How Many Cannabinoid Receptors Are There in a Human Body? (Complete Guide)

 

Quick Answer: Humans have two confirmed cannabinoid receptors, CB1 and CB2, with growing evidence for additional receptors such as GPR55, GPR18, and GPR119. These receptors are distributed throughout the brain, immune system, and other tissues, forming the foundation of the endocannabinoid system that regulates mood, sleep, pain, and overall balance.

Have you ever wondered why your body seems wired to respond to cannabis? It is not coincidence or chance. Long before the first human sparked a joint or infused a tincture, the endocannabinoid system was quietly shaping how we sleep, eat, handle stress, and heal. 

This built-in network of receptors is one of the most fascinating systems in human biology, influencing everything from mood to immunity. 

The more scientists uncover, the more it becomes clear that this system is far more complex than once believed. So, how many cannabinoid receptors are there in the human body?

Key Takeaways

• The human body contains confirmed cannabinoid receptors CB1 and CB2, with evidence for emerging receptors like GPR55, GPR18, and GPR119.

• CB1 receptors are most abundant in the brain and central nervous system, influencing memory, coordination, mood, and perception.

• CB2 receptors were first identified in immune cells but are now known to exist in the brain, skin, and other tissues, helping regulate inflammation and repair.

• THC binds strongly to CB1 receptors, explaining its psychoactive effects, while individual differences in receptor density and genetics shape unique responses.

• The endocannabinoid system includes endocannabinoids such as anandamide and 2-AG, along with enzymes FAAH and MAGL that regulate their activity.

• Receptor research is expanding, with discoveries of new receptor variants and their potential role in conditions such as Alzheimer’s disease, multiple sclerosis, and chronic pain.

• Mellow Fellow products are formulated with cannabinoid science in mind, targeting receptor networks for consistent and predictable effects.

Why Do Humans Have Cannabinoid Receptors?

The existence of cannabinoid receptors in humans long before cannabis use raises a profound question: why did we evolve these specialized proteins? The answer lies in the essential role these receptors play in maintaining balance and survival.

Research published in the Journal of Cannabis Therapeutics shows that cannabinoid receptors are phylogenetically ancient, first appearing at least 600 million years ago. 

This means they evolved hundreds of millions of years before the cannabis plant itself, and they are found across a wide range of species including mammals, birds, amphibians, fish, and even simple organisms like sea urchins and leeches.

The persistence of cannabinoid receptors across evolution underscores their critical importance. These receptors help regulate key processes such as immune response, pain perception, mood, and sleep. 

Your body even produces its own cannabis-like compounds, known as endocannabinoids, specifically to activate them. The first identified endocannabinoid, anandamide, is named after the Sanskrit word “ananda,” meaning bliss, highlighting its role in mood and well-being.

This ancient system explains why plant-derived cannabinoids interact so seamlessly with human biology - they mimic the compounds our bodies already produce to maintain health and stability.

The Complete Picture: How Many Cannabinoid Receptors Exist?

The simple answer to "how many cannabinoid receptors are there in a human body?" has evolved significantly since the 1990s. While CB1 and CB2 remain the primary confirmed cannabinoid receptors, evidence strongly suggests humans possess a more extensive cannabinoid receptor network.

Confirmed Cannabinoid Receptors

CB1 Receptors (Primary Brain Receptors): According to Harvard Medical School research, "the 'cannabinoid' receptors in the brain - the CB1 receptors - outnumber many of the other receptor types in the brain." These receptors are encoded by the CNR1 gene and consist of 472 amino acids, making them among the most abundant G-protein coupled receptors in the central nervous system.

CB2 Receptors (Immune System Receptors): Discovered in 1993, CB2 receptors concentrate primarily in immune cells, with about 44% protein sequence similarity to CB1 receptors. They play a central role in regulating inflammation, immune response, and tissue repair.

Emerging Cannabinoid Receptors

GPR55 (Potential CB3 Receptor): Recent research suggests GPR55 should be categorized as the CB3 receptor based on its response to cannabinoid ligands, though this classification awaits official confirmation. GPR55 responds to endocannabinoids and may regulate bone density and blood pressure.

