Cannabinoid Receptor 1 (CB1) Basics

What is Cannabinoid Receptor 1?

Cannabinoid receptor 1 (CB1) is a member of a specific family of receptor known as G-protein coupled receptors. Just like other receptors, these are found on the surface of many different cell types, and can trigger changes in various biological functions crucial to health and wellbeing.

CB1 is part of a larger system of receptors, chemical messengers (called endocannabinoids) and the enzymes that synthesise and destroy them. These make up a communication network, which is critical to how we experience health and disease.

Its called the endocannabinoid system - the bodies own cannabis system, basically. Its role is to continuously help us maintain balance, or homeostasis across core bodily processes like breathing, body temperature, acidity/alkalinity, digestion, metabolism, consciousness and immunity.

The significance of CB1 became apparent when scientists discovered that is was the most abundant receptor in the mammalian brain. This wasn’t long ago, only 20 years ago in fact, but it highlighted just how fundamental the role for the endocannabinod system is in controlling brain and central nervous system functions. 

CBD and the brain


Cannabis and CB1

CB1 is part of the dynamic interaction that cannabis has with the human body. Its the switch which is flicked ‘on’ when THC, the psychoactive component of cannabis is inhaled or ingested, producing the ‘high’.

CBD also has an interaction with CB1 but in a more indirect way, sort of like a dimmer switch rather than a black or white on/off function, like THC. CBD is whats known as a negative allosteric modulator of CB1. In english that means it subtly turns down the volume of CB1 signalling, and as a result the downstream biological activity. A great example of this is when CB1 reduces the negative side effects of THC from too much CB1 actuation, like anxiety or the munchies.

Its the way that each cannabinoid interacts with this receptor which dictates the effects they have in the body. Its also how some cannabinoids are legal and others illegal, by the way they ‘talk’ to CB1.

When cannabis is out of the picture, the bodies own (endo)cannabinoids 2-AG and AEA are keeping things in check by communicating with CB1.

Some peoples endocannabinoids aren’t able to give CB1 enough love, or even give it too much, which can lead to imbalances such as diabetes, obesity, IBD, PTSD, migraines, depression, anxiety, fibromyalgia and pain.

When (phyto)cannabinoids from cannabis are inhaled or ingested, they can help endocannabinoids restore healthy on/off balance of communication at CB1.

Dose matters though! Too much cannabis can leave you feeling anxious, tired and hungry. Its all about finding a balance.

What Do CB1 Receptors Do?

The main role of CB1 is to control brain and central nervous system functions, like pain, sleep, metabolism, movement and heart rate, by influencing how neurotransmitters are released.

CB1 is effectively a switch found on the outside of a cell. When toggled by a cannabinoid, CB1 initiates a signalling cascade inside the cell (like a line of dominoes falling), which translates into changes in neurotransmitter release.

The brain and CNS are like a superhighway for neurotransmitters, which effectively deliver messages via neurones. Neurotransmitters travel across gaps between neurones, telling them to either excite or calm down various biological functions.

The CB1 receptor is effectively a gatekeeper which limits whether neurotransmitters like glutamate, GABA, serotonin and dopamine are released from neurones into the synapse.

This mechanism is known as retrograde neurotransmission, and effectively allows CB1 to strike a balance between the firing of neurones which excite the body (Glutaminergic) and calm it down (GABAergic).

CBD and neurotransmitters

Image source

Many people with chronic diseases have an imbalance in Glutaminergic vs GABA neuronal firing, which manifests in anxiety, fibromyalgia and Alzheimer’s to name a few. Using cannabinoids to toggle activity at CB1 can help restore this balance.

CB1’s role in mainly central, as a key player in brain and CNS function. But it is also found on immune cells which influences immunity and inflammation. Its also found on various organs, and can control their function locally.

Where are CB1 Receptors Found?

CB1 is the most abundant receptor in the mammalian brain (*). Densely populated in the hippocampus, amygdala, and hypothalamus. To a lesser extent in other brain regions, central and peripheral nervous system and immune system.

