A New Era in Cannabis Medicine
Cannabis is far more than THC and CBD. The plant contains hundreds of biologically active compounds, including a family of medicinal compounds called "phytocannabinoids." These important molecules interact with the body’s natural endocannabinoid system (ECS) to promote balance and healing. Modern science continues to uncover how these phytocannabinoids offer therapeutic promise for pain, anxiety, inflammation, neuroprotection, autism, cancer, and even metabolic and skin disorders.
The Endocannabinoid System: Our Internal Balancing Act
Discovered in the late 20th century, the ECS was discovered and over a number of years, researchers figured out that it is highly involved in regulating our mood, sleep, immunity, pain sensation, and more. It works to keep our overall physiology balanced by making sure our cells are sending correct messages when we are facing stressors. This is called cellular homeostasis. Cannabinoid receptors (like CB1in the brain and CB2 in the immune system and gut) respond to both our own endocannabinoids and plant cannabinoids.
Meet the Minor Cannabinoids
1. Cannabigerol (CBG): The “Mother Cannabinoid”
CBG is often called "the mother of all other cannabinoids" as it is the precursor compound that goes on to form many other cannabinoids, like THC and CBD. CBG is non-impairing, meaning it does not have a "high" effect." Research shows it has pain-relieving, anti-anxiety, anti-inflammatory, neuroprotective, anti-cancer, and antidepressant properties. It also shows potential in managing psoriasis and metabolic disorders. It also may help to stimulate appetite, offering an alternative to THC, but without intoxicating effects for those who are looking to improve caloric intake. CBG has also been shown in animal studies to have significant potency in killing cancer cells, specifically in leukemia and glioblastoma.
In my medical practice, I have many patients using CBG either alone or in combination with other cannabinoids, for pain, anxiety, inflammation, psoriasis (using topical CBD+CBG seems particularly effective), symptoms of autism, and also dementia. Patients and caregivers report it helps with calming, focus, pain relief, inflammation and other challenging symptoms.
2. Cannabidiolic Acid (CBDA): The Raw Power of Cannabis
CBDA is the acidic precursor of CBD, found in raw cannabis. It is non-impairing and has been shown in research to have anti-nausea, antidepressant, and anti-anxiety effects at low doses. It is also a potent anti-inflammatory, which is, based on my experience, its main benefit in my patients. Studies suggest CBDA may help with chemotherapy-related nausea, epilepsy, and metabolic balance. It has demonstrated antiviral activity against SARS-CoV-2 in lab studies.
Many of my patients have been able to stop using other pain and inflammatory medications by substituting with CBDA, all without any unwanted side effects. I have also found that it has a calming effect in some of my pediatric patients with autism or other behavioral challenges, often combining it with CBD or other cannabinoids for synergistic benefits.
3. Cannabinol (CBN): The Restful Cannabinoid
CBN is found only in trace amounts in the cannabis flower (which is the plant's "factory" where all cannabinoids are made). CBN forms naturally as THC ages or is exposed to heat and light. It binds to both CB1 and CB2 receptors, like THC, but with much lower potency. Research on CBN reports that it offers a number of medicinal benefits, including sedation, pain relief, anti-inflammatory, anti-cancer, and antibacterial effects.
Recent human studies show CBN can improve sleep quality and reduce nighttime awakenings, making it an alternative to harsh sleeping pills. Currently there are numerous studies looking at CBN for pain and neuroinflammatory conditions.
Many of my patients are using CBN in combination with other cannabinoids to help with sleep and pain. Children with challenging behaviors due to autism or other conditions may benefit from CBN. My patient's parents have reported calming effects and improved mood with low doses of CBN.
4. Cannabidivarin (CBDV): The Neurological Ally
CBDV is another minor cannabinoid with tremendous medicinal potential. It is somewhat similar to CBD, with a slight difference in its chemical structure that changes some of its medicinal properties. CBDV acts on non-cannabinoid receptors, providing anti-seizure, anti-inflammatory, and behavioral-modulating effects. Early studies of CBDV in animals and in one human study of children with Rett syndrome (a genetic neurodevelopmental condition) demonstrated reduced seizures. In animal models of autism, researchers found improved sociability, less hyperactivity, better memory and less repetitive behaviors.
