TABLE 2

Clinical trials available on ClinicalTrials.gov investigating the use of psilocybin as a potential therapeutic approach for MDD and other psychiatric disorders

For completed trials, the references of the published work were added if available either from the ClinicalTrials.gov web site or PubMed upon searching the NCT identifier. If information was available on the main findings of the study, it was added. If the trial was not completed or it was completed but no information was available in the form of a published original manuscript, we reported the main research question(s) the study aims to address.

CompoundCohortRegimenResearch Question/Main FindingsStatusReference
PsilocybinMajor depressive disorderFirst session: 0.3 mg/kg, orally; second session (after 2 wk from first): 0.45 mg/kg, orally; third session (after 4 wk from second): 0.6 mg/kg, orallyPharmacokinetics study. No physical or psychological adverse events within 30 days of any dose. The dose of 0.6 mg/kg might be in excess of therapeutic dose. No psilocybin found in plasma or urine. Renal clearance of intact psilocin 2%. No dose reduction needed for subjects with mild to moderate renal impairment. High-dose psilocybin is associated with positive subjective effects in healthy volunteersCompletedClinicalTrials.gov identifier: NCT02163707 (Brown et al., 2017b; Nicholas et al., 2018)
PsilocybinTreatment-resistant depressionFirst session: 10 mg; second session: 25 mg (7 days apart)Treatment is well tolerated. No major adverse events. Transient anxiety, confusion, mild nausea, and headache. Psychological support recommended before, during, and after the session. Depressive symptoms reduced 1 wk, 5 wk, and 3 mo after psilocybin. Marked improvements in anxiety and anhedonia. Quality of the acute experience predicts the reduction in depressive scoresCompletedCarhart-Harris et al., 2016a, 2018
PsilocybinTreatment-resistant depressionFirst session: 10 mg; second session: 25 mg (7 days apart)Psilocybin (post-treatment) decreases cerebral blood flow in the temporal cortex and amygdala. Decreased amygdala activity correlates with the antidepressant effect of psilocybin. Increased functional connectivity between ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex and decreased functional connectivity between parahippocampus-PFC predicts treatment response at 5 wkCompletedCarhart-Harris et al., 2017
PsilocybinTreatment-resistant depressionFirst session: 10 mg; second session: 25 mg (7 days apart)Increased emotional responses to happy and fearful faces in the right amygdala after treatment. Psilocybin revives emotional responsiveness in patients with TRDCompletedRoseman et al., 2018
PsilocybinTreatment-resistant depressionFirst session: 10 mg; second session: 25 mg (7 days apart)Psilocybin treatment decreases authoritarianism and increases nature relatednessCompletedLyons and Carhart-Harris, 2018
PsilocybinMajor depressive disorder0.215 mg/kg, orally, onceEffects on depressive symptoms and brain functioning (fMRI)RecruitingClinicalTrials.gov identifier: NCT03715127
PsilocybinMajor depressive disorder25 mg, orally, oncePotential efficacy of a single 25-mg oral dose of psilocybin for MDDRecruitingClinicalTrials.gov identifier: NCT03866174
PsilocybinMajor depressive disorder0.1 and 0.3 mg/kg, orally, twiceAssess whether psilocybin enhances neuroplasticity in MDD patients (EEG + long-term potentiation task)RecruitingClinicalTrials.gov identifier: NCT03554174
PsilocybinMajor depressive disorder25 mg, orally, onceLong-term (up to 24 mo) follow-up study of patients with MDD who previously received psilocybinEnrolling by invitationClinicalTrials.gov identifier: NCT04353921
PsilocybinMajor depressive disorderModerate/high dose (dose N/A)Acute and persisting effects of psilocybin on depressive symptoms and other moods, attitudes, and behaviorActive, not recruitingClinicalTrials.gov identifier: NCT03181529
