Healthy
Conditions
Keywords
Psychedelics, LSD, Psilocybin, DMT
Brief summary
The primary objective of this study is to determine whether equivalent moderately high doses of LSD, psilocybin, and DMT produce qualitatively similar peak effects when the effect duration is standardized with ketanserin. A DMT infusion mimicking oral LSD and psilocybin administrations will be tested, as well as intravenously administered ketanserin.
Detailed description
Lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT) are serotonergic hallucinogens (psychedelics) and currently investigated as therapeutic tools for the treatment of various psychiatric disorders. They are usually administered in a dose range which induces an alteration of consciousness via the stimulation of the serotonin (5-HT)2A receptor. However, there are differences in the receptor activation profiles between the three substances that may induce different subjective effects. Moreover, they exhibit different pharmacokinetic qualities. In comparative studies of LSD and psilocybin blinding was impaired by the different duration of subjective effects. This study aims to ensure blinding by ending all experiences at the same time with the 5HT2A antagonist ketanserin. Moreover, no study has yet directly compared DMT to LSD and psilocybin. The DMT infusion will be modeled in accordance with the course of an oral LSD and psilocybin administration. Therefore, the LPD-study compares the acute and subacute effects of LSD, psilocybin, and DMT while standardizing the time course and the duration of action for all substances.
Interventions
DRUGLSD
A moderate to high oral dose of 150 µg LSD will be administered followed by 20 mg intravenous ketanserin after 3 h
DRUGPsilocybin
A moderate to high oral dose of 30 mg psilocybin will be administered followed by 20 mg intravenous ketanserin after 3 h
DRUGDMT
A moderate to high, dose-escalating, intravenous infusion up to 2 mg/min DMT will be administered followed by 20 mg intravenous ketanserin after 3 h
DRUGPlacebo
An oral and an intravenous placebo will be administered followed by 20 mg intravenous ketanserin after 3 h
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
4-period, random order, placebo-controlled, double-blind cross-over study
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Good understanding of the German language 2. Understanding of procedures and risks associated with the study 3. Willing to adhere to the protocol and signing of the consent form 4. Willing to refrain from the consumption of illicit psychoactive substances during the study 5. Willing not to operate heavy machinery within 48 h after administration of a study substance 6. Willing to use effective birth control throughout study participation 7. Body mass index 17 - 34.9 kg/m2
Exclusion criteria
1. Relevant chronic or acute medical condition 2. Current or previous major psychiatric disorder (e.g. psychotic disorder) 3. Psychotic disorder or bipolar disorder in first-degree relatives 4. Hypertension (SBP\>140/90 mmHg) or hypotension (SBP\<85 mmHg) 5. Bradycardia (\< 45 bpm) 6. Prolonged QTc interval (males: \>450 ms, females: \>470 ms) 7. AV block II° (Mobitz type and Webckebach type) and III° 8. Hallucinogenic substance use (not including cannabis) more than 20 times or any time within the previous two months 9. Pregnancy or current breastfeeding 10. Participation in another clinical trial (currently or within the last 30 days) 11. Use of medication that may interfere with the effects of the study medication 12. Tobacco smoking (\>10 cigarettes/day) 13. Excessive consumption of alcoholic beverages (\>15 drinks/week)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1. Altered state of consciousness profile (5D-ASC) | 18 months | 5 Dimensions of Altered States of Consciousness (5D-ASC) consisting of 94 items to be rated on a visual analog scale (0-100 mm), with higher values indicating stronger effects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mystical-type experiences (PES) | 18 months | This 100-item Psychedelic Experience Questionnaire/Scale (PES100) is rated on a six-point scale (0 indicating not at all and 5 indicatin extremely). It comprises distractor items as well as subscales which measure mystical-type effects. |
| Mystical-type experiences (PAE-PS-ext) | 18 months | This Phenomenological-Autobiographical-Existential Psychedelic Scale extended (PAE-PS-ext) questionnaire rates psychedelic experiences with a focus on phenomenological, autobiographical, and existential psychedelic experiences (scale from 0 - 100 percent with higher scores representing more intense effects). |
| 3. Emotional breakthrough inventory (EBI+) | 18 months | This 18-item questionnaire is a visual analog scale (from 0 - 100 percent with higher scores representing more intense effects) assessing emotional breakthrough throughout the study sessions. |
| Plasma levels of LSD | 18 months | Assessed 20 times on each study day via blood samples |
| Plasma levels of psilocybin | 18 months | Assessed 20 times on each study day via blood samples |
| Plasma levels of DMT | 18 months | Assessed 20 times on each study day via blood samples |
| Plasma levels of ketanserin | 18 months | Assessed 20 times on each study day via blood samples |
| Plasma levels of oxytocin | 18 months | Assessed 2 times on each study day via blood samples |
| Subjective effects (VASs) | 18 months | Visual Analog Scales assessing the intensity and duration of subjective effects on a scale from 0 - 100 percent with higher scores representing more intense effects. |
| Plasma levels of cortisol | 18 months | Assessed 2 times on each study day via blood samples |
| Autonomic effects I | 18 months | Assessed 16 times on each study day via systolic and diastolic blood pressure |
| Autonomic effects II | 18 months | Assessed 16 times on each study day via heart rate |
| Autonomic effects III | 18 months | Assessed one time at screening visit and twice on each study day via ECG (QT-time) |
| Adverse effects (B-LR) | 18 months | The 2011 revised Beschwerden-Liste (B-LR) consists of a 40-item list covering a wide variety of symptoms and complaints that are answered with a four-point intensity-scoring ranging from 0 indicating not at all to 3 indicating strong. |
| Adverse effects (SPSI) | 18 months | The Swiss Psychedelic Side Effects Inventory evaluates side effects associated with psychedelics using a binary yes or no approach. Severity is recorded using a three-point intensity scale ranging from 1 indicating light to 3 indicating strong. The impact is recorded using a five-point scale ranging from -2 very disadvantageous to +2 very advantageous. The relation to the drug is recorded using a five-point scale ranging from 0 indicating unknown to 4 indicating certain. |
| Adverse Events (AE) | 18 months | Any report of adverse events will be recorded on a AE-Form. |
| Plasma levels of prolactin | 18 months | Assessed 2 times on each study day via blood samples |
Countries
Switzerland
Contacts
Primary ContactMatthias E Liechti, Prof. Dr. MD
Backup ContactMélusine Humbert-Droz, MSc
Outcome results
None listed