How CBD works in the body

Image Source

CB1 is also found on organs, such as:

  • Liver
  • Fat tissue
  • Pancreas
  • Muscle
  • Throughout the Gastrointestinal System
  • Lungs
  • Reproductive organs

CB1 Functions

The reason cannabis has such a profound effect on the body is because its cannabinoids can modulate the endocannabinoid system via cannabinoid receptors like CB1.

Under normal conditions, the bodies own (endo)cannabinoids are busy maintaining balance across the body by periodically activating CB1, like an operator on a switchboard connecting calls.

Some (phyto)cannabinoids like THC also activate CB1, which can increase various physiological processes in the body like appetite and sleep.

On the flip side, other cannabinoids like THCV can block CB1, and reduce physiological processes like appetite.

CB1 is basically a gatekeeper to revving up or dampening down bodily functions. Whether its up or down depends on which cannabinoid is interacting with the receptor.

CB1 & Appetite

CB1 is found on neurones in the hypothalamus, the control centre in the brain that regulates appetite. The balance between hunger and fullness depends on the activity of two opposing neuronal systems; POMC/CART and NPY/AGRP.

CB1 activation can encourage firing of NPY/AGRP neurones which stimulate appetite, and result in the famous ‘munchies’ that come with using cannabis.

THC also stimulates CB1 in the stomach, instructing the hunger hormone Ghrelin to be made. Ghrelin also stimulates NPY/AGRP neurones to increase appetite.

Its no mystery that THC increases food consumption. Do I even need to cite a study?

Other cannabinoids like THCV and CBD have been studied for their effects at blocking CB1 or at least turning down the volume to reduce appetite, which may be useful for eating disorders.

A reported side effect of CBD is loss of appetite, and in rats CBD has also demonstrated a reduced appetite.

THCV also reduces appetite in rats.

CB1, Memory & Cognition

CB1 is also located on neurones in the hippocampus, the brains learning and memory centre. A well known side effect of using cannabis is loss of short term memory. Thats due to the effect of THC on activating CB1, and the firing of neurones that allow us to form and recall memories.

Learning and memory depend on a process called synaptic plasticity. Basically this is when neurones adapt to develop continuous connections to one another that help us stay responsive to our environments.

Too much THC can impair synaptic plasticity, by reducing the release of neurotransmitters that drive it.

Whats interesting is that CBD is being studied for its ability to offset the memory impairments of THC, by restoring synaptic plasticity. Its likely that this is happening at the level of the CB1 receptor.

CB1, Sleep & Body Clock

The firing of neurones also dictates whether we feel sleepy or awake. When we want to sleep, neurotransmitters such as GABA and Adenosine are released in the hypothalamus, and wake inducing ones such as acetylcholine, serotonin and glutamate….are dulled down

This balance can be thrown off by light exposure at night, exercise, and of course what we put in out bodies like alcohol, or cannabinoids to name a few.

CB1 is found on hypothalamic neurones, and can regulate the release of sleep inducing neurotransmitters to help us sleep. Its how THC helps us sleep, even if we’ve been exercising late into the night for example.

On the flip side, low doses of CBD have been found to induce wakefulness, due to its ability to reduce CB1 activation. High doses help induce sleep though.

CB1 is also found in the suprachiasmatic nucleus (SCN) of the hypothalamus, which controls our body clocks by influencing our sensitivity to light. Activating CB1 (with THC) can actually cause a shift in our body clock, and encourage us to wake up later, by reducing sensitivity to light.

This is known as a phase delay. It’s also the reason why its so much harder to get out of bed the night after a big smoke.

CB1 & Metabolism

Metabolism, essentially the rate at which our cells process energy, can influence our experience of physical and mental vitality, as well as our body weight (most famously).

The CB1 receptor can control metabolism at 2 levels.

Centrally, in the hypothalamus

CB1 is found in the hypothalamus, which governs the global metabolism of the body as a whole via the nervous system. The nervous system sends messages to metabolic organs, such as fat tissue and the liver to control their activity.

The sympathetic nervous system in particular allows us to rev up metabolic activity, to mobilise energy from fat stores to get us out of danger, or to meet ‘stressful’ environmental demands such as exercise.

