Healthy Participants Study
Conditions
Keywords
Intravenous DMT, DMT, Healthy, fMRI, Psychedelics, N,N-dimethyltryptamine
Brief summary
This study examines how the psychedelic substance DMT affects the human brain when administered by the intravenous (IV) route. DMT is a naturally occurring chemical in the body that is thought to help improve mood when ingested in a continuously monitored medical setting. Previous research has shown that a single IV injection of DMT can be given safely, but its effects, which include changes in perception, emotions, and thinking, usually wear off within 15-20 minutes. To better understand what happens when DMT's effects last longer, researchers have developed a method to give DMT slowly and continuously through an IV, which safely extends its effects for up to an hour or more. In this study, healthy volunteers who have prior experience using DMT will receive low and medium doses of DMT in this extended manner through an IV for 1 hour while undergoing a brain scanning technique known as functional magnetic resonance imaging (fMRI). These scans allow researchers to see changes in brain activity and blood flow in real time. Participants will complete psychological assessments before and after receiving DMT, and additional brain scans without DMT will be used for comparison. The researchers will also use advanced computer techniques to help identify brain patterns linked to the visual experiences people report during DMT. Overall, the goal of the study is to better understand how DMT affects the brain during an extended experience and to learn more about the biological processes behind its psychological effects.
Interventions
DRUGN,N-Dimethyltryptamine (15 mg)
Participants will receive one "low" dose (15 mg for 1 min + 1.5 mg/min for 59 min) of synthetic DMT (hemifumarate) via IV injection.
DRUGN,N-Dimethyltryptamine (17.5 mg)
Participants will receive one "medium" dose (17.5 mg for 1 min + 1.75 mg/min for 59 min) of synthetic DMT (hemifumarate) via IV injection.
Sponsors
Jon Dean
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* 18 to 65 years of age * Able to fluently communicate in English * Agree to sign the consent and HIPAA authorization * Not taking serotonergic antidepressant medication * Willing to refrain from using any non-prescribed psychoactive drugs, including alcohol, within 24 hours before and after study drug administration * Willing to refrain from consumption of illicit psychoactive substances during the study * Agree not to use any nonprescription medications, herbal medications, or supplements during the week prior to each drug session unless an exception is approved by the study investigators * Willing to refrain from smoking or use of nicotine from 8:00 AM on the morning of drug sessions until discharge at the end of the session * Have used classic serotonergic hallucinogens (e.g., LSD, psilocybin mushrooms, ayahuasca) without untoward/adverse effects and report "liking" psychedelic drugs with no previous adverse reactions to DMT or other psychedelics * Report at least 20 lifetime uses of psychedelics, including at least 5 uses of DMT (any form), at least one via inhalation, at least once within the past 2 years, and not within the past 3 months * Able to remain in an fMRI scanner without sedation and pass fMRI safety screening * Refrain from caffeine use prior to fMRI scanning * Women of childbearing potential must agree to use effective birth control from screening through the final visit * Have a relative or friend available to provide transportation after the drug session * Not taking medications acting as serotonin antagonists (e.g., cyclobenzaprine, ondansetron), dopamine antagonists (e.g., metoclopramide, promethazine, prochlorperazine), dopamine agonists (e.g., levodopa, pramipexole, apomorphine), psychostimulants (e.g., modafinil, armodafinil, solriamfetol, methylphenidate, dexmethylphenidate, atomoxetine, dextroamphetamine, mixed amphetamine salts, lisdexamfetamine), anticholinergics (e.g., benztropine, trihexyphenidyl, scopolamine, hyoscyamine), or NMDA receptor antagonists (e.g., amantadine, memantine, ketamine)
Exclusion criteria
* Pregnant or nursing females * Females of childbearing potential who are sexually active but not using birth control * MRI contraindications (e.g., pacemakers, metal implants, spinal cord stimulators) * Current DSM-5 diagnosis of depression or anxiety (or within past 6 months), bipolar disorder, schizophrenia, or other psychotic disorder * First-degree relative with bipolar disorder, schizophrenia, or other psychotic disorder * Suicide risk as determined by clinician assessment and/or C-SSRS * Active substance use disorder (excluding tobacco and caffeine) * Use of serotonergic dietary supplements (e.g., 5-hydroxytryptophan, St. John's wort, SAM-e) if unwilling to discontinue for study duration * Neurological conditions affecting cognition or perception (e.g., dementia, traumatic brain injury, mild cognitive impairment) * Positive urine drug screen for amphetamines, barbiturates, buprenorphine, cocaine, methamphetamine, MDMA, methadone, opiates, or