In my practice, I have recommended CBDV in pediatric patients with difficult-to-treat seizure disorders, most commonly in combination with CBD. Many of the parents report less frequent and shorter seizures and even some have seizure freedom with this combination. Additionally, some of my patients with severe autism have found benefits with CBDV, including less irritability, less hyperactivity and better social interactions.
Synergy and the Future of Cannabinoid Therapy
Each cannabinoid has unique molecular targets, but together they produce an “entourage effect," which is a synergistic interplay that enhances overall therapeutic outcomes. For example, combinations like CBD + CBG have shown superior anti-inflammatory and neuroprotective effects compared with single compounds in models of ALS and Parkinson’s disease.
As research expands, the focus is shifting toward personalized cannabinoid medicine, matching compounds and ratios to individual patient needs.
Rediscovering a Plant for Modern Medicine
From pain and anxiety to neurodegenerative and metabolic conditions, minor cannabinoids are reshaping how we understand cannabis as medicine. What once was considered a single-compound therapy (THC) is now recognized as a complex botanical system supporting the body’s natural healing mechanisms. The science is still evolving, but the message is clear: nature designed cannabis to heal us without harm.
Cannabis works best with knowledgeable guidance
It is important to understand that all of us have different responses to medications and plant compounds, and that cannabis medicine is not "one-size-fits-all." If you or a loved one are struggling and would like to explore cannabis medicine, we here at Goldstein Wellness can connect you to knowledgeable clinicians to help you find your effective cannabinoid regimen. We also offer medical discounts on vetted hemp products through your practitioner. You can register here to get started on your journey to healing and wellness.
CBG:
- Borrelli, Francesca, et al. "Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid." Carcinogenesis 35.12 (2014): 2787-2797.
- Brierley, Daniel I., et al. "A cannabigerol-rich Cannabis sativa extract, devoid of∆ 9-tetrahydrocannabinol, elicits hyperphagia in rats." Behavioural pharmacology 28.4 (2017): 280-284.
- Brierley, Daniel I., et al. "Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats." Psychopharmacology 233 (2016): 3603-3613.
- Brierley, Daniel I., et al. "Chemotherapy‐induced cachexia dysregulates hypothalamic and systemic lipoamines and is attenuated by cannabigerol." Journal of Cachexia, Sarcopenia and Muscle 10.4 (2019): 844-859.
- Cuttler, Carrie, et al. "Acute effects of cannabigerol on anxiety, stress, and mood: a double-blind, placebo-controlled, crossover, field trial." Scientific Reports 14.1 (2024): 16163.
- de Rezende Costa, F. H., Pellegrino de Oliveira, S., Spitz, M., & Rydz, E. (2022). Parkinson’s Disease and Dementia with Lewy Bodies, Patients Under Treatment with Standardized Extracts Enriched in Cannabidiol and Cannabigerol: Descriptive Observations in Preparation for a Phase 2a Clinical Trial. ECNE. https://doi.org/10.31080/ecne.2022.14.010
- Fellous, Tariq, et al. "Phytocannabinoids promote viability and functional adipogenesis of bone marrow-derived mesenchymal stem cells through different molecular targets." Biochemical Pharmacology 175 (2020): 113859.
- Fleisher-Berkovich, Sigal, et al. "Therapeutic potential of phytocannabinoid cannabigerol for multiple sclerosis: modulation of microglial activation in vitro and in vivo." Biomolecules 13.2 (2023): 376.
- Kadriya, Ahmad, Sarah Forbes-Robertson, and Mizied Falah. "The Anticancer Activity of Cannabinol (CBN) and Cannabigerol (CBG) on Acute Myeloid Leukemia Cells." Molecules 29.24 (2024): 5970.
