AnhedoniaPhase 2SARPNCT05357547
Serotonin-receptor Agonism in Reward Processing
A Phase 2 study testing Buspirone 20mg in people with Anhedonia, run by University of Oxford at 1 site in United Kingdom.
Trial summary
There is growing animal and human evidence for role of 5HT1A receptor agonism in treating depression and reward deficits. The next step is to translate this evidence directly into humans by characterising the effects of buspirone, as a 5HT1A agonist, on cognitive models of reward and emotional processing. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Anhedonia
- What is being tested?
- Buspirone 20mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 13 May 2022to 18 Apr 2023
- Phase
- Phase 2
- 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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participant is willing and able to give informed consent for participation in the research
- Male or female
- Body mass index in the range of 18 to 30
- Not currently taking any medications (except for contraception)
Who cannot join
- • Any current Axis 1 The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) psychiatric disorder
- Any previous episode of a severe mental illness,
- A first degree relative diagnosed with Bipolar Affective Disorder Type 1 or Schizophrenia
- Body Mass Index outside the range of 18 to 30 inclusive
- Any significant current medical condition likely to interfere with conduct of the study or analysis of data (epilepsy, renal disease, hepatic disease, myasthenia gravis, acute closed-angle glaucoma)
- Current use of psychoactive and / or medically significant medication as judged by a study medic, whether prescribed or bought over the counter (the contraceptive pill, the Depo-Provera injection or the progesterone implant will not result in exclusion)
Show all 11Show fewer
- Past history of dependence to illicit substances, and any consumption of illicit substances in the three months prior to the study
- Currently pregnant or breast feeding
- Known lactase deficiency or any other problem absorbing lactose, galactose, or glucose
- Participation in a study using the same tasks in the last year
- Any physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging. This includes any taste/olfactory disturbance e.g. secondary to Covid-19 infection
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Neurosciences building, Department of Psychiatry, Warneford hospital
Oxford, Oxfordshire, OX3 7JX
About this study
There is growing animal and human evidence for role of 5HT1A receptor agonism in treating depression and reward deficits. The next step is to translate this evidence directly into humans by characterising the effects of buspirone, as a 5HT1A agonist, on cognitive models of reward and emotional processing.
There is a paucity of behavioural evidence for the effect of 5HT1A receptor agonism, using buspirone as a probe, on primary reward processing (e.g. food), effort-based decision making or reward learning. Furthermore, the effects of 5HT1A agonism on non-emotive cognition, such as working memory, has yet to be investigated at a behavioural level in humans.
Read more
This study will characterise the effects of buspirone, as a probe for 5HT1A receptor agonism, on reward processing in human cognitive models. Furthermore it will examine its role in emotional processing and working memory. This will add to the evidence base of the neurocognitive effects of 5HT1A receptor agonism in humans, which is of relevance to the development of this as a target for future treatment development.
The study will be a double blinded, placebo controlled study involving healthy volunteers. Participants will receive a single dose of buspirone and then undergo a battery of psychometric testing to examine reward processing, emotional processing and a memory. Frequent monitoring of temperature and salivary cortisol shall be taken as surrogate markers of pre- and postsynaptic 5HT1A receptor activation.
- Conditions
- Anhedonia
- Being tested
- Buspirone 20mg, Placebo comparator
- Keywords
- 5HT1A receptor, Reward, Emotion, Memory, Buspirone
- Medical subject headings
- Anhedonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Buspirone 20mgDrug
Buspirone tablets in opaque capsule. Used as probe for 5HT1A agonism
Placebo comparatorDrug
Lactose-sucrose tablets in opaque capsule
| Study group | Role | What they receive |
|---|---|---|
| Buspirone | Experimental | Not described Receives: Drug: Buspirone 20mg |
| Control | Placebo comparator | Not described Receives: Drug: Placebo comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary reward perception
Visual Analogue Scale of anticipation of pleasure, intensity of taste and pleasure experienced when tasting one of four 4 tastes representing a primary reward stimulus processing.
