The Therapeutic Potential of Psilocybin in Anorexia Nervosa in Young Adults
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Region Skane
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- To assess the safety and tolerability of psilocybin 25 mg in young adults with anorexia nervosa, as measured by incidence of adverse events (AEs) and serious adverse events (SAEs).
研究概览
简要总结
The goal of this clinical trial is to learn if psilocybin, given with psychological support, is safe and helps treat anorexia nervosa in young adults. Anorexia nervosa is a serious eating disorder that currently has no approved medicine. Psilocybin is a psychedelic substance that may help the brain form new connections, which could make it easier for people with anorexia nervosa to develop healthier ways of thinking.
The main questions this study aims to answer are:
- Is psilocybin with psychological support safe and well-tolerated?
- Does psilocybin with psychological support help lower symptoms of anorexia nervosa?
- How might psilocybin work in the brain to support recovery from anorexia?
This study will compare psilocybin with psychological support to Treatment as Usual (TAU). Participants in the study will be randomly placed into one of the two groups. There will be 40 patients with anorexia nervosa included, 20 per group. TAU includes the standard care people receive for anorexia nervosa in a specialized eating disorder clinic in Region Skåne, Sweden.
Participants will:
- Be between 16 and 35 years old and have anorexia nervosa
- Take psilocybin (25 mg) by mouth two times, four weeks apart
- Receive psychological support before, during, and after each dosing session (including preparation and integration sessions)
- Complete questionnaires, have brain scans (magnetic resonance imaging) and blood tests to learn more about how psilocybin may work
- Share their personal experiences as part of a qualitative interview
This study hopes to learn if psilocybin, when given with the right support, can be a helpful and safe option for people living with anorexia nervosa.
详细描述
Background and Rationale Anorexia Nervosa (AN) is one of the most lethal psychiatric disorders, with mortality rates approximately five times higher than that of the general population. AN affects multiple organ systems due to severe weight loss and malnutrition and hence leads to a substantial decline in health-related quality of life. While psychotherapies have shown partial efficacy, data suggest that only 46% of patients recover within four years, and 20% remain chronically ill. Relapse rates exceed 50% among those who recover, underscoring the need for more effective treatments. Research suggests that several psychological factors, such as challenges in regulating emotions, black-and-white thinking, mental rigidity, and a limited capacity for mentalization may contribute to the persistence of severe, chronic anorexia nervosa. The age of onset for AN typically shows a bimodal distribution, peaking at 14 and 18 years of age, motivating the design of including patients as young as 16 years old in this study.
Psilocybin, a serotonergic psychedelic compound, primarily acts as an agonist of the 5-HT2A receptor, inducing profound effects on cognition, emotion, perception, and self-awareness. Although research on psilocybin remains limited, clinical trials across psychiatric disorders suggest its potential therapeutic benefit. For example personality changes such as increased openness, have been observed to persist up to a year following a single high dose. The inclusion of 16-17-year-olds in this study is particularly novel, as research on psychedelic therapy in adolescents and young adults remains scarce.
Emerging evidence highlights how psychedelics may benefit AN patients, such as enhanced serotonin signaling and cognitive flexibility. The ability of psychedelics to foster cognitive flexibility, a well-documented phenomenon, is considered a key factor in therapeutic processes. This is especially relevant for AN, where rigid thinking and behavior contribute to treatment resistance. One pilot study demonstrated that a 25 mg psilocybin dose, combined with psychological support, was well-tolerated by female AN patients with a body mass index (BMI) >16. The study reported significant reductions in eating disorder symptoms at one month post-treatment, with only mild and transient adverse events.
Recent studies indicate that psilocybin induces significant changes in brain function and network organization across key regions. Notably, psilocybin disrupts connectivity in the default mode network by causing desynchronization across spatial scales. These findings suggest a neurobiological basis for psilocybin´s therapeutic effect. However, further research is needed to elucidate long-term effects, particularly in clinical context. Functional magnetic resonance imaging (fMRI) has demonstrated utility in detecting neuronal abnormalities in AN. This study's use of fMRI before and after psilocybin treatment will provide critical insights into the neurobiological impacts of psilocybin on AN.