GPR18 and GPR119: Studies indicate these receptors may function as cannabinoid receptors, with GPR18 potentially mediating immune responses and GPR119 affecting glucose regulation. Research is ongoing to determine their exact roles in the endocannabinoid system.

TRPV1 and PPAR Receptors: While not traditional cannabinoid receptors, these proteins respond to certain cannabinoids and endocannabinoids, expanding the functional scope of cannabinoid activity beyond CB1 and CB2.

Where Are Cannabinoid Receptors Located in Your Body?

The effects of cannabinoids depend heavily on where their receptors are found in the body. Each receptor type is concentrated in certain tissues, which explains why cannabis products can influence everything from memory and mood to immunity and pain.

CB1 Receptor Distribution

CB1 receptors are most abundant in the central nervous system, but they are also present in many peripheral organs and tissues.

Brain Concentrations

• Highest Density: Basal ganglia, cerebellum, hippocampus, and neocortex

• Moderate Density: Brainstem and hypothalamus

• Lower Density: Spinal cord and peripheral nerves
  

These regions are central to movement, memory formation, coordination, and emotional regulation, which is why THC-containing products so strongly affect mood, perception, and motor control.

Peripheral CB1 Locations

• Cardiovascular system (heart and blood vessels)

• Gastrointestinal tract

• Liver and pancreas

• Reproductive organs

• Eye and skin tissue
  

This widespread distribution explains why cannabinoids like Delta 8 or Delta 9 THC can influence appetite, digestion, and pain perception in addition to cognitive effects.

CB2 Receptor Distribution

CB2 receptors were once thought to be confined mainly to immune cells, but research now shows a broader distribution across multiple tissues.

Primary Locations

• T cells, B cells, and macrophages

• Spleen, tonsils, and thymus

• Bone marrow and hematopoietic cells

• Microglial cells within the brain
  

Emerging Locations

• Skin (keratinocytes and hair follicles)

• Peripheral nerves

• Cardiovascular tissue

• Gastrointestinal system
  

Because CB2 receptors can regulate inflammation and immune response, their presence in the nervous system, skin, and cardiovascular tissues highlights potential therapeutic roles well beyond immunity alone.

THC Receptors in the Body: How Cannabis Compounds Interact

When people talk about “THC receptors in the body,” they are referring to how THC interacts with the body’s existing cannabinoid receptors. THC does not create new receptors but binds to the two primary receptor types your body already produces: CB1 and CB2.

 

THC and CB1 Receptor Interaction

THC has a strong affinity for CB1 receptors, which explains its psychoactive properties and therapeutic effects. Once bound, THC activates intracellular signaling pathways that reduce neurotransmitter release and alter neural activity. The duration and intensity of these effects depend on THC concentration, dosage, and an individual’s metabolism.

Regional Effects

Different brain regions with higher CB1 receptor concentrations respond in distinct ways:

• Hippocampus: Disruption of short-term memory and learning processes

• Cerebellum: Changes in coordination and motor control

• Basal Ganglia: Alterations in movement and motivational states

• Prefrontal Cortex: Impacts on decision-making, planning, and attention
  

Because CB1 receptors are spread throughout the nervous system, THC can influence a wide range of cognitive and physical functions.

Individual Receptor Variations

Not everyone experiences THC in the same way. Differences in receptor distribution and function help explain why some people are highly sensitive to cannabis while others require larger amounts for noticeable effects.

Key Factors Affecting Response

• Natural differences in CB1 receptor density, which can vary by as much as 40% between individuals

• Genetic variations (polymorphisms) in cannabinoid receptor genes, which can influence susceptibility to dependence and sensitivity to effects

• Differences in enzyme activity that control how quickly endocannabinoids are broken down

• Age-related changes in receptor density, with younger individuals typically having higher receptor availability
  

These variations mean that two people consuming the same dose of THC may have very different experiences. Formulations designed with multiple cannabinoids, such as balanced blends, can help smooth out these differences and provide more predictable effects.

Our pharmacist-formulated blends account for these variations by providing consistent, predictable effects.

