Why does the human body have cannabinoid receptors? The answer has nothing to do with cannabis plants. Long before humans cultivated, smoked or consumed cannabis, our ancestors already possessed a biological signaling system built around cannabinoid receptors and naturally produced chemicals. The body makes its own cannabinoids, uses them to regulate communication between cells and breaks them down when their job is finished. Cannabis happens to contain compounds that can interact with this ancient machinery. Understanding the endocannabinoid system explains why THC affects the brain, why cannabis influences appetite and memory, and why the human body has cannabinoid receptors in the first place.
The Discovery: Scientists Found the Receptor Before the Body's Own Cannabis
The story begins with a scientific puzzle.
In 1964, Israeli researchers Raphael Mechoulam and Yechiel Gaoni characterized the structure of THC, the principal intoxicating cannabinoid in cannabis.
For decades, scientists knew THC could produce powerful effects in the body. But an important question remained:
What was THC interacting with?
The answer began emerging in 1988.
Researchers William Devane, Allyn Howlett and colleagues demonstrated the existence of a specific cannabinoid-binding site in rat brain tissue.
This was a major discovery. If the brain had a receptor specifically capable of recognizing cannabinoids, it suggested that the receptor was not simply there for a plant compound.
Biology generally does not evolve specialized receptors in anticipation of something humans will discover thousands of years later.
The more logical possibility was that the body already produced its own chemicals capable of activating these receptors.
That hypothesis would soon be confirmed.
1990: The Discovery of CB1
The paper that started it — Matsuda et al., Nature (1990), reporting the first cloned cannabinoid receptor. Abstract via PubMed (PMID 2165569).
In 1990, researchers Matsuda, Bonner and colleagues successfully cloned the first cannabinoid receptor.
It was named:
CB1.
Published in Nature, the discovery provided the molecular identity of the receptor responsible for many of cannabis's effects in the nervous system.
CB1 belongs to a large family of proteins called G-protein-coupled receptors (GPCRs).
These receptors sit in cell membranes and translate chemical signals into changes in cellular activity.
CB1 turned out to be one of the most abundant GPCRs in the brain.
Its distribution also helped explain why cannabis affects so many different aspects of human experience.
CB1 is particularly concentrated in:
Basal ganglia: involved in movement and motor control.
Hippocampus: important for memory formation and learning.
Cerebral cortex: involved in thought, perception and higher cognitive functions.
Cerebellum: important for coordination and movement.
The receptor's distribution helps explain why THC can influence memory, movement, thought and coordination.
The scientists had identified the receptor. The next question was what naturally activated it.
1992: The Body's First Discovered Endocannabinoid
Two years after CB1 was cloned, researchers found the answer.
In 1992, William Devane, Lumír Hanuš, Raphael Mechoulam and colleagues isolated a naturally occurring cannabinoid from pig brain tissue.
They named it:
The name comes from the Sanskrit word ananda, meaning bliss or joy.
Anandamide became the first widely recognized endogenous cannabinoid, or endocannabinoid.
The discovery confirmed that the body produces its own chemicals capable of interacting with cannabinoid receptors.
THC was not introducing a completely foreign biological mechanism.
It was interacting with a system that already existed.
At CB1 receptors, anandamide generally acts as a partial agonist, producing a lower maximal response than a full agonist under comparable experimental conditions. Its activity at CB2 is weaker. By comparison, 2-AG generally exhibits higher efficacy at both cannabinoid receptors.
Its discovery opened the door to an entirely new area of neuroscience.
1993: The Discovery of CB2
The cannabinoid system turned out to have more than one major receptor.
In 1993, researchers Sean Munro and colleagues cloned a second cannabinoid receptor.
It became known as:
CB2.
Unlike CB1, CB2 is found predominantly on immune cells.
CB2 is strongly associated with immune cells and is expressed by microglia under certain conditions. Its presence in some neuronal populations has also been reported, although the extent of neuronal expression remains an area of scientific investigation.