In studies using cannabinoids, activating CB1 has been shown to slow metabolism and generally favour the accumulation of body fat by reducing sympathetic nervous system activity.

CBD and weight loss


Locally, on individual organs

CB1 is also found on individual organs and can regulate their metabolic activity at a local level. A few of these organs include fat tissue, the liver, muscles, the digestive system and the pancreas.

Likewise, studies show that activating CB1 reduces metabolic activity of muscles, encourages fat tissue to hold onto fat, and encourages the liver to make more fat.

Here’s a diagram which highlights how that happens in detail.

CBD and metabolism


Some peoples endocannabinoid systems can become overactive due to poor diet, stress and lack of exercise, which causes CB1 over-activation and the associated problems with metabolism.

Whats really interesting though, is that using THC (which is a CB1 activator) is actually associated with lower body weights and better markers of metabolism (Glucose, insulin, cholesterol, triglycerides, blood pressure) than people who don’t use it (*). Its thought that when its used long-term, it actually acts to block CB1 (*).

CBD and THCV are also CB1 blockers and silencers, so they could be useful tools against weight gain and problems regulating blood sugar and blood lipids.

CBD and weight loss

CB1, Immunity & Inflammation

CB1 can also be found on immune cells, although CB2 is found in greater numbers and has a more prominent role in regulating the immune system.

Generally, CB1 activation is protective, reduces inflammation and encourages healthy immune cell activity, although there are exceptions.

CB1 activation has been found to increase macrophage activity, a specialised immune cell which destroys other cells. CB1 activation actually increased the destruction of B-cells from the pancreas, in cases of diabetes.

CB1 is also found on mast cells in the gut, which play a role in gut inflammation and conditions such as IBD. CB1 activation reduces mast cell activation, which prevents gut inflammation.

CB1 is also found on astrocytes, a specialised type of immune cell in the brain which influences how neurones communicate. CB1 activation reduces atrocyote production of pro-inflammatory messengers. This is relevant for neurodegenerative diseases such as Alzheimer’s.

CB1 is also found on microglia, immune cells in the brain which influence levels of (neuro)inflammation. This is relevant for neuropsychiatric conditions such as a depression, anxiety and schizophrenia. CB1 activation has a protective effect by reducing microglia activation and associated inflammation.

CB1 & Mood

One of the best known effects of cannabis is on mood. In most users cannabis brings about feelings of happiness, relaxation and euphoria, and alleviates feelings of depression, anxiety, and anger to name a few.

Other users sometimes experience negative side effects from cannabis such as anxiety and paranoia, and perhaps even dysphoria. This is all to do with the delicate dance that cannabis does with every individuals cannabinoid receptors, particularly CB1.

CB1 is densely populated on neurones throughout the brain. Different neurones convey different messages, using neurotransmitters such as dopamine, adrenaline, noradrenaline and serotonin.

Its up to CB1 to make sure these messengers are acting in a balanced way, to maintain a healthy mood. CB1 acts almost like a gatekeeper on neurones, allowing the release of some neurotransmitters whilst stopping others.

This is why THC shakes things up so much when its introduced to CB1 in the brain. It encourages the release of feel good neurotransmitters, whilst minimising the suppressive ones. Its a delicate balance though, and this effect can be reversed when too much is used.

This is known as a biphasic effect - where opposite effects occur as a result of low vs high doses.

CBD also stimulates CB1, but not directly. It boosts levels of the bodies natural feel good chemical Anandamide which also activates CB1, but much more gently than THC. This means theres no sketchy effects with CBD.

CB1 & Digestion

Many people use cannabis for digestive problems and discomfort, and its all to do with the way it ‘talks’ to the digestive system, via cannabinoid receptors found throughout it.

The goal of digestion is to break down food so we can more easily absorb and access the nutrients to make cellular energy.

We do this two ways:

  1. Mechanically with muscular contractions
  2. Chemically with digestive secretions

CB1 is found throughout the digestive tract and it helps regulate both of these processes.

