CBD + THC for Chronic Pain

Overseen By Matt Hodgkinson, B.S.,RN

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Utah

Disqualifiers: Neurological illness, Substance abuse, Diabetes, Major mental illness, others

Compensation: Varies

Number of Visits: 9

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess how different treatments affect individuals with chronic non-cancer pain. Researchers will compare the pain relief provided by THC (Delta-9-Tetrahydrocannabinol), CBD (Cannabidiol), and a placebo (a substance with no active drug). Participants will continue their usual care while trying one of these options to determine if the new treatments offer additional benefits. Individuals who have used cannabis and experienced ongoing muscle or joint pain for at least three months may be suitable for this study, particularly those living near Salt Lake City, Utah. As an Early Phase 1 trial, this research focuses on understanding how these treatments work in people, offering a chance to explore new pain relief options.

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

The trial protocol does not specify if you need to stop taking your current medications.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators.

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

Research has shown that THC, a component of cannabis, can cause side effects like nausea and stomach pain. In some studies, a few participants stopped using it due to these effects, though this was uncommon. Other research indicates that medical cannabis, which includes THC, is generally safe for long-term pain management.

For CBD, another component of cannabis, studies suggest it is well tolerated, even in high amounts. Some individuals might experience mild side effects. One review found a higher risk of liver enzyme changes at very high doses, but this was rare at lower doses. Overall, CBD is considered safe for most people.

Both THC and CBD have been studied for safety, but results can vary based on the amount used and individual reactions. Participants should consider this when deciding to join a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Cannabidiol (CBD) and Delta-9-Tetrahydrocannabinol (THC) for chronic pain because these compounds offer a fresh approach compared to traditional painkillers like opioids and NSAIDs. CBD and THC work uniquely by interacting with the body's endocannabinoid system, potentially providing pain relief without the high risk of addiction associated with opioids. Additionally, these cannabis-derived compounds may offer fewer side effects than many standard treatments. This novel mechanism of action and potential for a safer side effect profile have researchers hopeful about their role in managing chronic non-cancer pain.

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

Research has shown that THC, a compound in cannabis, can help reduce chronic pain. In some studies, participants using THC reported less pain and greater satisfaction compared to those taking a placebo, a substance with no active ingredients. This trial includes an arm testing the analgesic effects of Delta-9-Tetrahydrocannabinol (THC) on subjects with chronic non-cancer pain. Another study found that medical cannabis, which contains THC, was more effective than regular pain medications over three months.

CBD, another compound in cannabis, has shown mixed results. Some studies suggest it can reduce pain by 42% to 66%, but other research indicates it might not be very effective. Many trials found no significant difference in pain relief with CBD compared to a placebo. This trial also includes an arm testing the analgesic effects of Cannabidiol (CBD) on subjects with chronic non-cancer pain. Thus, stronger evidence supports THC for pain relief compared to CBD, but both compounds are still under study for their potential benefits. ^{4 6 7 8 9}

Who Is on the Research Team?

Deborah Yurgelun-Todd, Ph.D.

Principal Investigator

University of Utah Brain Institute

Are You a Good Fit for This Trial?

This trial is for adults aged 18-50 with a history of cannabis use who suffer from chronic musculoskeletal and joint pain lasting at least 3 months. Participants must live within 60 miles of Salt Lake City, Utah.

Inclusion Criteria

Participants must live within a 60 mile radius of Salt Lake City, Utah to be eligible

I have had joint or muscle pain for 3 months or more.

History of cannabis use

Exclusion Criteria

Unstable medical conditions

Substance abuse or dependence within the prior 60 days

I have diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive daily doses of THC/CBD or placebo for five days, with assessments conducted before and after the fifth dose

1 week

5 visits (in-person)

Neuroimaging

Participants undergo MRI and MRS to assess brain changes before and after treatment

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain relief and neurocognitive performance assessments

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol
• Delta-9-Tetrahydrocannabinol
• Placebos

Trial Overview The study compares the effects on chronic non-cancer pain between three options: Delta-9-Tetrahydrocannabinol (THC), Cannabidiol (CBD), and a placebo to see which is more effective in managing pain.

