Terpenes + THC for Pain

Overseen By Vincent Acebo

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Los Angeles

Must not be taking: Prescription analgesics

Disqualifiers: Substance use disorder, Hypertension, Pregnancy, others

Compensation: Varies

Number of Visits: 1

Duration: 7 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different combinations of terpenes (natural compounds found in plants) and THC (the active ingredient in cannabis) affect pain relief. Researchers aim to determine how these combinations might help manage pain and influence participants' feelings. It is ideal for those who use cannabis recreationally but are not currently using it for medical reasons or experiencing ongoing pain. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

Yes, if you are currently using prescription pain medications or any medications that might affect the study outcomes, you will need to stop taking them to participate in this trial.

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

Research has shown that beta-caryophyllene (BCP) is generally safe for people. In a study involving patients with hand arthritis, BCP was safe when applied to the skin, and other research found no major safety issues.

For myrcene, some safety warnings exist. It can irritate the skin and may be harmful if swallowed, especially in high amounts. Lower doses might be safer.

Regarding THC, studies have found that it can cause side effects like mood changes and affect motor skills, but these effects are usually not serious. THC is already used in some approved medicines, suggesting it is relatively safe in controlled amounts.

Overall, these treatments have been studied and appear reasonably safe. However, since this is an early-phase study, the main goal is to assess how well people tolerate these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore the potential of terpenes and THC in pain management, offering an alternative to traditional painkillers like opioids and NSAIDs. Unlike standard treatments, these investigational therapies utilize terpenes such as beta-caryophyllene and myrcene, which are believed to interact with the body's endocannabinoid system, potentially reducing inflammation and pain. By combining various strengths of THC with these terpenes, the study aims to identify specific combinations that might offer pain relief with fewer side effects than current options. This approach is particularly promising as it might address pain through different biological pathways, offering new hope for those who haven't found relief through existing medications.

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

Research has shown that Beta-Caryophyllene (BCP), one of the compounds studied in this trial, can help reduce pain by decreasing inflammation. Studies have found that it affects the CB2 receptor, part of the body's natural pain control system. Myrcene, another compound under investigation, also reduces pain and inflammation, particularly in conditions like arthritis, by interacting with pain-related receptors. THC (tetrahydrocannabinol), also tested in this trial, has shown moderate effectiveness in managing various types of chronic pain, such as nerve pain and fibromyalgia. This trial will explore whether combining these elements might enhance pain relief by targeting different mechanisms of pain perception. ^{5 6 7 8 9}

Who Is on the Research Team?

Ziva D Cooper, PhD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

This trial is for adults aged 21-55 who use cannabis recreationally 1-7 times a week and are not seeking treatment for cannabis use. They must have a BMI of 18.5 - 34kg/m2, be able to do all study tasks, and use contraception. People with significant illnesses, pregnant women, those allergic to cannabis or on certain medications can't join.

Inclusion Criteria

You are not currently using marijuana as part of your treatment plan.

I am between 21 and 55 years old and not pregnant.

Urine test positive for recent cannabis use

Exclusion Criteria

You have a substance addiction, except for nicotine or caffeine.

I am experiencing pain.

Pregnancy is exclusionary due to the possible effects of the study medication on fetal development.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various combinations of terpenes and THC to assess analgesic and subjective effects

7 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• High Beta-Caryophyllene
• High Myrcene
• High THC
• Low Beta-Caryophyllene
• Low Myrcene
• Low THC
• Placebo

Trial Overview The study aims to evaluate the pain-relief and subjective effects of terpenes both alone and when combined with THC. Participants will receive varying levels of Beta-Caryophyllene (high/low), Myrcene (high/low), THC (high/low), or placebo in different sessions.

How Is the Trial Designed?

