CBG + THC for Pain

(ASCENT Trial)

Overseen By Vincent Acebo

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, Los Angeles

Must not be taking: Any medications

Disqualifiers: Moderate-severe CUD, Axis I disorder, others

Compensation: Varies

Number of Visits: Unknown

Duration: 7 hours per session

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how cannabigerol (CBG) and tetrahydrocannabinol (THC), both cannabinoids, work alone and together to manage pain, boost appetite, and affect mood. Participants will receive different combinations of CBG and THC to determine the most effective mix. Individuals who occasionally use cannabis (1-3 times a week) and do not have current pain or significant health issues may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any current medications at least 14 days before starting the trial, except for hormonal contraceptives. If you start a new medication during the trial, you will need to pause the trial for 14 days.

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

Studies have shown that CBG and THC each have distinct safety characteristics. CBG remains under study, and there is not yet enough reliable information to determine its safety or potential side effects. However, research suggests it may help with pain and inflammation.

THC is more well-known and has been used medically to alleviate pain and nausea. When used for long-term pain, it generally maintains a reasonable safety record. However, high doses or prolonged use can pose risks.

Combining CBG and THC might enhance pain relief, but there is limited information on the safety of their combination. This study is in an early stage, primarily focusing on understanding safety in humans. Researchers closely monitor participants to identify any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CBG and THC for pain relief because these compounds offer a novel approach to managing pain through the endocannabinoid system, which is different from traditional painkillers like opioids or NSAIDs. Unlike standard treatments that often come with significant side effects and addiction risks, CBG and THC are derived from cannabis and may provide a more natural alternative with potentially fewer side effects. Additionally, the combination of varying strengths of CBG and THC in the trial could offer personalized pain management options, tailoring treatment to individual patient needs and responses. This approach could revolutionize pain management by offering safer, more effective alternatives to current standard therapies.

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

This trial will evaluate different combinations of cannabigerol (CBG) and tetrahydrocannabinol (THC) for pain management. Studies have shown that CBG might reduce pain by altering how the nervous system sends pain signals. Research also suggests that CBG is safe and may benefit those with chronic pain. Evidence indicates that THC can lower pain levels and might reduce the need for opioids in managing chronic pain. When combined, CBG and THC could effectively manage pain. However, while these findings are promising, most information comes from early research and animal studies, so more human research is needed to confirm these effects. Participants in this trial will receive varying strengths of CBG and THC to assess their effectiveness in pain management. ^{1 2 4 6 7}

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?

The ASCENT trial is for men and non-pregnant, non-lactating women aged 21-55 who occasionally use cannabis but aren't seeking treatment for it. Participants must have a BMI of 18.5 - 34kg/m2 and agree to use contraception. Excluded are those with moderate-severe substance disorders (except mild Cannabis Use Disorder), certain mental health conditions, significant illnesses, current pain issues, or respiratory diseases.

Inclusion Criteria

I am not currently breastfeeding.

You are not currently receiving treatment for cannabis use.

You need to have a body weight that is considered healthy based on your height.

Exclusion Criteria

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

I have or had a lung or breathing problem.

Currently enrolled in another research protocol

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 CBG and THC to assess analgesic and appetite-stimulating effects

7 hours per session

Multiple sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cannabigerol (CBG)
• Placebo
• Tetrahydrocannabinol (THC)

Trial Overview This study examines the effects of cannabigerol (CBG) alone and combined with THC on pain relief and appetite stimulation. It involves different doses: high THC, low CBG, high CBG, low THC, and placebo to compare their impacts in a controlled environment.

How Is the Trial Designed?

Group I: Low strength CBG + High strength THC Active Control 2 Interventions

5 mg CBG + 15 mg THC

Group II: High strength THC Active Control 1 Intervention

0 mg CBG, 30 mg THC

Group III: High strength CBG + Low strength THC Active Control 2 Interventions

15 mg CBG + 5 mg THC

Group IV: High strength CBG Active Control 1 Intervention

15 mg CBG, 0 mg THC

Group V: Low strength CBG + Low strength THC Active Control 2 Interventions

5 mg CBG + 5 mg THC

Group VI: Low strength THC Active Control 1 Intervention

0 mg CBG, 5 mg THC

Group VII: Low strength CBG Active Control 1 Intervention

5 mg CBG, 0 mg THC

Group VIII: High strength CBG + High strength THC Active Control 2 Interventions

15 mg CBG + 15 mg THC

Group IX: Placebo Placebo Group 1 Intervention

0 mg CBG, 0 mg THC

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Center for Medicinal Cannabis Research

Collaborator

Trials

19

Recruited

630+

Published Research Related to This Trial

A survey of 127 CBG-predominant cannabis users revealed that most use it for medical purposes, particularly for treating anxiety, chronic pain, depression, and insomnia, with many reporting significant improvements in their conditions.

The study found a favorable safety profile for CBG, with 44% of users reporting no adverse effects and only a small percentage experiencing mild symptoms, suggesting that CBG-predominant cannabis may be a viable alternative to conventional medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey of Patients Employing Cannabigerol-Predominant Cannabis Preparations: Perceived Medical Effects, Adverse Events, and Withdrawal Symptoms. Russo, EB., Cuttler, C., Cooper, ZD., et al.[2023]

Cannabigerol has been identified as a potent agonist for alpha(2)-adrenoceptors, with an effective concentration (EC50) of 0.2 nM, indicating its potential role in modulating neurotransmitter release.

