CBG (Cannabigerol) in Medical Cannabis.

Cannabigerol (CBG) in Medical Cannabis: A Comprehensive Review of Therapeutic Benefits

Abstract

This paper examines the emerging therapeutic potential of Cannabigerol (CBG), a non-psychoactive cannabinoid found in cannabis that has garnered significant interest in recent years. Often overshadowed by THC and CBD, CBG is uniquely positioned as a precursor to several cannabinoids and offers a broad range of medical applications without psychoactive side effects. This review details CBG’s pharmacological profile, highlighting its interactions with the endocannabinoid system and exploring its promising role in managing inflammation, neurodegenerative disorders, pain, mood regulation, and cancer.

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1. Introduction

Cannabigerol, or CBG, is one of over 100 cannabinoids identified in cannabis, recognized as the biochemical precursor of well-known cannabinoids like THC (tetrahydrocannabinol) and CBD (cannabidiol). CBG has historically been less studied due to its lower natural abundance, typically present in early-harvest cannabis strains at low concentrations. However, scientific interest has surged recently due to its range of medical applications and non-intoxicating nature.

CBG has distinct mechanisms and potential benefits that set it apart from other cannabinoids. Its unique interaction with CB1 and CB2 receptors in the body, as well as various non-cannabinoid receptors, contributes to therapeutic effects like pain modulation, neuroprotection, and mood regulation. While research is still developing, the potential of CBG to treat numerous chronic illnesses positions it as a promising therapeutic agent in the field of medical cannabis.

2. CBG’s Mechanisms of Action

Understanding CBG’s therapeutic applications requires an exploration of how it interacts with the human body’s endocannabinoid system (ECS), a regulatory network comprising endocannabinoids, receptors (primarily CB1 and CB2), and enzymes. The ECS plays a central role in maintaining bodily homeostasis and affects processes such as mood, appetite, immune function, and pain response.

• CB1 and CB2 Receptors: Unlike THC, which binds primarily to CB1 receptors in the brain to produce psychoactive effects, CBG has a weak affinity for both CB1 and CB2 receptors. CB1 receptors are located in the central nervous system, while CB2 receptors are more prominent in immune cells and peripheral organs. This selective receptor affinity allows CBG to provide therapeutic effects without intoxication.
• Non-Endocannabinoid Receptor Interaction: CBG also interacts with various non-cannabinoid receptors, such as the α2-adrenergic and serotonin (5-HT1A) receptors. These interactions may help modulate anxiety, pain, and inflammation independently of the ECS, highlighting CBG’s versatility as a therapeutic agent.
• Neurogenesis and Neuroprotection: Preclinical studies indicate that CBG may stimulate neurogenesis, or the formation of new neurons, a property beneficial for neurodegenerative diseases. CBG’s neuroprotective effects are attributed to its ability to protect neurons from oxidative stress and inflammation, reducing the risk of cell death in degenerative diseases.

3. Therapeutic Benefits of CBG

3.1 Anti-Inflammatory Properties

Chronic inflammation is central to many diseases, from autoimmune conditions to metabolic disorders. CBG’s potent anti-inflammatory properties make it a promising candidate for treating several inflammation-related conditions:

• Inflammatory Bowel Disease (IBD): Inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, are characterized by persistent intestinal inflammation. CBG’s ability to reduce inflammation and tissue damage in the gut has been documented in animal studies, where it was shown to decrease levels of pro-inflammatory cytokines, such as TNF-alpha and nitric oxide, both of which contribute to IBD pathology. This indicates potential use in treatment-resistant cases or as a complementary therapy to standard treatments.
• Rheumatoid Arthritis: Rheumatoid arthritis is an autoimmune disease where chronic inflammation leads to joint damage and disability. CBG’s anti-inflammatory properties may benefit individuals with rheumatoid arthritis by reducing inflammation in joint tissues, offering pain relief, and possibly slowing disease progression.

3.2 Antibacterial and Antimicrobial Potential

One of the more promising applications of CBG is its antimicrobial action, especially its effectiveness against antibiotic-resistant bacteria.

