Dronabinol Effects Related to Cannabis Use

(THC-Gender-I Trial)

Overseen By Mohini Ranganathan, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Estrogen supplements

Disqualifiers: Cannabis naive, Major stressors, others

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

40 Participants Needed

Trial Summary

Do I need to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking estrogen supplements or oral contraceptive pills.

What evidence supports the effectiveness of the drug Dronabinol?

Dronabinol, a form of THC, has shown potential benefits in managing symptoms like pain, spasticity, and appetite loss in conditions such as chronic pain, multiple sclerosis, and cancer. Studies indicate that while it can cause side effects like dizziness and dry mouth, many patients report symptom improvement, suggesting it can be an effective treatment option. ^{1 2 3 4 5}

Is Dronabinol generally safe for human use?

Dronabinol, a cannabis-derived medicine, is generally considered to have a low risk profile with common side effects like dizziness and mood changes. Serious complications are rare, but it can affect heart rate and blood pressure, and may not be safe for people with heart issues or during pregnancy. ^{6 7 8 9 10}

How is the drug Dronabinol different from other treatments for cannabis use?

Dronabinol, which contains delta9-tetrahydrocannabinol (THC), is unique because it acts on the cannabinoid system in the brain, specifically targeting CB1 and CB2 receptors, which can help manage symptoms like nausea and appetite loss. Unlike other treatments, it can be administered orally and has a well-documented profile for treating conditions like nausea from chemotherapy and appetite issues in HIV/AIDS patients. ^{11 12 13 14 15}

What is the purpose of this trial?

The purpose of the study is to characterize the acute effects of cannabinoids in women relative to men and to begin probing the mechanisms that may underlie gender differences.

Eligibility Criteria

This trial is for healthy men and women who have tried cannabis at least once. Women must not be taking estrogen supplements or oral contraceptives, and participants with a sesame oil allergy cannot join. Those under major stress recently or currently are also excluded.

Inclusion Criteria

I am in good physical and mental health.

At least one lifetime exposure to cannabis

Exclusion Criteria

I am currently taking estrogen supplements or oral contraceptive pills.

Sesame oil allergy

Cannabis naive individuals

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single dose of 10 mg Dronabinol or placebo and are monitored for acute effects

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Dronabinol
• Placebo

Trial Overview The study aims to understand how cannabinoids affect men and women differently by comparing the effects of Dronabinol (a synthetic form of THC) to a placebo in healthy individuals.

Participant Groups

Group I: THC Active Control 1 Intervention

10 mg Dronabinol will be administered orally.

Group II: Placebo Placebo Group 1 Intervention

Placebo pill (no active cannabinoids).

Dronabinol 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
• Sleep apnea

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?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Findings from Research

In a meta-analysis of 16 trials, nabilone was associated with significantly higher rates of drowsiness, dizziness, and dry mouth compared to placebo, indicating a notable risk of these side effects.

Dronabinol also showed increased occurrences of dry mouth, dizziness, and headache compared to placebo, but the overall severity of adverse events was generally mild-to-moderate, suggesting that the benefits may outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. Bajtel, Á., Kiss, T., Tóth, B., et al.[2022]

In a survey of 10,010 patients in Germany, dronabinol was the most commonly prescribed cannabis-based medicine (65%), primarily for treating pain (73%), with side effects like tiredness and dizziness being consistent with known profiles of cannabis products.

Patients using cannabis flowers were generally younger and more likely to be male, with different treatment patterns and diagnoses compared to those using other cannabis medicines, indicating a need for careful monitoring and reporting in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Three years of cannabis as medicine-preliminary results of the survey accompanying the prescription of medical cannabis in Germany]. Schmidt-Wolf, G., Cremer-Schaeffer, P.[2021]

In a study of 2,112 adult patients with chronic pain, 92.5% reported improvement in their primary symptoms after using cannabis-based oral formulations, indicating high efficacy as an adjuvant treatment.

The majority of patients experienced minimal side effects, with 71.7% reporting none, and the most common mild side effects, such as somnolence and dizziness, tended to decrease over time, suggesting that these formulations are safe for chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex-Dependent Prescription Patterns and Clinical Outcomes Associated With the Use of Two Oral Cannabis Formulations in the Multimodal Management of Chronic Pain Patients in Colombia. Moreno-Sanz, G., Madiedo, A., Hernandez, P., et al.[2022]

A meta-analysis of 72 controlled clinical trials indicates that cannabinoids have significant therapeutic potential for various conditions, including as antiemetics, appetite stimulants, and analgesics.

Cannabinoids may be beneficial in treating debilitating diseases such as cancer and AIDS, as well as neurological disorders like multiple sclerosis and epilepsy, highlighting their diverse applications in medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids in medicine: A review of their therapeutic potential. Ben Amar, M.[2022]

In a study with 13 daily cannabis smokers, dronabinol (oral THC) was found to dose-dependently reduce cannabis withdrawal symptoms without causing significant cognitive impairment or adverse side effects, even at doses up to 120mg per day.

While dronabinol did not change the subjective effects of smoked cannabis, it did attenuate the increase in heart rate caused by cannabis at higher doses, suggesting a potential therapeutic role in managing withdrawal symptoms for those trying to quit cannabis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users. Vandrey, R., Stitzer, ML., Mintzer, MZ., et al.[2022]

A survey of delta-8-THC consumers revealed that over half (51%) use it to treat various health conditions, with anxiety and stress being the most common, suggesting potential therapeutic benefits.

