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

45 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research is to assess the analgesic and subjective effects of terpenes administered alone and in combination of THC.

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.

What data supports the effectiveness of this drug for pain relief?

Research shows that β-caryophyllene (BCP), a component of the treatment, can reduce pain by interacting with cannabinoid and opioid systems in the body. This suggests that BCP might help in pain relief, which could support the effectiveness of the treatment for pain. ^{1 2 3 4 5}

Is the combination of terpenes and THC safe for human use?

β-Caryophyllene (BCP), a terpene found in cannabis, is considered safe as it is approved by the FDA and European agencies as a food additive. It has been used for many years without significant safety concerns. ^{1 3 4 5 6}

What makes the drug Terpenes + THC for Pain unique compared to other pain treatments?

This drug is unique because it combines terpenes like β-caryophyllene (BCP) and myrcene with THC, which may offer pain relief through a novel mechanism involving the activation of the CB2 receptor, potentially reducing inflammation without the psychoactive effects associated with CB1 receptor activation. BCP also has potential anticancer properties, making it particularly valuable for patients experiencing chronic pain related to cancer. ^{1 3 4 5 7}

Research Team

Ziva D Cooper, PhD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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]

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]

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]

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) 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]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Polypharmacological Properties and Therapeutic Potential of β-Caryophyllene: A Dietary Phytocannabinoid of Pharmaceutical Promise. [2019]

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

β-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARγ pathway. [2021]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Effects of β -caryophyllene, A Dietary Cannabinoid, in Animal Models of Drug Addiction. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception. [2019]

5. Switzerland 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. [2020]

6. England pubmed.ncbi.nlm.nih.gov

β-Caryophyllene, a dietary terpenoid, inhibits nicotine taking and nicotine seeking in rodents. [2022]

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

β-caryophyllene and β-caryophyllene oxide-natural compounds of anticancer and analgesic properties. [2022]