• Methicillin-Resistant Staphylococcus aureus (MRSA): Studies indicate that CBG has significant antibacterial properties, showing efficacy against methicillin-resistant Staphylococcus aureus (MRSA), a pathogen associated with severe and often untreatable infections. CBG’s mechanism likely involves disrupting the bacterial cell membrane and inhibiting biofilm formation, making it difficult for bacteria to survive and replicate. This positions CBG as a potential candidate for new antimicrobial therapies, which are urgently needed due to rising antibiotic resistance.
• Other Bacterial Infections: Beyond MRSA, CBG demonstrates broad-spectrum antibacterial properties, including activity against other gram-positive bacteria. Ongoing studies are evaluating CBG’s efficacy in topical applications for skin infections and wound healing.

3.3 Pain Relief and Analgesic Potential

Pain, particularly chronic pain, is challenging to treat with conventional medications. The analgesic qualities of CBG provide a substitute for opioids, which have the potential to cause dependence and adverse effects.

• Neuropathic Pain: Neuropathic pain, a form of chronic pain often associated with nerve damage, is notoriously difficult to treat. Animal studies indicate that CBG may alleviate neuropathic pain by reducing inflammation in neural pathways and modulating pain signals. By activating α2-adrenergic receptors, CBG may suppress pain perception without producing the sedative side effects common in other analgesics.
• Chronic Pain Disorders: Chronic conditions, including fibromyalgia, multiple sclerosis (MS), and arthritis, often involve a pain component that is resistant to treatment. CBG’s dual action on both inflammatory and pain pathways presents it as a possible therapeutic for these types of chronic pain, potentially improving quality of life for affected individuals.

3.4 Neuroprotective and Cognitive Benefits

The neuroprotective qualities of CBG are of particular interest for neurodegenerative diseases, which involve progressive nerve cell loss and cognitive decline.

• Huntington’s Disease: The brain’s nerve cells degenerate in Huntington’s disease, an inherited neurodegenerative condition. Preclinical studies using animal models of Huntington’s disease have shown that CBG may help slow disease progression by protecting nerve cells from inflammation-induced damage and reducing neurotoxic levels of certain molecules associated with neurodegeneration.
• Parkinson’s and Alzheimer’s Diseases: By reducing neuroinflammation and protecting neurons from oxidative damage, CBG has potential applications in managing both Parkinson’s and Alzheimer’s disease. In Parkinson’s disease, CBG’s antioxidant properties may counteract the oxidative stress that leads to dopamine neuron death, a primary cause of the disease’s characteristic motor symptoms.

3.5 Antidepressant and Mood-Stabilizing Effects

Mental health disorders, such as depression and anxiety, represent a significant global health challenge, often inadequately managed by conventional therapies.

• Depression: CBG’s influence on serotonin receptors (5-HT1A) provides a mechanism for mood modulation. CBG may enhance serotonin signaling, producing mood-stabilizing and anti-depressive effects that could benefit individuals with treatment-resistant depression.
• Anxiety and PTSD: Animal studies suggest that CBG might help manage anxiety symptoms by acting on serotonin and adrenergic receptors. It may also reduce symptoms of PTSD by lowering levels of the stress hormone cortisol. These findings suggest that CBG could complement or potentially replace current pharmacotherapies for anxiety and PTSD in some cases.
• Psychiatric Disorders: Beyond anxiety and depression, CBG’s modulation of dopamine pathways suggests it might benefit psychiatric conditions like schizophrenia or bipolar disorder, where dopamine dysregulation is a factor. To validate these results in clinical settings, however, a great deal more research is required.

3.6 Appetite Stimulation

CBG has demonstrated the ability to increase appetite, which is a crucial characteristic for those who lose their appetite as a result of illness or adverse drug reactions.

• Cachexia and Anorexia: People suffering from anorexia or cachexia brought on by HIV/AIDS, cancer, or other chronic conditions may benefit from CBG’s appetite-stimulating properties. Unlike THC, which also stimulates appetite, CBG provides this benefit without psychoactive effects, making it more suitable for a broader range of patients, including those who may not tolerate THC well.

3.7 Anti-Cancer Potential

Although much of the study is still in the preclinical stages, preliminary findings indicate that CBG may have anti-cancer capabilities.