CB2 helped reveal that cannabinoid signaling was not limited to the nervous system. It also played a role in immune regulation and inflammation.
1995: The Discovery of 2-AG
2-AG (2-arachidonoylglycerol), chemical structure — public domain, via Wikimedia Commons
In 1995, two research groups independently identified another important endocannabinoid.
One was led by Raphael Mechoulam.
The other was led by Takayuki Sugiura.
Their research identified:
2-Arachidonoylglycerol, or 2-AG.
2-AG is particularly important because it generally behaves as a full agonist at both CB1 and CB2 in experimental receptor assays.
It is also considerably more abundant than anandamide.
A separate 1997 study by Stella, Schweitzer and Piomelli, published in Nature, found that 2-AG is present in rat brain tissue at roughly 170 times the level of anandamide.
Together, anandamide and 2-AG became the two best-known endogenous cannabinoids.
The body had its own cannabinoid-like signaling chemicals, and scientists were beginning to understand how they worked.
The Three Parts of the Endocannabinoid System
The endocannabinoid system is not one chemical or one receptor.
It is a biological network consisting of three main components.
1. The Receptors: CB1 and CB2
These are the receiving points for cannabinoid signals.
Both CB1 and CB2 are G-protein-coupled receptors.
When an appropriate chemical activates them, they trigger changes in cellular signaling.
CB1 is particularly important in the nervous system, while CB2 is strongly associated with immune function.
2. The Endocannabinoids: Anandamide and 2-AG
These are the body's naturally produced cannabinoid signaling molecules.
They activate cannabinoid receptors and help regulate communication between cells.
Unlike classic neurotransmitters, they are not stored in large vesicles waiting to be released.
Instead, the body produces them when needed.
3. The Enzymes: The Construction and Cleanup Crew
The third component consists of enzymes that build and break down endocannabinoids.
Endocannabinoid production also requires enzymes. DAGL-alpha is a major enzyme involved in 2-AG synthesis, while anandamide can be produced through several pathways, including one involving NAPE-PLD.
Two important enzymes involved in breaking down endocannabinoids are:
FAAH (fatty acid amide hydrolase)
FAAH breaks down anandamide.
MAGL (monoacylglycerol lipase)
Studies in mouse brain tissue found that MAGL accounts for approximately 85% of measured 2-AG hydrolysis activity, with other enzymes responsible for most of the remaining breakdown.
These enzymes help determine how long endocannabinoid signals remain active.
The system is designed to produce signals when needed, allow them to do their work and then remove them.
Your Body Makes Endocannabinoids on Demand
One of the most interesting differences between endocannabinoids and traditional neurotransmitters is how they are produced.
Many classic neurotransmitters are synthesized in advance and stored in small membrane-bound packages called vesicles.
When a neuron receives a signal, it releases those stored chemicals into the space between cells.
Endocannabinoids work differently.
They are produced on demand from membrane lipids.
That means the body makes them when a particular signaling situation requires them.
They then act locally and are rapidly broken down.
Anandamide is destroyed by FAAH, while MAGL handles most of the breakdown of 2-AG in the brain.
This gives the system precise control over when and where cannabinoid signaling happens.
It is not designed to keep every receptor constantly activated.
It is a tightly regulated communication system. Some signals are brief and activity-dependent, while others contribute to ongoing, tonic regulation.
The Secret: How Endocannabinoids Communicate Backward
One of the most important discoveries about the endocannabinoid system involved something called:
Retrograde signaling.
Traditionally, scientists understood communication between neurons as moving in one direction.
A presynaptic neuron releases neurotransmitters. Those chemicals travel across the synapse and activate receptors on the receiving neuron.
But endocannabinoids revealed that neurons could also communicate in the opposite direction.
The idea was not entirely new. In 1998, researchers had proposed that endocannabinoids might act as retrograde messengers based on the locations of CB1 receptors and the FAAH enzyme in the brain. The three landmark studies published in 2001 provided the experimental evidence that transformed this hypothesis into an established principle of synaptic signaling.
