Subjective Drug EffectsPhase 1NCT06378957
Behavioral Pharmacology of Orally Administered THC and D-limonene
A Phase 1 study testing D-Limonene and Delta-9-THC in people with Subjective Drug Effects and THC, run by Johns Hopkins University at 1 site in United States.
Trial summary
The current clinical trial will investigate the effects of orally administered d-limonene (limonene), delta-9-tetrahydrocannabinol (THC) and the combination in healthy adult volunteers. Read more about this study
- Who is it for?
- Ages 21 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Subjective Drug Effects, THC, D-limonene
- What is being tested?
- D-Limonene and Delta-9-THC
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Feb 2025to 31 Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 21 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Have provided written informed consent
- Be between the ages of 21 and 55
- Be in good general health based on a physical examination, medical history, vital signs, and screening urine and blood tests
- Test negative for drugs of abuse other than cannabis, including breath alcohol at the screening visit and at clinic admission
- Not be pregnant or nursing (if female). All females must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at clinic admission.
- Have a body mass index (BMI) in the range of 18 to 36 kg/m2
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- Blood pressure at Screening Visit does not exceed a systolic blood pressure (SBP) of 150 mmHg or a diastolic blood pressure (DBP) of 90 mmHg
- Have no allergies to any of the ingredients used to prepare (cellulose, THC, d-limonene).
- Report having used a high THC cannabis product in the past 3 years and having experienced anxiety after consuming cannabis at least once in lifetime.
Who cannot join
- Non-medical use of psychoactive drugs other than, nicotine, alcohol, or caffeine 3 month prior to the Screening Visit;
- History of or current evidence of significant medical (e.g. seizure disorder) or psychiatric illness (e.g. psychosis) judged by the investigator to put the participant at greater risk of experiencing an adverse event due to exposure or completion of other study procedures.
- Use of an over the counter (OTC), systemic or topical drug(s), herbal supplement(s), or vitamin(s) within 14 days of experimental sessions; which, in the opinion of the investigator or sponsor, will interfere with the study result or the safety of the subject.
- Use of a prescription medication (with the exception of birth control prescriptions) within 14 days of experimental sessions; which, in the opinion of the investigator or sponsor, will interfere with the study result or the safety of the subject.
- Average use of cannabis more than 2 times per week in the prior 3 months.
- History of clinically significant cardiac arrhythmias or vasospastic disease (e.g., Prinzmetal's angina).
- Enrolled in another clinical trial or have received any drug as part of a research study within 30 days prior to dosing.
- Individuals with anemia or who have donated blood in the prior 30 days
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins Behavioral Pharmacology Research Unit
Baltimore, Maryland, 21224
Austin Zamarripa
Austin Zamarripa, PhD
About this study
The current clinical trial will investigate the effects of orally administered d-limonene (limonene), delta-9-tetrahydrocannabinol (THC) and the combination in healthy adult volunteers.
Read the detailed description
The current clinical trial will investigate the interaction of orally administered d-limonene (limonene) and delta-9-tetrahydrocannabinol (THC). Limonene is a flavor/fragrance component common to many plants, including cannabis. The investigators have previously demonstrated that vaporized limonene can impact the acute effects of THC. The purpose of this study is to examine whether orally administered limonene modulates the acute effects of orally co-administered THC in a manner similar to when these substances are inhaled A controlled laboratory study will be completed at Johns Hopkins evaluating placebo, THC alone, and four ascending doses of d-limonene in combination with THC. Participants will be healthy adults with experience using cannabis. A total of 6 outpatient drug administration sessions will be conducted for each evaluable participant. The investigators will recruit study volunteers until 20 participants complete the protocol.
