Safety, Therapeutic Potential, and Mechanisms of Two Psilocybin Doses, Administered With Psychological Support in Young Adults With Anorexia Nervosa

NCT07169747 | Recruiting Phase 2

• 1 other identifier: 2024-515163-63-00
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anorexia Nervosa

Keywords

Psilocybin; Anorexia Nervosa; Young adults; fMRI; BDNF; Adolescents

Outcome Measures

Primary Outcomes (1)

• 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).

  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.

  From enrollment to the end of trial 12 month post-baseline.

Secondary Outcomes (18)

• 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.

• 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 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

Study Arms (2)

Psilocybin with Psychological Support

ACTIVE COMPARATOR

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.

Drug: Psilocybin

Treatment as Usual

NO INTERVENTION

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.

Interventions

Psilocybin DRUG

The intervention consists of two oral doses of 25 mg synthetic psilocybin administered in a controlled clinical setting, combined with psychological support. The psychological support includes preparatory sessions prior to psilocybin administration, support during the drug experience and integration sessions following each dosing session.

Psilocybin with Psychological Support

Eligibility Criteria

• Age: 16 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of AN per DSM-5
• Have experienced at least one period of remission (minimum BMI 17) followed by a relapse
• Age 16-35
• BMI \>16
• Stable contact with a psychiatric unit
• Ability to provide informed consent

You may not qualify if:

• Psychosis, bipolar disorder, substance use disorder, family history of psychosis or bipolar disorder, refusal of birth control, lifetime psychedelic use, unable to washout ongoing medications\* that would interfere negatively with the study drug
• 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
• 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)
• HT2A-antagonist need two weeks washout

Sponsors & Collaborators

• Region Skane: lead
• Sten Theanders fond: collaborator
• Lions Forskningsfond Skåne: collaborator
• NorrskenMind: collaborator

Study Sites (1)

Psykiatrikliniken, Baravägen 1

Lund, 22240, Sweden

RECRUITING

Related Publications (29)

• Halmi KA, Casper RC, Eckert ED, Goldberg SC, Davis JM. Unique features associated with age of onset of anorexia nervosa. Psychiatry Res. 1979 Oct;1(2):209-15. doi: 10.1016/0165-1781(79)90063-5.

  PMID: 298349 BACKGROUND

• Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, Martell J, Blemings A, Erritzoe D, Nutt DJ. Trial of Psilocybin versus Escitalopram for Depression. N Engl J Med. 2021 Apr 15;384(15):1402-1411. doi: 10.1056/NEJMoa2032994.

  PMID: 33852780 BACKGROUND

• Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, Bird C, Blom RE, Brennan C, Brusch D, Burke L, Campbell-Coker K, Carhart-Harris R, Cattell J, Daniel A, DeBattista C, Dunlop BW, Eisen K, Feifel D, Forbes M, Haumann HM, Hellerstein DJ, Hoppe AI, Husain MI, Jelen LA, Kamphuis J, Kawasaki J, Kelly JR, Key RE, Kishon R, Knatz Peck S, Knight G, Koolen MHB, Lean M, Licht RW, Maples-Keller JL, Mars J, Marwood L, McElhiney MC, Miller TL, Mirow A, Mistry S, Mletzko-Crowe T, Modlin LN, Nielsen RE, Nielson EM, Offerhaus SR, O'Keane V, Palenicek T, Printz D, Rademaker MC, van Reemst A, Reinholdt F, Repantis D, Rucker J, Rudow S, Ruffell S, Rush AJ, Schoevers RA, Seynaeve M, Shao S, Soares JC, Somers M, Stansfield SC, Sterling D, Strockis A, Tsai J, Visser L, Wahba M, Williams S, Young AH, Ywema P, Zisook S, Malievskaia E. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022 Nov 3;387(18):1637-1648. doi: 10.1056/NEJMoa2206443.

  PMID: 36322843 BACKGROUND

• Carbonaro TM, Bradstreet MP, Barrett FS, MacLean KA, Jesse R, Johnson MW, Griffiths RR. Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. J Psychopharmacol. 2016 Dec;30(12):1268-1278. doi: 10.1177/0269881116662634. Epub 2016 Aug 30.

  PMID: 27578767 BACKGROUND

• Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016 Jul;3(7):619-27. doi: 10.1016/S2215-0366(16)30065-7. Epub 2016 May 17.

