Understanding Cannabinoids vs. THC
Cannabinoids are a broad class of chemical compounds that includes THC as one specific member, along with hundreds of other compounds found in cannabis plants or synthesized in laboratories. 1
Key Definitions
Cannabinoids (The Umbrella Term)
Cannabinoids encompass all compounds that interact with endocannabinoid receptors throughout the central and peripheral nervous system, immune cells, and organs 1
This broad category includes three main types:
The cannabis plant contains hundreds of bioactive cannabinoid compounds, including dozens of phytocannabinoids, phenols, and terpenes 1
THC (One Specific Cannabinoid)
- Δ9-tetrahydrocannabinol (THC) is the primary psychoactive cannabinoid responsible for the euphoric "high" associated with cannabis use 1
- THC functions as a partial agonist at both CB1 and CB2 cannabinoid receptors in the brain and body 1
- Under U.S. federal law, cannabis containing more than 0.3% THC is classified as marijuana, while plants with ≤0.3% THC are classified as hemp 1
Critical Clinical Distinctions
CBD: Another Major Cannabinoid
- Cannabidiol (CBD) is the second most studied cannabinoid and produces psychoactive effects without inducing euphoria 1
- CBD is not an agonist at CB1 or CB2 receptors; rather, it acts as a negative allosteric modulator and has been shown to reduce adverse effects of THC 1
- CBD mechanisms include increasing endocannabinoid signaling, enhancing serotonin receptor 1A activity, and activating pain-sensing receptors 1
Potency and Composition Variability
- THC concentration in cannabis has nearly doubled from 9% in 2008 to 17% in 2017, with some concentrates reaching 70% THC 1, 4
- The specification and concentration of cannabinoids vary dramatically by cannabis strain and product, making effects unpredictable 1
- Cannabis products work through the "entourage effect"—complicated synergistic and inhibitory interactions between multiple cannabinoids, terpenes, and other compounds 1
Pharmacological Differences
Metabolism
- All cannabinoids, including THC, are metabolized through the liver's cytochrome P450 enzyme system (primarily CYP3A4 and CYP2C9) 5
- When THC is ingested orally, it undergoes first-pass metabolism into 11-hydroxy-THC, a more potent psychoactive metabolite than THC itself 5
- Different cannabinoids have varying bioavailability: inhaled THC is 10-35% bioavailable versus only 4-12% for oral THC 1
Synthetic Cannabinoids: A Dangerous Subset
- Synthetic cannabinoids typically have increased affinity and efficacy at CB1 receptors compared to natural THC, making them more potent and dangerous 2
- While THC is a relatively weak CB1 partial agonist, most synthetic cannabinoids are full agonists, resulting in more powerful effects and increased risk of adverse reactions 2
- Synthetic cannabinoids marketed as "Spice" or "K2" can cause intoxication, withdrawal, psychosis, and death—effects rarely seen with natural cannabis 3
Clinical Implications
Drug Interactions
- Cannabis and cannabinoids inhibit multiple CYP450 enzymes, creating potential for drug-drug interactions with medications metabolized through these pathways 1, 5
- High-risk interactions include warfarin (very high risk), buprenorphine, and tacrolimus (high risk) 1, 5
Therapeutic Applications
- Synthetic cannabinoids like dronabinol (synthetic THC) and nabilone are FDA-approved for specific medical indications, particularly chemotherapy-induced nausea and vomiting 1
- Evidence suggests cannabinoids may have utility in chronic pain, chemotherapy-induced nausea, multiple sclerosis spasticity, and fibromyalgia 1
Common Pitfall
- Clinicians and patients often mistakenly believe "cannabinoids" and "THC" are interchangeable terms, leading to confusion about product selection, dosing, and expected effects 1
- The variable composition of cannabis products means evidence for one cannabinoid (like THC) cannot be extrapolated to whole-plant cannabis or other cannabinoid formulations 1