phencyclidine * Use of DMT or another serotonergic hallucinogen within the past 3 months * Concomitant treatment with antipsychotic medications * Concomitant treatment with antidepressants, MAO inhibitors, or serotonin reuptake inhibitors (trazodone ≤50 mg/day for insomnia allowed but not within 48 hours of DMT session) * Severe hearing or visual impairment * History of seizure disorder or epilepsy * History of adverse reactions to rescue medications used in the study (benzodiazepines, antipsychotics, labetalol, nitroglycerin, ondansetron) * Cardiovascular disease or hypertension (SBP \>140 mmHg or DBP \>90 mmHg) * Resting heart rate \>90 bpm * Hypotension (SBP \<90 mmHg or DBP \<60 mmHg) * QTc prolongation (\>0.045 sec for men, \>0.047 sec for women) * History of stroke, angina, clinically significant ECG abnormality, or artificial heart valve * Severe renal impairment (GFR \<30 mL/min/1.73 m²) * Clinically significant laboratory abnormalities * History of syncope * History of vertigo * Myocardial infarction within 12 months * Child-Pugh class B or higher, or with alanine aminotransferase or aspartate aminotransferase \>2x upper limit of normal * Concomitant medications associated with serotonin syndrome (e.g., carbamazepine, dextromethorphan, lithium, linezolid, buspirone) * Severely compromised hepatic function * Trypanophobia (fear of needles/blood) * Treatment with another investigational drug within 30 days of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| fMRI - Blood Oxygen Level Dependent (BOLD) Signaling | Up to 3 months: Assessed at baseline fMRI (Visit 2) and dosing fMRI (Visits 6, 8). | Whole brain BOLD fMRI acquired during the peak subjective effects of IV administration of two separate doses ("low" and "medium") of DMT hemifumarate over a 60 min period for comparison across time, between dose, and versus rest/saline infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Numeric Rating Sale for current anxiety and pain, and feelings of compassion toward oneself and other | Up to 4 months: Assessed at baseline fMRI (Visit 2), dosing fMRI (Visits 6, 8), integration (Visits 7, 9), and follow-up (Visits 10, 11, 12) | Likert scale ranging from 0 to 10, with higher scores indicating higher anxiety, pain, and compassion, respectively |
| Numeric Rating Sale for current mood and stress | Up to 6 months: Assessed at baseline (Visit 2), dosing fMRI (Visits 6, 8), integration (Visits 7, 9), follow-up (Visits 10, 11, 12), and post-dosing fMRI (Visits 13, 14, 15) | Likert scale ranging from 0 to 10, with higher scores endorsing the feeling of being more upset and more stress, respectively |
| Numeric Rating Scale for immersion, visual effects, distortion in time perception, good and bad drug effects, drug intensity, and entity phenomena experienced | Up to 3 months: Assessed at baseline fMRI (Visit 2), and dosing fMRI (Visits 6, 8) | Likert scale ranging from 0 to 10, with higher scores indicating higher endorsement of respective constructs |
| Hallucinogen Rating Scale | Up to 3 months: Assessed at baseline fMRI (Visit 2), and dosing fMRI (Visits 6, 8) | Measures the acute subjective effects of hallucinogenic drugs across six domains: intensity, somaesthesia, affect, perception, cognition, and volition. Participants rate 100 items on a 5-point Likert scale (0-4), and domain scores are calculated as the mean of items within each domain, with higher scores indicating greater intensity of psychedelic effects |
| Autonomous Entity Questionnaire | Up to 3 months: Assessed at baseline fMRI (Visit 2), and dosing fMRI (Visits 6, 8) | Measures the presence and characteristics of perceived autonomous entities encountered during altered states of consciousness. Participants rate items assessing occurrence, emotional valence, perceived agency, and interaction with entities on Likert scales (0-100), with higher scores indicating stronger or more elaborate entity experiences |
| State Anxiety Inventory | Up to 4 months: Assessed at baseline fMRI (Visit 2), dosing fMRI (Visits 6, 8), integration (Visits 7, 9), and follow-up (Visits 10, 11, 12) | Measures current (state) anxiety using 20 self-report items rated on a 4-point Likert scale (1-4). Total scores range from 20 to 80, with higher scores indicating greater state anxiety. |
| End of Day Questionnaire | Up to 3 months: Assessed at dosing fMRI (Visits 6, 8) | Measures participants' overall experience following study drug administration, including perceived drug effects, adverse events, mood, and general well-being. Responses are collected using Likert scales (typically 0-10 or 1-5 depending on the item), and individual items are analyzed rather than a composite total score |
| 11-Dimensional Altered States of Consciousness Questionnaire | Up to 3 months: Assessed at baseline fMRI (Visit 2), and dosing fMRI (Visits 6, 8) | Measures multiple dimensions of altered conscious experience, including unity, insightfulness, bliss, disembodiment, anxiety, and visual alterations. Participants rate 42 items on visual analog scales ranging from 0 to 100, and scores are calculated separately for each of the 11 dimensions, with higher scores indicating greater intensity of each experience |
