HealthyPhase 1SERT-LSDNCT05175430
Effects of SERT Inhibition on the Subjective Response to LSD in Healthy Subjects
A Phase 1 study testing Paroxetine and Lysergic Acid Diethylamide in people with Healthy, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic acting on the serotonin 5-HT2A receptor. LSD is used recreationally and in psychiatric research. First studies suggest efficacy in psychiatric disorders, such as depression and anxiety. 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?
- Paroxetine and Lysergic Acid Diethylamide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteSwitzerland
- Study dates
- 24 Oct 2022to 7 Mar 2024
- 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
- Understanding of the German language.
- Understanding the procedures and the risks that are associated with the study.
- Participants must be willing to adhere to the protocol and sign the consent form.
- Participants must be willing to refrain from taking illicit psychoactive substances during the study.
- Participants must be willing to abstain from xanthine-based liquids from the evenings prior to the study sessions and during the sessions.
- Participants must be willing not to drive a traffic vehicle or to operate machines within 48h after 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, including a history of seizures.
- Current or previous major psychiatric disorder (e.g. psychotic disorders, mania / hypomania, anxiety disorders).
- Psychotic disorder in first-degree relatives, not including psychotic disorders secondary to an apparent medical reason, e.g. brain injury, dementia, or lesions of the brain.
- Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg); QT-time>450 ms (men) or >470 ms (women).
- Use of hallucinogenic substances (not including cannabis) more than 20 times or any time within the previous two months.
- History of acute glaucoma.
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- Pregnant or nursing women.
- Participation in another clinical trial (currently or within the last 30 days).
- Use of medications that may interfere with the effects of the study medications (any psychiatric medications and any medication with known pharmacokinetic or pharmacodynamic interactions with paroxetine).
- Tobacco smoking (>10 cigarettes/day).
- Consumption of alcoholic drinks (>20 drinks/week).
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Clinical Pharmacology & Toxicology, University Hospital Basel
Basel, 4031
About this study
Official title: Effects of Serotonin Transporter Inhibition on the Subjective Response to LSD in Healthy Subjects
Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic acting on the serotonin 5-HT2A receptor. LSD is used recreationally and in psychiatric research. First studies suggest efficacy in psychiatric disorders, such as depression and anxiety. SSRIs like paroxetine are first-line treatments for depression and anxiety disorders. Paroxetine acts as a serotonin transporter (SERT) inhibitor. However, the link between this mechanism and its positive effects on mood remains to be established. Several studies suggest a possible downregulation of postsynaptic serotonin (5-HT) receptors such as the 5-HT2A receptor. The aim of the study is to assess whether SERT inhibition reduces expression of the gene coding for the 5-HT2A receptor and the response to LSD.
Read the detailed description
Participants will be treated with paroxetine (Paroxetine 10 mg daily for 1 week followed by 20 mg daily for 5 weeks) or placebo for 6 weeks. Pretreatment is followed the first study day. A single dose of LSD (0.1 mg) will be administered. Primary study endpoint are the subjective effects on consciousness (5D-ASC total score). Secondary study endpoints include additional psychological measurements, plasma concentrations of LSD and paroxetine, as well as some safety measures (autonomic effects, ECG). The washout between the first study day and the second pretreatment will be at least 2 days. In the second pretreatment period, participants will be treated with placebo or paroxetine (cross-over) for another 6 weeks. This is followed by the second study day and administration of LSD (0.1 mg).
Based on a power analysis the sample size is 24 participants (12 female and 12 male).
- Conditions
- Healthy
- Being tested
- Paroxetine, Lysergic Acid Diethylamide, Placebo
- Keywords
- LSD, psychedelics, SSRI, healthy subjects, serotonin, 5-HT2A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParoxetineDrug
Paroxetine (per os) will be used as pharmacological tool to downregulate 5-HT1/2 receptors.
Lysergic Acid DiethylamideDrug
Also called LSD
LSD (per os) will be used to see if 5-HT 1/2 receptors were downregulated by paroxetine.