PsilocybinMajor depressive disorderMultiple dosing days (dose and frequency N/A)Comparing antidepressant action and mechanisms of action of psilocybin and the SSRI escitalopram (fMRI)Active, not recruitingClinicalTrials.gov identifier: NCT03429075
PsilocybinMajor depressive disorder25 mg, orally, onceLong-term therapeutic effects of psilocybin (fMRI, peripheral gene expression and molecules as predictor biomarkers of treatment outcome)Not yet recruitingClinicalTrials.gov identifier: NCT03380442
PsilocybinMDD with mild cognitive impairment or early Alzheimer diseaseFirst session: 15 mg/70 kg; second session (2 wk after): 15 or 25 mg/70 kgSafety and efficacy of psilocybin given under supportive conditions in depressed people with MCI or early AD. Follow-up assessment of long-term therapeutic effectsRecruitingClinicalTrials.gov identifier: NCT04123314
Treatment-Resistant Depression
PsilocybinTreatment-resistant depressionLow, medium, high dose (dose and frequency N/A)Safety and efficacy of psilocybin in patients with TRDRecruitingClinicalTrials.gov identifier: NCT03775200
Alcohol, Tobacco, and Substance Use Disorder
PsilocybinAlcohol use disorder0.3–0.4 mg/kg, orally, twiceAbstinence increased after psilocybin. Gains maintained at 36 wk. Experience intensity in the first psilocybin session predicts decreases in drinking and craving and increases in abstinence. No significant treatment-related adverse eventsActive, not recruitingClinicalTrials.gov identifier: NCT02061293 (Bogenschutz et al., 2015; Nielson et al., 2018)
PsilocybinAlcohol use disorder25 mg, orally, onceClinical and mechanistic effects of psilocybin in patients with alcohol addiction (3- and 6-mo follow-up)Not yet recruitingClinicalTrials.gov identifier: NCT04141501
PsilocybinOpioid use disorderTwo doses 4 wk apart, orally (dose N/A)Psilocybin augmentation of buprenorphine/naloxone maintenance therapy for OUD with guided counseling. Assess changes in pain and life qualityNot yet recruitingClinicalTrials.gov identifier: NCT04161066
PsilocybinTobacco use disorder20 and 30 mg/70 kg, onceComparing psilocybin to transdermal nicotine patch in individuals seeking to quit smoking (3-, 6-, and 12-mo follow-up). Previous trial: 80% abstinence after 7 days, 67% abstinence at 12- mo follow-up. Psilocybin experiences among the five most personally meaningful and spiritually significant experiences of participants’ livesRecruitingClinicalTrials.gov identifier: NCT01943994 (Garcia-Romeu et al., 2014; Johnson et al., 2014, 2017)
PsilocybinCocaine use disorder0.36 mg/kg, orally, onceFeasibility and efficacy of psilocybin-facilitated treatment of cocaine use. Impact of psilocybin-facilitated treatment on other drug use and outcomes relevant to cocaine involvement (such as criminal involvement). Default mode network changes investigated by fMRIRecruitingClinicalTrials.gov identifier: NCT02037126
Obsessive-Compulsive Disorder
PsilocybinObsessive-compulsive disorder0.25 mg/kg, orally, onceInvestigate neural mechanisms underpinning OCD symptom improvements by psilocybin (fMRI)RecruitingClinicalTrials.gov identifier: NCT03356483
PsilocybinObsessive-compulsive disorder0.1 and 0.3 mg/kg, orally, once weekly for 8 wkSafety, tolerability, and mechanism of action of psilocybin (and the anxiolytic lorazepam) as OCD treatments. Functional connectivity changes between the caudate nucleus and orbital frontal cortexRecruitingClinicalTrials.gov identifier: NCT03300947 (Moreno et al., 2006)
Patients with Cancer
PsilocybinPotentially life-threatening cancer1–3 or 22–30 mg/kg, orally, twicePsilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer. Improved quality of life, life meaning, and optimism and decreases in death anxiety. Changes sustained at 6-mo follow-up in 80% of participants. Improvements in attitudes about life/self, mood, relationships, and spirituality. Increased well-being/life satisfactionCompletedClinicalTrials.gov identifier: NCT00465595 (Griffiths et al., 2016)