| Challenging Experiences Questionnaire | Up to 3 months: Assessed at baseline fMRI (Visit 2), and dosing fMRI (Visits 6, 8) | Measures psychologically difficult experiences during psychedelic administration across domains including fear, grief, paranoia, insanity, isolation, death, and physical distress. Participants rate 26 items on a 6-point scale (0-5), and domain scores are calculated as mean item scores, with higher scores indicating more intense challenging experiences |
| Persisting Effects Questionnaire | Up to 4 months: Assessed at baseline fMRI (Visit 2), dosing fMRI (Visits 6, 8), integration (Visits 7, 9), and follow-up (Visits 10, 11, 12) | Measures long-term perceived changes attributed to the psychedelic experience, including changes in attitudes, mood, behavior, relationships, spirituality, and well-being. Participants rate positive and negative changes on Likert scales (-3 to +3 or 0-5), with higher positive scores reflecting greater beneficial persisting effects |
| Visual Effects Questionnaire | Up to 4 months: Assessed at baseline fMRI (Visit 2), dosing fMRI (Visits 6, 8), integration (Visits 7, 9), and follow-up (Visits 10, 11, 12) | Measures the intensity and frequency of visual phenomena experienced during altered states, including geometric imagery, color enhancement, motion, patterning, and visual distortions. Participants rate items on visual analog scales ranging from 0 to 100, with higher scores indicating greater visual alterations |
| Vividness of Visual Imagery Questionnaire | Up to 4 months: Assessed at baseline fMRI (Visit 2), dosing fMRI (Visits 6, 8), integration (Visits 7, 9), and follow-up (Visits 10, 11, 12) | Measures the vividness of voluntarily generated mental imagery across everyday visual scenarios. Participants rate 16 items on a 5-point scale (1-5). Total scores range from 16 to 80, with higher scores indicating more vivid visual imagery |
| Pittsburgh Sleep Quality Index | Up to 4 months: Assessed at baseline fMRI (Visit 2), dosing fMRI (Visits 6, 8), integration (Visits 7, 9), and follow-up (Visits 10, 11, 12) | Measures subjective sleep quality across seven components including sleep duration, latency, efficiency, disturbances, medication use, and daytime dysfunction. Component scores (0-3) are summed to produce a global score ranging from 0 to 21, with higher scores indicating poorer sleep quality |
| Quick Inventory of Depressive Symptomatology | Up to 4 months: Assessed at baseline fMRI (Visit 2), dosing fMRI (Visits 6, 8), and follow-up (Visits 10, 11, 12) | Measures the severity of depressive symptoms across nine DSM symptom domains using 16 self-report items rated from 0 to 3. Total scores range from 0 to 27, with higher scores indicating greater depression severity |
| Five Facet Mindfulness Questionnaire | Up to 4 months: Assessed at baseline fMRI (Visit 2), dosing fMRI (Visits 6, 8), integration (Visits 7, 9), and follow-up (Visits 10, 11, 12) | Measures trait mindfulness across five domains: observing, describing, acting with awareness, nonjudging of inner experience, and nonreactivity to inner experience. Uses a 5-point Likert scale (1-5). Total scores range from 39 to 195, with higher scores indicating greater mindfulness |
| Montreal Cognitive Assessment | Up to 4 months: Assessed at baseline fMRI (Visit 2), integration (Visit 9), and follow-up (Visit 12) | Measures global cognitive function across domains including attention, executive function, memory, language, visuospatial ability, abstraction, and orientation. Total scores range from 0 to 30, with higher scores indicating better cognitive performance |
| Adverse events | Up to 6 months: Tracked across all study visits | Tracking all adverse and serious adverse events throughout study participant |
| Blood Pressure | Up to 3 months: Assessed at screening (Visit 1), baseline fMRI (Visit 2), preparatory session (Visit 5), dosing fMRI (Visits 6, 8) | Tracking blood pressure readings for \>140/90 mmHg and \<90/60 mmHg cutoffs |
| Heart Rate | Up to 3 months: Assessed at screening (Visit 1), baseline fMRI (Visit 2), preparatory session (Visit 5), dosing fMRI (Visits 6, 8) | Tracking heart rate for \>90 bmp exclusion at screening and 110 bpm and (220 - age) \* 0.85 bpm during dosing |
| Columbia Suicide Severity Rating Scale | Assessed at all study visits from enrollment through completion of the 4-week post-dosing follow-up (Visit 12) | Measures the severity of suicidal ideation and suicidal behavior through structured clinician-administered questions assessing the presence, intensity, frequency, duration, controllability, deterrents, and reasons for suicidal thoughts, as well as suicidal behaviors. Suicidal ideation severity is categorized on a 5-point scale (1-5) ranging from a wish to be dead (1) to active suicidal ideation with specific plan and intent (5), while suicidal behaviors are recorded as present or absent |
Countries
United States
Contacts
CONTACTYasmeen Esshaki
PRINCIPAL_INVESTIGATORJon Dean, PhD
UCSD
Outcome results
None listed