Medical Cannabis for Chronic Pain

Overseen By Angela Birnbaum, Ph.D., MLS(ASCP), FAES

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Disqualifiers: Neurological conditions, Psychotic disorders, Bipolar, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 16 weeks

180 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications, as long as they are prescribed treatments. However, you must abstain from alcohol, nicotine, and other non-treatment drugs for 24 hours before the study.

What data supports the effectiveness of the drug medical cannabis for chronic pain?

Research shows that medical cannabis may provide moderate relief for neuropathic pain (pain from nerve damage), but its effectiveness for other types of chronic pain is less clear. Some studies suggest that while it can reduce pain slightly more than a placebo, the overall benefits might be limited, and there are potential side effects to consider. ^{1 2 3 4 5}

Is medical cannabis safe for humans?

Research shows that medical cannabis has a reasonable safety profile for chronic pain, with no increased risk of serious adverse events, though users may experience more mild to moderate non-serious side effects compared to non-users. ^{5 6 7 8 9}

How is medical cannabis different from other drugs for chronic pain?

Medical cannabis is unique because it is often used when standard pain medications are not effective or cause intolerable side effects. It is considered an alternative or adjunctive treatment, particularly for chronic neuropathic pain, and requires careful monitoring by experienced clinicians. ^{10 11 12 13 14}

What is the purpose of this trial?

This study will assess cognition, neural function, and drug exposure in chronic pain patients who have been prescribed medical cannabis and will differentiate outcomes based on use of specific CBD-dominant versus THC-dominant treatment products. This longitudinal study will recruit medical cannabis users from local dispensaries. Each participant will complete a baseline assessment prior to the start of medical cannabis use, monthly phone calls to assess treatment adherence, and a four-month follow- up assessment. The aims of this project are: Aim 1. To assess impacts of medical cannabis compounds on executive functions, learning and memory in adults to determine whether cognitive impairments are evident after the onset of cannabis use; Aim 2. To assess the impacts of medical cannabis compounds on white matter microstructure, functional brain activity and functional connectivity; Aim 3. To differentiate change over four months in these outcomes as a function of (a) age and (b) pre-to-post-treatment changes in blood levels of cannabinoid compounds.

Eligibility Criteria

This trial is for adults aged 35-65 with chronic pain, prioritizing those with orthopedic issues. Participants must be new medical cannabis users or non-users, able to perform tasks and communicate by phone. They should not have a history of substance abuse or severe psychiatric conditions, and cannot be pregnant or recent mothers.

Inclusion Criteria

I use medical cannabis for chronic pain, am between 35-65 years old, and my pain is mainly orthopedic.

I can talk on the phone with researchers for updates.

I can attend a long session and use a computer for tests.

Exclusion Criteria

Contraindications to MRI scanning

Lifetime history of severe DSM-V psychopathology (psychotic disorders, bipolar disorder), unless currently treated mood for anxiety disorders is stable

Current pregnancy or pregnancy within the prior 3 months, lactating

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete a comprehensive pre-treatment behavioral assessment and multimodal brain MRI assessments

1 week

1 visit (in-person)

Treatment

Participants use medical cannabis and complete monthly phone interviews to assess treatment adherence, pain levels, quality of life, and substance use

16 weeks

4 phone calls (monthly)

Follow-up

Participants complete a four-month follow-up assessment including behavioral and MRI assessments

1 week

1 visit (in-person)

Treatment Details

Interventions

• Medical Cannabis

Trial Overview The study tests how different cannabis compounds (CBD vs THC) affect cognition and brain function in chronic pain patients using medical cannabis. It involves initial assessments, monthly check-ins, and follow-up testing including fMRI scans and cognitive evaluations over four months.

Participant Groups

Group I: Experimental cognitive and fMRI-based tasks Experimental Treatment 3 Interventions

One primary aim of this study is to examine cognitive functioning in individuals who use medical cannabis. All participants in the study will complete cognitive measures that include measures of attention, learning, memory and executive function. All participants will complete task fMRI-based measures of learning and inhibitory control. NIH considers the cognitive and fMRI tasks to be interventions. The fMRI learning task measures face-name associative learning. The fMRI inhibitory control task is a go/no-go task whereby participants respond on some trials to "go" stimuli and withhold responses on other trials to "no-go" stimuli. Brain activations are measured in response to each task. Each participant will complete two cognitive testing sessions as well as two fMRI sessions during the course of the study.