CB1 is found on neurones within the enteric (gut) nervous system, which means it can control intestinal motility - the contraction of the intestines, which helps food move through them.

Cannabis is widely used to treat diarrhoea, which is often a result of too much motility. Thats because activating CB1 reduces motility and the transit of waste from the intestine. This helps us retain electrolytes and nutrients.

On the flip side cannabis can also work for constipation, by increasing intestinal motility and the transit of waste. This helps us expel toxicity so it cannot recirculate and ‘bog’ us down.

Weird right?

Well, whether the effect is one way or the other depends on the dose of cannabinoids used, which  changes how they behave at cannabinoid receptors. The effects also depend on how our our ECS needs balancing.

CBD and digestion


CB1 can also control the contraction stomach muscles, because its found on the end of nerves attached to the stomachs wall. Activating CB1 can reduce gastric emptying, the movement of food from the stomach into the small intestine. Paradoxically, cannabis can also speed gastric emptying in cases of gastroparesis, which may help the condition. It all depends on the individual.

In terms of digestive secretions, CB1 is also found on parietal cells in the stomach, which release hydrochloric acid used to break food down. Studies show that stimulating CB1 with THC and cannabis reduces stomach acid, but can also stimulate it at low doses.

Cannabis can either be a good or bad thing here, depending on whether someone produces too little, or too much stomach acid.

CB1 also controls the contraction of the lower oesophageal sphincter (LES), which may be helpful for GERD. When the LES is weak, stomach acid can leak into the oesophagus and cause damage to the lining. Cannabis and THC can help reduce acid secretion, protect the lining from inflammation and help restore LES function.

In general THC and CBD are powerful anti-inflammatories in the gut, partly via CB1 but mostly via CB2. They also help maintain healthy motility, and protect the gut lining by keeping inflammation in check.

CB1 & Stress

Cannabis is a powerful antidote to stress, which is one of the reasons it makes such a good medicine across the board.

The CB1 receptor plays a leading role in regulating the stress response, via controlling the flow of hormones and neurotransmitters along the highway that connects the mind with the body.

CB1 is found along this highway, starting with the PVN in the hypothalamus, through the pituitary all the way down to the adrenal glands where it controls the release of stress chemicals. 

Under normal conditions CB1 activation by our bodies own cannabinoids dampens the release of stress hormones CRH, ACTH and cortisol, helping to maintain a stress free experience. You can think of CB1 as a flood gate that keeps stress at bay.

But when a stressful event occurs, our cannabinoids dip, and CB1 loses its grip on stress hormones and the flood gates open. Cortisol is released from the adrenal glands, and so is adrenaline which circulates the nervous system initiating the flight or fright response.

CBD and stress


This is where THC and CBD come in really handy, because a lot of people have trouble closing the flood gates with their own cannabinoids after stress occurs.

  • At low doses, THC activates CB1 and puts the brakes on stress.
  • CBD can do the same by boosting the bodies own cannabinoids, helping tighten their grip on stress via increasing CB1 activation.

The levels of CB1 can vary genetically and in response to environment, which is also a factor which predisposes people to more or less stress. Its partly why some people can manage stress without cannabis, but others find they need it.

CB1 & Pain

Since CB1 is a major part of the central nervous system, it plays a leading role in pain signalling. Pain arises from a disruption in the signalling of neurotransmitters throughout the nervous system.

CB1 activation leads to a disruption of pain signalling via the inhibition of the neurotransmitters that deliver pain messages.

Its via CB1 that cannabinoids like THC, CBG and CBN exert their pain relieving effects by binding and activating the receptor, restoring balanced neuronal communication.

Activating CB1 can also indirectly stimulate opioid receptors, which are a central target for modulating pain signalling. Pharmaceuticals target opioid receptors to relive pain, but have serious side effects. Cannabinoids represent a safer and effective way of managing pain, due to their interaction with the opioid system.

CB1 can also play a role in pain via the immune system. Its activation on immune cells inhibits the release of inflammatory messengers which signal for inflammatory pain.

The only caveat with using THC to relieve pain are the side effects like intoxication and drowsiness, which a lot of people don’t like.