Group I: Low strength BCP Active Control 1 Intervention

0 mg THC, 0 mg myrcene, 0.5 mg BCP

Group II: High strength myrcene Active Control 1 Intervention

0 mg THC, 12.0 mg myrcene, 0 mg BCP

Group III: High THC + Low myrcerne Active Control 2 Interventions

15 mg THC, 0.5 mg myrcene, 0 mg BCP

Group IV: High strength BCP Active Control 2 Interventions

15 mg THC, 0 mg myrcene, 7.5 mg BCP

Group V: Low strength myrcene Active Control 1 Intervention

0 mg THC, 0.5 mg myrcene, 0 mg BCP

Group VI: Higher strength THC Active Control 1 Intervention

15 mg THC, 0 mg myrcene, 0 mg BCP

Group VII: High THC + High BCP Active Control 2 Interventions

15 mg THC, 0 mg myrcene, 7.5 mg BCP

Group VIII: Low THC + Low myrcene Active Control 2 Interventions

5 mg THC, 0.5 mg myrcene, 0 mg BCP

Group IX: Low THC + High myrcene Active Control 2 Interventions

5 mg THC, 12.0 mg myrcene, 0 mg BCP

Group X: High THC + High myrcene Active Control 2 Interventions

15 mg THC, 12.0 mg myrcene, 0 mg BCP

Group XI: Low THC + Low BCP Active Control 2 Interventions

5 mg THC, 0 mg myrcene, 0.5 mg BCP

Group XII: Low THC + High BCP Active Control 2 Interventions

5 mg THC, 0 mg myrcene, 7.5 mg BCP

Group XIII: High THC + Low BCP Active Control 2 Interventions

15 mg THC, 0 mg myrcene, 0.5 mg BCP

Group XIV: Low strength THC Active Control 1 Intervention

5 mg THC, 0 mg myrcene, 0 mg BCP

Group XV: Placebo Placebo Group 1 Intervention

0 mg THC, 0 mg myrcene, 0 mg BCP

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Published Research Related to This Trial

Intraplantar injection of β-caryophyllene (BCP) effectively reduces pain in mice by activating peripheral CB2 cannabinoid receptors, which leads to the release of the body's own opioid, β-endorphin.

Combining BCP with morphine enhances pain relief, suggesting that this combination could be a promising alternative for treating pain, particularly chemogenic pain, while the antinociceptive effects of BCP are blocked by opioid antagonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception. Katsuyama, S., Mizoguchi, H., Kuwahata, H., et al.[2019]

The plant metabolite (E)-β-caryophyllene (BCP) effectively reduces inflammation and colonic damage in a mouse model of colitis, indicating its potential as a treatment for inflammatory bowel disease.

The anti-inflammatory effects of BCP are mediated through the activation of cannabinoid receptor 2 (CB2) and the peroxisome proliferator-activated receptor-γ (PPARγ) pathway, as evidenced by the reversal of its benefits when these receptors were blocked.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARγ pathway. Bento, AF., Marcon, R., Dutra, RC., et al.[2021]

β-caryophyllene (BCP) and its oxidized form, β-caryophyllene oxide (BCPO), show significant anticancer activities by affecting cancer cell growth and proliferation, with BCP specifically activating the cannabinoid receptor type 2 (CB2) without psychoactive effects.

BCPO operates through different mechanisms, altering key cancer development pathways and enhancing the efficacy of traditional chemotherapy, making BCP a promising candidate for dual action as both an anticancer and analgesic agent in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-caryophyllene and β-caryophyllene oxide-natural compounds of anticancer and analgesic properties. Fidyt, K., Fiedorowicz, A., Strządała, L., et al.[2022]

β-Caryophyllene (BCP) significantly reduces nicotine self-administration and motivation for nicotine-seeking behavior in animal models, indicating its potential as a treatment for nicotine addiction.

