Clinical trial treatments including psilocybin, MDMA, and other breakthrough therapies currently under research.
5-MeO-DMT therapy involves the carefully screened, clinically supervised administration of 5-methoxy-N,N-dimethyltryptamine. The compound produces a rapid-onset, ultra-short psychedelic experience often characterized by ego dissolution and non-dual awareness. Early research and observational reports suggest potential benefits for depression, anxiety, trauma-related symptoms, and existential distress. Because of the experience’s intensity, rigorous preparation, risk screening, medical safeguards, and structured integration are essential.
Trial Phase
Phase I–II (varies by protocol)
Status
Investigational / Controlled Substance (jurisdiction-dependent)
Session Time
Primary effects 10–30 minutes; total visit 2–4 hours including monitoring
Course Length
Single-session
AMPA modulators—often called 'ampakines' or AMPA positive allosteric modulators (PAMs)—increase the activity of AMPA-type glutamate receptors without directly activating them. By slowing receptor desensitization and/or deactivation, these agents can strengthen excitatory neurotransmission, promote long-term potentiation (LTP), and upregulate neurotrophic factors such as BDNF. A growing pipeline of AMPA PAMs is being investigated for major depressive disorder, cognitive impairment, schizophrenia (negative/cognitive symptoms), attention disorders, and other neuropsychiatric conditions.
Trial Phase
Phase I–II (varies by compound)
Status
Investigational
Session Time
Daily dosing or study-defined titration windows
Course Length
Short-term
Ayahuasca is a psychoactive brew prepared from the Banisteriopsis caapi vine and the Psychotria viridis (or Diplopterys cabrerana) leaf. It combines β-carboline alkaloids (harmine, harmaline, tetrahydroharmine) that act as MAO inhibitors with the psychedelic tryptamine DMT. In ceremonial and clinical contexts, ayahuasca induces intense visionary experiences, emotional catharsis, and altered states of consciousness. Early research and growing clinical interest suggest potential efficacy for treatment-resistant depression, PTSD, anxiety, and substance use disorders when combined with structured preparation and integration support.
Trial Phase
Phase I–II (varies by study)
Status
Controlled in many jurisdictions; authorized in some religious/spiritual contexts
Session Time
4–6 hours
Course Length
Single ceremony
Brain-computer interfaces (BCIs) are systems that establish a direct pathway between brain activity and external devices such as computers, prosthetics, or stimulation systems. They may be invasive (implanted electrodes) or non-invasive (EEG, MEG, fNIRS). BCIs are being explored for restoring communication in paralyzed patients, enhancing motor recovery after stroke, controlling neuroprosthetics, and modulating brain activity in psychiatric conditions. Research is ongoing to determine safety, reliability, and therapeutic efficacy across diverse conditions.
Trial Phase
Phase I–II
Status
Investigational; FDA Breakthrough Device Designations in some cases
Session Time
30 minutes – several hours
Course Length
Single sessions
Chemogenetics involves genetically engineering neurons to express Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). These engineered receptors respond only to specific synthetic ligands, such as clozapine-N-oxide (CNO), which are otherwise biologically inert. By selectively activating or silencing neuronal populations, researchers can precisely probe brain circuits underlying psychiatric and neurological disorders. While primarily a research tool, chemogenetics is being investigated for therapeutic applications in epilepsy, Parkinson’s disease, depression, addiction, and chronic pain. Translation to humans faces significant hurdles, including safe gene delivery, receptor stability, and ethical considerations.
Trial Phase
Preclinical, early translational
Status
Investigational (no approved therapeutic use)
Session Time
Ligand administration typically short (minutes–hours), but genetic modification is permanent
Course Length
L
Unlike open-loop neuromodulation, which delivers stimulation continuously or in pre-set patterns, closed-loop neurostimulation dynamically adjusts its output based on recorded neural or physiological signals. Devices use sensors to detect abnormal brain or nervous system activity, and algorithms trigger or modulate stimulation accordingly. This responsive system aims to improve efficacy, minimize side effects, and extend device lifespan. Current clinical applications include the NeuroPace RNS® System for drug-resistant epilepsy and investigational systems for depression, Parkinson’s disease, and chronic pain.