Measured: On day of intervention (30 minutes pre-intervention and post-intervention (60 - 180 minutes))
Effort based reward task:
offer acceptance based upon effort required (grip force on hand held dynamometer) to obtain outcome and success rate in expending correct amount of effort required for reward
Measured: On day of intervention ( 90 - 180 minutes post intervention)
Changes in reward sensitivity
Sensitivity to reward as measured by the Probabilistic Instrumental Learning Task (Amount won, amount lost, total monetary amount earned , proportion of participants choosing the correct symbol in win and loss trials)
Measured: On day of intervention (90 - 180 minutes post intervention)
Secondary outcomes (8)
Changes in recognition of emotional facial expressions
Accuracy of emotion labels (e.g. disgusted face) assigned by participants to expressive faces which have appeared on a computer screen for a period of 500ms.
Measured: On day of intervention (90 - 180 minutes post intervention)
Changes in categorisation of emotional words
Accuracy to categorise positive and negative descriptor words
Measured: On day of intervention (90 - 180 minutes post intervention)
Changes in recall of emotional words
Number of words accurately recalled
Measured: On day of intervention (90 - 180 minutes post intervention)
Change in N-back task performance
Accuracy on the N-back task
Measured: On day of intervention (90 - 180 minutes post intervention)
Change in Auditory Verbal Learning Task
Accuracy on AVLT (number of items recalled across blocks)
Measured: On day of intervention (90 - 180 minutes post intervention)
Cortisol measurement
Salivary cortisol measurement at 30 minute intervals as surrogate of 5HT1A receptor activation
Measured: On day of intervention (30 minutes pre-intervention, at time of intervention, at 30 minute intervals thereafter)
Temperature measurement
Temperature measurement at 30 minute intervals as surrogate of 5HT1A receptor activation
Measured: On day of intervention (30 minutes pre-intervention, at time of intervention, at 30 minute intervals thereafter)
Temporal Experience of Pleasure scale (TEPS)
Measure of anticipatory and consummatory aspects of reward (state measure). 18 item questionnaire (10 items for anticipatory; 8 items for consummatory). Each item scored on 6 point Likert scale (1 = very false for me to 6 = very true for me).
Lower score indicates greater anhedonia.
Measured: On screening day and testing day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2022
- Study start13 May 2022
- Primary completion18 Apr 2023
- Study completion18 Apr 2023
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 AnhedoniaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Catherine Harmer, DPhil, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05357547
- Sponsor's protocol ID
- SARP01
- Acronym
- SARP
- Status last verified
- Apr 2022
- First submitted
- 24 Mar 2022
- Last updated
- 11 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: An anonymised dataset will be published as open access data on a secure repository (e.g. Open Science Framework https://osf/io/).
Publications
Smith ALW, Hamilton S, Murphy SE, Cowen PJ, Harmer CJ. The behavioural effects of the serotonin 1A receptor agonist buspirone on reward processing in healthy volunteers: A randomised, placebo-controlled study. J Psychopharmacol. 2026 Sep;40(9):1381-1391. doi: 10.1177/02698811261430527. Epub 2026 Mar 28.
PubMed 41902663
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serotonin-receptor Agonism in Reward Processing
- ClinicalTrials.gov ID
- NCT05357547
- Acronym / sponsor ID
- SARP / SARP01
- Conditions
- Anhedonia
- Keywords
- 5HT1A receptor, Reward, Emotion, Memory, Buspirone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 13 May 2022 (actual)
- Primary completion
- 18 Apr 2023 (actual)
- Study completion
- 18 Apr 2023 (actual)
- First posted
- 3 May 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.
There is growing animal and human evidence for role of 5HT1A receptor agonism in treating depression and reward deficits. The next step is to translate this evidence directly into humans by characterising the effects of buspirone, as a 5HT1A agonist, on cognitive models of reward and emotional processing.
There is a paucity of behavioural evidence for the effect of 5HT1A receptor agonism, using buspirone as a probe, on primary reward processing (e.g. food), effort-based decision making or reward learning. Furthermore, the effects of 5HT1A agonism on non-emotive cognition, such as working memory, has yet to be investigated at a behavioural level in humans.
This study will characterise the effects of buspirone, as a probe for 5HT1A receptor agonism, on reward processing in human cognitive models. Furthermore it will examine its role in emotional processing and working memory. This will add to the evidence base of the neurocognitive effects of 5HT1A receptor agonism in humans, which is of relevance to the development of this as a target for future treatment development.
