What Are Cannabinoids / Endocannabinoids
- Travis C
- 1 day ago
- 12 min read
What Are Cannabinoids?
The Most Complete 2025 Guide for Curious Humans & Cannabinoid Nerds Alike
Cannabinoids are everywhere in the wellness conversation now—CBD oils, THC vapes, CBG gummies, CBN sleep drops. But what actually is a cannabinoid? How does it work in your body? And how do phytocannabinoids (like CBD) differ from the cannabinoids your own body makes?
Below is a deep dive built from current scientific reviews and major reference texts (PubMed, NCBI/NIH, MDPI, Frontiers, etc.), with plain-text links so you can check the sources yourself.
Quick Summary (for Skimmers)
Cannabinoids are a broad family of compounds that can interact with the endocannabinoid system (ECS)—usually by binding to cannabinoid receptors (CB1, CB2) or influencing their signaling.
There are three main categories:
Endocannabinoids – made by your body (e.g., anandamide / AEA and 2-AG).
Phytocannabinoids – produced by plants, especially Cannabis sativa (e.g., THC, CBD, CBG, CBC, CBN).
Synthetic cannabinoids – lab-made compounds (some are approved medicines, others are dangerous street drugs like “Spice/K2”).
Cannabis plants contain 100+ identified cannabinoids (many sources now estimate >150), plus hundreds of terpenes and other compounds.
https://adf.org.au/drug-facts/cannabinoids/
The ECS helps regulate homeostasis—things like pain, mood, appetite, stress response, immune function, sleep, temperature, and more.Harvard Health
Medical evidence is strongest for:
Spasticity in multiple sclerosis
Chemotherapy-induced nausea/vomiting
Certain rare epilepsies (e.g., Dravet, Lennox-Gastaut with purified CBD) NCBI
Cannabinoids also have risks: impaired concentration & driving, anxiety or psychosis in vulnerable people, dependence (particularly with high-THC), and drug–drug interactions via liver enzymes (CYP450). NCBI
Table of Contents
Medical disclaimer: This article is informational and not a substitute for medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional before starting or changing any cannabinoid regimen.
What Are Cannabinoids? Formal Definition
There are two complementary ways scientists define “cannabinoid”:
Functional definition (receptor-based)
Cannabinoids are substances that bind to cannabinoid receptors (CB1, CB2, and sometimes related receptors) and influence their signaling.Biotics Research Blog
Structural/chemical definition
Cannabinoids are compounds structurally related to the plant molecules found in Cannabis sativa (particularly THC and its relatives), including plant-derived, endogenous, and synthetic analogues.Wikipedia
In practice, modern literature uses “cannabinoid” to cover:
Endocannabinoids – made inside the body
Phytocannabinoids – made by plants
Synthetic cannabinoids – made in labs
…and even a few cannabinoid-like molecules (terpenes, flavonoids, and lipids) that don’t look like THC but still modulate the ECS.
The Three Major Families of Cannabinoids
1. Endocannabinoids (Produced by Your Body)
Endocannabinoids are lipid-based signaling molecules your cells make “on demand,” not stored in vesicles like classic neurotransmitters. The best-studied are: PubMed
Anandamide (AEA) – named from ananda (“bliss” in Sanskrit)
2-arachidonoylglycerol (2-AG)
They bind to CB1 and CB2 receptors and help fine-tune processes like pain, mood, stress, and immune responses.
2. Phytocannabinoids (Plant-Derived)
Phytocannabinoids are cannabinoids made by plants—most famously by cannabis/hemp, but also by a few other plants. PMC
Key points:
Cannabis produces these mainly in glandular trichomes (tiny resin glands on flowers and leaves).
They’re typically first made as acid forms (e.g., THCA, CBDA, CBGA) and then decarboxylated (by heat, time, or light) into neutral forms (THC, CBD, CBG, etc.). Wikipedia
Modern analyses suggest 100–150+ distinct phytocannabinoids have been identified so far. Alcohol and Drug Foundation
3. Synthetic Cannabinoids (Lab-Made)
Synthetic cannabinoids are compounds created in the lab to: NCBI
Study cannabinoid receptors
Develop new drugs (e.g., dronabinol, nabilone, nabiximols)
Or, unfortunately, to make unregulated recreational products (“Spice,” “K2”) that often have stronger and more dangerous effects than natural THC.
Some synthetic cannabinoids are medications with standardized doses; others are illicit products linked to severe side effects, including psychosis, seizures, and organ damage.