Brain-Derived Neurotrophic Factor (BDNF) is a protein that plays a crucial role in neuroplasticity. Preclinical studies show that psilocybin promotes neuritogenesis and synaptic plasticity, potentially via increased cortical BDNF expression. Given that individuals with AN exhibit reduced serum BDNF levels, this study will assess changes in BDNF pre- and post-treatment to elucidate psilocybin's impact on neurobiological mechanisms. These insights may advance treatment optimization and efficacy predictions for AN patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of AN per DSM-5, including anorexia nervosa in partial remission.
- •Have experienced at least one period of weight restoration to a minimum BMI of 17 followed by subsequent weight loss.
- •Age 16-35
- •Stable contact with a psychiatric unit
- •Ability to provide informed consent
排除标准
- •Psychosis, bipolar disorder, substance use disorder, family history of psychosis or bipolar disorder, refusal of birth control, lifetime psychedelic use.
- •Cardiovascular conditions
- •Resting systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg at screening or baseline
- •Clinically significant arrhythmias, tachycardia and QT prolongation
- •History of stroke, myocardial infarction, or other significant cardiovascular events
- •Seizure disorders or history of epilepsy
- •Diabetes mellitus, positive drug tests, suicidal intent, allergy or intolerance to drug content, blood or needle phobia
- •Only for the MRI-part of the study: Metal pieces in the body (contraindicated by fMRI, assessed in each case by MR-technician). Non-compliance to fMRI will not lead to study exclusion
- •Any other clinically significant medical condition that, in the investigator's opinion, may pose a risk to the participant or interfere with study results
- •Care under the Swedish Compulsory Psychiatric Care Act (LPT)
- •Ongoing treatment with medications that have clinically relevant 5-HT2A-receptor antagonistic properties and are therefore expected to directly block or substantially interfere with the pharmacodynamic effects of psilocybin. Such medications require an appropriate washout period prior to psilocybin administration, based on pharmacokinetic properties and clinical judgement. Medications without direct 5-HT2A-antagonistic effects are not excluded on this basis.
- •BMI > 21.0 for ≥ 6 consecutive months within the 12 months prior to screening, as documented in medical records.
研究组 & 干预措施
Treatment as Usual
This arm will receive treatment as usual which includes specialised care offered in an eating disorder unit in Region Skåne, Sweden. If the active treatment arm is determined to be safe, tolerable, and preliminarily effective during the follow-up assessment at 6 months, participants in the control group will have the option to switch to the active treatment while maintaining their usual specialised care.
Psilocybin with Psychological Support
This arm will receive two separate doses of psilocybin 25 mg administered four weeks apart, with psychological support, along side treatment as usual. The psychological support includes preparation sessions before, support during, and integration sessions after psilocybin intake.
干预措施: Psilocybin (Drug)
结局指标
主要结局
To assess the safety and tolerability of psilocybin 25 mg in young adults with anorexia nervosa, as measured by incidence of adverse events (AEs) and serious adverse events (SAEs).
时间窗: From first dosing to the end of trial 12 month post-baseline.
Adverse events (AEs) refers to any unwelcome medical occurrence in a patient who has been administered psilocybin or TAU, which may not necessarily be caused by the treatment. Serious Adverse Event (SAE) includes any medical incident or effect, irrespective of dosage, that a) leads to death, b) is life-threatening, c) necessitates hospitalization, or d) results in persistent or significant disability or incapacity. Events will be assessed by the clinical team for causality, intensity, and seriousness and potential relationship to treatment (psilocybin or TAU). All AEs will be categorized based on their severity and likelihood of treatment attribution.