How Is the Trial Designed?

Group I: Delta-9-Tetrahydrocannabinol's (Delta-9-THC) effects on pain Active Control 1 Intervention

This arm will be testing the analgesic effects of orally dosed Delta-9-Tetrahydrocannabinol on subjects with chronic non-cancer pain.

Group II: Cannabidiol's (CBD) effects on pain Active Control 1 Intervention

This arm will be testing the analgesic effects of orally dosed Cannabidiol on subjects with chronic non-cancer pain.

Group III: Placebo Placebo Group 1 Intervention

This Placebo arm will act as the control as standard of care medications will be continued through the study. This arm will allow us to compare the analgesic effects of the other two arms with the standard of care treatments for chronic non-cancer pain.

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 Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Published Research Related to This Trial

Chronic pain affects 20% of the general population, significantly impairing daily activities and quality of life, highlighting the need for effective management strategies.

The oromucosal spray containing THC and CBD (nabiximols) shows promise as an add-on treatment for chronic neuropathic pain, based on clinical trials and data from the German Pain e-Registry, but more precise studies are needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Scientific Evidence for THC:CBD Oromucosal Spray (Nabiximols) in the Management of Chronic Pain. Überall, MA.[2020]

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]

In a pilot study involving 20 former elite athletes, topical cannabidiol (CBD) was found to be well-tolerated, with 50% of participants reporting only minor adverse effects such as skin dryness and rash, none of which required medical attention.

Participants experienced significant reductions in self-reported pain levels and pain-related disability over the 6-week study period, indicating that CBD may be an effective option for managing chronic pain in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical cannabidiol is well tolerated in individuals with a history of elite physical performance and chronic lower extremity pain. Hall, N., James, B., Bhuiyan, MAN., et al.[2023]

In a study involving 17 healthy noncannabis users, cannabidiol (CBD) did not consistently improve pain threshold or tolerance in a cold pressor test, and in some cases, it even increased pain ratings compared to placebo.

While CBD was found to be safe and well tolerated, with minor decreases in blood pressure, it showed only modest effects on mood and potential abuse liability, suggesting that its analgesic effects may not be reliable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A placebo-controlled investigation of the analgesic effects, abuse liability, safety and tolerability of a range of oral cannabidiol doses in healthy humans. Arout, CA., Haney, M., Herrmann, ES., 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]

Combination THC/CBD medicines are effective for chronic pain, particularly neuropathic and inflammatory pain, and have a good safety profile compared to opioids, with low potential for dependence.

CBD-only medications show substantial effectiveness for stress and moderate effectiveness for anxiety and insomnia, but should be used cautiously in patients with a history of depression or psychosis, as they may exacerbate these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions. Henson, JD., Vitetta, L., Hall, S.[2022]

Cannabidiol (CBD) is not just a passive substance; it interacts with brain receptors like dopamine and serotonin, leading to potential psychoactive effects such as sedation and drowsiness.

There are significant concerns about CBD's interactions with various medications, which could affect treatment for chronic diseases, and its use in vaping may produce harmful byproducts, highlighting the need for careful regulation and public health measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacology of cannabidiol: Red flags, consequences and risks in humans]. Micallef, J., Batisse, A., Revol, B.[2023]

In a study of 28 patients with chronic neck or back pain, a combination of cannabidiol (CBD) and Δ9-THC was found to be well tolerated, with most side effects being mild, such as nausea and fatigue.

Patients experienced significant reductions in pain scores with higher doses (1.0 mL and 1.5 mL twice daily), achieving reductions of 28.8% and 34.1% respectively, indicating the efficacy of this treatment for chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and Efficacy of a 10:25 Preparation of Δ9-Tetrahydrocannabinol and Cannabidiol for Treatment of Chronic Back or Neck Pain: A Multiple-Dose Escalation Study. Glare, P., Chye, R., Bloch, M., et al.[2023]

In a study of 800 patients with severe chronic pain, the oromucosal spray containing THC and CBD resulted in a significant average symptom relief improvement of 39% after 12 weeks, with particularly strong effects observed in patients with neuropathic pain.