The Endocannabinoid System (ECS): Your Internal Cannabinoid Network
The endocannabinoid system (ECS) is the biological network that cannabinoids interact with. It’s present in humans and many animals and appears to play a role in maintaining homeostasis across multiple body systems. PMC
Core Components of the ECS
Cannabinoid receptors
CB1 receptors
Highly expressed in the brain and central nervous system, especially in regions regulating pain, memory, mood, appetite, and motor control.
Also present in peripheral tissues (liver, fat, GI tract, reproductive organs, etc.). PMC
CB2 receptors
Found primarily on immune cells and in tissues like the spleen, tonsils, and some brain regions.
Involved in immune modulation and inflammation. PMC
Endocannabinoid ligands
Anandamide (AEA) and 2-AG are the main ones, plus others like PEA and OEA that interact with ECS-related targets.
Enzymes
FAAH (fatty acid amide hydrolase) – breaks down AEA
MAGL (monoacylglycerol lipase) – breaks down 2-AG
Other enzymes synthesize and degrade minor endocannabinoids. PubMed
What Does the ECS Do?
Research suggests the ECS helps regulate: Harvard Health
Pain perception
Mood and emotional processing
Stress response and fear extinction
Appetite and energy balance
Learning and memory
Reproductive and endocrine function
Harvard Health summarizes it as a system that “regulates and controls many of our most critical bodily functions.”
Harvard explainer:https://www.health.harvard.edu/blog/the-endocannabinoid-system-essential-and-mysterious-202108112569
Endocannabinoids in Detail: AEA, 2-AG & Friends
Anandamide (AEA)
Chemically, AEA is an ethanolamide of arachidonic acid.
It’s a partial agonist at CB1 receptors and interacts with CB2 more weakly.
AEA also activates TRPV1 (capsaicin) receptors, which is important for pain and temperature signaling.PubMed
It’s involved in mood, pain modulation, appetite, memory, and stress responses.
Key review:https://pubmed.ncbi.nlm.nih.gov/22801993/
2-AG (2-arachidonoylglycerol)
A full agonist at both CB1 and CB2 receptors.
Present at higher baseline levels than AEA in the brain. Nature
Plays a big role in retrograde signaling – released from post-synaptic neurons, travels backward across the synapse, and dampens neurotransmitter release from the presynaptic neuron (a brake on excess signaling).
Other Endocannabinoid-Related Molecules
Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) – “endocannabinoid-like” lipids that mainly act at PPAR-α and other targets but can modulate ECS tone.MDPI
Phytocannabinoids in Detail: THC, CBD, CBG, CBN, CBC & More
How Phytocannabinoids Are Made in the Plant
Cannabis synthesizes cannabinoids via a common precursor CBGA (cannabigerolic acid), formed from geranyl pyrophosphate + olivetolic acid. CBGA is then enzymatically converted into:Wikipedia
THCA (→ THC when heated)
CBDA (→ CBD)
CBCA (→ CBC)
…and sometimes retained as CBGA/CBG.
Review on phytocannabinoid classes:https://pmc.ncbi.nlm.nih.gov/articles/PMC11050509/https://pmc.ncbi.nlm.nih.gov/articles/PMC8625816/
Major Phytocannabinoids & What We Know
(Note: Effects below summarize early clinical and preclinical data. They are not guarantees or medical claims.)
Δ9-THC (Tetrahydrocannabinol)
Primary psychoactive cannabinoid in most cannabis chemotypes.
Partial agonist at CB1 and CB2.NCBI
Responsible for euphoria, altered perception, appetite stimulation, and intoxication (“high”).
Medical uses (in standardized formulations like dronabinol, nabilone): nausea/vomiting, appetite loss, some pain and spasticity indications.NCBI
CBD (Cannabidiol)
Non-intoxicating; does not activate CB1 like THC.
Acts as a negative allosteric modulator of CB1 and interacts with many other targets (5-HT1A, TRPV1, PPAR-γ, etc.).ScienceDirect
FDA-approved in purified form (Epidiolex) for certain epilepsies.
Widely studied for potential roles in anxiety, inflammation, pain, sleep, and neuroprotection, though evidence quality varies by condition.PMC
CBG (Cannabigerol)
Sometimes called the “mother cannabinoid” because CBGA is the biochemical precursor to many others. PMC
Mild affinity for CB1/CB2, plus other receptors (α-2 adrenergic, 5-HT1A, TRP channels).
Preclinical studies suggest potential for inflammation, neuroprotection, glaucoma, and IBS-like conditions, but human data are very limited so far. MDPI
CBN (Cannabinol)
Formed mainly by oxidation of THC (aging/degraded cannabis).PMC
Mildly psychoactive, weaker CB1 agonist than THC.
