Cannabis for Cigarette Smoking

Overseen By Dustin Lee, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Johns Hopkins University

Disqualifiers: Illicit drugs, Suicidal behavior, Cardiac arrhythmias, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the impact of tetrahydrocannabinol (THC) administration on motivational, subjective, and physiological effects of cigarettes. The study's goals are to test demand for cigarettes, tobacco craving, affect, heart rate, blood pressure, expired breath carbon monoxide, and cognitive performance. Researchers will compare multiple doses of THC and a placebo in participants who smoke cigarettes and either smoke or vape THC in the laboratory.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot participate if you test positive for illicit drugs other than cannabis and tobacco.

What data supports the effectiveness of the drug THC, Tetrahydrocannabinol, Δ9-THC, Dronabinol, Marinol, Syndros for cigarette smoking cessation?

Research shows that dronabinol, a form of THC, has been effective in reducing pain and increasing satisfaction in patients with chronic pain, suggesting it may have potential benefits for other conditions. However, there is no direct evidence from the provided studies about its effectiveness for cigarette smoking cessation. ^{1 2 3 4 5}

Is cannabis generally safe for human use?

Cannabis and its components, like THC, have been used both recreationally and medically, but they can cause side effects such as increased heart rate, low blood pressure, lung irritation (if smoked), and mental effects like anxiety or paranoia. Synthetic THC, like dronabinol, is considered safer due to its slower onset and lower potency, but caution is advised, especially for people with heart, lung, or mental health issues. ^{6 7 8 9 10}

How does the drug THC differ from other treatments for cigarette smoking?

THC (Tetrahydrocannabinol) is unique because it is primarily known for its psychoactive effects and is being explored for its potential to help with cigarette smoking, which is not a standard use. Unlike traditional nicotine replacement therapies, THC works by interacting with the brain's cannabinoid receptors, which may influence smoking behavior differently. ^{11 12 13 14 15}

Research Team

Dustin Lee, PhD

Principal Investigator

Johns Hopkins School of Medicine

Eligibility Criteria

This trial is for individuals who regularly use tobacco and cannabis. Participants should be willing to smoke or vape THC in a lab setting. The study excludes those with certain health conditions, but specific exclusion criteria are not listed.

Inclusion Criteria

I am willing to use effective birth control during the study.

I am 21 or older and not currently seeking any medical treatment.

I smoke tobacco cigarettes every day.

Exclusion Criteria

Are currently pregnant, planning to become pregnant in the next three months or are currently breastfeeding

I have a history of serious heart rhythm problems or vasospastic disease.

I plan to cut down or quit smoking or using cannabis soon.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of THC and placebo to assess the impact on cigarette use behavior

6 visits

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• THC (Cannabinoid)

Trial Overview The study examines the effects of different doses of THC (5mg, 30mg, and a placebo with no THC) on cigarette smokers' behavior, cravings, mood changes, heart rate, blood pressure, lung function via breath carbon monoxide levels and thinking skills.

Participant Groups

Group I: Vaporized THC Experimental Treatment 5 Interventions

Each participant in this arm will receive 0, 5, and 30mg of THC over the course of six visits. Each participant will also receive combustible cigarettes containing 0.03mg and 0.80mg of nicotine.

Group II: Smoked THC Experimental Treatment 5 Interventions

Each participant in this arm will receive 0, 5, and 30mg of THC over the course of six visits. Each participant will also receive combustible cigarettes containing 0.03mg and 0.80mg of nicotine.

THC is already approved in Canada for the following indications:

Approved in Canada as Dronabinol for:

• Appetite loss and weight loss in HIV/AIDS
• Nausea and vomiting from chemotherapy

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

A daily dose of 40 mg of rimonabant for 15 days effectively reduced the physiological effects of smoked cannabis, such as tachycardia, similar to a single higher dose of 90 mg on the first day of treatment.

While the 40 mg dose significantly decreased subjective effects of cannabis on day 8, it did not maintain this effect by day 15, indicating that repeated dosing may not consistently reduce the subjective experience of cannabis effects over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users. Huestis, MA., Boyd, SJ., Heishman, SJ., et al.[2019]

In a study involving 30 patients on opioids for chronic pain, dronabinol (synthetic THC) was found to significantly reduce pain intensity and increase treatment satisfaction compared to a placebo, indicating its potential as an effective adjuvant treatment.

The extended Phase II trial showed that titrated doses of dronabinol provided significant pain relief and reduced pain bothersomeness, although side effects were dose-related, suggesting careful monitoring is needed when using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. Narang, S., Gibson, D., Wasan, AD., et al.[2013]

In a study of 1,145 patients with refractory chronic pain, adding Δ9-tetrahydrocannabinol (dronabinol) to their treatment significantly reduced average pain intensity from 46.3 to 26.8 mm on a visual analog scale over 12 weeks.

Dronabinol was well tolerated, with 46.8% of patients reporting mild drug-related adverse events, and many patients were able to reduce or stop other pain medications during the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Tolerability of Dronabinol Use in Patients with Chronic Pain: A Retrospective Analysis of 12-Week Open-Label Real-World Data Provided by the German Pain e-Registry. Ueberall, MA., Horlemann, J., Schuermann, N., et al.[2022]

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]

The FDA approved Syndros, an oral solution containing dronabinol (delta-9-THC), on July 1, 2016, indicating its recognized therapeutic use.

