Major and Minor Cannabinoids

One way to distinguish between major and minor cannabinoids is the extent to which these compounds occur naturally in the cannabis plant. Major cannabinoids compose much of the cannabis plant, whereas minor cannabinoids are present in much smaller and rare quantities.¹  

Major Cannabinoids

The following 2 cannabinoids are considered major phytocannabinoids¹:

• Delta-9-tetrahydrocannabinol (THC): THC is the primary component of the cannabis plant and is known for causing psychoactive side effects. THC also may help reduce nausea, chronic pain, inflammation, and muscle spasms, improve appetite and sleep, treat glaucoma, and protect the nervous system.²
• Cannabidiol (CBD): Scientists first discovered this major cannabinoid, which accounts for up to 40% of cannabis plant extract. The FDA has approved CBD as the drug, Epidiolex, to treat certain forms of epilepsy. Current research is investigating the benefits of CBD in treating Parkinson’s disease, ulcerative colitis, schizophrenia, substance use disorders, anxiety, nausea, inflammation, pain, and psychosis.² 

A Cause for Confusion: Major vs Minor

The literature is confusing as to which cannabinoids are major and minor. Some minor cannabinoids are major cannabinoids because of how early they were isolated and how easy they were to synthesize.² 

Cannabigerol (CBG) and cannabichromene (CBC) are minor cannabinoids that are sometimes listed as major cannabinoids, along with CBD and THC.^1,3 Together, these 4 phytocannabinoids are called the “Big 4.”³ 

Conflictingly, some sources classify CBG as a minor cannabinoid,¹ whereas others classify CBG as a major cannabinoid along with CBD and THC.⁴

Although CBC is listed as one of the 4 major cannabinoids,^3,5 it is technically one of the most abundant minor cannabinoids.¹ CBC is a minor cannabinoid because the amounts of CBC within the cannabis plant are much lower than CBD, CBG, and THC.^1,6

Minor Cannabinoids

In addition to THC and CBD, cannabis plants produce more than 150 other cannabinoids known as minor or rare cannabinoids.³ Minor cannabinoids are classified into neutral, acidic, and varinic phytocannabinoids. 

Acidic cannabinoids are the natural form of cannabinoids within plants and are believed to carry antioxidant and defensive properties (insecticidal, antimicrobial) for the plant. When heated, these acidic compounds undergo decarboxylation, converting to neutral cannabinoid forms (eg, tetrahydrocannabinolic acid (THCA) converts to THC, and cannabidioloic acid converts to CBD).¹

Varinic cannabinoids are rarer forms with 2 fewer carbon atoms than their neutral counterparts. Varinic cannabinoids demonstrate unique therapeutic properties that are presently undergoing intense research investigation. Plants that contain these varinic compounds are becoming new targets of selective breeding.¹ 

Some important minor cannabinoids include the following¹:

• Neutral cannabinoids
  • Cannabinol (CBN): CBN is derived from the cannabis plant’s main psychoactive component, THC. CBN often develops in aged, older, or stored flowers or cannabis plants exposed to oxygen. CBN is helpful as a sleep aid, antibacterial, neuroprotectant, anti-inflammatory, and appetite stimulant.² 
  • CBC: CBC has a similar structure to THC, CBD, and CBN and may work in tandem with other cannabinoids—a term researchers call the entourage effect. CBC demonstrates analgesic, anti-inflammatory, antidepressant, and anti-acne health benefits.²
  • CBG: CBG comprises about 1% of the cannabis plant, whereas most CBG is converted into the major cannabinoids—CBD and THC. CBG has been associated with anti-nausea, analgesic, anti-inflammatory, antibacterial, and anti-cancer properties. It also reduces eye pressure in the treatment of glaucoma. CBG shares similarities with CBD, as both cannabinoids affect the endocannabinoid system (ECS).²
• Acidic phytocannabinoids
  • Cannabidioloic acid (CBDA): CBD is derived from CBDA via decarboxylation. CBDA helps reduce nausea, inflammation, seizures, and tumors.²
  • THCA: THC is derived from THCA via decarboxylation through intense heating. THCA is known for its anti-inflammatory, anti-obesity, anti-emetic, nonintoxicating, and neuroprotective qualities.
  • Cannabinolic acid (CBNA): CBNA is a nonintoxicating cannabinoid in the cannabis plant. CBNA derives from THC and is a precursor for CBN. Decarboxylation through intense heat or ultraviolet light converts CBNA to CBN. CBNA’s health benefits include antibacterial, anti-inflammatory, and anti-cancer properties and as a treatment for glaucoma and an appetite stimulant.⁷
• Varinic cannabinoids
  • Cannabidivarin (CBDV): CBDV is a nonpsychoactive strain of cannabis that decreases seizure activity. CBDV occurs most commonly in cannabis indica strains from Asia and Africa. CBDV is often higher in strains with lower amounts of THC and higher amounts of CBD.²
  • Tetrahydrocannabivarin (THCV): Most cannabis strains contain THCV, but this compound is especially prevalent in cannabis sativa strains cultivated in central Asia and South Africa. THCV works against THC by decreasing the psychoactive side effects. THCV reduces appetite and panic attacks, increases bone growth and the feeling of fullness, and manages obesity.²
  • Cannabigerovarin (CBGV): CBGV is nonintoxicating and derived from its counterpart, CBG, along with THC and CBD. Heat or light can convert CBGV into CBD. CBGV acts on the ECS through CB₁ receptors in the peripheral and central nervous systems. CBGV may be beneficial in treating skin and eye diseases and cancer.⁸
  • Cannabichromevarin (CBCV): CBCV is a phytocannabinoid and a propyl-cannabinoid containing a propyl chain. CBCV is closely related to CBC. It works on the ECS. It is unknown whether CBCV binds more to CB₁ or CB₂ receptors, but binding to both receptor types is assumed, given CBCV’s medicinal effects. CBCV may help to treat glaucoma, inflammatory bowel disease, colon cancer, acute and chronic pain, and seizures.⁹

This list describes 10 of the 150 possible minor cannabinoids that have been identified, translating into limitless therapeutic possibilities. 

Future Direction for Minor Cannabinoids

The National Institutes of Health is funding research to uncover the therapeutic benefits of minor cannabinoids, especially for analgesic effects without the psychoactive side effects found in THC.¹⁰

The market for minor cannabinoids as alternatives to conventional therapeutics is projected to grow by 16.4% from $9.2 billion in 2023 to more than $14 billion by 2030. This projected growth is due to the positive health benefits of minor cannabinoids for treating cancer, chronic pain, arthritis, and neurologic and metabolic disorders.¹¹