In March 2001, three important research papers established endocannabinoid-mediated retrograde signaling. Wilson and Nicoll's study appeared in Nature on March 29, while two additional landmark studies appeared in the March issue of Neuron:
Wilson and Nicoll, published in Nature.
Ohno-Shosaku and colleagues, published in Neuron.
Kreitzer and Regehr, published in Neuron.
Together, these studies helped establish that endocannabinoids function as retrograde messengers.
How Does Retrograde Signaling Work?
Imagine two neurons communicating across a synapse.
One neuron becomes strongly activated.
Instead of simply receiving signals, that neuron produces endocannabinoids from its membrane lipids.
Those endocannabinoids travel backward across the synapse to receptors on the presynaptic neuron.
They activate CB1 receptors and temporarily reduce the release of neurotransmitters from that neuron.
In other words, the receiving neuron sends a message back to the neuron that was transmitting.
The message effectively says:
Turn it down.
This is one of the ECS's most important functions.
It provides a temporary volume control for neural communication.
Scientists describe two important forms of this process:
DSI: Depolarization-induced suppression of inhibition.
DSE: Depolarization-induced suppression of excitation.
These mechanisms allow neurons to temporarily regulate inhibitory and excitatory signaling.
Rather than simply switching brain activity on or off, the endocannabinoid system helps fine-tune how strongly different neural circuits communicate.
What Does the Endocannabinoid System Actually Regulate?
Endocannabinoid system distribution in the human body — U3216963, via Wikimedia Commons (CC BY-SA 4.0)
The ECS is involved in a wide range of biological processes.
Its overall purpose is closely connected to a concept called:
Homeostasis.
Homeostasis refers to the body's ability to maintain internal balance despite constantly changing conditions.
The endocannabinoid system contributes to this process through both localized, activity-dependent signaling and ongoing tonic regulation.
The endocannabinoid system is one of several biological signaling networks that contribute to homeostasis.
Its functions include several areas people may recognize from their cannabis experiences.
Learning and Memory
The ECS influences synaptic plasticity, the ability of connections between neurons to strengthen or weaken.
This process is fundamental to learning and memory formation.
Endocannabinoid signaling helps regulate how strongly neurons communicate, allowing the brain to adjust its connections in response to experience.
Appetite and Energy Balance
Cannabinoid receptors are involved in appetite regulation and energy balance.
This is one reason THC can increase appetite.
The relationship between cannabinoid signaling and feeding behavior is one of the best-known functions of the ECS.
Pain Regulation
Endocannabinoid signaling participates in the body's regulation of pain.
CB1 receptors in the nervous system influence how pain signals are processed, while CB2 signaling contributes to processes involving immune cells and inflammation.
The ECS is therefore an important area of research into the body's natural pain-regulation mechanisms.
Mood and Anxiety
Endocannabinoid signaling is involved in emotional regulation and stress responses.
Anandamide and 2-AG influence neural circuits associated with mood and anxiety.
The relationship is complex, and the effects depend on the receptor, location and signaling conditions involved.
Learning to Forget: The Fear Connection
One particularly fascinating function involves the extinction of aversive memories.
This is sometimes described as:
Learning to forget fear.
In 2002, researchers Giovanni Marsicano, Beat Lutz and their colleagues published an important study in Nature examining the role of CB1 receptors in fear-memory extinction.
The researchers found that mice lacking CB1 receptors could not extinguish conditioned fear normally.
In other words, they had difficulty learning that something previously associated with danger was no longer threatening.
This demonstrated that the endocannabinoid system participates in the process of reducing learned fear responses.
It is an important example of how cannabinoid signaling influences emotional learning.
Sleep
Research suggests that endocannabinoid signaling contributes to sleep-wake regulation. However, the precise mechanisms and the extent of its influence in humans remain incompletely understood.
Immune Function and Inflammation
CB2 receptors are particularly important in immune signaling.
Their presence on immune cells and microglia helps explain why the endocannabinoid system is involved in regulating immune responses and inflammation.