- Conditions
- Subjective Drug Effects, THC, D-limonene
- Being tested
- D-Limonene, Delta-9-THC, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-LimoneneDrug
Oral Limonene administered via capsule
Delta-9-THCDrug
Also called THC
Oral delta-9-THC in ethanol vehicle administered via capsule
PlaceboDrug
Placebo (cellulose) administered via capsule
| Study group | Role | What they receive |
|---|---|---|
| Oral Placebo | Placebo comparator | Placebo (cellulose), via capsule Receives: Drug: Placebo |
| Oral THC 30mg | Experimental | 30mg pure THC in ethanol vehicle, via capsule Receives: Drug: Delta-9-THC |
| Oral THC 30mg + D-Limonene 25mg | Experimental | 30mg pure THC in ethanol vehicle, via capsule 25mg pure D-Limonene, via capsule Receives: Drug: D-Limonene; Drug: Delta-9-THC |
| Oral THC 30mg + D-Limonene 50mg | Experimental | 30mg pure THC in ethanol vehicle, via capsule 50mg pure D-Limonene, via capsule Receives: Drug: D-Limonene; Drug: Delta-9-THC |
| Oral THC 30mg + D-Limonene 100mg | Experimental | 30mg pure THC in ethanol vehicle, via capsule 100mg pure D-Limonene, via capsule Receives: Drug: D-Limonene; Drug: Delta-9-THC |
| Oral THC 30mg + D-Limonene 200mg | Experimental | 30mg pure THC in ethanol vehicle, via capsule 200mg pure D-Limonene, via capsule Receives: Drug: D-Limonene; Drug: Delta-9-THC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subjective Drug Effect as assessed by Visual Analog Scale
Subjective drug effect will be measured on a 100 point visual analog scale (VAS) where 0 = no drug effect and 100 = strongest drug effect imaginable
Measured: 8 hours after dosing
Secondary outcomes (4)
Subjective Drug Liking as assessed by Visual Analog Scale
Subjective drug liking will be measured on a 100 point visual analog scale (VAS) where 0 = no drug effect and 100 = strongest drug effect imaginable
Measured: 8 hours after dosing
Subjective anxiety as assessed by Visual Analog Scale
Subjective anxiety will be measured on a 100 point visual analog scale (VAS) where 0 = no drug effect and 100 = strongest drug effect imaginable
Measured: 8 hours after dosing
Subjective hunger as assessed by Visual Analog Scale
Subjective hunger will be measured on a 100 point visual analog scale (VAS) where 0 = no drug effect and 100 = strongest drug effect imaginable
Measured: 8 hours after dosing
Subjective paranoia as assessed by Visual Analog Scale
Subjective paranoia will be measured on a 100 point visual analog scale (VAS) where 0 = no drug effect and 100 = strongest drug effect imaginable
Measured: 8 hours after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2024
- Study start14 Feb 2025
- Primary completion1 Jul 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Subjective Drug EffectsStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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
- Within-subjects design where participants are randomly assigned to dose conditions
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Austin Zamarripa, PhD, Principal investigator, Johns Hopkins School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06378957
- Sponsor's protocol ID
- IRB00436545
- Status last verified
- May 2026
- First submitted
- 18 Apr 2024
- Last updated
- 28 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Behavioral Pharmacology of Orally Administered THC and D-limonene
- ClinicalTrials.gov ID
- NCT06378957
- Acronym / sponsor ID
- IRB00436545
- Conditions
- Subjective Drug Effects, THC, D-limonene
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- 14 Feb 2025 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 23 Apr 2024 (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 current clinical trial will investigate the effects of orally administered d-limonene (limonene), delta-9-tetrahydrocannabinol (THC) and the combination in healthy adult volunteers.