The study will be a double blinded, placebo controlled study involving healthy volunteers. Participants will receive a single dose of buspirone and then undergo a battery of psychometric testing to examine reward processing, emotional processing and a memory. Frequent monitoring of temperature and salivary cortisol shall be taken as surrogate markers of pre- and postsynaptic 5HT1A receptor activation.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Buspirone | Experimental | Drug: Buspirone 20mg |
| Control | Placebo comparator | Drug: Placebo comparator |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Participant is willing and able to give informed consent for participation in the research
- Male or female
- Body mass index in the range of 18 to 30
- Not currently taking any medications (except for contraception)
Key exclusion criteria (11 listed)
- • Any current Axis 1 The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) psychiatric disorder
- Any previous episode of a severe mental illness,
- A first degree relative diagnosed with Bipolar Affective Disorder Type 1 or Schizophrenia
- Body Mass Index outside the range of 18 to 30 inclusive
- Any significant current medical condition likely to interfere with conduct of the study or analysis of data (epilepsy, renal disease, hepatic disease, myasthenia gravis, acute closed-angle glaucoma)
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 |
|---|---|---|
| Buspirone 20mgBuspirone tablets in opaque capsule. Used as probe for 5HT1A agonism | Drug | Buspirone |
| Placebo comparatorLactose-sucrose tablets in opaque capsule | Drug | Control |
Primary outcome
Primary reward perception
Time frame: On day of intervention (30 minutes pre-intervention and post-intervention (60 - 180 minutes))
Visual Analogue Scale of anticipation of pleasure, intensity of taste and pleasure experienced when tasting one of four 4 tastes representing a primary reward stimulus processing.
Effort based reward task:
Time frame: On day of intervention ( 90 - 180 minutes post intervention)
offer acceptance based upon effort required (grip force on hand held dynamometer) to obtain outcome and success rate in expending correct amount of effort required for reward
Changes in reward sensitivity
Time frame: On day of intervention (90 - 180 minutes post intervention)
Sensitivity to reward as measured by the Probabilistic Instrumental Learning Task (Amount won, amount lost, total monetary amount earned , proportion of participants choosing the correct symbol in win and loss trials)
8 secondary outcomes
Changes in recognition of emotional facial expressions
Time frame: On day of intervention (90 - 180 minutes post intervention)
Changes in categorisation of emotional words
Time frame: On day of intervention (90 - 180 minutes post intervention)
Changes in recall of emotional words
Time frame: On day of intervention (90 - 180 minutes post intervention)
Change in N-back task performance
Time frame: On day of intervention (90 - 180 minutes post intervention)
Change in Auditory Verbal Learning Task
Time frame: On day of intervention (90 - 180 minutes post intervention)
Cortisol measurement
Time frame: On day of intervention (30 minutes pre-intervention, at time of intervention, at 30 minute intervals thereafter)
Temperature measurement
Time frame: On day of intervention (30 minutes pre-intervention, at time of intervention, at 30 minute intervals thereafter)
Temporal Experience of Pleasure scale (TEPS)
Time frame: On screening day and testing day
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 11 May 2023.
- Derived from this study: PubMed 41902663Smith ALW, Hamilton S, Murphy SE, Cowen PJ, Harmer CJ. The behavioural effects of the serotonin 1A receptor agonist buspirone on reward processing in healthy volunteers: A randomised, placebo-controlled study. J Psychopharmacol. 2026 Sep;40(9):1381-1391. doi: 10.1177/02698811261430527. Epub 2026 Mar 28.
- Individual participant dataSharing planned: Yes. An anonymised dataset will be published as open access data on a secure repository (e.g. Open Science Framework https://osf/io/).
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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.
Catherine Harmer, DPhil principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Buspirone 20mg in people with Anhedonia, run by University of Oxford at 1 site in United Kingdom.
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 4 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 11 May 2023. 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 United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Primary reward perception (time frame: On day of intervention (30 minutes pre-intervention and post-intervention (60 - 180 minutes))). The study lists 3 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 NCT05357547, 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 11 May 2023; AzTrials last refreshed its copy on 28 Oct 2026.