HealthyPhase 1LSD-MDMANCT04516902
Effects of MDMA Co-administration on the Response to LSD in Healthy Subjects
A Phase 1 study testing Lysergic Acid Diethylamide and 3,4-methylenedioxymethamphetamine in people with Healthy, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
The acute subjective effects of serotonin (5-HT)2A receptor stimulation with lysergic acid diethylamide (LSD) in humans are mostly positive. However, negative effects such as anxiety, paranoid thinking or loss of trust towards other people are common effects, depending on the dose administered, the personality traits… Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Lysergic Acid Diethylamide and 3,4-methylenedioxymethamphetamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Jan 2021to 22 Aug 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 25 and 65 years old
- Sufficient understanding of the German language
- Understanding of procedures and risks associated with the study
- Willing to adhere to the protocol and signing of the consent form
- Willing to refrain from the consumption of illicit psychoactive substances during the study
- Abstaining from xanthine-based liquids from the evenings prior to the study sessions and during the sessions
Show all 9Show fewer
- Willing not to operate heavy machinery within 48 h of substance administration
- Willing to use double-barrier birth control throughout study participation
- Body mass index between 18-29 kg/m2
Who cannot join
- Chronic or acute medical condition
- Current or previous major psychiatric disorder
- Psychotic disorder or bipolar disorder in first-degree relatives
- Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg)
- Use of hallucinogenic substances (not including cannabis) more than 20 times or any time within the previous two months
- Use of MDMA more than 20 times or any time within the previous two months
Show all 11Show fewer
- Pregnancy or currently breastfeeding
- Participation in another clinical trial (currently or within the last 30 days)
- Use of medication that may interfere with the effects of the study medication
- Tobacco smoking (>10 cigarettes/day)
- Consumption of alcoholic beverages (>20 drinks/week)
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Basel, Clinical Trial Unit
Basel, Canton of Basel-City, 4056
About this study
The acute subjective effects of serotonin (5-HT)2A receptor stimulation with lysergic acid diethylamide (LSD) in humans are mostly positive. However, negative effects such as anxiety, paranoid thinking or loss of trust towards other people are common effects, depending on the dose administered, the personality traits of the person consuming it (set), or the environment in which LSD is taken (setting). Negative psychedelic effects may cause acute distress to the subject and acute anxiety has been linked to less favourable long-term outcomes in patients experimentally treated with LSD or similar substances for the treatment of depression. The 5-HT and oxytocin releaser 3,4-methylenedioxymethamphetamine (MDMA) reliably induces positive mood up to euphoria, comfort, empathy, and feelings of trust. If administered in combination with LSD, MDMA may increase positive subjective drug effects including positive mood, empathy, and trust and reduce negative emotions and anxiety associated with LSD and overall produce a more positive over negative experience. The present study will assess subjective and autonomic effects of LSD alone and in combination with MDMA.
Read the detailed description
LSD is a so-called "classic" or serotonergic hallucinogen or psychedelic. Its psychedelic effects are mainly attributed to its potent partial serotonin (5-HT) 5-HT2A receptor agonism. The effects of LSD have been frequently investigated in the past in both healthy participants and patients. Several of these studies described robust and sustained effects of LSD in patients suffering from addiction, anxiety and depression. The acute subjective effects elicited by LSD are mostly positive in humans. However, psychedelic substances like LSD may also cause unpleasant subjective effects like negative thoughts, rumination, anxiety, panic, paranoia, loss of trust towards other people and perceived loss of control, depending on the dose of LSD used, the personality traits of the person consuming it (i.e. 'set'), the environment in which it is consumed (i.e. 'setting'), and other factors yet to be determined. Acute negative psychological effects are considered the main risk of psychedelic substance use in humans. Inducing an overall positive acute response to the psychedelic is critical because several studies showed that a more positive experience is predictive of a greater therapeutic long-term effect of the psychedelic. Therefore, there is a need for methods which are capable of reducing bad drug effects while enhancing good drug effects to optimize a psychedelic experience.