Trial Phase
FDA-approved for epilepsy; investigational for other conditions
Status
Partially approved (RNS for epilepsy); investigational for depression, Parkinson’s, chronic pain
Session Time
Continuous, device-driven
Course Length
C
CRISPR-based therapeutics use programmable nucleases and effectors to edit DNA or regulate gene expression. While CRISPR has advanced rapidly in monogenic and systemic diseases, psychiatric applications remain investigational due to polygenic risk, complex brain circuitry, and delivery barriers to the CNS. Approaches under study include in vivo CRISPR gene editing, CRISPR interference/activation (CRISPRi/a) for transcriptional tuning, base and prime editing for precise changes, and RNA-targeting systems. Targets of interest include stress-response genes (e.g., FKBP5), serotonergic and glutamatergic pathways (e.g., SLC6A4, GRIN genes), neuroplasticity regulators (e.g., BDNF), and epigenetic marks linked to trauma. Translation requires safe, cell-type–specific delivery (AAV, LNP, engineered capsids), rigorous off-target profiling, and ethical safeguards.
Trial Phase
Preclinical; early human feasibility in non-psychiatric CNS diseases
Status
Investigational; no clinical approval for psychiatric use
Session Time
One-time or limited dosing; biological effects can be durable
Course Length
Long-term expression (AAV)
DMT is a potent, fast-acting serotonergic psychedelic naturally occurring in plants and endogenous human metabolism. In therapeutic contexts, DMT is administered via intravenous or intramuscular routes, producing an intense but brief psychedelic state (5–30 minutes). Early-phase clinical studies and preclinical work suggest rapid effects on mood and neural plasticity, potentially offering a novel treatment for mental health disorders. Investigational protocols pair DMT with psychotherapy, preparation, and integration. Its extremely short duration differentiates it from psilocybin or LSD, raising interest in its potential as a more clinic-manageable psychedelic intervention.
Trial Phase
Phase 1–2 clinical trials
Status
Schedule I (US); investigational only
Session Time
5–30 minutes (psychedelic experience), with 1–2 hours preparation and integration
Course Length
S
Experimental gene therapy for mental health aims to alter gene expression or introduce corrective genetic material in specific neural circuits. Approaches include AAV- or lentiviral-based gene delivery, RNA interference (siRNA/shRNA), antisense oligonucleotides (ASOs), and programmable systems for transcriptional tuning (e.g., CRISPRi/a) delivered via adeno-associated virus or lipid nanoparticles. Targets span stress-response signaling, monoaminergic transporters and receptors, glutamatergic plasticity genes, neurotrophic factors, and synaptic scaffolding proteins. While gene therapy is established in some non-psychiatric conditions, psychiatric applications face unique challenges: polygenic risk architecture, cell-type specificity, durable yet controllable expression, blood–brain barrier delivery, and ethical safeguards.
Trial Phase
Preclinical to early human feasibility (primarily non-psychiatric CNS to date)
Status
Investigational; no approved psychiatric indications
Session Time
Dose administration typically brief; expression may persist months–years (vector/platform dependent)
Course Length
One-time dosing (AAV/viral)
Glutamate is the brain’s primary excitatory neurotransmitter, central to synaptic plasticity, learning, memory, and mood regulation. Dysregulation of glutamatergic signaling has been implicated in depression, anxiety, OCD, PTSD, and schizophrenia. Experimental glutamate modulators explore a wide range of mechanisms—beyond ketamine and esketamine (already FDA-approved)—such as NMDA receptor subunit–selective antagonists (e.g., NR2B-selective), glycine-site modulators, AMPA receptor positive allosteric modulators (AMPAR PAMs), mGluR2/3 agonists or antagonists, and triple reuptake inhibitors with glutamatergic activity. The aim is to achieve rapid, durable antidepressant and anxiolytic effects without dissociation or abuse liability.