PsilocybinPotentially life-threatening cancer0.2 mg/kg, orally, onceReduction in anxiety scores at 1 and 3 mo and improvements in depression scores at 6 moCompletedClinicalTrials.gov identifier: NCT00302744 (Grob et al., 2011)
PsilocybinPotentially life-threatening cancer0.3 mg/kg, orally, onceImmediate, substantial, and sustained improvements in anxiety and depression. Decreases in cancer-related demoralization and hopelessness, improved spiritual well-being, and increased quality of life. Enduring anxiolytic and antidepressant effects and reductions in depression and anxiety at 6-mo follow-up in 60%–80% of patients. Sustained benefits in existential distress and quality of life and improved attitudes toward death. Psilocybin-occasioned mystical experiences mediate the therapeutic effects on anxiety and depressionActive, not recruitingClinicalTrials.gov identifier: NCT00957359 (Ross et al., 2016)
Others
PsilocybinAnorexia nervosaFirst session: the lesser of 20 mg or 0.6 mg/kg; second session: the lesser of 25 mg or 0.6 mg/kg.Assess the safety and efficacy of moderate- to high-dose psilocybin in people suffering from AN. Assess whether long-term positive behavioral changes (eating habits, anxiety, and depression) can be elicited in a supportive setting with close follow-up. Assess whether psilocybin decreases eating disorder pathophysiologyRecruitingClinicalTrials.gov identifier: NCT04052568
PsilocybinAIDS survivorsOnce, orally (dose N/A)Safety, tolerability, and feasibility of psilocybin-assisted group therapy for demoralization in long-term AIDS survivors. Effects on demoralization, complicated grief, anxiety, life quality, functional social support, post-traumatic growth, openness to experience, mindfulness, social connection, nature relatedness, and medication adherenceCompletedClinicalTrials.gov identifier: NCT02950467
PsilocybinLong-term meditatorsOnce or twice, dose manipulation (dose N/A)Characterize performance of tasks, brain functioning, and the effects of psilocybin in long-term meditators. Psychological function, behavioral and cognitive tasks, brain resting-state functional connectivityCompletedClinicalTrials.gov identifier: NCT01988311
PsilocybinLong-term meditatorsVery low dose, moderately low dose, moderately high dose (dose N/A)Acute and persisting effects of psilocybin on meditation, spirituality, health, well-being, prosocial attitudes, and brain functioning (fMRI)CompletedClinicalTrials.gov identifier: NCT02145091
Religious Professional Leaders
PsilocybinReligious professional leadersFirst session: 20 mg/70 kg, orally; second session: 20 or 30 mg/70 kg, orallyUtility of psilocybin for professional religious leaders. Further understanding of mystical-type experiences. Changes in psychological functioning, spirituality, health, well-being, and prosocial attitudesRecruitingClinicalTrials.gov identifier: NCT02421263
PsilocybinReligious professional leadersFirst session: 20 mg/70 kg, orally; second session: 20 or 30 mg/70 kg, orallyEffects and utility of psilocybin-facilitated experiences for professional religious leadersRecruitingClinicalTrials.gov identifier: NCT02243813
Healthy Volunteers
PsilocybinHealthy volunteers25 mg/70 kg, orally, onceReduction of negative affect and amygdala response to facial affect stimuli at 1 wk postpsilocybin. Increase in positive affect and dorsal lateral prefrontal and medial orbitofrontal cortex responses to emotionally conflicting stimuli after 1 wk. Negative affective and amygdala response to facial affect stimuli back to baseline after 1 mo, whereas positive affect remains elevated, and trait anxiety reduced. Increased resting-state functional connectivity at 1 wk and 1 mo postpsilocybin. Psilocybin may increase emotional and brain plasticity, and negative affect may be targeted with psilocybinCompletedClinicalTrials.gov identifier: NCT02971605 (Barrett et al., 2020)
