THC + D-Limonene for Heartburn

Overseen By Lauren S Pollak, MSc

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Must not be taking: OTC drugs, Prescription drugs

Disqualifiers: Seizure disorder, Psychosis, Cardiac arrhythmias, others

Compensation: Varies

Number of Visits: 6

Duration: 6 sessions

65 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any over-the-counter drugs, herbal supplements, vitamins, or prescription medications (except birth control) at least 14 days before the experimental sessions, as they might interfere with the study.

What data supports the effectiveness of the drug THC + D-Limonene for heartburn?

Research shows that delta9-tetrahydrocannabinol (THC) can affect the lower oesophageal sphincter, which is involved in gastro-oesophageal reflux, a condition related to heartburn. This suggests that THC might help manage heartburn by influencing this mechanism. ^{1 2 3 4 5}

Is THC safe for human use?

THC (Delta-9-tetrahydrocannabinol) is generally considered safe for medical use, as it is approved for conditions like nausea from chemotherapy and HIV-related anorexia. However, it can cause side effects like increased heart rate and intoxication, and its safety profile may vary depending on the form of administration and individual health conditions. Long-term safety monitoring is recommended. ^{1 2 4 6 7}

How does the drug THC + D-Limonene for heartburn differ from other treatments?

This drug is unique because it combines Delta-9-THC, known for its use in treating nausea and appetite loss, with D-Limonene, a compound found in citrus oils, potentially offering a novel approach to heartburn by utilizing different mechanisms than traditional antacids or proton pump inhibitors. ^{1 3 8 9 10}

Research Team

Austin Zamarripa, PhD

Principal Investigator

Johns Hopkins School of Medicine

Eligibility Criteria

This trial is for healthy adults who want to participate in a study examining the effects of d-limonene, THC, and their combination when taken by mouth. Specific eligibility criteria are not provided.

Inclusion Criteria

Test negative for drugs of abuse other than cannabis, including breath alcohol at the screening visit and at clinic admission

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

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

Exclusion Criteria

I have a history of serious heart rhythm problems or spasms in my blood vessels.

I haven't taken any prescription drugs in the last 14 days that could affect the study.

Average use of cannabis more than 2 times per week in the prior 3 months

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive orally administered THC and D-limonene in various doses across 6 outpatient drug administration sessions

6 sessions

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Delta-9-THC
• D-Limonene

Trial Overview The study is testing how orally administered d-limonene, delta-9-THC (the active ingredient in cannabis), and their combination affect individuals. Some participants will receive a placebo instead of the active substances.

Participant Groups

Group I: Oral THC 30mg + D-Limonene 50mg Experimental Treatment 2 Interventions

30mg pure THC in ethanol vehicle, via capsule 50mg pure D-Limonene, via capsule

Group II: Oral THC 30mg + D-Limonene 25mg Experimental Treatment 2 Interventions

30mg pure THC in ethanol vehicle, via capsule 25mg pure D-Limonene, via capsule

Group III: Oral THC 30mg + D-Limonene 200mg Experimental Treatment 2 Interventions

30mg pure THC in ethanol vehicle, via capsule 200mg pure D-Limonene, via capsule

Group IV: Oral THC 30mg + D-Limonene 100mg Experimental Treatment 2 Interventions

30mg pure THC in ethanol vehicle, via capsule 100mg pure D-Limonene, via capsule

Group V: Oral THC 30mg Experimental Treatment 1 Intervention

30mg pure THC in ethanol vehicle, via capsule

Group VI: Oral Placebo Placebo Group 1 Intervention

Placebo (cellulose), via capsule

Delta-9-THC is already approved in United States, Canada for the following indications:

Approved in United States as Marinol for:

• HIV/AIDS-induced anorexia
• chemotherapy-induced nausea and vomiting

Approved in United States as Syndros for:

• HIV/AIDS-induced anorexia
• chemotherapy-induced nausea and vomiting

Approved in Canada as REDUVO for:

• HIV/AIDS-induced anorexia
• chemotherapy-induced nausea and vomiting

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

In a study involving 10 experienced marijuana smokers, oral Delta-9-tetrahydrocannabinol (Delta(9)-THC) was found to be chosen more often than a placebo, indicating some reinforcing effects, although participants selected it less than 50% of the time.