次要结局
- To evaluate the efficacy of two doses of psilocybin, administred with psychological support, in reducing AN symptoms compared to TAU, as measured by time to response, time to remission and time to relapse.(Efficacy will be evaluated during the 12-month follow-up.)
- To conduct a qualitative analysis of how participants, their relatives, and therapists experience and perceive the intervention(Assessments will be preformed at different timepoints during the 12-month follow-up.)
- To assess changes in symtoms of depression before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 12-month follow-up)
- To assess changes in symtoms of anxiety before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 12-month follow-up.)
- To assess changes in eating disorder symptoms before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 12-month follow-up.)
- To assess changes in suicidal ideation and behavior before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 12-month follow-up.)
- To assess changes in psychiatric symptom severity before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 12-month follow-up.)
- To assess changes in life satisfaction before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 6-month follow-up.)
- To assess changes in positive and negative affect before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 6-month follow-up.)
- Assess potential mechanisms of action through neuroimaging (fMRI), before and after the two-dose psilocybin treatment, administered with psychological support(fMRI will be preformed at baseline (week 0), after first dosing (week 1) and at primary endpoint (week 8).)
- Changes in serum brain-derived neurotrophic factor (BDNF) levels from before and after treatment with two doses of 25 mg psilocybin, administered with psychological support.(BDNF samples will be taken at five key time points: (1) before treatment (baseline), (2) and (3) at first integration session after Psilocybin 25mg dosing, (4) at 8 weeks, and (5) during the 6-month follow-up.)
- To evaluate changes in the metric assessment of perceived body size.(Metric assessment of body size perception will be conducted at baseline, at the primary endpoint, and at the 6-month follow-up.)
- Changes in serum brain-derived neurotrophic factor (BDNF) levels from before and after treatment with two doses of 25 mg psilocybin, administered with psychological support.(BDNF will be measured at baseline (week 0), after second dosing (week 4), at primary end point (week 8) and at 6-month follow-up)
- To conduct a qualitative analysis of how participants, their relatives, and therapists experience and perceive the intervention(Assessments will be preformed at different timepoints during the 12-month follow-up.)
- To assess changes in eating disorder symptoms before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 12-month follow-up.)
- To assess changes in suicidal ideation and behavior before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 12-month follow-up.)
- To assess changes in symtoms of anxiety before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 12-month follow-up.)
- To assess changes in life satisfaction before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 6-month follow-up.)
- To evaluate the efficacy of two doses of psilocybin, administred with psychological support, in reducing AN symptoms compared to TAU, as measured by time to response, time to remission and time to relapse.(Efficacy will be evaluated during the 12-month follow-up.)
- To assess changes in symtoms of depression before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 12-month follow-up)
- To assess changes in psychiatric symptom severity before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 12-month follow-up.)
- To assess changes in positive and negative affect before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 6-month follow-up.)
- To assess changes in harmony in life before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 6-month follow-up.)
- To assess changes in personality traits before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 12-month follow-up.)
- To assess changes in general change mechanisms before and after two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Changes will be assessed at baseline and then repeatedly within the 6-month follow-up.)
- Change in dark personality traits measured by the Honesty-Humility Scale (HH) before and after two psilocybin dosing sessions with psychological support in young adults with anorexia nervosa(Changes will be assessed at baseline and then repeatedly within the 6-month follow-up.)
- To assess how treatment expectation affect outcomes of two-doses of psilocybin, administered with psychological support, in young adults with anorexia nervosa.(Treatment expectations will be measured at baseline with the Expectation for Treatment Scale - Brief Form (ETS-BF).)
- Readiness and motivation for change assessed by the RMQ before and after two psilocybin doses with psychological support in young adults with anorexia nervosa(Changes will be assessed at baseline and then repeatedly within the 6-month follow-up.)
研究者
Pouya Movahed Rad
Associate Professor and Senior Consultant in Psychiatry
Region Skane