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

In a 12-month study involving 751 chronic pain patients, plant-based medical cannabis significantly reduced pain severity and interference, with improvements observed as early as one month and maintained throughout the year.

Patients also experienced enhanced physical and mental health, along with reduced use of opioid medications, suggesting that medical cannabis can be a safe and effective alternative or complement to traditional pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical Cannabis for the Management of Pain and Quality of Life in Chronic Pain Patients: A Prospective Observational Study. Safakish, R., Ko, G., Salimpour, V., et al.[2021]

Recent systematic reviews show that while there is moderate quality evidence for cannabis medicines providing moderate relief for neuropathic pain, they are generally considered a third-line treatment option.

The conclusions of these reviews can be influenced by the thoroughness of literature searches and study inclusion criteria, with many studies indicating a lack of efficacy for other types of chronic pain, highlighting the need for more rigorous research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evidence of the efficacy and safety of cannabis medicines for chronic pain management : A methodological minefield]. Häuser, W., Petzke, F.[2019]

A review of 104 studies involving nearly 10,000 participants found that cannabinoids provided a modest benefit in reducing chronic noncancer pain, with a 30% pain reduction rate of 29.0% compared to 25.9% for placebo, indicating a significant but limited efficacy.

The analysis revealed a high number needed to treat (NNT) to benefit of 24, suggesting that cannabinoids may not be highly effective for chronic noncancer pain, especially considering the relatively high rate of adverse events (81.2% for cannabinoids vs. 66.2% for placebo).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. Stockings, E., Campbell, G., Hall, WD., et al.[2019]

In a study of 1,668 patients with chronic pain, those who reported ongoing cannabis use experienced slightly worse sleep, higher pain intensity, and greater emotional distress compared to non-users, although these differences were small.

Longitudinal analysis showed no significant differences in changes to pain-related variables over time between cannabis users and non-users, suggesting that cannabis use may not impact the long-term trajectory of chronic pain outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Profiles of Concurrent Cannabis Use in Chronic Pain: A CHOIR Study. Sturgeon, JA., Khan, J., Hah, JM., et al.[2021]

A systematic review of 43 randomized controlled trials involving 4436 participants found that current cannabinoid trials for chronic pain often fail to meet key safety reporting standards, with an average of 3 to 4 CONSORT guidelines not being followed.

Many trials lacked adequate assessment and reporting of adverse events, with 17 trials not detailing their methods for assessing adverse events and 14 trials failing to report serious adverse events, highlighting a significant gap in safety evaluation in cannabinoid research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to Consolidated Standards of Reporting Trials (CONSORT) Guidelines for Reporting Safety Outcomes in Trials of Medical Cannabis and Cannabis-based Medicines for Chronic Noncancer Pain: A Systematic Review. Mohiuddin, MM., Mizubuti, GB., Haroutounian, S., et al.[2021]

A study involving 431 individuals with chronic non-cancer pain found that using a standardized herbal cannabis product for one year did not increase the risk of serious adverse events compared to non-users, suggesting a reasonable safety profile for medical cannabis.

However, cannabis users experienced a higher rate of non-serious adverse events, mostly mild to moderate, indicating that while cannabis may be safe for serious complications, it can still lead to some side effects that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). Ware, MA., Wang, T., Shapiro, S., et al.[2022]

A systematic review of 34 trials found little evidence supporting the effectiveness of cannabinoids as an adjuvant or analgesic for cancer pain, leading to a recommendation against their use for this purpose.

The review highlighted inconsistent evidence regarding the risks and adverse events associated with cannabinoid use in cancer patients, emphasizing the need for careful consideration of potential harms, especially when combined with treatments like checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MASCC guideline: cannabis for cancer-related pain and risk of harms and adverse events. To, J., Davis, M., Sbrana, A., et al.[2023]

In a study of 338 patients over 12 months, the use of a 19% cannabis decoction significantly reduced pain intensity, pain disability, and symptoms of anxiety and depression, indicating its potential effectiveness in managing chronic pain.