- Lah, Tamara T., et al. "Cannabigerol is a potential therapeutic agent in a novel combined therapy for glioblastoma." Cells 10.2 (2021): 340.
- Li, Shijia, et al. "Cannabigerol (CBG): a comprehensive review of its molecular mechanisms and therapeutic potential." Molecules 29.22 (2024): 5471.
- Mammana, Santa, et al. "Could the combination of two non-psychotropic cannabinoids counteract neuroinflammation? Effectiveness of cannabidiol associated with cannabigerol." Medicina 55.11 (2019): 747.
- Mendiguren, Aitziber, et al. "Cannabigerol modulates α2-adrenoceptor and 5-HT1A receptor-mediated electrophysiological effects on dorsal raphe nucleus and locus coeruleus neurons and anxiety behavior in rat." Frontiers in Pharmacology 14 (2023): 1183019.
- Nachnani, Rahul, et al. "Chronic Cannabigerol as an Effective Therapeutic for Cisplatin-Induced Neuropathic Pain." Pharmaceuticals 16.10 (2023): 1442.
- Nachnani, Rahul, Wesley M. Raup-Konsavage, and Kent E. Vrana. "The pharmacological case for cannabigerol." Journal of Pharmacology and Experimental Therapeutics 376.2 (2021): 204-212.
- O'Brien, Lesley D., et al. "Effect of chronic exposure to rimonabant and phytocannabinoids on anxiety-like behavior and saccharin palatability." Pharmacology Biochemistry and Behavior 103.3 (2013): 597-602.
- Perez, Eduardo, et al. "In Vitro and Clinical Evaluation of Cannabigerol (CBG) Produced via Yeast Biosynthesis: A Cannabinoid with a Broad Range of Anti-Inflammatory and Skin Health-Boosting Properties." Molecules 27.2 (2022): 491.
- Russo, Ethan B., et al. "Survey of patients employing cannabigerol-predominant cannabis preparations: perceived medical effects, adverse events, and withdrawal symptoms." Cannabis and Cannabinoid Research 7.5 (2022): 706-716.
- Sepulveda, Diana E., et al. "Cannabigerol (CBG) attenuates mechanical hypersensitivity elicited by chemotherapy‐induced peripheral neuropathy." European Journal of Pain 26.9 (2022): 1950-1966.
- Zagzoog, Ayat, et al. "In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa." Scientific reports 10.1 (2020): 20405.
CBDA:
- Anderson, Lyndsey L., et al. "Pharmacokinetics of phytocannabinoid acids and anticonvulsant effect of cannabidiolic acid in a mouse model of Dravet syndrome." Journal of natural products 82.11 (2019): 3047-3055.
- Bolognini, D., et al. "Cannabidiolic acid enhances 5-HT1A receptor activation and prevents vomiting in Suncus murinus and nausea-like behaviour in rats with greater potency and selectivity than cannabidiol." British Journal of Pharmacology 168.6 (2013): 1456-1470.
- Bolognini, D., et al. "Cannabidiolic acid prevents vomiting in S uncus murinus and nausea‐induced behaviour in rats by enhancing 5‐HT1A receptor activation." British journal of pharmacology 168.6 (2013): 1456-1470.
- Boulebd, Houssem. "Is cannabidiolic acid an overlooked natural antioxidant? Insights from quantum chemistry calculations." New Journal of Chemistry 46.1 (2022): 162-168.
- De Petrocellis, Luciano, and Vincenzo Di Marzo. "Non-CB 1, non-CB 2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: Focus on G-protein-coupled receptors and transient receptor potential channels." Journal of Neuroimmune Pharmacology 5 (2010): 103-121.
- De Petrocellis, Luciano, et al. "Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8." Journal of Pharmacology and Experimental Therapeutics 325.3 (2008): 1007-1015.
- Fellous, Tariq, et al. "Phytocannabinoids promote viability and functional adipogenesis of bone marrow-derived mesenchymal stem cells through different molecular targets." Biochemical Pharmacology 175 (2020): 113859.
