Cannabidiol for Older Adult Cannabis Users

(QUARTz Trial)

Overseen By Kyle A Chrystal, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Boulder

Must be taking: Pain, sleep, mood medications

Must not be taking: Anti-epileptics, antipsychotics, others

Disqualifiers: Psychosis, chemotherapy, other drug use, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

385 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not be using certain medications like anti-epileptic drugs or those with major interactions with Epidiolex. You must also be taking medications for pain, sleep, or mood to participate.

What data supports the effectiveness of the drug Cannabidiol (CBD) for older adult cannabis users?

Research suggests that CBD may have therapeutic effects for conditions like social anxiety disorder and substance use disorders, and it is generally well tolerated with mild side effects. Additionally, CBD has shown potential benefits for people with cannabis use disorder, which might be relevant for older adult cannabis users. ^{1 2 3 4 5}

Is cannabidiol (CBD) generally safe for human use?

CBD is generally well tolerated in humans, but it can cause some side effects like diarrhea, sleepiness, and changes in liver function. It may also interact with other medications, so it's important to monitor for any adverse effects, especially if you are taking other drugs. ^{4 5 6 7 8}

How is the drug Cannabidiol (CBD) unique for older adult cannabis users?

Cannabidiol (CBD) is unique because it is a non-psychoactive compound from cannabis that has anti-inflammatory, anti-anxiety, and antioxidant properties, which may help older adults who use cannabis. Unlike other treatments, CBD interacts with the body's oxidative stress pathways, potentially offering protective effects without the high associated with cannabis. ^{9 10 11 12 13}

What is the purpose of this trial?

Cannabis use increased 10 fold among adults over the age of 65 between 2014 and 2016 but very little data exists on the extent of their harmful effects on health and behavior. The overarching goal of this project is to test a novel harm reduction strategy in which older individuals who seek to use cannabis for pain, anxiety or mood problems (depression/anxiety) will be randomly assigned to one of three conditions in an 8 week randomized controlled trial: hemp-derived CBD+THC, hemp-derived CBD-THC, or placebo. This work has the ability to directly inform individual choices regarding the use of cannabis products among older adults, and direct policy decisions regulating cannabis formulations on the legal market.

Eligibility Criteria

This trial is for older adults who use cannabis to manage pain, anxiety, or mood problems like depression. Participants will be randomly assigned to one of three groups: one receiving hemp-derived CBD with THC (fsCBD), another getting CBD without THC (bsCBD), and a placebo group.

Inclusion Criteria

I am 60 years old or older.

My liver tests (ALT and AST) are within twice the normal limit.

Able to provide informed consent

Exclusion Criteria

I or someone in my family has been diagnosed with psychosis.

Blood alcohol level > 0 at screening (to sign consent form)

Report of other drug use (cocaine, opiates, methamphetamine) in the past 90 days or fail urine screen for any of these drugs

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to one of three conditions: hemp-derived CBD+THC, hemp-derived CBD-THC, or placebo for an 8-week period

8 weeks

Baseline, 4 weeks, 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cannabidiol

Trial Overview The study aims to test the effectiveness of two types of cannabidiol (CBD) as a harm reduction strategy for older cannabis users over an 8-week period. It compares full-spectrum CBD that includes THC (fsCBD) and broad-spectrum CBD that excludes THC (bsCBD) against a placebo.

Participant Groups

Group I: Full-Spectrum Hemp-Derived CBD (fsCBD) Experimental Treatment 1 Intervention

8 weeks of use of a daily dose of cannabis (200mg CBD/4mg THC)

Group II: Broad-Spectrum Hemp-Derived CBD (bsCBD) Experimental Treatment 1 Intervention

8 weeks of use of a daily dose of cannabis (200mg CBD)

Group III: Placebo Placebo Group 1 Intervention

Cannabidiol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

University of Colorado, Boulder

Lead Sponsor

Trials

128

Recruited

29,600+

Findings from Research

A review of 25 studies involving 927 patients suggests that cannabidiol (CBD) has potential therapeutic effects for conditions like social anxiety disorder and psychotic disorders, particularly with acute administration.

While CBD was generally well tolerated with only mild side effects, the studies showed significant variability in dosage and administration methods, indicating a need for standardized protocols in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosage, Efficacy and Safety of Cannabidiol Administration in Adults: A Systematic Review of Human Trials. Larsen, C., Shahinas, J.[2020]

In a study involving 20 patients with severe behavioral and psychological symptoms of dementia (BPSD), those treated with 3% cannabidiol (CBD) showed significant improvement compared to those receiving usual medical treatment over a six-month period.

The results suggest that CBD may be a safer and more effective option for managing BPSD, indicating a need for larger randomized clinical trials to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Cannabidiol 3% on Neuropsychiatric Symptoms in Dementia - Six-Month Follow-Up. Alexandri, F., Papadopoulou, L., Tsolaki, A., et al.[2023]

11% of surveyed cannabis users reported using CBD primarily to reduce their cannabis consumption, with significant associations found for those who also smoke tobacco or drink alcohol.

Among those using CBD for reduction, 58.7% reported a large decrease in cannabis use, particularly linked to non-daily cannabis use and daily CBD consumption, with many citing reduced withdrawal symptoms as a key benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A "Good" Smoke? The Off-Label Use of Cannabidiol to Reduce Cannabis Use. Fortin, D., Di Beo, V., Massin, S., et al.[2022]

A systematic review of 4186 studies on cannabidiol (CBD) revealed that most research focuses on neurological outcomes, with significant adverse events reported in this area, highlighting the need for careful assessment of CBD's safety.