Syndros is classified as a Schedule II controlled substance by the DEA, highlighting its potential for abuse but also its medical value.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-trans- tetrahydrocannabinol (delta-9-THC)] in Schedule II. Final rule. [2018]

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]

Natural cannabinoids are increasingly used in medical settings and consumer health products, but they carry risks of adverse drug events and interactions due to their complex pharmacology.

Synthetic cannabinoids are more potent than natural ones and can lead to severe reactions, highlighting the need for caution, especially in vulnerable populations at risk for drug-drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural and Synthetic Cannabinoids: Pharmacology, Uses, Adverse Drug Events, and Drug Interactions. Brown, JD., Rivera Rivera, KJ., Hernandez, LYC., et al.[2022]

This paper introduces a framework for assessing the safety of additives in cannabis concentrates, aimed at helping regulators and manufacturers without extensive toxicological expertise.

Based on data from over 54,000 users of smart vaporization devices, the study suggests a standard consumption assumption of 100 mg per day for cannabis concentrates to facilitate risk assessments of these additives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A First-Tier Framework for Assessing Toxicological Risk from Vaporized Cannabis Concentrates. Vreeke, S., Faulkner, DM., Strongin, RM., et al.[2022]

In 2016, the quit ratios for cigarette smoking were significantly lower among individuals with cannabis use (23%) and cannabis use disorders (CUDs, 15%) compared to those without cannabis use (51% and 48%).

From 2002 to 2016, quit ratios did not improve for individuals with CUDs, highlighting a need for targeted public health strategies to support smoking cessation in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cigarette smoking quit ratios among adults in the USA with cannabis use and cannabis use disorders, 2002-2016. Weinberger, AH., Pacek, LR., Wall, MM., et al.[2021]

Daily cannabis users show a significantly higher prevalence of cigarette dependence compared to non-daily or non-cannabis users, indicating a potential link between cannabis use and increased cigarette addiction.

From 2002 to 2019, there has been a notable increase in cigarette dependence among both non-daily cannabis users and light to moderate smokers who do not use cannabis, suggesting a growing public health concern regarding smoking cessation efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cigarette dependence is more prevalent and increasing among US adolescents and adults who use cannabis, 2002-2019. Weinberger, AH., Dierker, L., Zhu, J., et al.[2023]

Early cannabis use before age 17 is associated with a significantly higher likelihood of developing nicotine dependence, with early users being about twice as likely to report this compared to their co-twins who only experimented with cigarettes.

The increased risk for nicotine dependence in early cannabis users is largely due to shared genetic factors rather than a direct causal relationship between cannabis use and nicotine dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early cannabis use and DSM-IV nicotine dependence: a twin study. Agrawal, A., Lynskey, MT., Pergadia, ML., et al.[2021]

From 2002 to 2016, the overall prevalence of cannabis use disorder (CUD) decreased, but it significantly increased among non-daily cigarette smokers, indicating a growing concern in this subgroup.

In 2016, CUD was notably more prevalent among non-daily (4.32%) and daily (2.92%) cigarette smokers compared to former (0.99%) and never smokers (1.11%), highlighting the association between cigarette smoking and higher rates of CUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in cannabis use disorder by cigarette smoking status in the United States, 2002-2016. Weinberger, AH., Pacek, LR., Wall, MM., et al.[2019]

In a study of 3787 female twins aged 18-29, cannabis users were found to have a 4.4 times higher risk of progressing from initiating cigarette smoking to regular smoking, and a 2.8 times higher risk of moving from regular smoking to nicotine dependence.

These findings highlight a significant public health concern, as cannabis use may lead to increased rates of cigarette smoking and nicotine dependence, which are associated with high mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transitions to regular smoking and to nicotine dependence in women using cannabis. Agrawal, A., Madden, PA., Bucholz, KK., et al.[2021]

References

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

Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users. [2019]

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

Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Effectiveness and Tolerability of Dronabinol Use in Patients with Chronic Pain: A Retrospective Analysis of 12-Week Open-Label Real-World Data Provided by the German Pain e-Registry. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Co-exposure of cocaine and cannabinoids and its association with select biological, behavioural and health outcomes: A systematic scoping review of multi-disciplinary studies. [2022]

5. 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]

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

Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-trans- tetrahydrocannabinol (delta-9-THC)] in Schedule II. Final rule. [2018]

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

Methods for clinical research involving cannabis administration. [2019]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Natural and Synthetic Cannabinoids: Pharmacology, Uses, Adverse Drug Events, and Drug Interactions. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

A First-Tier Framework for Assessing Toxicological Risk from Vaporized Cannabis Concentrates. [2022]

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

Cigarette smoking quit ratios among adults in the USA with cannabis use and cannabis use disorders, 2002-2016. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Cigarette dependence is more prevalent and increasing among US adolescents and adults who use cannabis, 2002-2019. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Early cannabis use and DSM-IV nicotine dependence: a twin study. [2021]

14. Ireland pubmed.ncbi.nlm.nih.gov

Trends in cannabis use disorder by cigarette smoking status in the United States, 2002-2016. [2019]

15. Ireland pubmed.ncbi.nlm.nih.gov

Transitions to regular smoking and to nicotine dependence in women using cannabis. [2021]