Cannabis therapy, when used alongside traditional pain medications, may enhance the overall management of chronic pain and its psychological effects, although further randomized controlled trials are necessary to validate these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical Cannabis in Patients with Chronic Pain: Effect on Pain Relief, Pain Disability, and Psychological aspects. A Prospective Non randomized Single Arm Clinical Trial. Poli, P., Crestani, F., Salvadori, C., et al.[2018]

In a survey of 1,321 medical cannabis users with chronic pain, about 80% reported substituting cannabis for traditional pain medications, particularly opioids, due to fewer side effects and better symptom management.

Experienced cannabis users (≥1 year) reported improved health and were less likely to take other pain medications compared to novice users (<1 year), suggesting that longer use may enhance the therapeutic benefits of cannabis in managing chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pills to Pot: Observational Analyses of Cannabis Substitution Among Medical Cannabis Users With Chronic Pain. Boehnke, KF., Scott, JR., Litinas, E., et al.[2020]

Cannabis-based medicines may be considered for chronic neuropathic pain, but should only be used by experienced clinicians as part of a multidisciplinary treatment plan, especially when standard therapies have not been effective.

For other types of chronic pain, such as cancer or non-neuropathic pain, cannabis should be treated as an individual trial, with close monitoring for efficacy and potential adverse effects, and treatment should be stopped if predefined goals are not met.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Pain Federation (EFIC) position paper on appropriate use of cannabis-based medicines and medical cannabis for chronic pain management. Häuser, W., Finn, DP., Kalso, E., et al.[2019]

There is low-strength evidence from 27 trials that plant-based cannabis can help alleviate neuropathic pain, but there is insufficient evidence to support its effectiveness for other types of chronic pain.

Cannabis use is associated with potential harms, including an increased risk of motor vehicle accidents, psychotic symptoms, and short-term cognitive impairment, particularly in the general adult population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. Nugent, SM., Morasco, BJ., O'Neil, ME., et al.[2022]

This scoping review analyzed 5 studies focusing on the perspectives of health professionals and medical cannabis users in New Zealand and Australia, highlighting the challenges they face with medical cannabis treatment for chronic pain.

The findings suggest that educating health professionals about medical cannabis could improve access and inform policy reforms, emphasizing the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analyzing the Perspectives of Health Professionals and Legal Cannabis Users on the Treatment of Chronic Pain With Cannabidiol: Protocol for a Scoping Review. Kumar, P., Mpofu, C., Wepa, D.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Medical Cannabis for the Management of Pain and Quality of Life in Chronic Pain Patients: A Prospective Observational Study. [2021]

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

[Evidence of the efficacy and safety of cannabis medicines for chronic pain management : A methodological minefield]. [2019]

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

Cannabis and cannabinoids for the treatment of people with chronic noncancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. [2019]

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

Cannabinoids, cannabis, and cannabis-based medicine for pain management: a protocol for an overview of systematic reviews and a systematic review of randomised controlled trials. [2023]

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

Clinical Profiles of Concurrent Cannabis Use in Chronic Pain: A CHOIR Study. [2021]

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

Adherence to Consolidated Standards of Reporting Trials (CONSORT) Guidelines for Reporting Safety Outcomes in Trials of Medical Cannabis and Cannabis-based Medicines for Chronic Noncancer Pain: A Systematic Review. [2021]

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

Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). [2022]

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

MASCC guideline: cannabis for cancer-related pain and risk of harms and adverse events. [2023]

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

Medicinal Cannabis for the Treatment of Chronic Refractory Pain: An Investigation of the Adverse Event Profile and Health-Related Quality of Life Impact of an Oral Formulation. [2022]

10. Italy pubmed.ncbi.nlm.nih.gov

Medical Cannabis in Patients with Chronic Pain: Effect on Pain Relief, Pain Disability, and Psychological aspects. A Prospective Non randomized Single Arm Clinical Trial. [2018]

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

Pills to Pot: Observational Analyses of Cannabis Substitution Among Medical Cannabis Users With Chronic Pain. [2020]

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

European Pain Federation (EFIC) position paper on appropriate use of cannabis-based medicines and medical cannabis for chronic pain management. [2019]

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

The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms: A Systematic Review. [2022]

14. Canada pubmed.ncbi.nlm.nih.gov

Analyzing the Perspectives of Health Professionals and Legal Cannabis Users on the Treatment of Chronic Pain With Cannabidiol: Protocol for a Scoping Review. [2023]