Participants reported favorably comparing delta-8-THC to delta-9-THC and pharmaceutical drugs, indicating it may have similar efficacy with potentially fewer adverse effects, although knowledge about safe dosages and medical integration remains low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consumer Experiences with Delta-8-THC: Medical Use, Pharmaceutical Substitution, and Comparisons with Delta-9-THC. Kruger, DJ., Kruger, JS.[2023]

Cannabis-derived medications like dronabinol and nabilone are effective for treating nausea and vomiting from chemotherapy and appetite loss in AIDS patients, while medical cannabis is commonly recommended for pain and muscle spasms, showing significant improvement in these conditions.

While the adverse effects of cannabis are generally mild, such as dizziness, there are serious safety concerns, particularly regarding adolescent use leading to increased schizophrenia risk and cognitive impairments, as well as risks of accidental ingestion in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacologic and clinical effects of medical cannabis. Borgelt, LM., Franson, KL., Nussbaum, AM., et al.[2022]

Cannabinoids can cause a range of side effects, including euphoric mood changes, impaired cognitive and psychomotor performance, and potential acute psychotic episodes, particularly in individuals predisposed to schizophrenia.

Despite these side effects, the overall risk profile of cannabinoids appears low, with life-threatening complications being very rare; however, they are contraindicated during pregnancy and for individuals with a history of cardiac ischemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A review of side effects and complications with cannabinoid treatment]. Radbruch, L., Nauck, F.[2006]

In a study involving 30 HIV-positive marijuana smokers, both smoked marijuana and lower doses of dronabinol (10 and 20 mg) were well tolerated and significantly increased caloric intake, particularly in those with muscle mass loss.

The highest dose of dronabinol (30 mg) was poorly tolerated by some participants, indicating that while both treatments can enhance food intake, careful dosing is important for safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronabinol and marijuana in HIV(+) marijuana smokers: acute effects on caloric intake and mood. Haney, M., Rabkin, J., Gunderson, E., et al.[2022]

The rise in recreational cannabis use, particularly synthetic cannabinoids, has been linked to an increase in serious cardiovascular events, including sudden cardiac death and arrhythmias, especially among young men with few risk factors.

Older individuals and those with existing cardiovascular conditions may be at even greater risk, highlighting the need for further understanding of the complex interactions between cannabinoids and the cardiovascular system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Complications of Marijuana and Related Substances: A Review. Singh, A., Saluja, S., Kumar, A., et al.[2020]

Delta(9)-tetrahydrocannabinol (Delta(9)-THC) has well-documented therapeutic benefits, including reducing nausea from chemotherapy, increasing appetite, alleviating pain, and relieving symptoms of multiple sclerosis, supported by extensive research over the past 30 years.

While Delta(9)-THC can impair cognitive functions such as memory and perception, and may induce negative psychological effects like panic and hallucinations, the long-term impacts are still unknown, leading to a proposal by WHO to reschedule it as a low-risk substance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The good and the bad effects of (-) trans-delta-9-tetrahydrocannabinol (Delta 9-THC) on humans. Carlini, EA.[2013]

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 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]

The compounds delta9-tetrahydrocannabinol, 11-OH-delta9-tetrahydrocannabinol, and 9-nor-9beta-OH-hexahydrocannabinol were found to induce hypothermia and increase catecholamine synthesis in the brains of mice, indicating potential effects on body temperature regulation and stress response.

In contrast, cannabinol and cannabidiol did not show any activity in these tests, suggesting that not all cannabinoids have the same physiological effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of cannabinoids on body temperature and brain catecholamine synthesis. Bloom, AS., Johnson, KM., Dewey, WL.[2013]

Delta9-tetrahydrocannabinol (delta9-THC) does not achieve the maximum activation of cannabinoid receptors compared to stronger agonists like CP55940, and at high concentrations, it can act as an antagonist.

Cannabinol is identified as a weak agonist of cannabinoid receptors, while cannabidiol functions as an antagonist at micromolar concentrations, indicating diverse roles of these cannabinoids in receptor activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complex pharmacology of natural cannabinoids: evidence for partial agonist activity of delta9-tetrahydrocannabinol and antagonist activity of cannabidiol on rat brain cannabinoid receptors. Petitet, F., Jeantaud, B., Reibaud, M., et al.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

[Three years of cannabis as medicine-preliminary results of the survey accompanying the prescription of medical cannabis in Germany]. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Sex-Dependent Prescription Patterns and Clinical Outcomes Associated With the Use of Two Oral Cannabis Formulations in the Multimodal Management of Chronic Pain Patients in Colombia. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Cannabinoids in medicine: A review of their therapeutic potential. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users. [2022]

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

Consumer Experiences with Delta-8-THC: Medical Use, Pharmaceutical Substitution, and Comparisons with Delta-9-THC. [2023]

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

The pharmacologic and clinical effects of medical cannabis. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

[A review of side effects and complications with cannabinoid treatment]. [2006]

9. Germany pubmed.ncbi.nlm.nih.gov

Dronabinol and marijuana in HIV(+) marijuana smokers: acute effects on caloric intake and mood. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Cardiovascular Complications of Marijuana and Related Substances: A Review. [2020]

11. England pubmed.ncbi.nlm.nih.gov

The good and the bad effects of (-) trans-delta-9-tetrahydrocannabinol (Delta 9-THC) on humans. [2013]

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

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

13. Germany pubmed.ncbi.nlm.nih.gov

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

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

The effects of cannabinoids on body temperature and brain catecholamine synthesis. [2013]

15. Netherlands pubmed.ncbi.nlm.nih.gov

Complex pharmacology of natural cannabinoids: evidence for partial agonist activity of delta9-tetrahydrocannabinol and antagonist activity of cannabidiol on rat brain cannabinoid receptors. [2019]