Detailed description
The current clinical trial will investigate the interaction of orally administered d-limonene (limonene) and delta-9-tetrahydrocannabinol (THC). Limonene is a flavor/fragrance component common to many plants, including cannabis. The investigators have previously demonstrated that vaporized limonene can impact the acute effects of THC. The purpose of this study is to examine whether orally administered limonene modulates the acute effects of orally co-administered THC in a manner similar to when these substances are inhaled A controlled laboratory study will be completed at Johns Hopkins evaluating placebo, THC alone, and four ascending doses of d-limonene in combination with THC. Participants will be healthy adults with experience using cannabis. A total of 6 outpatient drug administration sessions will be conducted for each evaluable participant. The investigators will recruit study volunteers until 20 participants complete the protocol.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 6
- Model description
- Within-subjects design where participants are randomly assigned to dose conditions
| Arm | Type | Receives |
|---|---|---|
| Oral Placebo | Placebo comparator | Drug: PlaceboPlacebo (cellulose), via capsule |
| Oral THC 30mg | Experimental | Drug: Delta-9-THC30mg pure THC in ethanol vehicle, via capsule |
| Oral THC 30mg + D-Limonene 25mg | Experimental | Drug: D-Limonene, Drug: Delta-9-THC30mg pure THC in ethanol vehicle, via capsule 25mg pure D-Limonene, via capsule |
| Oral THC 30mg + D-Limonene 50mg | Experimental | Drug: D-Limonene, Drug: Delta-9-THC30mg pure THC in ethanol vehicle, via capsule 50mg pure D-Limonene, via capsule |
| Oral THC 30mg + D-Limonene 100mg | Experimental | Drug: D-Limonene, Drug: Delta-9-THC30mg pure THC in ethanol vehicle, via capsule 100mg pure D-Limonene, via capsule |
| Oral THC 30mg + D-Limonene 200mg | Experimental | Drug: D-Limonene, Drug: Delta-9-THC30mg pure THC in ethanol vehicle, via capsule 200mg pure D-Limonene, via capsule |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Have provided written informed consent
- Be between the ages of 21 and 55
- Be in good general health based on a physical examination, medical history, vital signs, and screening urine and blood tests
- Test negative for drugs of abuse other than cannabis, including breath alcohol at the screening visit and at clinic admission
- Not be pregnant or nursing (if female). All females must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at clinic admission.
Key exclusion criteria (8 listed)
- Non-medical use of psychoactive drugs other than, nicotine, alcohol, or caffeine 3 month prior to the Screening Visit;
- History of or current evidence of significant medical (e.g. seizure disorder) or psychiatric illness (e.g. psychosis) judged by the investigator to put the participant at greater risk of experiencing an adverse event due to exposure or completion of other study procedures.
- Use of an over the counter (OTC), systemic or topical drug(s), herbal supplement(s), or vitamin(s) within 14 days of experimental sessions; which, in the opinion of the investigator or sponsor, will interfere with the study result or the safety of the subject.
- Use of a prescription medication (with the exception of birth control prescriptions) within 14 days of experimental sessions; which, in the opinion of the investigator or sponsor, will interfere with the study result or the safety of the subject.
- Average use of cannabis more than 2 times per week in the prior 3 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 |
|---|---|---|
| D-LimoneneOral Limonene administered via capsule | Drug | Oral THC 30mg + D-Limonene 100mg, Oral THC 30mg + D-Limonene 200mg, Oral THC 30mg + D-Limonene 25mg, Oral THC 30mg + D-Limonene 50mg |
| Delta-9-THCAlso: THCOral delta-9-THC in ethanol vehicle administered via capsule | Drug | Oral THC 30mg, Oral THC 30mg + D-Limonene 100mg, Oral THC 30mg + D-Limonene 200mg, Oral THC 30mg + D-Limonene 25mg, Oral THC 30mg + D-Limonene 50mg |
| PlaceboPlacebo (cellulose) administered via capsule | Drug | Oral Placebo |
Primary outcome
Subjective Drug Effect as assessed by Visual Analog Scale
Time frame: 8 hours after dosing
Subjective drug effect will be measured on a 100 point visual analog scale (VAS) where 0 = no drug effect and 100 = strongest drug effect imaginable
4 secondary outcomes
Subjective Drug Liking as assessed by Visual Analog Scale
Time frame: 8 hours after dosing
Subjective anxiety as assessed by Visual Analog Scale
Time frame: 8 hours after dosing
Subjective hunger as assessed by Visual Analog Scale
Time frame: 8 hours after dosing
Subjective paranoia as assessed by Visual Analog Scale
Time frame: 8 hours after dosing
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
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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.
Austin Zamarripa, PhD principal investigator
Johns Hopkins School of Medicine
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 D-Limonene and Delta-9-THC in people with Subjective Drug Effects and THC, run by Johns Hopkins University at 1 site in United States.
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 8 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: looking for participants now, as of the sponsor's last update on 28 May 2026. 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 States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Austin Zamarripa, PhD (410-550-6969, czamarr2@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Subjective Drug Effect as assessed by Visual Analog Scale (time frame: 8 hours after dosing). 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 28 May 2026.