Psilocybin

Researchers are investigating whether the antidepressant effects of N,N-dimethyltryptamine (DMT) in people with major depressive disorder (MDD) come from biological changes like brain plasticity and reduced inflammation or from the psychedelic experience itself. This study focuses on adults diagnosed with moderate to severe depression and compares DMT's effects with and without the psychedelic experience by masking it using sedation with propofol. Participants will be randomly assigned to one of four groups: DMT with sedation, DMT without sedation, placebo with sedation, or placebo without sedation. The DMT or placebo is given as a 20-minute infusion, while sedation with propofol lasts 30 minutes when used. This design allows researchers to understand if the psychedelic experience is necessary for antidepressant effects or if biological mechanisms alone are responsible. During the study, participants will be assessed for changes in depressive symptoms using several scales at various times up to 14 days after treatment. Researchers will also monitor anxiety, quality of life, psychedelic effects, safety events, and biological markers like neuroplasticity and inflammation. The study includes baseline and follow-up evaluations, mood and personality assessments, and sedation level monitoring, offering a thorough picture of DMT's impact on depression over time.

Researchers are studying whether various psychoactive substances can cause experiences similar to those produced by classic psychedelics. This double-blind, placebo-controlled study involves healthy adult volunteers aged 25 to 55 and aims to understand the subjective effects of these substances. The study is sponsored by Johns Hopkins University and includes a randomized design with both participants and staff unaware of the drug given during sessions. Participants may receive one of several psychoactive drugs, including psilocybin, ketamine, dextromethorphan (DXM), dimethyltryptamine (DMT), methylenedioxymethamphetamine (MDMA), delta-9-tetrahydrocannabinol (THC), or an inactive placebo. Doses are oral and limited to amounts safely administered previously in laboratory settings. The study includes up to six experimental drug sessions per participant, preceded by two preparation sessions totaling four hours. After each drug session, participants attend follow-up visits to discuss their experiences. During the study, participants undergo medical and psychiatric screening with blood tests, physical exams, interviews, and questionnaires. Researchers assess the mystical effects of the substances using the Mystical Experience Questionnaire and evaluate drug effects with the Drug Effects Questionnaire at weeks two and seven. The study monitors participant responses closely and continues until December 2027, with healthy volunteers contributing data on the psychedelic-like effects of these substances.

Researchers are studying the feasibility, safety, and effects of psilocybin-assisted psychotherapy on depression and anxiety in people with advanced cancer who are currently receiving maintenance therapy. This Phase 2 trial aims to see if at least 20% of eligible participants agree to join and if 60% complete the two treatment doses. The study also explores improvements in quality of life, psychosocial well-being, functional status, cancer treatment adherence, inflammatory markers, brain function through fMRI, and symptom impact measures. Participants will be randomly assigned to receive either psilocybin (25 mg) or a placebo of 100 mg niacin, both given by mouth. The study includes two doses of treatment, with careful monitoring and assessments before, during, and after these sessions. The trial uses a quadruple-blind design so that participants, caregivers, researchers, and analysts do not know who receives psilocybin or placebo. During the study, participants will attend all treatment and follow-up visits at the cancer center, complete questionnaires and clinical interviews, and undergo brain imaging, blood tests, and immune monitoring. Researchers will track safety and adverse events throughout the approximately one-year participation period. They will also measure changes in depression, anxiety, quality of life, and biological markers to understand the impact of psilocybin-assisted psychotherapy on these symptoms and cancer treatment adherence.

Researchers are evaluating a customized psychedelic-assisted group program designed for firefighters and first responders to promote cognitive resilience and mental health. This feasibility study compares a 12-week group program combined with either a 10mg dose of oral psilocybin or a breathwork day at Week 10. The program includes weekly sessions focused on breath-work, mindfulness, self-compassion, embodiment, and Internal Family Systems work, delivered in a trauma-informed safe space. All participants attend a 12-week group program with one weekly session. The first session and Week 10 session happen in person, while other sessions are remote. At Week 10, participants either receive a 10mg oral psilocybin dose under clinical supervision or complete a breathwork day if assigned to the control group. Psilocybin is given in capsules containing a partially purified mushroom extract called PYEX, with trained clinicians present during dosing. Participants will be assessed at baseline, mid-program (Week 6), end of program (Week 12), and at 6 months follow-up. Researchers monitor recruitment, retention, and adherence rates. Mental health outcomes such as anxiety levels are measured using the GAD-7 Anxiety Scale. Safety and overall study participation last about 8 months, with participants attending both in-person and remote sessions and receiving clinical support during dosing days.

Researchers are evaluating the safety of administering microdoses of psilocybin trihydrate at home to healthy adults aged 21 to 60 years. The study aims to identify which doses can be safely taken outside a clinical setting by using ascending doses and a randomized placebo in a controlled laboratory environment. This Phase 1 study involves 20 participants and is sponsored by Johns Hopkins University. Participants will receive single oral microdoses of psilocybin trihydrate at 1.2 mg, 2.0 mg, 3.0 mg, and 4.2 mg, as well as a placebo, across five double-blind dosing sessions at the research site. The doses are given in ascending order on separate days. Baseline questionnaires and safety assessments will be completed before and during each dosing session. The study will determine the highest dose that meets safety criteria for at-home use for each participant. Participants will undergo an initial medical and psychological screening lasting about 4 hours, which may be partly remote. During each dosing visit, safety checks including blood pressure, heart rate, field sobriety tests, and psychological status exams will be conducted at specific intervals post-dose. Driving performance will be assessed at baseline and after dosing using a simulation. The total participation includes screening and five dosing sessions with monitoring to evaluate safety outcomes related to vital signs, sobriety, psychology, and driving ability.

Researchers are evaluating whether combining a single dose of psilocybin with non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) can improve long-term behavioral benefits by helping memory for insights gained during the psychedelic experience stay vivid. This study involves medically healthy adults with a modest decrease in wellbeing and aims to compare active taVNS with sham taVNS or no stimulation following psilocybin dosing. Participants will receive a single 25 mg dose of psilocybin with psychological support lasting 2 to 4 hours before dosing and integration sessions 1 and 9 days after. They will be randomized into four groups to receive different combinations of active or sham taVNS before and after psilocybin dosing, or psychosocial support alone. The taVNS sessions last 20 minutes twice daily for seven days and are done at home. During the study, participants will undergo assessments including memory questionnaires, brain imaging with fMRI on dosing day and 56 days later, and mental wellbeing scales over 8 weeks. Researchers will monitor adverse events and compare the effects of taVNS administration versus usual treatment. The total participation involves preparation, dosing, multiple follow-up sessions, and safety monitoring lasting up to 8 weeks.

Researchers are investigating how inducing neuroplasticity, which is the brain's ability to adapt and change, affects the behavioral impact of psilocybin in adults who have experienced a mild decline in emotional wellbeing. This Phase 1 study compares different doses of psilocybin combined with either midazolam or a placebo to understand which dose may increase wellbeing. Participants will be randomly assigned to one of four groups receiving either 25 mg or 1 mg of psilocybin combined with intravenous midazolam or saline placebo. Midazolam is used to induce amnesia of the psychedelic experience without over-sedation. During the study, participants will receive these medication combinations under controlled conditions. Throughout the trial, participants will undergo MRI scans, transcranial magnetic stimulation (TMS), and EEG assessments. They will complete questionnaires measuring wellbeing and psychological responses at baseline and up to 28 days after dosing. The primary outcomes include changes in mental wellbeing, experiential avoidance, learning tasks, and brain activity from baseline to 7 days post-dose. Safety and behavioral effects will be monitored, with the total participation lasting several weeks.