Minor Cannabinoids Show Preclinical Promise in Neurodegenerative Disease Research

A 2024 review examines how lesser-known cannabis compounds—including cannabigerol (CBG), tetrahydrocannabivarin (THCV), and cannabidivarin (CBDV)—might contribute to future treatments for neurological disorders. The paper, published in Biomolecules by researchers at the Nathan Kline Institute for Psychiatric Research and New York University, surveys evidence involving Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, epilepsy, and substance-use disorders.

The findings are promising but preliminary. This was a literature review, not a clinical trial testing CBG, THCV, or CBDV in patients. Much of the research discussed comes from cell cultures and animal models, so the results do not establish that minor cannabinoids can prevent, slow, or treat neurodegenerative disease in people.

Cannabis contains more than THC and cannabidiol (CBD), its two best-known cannabinoids. Researchers have identified more than 100 other cannabinoids, along with terpenes, flavonoids, and alkaloids. These compounds can interact with the body’s endocannabinoid system and with other receptors, ion channels, and signaling pathways involved in inflammation, oxidative stress, immune activity, and neuronal function.

Those mechanisms help explain why minor cannabinoids have attracted interest in neurodegenerative-disease research. Chronic neuroinflammation and oxidative damage are associated with disorders such as Alzheimer’s and Parkinson’s disease. In laboratory and animal studies, some compounds have shown antioxidant, anti-inflammatory, or neuromodulatory activity—effects that could potentially protect nerve cells or modify disease-related processes.

CBG, sometimes called a “mother cannabinoid” because it is a chemical precursor to THC and CBD in the plant, has displayed several potentially relevant biological actions in preclinical studies. CBDV has also been investigated in models of neurological disease, including research involving abnormal alpha-synuclein accumulation, a protein-related process associated with Parkinson’s disease. THCV has a distinctive pharmacological profile and has shown activity in experimental models, but its effects can vary with dose and biological target; it should not automatically be treated as entirely free of psychoactive or other unwanted effects.

The review also discusses evidence involving other minor cannabinoids, including cannabichromene (CBC) and cannabinol (CBN). Some studies have examined their effects on inflammation, cancer-cell behavior, bone-related processes, or neuronal injury. These findings may help identify new drug targets, but they are not evidence that cannabis products or isolated cannabinoids are effective treatments for cancer, bone disease, Parkinson’s disease, or Alzheimer’s disease.

Another topic is the so-called “entourage effect,” the idea that cannabinoids and other cannabis constituents may produce different or stronger effects when used together than when administered individually. Terpenes, which contribute to the plant’s aroma and flavor, have shown anti-inflammatory, analgesic, or anxiety-related effects in some experiments. However, the extent to which combinations improve treatment outcomes in humans remains uncertain, and the optimal ratios, doses, and delivery methods have not been established.

Clinical evidence is considerably less developed than the preclinical literature. A separate review of cannabis-based products in neurodegenerative disease concluded that laboratory findings were more encouraging than human clinical data and called for larger, better-designed randomized trials. The current evidence does not support replacing established Parkinson’s or Alzheimer’s treatments with over-the-counter cannabis or cannabinoid products.

There are also practical safety concerns. The National Center for Complementary and Integrative Health notes that cannabis and cannabinoid products can cause side effects, interact with medications, and vary substantially in their labeled and actual contents. The FDA has approved specific cannabinoid medicines for a limited number of conditions, but the cannabis plant itself has not been approved as a treatment for neurodegenerative disease.

The value of the 2024 review is therefore mainly exploratory. It organizes evidence suggesting that compounds beyond THC and CBD may influence biological pathways relevant to brain disease and identifies areas where more rigorous research is needed. Before CBG, THCV, CBDV, or cannabinoid combinations can be considered viable treatments for Parkinson’s or Alzheimer’s disease, researchers will need to establish their pharmacology, dosing, long-term safety, and effectiveness in well-controlled human trials.