  PMID: 27210031 BACKGROUND

• Studerus E, Kometer M, Hasler F, Vollenweider FX. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. J Psychopharmacol. 2011 Nov;25(11):1434-52. doi: 10.1177/0269881110382466. Epub 2010 Sep 20.

  PMID: 20855349 BACKGROUND

• Kurtom M, Henning A, Espiridion ED. Hallucinogen-persisting Perception Disorder in a 21-year-old Man. Cureus. 2019 Feb 14;11(2):e4077. doi: 10.7759/cureus.4077.

  PMID: 31019855 BACKGROUND

• Bogenschutz MP, Ross S, Bhatt S, Baron T, Forcehimes AA, Laska E, Mennenga SE, O'Donnell K, Owens LT, Podrebarac S, Rotrosen J, Tonigan JS, Worth L. Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Oct 1;79(10):953-962. doi: 10.1001/jamapsychiatry.2022.2096.

  PMID: 36001306 BACKGROUND

• Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, Jesse R. Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology (Berl). 2011 Dec;218(4):649-65. doi: 10.1007/s00213-011-2358-5. Epub 2011 Jun 15.

  PMID: 21674151 BACKGROUND

• Griffiths RR, Richards WA, McCann U, Jesse R. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology (Berl). 2006 Aug;187(3):268-83; discussion 284-92. doi: 10.1007/s00213-006-0457-5. Epub 2006 Jul 7.

  PMID: 16826400 BACKGROUND

• Johnson M, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008 Aug;22(6):603-20. doi: 10.1177/0269881108093587. Epub 2008 Jul 1.

  PMID: 18593734 BACKGROUND

• Nakazato M, Hashimoto K, Shimizu E, Kumakiri C, Koizumi H, Okamura N, Mitsumori M, Komatsu N, Iyo M. Decreased levels of serum brain-derived neurotrophic factor in female patients with eating disorders. Biol Psychiatry. 2003 Aug 15;54(4):485-90. doi: 10.1016/s0006-3223(02)01746-8.

  PMID: 12915293 BACKGROUND

• Ly C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson PC, Burbach KF, Soltanzadeh Zarandi S, Sood A, Paddy MR, Duim WC, Dennis MY, McAllister AK, Ori-McKenney KM, Gray JA, Olson DE. Psychedelics Promote Structural and Functional Neural Plasticity. Cell Rep. 2018 Jun 12;23(11):3170-3182. doi: 10.1016/j.celrep.2018.05.022.

  PMID: 29898390 BACKGROUND

• Cohen-Cory S, Kidane AH, Shirkey NJ, Marshak S. Brain-derived neurotrophic factor and the development of structural neuronal connectivity. Dev Neurobiol. 2010 Apr;70(5):271-88. doi: 10.1002/dneu.20774.

  PMID: 20186709 BACKGROUND

• Lohof AM, Ip NY, Poo MM. Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature. 1993 May 27;363(6427):350-3. doi: 10.1038/363350a0.

  PMID: 8497318 BACKGROUND

• Siegel JS, Subramanian S, Perry D, Kay B, Gordon E, Laumann T, Reneau R, Gratton C, Horan C, Metcalf N, Chacko R, Schweiger J, Wong D, Bender D, Padawer-Curry J, Raison C, Raichle M, Lenze EJ, Snyder AZ, Dosenbach NUF, Nicol G. Psilocybin desynchronizes brain networks. medRxiv [Preprint]. 2023 Aug 24:2023.08.22.23294131. doi: 10.1101/2023.08.22.23294131.

  PMID: 37701731 BACKGROUND

• Daws RE, Timmermann C, Giribaldi B, Sexton JD, Wall MB, Erritzoe D, Roseman L, Nutt D, Carhart-Harris R. Increased global integration in the brain after psilocybin therapy for depression. Nat Med. 2022 Apr;28(4):844-851. doi: 10.1038/s41591-022-01744-z. Epub 2022 Apr 11.

  PMID: 35411074 BACKGROUND

• Peck SK, Shao S, Gruen T, Yang K, Babakanian A, Trim J, Finn DM, Kaye WH. Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study. Nat Med. 2023 Aug;29(8):1947-1953. doi: 10.1038/s41591-023-02455-9. Epub 2023 Jul 24.