"Relax, Eat, Sleep, Forget and Protect"
In a 1998 review, Vincenzo Di Marzo and colleagues offered a memorable but explicitly tentative description of endocannabinoid signaling:
"Relax, eat, sleep, forget and protect."
They proposed that these might be among the messages produced by endocannabinoids, alone or alongside other biological mediators.
This was a summary phrase describing the system's broad regulatory role, not the result of one individual experiment.
But it captures an important concept.
The ECS is not responsible for just one bodily function.
It participates in multiple systems that help maintain internal balance.
Much endocannabinoid signaling is local and transient, but some signaling is tonic and provides ongoing regulation.
The Evolutionary Surprise: The System Is Older Than Cannabis
Here is where the story becomes even more interesting.
The endocannabinoid system did not evolve because humans discovered cannabis.
Its origins reach back hundreds of millions of years into vertebrate evolution.
Research into evolutionary biology has identified cannabinoid-type receptors in chordates, the broader animal group that includes vertebrates.
The Sea Squirt: An Ancient Relative
The sea squirt, scientifically identified as Ciona intestinalis, possesses an ancestral cannabinoid-receptor-related protein called CiCBR. Researchers found that this receptor is targeted toward axons, suggesting an ancient role in regulating neuronal signaling. However, its pharmacological properties have not been fully established, so scientists cannot assume it responds to anandamide and 2-AG exactly as mammalian CB1 and CB2 receptors do.
How CB1 and CB2 Emerged
The current understanding is that CB1 and CB2 developed through a gene duplication event in an early vertebrate ancestor.
An ancestral receptor was duplicated, allowing the two resulting receptor systems to evolve different distributions and functions.
CB1 became particularly important in neural signaling.
CB2 became strongly associated with immune function.
The two receptors are related, but their biological roles are not identical.
More Than 400 Million Years of Evolution
In his 2012 evolutionary review, Maurice Elphick explained that endocannabinoid signaling has been a fundamental mechanism of synaptic plasticity throughout more than 400 million years of vertebrate brain evolution.
That is the important evolutionary timeframe.
The system existed long before humans, modern cannabis cultivation or the development of cannabis products.
Its biological purpose was already established through evolution.
Insects Do Not Have CB1 or CB2
There is another surprising detail.
Not every animal possesses the same cannabinoid receptor system.
Insects, including fruit flies, do not have CB1/CB2-type receptors.
This does not mean insects lack all endocannabinoid-related chemistry. Some enzymes and lipid-signaling components are much more widely distributed across the animal kingdom than CB1 and CB2 receptors.
The evolutionary history of cannabinoid receptors is specifically connected to chordates and vertebrates.
2019: The Woman Who Could Barely Feel Pain
One unusual human case helped illustrate how important the body's own cannabinoid regulation can be.
In 2019, researchers published a case report in the British Journal of Anaesthesia involving a Scottish woman with two unusual genetic findings:
A deletion involving the FAAH-OUT pseudogene.
A reduced-function variant of the FAAH gene.
Blood testing found that the patient's circulating anandamide concentration was approximately 70% higher than in four control samples. Two other FAAH substrates, palmitoylethanolamide and oleoylethanolamine, were approximately three times higher, while 2-AG levels were largely unchanged.
The woman reportedly experienced lifelong pain insensitivity and very low anxiety.
This case attracted attention because FAAH is one of the enzymes responsible for breaking down anandamide.
When FAAH function is reduced, anandamide can remain elevated.
The case helped illustrate the relationship between FAAH activity, endocannabinoid levels and pain regulation.
But an important distinction must be maintained.
This was a single-patient case report.
It does not establish that reducing FAAH activity would produce the same effects in the general population, nor does it demonstrate a universally safe or effective approach to pain treatment.
Its significance lies in showing how changes in the body's natural cannabinoid regulation can be associated with unusual biological effects.
The Runner's High: Could Endocannabinoids Be Involved?
Fuss et al., Proceedings of the National Academy of Sciences (2015) — the mouse study tying the runner's high to cannabinoid receptors. Abstract via PubMed (PMID 26438875).