The treatment was generally well-tolerated, with 19.9% of patients reporting mild side effects, such as increased appetite and changes in taste, and only 4% discontinuing due to adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and tolerability of THC:CBD oromucosal spray as add-on measure in patients with severe chronic pain: analysis of 12-week open-label real-world data provided by the German Pain e-Registry. Ueberall, MA., Essner, U., Mueller-Schwefe, GH.[2020]

Serious adverse effects (SAEs) from cannabidiol (CBD) are rare, with most being mild to moderate, and primarily include elevated liver enzymes, sedation, and respiratory infections, particularly when used with certain medications.

Elevated liver enzymes were specifically linked to the use of valproate, while sedation and lethargy were associated with clobazam, indicating that patients, especially those with epilepsy, should be closely monitored for potential drug-drug interactions when using CBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse effects of cannabidiol (CBD): a review of randomized controlled trials. Dos Santos, RG., Guimarães, FS., Crippa, JAS., et al.[2022]

In a 15-week study involving 246 patients with peripheral neuropathic pain, the THC/CBD oromucosal spray showed a statistically significant improvement in the 30% responder rate compared to placebo, indicating its efficacy in managing pain.

The THC/CBD spray also led to significant improvements in sleep quality and overall patient-reported change in condition, while being well tolerated with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. Serpell, M., Ratcliffe, S., Hovorka, J., et al.[2022]

In a study involving male and female rats with inflammatory pain, THC alone was effective in reducing pain and inflammation, while CBD also showed pain-relieving effects but did not enhance THC's benefits when combined.

The combination of CBD and THC may actually reduce the effectiveness of THC for pain relief and increase anxiety-like behaviors, especially in female rats, suggesting that using THC alone might be more beneficial for treating chronic inflammatory pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol and Delta-9-Tetrahydrocannabinol Interactions in Male and Female Rats With Persistent Inflammatory Pain. Britch, SC., Craft, RM.[2023]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37953193/

Effectiveness of Cannabidiol to Manage Chronic Pain The majority of the studies indicated pain reduction ranging from 42% - 66% with CBD alone and CBD with Tetrahydrocannabinol.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1524904223001935

Effectiveness of Cannabidiol to Manage Chronic Pain The majority of the studies indicated pain reduction ranging from 42% - 66% with CBD alone and CBD with Tetrahydrocannabinol.

3. jpain.org jpain.org/article/S1526-5900(23)00582-5/fulltext

Cannabidiol (CBD) Products for Pain: Ineffective ... Ten of these 11 trials showed that CBD produced little or no pain relief, with no statistical or clinically significant difference between CBD ...

4. aafp.org aafp.org/pubs/afp/afp-community-blog/entry/cbd-effectiveness-in-treating-chronic-pain-remains-questionable.html

CBD Effectiveness in Treating Chronic Pain Remains ... Many patients use CBD products hoping for relief from chronic pain, but a recently published study shows only minimal, if any, benefit for this indication.

5. mdpi.com mdpi.com/2035-8377/17/9/141

Cannabinoids in Chronic Pain: Clinical Outcomes, Adverse ... Inhaled cannabis containing 6% THC and 11% CBD relieved pain in 67.2% of patients and eliminated pain completely in 34.5% within two hours, significantly ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9288157/

Efficacy, Safety, and Regulation of Cannabidiol on Chronic Pain We conducted a systematic review to determine the efficacy and safety of cannabidiol (CBD) for chronic pain. The systematic review is according ...

7. fda.gov fda.gov/drugs/regulatory-science-action/cder-investigators-address-safety-cbd-randomized-trial

CDER Investigators Address the Safety of CBD in a ... At labeled doses up to 25 mg/kg/day, an increased risk of liver enzyme elevation was observed., Liver enzyme elevations typically occurred after ...

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

An Update on Safety and Side Effects of Cannabidiol Chronic use and high doses of up to 1500 mg per day have been repeatedly shown to be well tolerated by humans. Nonetheless, some side effects have been reported ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04726579

NCT04726579 | CBD Oil in Mechanical Back Pain All adverse reactions will be recorded in the study electronic medical record (EMR), InputHealth. Statistical Analysis: The primary analysis will be measured in ...