Beyond CB1 & CB2: How Cannabis Affects More Than You Think

 

Most people think of cannabis as working through just two receptors—CB1 and CB2—but that’s only part of the story. In reality, cannabis interacts with a wide network of biological systems, from mood and pain to metabolism, inflammation, and even bone health. Beyond the classic cannabinoid receptors, cannabis influences serotonin, dopamine, opioid, TRP, PPAR, and GPR pathways, as well as enzymes like FAAH and MAGL that regulate your body’s own endocannabinoids. This expanded view of the Endocannabinoid System (ECS) helps explain why cannabis can be so effective for such a broad range of conditions—and why personalized, evidence-based guidance matters more than ever.

You may have heard of CB1 and CB2 receptors, but the Endocannabinoid System (ECS) is much more complex. Cannabis influences many other receptors, enzymes, and pathways, each contributing to different therapeutic effects.

🔬 TRPV1 (Vanilloid Receptors) – Play a role in pain perception, inflammation, and body temperature regulation. These receptors are also activated by spicy foods like chili peppers (capsaicin).

🧬 PPARs (Peroxisome Proliferator-Activated Receptors) – Involved in metabolism, immune function, and neuroprotection. These receptors explain why cannabis may have potential in neurodegenerative diseases like Alzheimer’s and Parkinson’s.

🔎 GPR55 (Orphan Receptor) – Sometimes called the “third cannabinoid receptor,” this receptor may be involved in bone health, cancer progression, and inflammation regulation.

🛠 FAAH & MAGL Enzymes – These enzymes break down endocannabinoids like anandamide (often called the “bliss molecule”). By slowing this breakdown, cannabis can enhance natural mood stabilization, pain relief, and stress reduction.

💡 Why does this matter? Understanding these additional pathways helps explain why cannabis works for such a wide variety of conditions, from chronic pain and anxiety to neurodegenerative diseases and metabolic disorders.

📌 Want to learn more? Schedule a consultation to discuss how cannabis affects your unique physiology.

 

🌍 Cannabis & The Expanded ECS: More Than Just Two Receptors

 

Cannabis does far more than just activate CB1 (brain) and CB2 (immune system) receptors. It interacts with multiple signaling pathways, receptor families, and enzymes that affect pain, mood, metabolism, digestion, inflammation, and even bone health.

Here’s a deeper look at other key players in the Endocannabinoid System (ECS) and beyond.

🧠 Dopamine, Serotonin & Opioid Receptors – The Brain’s Reward & Mood Regulators

 

Cannabinoids influence the same neurotransmitter systems that antidepressants, opioids, and stimulants target, which helps explain its effects on mood, motivation, pain relief, and reward processing.

✔️ Dopamine Receptors (D1-D5) – Cannabis can increase or modulate dopamine, influencing motivation, pleasure, and reward-seeking behavior.

✔️ Serotonin Receptors (5-HT1A, 5-HT2A) – CBD interacts with serotonin receptors, reducing anxiety and depression.

✔️ Opioid Receptors (μ, κ, δ) – Cannabinoids affect opioid pathways, enhancing pain relief and reducing opioid withdrawal symptoms.

📌 Why it matters: This explains why cannabis reduces anxiety, depression, and pain while also offering potential in addiction treatment.

🔥 The TRP Family: How Cannabis Influences Pain, Inflammation & Sensory Perception

 

Cannabis doesn’t just numb pain—it actively changes how pain is processed.

✔️ TRPV1 (“Capsaicin Receptor”) – Helps regulate pain perception, inflammation, and body temperature. Activated by both cannabis and spicy foods like chili peppers.

✔️ TRPV2 & TRPV4 – Involved in neuropathic pain, heat sensitivity, and inflammatory responses.

✔️ TRPA1 (“Wasabi Receptor”) – Affects pain sensation, gut inflammation, and respiratory conditions like asthma.

📌 And Why Should We Care?!: This explains why cannabis helps with nerve pain, migraines, muscle spasms, and inflammatory pain syndromes.

🛡️ The PPAR System: Cannabis & Metabolism, Inflammation, and Neuroprotection

 

PPARs (Peroxisome Proliferator-Activated Receptors) regulate fat metabolism, immune function, and brain cell survival.

✔️ PPAR-α & PPAR-γ – Found in liver, fat cells, and brain tissue, affecting blood sugar control, inflammation, and neurodegeneration.