Marketed for sleep, but human data are sparse; most evidence is anecdotal or from small preclinical studies.
CBC (Cannabichromene)
Non-intoxicating cannabinoid with weak CB1/CB2 binding but activity at TRPA1, TRPV1, and TRPV3. PMC
Preclinical work suggests roles in inflammation, mood, and neurogenesis, but clinical evidence is minimal.
THCV, CBDV & Other “Minor” Cannabinoids
THCV (Tetrahydrocannabivarin) – may act as a CB1 antagonist at low doses and partial agonist at higher doses; studied for appetite, metabolic disorders, and glycemic control.
CBDV (Cannabidivarin) – structurally similar to CBD, under investigation for epilepsy and neurodevelopmental conditions. MDPI
Newer discoveries like THCP, CBDP have much higher receptor affinity in vitro, but real-world effects and safety are still being mapped. Cheef Botanicals
Synthetic Cannabinoids: Medicines & High-Risk Street Drugs
Pharmaceutical Synthetic/Semi-Synthetic Cannabinoids
Examples include: NCBI
Dronabinol (synthetic Δ9-THC) – used for chemotherapy-induced nausea and appetite loss in HIV/AIDS.
Nabilone – THC analogue for chemotherapy-induced nausea/vomiting.
Nabiximols (Sativex) – mouth spray combining THC + CBD, approved in several countries for MS-related spasticity and some pain conditions.
Key review (National Academies): https://www.ncbi.nlm.nih.gov/books/NBK425767/
High-Risk Street Synthetics (Spice, K2, etc.)
These are non-classical cannabinoids (e.g., aminoalkylindoles, diarylpyrazoles) often made to evade legal restrictions. Wikipedia
Many act as full CB1 agonists with much higher potency than THC.
Linked to severe poisonings, including psychosis, seizures, cardiovascular events, kidney injury, and deaths.
Because they are unregulated, frequently reformulated, and poorly tested, most public health organizations urge avoiding synthetic “herbal incense” / “legal high” products entirely.
How Cannabinoids Work: Receptors, Signaling & Other Targets
1. CB1 & CB2 Receptors (Classical Targets)
CB1 (Cannabinoid receptor type 1)
A G-protein–coupled receptor (GPCR) heavily expressed in brain neurons.
When activated, it reduces neurotransmitter release by inhibiting calcium channels and activating potassium channels. PMC
CB2 (Cannabinoid receptor type 2)
Primarily expressed in immune cells and peripheral tissues.
Modulates cytokine release, inflammation, and immune cell migration. PMC
2. Other Molecular Targets
Cannabinoids and cannabinoid-like molecules also interact with: ScienceDirect
TRP channels (TRPV1, TRPA1, TRPM8) – important in pain and temperature sensing.
Serotonin receptors (e.g., 5-HT1A) – relevant to anxiety and mood.
PPAR nuclear receptors – affect gene transcription related to inflammation and metabolism.
GPR55, GPR18, GPR119 – orphan GPCRs now considered “ECS-related” receptors.
Ion channels and transporters – altering neuronal excitability.
This broad “polypharmacology” is part of why cannabinoids can have wide-ranging effects but also why predicting individual responses is complicated.
Evidence-Based Medical Uses of Cannabinoids
The strongest systematic evidence comes from large reviews such as:
National Academies of Sciences, Engineering, and Medicine (2017) – “The Health Effects of Cannabis and Cannabinoids” https://www.ncbi.nlm.nih.gov/books/NBK425767/
JAMA systematic review (Whiting et al., 2015) – “Cannabinoids for Medical Use” https://jamanetwork.com/journals/jama/fullarticle/2338251
More recent comprehensive reviews on therapeutic potential: https://pmc.ncbi.nlm.nih.gov/articles/PMC10604755/
Conditions With Strongest Evidence
1. Chronic Pain
Reviews conclude substantial/“conclusive or substantial” evidence that cannabis/cannabinoids can help some chronic pain in adults, especially neuropathic pain. NCBI
Newer large trials (e.g., experimental cannabis-based drugs for low back pain) continue to support a moderate but meaningful pain reduction in some patients. AP News
2. Multiple Sclerosis (MS)–Related Spasticity
Nabiximols and similar THC/CBD combinations show clinically significant reductions in spasticity and associated symptoms in some people with MS.NCBI
3. Chemotherapy-Induced Nausea & Vomiting
THC-based pharmaceuticals (dronabinol, nabilone) are approved and show moderate to strong effectiveness when standard antiemetics fail. NCBI
4. Certain Epilepsies
Purified plant-derived CBD (Epidiolex) has robust randomized trial evidence for reducing seizure frequency in Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex–related seizures. PMC
Areas With Emerging / Limited Evidence
Evidence is promising but not yet definitive for:
Anxiety and PTSD symptoms
Tourette syndrome
Peripheral neuropathy, inflammatory conditions, psoriasis, IBS, migraine
Most reviews label the evidence for these as low or very low quality, often due to small sample sizes, mixed study designs, or lack of long-term data. NCBI
Risks, Side Effects & Drug Interactions
No discussion of cannabinoids is complete without risks. They vary by compound, dose, route, age, and individual susceptibility.