Other cannabinoids like CBN and CBG are less and non-intoxicating, because they stimulate CB1 more gently.

CBD also gently stimulates CB1, but indirectly. It also relives pain via many other mechanisms, which minimises the side effects a lot of people find undesirable.

CB1 & Movement

Cannabinoids are being studied and used in movement disorders like dystonia and dyskinesia prevalent in Parkinsons and Huntingtons disease.

The neurotransmitter dopamine is key to regulating bodily movement. In Parkinsons, dopaminergic neurones progressively deteriorate in the Substantia nigra, lowering the amount of dopamine available for the signalling of proper balance, co-ordination and reflexes.

The role of CB1 is to ensure balanced neuronal communication, buffering excessive or deficient neurotransmitter signalling accordingly.

CB1 can indirectly control the release of dopamine, and therefore restore signalling throughout the dopaminergic system. In Parkinsons, CB1 activation in the Substantia nigra may help partially restore dopamine signalling (*), helping to correct movement.

In Huntingtons a genetic mutation causes a progressive loss of neurones in the basal ganglia which results in fluctuations of dopamine levels in the brain. Dopamine fluctuates from higher to lower levels as the disease progresses, manifesting as excessive movement leading to lack of movement.

CB1 is found within the basal ganglia and is key to controlling dopamine release. Hence losing neurones here means less CB1 receptors, and loss of movement control. Research has actually found that using cannabinoids like THC to strongly activate CB1 makes up for the decline in numbers, restoring motor function and slowing loss of neurones (*).

Activating CB1 with cannabinoids may also offer protection to neurones against deterioration, and the progression of Parkinsons disease. CB1 activation can help keep levels of brain inflammation in check, and reduce excessive glutamate signalling, which is toxic to neurones.

However since Huntingtons is caused by a genetic mutation, its hard to say to what extent CB1 activation can affect its progression.

CB1 & Blood Pressure

The cannabinoid system is a critical regulator of the cardiovascular system, using CB1 receptors throughout the nervous system to control it.

CB1 receptors can control the muscular contractions of the heart, changing heart rate and blood flow as and when we need. CB1 can also control the dilation and contraction of blood vessels. Together, this means cannabinoids can regulate blood pressure via CB1 activation.

Generally, CB1 activation reduces heart rate and dilates blood vessels leading to a lower blood pressure. However, it depends on what cannabinoid is being used, and at what time and what dose. 

CBD and blood pressure

Adapted from Source

THC has been found to acutely increase heart rate and blood pressure, but does the opposite when used long term. Higher does of THC stimulate the flight or flight system raising blood pressure, whereas lower doses engage the parasympathetic relaxation response reducing it.

CBD appears to lower blood pressure, and heart rate possibly due to its ability to increase the natural cannabinoid Anandamide, which has a suppressive effect on the cardiovascular system (*).

CB1, Breathing & Thermoregulation

The hypothalamus is a central regulator of breathing and temperature regulation, and its densely populated with CB1 receptors.

Generally, CB1 ensures we are taking in enough oxygen, and not too much by regulating breathing rate - balancing hypo and hyperventilation. This helps us achieve normoxia - a supply of oxygen that is optimal for balancing blood PH and fuelling cellular metabolism.

Using cannabinoids to activate CB1 has been found to effect breathing rate in both directions, and it depends on dose.

Low doses of THC can actually increase ventilation and act as a respiratory stimulant. On the other hand, high doses of THC may actually depress respiration. These effects are controlled by the dilation and contraction of the bronchus, which controls air flow into the lungs (*).

Similarly, CB1 is important for maintaining the balance between hyper and hypothermia, ensuring optimal body temperature.

Activating CB1 with THC progressively lowered body temperature as the dose increased. In real terms, only very high doses of THC are likely to reduce body temperature in any meaningful way.

On the flip side, since cannabinoids act in a see saw way to ensure balance via CB1, lower doses can actually increase body temperature.

A phenomenon known as cannabinoid-induced hyperthermia can occur from using small doses of cannabinoids (*).

So its really all about the dose, which determines the level CB1 activation.