PlaceboDrug
Placebo (per os) for the Paroxetine condition will be used to compare the data from the study day with LSD between both arms.
| Study group | Role | What they receive |
|---|---|---|
| Pretreatment with paroxetine | Active comparator | Pretreatment with paroxetine (10 mg daily for 1 week followed by 20 mg daily for 5 weeks, per os), followed by administration of LSD (0.1 mg, per os) on the study day Receives: Drug: Paroxetine; Drug: Lysergic Acid Diethylamide |
| Pretreatment with placebo | Placebo comparator | Pretreatment with placebo for 6 weeks (mannitol, per os), followed by administration of LSD (0.1 mg, per os) on the study day Receives: Drug: Lysergic Acid Diethylamide; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
5 dimensions of altered state of consciousness (5D-ASC) total OAV score
Visual analog scale consisting of 94 items. Constructed of five scales and allows assessing mood, anxiety, derealization, depersonalization, changes in perception, auditory alterations, and reduced vigilance. Scales will be presented as 100 mm long horizontal lines marked with vertical lines by the participant.
Measured: Study sessions per participant will be separated by at least 43 days
Visual Analog Scales (VAS) good effect rating
VAS will be presented as 100 mm long horizontal lines marked with "not at all" on the left and "extremely" on the right. The following VAS items will be used: "any drug effect", "good drug effect", "bad drug effect", "drug high", "anxiety", "nausea", "feeling depressed", "alteration of vision", "alterations of hearing", "sounds seem to influence what I see", "alteration of sense of time", "the boundaries between myself and my surroundings seem to blur", "I gain insights into contexts that were previously were inscrutable to me", "talkative", "open", "trust" and "the context of my thought is personal/impersonal". Subjects will mark the scale with vertical lines.
Measured: Study sessions per participant will be separated by at least 43 days
Secondary outcomes (11)
Adjective mood rating scale (AMRS)
The adjective mood rating scale (AMRS or EWL60S) is a 60-item Likert scale that allows repeated assessment of mood in 6 dimensions: activation, inactivation, well-being, anxiety/depressed mood, extroversion and introversion, and emotional excitability.The AMRS consists of subscales measuring "activation", "positive mood", "extroversion", "introversion", "inactivation", and "emotional excitability.
Measured: Study sessions per participant will be separated by at least 43 days
States of consciousness questionnaire (SCQ)
This 100-item questionnaire is rated on a six-point scale. Forty-three items embedded into this questionnaire comprise the Mystical Experience Questionnaire (MEQ). which is sensitive to the effects of psilocybin. The 43 items provide scale scores for each of seven domains of mystical experiences: internal unity (pure awareness, a merging with ultimate reality), external unity (unity of all things, all things are alive, all is one), sense of sacredness (reverence, sacred), noetic quality (encounter with ultimate reality, more real than everyday reality), transcendence of time and space, deeply felt positive mood (joy, peace, love), paradoxicality/ineffability (claim of difficulty in describing the experience in words). We will also derived the four scale scores of the newly validated revised 30-item MEQ: mystical, positive mood, transcendence of time and space, and ineffability.
Measured: Study sessions per participant will be separated by at least 43 days
Spiritual Realm Questionnaire (SRQ)
This questionnaire has recently been developed by linguist and psychologist K. Stocker, Swiss Federal Institute of Technology Zürich and University of Zürich, to rate psychedelic (entheogenic) experiences with a focus on spiritual aspects insufficiently covered by the 5D-ASC and SCQ. The scale includes 11 main questions to be answered on a total of 65 sub-ordered visual rating scales. Results will be used to validate the scale and will be analyzed similar to the 5D-ASC using paired t-tests and comparing the constructs defined by the 11 main questions contained within the four main dimensions religious-psychological spirituality spectrum of humanity, human condition and life meaningfulness, dealing with personal problems, and worldview/belief.
Measured: Study sessions per participant will be separated by at least 43 days
Psychological Insight Questionnaire (PIQ)
This is a newly developed instrument to assess the degree to which an event has facilitated acute insight and gained awareness into emotions, behaviors, beliefs, memories, or relationships. The 14 items resulting from a recent validation process are to be rated on a 6-point Likert scale ranging from 0 = "No; not at all" to 5 = "Extremely (more than ever before in my life)".
