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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how THC (Delta-9-tetrahydrocannabinol) and d-limonene, taken orally, affect heartburn in healthy adults. Researchers aim to determine how these substances work individually and together to potentially ease heartburn symptoms. Participants will receive different treatments: a placebo, THC alone, or THC combined with various doses of d-limonene. Ideal candidates are healthy adults who have previously used high THC cannabis and experienced anxiety from it at least once. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to explore new therapeutic possibilities.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both THC and d-limonene have some safety information available. THC, used in medicines like Marinol, can cause side effects such as dependency and memory problems. It is considered safe for certain conditions, though some may find the side effects unpleasant.

Studies have indicated that d-limonene, a compound found in citrus oils, does not pose serious health risks like cancer or kidney damage. It has been used safely in various applications, including dissolving gallstones.

This trial is in an early phase, primarily focusing on safety. The trial aims to assess how well participants can tolerate the treatment. While THC and d-limonene have been used separately in other contexts, their combination is still under study for safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Delta-9-THC and D-Limonene for heartburn because they bring a fresh approach compared to the usual antacids or proton pump inhibitors. Delta-9-THC, known for its properties in managing nausea and vomiting, might offer unique relief for heartburn by potentially calming the digestive system differently than traditional treatments. D-Limonene, a compound found in citrus oils, has shown promise in soothing the esophagus and stomach lining, potentially reducing acid reflux symptoms. Together, these compounds offer a novel mechanism that could complement or even surpass current treatments.

What evidence suggests that this trial's treatments could be effective for heartburn?

Research has shown that THC, a compound in cannabis, can reduce heartburn by decreasing the frequency of acid reflux into the esophagus. One study found that THC significantly reduced these episodes in the first hour after eating. It also helped prevent the relaxation of a muscle at the bottom of the esophagus, which often allows acid to rise. Meanwhile, D-limonene, a compound in citrus fruits, may alleviate GERD (gastroesophageal reflux disease) symptoms by calming the stomach and aiding digestion. This trial will test various combinations of THC and D-limonene to explore their potential benefits for relieving heartburn. ^{6 7 8 9 10}

Who Is on the Research Team?

Austin Zamarripa, PhD

Principal Investigator

Johns Hopkins School of Medicine

Are You a Good Fit for This Trial?

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

Have provided written informed consent

Exclusion Criteria

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2697772/

Effect of Δ9-tetrahydrocannabinol, a cannabinoid receptor ... During the first postprandial hour the amount of reflux episodes was decreased from 1.83 ± 0.5 (placebo) to 0.67 ± 0.4 [Δ9-tetrahydrocannabinol (Δ9-THC) 20 mg].

2. researchgate.net researchgate.net/publication/23643423_Effect_of_D9-tetrahydrocannabinol_a_cannabinoid_receptor_agonist_on_the_triggering_of_transient_lower_oesophageal_sphincter_relaxations_in_dogs_and_humans

Effect of Δ9‐tetrahydrocannabinol, a cannabinoid receptor ... Similarly, in healthy volunteers, delta(9)-THC significantly reduced the number of TLESRs and caused a non-significant reduction of acid reflux ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1995764516300712

Gastric acid inhibitory and gastric protective effects of ... Given the data suggesting that the CB1 agonist THC reduces transient lower oesophageal sphincter relaxations and gastro-oesophageal reflux [30], cannabinoid- ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19068079/

Effect of delta9-tetrahydrocannabinol, a cannabinoid ... Similarly, in healthy volunteers, delta(9)-THC significantly reduced the number of TLESRs and caused a non-significant reduction of acid reflux episodes in the ...

5. academic.oup.com academic.oup.com/dote/article/30/2/1/2725531

Dronabinol increases pain threshold in patients with functional ... It is postulated that Δ9-THC will be effective among all types of NCCP with decreased pain threshold including GERD, and in particular PPI resistant GERD ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/018651s029lbl.pdf

MARINOL (dronabinol) capsules, for oral use The safety and effectiveness of MARINOL have not been established in pediatric patients. ... Advise patients, especially those with cardiac ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/dronabinol-oral-route/description/drg-20063560

Dronabinol (oral route) - Side effects & dosage Safety and efficacy have not been established. ... Appropriate studies performed to date have not demonstrated geriatric-specific problems that ...

8. webmd.com webmd.com/drugs/2/drug-8774-1840/dronabinol-oral/dronabinol-solution-oral/details

Dronabinol (Marinol, Syndros) - Uses, Side Effects, and More Dronabinol is a controlled substance because it can be misused or lead to dependence. Store dronabinol in a safe place to protect it from theft.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10336994/

Should gastroenterologists prescribe cannabis? The highs ... However, both its acute and chronic use can lead to undesirable side effects such as dependency and addiction, cognitive impairment and cannabinoid hyperemesis ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5569602/

An Update on Safety and Side Effects of Cannabidiol Acute Clinical Data. Bergamaschi et al. list an impressive number of acute and chronic studies in humans, showing CBD safety for a wide array of side effects.