Using cannabinoids to control these core bodily functions could be interesting when it comes to exercise, and conditions which are affected by oxygen, PH and metabolic rate (like cancer, obesity, COPD, apnea etc.).

CB1 & Bone Density

CB1 is an important receptor for controlling both the making of new bone material and breaking of the old. It plays a leading role in the growth of new bone in children and adolescents, and in adults is involved in the repair and maintenance of broken and existing bones.

CB1 is found on different types of bone cells. Osteoclasts are cells that break down bone, which have CB1 receptors allowing their function to be altered by cannabinoids. Also the cells that make new bone, osteoblasts also have CB1 receptors.

Attention is very much on conditions which involve the degradation of bone mass, such as Osteoporosis. Bones are weak, fragile and easily fractured in this condition. Here, osteoclasts are overactive, whereas osteoblasts under active. The CB1 receptor has a role to play here.


Whats amazing is that the effects of the CB1 receptor appear to be dependent on age. Activating CB1 in adult mice encourages breakdown of bone, whereas in aged mice it actually reduces the loss of bone (*).

In line with this, heavy THC use is associated with lower bone mineral density (because THC activates CB1) (*).

However, CBD has actually been found to strengthen bones, and accelerate fracture healing (*). The impact on bone mineral density may not only depend on age, but also the balance of THC:CBD in cannabinoid medicines.

CB1 Genetics

CNR1 is the gene that encodes the proteins that make up the CB1 receptor. Variations in CNR1 genes can influence the activity and number of CB1 receptors a person has.

There are several SNP’s (variations) in the ‘spelling’ of the CNR1 gene that can influence a persons disease risk and health.

CNR1 variations don’t necessarily lead to disease. Lifestyle and environmental factors like stress, infection and toxicity can also lead to higher or lower CB1 receptor levels. When combined with genetic susceptibility, these factors may increase disease risk.

CNR1: rs1049353 

Most people have either a CC ‘spelling’ of this variation (77%). However, the T ‘spelling’ (CT/TT)

is associated with:

  • Intestinal inflammation (*)
  • A higher risk for IBD
  • Higher risk for depression
  • Anxiety
  • A greater stress response
  • Lower body weight (*)

CNR1: rs12720071

Most people have a TT ‘spelling’ of this variation. However, the C ‘spelling’ (TC/CC) is associated with:

  • Higher extraversion (*)
  • Shorter attention span (*)
  • Worse problem solving skills (*)

CNR1: rs806380

Most people have an AA ‘spelling’ of this variation. However, the G ‘spelling’ (AG/GG) is associated with: 

  • Lower levels of the CB1 receptor (*).
  • Higher risk of schizophrenia (*)
  • Higher risk of drug use and addiction (*)
  • Depression and anxiety (*)

CNR1: rs806368

Most people have a TT ‘spelling’ of this variation. However, the C ‘spelling’ (TC/CC) is associated with:

  • Lower openness in personality tests (*)
  • Impulsive behaviour on personality tests (*)
  • Higher waist to hip ratio (measuring obesity) (*)

CNR1: rs7766029

Most people have a TT ‘spelling’ of this variation. However, the C ‘spelling’ (TC/CC) is associated with:

  • Higher risk of depression after a stressful event (*)

CNR1: rs806378 

Most people have a CC ‘spelling’ of this variation. However, the T ‘spelling’ (CT/TT) is associated with:

  • Higher levels of CB1 receptor (greater activation) (*)
  • Reduced fullness after eating (*)
  • Slower movement of food through the colon (*)
  • Gained about 2.2 kg more weight (CT/TT vs CC) (*)

CNR1: rs806369

Most people have a CC ‘spelling’ of this variation. However, the T ‘spelling’ (CT/TT) is associated with:

  • Lower extraversion and lower conscientiousness (*)
  • Headache and Nausea in the presence of life stress (*)

CNR1: rs806377

Most people have a TT ‘spelling’ of this variation. However, the C ‘spelling’ (TC/CC) is associated with:

  • Higher risk of ADHD (Males more so than females) (*)