  PMID: 37488291 BACKGROUND

• Foldi CJ, Liknaitzky P, Williams M, Oldfield BJ. Rethinking Therapeutic Strategies for Anorexia Nervosa: Insights From Psychedelic Medicine and Animal Models. Front Neurosci. 2020 Feb 4;14:43. doi: 10.3389/fnins.2020.00043. eCollection 2020.

  PMID: 32116500 BACKGROUND

• MacLean KA, Johnson MW, Griffiths RR. Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. J Psychopharmacol. 2011 Nov;25(11):1453-61. doi: 10.1177/0269881111420188. Epub 2011 Sep 28.

  PMID: 21956378 BACKGROUND

• Carhart-Harris RL, Goodwin GM. The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology. 2017 Oct;42(11):2105-2113. doi: 10.1038/npp.2017.84. Epub 2017 Apr 26.

  PMID: 28443617 BACKGROUND

• Mertens LJ, Preller KH. Classical Psychedelics as Therapeutics in Psychiatry - Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders. Pharmacopsychiatry. 2021 Jul;54(4):176-190. doi: 10.1055/a-1341-1907. Epub 2021 Jan 20.

  PMID: 33472250 BACKGROUND

• Swanson LR. Unifying Theories of Psychedelic Drug Effects. Front Pharmacol. 2018 Mar 2;9:172. doi: 10.3389/fphar.2018.00172. eCollection 2018.

  PMID: 29568270 BACKGROUND

• Halmi KA. Perplexities of treatment resistance in eating disorders. BMC Psychiatry. 2013 Nov 7;13:292. doi: 10.1186/1471-244X-13-292.

  PMID: 24199597 BACKGROUND

• Khalsa SS, Portnoff LC, McCurdy-McKinnon D, Feusner JD. What happens after treatment? A systematic review of relapse, remission, and recovery in anorexia nervosa. J Eat Disord. 2017 Jun 14;5:20. doi: 10.1186/s40337-017-0145-3. eCollection 2017.

  PMID: 28630708 BACKGROUND

• Steinhausen HC. The outcome of anorexia nervosa in the 20th century. Am J Psychiatry. 2002 Aug;159(8):1284-93. doi: 10.1176/appi.ajp.159.8.1284.

  PMID: 12153817 BACKGROUND

• DeJong H, Oldershaw A, Sternheim L, Samarawickrema N, Kenyon MD, Broadbent H, Lavender A, Startup H, Treasure J, Schmidt U. Quality of life in anorexia nervosa, bulimia nervosa and eating disorder not-otherwise-specified. J Eat Disord. 2013 Nov 26;1:43. doi: 10.1186/2050-2974-1-43. eCollection 2013.

  PMID: 24999421 BACKGROUND

• Westmoreland P, Krantz MJ, Mehler PS. Medical Complications of Anorexia Nervosa and Bulimia. Am J Med. 2016 Jan;129(1):30-7. doi: 10.1016/j.amjmed.2015.06.031. Epub 2015 Jul 10.

  PMID: 26169883 BACKGROUND

• Arcelus J, Mitchell AJ, Wales J, Nielsen S. Mortality rates in patients with anorexia nervosa and other eating disorders. A meta-analysis of 36 studies. Arch Gen Psychiatry. 2011 Jul;68(7):724-31. doi: 10.1001/archgenpsychiatry.2011.74.

  PMID: 21727255 BACKGROUND

MeSH Terms

Conditions

Anorexia Nervosa

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Feeding and Eating Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Pouya Movahed Rad, Associate Professor

  Department of Clinical Sciences, Lund University, Sweden

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Sjöström, MD, PhD-student

CONTACT

+46739075390; david.sjostrom@med.lu.se

Olea Schau Rybäck, MD, PhD-student

CONTACT

+46736698415; olea.schau_ryback@med.lu.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor and Senior Consultant in Psychiatry

Model Details: If the psilocybin treatment is determined to be safe, tolerable and preliminarly effective, participants in the control group will have the option to swith to psilocybin treatment (while maintaining their usual specialized care). This will be offered after 6 months post-baseline.

Study Record Dates

• First Submitted: August 21, 2025
• First Posted: September 12, 2025
• Study Start: April 20, 2026
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

SE (1)