The effects of BCP are mediated through both CB2 receptors and other mechanisms, as shown by the blockade of its effects with a CB2 antagonist and the involvement of dopamine pathways in its action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-Caryophyllene, a dietary terpenoid, inhibits nicotine taking and nicotine seeking in rodents. He, Y., Galaj, E., Bi, GH., et al.[2022]

β-Caryophyllene (BCP) acts as a full agonist on cannabinoid type 2 (CB2) receptors, which are important for treating various diseases without the psychotropic effects associated with CB1 receptors, making it a safer option for therapeutic use.

BCP exhibits a wide range of pharmacological activities, including anti-inflammatory, neuroprotective, and cardioprotective effects, and shows promise for treating conditions like neuropathic pain and neurodegenerative diseases, highlighting its potential as a novel therapeutic candidate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polypharmacological Properties and Therapeutic Potential of β-Caryophyllene: A Dietary Phytocannabinoid of Pharmaceutical Promise. Sharma, C., Al Kaabi, JM., Nurulain, SM., et al.[2019]

β-caryophyllene (BCP) shows promise as a potential treatment for substance use disorders, as preclinical studies in animal models demonstrated its ability to prevent or reverse behavioral changes associated with drug exposure, including cocaine, nicotine, alcohol, and methamphetamine.

The mechanism of action for BCP likely involves activation of the cannabinoid CB2 receptor, but it may also interact with other molecular targets, such as the peroxisome proliferator-activated receptor, indicating a complex pharmacological profile that requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of β -caryophyllene, A Dietary Cannabinoid, in Animal Models of Drug Addiction. Asth, L., Cruz, LC., Soyombo, N., et al.[2023]

β-caryophyllene (BCP) significantly reduces the severity of arthritis in a collagen antibody-induced model by lowering pro-inflammatory cytokines and increasing anti-inflammatory cytokines, indicating its potential as an effective treatment for inflammation-related conditions.

The therapeutic effects of BCP are linked to its interaction with cannabinoid receptor 2 (CB2) and peroxisome proliferator-activated receptor gamma (PPAR-γ), suggesting that BCP may work by modulating these pathways to alleviate arthritis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors. Irrera, N., D'Ascola, A., Pallio, G., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7692661/

Protective Effects of (E)-β-Caryophyllene (BCP) in Chronic ... In neuropathic pain models, BCP reduced spinal neuroinflammation and the oral administration was more effective than the subcutaneously injected synthetic CB2 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1043661825004128

Cannabidiol and Beta-Caryophyllene: chronic ... Additionally, our data show that the anti-inflammatory action of this combination may explain its beneficial effects on pain and depression.

3. mdpi.com mdpi.com/1422-0067/26/9/4430

Intraplantar β-Caryophyllene Alleviates Pain and ... BCP's therapeutic efficacy is primarily attributed to its ability to suppress pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. It also mitigates ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0924977X13003027

The cannabinoid CB2 receptor-selective phytocannabinoid ... We demonstrate that orally administered BCP reduced inflammatory (late phase) pain responses in the formalin test in a CB 2 receptor-dependent manner.

5. pnas.org pnas.org/doi/10.1073/pnas.0803601105

Beta-caryophyllene is a dietary cannabinoid In particular, CB2 receptor ligands have been shown to inhibit inflammation and edema formation (15), exhibit analgesic effects (16), and play a protective role ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04794205

Acute Changes In Thermal Pain Response Following ... Betacaryophyllene (BCP) may be a possible candidate because it is isolatable, has shown evidence as a potential analgesic in preclinical ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5083753/

β‐caryophyllene and β‐caryophyllene oxide—natural ... This review is focused on anticancer and analgesic activities of BCP and BCPO, the mechanisms of their actions, and potential therapeutic utility.

8. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/caryophyllene

Caryophyllene - an overview | ScienceDirect Topics Data on β-caryophyllene provided a calculated Margin of Exposure (MOE) ... Data show that there are no safety concerns for β-caryophyllene for skin ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10970213/

Beta-Caryophyllene, a Cannabinoid Receptor Type 2 ... In a recent placebo-controlled clinical study in patients with hand arthritis, topically applied BCP was found to be safe, well tolerated and ...