The present study uses 3,4-methylenedioxymethamphetamine (MDMA) as a pharmacological tool to optimize LSD's effects profile by inducing positive mood. MDMA is an amphetamine derivative which, unlike prototypical amphetamines, predominantly enhances serotonergic neurotransmission via release of 5-HT through the serotonin transporter (SERT). Furthermore, MDMA is known to trigger oxytocin release which may contribute to its effects to increase trust, prosociality, and enhanced empathy. The state of well-being induced by MDMA including increased activation and emotional excitation is known to be associated with a better response to psychedelics. Due to its psychological profile, MDMA could be a reliable pharmacological tool to serve as an optimizer of a psychedelic experience by inducing positive emotions.
- Conditions
- Healthy
- Being tested
- Lysergic Acid Diethylamide, 3,4-methylenedioxymethamphetamine, LSD Placebo, MDMA Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lysergic Acid DiethylamideDrug
Also called LSD
A moderate dose of 100 μg LSD will be administered.
3,4-methylenedioxymethamphetamineDrug
Also called MDMA
A moderate dose of 100 mg MDMA will be administered.
LSD PlaceboOther
Pure alcohol instead of an alcoholic solution containing LSD
MDMA PlaceboOther
Mannitol capsules instead of capsules containing MDMA
| Study group | Role | What they receive |
|---|---|---|
| 100 μg LSD + MDMA placebo | Experimental | 100 μg LSD + MDMA placebo Receives: Drug: Lysergic Acid Diethylamide; Other: MDMA Placebo |
| LSD placebo +100 mg MDMA | Experimental | LSD placebo +100 mg MDMA Receives: Drug: 3,4-methylenedioxymethamphetamine; Other: LSD Placebo |
| 100 μg LSD + 100 mg MDMA | Experimental | 100 μg LSD + 100 mg MDMA Receives: Drug: Lysergic Acid Diethylamide; Drug: 3,4-methylenedioxymethamphetamine |
| LSD placebo+ MDMA placebo | Placebo comparator | LSD placebo+ MDMA placebo Receives: Other: LSD Placebo; Other: MDMA Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute subjective effects I
Visual Analog Scales (VAS) assessing the intensity and duration of subjective effects on a scale from 0% - 100% with higher scores representing more intense effects
Measured: 12 months
Acute subjective effects II
Adjective Mood Rating Scale (AMRS) assesses the occurrence and intensity of 60 moods on a 4-point Likert scale ranging from "not at all" to "extremely"
Measured: 12 months
Acute subjective effects III
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
Measured: 12 months
Autonomic effects I
Assessed 18 times on each study day via systolic and diastolic blood pressure
Measured: 12 months
Autonomic effects II
Assessed 18 times on each study day via heart rate
Measured: 12 months
Autonomic effects III
Assessed 18 times on each study day via tympanic body temperature
Measured: 12 months
Secondary outcomes (12)
Plasma levels of LSD
Assessed 18 times on each study day via blood samples
Measured: 12 months
Plasma levels of MDMA
Assessed 18 times on each study day via blood samples
Measured: 12 months
Plasma levels of blood-derived neurotrophic factor (BDNF)
Assessed 21 times on each study day via blood samples
Measured: 12 months
Plasma levels of oxytocin
Assessed 4 times on each study day via blood samples
Measured: 12 months
Psychological Insight Questionnaire
Assesses the degree of psychological insight caused by a psychedelic experience through 14-items to be answered on a 6-point Likert scale ranging from 0 ("not at all") to 5 ("extremely")
Measured: 12 months
States of Consciousness Questionnaire
Assesses the emergence and intensity of phenomenons occurring in altered states of consciousness on a 6-point Likert scale ranging from 0 ("not at all") to 5 ("extremely")
Measured: 12 months
Spiritual Realms Questionnaire
Assesses the spiritual phenomenons elicited by psychedelic substances through 11 main questions to be answered on a total of 65 sub-ordered 100mm visual analog scales
Measured: 12 months
Effect moderation through personality traits I
Assessed via NEO-Five-Factor-Inventory (NEO-FFI)
Measured: Baseline
Effect moderation through personality traits II
Assessed via Freiburger Personality Inventory (FPI)
Measured: Baseline
Effect moderation through personality traits III
Assessed via Saarbrücker Personality Questionnaire (SPF)
Measured: Baseline
Effect moderation through personality trait IV
Assessed via HEXACO personality inventory
Measured: Baseline
Effect moderation through personality trait V
Assessed via Defense Style Questionnaire (DSQ-40)
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2020
- Study start1 Jan 2021
- Primary completion22 Aug 2022
- Study completion22 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-blind, placebo-controlled, 4-period cross-over design with four treatment conditions: 1. 100 μg LSD+MDMA placebo 2. LSD placebo +100 mg MDMA 3. 100 μg LSD + 100 mg MDMA 4. LSD placebo+ MDMA placebo
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthias E Liechti, Prof. Dr. MD, Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04516902
- Sponsor's protocol ID
- BASEC 2020-01829
- Acronym
- LSD-MDMA
- Status last verified
- Aug 2022
- First submitted
- 13 Aug 2020
- Last updated
- 23 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Straumann I, Ley L, Holze F, Becker AM, Klaiber A, Wey K, Duthaler U, Varghese N, Eckert A, Liechti ME. Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants. Neuropsychopharmacology. 2023 Dec;48(13):1840-1848. doi: 10.1038/s41386-023-01609-0. Epub 2023 May 31.