Trial Phase
Phase I–II (compound-specific)
Status
Investigational; none approved for psychiatric use beyond ketamine/esketamine
Session Time
Minutes to hours (depending on administration)
Course Length
Single-dose studies
Fecal microbiota transplantation (FMT) involves transferring processed stool from a healthy donor into the gastrointestinal tract of a recipient. This therapy aims to reestablish microbial diversity and function, which may be disrupted in various diseases. While already established for recurrent Clostridioides difficile infection, FMT is being investigated in psychiatry and neurology for conditions such as depression, autism spectrum disorder, and Parkinson’s disease, based on evidence linking gut microbiota to brain function via the gut–brain axis.
Trial Phase
N/A
Status
N/A
Session Time
Procedure duration varies (30–60 minutes for colonoscopy; oral capsules taken over days)
Course Length
Single administration or repeated doses over weeks
Focused Ultrasound (FUS) is an emerging neuromodulation modality that delivers acoustic energy through the skull to precise brain targets without open surgery. Depending on intensity and frequency, FUS can be used for noninvasive neuromodulation (low-intensity FUS, or LIFU) or permanent lesioning (high-intensity focused ultrasound, HIFU). MR-guided FUS allows real-time targeting and monitoring. Research applications in psychiatry include modulation of the anterior cingulate cortex, amygdala, and striatum to reduce symptoms of depression, OCD, and anxiety, as well as permanent lesioning of circuits implicated in severe treatment-resistant cases.
Trial Phase
Phase I–II (psychiatric use)
Status
FDA-approved for essential tremor and tremor-dominant Parkinson’s disease; investigational for psychiatric disorders
Session Time
1–3 hours (including MRI setup and procedure)
Course Length
Single-session for lesioning
Glucagon-like peptide-1 (GLP-1) receptor agonists enhance glucose-dependent insulin secretion, slow gastric emptying, and reduce appetite. Beyond metabolic effects, GLP-1 receptors are expressed in brain regions involved in reward, motivation, and mood (e.g., VTA, nucleus accumbens, prefrontal cortex). Early clinical and preclinical research suggests potential benefits for major depressive disorder, anhedonia, cognitive impairment, and substance use disorders by modulating dopamine signaling, reducing neuroinflammation, and improving metabolic health. Psychiatric applications remain investigational.
Trial Phase
N/A
Status
N/A
Session Time
N/A
Course Length
Short-term
Ibogaine is a naturally occurring indole alkaloid found in the root bark of the African shrub *Tabernanthe iboga*. Traditionally used in Bwiti spiritual practices, it has gained attention for its purported ability to rapidly reduce withdrawal symptoms and cravings in opioid and stimulant addiction. Its complex pharmacology includes interactions with NMDA, opioid, sigma, and serotonergic receptors, as well as modulation of neurotrophic factors. Despite anecdotal and early clinical evidence, ibogaine remains investigational due to serious safety concerns, especially cardiotoxicity and risk of fatal arrhythmias. Research continues into safer analogs such as noribogaine.
Trial Phase
Phase I–II (early human trials, observational studies)
Status
Schedule I (U.S.); available in some countries (Mexico, Brazil, New Zealand) in specialized clinics; investigational globally
Session Time
12–24 hours acute psychedelic phase, followed by integration
Course Length
Typically single session, may be followed by booster or integration therapy
LSD (lysergic acid diethylamide) is a potent serotonergic psychedelic that profoundly alters perception, cognition, and sense of self. When administered in a controlled therapeutic setting, LSD is paired with psychotherapy to facilitate emotional release, enhanced self-reflection, and potential restructuring of maladaptive cognitive and behavioral patterns. Current research focuses on LSD-assisted therapy for anxiety associated with life-threatening illness, treatment-resistant depression, cluster headaches, and substance use disorders. While promising, LSD therapy remains investigational and highly regulated.
