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

Trial Summary

What is the purpose of this trial?

This study will assess the analgesic, appetite-stimulating, and subjective effects of cannabigerol (CBG) alone and in combination with THC.

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.

What evidence supports the effectiveness of the drug CBG + THC for pain relief?

Research suggests that CBG, a component of the drug, may help reduce chronic pain, as a survey found that many users reported significant improvement in pain and other conditions like anxiety and depression when using CBG-predominant cannabis. Additionally, CBG has been shown to reduce neuron excitability, which might contribute to its pain-relieving properties. ^{1 2 3 4 5}

Is CBG + THC safe for human use?

Research on CBG (Cannabigerol) is limited, but a survey of users reported that 44% experienced no adverse effects, while some noted dry mouth, sleepiness, increased appetite, and dry eyes. Most users did not report withdrawal symptoms, suggesting a generally benign safety profile, but more studies are needed to confirm these findings. ^{1 2 3 5 6}

How is the drug CBG + THC for pain different from other treatments?

CBG + THC is unique because it combines cannabigerol (CBG), which is non-psychoactive and interacts with various receptors involved in pain perception, with tetrahydrocannabinol (THC), known for its analgesic effects. This combination may offer a novel approach to pain management by targeting different pathways compared to traditional pain medications. ^{1 2 3 4 7}

Research Team

Ziva D Cooper, PhD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

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.

I can participate in all required study activities.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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]

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]

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]

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]

References

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

Cannabigerol (CBG) attenuates mechanical hypersensitivity elicited by chemotherapy-induced peripheral neuropathy. [2022]

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

The Pharmacological Case for Cannabigerol. [2021]

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

Pharmacological Aspects and Biological Effects of Cannabigerol and Its Synthetic Derivatives. [2022]

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

Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability. [2022]

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

Survey of Patients Employing Cannabigerol-Predominant Cannabis Preparations: Perceived Medical Effects, Adverse Events, and Withdrawal Symptoms. [2023]

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

Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. [2021]

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

Dose-Related Inhibition of Capsaicin Responses by Cannabinoids CBG, CBD, THC and their Combination in Cultured Sensory Neurons. [2022]