Another interesting area of research involves the familiar runner's high.
For years, researchers have investigated whether the feeling of well-being after prolonged exercise is related to endorphins or the endocannabinoid system.
Research published in PNAS in 2015 by Fuss and colleagues found strong evidence in mice that endocannabinoid signaling contributes to exercise-related reductions in anxiety and pain sensitivity.
Endocannabinoid levels also increase with exercise in humans.
This has made the ECS a leading candidate for explaining some aspects of the runner's high.
However, the evidence has important limitations.
Human studies have found increases in circulating endocannabinoids following endurance exercise. However, a 2023 systematic review concluded that the evidence has not yet established that endocannabinoids directly cause the human runner's high. Animal experiments provide stronger causal evidence, but the human mechanism remains unresolved.
The evidence is strong in animal models, and human observations are consistent with the theory, but the human causal mechanism has not been established.
An Interesting Theory: Clinical Endocannabinoid Deficiency
Some researchers have proposed that certain conditions might involve insufficient endocannabinoid signaling.
This idea is known as:
Clinical Endocannabinoid Deficiency.
The hypothesis was proposed by Ethan Russo in 2004 and revisited in a 2016 publication.
It suggests that inadequate endocannabinoid activity could contribute to certain conditions.
However, this remains a hypothesis rather than an established medical diagnosis.
There is currently no validated clinical test that can diagnose a person with clinical endocannabinoid deficiency.
The distinction matters because the existence of an important biological system does not automatically mean every unexplained symptom can be attributed to a deficiency in that system.
Cannabis Does Not Explain the Endocannabinoid System. The Endocannabinoid System Explains Cannabis.
The discovery of the endocannabinoid system changed how scientists understand cannabis and the human body.
In 1990, researchers identified CB1. Two years later, they discovered anandamide. In 1993, CB2 was cloned, and in 1995, researchers independently identified 2-AG.
By 2001, scientists had established one of the system's most fascinating functions: retrograde signaling, through which neurons produce their own cannabinoids to temporarily regulate communication with neighboring neurons.
The evolutionary evidence pushed the story much further back.
CB-type receptors and their signaling mechanisms have roots extending more than 400 million years into vertebrate evolution.
That means the system was already part of biology long before cannabis became a plant that humans cultivated or consumed.
The body produces its own cannabinoids, uses them to regulate important biological processes and breaks them down when their work is finished.
THC works because it can interact with this existing machinery.
Your body did not evolve cannabinoid receptors for cannabis. Cannabis contains compounds that happen to fit into a biological system your body already had.
That is the real story behind the endocannabinoid system.
Read next
Sources
- Gaoni, Yechiel, and Raphael Mechoulam. "Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish." Journal of the American Chemical Society, 1964. DOI: 10.1021/ja01062a046 Establishes the characterization of THC.
- Devane, William A., et al. "Determination and Characterization of a Cannabinoid Receptor in Rat Brain." Molecular Pharmacology, 1988. PMID: 2848184. Supports the discovery of the cannabinoid receptor binding site.
- Matsuda, L. A., et al. "Structure of a Cannabinoid Receptor and Functional Expression of the Cloned cDNA." Nature, 1990. DOI: 10.1038/346561a0 Establishes the molecular identification and cloning of CB1.
- Herkenham, M., et al. "Cannabinoid Receptor Localization in Brain." Proceedings of the National Academy of Sciences, 1990. DOI: 10.1073/pnas.87.5.1932 Documents the distribution of cannabinoid receptors in the brain.
- Devane, W. A., et al. "Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor." Science, 1992. DOI: 10.1126/science.1470919 Reports the discovery and identification of anandamide.
- Munro, S., et al. "Molecular Characterization of a Peripheral Receptor for Cannabinoids." Nature, 1993. DOI: 10.1038/365061a0 Establishes the cloning and characterization of CB2.
- Mechoulam, Raphael, et al. "Identification of an Endogenous 2-Monoglyceride, Present in Canine Gut, That Binds to Cannabinoid Receptors." Biochemical Pharmacology, 1995. PMID: 7605349. Supports the identification and characterization of 2-AG.