The Endocannabinoid System: Beyond Just Receptors

Cannabinoid receptors are only part of a larger network known as the endocannabinoid system (ECS). This system regulates mood, memory, appetite, pain, immune response, and sleep. It is made up of endocannabinoids (naturally produced compounds in the body), receptors (CB1 and CB2), and enzymes that control how long signals last.

Endocannabinoids: The Body’s Natural Cannabis

Your body produces several endocannabinoids that bind to cannabinoid receptors.

Anandamide (AEA)

• Discovered in 1992 as the first identified endocannabinoid

• Binds mainly to CB1 receptors in the brain

• Regulates mood, appetite, and pain perception

• Rapidly broken down by the enzyme FAAH, limiting its effects
  

2-Arachidonoylglycerol (2-AG)

• The most abundant endocannabinoid in the brain

• Activates both CB1 and CB2 receptors

• Found at levels much higher than anandamide

• Produces longer-lasting effects before being broken down
  

Emerging Endocannabinoids

Recent studies continue to identify additional molecules with cannabinoid-like activity, such as pentadecanoylcarnitine and fatty acid derivatives. These discoveries suggest that the ECS is more complex than initially understood.

Enzyme Systems

Specialized enzymes regulate how long endocannabinoids remain active.

FAAH (Fatty Acid Amide Hydrolase)

• Breaks down anandamide and related compounds

• Prevents excessive CB1 receptor activation

• Genetic differences in FAAH can affect mood and stress responses
  

MAGL (Monoacylglycerol Lipase)

• Degrades 2-AG after receptor activation

• Controls the duration and intensity of endocannabinoid signaling

• Considered a promising therapeutic target for extending natural endocannabinoid activity

How Mellow Fellow Products Interact with Your Receptors

Understanding receptor science helps explain why different Mellow Fellow cannabinoid products create distinct experiences. Each cannabinoid in our formulations interacts differently with your receptor network.

Delta 8 THC Receptor Interactions

Delta 8 THC binds to CB1 receptors with approximately 60-70% of Delta 9's affinity, creating milder psychoactive effects. Our Delta 8 products take advantage of this reduced binding affinity for controlled, manageable experiences.

Delta 8 Potential Benefits

• Lower anxiety risk due to reduced CB1 activation

• Longer-lasting effects through slower receptor binding

• Enhanced focus maintenance compared to stronger cannabinoids

• Reduced memory impairment while maintaining therapeutic benefits

Multi-Cannabinoid Receptor Targeting

Our premium blends combine multiple cannabinoids to create targeted receptor activation patterns:

Euphoria Blend Profile

• Delta 8: Moderate CB1 activation for relaxation

• HHC: Balanced CB1/CB2 binding for mood enhancement

• THCp: Potent CB1 agonism for intensity

• CBG and CBD: Modulating effects through additional receptors

This multi-cannabinoid approach mimics your body's natural endocannabinoid diversity, potentially creating more balanced and therapeutic effects than single-cannabinoid products.

Terpene Receptor Interactions

Our live resin products preserve natural terpenes that interact with cannabinoid receptors and other systems:

• Myrcene: Enhances CB1 receptor sensitivity

• Limonene: Modulates serotonin and dopamine systems

• Pinene: Interacts with GABA receptors for alertness

• Linalool: Affects adenosine receptors for relaxation

Receptor Research: What Scientists Are Currently Discovering

Cannabinoid receptor research accelerates annually, revealing new therapeutic possibilities and biological mechanisms. Recent breakthroughs are reshaping our understanding of how these receptors function and their potential applications.

CB1 Receptor Variants

Scientists have identified two additional isoforms with shorter N-terminus of CB1 receptors resulting from alternative splicing. These variants, including CB1b, show different expression patterns:

• Full-length CB1 dominates brain and muscle tissue

• CB1b variants concentrate in liver and pancreatic cells

• Different variants may explain tissue-specific cannabinoid effects

CB2 Receptor Brain Functions

CB2 receptors were once believed to exist only in immune cells, but they are now understood to play key roles in the brain. Research shows that neuronal CB2 receptors help regulate synaptic activity and are involved in processes such as drug dependence and synaptic plasticity.