- Formato, Marialuisa, et al. "(‒)-Cannabidiolic acid, a still overlooked bioactive compound: an introductory review and preliminary research." Molecules 25.11 (2020): 2638.
- Goerl, Brett, et al. "Cannabidiolic acid exhibits entourage-like improvements of anticonvulsant activity in an acute rat model of seizures." Epilepsy research 169 (2021): 106525.
- Hen-Shoval, Danielle, et al. "Cannabinoid Receptor 2 Blockade Prevents Anti-Depressive-like Effect of Cannabidiol Acid Methyl Ester in Female WKY Rats." International Journal of Molecular Sciences 24.4 (2023): 3828.
- Nadal, Xavier, et al. "Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity." British journal of pharmacology 174.23 (2017): 4263-4276.
- Rock, E. M., and L. A. Parker. "Effect of low doses of cannabidiolic acid and ondansetron on LiCl‐induced conditioned gaping (a model of nausea‐induced behaviour) in rats." British journal of pharmacology 169.3 (2013): 685-692.
- Rock, Erin M., Cheryl L. Limebeer, and Linda A. Parker. "Effect of cannabidiolic acid and∆ 9-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain." Psychopharmacology 235 (2018): 3259-3271.
- Rock, Erin M., et al. "Effect of prior foot shock stress and Δ 9-tetrahydrocannabinol, cannabidiolic acid, and cannabidiol on anxiety-like responding in the light-dark emergence test in rats." Psychopharmacology 234 (2017): 2207-2217.
- Rock, Erin M., et al. "Evaluation of repeated or acute treatment with cannabidiol (CBD), cannabidiolic acid (CBDA) or CBDA methyl ester (HU-580) on nausea and/or vomiting in rats and shrews." Psychopharmacology 237 (2020): 2621-2631.
- Suzuki, Masayo, et al. "Cannabidiolic acid-mediated interference with AP-1 transcriptional activity in MDA-MB-231 breast cancer cells." Natural Product Communications 12.5 (2017): 1934578X1701200520.
- Takeda, Shuso, et al. "Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis." Drug metabolism and disposition 36.9 (2008): 1917-1921.
- Takeda, Shuso, et al. "Cannabidiolic acid, a major cannabinoid in fiber-type cannabis, is an inhibitor of MDA-MB-231 breast cancer cell migration." Toxicology letters 214.3 (2012): 314-319.
- Takeda, Shuso, et al. "Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells." The Journal of Toxicological Sciences 39.5 (2014): 711-716.
- Tamburello, Martina, et al. "Antiviral activity of cannabidiolic acid and its methyl ester against SARS-CoV-2." Journal of Natural Products 86.7 (2023): 1698-1707.
- van Breemen, Richard B., et al. "Cannabinoids block cellular entry of SARS-CoV-2 and the emerging variants." Journal of natural products 85.1 (2022): 176-184.
CBN:
- Aiken, Charity T., Allan J. Tobin, and Erik S. Schweitzer. "A cell-based screen for drugs to treat Huntington's disease." Neurobiology of disease 16.3 (2004): 546-555.
- Bonn-Miller, Marcel O., et al. "A double-blind, randomized, placebo-controlled study of the safety and effects of CBN with and without CBD on sleep quality." Experimental and Clinical Psychopharmacology (2023).
- Corroon, Jamie. "Cannabinol and sleep: separating fact from fiction." Cannabis and cannabinoid research 6.5 (2021): 366-371.
- Elsohly, M. A., et al. "Cannabinoids in glaucoma: a primary screening procedure." The Journal of Clinical Pharmacology 21.S1 (1981): 472S-478S.
- Farrimond, Jonathan A., Benjamin J. Whalley, and Claire M. Williams. "Cannabinol and cannabidiol exert opposing effects on rat feeding patterns." Psychopharmacology 223 (2012): 117-129.
