite a high prevalence of STH with 68% and 80% at Kiri and Pendjua HZs, respectively. In Maniema, intestinal schistosomiasis was detected by both Kato-Katz and POC-CCA with an average prevalence by Kato-Katz of 32.8% and by POC-CCA of 42.1%. Comparative studies confirmed the greater sensitivity (and operational feasibility) of the POC-CCA test on urine compared to Kato-Katz examination of stool for diagnosing intestinal schistosomiasis even in areas of comparatively light infections. STH was widely distributed and present in all HZs with a mean prevalence (95% CI) of 59.62% (46.00-65.00%). The prevalence of hookworm, roundworm and whipworm were 51.62% (32.40%-71.50%), 15.77% (0.50%-39.60%) and 13.46 (0.50%-33.20%), respectively. CONCLUSION: This study provided the evidence base for implementing programs targeting SCH and STH in these Health Zones. Observations also reinforce the operational value and feasibility of the POC-CCA test to detect S. mansoni and, for the first time, S. intercalatum infections in a routine NTD program setting.

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.

Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report.

This case study illustrates the use of cannabidiol (CBD) oil to decrease the addictive use of marijuana and provide anxiolytic and sleep benefits. Addiction to marijuana is a chronic, relapsing disorder, which is becoming a prevalent condition in the United States. The most abundant compound in the marijuana, which is called tetrahydrocannabinol (THC), has been widely studied and known for its psychoactive properties. The second most abundant component-CBD-has been suggested to have the medicinal effects of decreasing anxiety, improving sleep, and other neuro-protective effects. The mechanism of action for CBD has been suggested to be antagonistic to the psychoactive properties of THC in many locations within the central nervous system. Such action raises the issue of whether it might be beneficial to use CBD in isolation to facilitate withdrawal of marijuana use. The specific use of CBD for marijuana reduction has not been widely studied. The patient was a 27-y-old male who presented with a long-standing diagnosis of bipolar disorder and a daily addiction to marijuana use. In the described intervention, the only change made to the patient's treatment was the addition of CBD oil with the dosage gradually decreasing from 24 to 18 mg. With use of the CBD oil, the patient reported being less anxious, as well as settling into a regular pattern of sleep. He also indicated that he had not used any marijuana since starting the CBD oil. With the decrease in the dosage to 18 mg, the patient was able to maintain his nonuse of marijuana.

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.

Costs for 'hospital at home' patients were 19 percent lower, with equal or better outcomes compared to similar inpatients.

Hospitals are the standard acute care venues in the United States, but hospital care is expensive and can pose health threats for older people. Albuquerque, New Mexico-based Presbyterian Healthcare Services adapted the Hospital at Home® model developed by the Johns Hopkins University Schools of Medicine and Public Health to provide acute hospital-level care within patients' homes. Patients show comparable or better clinical outcomes compared with similar inpatients, and they show higher satisfaction levels. Available to Medicare Advantage and Medicaid patients with common acute care diagnoses, this program achieved savings of 19 percent over costs for similar inpatients. These savings were predominantly derived from lower average length-of-stay and use of fewer lab and diagnostic tests compared with similar patients in hospital acute care. Hospital at Home advances the Triple Aim of clinical quality, affordability, and exceptional patient experience.

Evaluating treatments in health care: the instability of a one-legged stool.

BACKGROUND: Both scientists and the public routinely refer to randomized controlled trials (RCTs) as being the 'gold standard' of scientific evidence. Although there is no question that placebo-controlled RCTs play a significant role in the evaluation of new pharmaceutical treatments, especially when it is important to rule out placebo effects, they have many inherent limitations which constrain their ability to inform medical decision making. The purpose of this paper is to raise questions about over-reliance on RCTs and to point out an additional perspective for evaluating healthcare evidence, as embodied in the Hill criteria. The arguments presented here are generally relevant to all areas of health care, though mental health applications provide the primary context for this essay. DISCUSSION: This article first traces the history of RCTs, and then evaluates five of their major limitations: they often lack external validity, they have the potential for increasing health risk in the general population, they are no less likely to overestimate treatment effects than many other methods, they make a relatively weak contribution to clinical practice, and they are excessively expensive (leading to several additional vulnerabilities in the quality of evidence produced). Next, the nine Hill criteria are presented and discussed as a richer approach to the evaluation of health care treatments. Reliance on these multi-faceted criteria requires more analytical thinking than simply examining RCT data, but will also enhance confidence in the evaluation of novel treatments. SUMMARY: Excessive reliance on RCTs tends to stifle funding of other types of research, and publication of other forms of evidence. We call upon our research and clinical colleagues to consider additional methods of evaluating data, such as the Hill criteria. Over-reliance on RCTs is similar to resting all of health care evidence on a one-legged stool.

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.