✔️ PPAR activation by cannabinoids may explain cannabis’ potential benefits in diabetes, Alzheimer’s, and autoimmune conditions.

📌 Ok, And??: This highlights cannabis’ potential role in neurodegenerative diseases, metabolic disorders, and chronic inflammation.

🔄 GPR Receptors: The “Forgotten” Cannabinoid Targets

 

GPR receptors (G Protein-Coupled Receptors) are involved in immune response, bone growth, and metabolic regulation.

✔️ GPR18 – Regulates immune response and inflammation, with potential in autoimmune diseases like multiple sclerosis.

✔️ GPR55 (“CB3 Receptor”) – Affects bone health, cancer growth, and gut function.

✔️ GPR119 – Involved in insulin secretion and appetite regulation, making it relevant for diabetes and obesity research.

📌 Wow! Ok, Yes: GPR receptors expand cannabis’ role beyond pain relief, into immune function, metabolic balance, and bone health.

🩸 The Endothelial System: Cannabis & Cardiovascular Health

 

Cannabis affects blood flow, vascular inflammation, and heart rate through its interactions with endothelial cells and vascular receptors.

✔️ Cannabinoids like CBD may lower blood pressure by dilating blood vessels.

✔️ Cannabis reduces inflammation in arterial walls, potentially benefiting cardiovascular health.

✔️ THC and CBD interact with nitric oxide pathways, which regulate blood vessel function.

📌 Seriously?!: Cannabis’ cardiovascular effects are complex—some people may benefit from its anti-inflammatory properties, while others may experience an increase in heart rate.

🔬 FAAH & MAGL: How Cannabis Extends the Life of Your Natural Endocannabinoids

 

Your body produces its own cannabinoids—anandamide (the “bliss molecule”) and 2-AG. But enzymes break them down quickly.

✔️ FAAH (Fatty Acid Amide Hydrolase) – Breaks down anandamide, reducing its natural calming effects. CBD inhibits FAAH, allowing anandamide levels to stay higher for longer.

✔️ MAGL (Monoacylglycerol Lipase) – Degrades 2-AG, which influences pain, inflammation, and brain plasticity.

📌 Why it matters: This helps explain why CBD is non-intoxicating yet still enhances mood, reduces anxiety, and alleviates pain.

🌍 The Bigger Picture: Why This Matters for Medical Cannabis

 

Understanding cannabis beyond CB1 & CB2 helps explain:

✔️ Why cannabis works for such a wide range of conditions (pain, inflammation, metabolism, mood disorders, neurodegenerative diseases, and more).

✔️ Why different cannabinoids and terpenes matter—they activate different receptor systems.

✔️ Why cannabis affects people differently—genetics, metabolism, and existing conditions all play a role.

📌 Takeaway: Cannabis is far more than a simple “CB1/CB2 activator.” Its effects extend across multiple biological systems, influencing health and disease in ways modern medicine is only beginning to understand.

 Next Steps: Your Cannabis Journey Begins Here

 

🚀 Now that you understand the basics, what’s next?

✔️ Step 1: Check if you qualify for medical cannabis—if you’re experiencing chronic pain, anxiety, sleep disturbances, or other health challenges, you may be eligible. Learn about qualifying conditions.

✔️ Step 2: Book a consultation with a licensed provider to discuss whether cannabis is right for you. Schedule your appointment today.

✔️ Step 3: Register for the Massachusetts Medical Use of Marijuana Program and get your medical cannabis card. Learn how to register.

✔️ Step 4: Visit a licensed dispensary and choose the best products for your needs. Check out our Dispensary Guide.

Ready to Take Control of Your Health?

 

📌 For a comprehensive, evidence-based guide to using cannabis effectively on your own, check out The Doctor-Approved Cannabis Handbook—your go-to resource for science-backed insights and practical strategies.

📌 Book Your Consultation Today – For personalized guidance tailored to your unique needs, schedule personalized medical cannabis guidance with Dr. Caplan here and get expert support on your cannabis journey

📌 Join Our Newsletter – Stay updated on cannabis research, product recommendations, and exclusive patient insights. Sign up here.

📌 Questions? Check out our Frequently Asked Questions (FAQ) or reach out directly:  Ask Dr Caplan   |   Email CED Clinic  |