- Sugiura, Takayuki, et al. "2-Arachidonoylglycerol: A Possible Endogenous Cannabinoid Receptor Ligand in Brain." Biochemical and Biophysical Research Communications, 1995. DOI: 10.1006/bbrc.1995.2437 Independently reports the discovery of 2-AG as an endogenous cannabinoid.
- Stella, Nephi, Paul Schweitzer, and Daniele Piomelli. "A Second Endogenous Cannabinoid That Modulates Long-Term Potentiation." Nature, 1997. DOI: 10.1038/42015 Supports the comparison of 2-AG and anandamide concentrations in rat brain tissue.
- Di Marzo, Vincenzo, et al. "Endocannabinoids: Endogenous Cannabinoid Receptor Ligands with Neuromodulatory Action." Trends in Neurosciences, 1998. DOI: 10.1016/S0166-2236(98)01283-1 Provides the tentative "relax, eat, sleep, forget and protect" description of endocannabinoid signaling.
- Wilson, R. I., and R. A. Nicoll. "Endogenous Cannabinoids Mediate Retrograde Signalling at Hippocampal Synapses." Nature, 2001. DOI: 10.1038/35069076 Demonstrates endocannabinoid-mediated retrograde signaling.
- Ohno-Shosaku, T., et al. "Endogenous Cannabinoids Mediate Retrograde Signals from Depolarized Postsynaptic Neurons to Presynaptic Terminals." Neuron, vol. 29, no. 3, 2001, pp. 729–738. DOI: 10.1016/S0896-6273(01)00247-1 Provides experimental evidence for retrograde endocannabinoid signaling.
- Kreitzer, A. C., and W. G. Regehr. "Retrograde Inhibition of Presynaptic Calcium Influx by Endogenous Cannabinoids at Excitatory Synapses onto Purkinje Cells." Neuron, vol. 29, no. 3, 2001, pp. 717–727. DOI: 10.1016/S0896-6273(01)00246-X Demonstrates endocannabinoid-mediated regulation of neurotransmitter release.
- Cravatt, Benjamin F., et al. "Molecular Characterization of an Enzyme That Degrades Neuromodulatory Fatty-Acid Amides." Nature, 1996. DOI: 10.1038/384083a0 Identifies FAAH and establishes its role in anandamide breakdown.
- Blankman, Jonathan L., Gregory M. Simon, and Benjamin F. Cravatt. "A Comprehensive Profile of Brain Enzymes That Hydrolyze the Endocannabinoid 2-Arachidonoylglycerol." Chemistry & Biology, 2007. DOI: 10.1016/j.chembiol.2007.11.006 Establishes the contribution of MAGL and other enzymes to 2-AG breakdown.
- Liu, Jing, et al. "Multiple Pathways Involved in the Biosynthesis of Anandamide." Neuropharmacology, 2008. DOI: 10.1016/j.neuropharm.2007.05.020 Demonstrates that anandamide can be produced through multiple biosynthetic pathways.
- Elphick, Maurice R., Yasushi Satou, and Yoriko Satoh. "The Invertebrate Ancestry of Endocannabinoid Signalling: An Orthologue of Vertebrate Cannabinoid Receptors in the Urochordate Ciona intestinalis." Gene, 2003. DOI: 10.1016/S0378-1119(02)01094-6 Supports the investigation of ancestral cannabinoid-receptor-related proteins.
- Egertová, Michaela, and Maurice R. Elphick. "Localization of CiCBR in the Invertebrate Chordate Ciona intestinalis: Evidence of an Ancient Role for Cannabinoid Receptors as Axonal Regulators of Neuronal Signalling." Journal of Comparative Neurology, 2007. DOI: 10.1002/cne.21331 Investigates CiCBR localization in Ciona intestinalis, including its presence in axons, suggesting an ancient role for cannabinoid receptors in regulating neuronal signaling.