This discovery suggests CB2-targeted therapies could address neurological conditions without CB1-mediated psychoactive effects, opening new therapeutic avenues for conditions like:

• Alzheimer's disease

• Multiple sclerosis

• Chronic pain

• Addiction treatment

Making Sense of Your Body's Cannabinoid Network

Cannabinoid receptors are far more than points of interaction for cannabis compounds. They are ancient biological structures that evolved over 600 million years ago and play a critical role in regulating mood, memory, pain, sleep, and immunity. 

While CB1 and CB2 remain the primary confirmed receptors, research into GPR55, GPR18, GPR119, and other proteins suggests a broader network than once believed. 

Their distribution across the brain, immune system, and peripheral organs explains why cannabinoids influence such a wide range of physiological functions. Variations in receptor density and activity also clarify why individuals respond differently to cannabinoids. 

With continued research, these discoveries may shape new therapeutic approaches and deepen our understanding of human biology.

Ready to experience scientifically-formulated cannabinoid products designed with your receptor system in mind? Browse our complete collection and discover how proper receptor targeting can transform your cannabinoid experience.

Frequently Asked Questions

Can You Have Too Few or Too Many Cannabinoid Receptors?

Yes, receptor density varies significantly between individuals and can change over time. Some people naturally have 30-40% fewer CB1 receptors, affecting their sensitivity to cannabinoids. Chronic cannabinoid use can also reduce receptor density through downregulation.

Do Cannabinoid Receptors Change with Age?

Research shows CB1 receptor density generally decreases with age, particularly in brain regions affecting memory and cognition. This may explain why older adults often need different cannabinoid doses than younger users.

Can You Increase Your Natural Cannabinoid Receptor Function?

While you can't directly increase receptor numbers, certain activities may enhance endocannabinoid production and receptor sensitivity. Exercise, meditation, and omega-3 fatty acid consumption all support healthy endocannabinoid function.

Why Do Some People Need More Cannabinoids Than Others?

Individual differences in receptor density, enzyme activity, and metabolism significantly affect cannabinoid sensitivity. Genetic variations can cause 10-fold differences in required doses between individuals.

Are There Cannabinoid Receptors Outside the Brain?

Absolutely. CB1 receptors appear throughout the body, including the liver, digestive system, reproductive organs, and skin. CB2 receptors concentrate in immune cells but also exist in the brain and peripheral tissues.

Sources

• Sourcing the Code: Searching for the Evolutionary Origins of Cannabinoid Receptors, Vanilloid Receptors, and Anandamide: Journal of Cannabis Therapeutics: Vol 2, No 1

• CB1 Receptor Signaling in the Brain: Extracting Specificity from Ubiquity | Neuropsychopharmacology

• CB2 cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies - PMC

• GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current - PMC

• Potential Metabolic and Behavioural Roles of the Putative Endo-
cannabinoid Receptors GPR18, GPR55 and GPR119 in Feeding - PMC

• An update on PPAR activation by cannabinoids - PMC

• Diverse TRPV1 responses to cannabinoids - PMC

• Therapeutic Effects of Cannabis and Cannabinoids - The Health Effects of Cannabis and Cannabinoids - NCBI Bookshelf

• Emerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospects - PMC

• Cannabis effects on brain structure, function, and cognition: considerations for medical uses of cannabis and its derivatives - PMC

• Brain activity of anandamide: a rewarding bliss? - PMC

• The Endocannabinoid 2-Arachidonoylglycerol Is Responsible for the Slow Self-Inhibition in Neocortical Interneurons - PMC

• Pentadecanoylcarnitine is a newly discovered endocannabinoid with pleiotropic activities relevant to supporting physical and mental health - PubMed

• Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders - PMC

• Monoacylglycerol lipase – a target for drug development? - PMC

• Review of delta‐8‐tetrahydrocannabinol (Δ8‐THC): Comparative pharmacology with Δ9‐THC - Tagen - 2022 - British Journal of Pharmacology - Wiley Online Library

• Discovery and characterization of two novel CB1 receptor splice variants with modified N-termini in mouse - PMC

• Brain cannabinoid receptor 2: expression, function and modulation | Acta Pharmacologica Sinica

• The endocannabinoid system: Essential and mysterious - Harvard Health