Both doses of Delta(9)-THC (10 mg and 20 mg) led to significant increases in positive subjective effects, impaired psychomotor performance, and increased heart rate, suggesting potential safety concerns alongside its therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reinforcing effects of oral Delta9-THC in male marijuana smokers in a laboratory choice procedure. Hart, CL., Haney, M., Vosburg, SK., et al.[2022]

Chronic administration of Δ(9)-THC did not significantly affect the progression of SIV infection in male Chinese-derived rhesus macaques, as there were no notable differences in viral loads compared to the placebo group.

Long-term Δ(9)-THC treatment was associated with a significant reduction in circulating IgE(+)B cells, suggesting potential immunomodulatory effects, but it did not enhance the pathogenicity of the SIV infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic Δ(9)-Tetrahydrocannabinol Administration Reduces IgE(+)B Cells but Unlikely Enhances Pathogenic SIVmac251 Infection in Male Rhesus Macaques of Chinese Origin. Wei, Q., Liu, L., Cong, Z., et al.[2018]

Aerosolized delta9-tetrahydrocannabinol (THC) significantly increased airway conductance in healthy subjects, showing a maximum effect of 33-41% after 1-2 hours, although it was less effective than isoproterenol initially but surpassed it after 1-3 hours.

While aerosolized THC had minimal systemic side effects and showed some bronchodilation in asthmatic subjects, it also caused moderate to severe bronchoconstriction in some cases, indicating potential local irritation that may limit its therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bronchial effects of aerosolized delta 9-tetrahydrocannabinol in healthy and asthmatic subjects. Tashkin, DP., Reiss, S., Shapiro, BJ., et al.[2013]

In a study involving 7 HIV-positive marijuana smokers, high doses of dronabinol (10 mg QID) were found to safely increase caloric intake and improve sleep quality, but only during the first 8 days of treatment.

Participants experienced sustained mood enhancement over the 16-day study, indicating that while dronabinol is effective, there may be a need for higher doses to maintain its appetite-stimulating effects due to the development of tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study. Bedi, G., Foltin, RW., Gunderson, EW., et al.[2022]

The safety of cannabis and cannabinoid medications is a significant concern, and while some safety information can be drawn from recreational use studies, medical and recreational users may experience different effects.

There is a pressing need for long-term safety monitoring of cannabinoid use in patients, as clinical experience is still developing, which will help inform both therapeutic decisions and public policy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety issues concerning the medical use of cannabis and cannabinoids. Ware, MA., Tawfik, VL.[2019]

In a study involving six volunteers, both liquid and capsule forms of THC-containing hemp oils produced plasma THC levels comparable to synthetic THC (dronabinol) used for appetite stimulation, indicating their potential efficacy as dietary supplements.

The study found that THC and its metabolites were detectable in plasma for varying durations, with THCCOOH persisting for up to 39.5 hours after dosing, suggesting a prolonged effect of THC from hemp oils compared to synthetic forms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delta(9)-tetrahydrocannabinol, 11-hydroxy-delta(9)-tetrahydrocannabinol and 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol in human plasma after controlled oral administration of cannabinoids. Goodwin, RS., Gustafson, RA., Barnes, A., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Reinforcing effects of oral Delta9-THC in male marijuana smokers in a laboratory choice procedure. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

A Phase I Trial to Determine the Pharmacokinetics, Psychotropic Effects, and Safety Profile of a Novel Nanoparticle-Based Cannabinoid Spray for Oromucosal Delivery. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Chronic Δ(9)-Tetrahydrocannabinol Administration Reduces IgE(+)B Cells but Unlikely Enhances Pathogenic SIVmac251 Infection in Male Rhesus Macaques of Chinese Origin. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Bronchial effects of aerosolized delta 9-tetrahydrocannabinol in healthy and asthmatic subjects. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Effect of delta9-tetrahydrocannabinol, a cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Safety issues concerning the medical use of cannabis and cannabinoids. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of antiulcer activity of delta9-tetrahydrocannabinol in the Shay rat test. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Recent advantages in cannabinoid research. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Delta(9)-tetrahydrocannabinol, 11-hydroxy-delta(9)-tetrahydrocannabinol and 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol in human plasma after controlled oral administration of cannabinoids. [2022]