Measured: Study sessions per participant will be separated by at least 43 days
Blood pressure
Repeatedly measured using blood pressure / pulse apparatus (mmHg scale)
Measured: Study sessions per participant will be separated by at least 43 days
Heart rate
Repeatedly measured using blood pressure / pulse apparatus (beats per minute scale)
Measured: Study sessions per participant will be separated by at least 43 days
Body temperature
Repeatedly measured using ear thermometer (degree Celsius scale)
Measured: Study sessions per participant will be separated by at least 43 days
Plasma concentrations of paroxetine
Paroxetine plasma concentrations will be measured repeatedly over time using LC-MS/MS techniques (nanogram per milliliter scale)
Measured: Study sessions per participant will be separated by at least 43 days
Plasma concentrations of LSD
LSD plasma concentrations will be measured repeatedly over time using LC-MS/MS techniques (nanogram per milliliter scale)
Measured: Study sessions per participant will be separated by at least 43 days
HTR gene expression
Messenger ribonucleic acid (mRNA) expression levels in whole blood as a peripheral marker of spiny neuronal gene (CNS) expression will be used to measure expression of HTR genes as well as expression of the SERT gene.
Measured: Study sessions per participant will be separated by at least 43 days
Changes in the electrocardiogram (ECG)
Corrected QT time (QTc) will be measured twice on the study days (baseline and at peak drug effect) to examine possible drug-induced changes in the ECG as well as a safety measure (millisecond scale).
Measured: Study sessions per participant will be separated by at least 43 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2022
- Study start24 Oct 2022
- Primary completion20 Feb 2024
- Study completion7 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 2-period cross-over, randomized, double-blind (paroxetine vs. placebo) study
- 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, Dr., MD, Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05175430
- Sponsor's protocol ID
- BASEC 2021-02223
- Acronym
- SERT-LSD
- Status last verified
- Mar 2024
- First submitted
- 14 Dec 2021
- Last updated
- 13 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Serotonin Transporter Inhibition on the Subjective Response to LSD in Healthy Subjects
- ClinicalTrials.gov ID
- NCT05175430
- Acronym / sponsor ID
- SERT-LSD / BASEC 2021-02223
- Conditions
- Healthy
- Keywords
- LSD, psychedelics, SSRI, healthy subjects, serotonin, 5-HT2A
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 24 Oct 2022 (actual)
- Primary completion
- 20 Feb 2024 (actual)
- Study completion
- 7 Mar 2024 (actual)
- First posted
- 3 Jan 2022 (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.
Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic acting on the serotonin 5-HT2A receptor. LSD is used recreationally and in psychiatric research. First studies suggest efficacy in psychiatric disorders, such as depression and anxiety. SSRIs like paroxetine are first-line treatments for depression and anxiety disorders. Paroxetine acts as a serotonin transporter (SERT) inhibitor. However, the link between this mechanism and its positive effects on mood remains to be established. Several studies suggest a possible downregulation of postsynaptic serotonin (5-HT) receptors such as the 5-HT2A receptor. The aim of the study is to assess whether SERT inhibition reduces expression of the gene coding for the 5-HT2A receptor and the response to LSD.
Detailed description
Participants will be treated with paroxetine (Paroxetine 10 mg daily for 1 week followed by 20 mg daily for 5 weeks) or placebo for 6 weeks. Pretreatment is followed the first study day. A single dose of LSD (0.1 mg) will be administered. Primary study endpoint are the subjective effects on consciousness (5D-ASC total score). Secondary study endpoints include additional psychological measurements, plasma concentrations of LSD and paroxetine, as well as some safety measures (autonomic effects, ECG). The washout between the first study day and the second pretreatment will be at least 2 days. In the second pretreatment period, participants will be treated with placebo or paroxetine (cross-over) for another 6 weeks. This is followed by the second study day and administration of LSD (0.1 mg).
Based on a power analysis the sample size is 24 participants (12 female and 12 male).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 2-period cross-over, randomized, double-blind (paroxetine vs. placebo) study
| Arm | Type | Receives |
|---|---|---|
| Pretreatment with paroxetine | Active comparator | Drug: Paroxetine, Drug: Lysergic Acid DiethylamidePretreatment with paroxetine (10 mg daily for 1 week followed by 20 mg daily for 5 weeks, per os), followed by administration of LSD (0.1 mg, per os) on the study day |
| Pretreatment with placebo | Placebo comparator | Drug: Lysergic Acid Diethylamide, Drug: PlaceboPretreatment with placebo for 6 weeks (mannitol, per os), followed by administration of LSD (0.1 mg, per os) on the study day |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Understanding of the German language.