Short-Term Side Effects
Most common with THC-dominant products : NCBI
Dry mouth, red eyes
Increased heart rate
Impaired coordination and reaction time (dangerous when driving)
Anxiety, paranoia, or panic in some individuals
Short-term memory and attention problems
Dizziness, light-headedness
High-CBD products usually have milder short-term effects but can still cause GI upset, fatigue, and changes in appetite.
Long-Term / High-Dose Risks
Evidence from longitudinal and observational studies suggests potential risks from heavy, long-term, high-THC use, especially starting in adolescence: PMC
Increased risk of cannabis use disorder (dependence)
Worsening of psychotic disorders or triggering psychosis in vulnerable individuals
Worsening anxiety or mood symptoms in some users
Cognitive impacts (attention, memory, processing speed), particularly when heavy use begins during brain development
Drug–Drug Interactions
Many cannabinoids—especially CBD—affect liver enzymes (cytochrome P450 system), altering blood levels of other medications.Frontiers
CBD is a notable inhibitor of CYP3A4 and CYP2C19, which can raise levels of:
Some antiepileptics (clobazam, valproate)
Certain antidepressants and benzodiazepines
Some immunosuppressants and chemotherapeutic agents
Key review on cannabinoids & CYP450: https://www.frontiersin.org/articles/10.3389/fphar.2025.1599012/full
This is one reason medical supervision is important for people taking other prescription meds.
The Entourage Effect: Synergy or Hype?
The “entourage effect” is the idea that cannabinoids, terpenes, and other cannabis compounds work better together than isolated components alone.
What the Theory Says
Full-spectrum cannabis products might provide greater therapeutic benefit and fewer side effects than isolated THC or CBD.PMC
Terpenes (like myrcene, limonene, linalool, β-caryophyllene) may:
Modulate CB1/CB2 activity
Influence blood–brain barrier permeability
Contribute independent anti-inflammatory or analgesic effects Health Sciences
Key reviews: https://pmc.ncbi.nlm.nih.gov/articles/PMC10452568/https://pmc.ncbi.nlm.nih.gov/articles/PMC11870048/
What the Evidence Shows (So Far)
Preclinical data (cell and animal studies) show real synergy between certain cannabinoids and terpenes. PMC
Human evidence is mixed and limited – few rigorous trials directly compare full-spectrum vs isolated compounds at equal doses. PMC
Some experts argue the entourage effect is plausible but not yet conclusively proven in humans.
In short: entourage effect = promising hypothesis, not magic law of nature. It’s reasonable to experiment (safely) with full-spectrum vs isolates, but marketing often outruns the science.
Cannabinoids Beyond Cannabis: Other Plants & Novel Compounds
Cannabis isn’t the only game in town.
Cannabinoid-Like Compounds in Other Plants
Research has found cannabinoid or ECS-related ligands in several species: Wikipedia
Echinacea spp. – alkylamides acting at CB2-like receptors
Radula marginata (a liverwort) – perrottetinene, a mildly psychoactive cannabinoid
Helichrysum umbraculigerum, Acmella oleracea, and others – cannabinoid-like or ECS-active compounds
β-caryophyllene – a terpene found in black pepper, cloves, and cannabis that selectively activates CB2
Wikipedia has a good overview with primary literature references: https://en.wikipedia.org/wiki/Cannabinoid
These findings suggest that ECS-active molecules are more widespread in nature than we once thought.
Evaluating Cannabinoid Products (Consumer Guide)
Even though this article is about what cannabinoids are, most readers are also asking: how do I choose products that make sense and are safe?
1. Check the Cannabinoid Spectrum
Full-spectrum – includes THC (within legal limits), CBD, minor cannabinoids, and terpenes.
Broad-spectrum – similar, but typically no detectable THC.
Isolate – single compound (e.g., pure CBD).
Each has pros/cons:
Full/broad spectrum may leverage entourage mechanisms but are less standardized.