There is a notable gap in research regarding the reproductive and developmental toxicity of CBD, suggesting that future studies should prioritize these areas to establish safe intake levels for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Safety Data: A Systematic Mapping Study. Henderson, RG., Franke, KS., Payne, LE., et al.[2023]

In a survey of 239 young adults using cannabis, those who preferred CBD-dominant products were more likely to be female, use cannabis less frequently, and report using it primarily for medical reasons such as pain and psychological issues.

The study found a concerning association between CBD use and increased illicit drug use, suggesting that some individuals may be using CBD as a form of self-medication for underlying psychological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol (CBD) and other drug use among young adults who use cannabis in Los Angeles. Fedorova, EV., Wong, CF., Ataiants, J., et al.[2022]

Nearly 50% of CBD users experienced adverse drug events (ADEs), with common issues including elevated liver enzymes, sedation, and sleep disturbances, indicating a significant safety concern.

CBD has a high potential for drug-drug interactions (DDIs) due to its effects on drug metabolism, particularly with enzymes like CYP3A4 and CYP2C19, suggesting that careful monitoring and dose adjustments may be necessary for patients on multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. Brown, JD., Winterstein, AG.[2020]

Serious suspected adverse reactions (SARs) to unlicensed cannabidiol (CBD) products were found to be 18.9% of all adverse events, with a higher frequency in men and adults, indicating a need for careful monitoring of its use.

The most common adverse effects associated with unlicensed CBD included mental disorders, hepatic disorders, and worsening of pre-existing epilepsy, particularly in patients also taking antiepileptic medications like clobazam and valproic acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. Calapai, F., Esposito, E., Ammendolia, I., et al.[2023]

A systematic review of 12 clinical trials involving 803 participants found that cannabidiol (CBD) is associated with a higher likelihood of withdrawal due to adverse effects compared to placebo, particularly in studies related to childhood epilepsy.

While CBD generally appears well tolerated, significant adverse effects such as abnormal liver function tests and sedation were noted, especially in combination with other medications, highlighting the need for careful monitoring of drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Chesney, E., Oliver, D., Green, A., et al.[2021]

In a study involving six groups of rats, CBD oil significantly improved liver function and antioxidant levels in rats with DMBA-induced leukemia, indicating its potential therapeutic benefits.

The results showed that treating rats with CBD after leukemia induction was more effective than using it as a preventive measure, highlighting its role in improving biochemical and molecular health in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential protective and therapeutic effects of cannabidiol oil on experimental Leukemia induced by DMBA in male rats. Soliman, NA., El Dahmy, SI., Khamis, T., et al.[2023]

Cannabidiol (CBD) has potential therapeutic effects against oxidative stress-related diseases by regulating the Nrf2 pathway, which is crucial for maintaining redox balance and inflammation.

The study highlights that CBD can exhibit both antioxidant and pro-oxidative effects, depending on the cellular context, and its interaction with Nrf2 and NF-κB may influence the cellular response to oxidative stress and cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The molecular activity of cannabidiol in the regulation of Nrf2 system interacting with NF-κB pathway under oxidative stress. Atalay Ekiner, S., Gęgotek, A., Skrzydlewska, E.[2023]

DMDD significantly inhibits the growth of diffuse large B lymphoma (DLBCL) tumors in mice and prolongs their survival, demonstrating its potential as an effective treatment.

In cell studies, DMDD induces apoptosis in DLBCL cells by activating the mitochondrial apoptosis pathway and down-regulating key survival proteins, suggesting a specific mechanism of action through the JAK2/STAT3 and NF-kappa B signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of 2-12alkyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione(DMDD)on diffuse large B lymphoma and its mechanism]. Hong, K., Jiang, PR., Ke, RJ., et al.[2020]

Older patients with diffuse large B-cell lymphoma (DLBCL) face higher risks of treatment-related toxicity, especially if they are deemed unfit or frail based on comprehensive geriatric assessment (CGA).

Despite these challenges, many older patients can still achieve curative outcomes with standard R-CHOP chemotherapy, highlighting the importance of careful assessment of frailty and comorbidities to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diffuse Large B-Cell Lymphoma in the Elderly: Current Approaches. Allen, P.[2021]

Next-generation sequencing has enhanced our understanding of the molecular pathways involved in diffuse large B-cell lymphoma (DLBCL), which is crucial for developing targeted therapies.

There are many promising new drugs and immunotherapy options being developed that aim to improve DLBCL treatment by overcoming resistance and exploiting synergistic effects when used in combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel targeted therapies in diffuse large B-cell lymphoma. Mehta-Shah, N., Younes, A.[2018]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Dosage, Efficacy and Safety of Cannabidiol Administration in Adults: A Systematic Review of Human Trials. [2020]

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

The Effect of Cannabidiol 3% on Neuropsychiatric Symptoms in Dementia - Six-Month Follow-Up. [2023]

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

A "Good" Smoke? The Off-Label Use of Cannabidiol to Reduce Cannabis Use. [2022]

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

Cannabidiol Safety Data: A Systematic Mapping Study. [2023]

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

Cannabidiol (CBD) and other drug use among young adults who use cannabis in Los Angeles. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. [2021]

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

The potential protective and therapeutic effects of cannabidiol oil on experimental Leukemia induced by DMBA in male rats. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

The molecular activity of cannabidiol in the regulation of Nrf2 system interacting with NF-κB pathway under oxidative stress. [2023]

11. China pubmed.ncbi.nlm.nih.gov

[Effects of 2-12alkyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione(DMDD)on diffuse large B lymphoma and its mechanism]. [2020]

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

Diffuse Large B-Cell Lymphoma in the Elderly: Current Approaches. [2021]

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

Novel targeted therapies in diffuse large B-cell lymphoma. [2018]