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 DMTs 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 DMTs impact on depression over time.

Researchers are investigating the use of psilocybin-assisted psychotherapy PAP to prevent relapse in adults with alcohol use disorder AUD who also experience depressive symptoms. This study compares the effects of high-dose versus low-dose psilocybin in reducing relapse risk over six months. The study builds on earlier pilot findings suggesting psilocybin may reduce drinking days and cravings, offering a potentially faster-acting option than traditional antidepressants for individuals with AUD and depression. Participants receive two doses of psilocybin, either a high dose of 25 mg or a low dose of 3 mg, administered three weeks apart. The study uses a randomized, parallel design, with participants assigned to either the high-dose or low-dose group to evaluate differences in relapse prevention. A third dose may be offered later based on participant request and study assessments. During the study, participants are closely monitored with scheduled assessments of drinking behavior, craving, depressive symptoms, anxiety, quality of life, and other psychological factors. Various tests and questionnaires are administered at baseline and multiple follow-up points up to 51 weeks. Safety and tolerance of psilocybin are also evaluated. The total participation duration extends to about one year, allowing detailed observation of relapse rates and related outcomes.

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 evaluating the effects of blocking 5-HT1A receptors on the immediate subjective and brain activity responses to psilocybin in healthy volunteers aged 21 to 60. This early phase 1, double-blind, randomized, crossover study aims to understand how psilocybin changes perception and consciousness and its impact on sleep and dreaming after use. The study is sponsored by Johns Hopkins University and involves careful measurement of these effects through surveys and brain wave recordings. Participants will receive moderate doses of psilocybin trihydrate 18 mg combined either with pindolol, a 5-HT1A antagonist drug, or a placebo. Each participant undergoes both treatment conditions in a random order to compare effects. Around each drug administration session, participants will keep sleep and dream diaries for 10 days before and after, and wear an at-home sleep EEG device for 5 days before and after each session to monitor sleep patterns. During the study, participants will complete self-report measures and have their brain activity recorded using acute EEG during dosing sessions. Researchers will assess mystical experiences and changes in brain wave alpha power approximately over a 10-day period following dosing. The study includes screening for medical and psychiatric health, and participants must abstain from certain medications and substances before dosing. The total participation time varies based on the dosing schedule and diary monitoring periods.

Researchers are evaluating psilocybin-assisted psychotherapy for people with depression andor anxiety who are actively receiving treatment for advanced cancer. This Phase 2 trial aims to study the feasibility, safety, and potential effects of this therapy on psychological symptoms and quality of life. The study also looks at how this treatment may affect cancer therapy adherence and biological markers related to inflammation and brain function. Participants are randomly assigned to receive either psilocybin 25 mg or a placebo 100 mg of niacin by mouth. The study uses a quadruple-blind design to compare the effects of these interventions. The treatment involves two doses of psilocybin-assisted psychotherapy, with careful monitoring throughout. The trial will assess various psychological, functional, and biological outcomes during and after treatment. During the study, participants attend treatment and follow-up sessions at the cancer center and complete a range of assessments including questionnaires on mood, anxiety, quality of life, and mystical experiences. Researchers will also use brain imaging fMRI and blood tests to study immune function and brain plasticity. Safety and adverse events will be tracked throughout the average one-year study period. Participants must be willing to complete all visits and evaluations as required.

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 studying whether combining a single dose of psilocybin with non-invasive transcutaneous auricular vagus nerve stimulation taVNS, which may boost brain plasticity and memory, can improve the long-term positive effects on behavior compared to psilocybin alone or with sham stimulation. This Phase 1 study involves medically healthy adults with slight decreases in well-being. Participants receive one 25 mg dose of psilocybin with psychological support in a controlled environment lasting several hours. They are randomly assigned to one of four groups receiving 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 performed at home using devices that stimulate the left ear. During the study, participants undergo preparation, a dosing session, and integration sessions after dosing. Researchers collect brain imaging and memory questionnaire data at baseline and eight weeks post-dosing. Mental well-being and adverse events are also monitored throughout. The total study duration includes seven days of taVNS or sham stimulation before and after psilocybin, with follow-up assessments up to eight weeks.

Researchers are investigating how inducing neuroplasticity, which is the brains 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.