- Understanding the procedures and the risks that are associated with the study.
- Participants must be willing to adhere to the protocol and sign the consent form.
- Participants must be willing to refrain from taking illicit psychoactive substances during the study.
- Participants must be willing to abstain from xanthine-based liquids from the evenings prior to the study sessions and during the sessions.
Key exclusion criteria (11 listed)
- Chronic or acute medical condition, including a history of seizures.
- Current or previous major psychiatric disorder (e.g. psychotic disorders, mania / hypomania, anxiety disorders).
- Psychotic disorder in first-degree relatives, not including psychotic disorders secondary to an apparent medical reason, e.g. brain injury, dementia, or lesions of the brain.
- Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg); QT-time>450 ms (men) or >470 ms (women).
- 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 |
|---|---|---|
| ParoxetineParoxetine (per os) will be used as pharmacological tool to downregulate 5-HT1/2 receptors. | Drug | Pretreatment with paroxetine |
| Lysergic Acid DiethylamideAlso: LSDLSD (per os) will be used to see if 5-HT 1/2 receptors were downregulated by paroxetine. | Drug | Pretreatment with paroxetine, Pretreatment with placebo |
| PlaceboPlacebo (per os) for the Paroxetine condition will be used to compare the data from the study day with LSD between both arms. | Drug | Pretreatment with placebo |
Primary outcome
5 dimensions of altered state of consciousness (5D-ASC) total OAV score
Time frame: Study sessions per participant will be separated by at least 43 days
Visual analog scale consisting of 94 items. Constructed of five scales and allows assessing mood, anxiety, derealization, depersonalization, changes in perception, auditory alterations, and reduced vigilance. Scales will be presented as 100 mm long horizontal lines marked with vertical lines by the participant.
Visual Analog Scales (VAS) good effect rating
Time frame: Study sessions per participant will be separated by at least 43 days
VAS will be presented as 100 mm long horizontal lines marked with "not at all" on the left and "extremely" on the right. The following VAS items will be used: "any drug effect", "good drug effect", "bad drug effect", "drug high", "anxiety", "nausea", "feeling depressed", "alteration of vision", "alterations of hearing", "sounds seem to influence what I see", "alteration of sense of time", "the boundaries between myself and my surroundings seem to blur", "I gain insights into contexts that were previously were inscrutable to me", "talkative", "open", "trust" and "the context of my thought is personal/impersonal". Subjects will mark the scale with vertical lines.
11 secondary outcomes
Adjective mood rating scale (AMRS)
Time frame: Study sessions per participant will be separated by at least 43 days
States of consciousness questionnaire (SCQ)
Time frame: Study sessions per participant will be separated by at least 43 days
Spiritual Realm Questionnaire (SRQ)
Time frame: Study sessions per participant will be separated by at least 43 days
Psychological Insight Questionnaire (PIQ)
Time frame: Study sessions per participant will be separated by at least 43 days
Blood pressure
Time frame: Study sessions per participant will be separated by at least 43 days
Heart rate
Time frame: Study sessions per participant will be separated by at least 43 days
Body temperature
Time frame: Study sessions per participant will be separated by at least 43 days
Plasma concentrations of paroxetine
Time frame: Study sessions per participant will be separated by at least 43 days
Plasma concentrations of LSD
Time frame: Study sessions per participant will be separated by at least 43 days
HTR gene expression
Time frame: Study sessions per participant will be separated by at least 43 days
Changes in the electrocardiogram (ECG)
Time frame: Study sessions per participant will be separated by at least 43 days
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 13 Mar 2024.
- Individual participant dataSharing planned: No
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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, 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 Paroxetine and Lysergic Acid Diethylamide 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 8 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 13 Mar 2024. 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?
5 dimensions of altered state of consciousness (5D-ASC) total OAV score (time frame: Study sessions per participant will be separated by at least 43 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2024.