Trial Phase
Phase II (psychiatric research)
Status
Schedule I controlled substance in most jurisdictions; investigational use only
Session Time
6–10 hours (including preparation and integration)
Course Length
Single or multiple sessions spaced weeks apart
3,4-Methylenedioxymethamphetamine (MDMA) is a psychoactive compound known for its empathogenic and prosocial effects. In clinical settings, MDMA is paired with psychotherapy to facilitate trauma processing, emotional openness, and reduction of fear responses. Research, particularly through MAPS-sponsored trials, has demonstrated robust efficacy for severe, treatment-resistant PTSD. MDMA-assisted psychotherapy is being investigated for depression, social anxiety, and substance use disorders. It is currently in late-stage clinical development and under FDA review.
Trial Phase
Phase III (for PTSD)
Status
Schedule I controlled substance in most jurisdictions; FDA Breakthrough Therapy designation for PTSD
Session Time
6–8 hours per dosing session
Course Length
Typically 2–3 MDMA sessions with preparatory and integration therapy
Mescaline is a classic psychedelic alkaloid found in peyote, San Pedro, and Peruvian torch cacti. Historically used in Native American religious and healing practices, it produces profound alterations in perception, cognition, and emotional experience. Emerging modern research suggests mescaline may offer therapeutic benefits for depression, anxiety, and addiction when combined with structured psychotherapy. Scientific exploration is still at an early stage compared to psilocybin and MDMA, but growing interest in mescaline's long duration and spiritual quality of experiences is fueling investigational studies.
Trial Phase
Early-stage clinical and observational research
Status
Schedule I controlled substance in most jurisdictions; not FDA-approved
Session Time
8–12 hours per dosing session
Course Length
1–3 mescaline sessions with preparatory and integration therapy
Unlike traditional SSRIs and SNRIs, multimodal antidepressants act on multiple neurotransmitter systems simultaneously. For example, vortioxetine and vilazodone not only inhibit serotonin reuptake but also directly modulate serotonin receptor subtypes. This approach aims to enhance antidepressant efficacy, improve cognitive symptoms, and reduce side effects like sexual dysfunction. Research continues to evaluate the comparative benefits of these newer medications over conventional antidepressants.
Trial Phase
Approved in some countries; ongoing comparative and expansion studies
Status
FDA-approved (vortioxetine, vilazodone) for major depressive disorder
Session Time
Daily oral dosing
Course Length
Chronic, ongoing treatment
NMDA antagonists act on the N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptor critical in excitatory neurotransmission and synaptic plasticity. By modulating glutamate signaling, these drugs can induce rapid antidepressant effects, sometimes within hours. Ketamine, delivered intravenously, and intranasal esketamine are the leading examples, with FDA approval for treatment-resistant depression and depressive symptoms in major depressive disorder with acute suicidal ideation. Other NMDA antagonists, including investigational agents like rapastinel and apimostinel, are being studied to achieve similar efficacy with improved safety and tolerability.
Trial Phase
Phase II–III for novel agents; ketamine/esketamine FDA-approved for TRD
Status
FDA-approved for esketamine in TRD and depressive symptoms with suicidality; ketamine off-label use in psychiatry
Session Time
40 minutes (IV ketamine) to 2 hours (including monitoring)
Course Length
Acute and maintenance protocols, often weeks to months
Novel antidepressants represent a new wave of pharmacological strategies for mood disorders, particularly treatment-resistant depression (TRD). Unlike conventional antidepressants, which primarily act on monoamine neurotransmitters (serotonin, norepinephrine, dopamine), these therapies focus on alternative systems, including NMDA receptor modulation, AMPA potentiation, kappa-opioid receptor antagonism, and neurotrophic pathways such as BDNF signaling. Examples include esketamine (NMDA antagonist, FDA-approved), zuranolone (neurosteroid modulator), and investigational compounds like rapastinel, an NMDA partial agonist, and SAGE-217. They hold promise for rapid-acting effects, better safety profiles, and improved outcomes in TRD and comorbid psychiatric conditions.
Trial Phase
Phase II–III for most investigational agents; some FDA-approved
Status
Esketamine and zuranolone FDA-approved; other agents investigational
Session Time
30–120 minutes (depending on administration)
Course Length
Acute courses with possible maintenance protocols
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The information provided here is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider before starting any new treatment.