• Colon Cancer: In vitro studies suggest that CBG may inhibit the growth of colorectal cancer cells by blocking the TRPM8 channel, which plays a role in cell proliferation. By disrupting cancer cell signaling, CBG may slow tumor growth and reduce metastasis, potentially enhancing survival outcomes.
• Breast and Prostate Cancers: CBG’s potential as an anti-cancer agent extends to hormone-sensitive cancers such as breast and prostate cancer. Studies are exploring CBG’s ability to inhibit cancer cell proliferation and induce apoptosis, offering a potential complementary therapy for conventional cancer treatments.

4. Clinical Studies and Preclinical Research on CBG

While much of the research on CBG remains preclinical, several studies underscore its potential in clinical applications:

• Animal Models: Animal studies have provided evidence for CBG’s efficacy in various models, including those for inflammation, neurodegeneration, and cancer. These studies serve as a foundation for understanding CBG’s mechanisms and therapeutic potential, highlighting the need for human trials.
• Human Trials: Limited human data are available, but small-scale clinical trials have been conducted with promising results. These trials suggest that CBG is well-tolerated, with mild to no adverse effects, supporting its safe use in medical settings.

5. CBG and Cannabinoid Synergy: The Entourage Effect

The entourage effect hypothesizes that cannabinoids work synergistically to enhance therapeutic effects. CBG, when combined with other cannabinoids, may amplify the benefits of cannabis formulations.

• CBG and CBD: Combined formulations of CBG and CBD may offer enhanced anti-inflammatory and analgesic effects. CBG and CBD work on different receptors, allowing for complementary effects that may benefit conditions like arthritis, where both inflammation and pain management are critical.
• CBG and THC: CBG’s interaction with THC is especially relevant in reducing the latter’s psychoactive effects. This makes it possible to create therapeutic formulations with THC’s medicinal benefits and fewer side effects, ideal for patients sensitive to THC.

6. Future Directions and Research Needs

While CBG research is still nascent, it offers promising avenues for future exploration:

• Larger Clinical Trials: Robust, large-scale human trials are necessary to confirm CBG’s safety and efficacy across various conditions, particularly neurodegenerative diseases, cancer, and chronic pain.
• Therapeutic Development: Development of CBG-based topical and oral formulations is underway, with researchers aiming to create targeted therapies for inflammatory and skin conditions.
• Drug Development: Because of its special qualities, CBG is a promising candidate for the development of new medications, especially in the fields of antibacterial and anticancer research.

Restrictions on Using Cannabis in Medical Practice as a Last-Resort Option: THC Monitoring to Prevent Psychoactive Effects

Cannabis-based treatments, despite their growing popularity and documented therapeutic benefits, remain strictly regulated within the medical field. The therapeutic application of cannabis-derived medications, particularly those containing psychoactive compounds like THC (tetrahydrocannabinol), is often limited to cases where conventional treatments have failed or are inadequate. Such restrictions ensure that cannabis is used responsibly in medical settings, safeguarding patients from potential psychoactive side effects and reinforcing cannabis’s role as a last-resort option rather than a first-line treatment.

Medical Cannabis as a Last-Resort Treatment

In many regions and medical guidelines, cannabis-based treatments are designated as “last-resort” options, intended only for patients who have not responded to standard treatments. This cautious approach is particularly common in cases involving chronic pain, epilepsy, multiple sclerosis (MS), and cancer-related symptoms where traditional medications have proven ineffective. The “last-resort” designation reflects ongoing concerns about the safety, long-term effects, and potential for misuse associated with cannabis-based treatments.

Medical professionals are advised to exhaust conventional options first, including FDA-approved medications and established therapies. Cannabis-based treatments may then be considered if these traditional methods fail to provide relief or cause adverse effects that outweigh their benefits. The restriction reinforces the principle of “do no harm,” ensuring that cannabis use is medically justified and not driven by patient preference or non-medical factors.