PubMed 37258715
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of MDMA Co-administration on the Response to LSD in Healthy Subjects
- ClinicalTrials.gov ID
- NCT04516902
- Acronym / sponsor ID
- LSD-MDMA / BASEC 2020-01829
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 22 Aug 2022 (actual)
- Study completion
- 22 Aug 2022 (actual)
- First posted
- 18 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The acute subjective effects of serotonin (5-HT)2A receptor stimulation with lysergic acid diethylamide (LSD) in humans are mostly positive. However, negative effects such as anxiety, paranoid thinking or loss of trust towards other people are common effects, depending on the dose administered, the personality traits of the person consuming it (set), or the environment in which LSD is taken (setting). Negative psychedelic effects may cause acute distress to the subject and acute anxiety has been linked to less favourable long-term outcomes in patients experimentally treated with LSD or similar substances for the treatment of depression. The 5-HT and oxytocin releaser 3,4-methylenedioxymethamphetamine (MDMA) reliably induces positive mood up to euphoria, comfort, empathy, and feelings of trust. If administered in combination with LSD, MDMA may increase positive subjective drug effects including positive mood, empathy, and trust and reduce negative emotions and anxiety associated with LSD and overall produce a more positive over negative experience. The present study will assess subjective and autonomic effects of LSD alone and in combination with MDMA.
Detailed description
LSD is a so-called "classic" or serotonergic hallucinogen or psychedelic. Its psychedelic effects are mainly attributed to its potent partial serotonin (5-HT) 5-HT2A receptor agonism. The effects of LSD have been frequently investigated in the past in both healthy participants and patients. Several of these studies described robust and sustained effects of LSD in patients suffering from addiction, anxiety and depression. The acute subjective effects elicited by LSD are mostly positive in humans. However, psychedelic substances like LSD may also cause unpleasant subjective effects like negative thoughts, rumination, anxiety, panic, paranoia, loss of trust towards other people and perceived loss of control, depending on the dose of LSD used, the personality traits of the person consuming it (i.e. 'set'), the environment in which it is consumed (i.e. 'setting'), and other factors yet to be determined. Acute negative psychological effects are considered the main risk of psychedelic substance use in humans. Inducing an overall positive acute response to the psychedelic is critical because several studies showed that a more positive experience is predictive of a greater therapeutic long-term effect of the psychedelic. Therefore, there is a need for methods which are capable of reducing bad drug effects while enhancing good drug effects to optimize a psychedelic experience.