Isolates are clean and predictable, preferred when THC must be avoided (drug testing, high sensitivity, or specific medical contexts).
2. Look for Third-Party Lab Tests
Reputable products provide Certificates of Analysis (COAs) showing:
Actual cannabinoid profile and potency
Terpene profile (sometimes)
Contaminants – pesticides, heavy metals, residual solvents, microbes
If a brand doesn’t provide COAs, that’s a red flag.
3. Start Low, Go Slow
Because cannabinoids interact with so many systems and vary in effect person-to-person:
Start at a low dose (especially with THC).
Increase gradually, watching for both benefits and side effects.
Consider route (sublingual, edible, inhaled, topical) – each has different onset, intensity, and duration.
4. Talk to a Clinician, Especially If…
You take prescription meds metabolized by CYP3A4 or CYP2C19.
You have a history of psychiatric illness, especially psychosis or severe anxiety.
You’re pregnant, breastfeeding, or under 25 (developing brain).
Legal & Regulatory Overview (High-Level)
(This is a rapidly evolving landscape; always check current local laws.)
United States
Under federal law, “hemp” is cannabis with ≤0.3% Δ9-THC by dry weight, legalized in the 2018 Farm Bill for cultivation and sale (with restrictions).
Many CBD and hemp-derived products are widely sold, but the FDA only formally approves a few specific cannabinoid drugs (like Epidiolex). Regulatory guidance for supplements and foods is still evolving.
State laws vary widely regarding THC-rich cannabis, adult-use programs, medical cannabis, and newer hemp-derived intoxicants (Δ8-THC, THCP, HHC, etc.).
Outside the U.S.
Policies range from total prohibition to full legalization.
Many countries allow pharmaceutical cannabinoids while restricting plant products.
Because laws change frequently, consult official government or health authority websites for current regulations in your area.
Frequently Asked Questions About Cannabinoids
1. How many cannabinoids are there?
In cannabis, chemists have identified at least 100–150+ phytocannabinoids, depending on how strictly you define them. Alcohol and Drug Foundation
New minor cannabinoids and analogues continue to be discovered.
2. Are cannabinoids only found in cannabis?
No. While cannabis has the richest and most diverse set of phytocannabinoids, cannabinoid-like molecules and ECS-active compounds exist in other plants like Echinacea, Radula, and others. Wikipedia
3. What’s the difference between CBD and THC?
THC is intoxicating, producing a “high” primarily by activating CB1 receptors.
CBD is non-intoxicating, modulates CB1 and multiple other receptors, and can actually soften some THC effects like anxiety at certain ratios. NCBI
4. Is CBD completely safe?
“Safe” is relative. CBD is generally well-tolerated, but at higher doses or with certain medications it can: PMC
Cause GI upset, fatigue, or changes in appetite
Alter blood levels of other drugs via CYP450 inhibition
Rarely, affect liver enzymes in susceptible individuals
Medical supervision is especially important in children, those with liver disease, or people on multiple medications.
5. Do cannabinoids work the same for everyone?
No. Responses depend on:
Genetics
ECS tone and receptor density
Metabolism (liver enzymes)
Gut microbiome, diet, and overall health
Product type, cannabinoid mix, and dose
This variability is one reason personal experimentation (within safe limits) and professional guidance are key.
6. Where can I read high-quality science on cannabinoids?
Some good starting points:
Cannabinoids – StatPearls (NCBI Bookshelf): https://www.ncbi.nlm.nih.gov/books/NBK556062/
Review of the Endocannabinoid System – Lu & Mackie (2020): https://pmc.ncbi.nlm.nih.gov/articles/PMC7855189/
Phytocannabinoids & Therapeutic Potential – Blebea et al. (2024) / Jurga et al. (2024): https://pmc.ncbi.nlm.nih.gov/articles/PMC11050509/https://www.mdpi.com/1422-0067/25/20/11258
Therapeutic Effects of Cannabis and Cannabinoids – National Academies report: https://www.ncbi.nlm.nih.gov/books/NBK425767/
Cannabinoids for Medical Use – Whiting et al., JAMA 2015: https://jamanetwork.com/journals/jama/fullarticle/2338251
Therapeutic Potential of Cannabis – Leinen et al. 2023: https://pmc.ncbi.nlm.nih.gov/articles/PMC10604755/
Disclaimer:
The information provided on this website should not be considered medical advice. These products are not intended to diagnose, treat, cure, or prevent any disease. Always consult with a healthcare professional before starting any new supplement or health regimen, especially if you have a medical condition or are taking prescription medications. The efficacy of CBD for pain relief, anxiety, and other ailments will vary between individuals.