- Atwood, Brady K., and Ken Mackie. "CB2: A Cannabinoid Receptor with an Identity Crisis." British Journal of Pharmacology, 2010. DOI: 10.1111/j.1476-5381.2010.00729.x Reviews CB2 distribution and the scientific questions surrounding its expression in the nervous system.
- Marsicano, Giovanni, et al. "The Endogenous Cannabinoid System Controls Extinction of Aversive Memories." Nature, 2002. DOI: 10.1038/nature00839 Establishes the involvement of CB1 receptors in fear-memory extinction.
- Kano, M., et al. "Endocannabinoid-Mediated Control of Synaptic Transmission." Physiological Reviews, 2009. DOI: 10.1152/physrev.00019.2008 Comprehensive review of endocannabinoid signaling, retrograde communication, DSI and DSE.
- Elphick, Maurice R. "The Evolution and Comparative Neurobiology of Endocannabinoid Signalling." Philosophical Transactions of the Royal Society B, 2012. DOI: 10.1098/rstb.2011.0394 Reviews the evolutionary history of cannabinoid receptors and the role of endocannabinoid signaling throughout vertebrate brain evolution.
- Fuss, Johannes, et al. "A Runner's High Depends on Cannabinoid Receptors in Mice." Proceedings of the National Academy of Sciences, 2015. DOI: 10.1073/pnas.1514996112 Examines the role of cannabinoid receptors in exercise-related anxiety and pain responses in mice.
- Raichlen, David A., et al. "Wired to Run: Exercise-Induced Endocannabinoid Signaling in Humans and Cursorial Mammals with Implications for the 'Runner's High'." Journal of Experimental Biology, 2012. DOI: 10.1242/jeb.063677 Investigates exercise-related endocannabinoid changes across humans, dogs and ferrets.
- Habib, A. M., et al. "Microdeletion in a FAAH Pseudogene Identified in a Patient with High Anandamide Concentrations and Pain Insensitivity." British Journal of Anaesthesia, 2019. DOI: 10.1016/j.bja.2019.02.019 Documents the unusual FAAH-related genetic findings, elevated circulating anandamide and pain insensitivity in a single Scottish patient.
- Miranda, Alannah, Elizabeth Peek, Sonia Ancoli-Israel, Jared W. Young, William Perry, and Arpi Minassian. "The Role of Cannabis and The Endocannabinoid System in Sleep Regulation and Cognition: A Review of Human and Animal Studies." Behavioral Sleep Medicine, 2024. DOI: 10.1080/15402002.2023.2232497 Reviews the relationship between the endocannabinoid system and sleep.
- Russo, Ethan B. "Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes." Cannabis and Cannabinoid Research, 2016. DOI: 10.1089/can.2016.0009 Discusses the clinical endocannabinoid deficiency hypothesis, which remains an unvalidated theory rather than an established diagnosis.
- Russo, Ethan B. "Clinical Endocannabinoid Deficiency (CECD): Can This Concept Explain Therapeutic Benefits of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and Other Treatment-Resistant Conditions?" Neuro Endocrinology Letters, 2004. PMID: 15159679. Original proposal of the clinical endocannabinoid deficiency hypothesis.
- Siebers, Michael, Sarah V. Biedermann, and Johannes Fuss. "Do Endocannabinoids Cause the Runner's High? Evidence and Open Questions." The Neuroscientist, vol. 29, no. 3, June 2023, pp. 352–369. DOI: 10.1177/10738584211069981 Systematic review of human runner's-high evidence, including limitations in establishing causation in humans.
- Egertová, Michaela, et al. "A New Perspective on Cannabinoid Signalling: Complementary Localization of Fatty Acid Amide Hydrolase and the CB1 Receptor in Rat Brain." Proceedings of the Royal Society B, vol. 265, no. 1410, 1998, pp. 2081–2085. DOI: 10.1098/rspb.1998.0543 The 1998 paper whose complementary FAAH/CB1 localization supported the retrograde-signaling hypothesis before the 2001 experiments.
0 comments