THC Monitoring in Medical Cannabis

A critical element in regulating medical cannabis is the careful monitoring of THC levels within prescribed medications. THC, the primary psychoactive compound in cannabis, has therapeutic benefits but can also cause mood alteration, euphoria, and impaired cognitive function. For patients who require medical cannabis but must avoid psychoactive effects, THC levels are typically minimized or excluded altogether, especially in products for children, elderly patients, or individuals with psychiatric conditions.

• Low-THC or THC-Free Formulations: Many medical cannabis products, particularly those designed for patients susceptible to psychoactive effects, contain little to no THC. Instead, these formulations emphasize non-psychoactive cannabinoids such as CBD (cannabidiol) or CBG (cannabigerol), which can offer therapeutic benefits without altering mental state. For example, CBD is preferred in treatments for epilepsy, inflammation, and anxiety, as it provides therapeutic relief without the risks associated with THC.
• Dose-Response Monitoring: For patients who may benefit from THC, such as those experiencing severe cancer-related pain or chemotherapy-induced nausea, THC levels are carefully controlled. Medical practitioners often start with the lowest effective dose to gauge patient response, incrementally increasing THC only as necessary to achieve symptom relief while minimizing psychoactive side effects. This dose-response approach helps to balance efficacy with safety, allowing healthcare providers to individualize treatment plans based on patient tolerance and therapeutic needs.

The Role of THC Monitoring in Patient Safety and Compliance

Rigorous THC monitoring is essential for maintaining patient safety and compliance with medical guidelines. Monitoring THC levels helps prevent unintended psychoactive effects, which can interfere with daily activities, cognitive function, and mental health. By adhering to established THC limits, healthcare providers can safeguard vulnerable populations—such as pediatric, geriatric, and psychiatric patients—who may be more susceptible to THC’s psychoactive effects.

• Medical Cannabis Regulations and Compliance: Various regulatory frameworks govern the permissible THC levels in medical cannabis, with strict limits placed on products available for therapeutic use. Many regions require regular third-party testing to confirm THC concentrations in cannabis-based medications, ensuring compliance with established medical and legal standards. This transparency provides healthcare providers and patients with confidence in the safety and consistency of their medications.
• Balancing Efficacy and Safety: In practice, achieving the therapeutic benefits of THC without inducing psychoactive effects requires careful balancing. For conditions where THC’s analgesic or antiemetic properties are indispensable, the medication is administered in controlled, gradually adjusted doses, often under close supervision. This cautious approach ensures that the therapeutic benefits are accessible to patients while minimizing risks, promoting responsible cannabis use within medical treatment plans.

Conclusion

In summary, the medical use of cannabis, particularly cannabinoids like CBG and THC, represents a promising but carefully regulated field, governed by restrictions that prioritize patient safety and therapeutic efficacy. Cannabigerol (CBG) has emerged as a non-psychoactive cannabinoid with a range of therapeutic applications, including anti-inflammatory, neuroprotective, and antimicrobial properties. As research progresses, CBG shows potential in addressing chronic conditions like inflammatory bowel disease, neurodegenerative disorders, and even antibiotic-resistant infections, making it a valuable addition to medical cannabis options without the psychoactive risks associated with THC.

The cautious approach to medical cannabis use emphasizes its role as a last-resort option, reserved for cases where conventional treatments have proven ineffective. This guideline ensures cannabis-based treatments are introduced responsibly, after other therapeutic avenues have been explored. Monitoring and controlling THC levels within medical cannabis products is essential for patient safety, especially in populations vulnerable to psychoactive effects, such as children, the elderly, and those with psychiatric conditions. The focus on low-THC or THC-free formulations, particularly for managing conditions like epilepsy, anxiety, and chronic pain, has expanded the therapeutic reach of cannabis without compromising cognitive function or daily quality of life.

Overall, stringent regulations and THC monitoring allow healthcare providers to balance the benefits of cannabinoids with their potential risks, delivering a controlled, effective treatment while minimizing unwanted effects. As more clinical studies validate the safety and efficacy of cannabinoids like CBG, cannabis may continue to evolve as a viable medical option across a broader range of conditions. These regulations and safety measures uphold the integrity of medical cannabis use, enabling healthcare providers to offer targeted, cannabinoid-based therapies that address otherwise unmet medical needs while prioritizing patient well-being.