PsilocybinHealthy volunteers2 mg by i.v. infusion, onceProfound changes in consciousness. Decreased BOLD fMRI signals in thalamus, anterior and posterior cingulate cortex, and mPFC. Decrease in positive coupling between the mPFC and PCC. Psychedelics may induce a state of “unrestrained cognition”CompletedCarhart-Harris et al., 2012
PsilocybinHealthy volunteers2 mg by i.v. infusion, oncePsilocybin increases DMN-TPN functional connectivity, as observed in psychosis and meditative states. Thalamocortical functional connectivity not affectedCompletedCarhart-Harris et al., 2013
PsilocybinHealthy volunteers2 mg by i.v. infusion, onceDuring the psychedelic state, the brain biases a mode of whole-brain functional integration at the expense of local networksCompletedBioRxiv 10.1101/376491v1
PsilocybinHealthy volunteers2 mg by i.v. infusion, onceThe subjective effects of psilocybin might arise as a result of cortical oscillatory rhythm desynchronization, potentially arising from the stimulation of deep-layer 5-HT2A receptors on pyramidal neuronsCompletedMuthukumaraswamy et al., 2013
PsilocybinHealthy volunteers2 mg by i.v. infusion, onceAssociation between ego dissolution and decreased functional connectivity between medial temporal lobe and high-level cortical regions. Ego dissolution also associated with “disintegration” of the salience network and reduced interhemispheric communicationCompletedLebedev et al., 2015
PsilocybinHealthy volunteers2 mg by i.v. infusion, onceIncreased between-network resting-state functional connectivityCompletedRoseman et al., 2014
PsilocybinHealthy volunteers30 mg/70 kg, oncePsilocybin increases measures of mystical experience. Psilocybin experience has substantial personal meaning and spiritual significance. Sustained positive changes in attitudes and behavior attributed to the experience. Around 60% of participants rate their psilocybin experience among the most significant and spiritual in their livesCompletedClinicalTrials.gov identifier: NCT00802282 (Griffiths et al., 2006, 2008)
PsilocybinHealthy volunteers10–20–30 mg/70 kg (low, moderate, and high dose, respectively)Dose-dependent effects of psilocybin on psychomotor performance, working memory, episodic memory, associative learning, and visual perception. No delirium or global cognitive impairment observedCompletedClinicalTrials.gov identifier: NCT02033707 Barrett et al., 2018
PsilocybinHealthy volunteers15–20–30 mg, orally, onceCompare altered states of consciousness induced by psilocybin, LSD, and mescalineRecruitingClinicalTrials.gov identifier: NCT03604744, NCT04227756
PsilocybinHealthy volunteers25 mg, orally, onceEffects of SERT inhibition (escitalopram) on the subjective response to psilocybin in healthy subjectsRecruitingClinicalTrials.gov identifier: NCT03912974
PsilocybinHealthy volunteersN/AApplication of PCI based on IIT. Combination of transcranial magnetic stimulation and high-density electroencephalography to measure electrocortical responses as distributed cerebral interactions (integration) and spatiotemporal pattern (information)RecruitingClinicalTrials.gov identifier: NCT03853577
PsilocybinHealthy volunteers0.2–0.215–0.315 mg/kg, orally, onceNeuropharmacological mechanisms underlying ego dissolution. Integration of functional connectivity in sensory regions and disintegration in associative regions may underlie the psychedelic stateActive, not recruitingClinicalTrials.gov identifier: NCT03736980 (Preller et al., 2020)
  • AD, Alzheimer’s disease; AIDS, acquired immunodeficiency syndrome; AN, anorexia BOLD, blood oxygen level–dependent; EEG, electroencephalogram; fMRI, functional magnetic resonance imaging; IIT, integrated information theory; MCI, mild cognitive impairment; NCT, ClinicalTrials.gov identifier; N/A, not available; OUD, opioid use disorder; PCI, perturbational complexity index; TPN, task-positive network; TRD, treatment-resistant depression.