The present study uses 3,4-methylenedioxymethamphetamine (MDMA) as a pharmacological tool to optimize LSD's effects profile by inducing positive mood. MDMA is an amphetamine derivative which, unlike prototypical amphetamines, predominantly enhances serotonergic neurotransmission via release of 5-HT through the serotonin transporter (SERT). Furthermore, MDMA is known to trigger oxytocin release which may contribute to its effects to increase trust, prosociality, and enhanced empathy. The state of well-being induced by MDMA including increased activation and emotional excitation is known to be associated with a better response to psychedelics. Due to its psychological profile, MDMA could be a reliable pharmacological tool to serve as an optimizer of a psychedelic experience by inducing positive emotions.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- Model description
- Double-blind, placebo-controlled, 4-period cross-over design with four treatment conditions: 1. 100 μg LSD+MDMA placebo 2. LSD placebo +100 mg MDMA 3. 100 μg LSD + 100 mg MDMA 4. LSD placebo+ MDMA placebo
| Arm | Type | Receives |
|---|---|---|
| 100 μg LSD + MDMA placebo | Experimental | Drug: Lysergic Acid Diethylamide, Other: MDMA Placebo100 μg LSD + MDMA placebo |
| LSD placebo +100 mg MDMA | Experimental | Drug: 3,4-methylenedioxymethamphetamine, Other: LSD PlaceboLSD placebo +100 mg MDMA |
| 100 μg LSD + 100 mg MDMA | Experimental | Drug: Lysergic Acid Diethylamide, Drug: 3,4-methylenedioxymethamphetamine100 μg LSD + 100 mg MDMA |
| LSD placebo+ MDMA placebo | Placebo comparator | Other: LSD Placebo, Other: MDMA PlaceboLSD placebo+ MDMA placebo |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age between 25 and 65 years old
- Sufficient understanding of the German language
- Understanding of procedures and risks associated with the study
- Willing to adhere to the protocol and signing of the consent form
- Willing to refrain from the consumption of illicit psychoactive substances during the study
Key exclusion criteria (11 listed)
- Chronic or acute medical condition
- Current or previous major psychiatric disorder
- Psychotic disorder or bipolar disorder in first-degree relatives
- Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg)
- Use of hallucinogenic substances (not including cannabis) more than 20 times or any time within the previous two months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lysergic Acid DiethylamideAlso: LSDA moderate dose of 100 μg LSD will be administered. | Drug | 100 μg LSD + 100 mg MDMA, 100 μg LSD + MDMA placebo |
| 3,4-methylenedioxymethamphetamineAlso: MDMAA moderate dose of 100 mg MDMA will be administered. | Drug | 100 μg LSD + 100 mg MDMA, LSD placebo +100 mg MDMA |
| LSD PlaceboPure alcohol instead of an alcoholic solution containing LSD | Other | LSD placebo +100 mg MDMA, LSD placebo+ MDMA placebo |
| MDMA PlaceboMannitol capsules instead of capsules containing MDMA | Other | 100 μg LSD + MDMA placebo, LSD placebo+ MDMA placebo |
Primary outcome
Acute subjective effects I
Time frame: 12 months
Visual Analog Scales (VAS) assessing the intensity and duration of subjective effects on a scale from 0% - 100% with higher scores representing more intense effects
Acute subjective effects II
Time frame: 12 months
Adjective Mood Rating Scale (AMRS) assesses the occurrence and intensity of 60 moods on a 4-point Likert scale ranging from "not at all" to "extremely"
Acute subjective effects III
Time frame: 12 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
Autonomic effects I
Time frame: 12 months
Assessed 18 times on each study day via systolic and diastolic blood pressure
Autonomic effects II
Time frame: 12 months
Assessed 18 times on each study day via heart rate
Autonomic effects III
Time frame: 12 months
Assessed 18 times on each study day via tympanic body temperature
12 secondary outcomes
Plasma levels of LSD
Time frame: 12 months
Plasma levels of MDMA
Time frame: 12 months
Plasma levels of blood-derived neurotrophic factor (BDNF)
Time frame: 12 months
Plasma levels of oxytocin
Time frame: 12 months
Psychological Insight Questionnaire
Time frame: 12 months
States of Consciousness Questionnaire
Time frame: 12 months
Spiritual Realms Questionnaire
Time frame: 12 months
Effect moderation through personality traits I
Time frame: Baseline
Effect moderation through personality traits II
Time frame: Baseline
Effect moderation through personality traits III
Time frame: Baseline
Effect moderation through personality trait IV
Time frame: Baseline
Effect moderation through personality trait V
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2022.
- Derived from this study: PubMed 37258715Straumann I, Ley L, Holze F, Becker AM, Klaiber A, Wey K, Duthaler U, Varghese N, Eckert A, Liechti ME. Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants. Neuropsychopharmacology. 2023 Dec;48(13):1840-1848. doi: 10.1038/s41386-023-01609-0. Epub 2023 May 31.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthias E Liechti, Prof. Dr. MD principal investigator
University Hospital, Basel, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lysergic Acid Diethylamide and 3,4-methylenedioxymethamphetamine in people with Healthy, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute subjective effects I (time frame: 12 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04516902, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2022.