- Karler, Ralph, William Cely, and Stuart A. Turkanis. "The anticonvulsant activity of cannabidiol and cannabinol." Life Sciences 13.11 (1973): 1527-1531.
- Leelawat, Surang, et al. "Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft." Asian Pacific Journal of Tropical Biomedicine 12.8 (2022): 323-332.
- Leelawat, Surang, et al. "Antitumor Effects of Delta (9)-Tetrahydrocannabinol and Cannabinol on Cholangiocarcinoma Cells and Xenograft Mouse Models." Evidence-Based Complementary and Alternative Medicine 2022 (2022).
- Maioli, Chiara, et al. "Cannabinol: History, Syntheses, and Biological Profile of the Greatest “Minor” Cannabinoid." Plants 11.21 (2022): 2896.
- Wong, Hayes, and Brian E. Cairns. "Cannabidiol, cannabinol and their combinations act as peripheral analgesics in a rat model of myofascial pain." Archives of oral biology 104 (2019): 33-39.
CBDV:
- Amada, Naoki, et al. "Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression." PeerJ 1 (2013): e214.
- Hill, A. J., et al. "Cannabidivarin is anticonvulsant in mouse and rat." British journal of pharmacology 167.8 (2012): 1629-1642.Hill, T. D. M., et al. "Cannabidivarin‐rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor‐independent mechanism." British journal of pharmacology 170.3 (2013): 679-692.
- Huizenga, Megan N., Alberto Sepulveda-Rodriguez, and Patrick A. Forcelli. "Preclinical safety and efficacy of cannabidivarin for early life seizures." Neuropharmacology 148 (2019): 189-198.
- Hurley, Ellen N., et al. "Efficacy and safety of cannabidivarin treatment of epilepsy in girls with Rett syndrome: A phase 1 clinical trial." Epilepsia 63.7 (2022): 1736-1747.
- Iannotti, Fabio Arturo, et al. "Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability." ACS chemical neuroscience 5.11 (2014): 1131-1141.
- Iannotti, Fabio Arturo, et al. "Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability." ACS chemical neuroscience 5.11 (2014): 1131-1141.
- Maione, Sabatino, et al. "Cannabinoids for use in the treatment of neuropathic pain." U.S. Patent No. 9,895,342. 20 Feb. 2018.
- Morano, Alessandra, et al. "Cannabis in epilepsy: From clinical practice to basic research focusing on the possible role of cannabidivarin." Epilepsia open 1.3-4 (2016): 145-151.
- Navarro, Gemma, et al. "Pharmacological data of cannabidiol-and cannabigerol-type phytocannabinoids acting on cannabinoid CB1, CB2 and CB1/CB2 heteromer receptors." Pharmacological Research 159 (2020): 104940.
- Pagano, E., et al. "The non-euphoric phytocannabinoid cannabidivarin counteracts intestinal inflammation in mice and cytokine expression in biopsies from UC pediatric patients." Pharmacological Research 149 (2019): 104464.
- Pretzsch, Charlotte M., et al. "Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without Autism Spectrum Disorder (ASD): a single dose trial during magnetic resonance spectroscopy." Translational psychiatry 9.1 (2019): 313.
- Pretzsch, Charlotte M., et al. "Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin." Molecular autism 12.1 (2021): 1-14.
- Vigli, Daniele, et al. "Chronic treatment with the phytocannabinoid Cannabidivarin (CBDV) rescues behavioural alterations and brain atrophy in a mouse model of Rett syndrome." Neuropharmacology 140 (2018): 121-129.
- Zamberletti, Erica, et al. "Cannabidivarin completely rescues cognitive deficits and delays neurological and motor defects in male Mecp2 mutant mice." Journal of Psychopharmacology 33.7 (2019): 894-907.
- Zamberletti, Erica, et al. "Cannabidivarin treatment ameliorates autism-like behaviors and restores hippocampal endocannabinoid system and glia alterations induced by prenatal valproic acid exposure in rats." Frontiers in cellular neuroscience 13 (2019): 367.