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

53 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing THC and CBD on people with chronic non-cancer pain. THC can help reduce pain by affecting brain areas that process pain signals, while CBD may help by reducing inflammation and interacting with pain receptors. THC and CBD have been studied for their potential to manage chronic pain, with THC showing effectiveness in reducing pain signals and CBD being noted for its anti-inflammatory properties.

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.

What safety data exists for CBD and THC in treating chronic pain?

Existing safety data for CBD and THC indicates that most adverse effects are mild to moderate, with rare serious adverse effects. CBD can interact with other drugs, potentially causing sedation, drowsiness, and other psychoactive effects. Serious adverse reactions have been reported, especially when used with other medications like antiepileptics. Common adverse effects include transaminase elevations, sedation, sleep disturbances, infection, and anemia. CBD's interactions with drug metabolism enzymes suggest a high potential for drug-drug interactions. More research is needed on reproductive and developmental toxicity and immune outcomes. ^{1 2 3 4 5}

Is CBD and THC safe for human use?

CBD and THC are generally considered safe for human use, with most side effects being mild to moderate. However, there are potential serious adverse effects, especially when CBD interacts with other medications, and it can cause sedation, drowsiness, and other psychoactive effects. It's important to monitor for drug interactions and adverse effects, particularly in people with complex medical conditions. ^{1 2 3 4 5}

Is the drug Cannabidiol and Delta-9-Tetrahydrocannabinol (CBD and THC) promising for treating chronic pain?

Yes, the combination of CBD and THC shows promise as a treatment for chronic pain, especially for neuropathic pain. Studies suggest it can effectively reduce pain and is generally well-tolerated, making it a potential option for those who have not found relief with other treatments. ^{6 7 8 9 10}

How does the CBD + THC drug for chronic pain differ from other treatments?

The CBD + THC drug, often used as an oromucosal spray, is unique because it combines two active components of cannabis to enhance pain relief, particularly for neuropathic pain, while minimizing some side effects. Unlike traditional pain medications like opioids, it has a lower risk of dependence and abuse, making it a safer option for long-term management of chronic pain. ^{6 7 8 9 10}

What data supports the idea that CBD + THC for Chronic Pain is an effective drug?

The available research shows that a spray containing CBD and THC was effective in reducing chronic pain, especially neuropathic pain, in a study involving patients with severe chronic pain. After 12 weeks, many patients experienced significant pain relief, with 56% showing at least a 50% improvement in their symptoms. This suggests that CBD + THC can be a helpful option for managing chronic pain, particularly when other treatments haven't worked. ^{6 7 11 12 13}

What data supports the effectiveness of the drug CBD + THC for chronic pain?

Research shows that a spray containing THC and CBD can effectively reduce chronic pain, especially neuropathic pain (pain from nerve damage), with many patients experiencing significant symptom relief. This combination has been found to be well-tolerated, with most side effects being mild. ^{6 7 11 12 13}

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

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 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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

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

Topical cannabidiol is well tolerated in individuals with a history of elite physical performance and chronic lower extremity pain. [2023]

2. New Zealand 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. [2020]

3. Switzerland 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. [2023]

4. England 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. [2022]

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

A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment. [2022]

6. France pubmed.ncbi.nlm.nih.gov

[Pharmacology of cannabidiol: Red flags, consequences and risks in humans]. [2023]

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

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

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

Serious adverse effects of cannabidiol (CBD): a review of randomized controlled trials. [2022]

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

Pharmacovigilance of unlicensed cannabidiol in European countries. [2023]

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

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

11. New Zealand pubmed.ncbi.nlm.nih.gov

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

12. Switzerland pubmed.ncbi.nlm.nih.gov

Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions. [2022]

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

Cannabidiol and Delta-9-Tetrahydrocannabinol Interactions in Male and Female Rats With Persistent Inflammatory Pain. [2023]