The study also found that cannabigerol can act as a competitive antagonist at CB(1) receptors and block 5-HT(1A) receptors, suggesting it has a complex pharmacological profile that could influence various physiological processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. Cascio, MG., Gauson, LA., Stevenson, LA., et al.[2021]

Cannabigerol (CBG) shows potential therapeutic benefits for neurological disorders and inflammatory bowel disease, with unique interactions at cannabinoid receptors and other receptors like α-2 adrenoceptors and 5-HT1A.

Despite its promising effects, CBG is largely unregulated and under-researched compared to other cannabinoids like CBD, highlighting the need for further studies to understand its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Pharmacological Case for Cannabigerol. Nachnani, R., Raup-Konsavage, WM., Vrana, KE.[2021]

Cannabigerol (CBG) acts as a state-dependent inhibitor of Nav 1.7 channels, which are important for pain signaling, suggesting that CBG may have potential as an analgesic by reducing neuronal excitability.

At lower concentrations, CBG primarily blocks sodium currents and slows recovery from inactivation, while higher concentrations induce a shift in the voltage at which these channels inactivate, indicating a selective action on pain pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability. Ghovanloo, MR., Estacion, M., Higerd-Rusli, GP., et al.[2022]

Cannabigerol (CBG) effectively reduces mechanical hypersensitivity in mice with cisplatin-induced peripheral neuropathy, suggesting its potential as a treatment for neuropathic pain.

The anti-nociceptive effects of CBG are mediated through specific receptors, as its efficacy was blocked by α2-adrenergic and CB1/CB2 receptor antagonists, but not by TRPV1 antagonists, indicating a targeted mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabigerol (CBG) attenuates mechanical hypersensitivity elicited by chemotherapy-induced peripheral neuropathy. Sepulveda, DE., Morris, DP., Raup-Konsavage, WM., et al.[2022]

In an in vitro study using rat dorsal root ganglion neurons, individual cannabinoids (CBG, CBD, and THC) showed dose-dependent inhibition of capsaicin responses, indicating their potential as effective analgesics.

The combination of CBG, CBD, and THC at a 1:1:1 ratio enhanced the analgesic effects compared to individual cannabinoids, suggesting that using these compounds together could improve pain relief and tolerability, warranting further in vivo research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons. Anand, U., Oldfield, C., Pacchetti, B., et al.[2022]

Cannabigerol (CBG) is a non-psychoactive cannabinoid that shows promise for various therapeutic applications, including reducing intraocular pressure and exhibiting anti-inflammatory and anti-tumoral effects, based on pre-clinical studies.

CBG acts as a partial agonist at cannabinoid receptors and interacts with other receptors, suggesting it could be a valuable component in developing treatments for conditions like anxiety and neuroprotection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological Aspects and Biological Effects of Cannabigerol and Its Synthetic Derivatives. Calapai, F., Cardia, L., Esposito, E., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11597810/

Cannabigerol (CBG): A Comprehensive Review of Its ... Current studies revealed that CBG has potential therapeutic effects on neuroprotection, inflammation, antibacterials, metabolic syndrome, pain ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11940634/

Cannabinoids in Chronic Pain Management: A Review of the ... Evidence suggests that cannabinoids provide moderate efficacy in managing neuropathic pain, fibromyalgia, cancer-related pain, and multiple sclerosis-related ...

3. news.yale.edu news.yale.edu/2025/01/21/cannabinoids-offer-new-hope-safe-and-effective-pain-relief

Cannabinoids offer new hope for safe and effective pain relief Chemicals found in cannabis show promise for treating chronic pain, a new Yale study shows, and may present an alternative to opioids.

4. cmcr.ucsd.edu cmcr.ucsd.edu/index.php/studies/active-studies/274-analgesic-appetite-stimulating-and-subjective-effects-of-cannabigerol-administered-alone-and-in-combination-with-delta-9-tetrahydrocannabinol

Analgesic, appetite-stimulating, and subjective effects of ... Preclinical studies point to CBG's potential pain-relieving and appetite stimulating effects but these findings have yet to be translated to humans. It has been ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0022356524257438

The Pharmacological Case for Cannabigerol Studies indicate that CBG may have therapeutic potential in treating neurologic disorders (eg, Huntington disease, Parkinson disease, and multiple sclerosis)

6. webmd.com webmd.com/vitamins/ai/ingredientmono-1690/delta-9-tetrahydrocannabinol-thc

Delta-9-Tetrahydrocannabinol (Thc) - Uses, Side Effects, ... Side Effects · When taken by mouth: THC is possibly unsafe when used in large amounts or long-term. · When applied to the skin: A specific cannabis extract spray ...

7. link.springer.com link.springer.com/article/10.1007/s11916-024-01252-4

Cannabinoids for Acute Pain Management Cannabinoids could potentially contribute to a better pain management and to a reduction in opioid doses while maintaining effective analgesia with minimum ...