What is the Endocannabinoid System?

Have you ever wondered how your body maintains balance when life keeps throwing curveballs your way? Meet your endocannabinoid system (ECS). This complex cell-signaling mechanism maintains homeostasis in your body and fine-tunes vital functions to keep us up and running.

Let’s look at the intricate structure of the endocannabinoid system, its components, functions, and therapeutic interactions with cannabis.

Article jumplinks:

What is the endocannabinoid system?
Is the ECS system real?
What is an ECS deficiency?
How do cannabinoids affect the ECS?
What is the entourage effect?
What are the benefits of microdosing?

Cannabis microdosing can help modulate the ECS. Check out our article on the potential benefits of taking small amounts of cannabis every day.

We’re going to talk about THC a lot here, so make sure to refresh your memory on Delta 9 THC with our in-depth guide.

What Is the Endocannabinoid System?

The ECS is a complex network of chemical signals and receptors that, according to Lerner, et. al., “serves pivotal roles in a diverse range of physiological and pathophysiological states, including behavior, pain, schizophrenia, obesity, Alzheimer disease, multiple sclerosis and cardiovascular disease.”

The main role of the endocannabinoid system is to maintain homeostasis, or internal balance and stability. The ECS achieves homeostasis by regulating a vast range of bodily functions:


Mood	Coordination and motor control
Sleep	Gut health and digestion
Appetite and metabolism	Repoductive health
Pain perception	Blood pressure and cardiac function
Immunological response	Bone formation
Response to stress	Wound healing
Learning and memory	Neuroprotection

The ECS is composed of endocannabinoids, cannabinoid receptors, and enzymes.

The Role of Endocannabinoids

Endocannabinoids are naturally occurring, lipid-based neurotransmitters that our bodies produce. They are generated on demand in response to certain stimuli, such as inflammation, brain signals, or state changes.

Here are some examples of how endocannabinoids can help regulate bodily functions:

Endocannabinoids can help relieve chronic pain by acting on cannabinoid receptors in the central and peripheral nervous systems. They suppress the release of neurotransmitters that send pain signals while activating systems that fight inflammation and promote healing. (Hoogen, et. al.)
By activating the CB1 cannabinoid receptor, endocannabinoids can regulate appetite and increase eating motivation. (Kirkham, et. al.)
Endocannabinoids can regulate the sleep-wake cycle and help promote restful sleep. Research suggests that endocannabinoids promote non-rapid eye movement sleep by interacting with certain neurons in the brain. In animal models of insomnia, pharmaceutical CB1 blockage lowers sleep and increases awakeness, whereas endocannabinoids restore sleep. (Prospéro-García, et. al.)
Endocannabinoid signaling can be therapeutically targeted for treating age-related neuroinflammatory and neurodegenerative diseases. (Di Marzo, et. al.)
Endocannabinoids can modify the immune response in different cell types, influence the production of cytokines (pro-inflammatory molecules), promote apoptosis in immune cells, and suppress innate and adaptive immunological responses. (Pandey, et. al.)

Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the two most researched endocannabinoids. Anandamide is synthesized from arachidonic acid, whereas 2-AG is made from diacylglycerol (a secondary lipid messenger important for the activation, proliferation, and function of immune cells).

Endocannabinoids work by binding to our cannabinoid receptors to signal them that the ECS needs to take action.

While endocannabinoids are endogenous cannabinoids (our bodies produce them), exogenous cannabinoids—like THC and CBD—come from cannabis plants.

Cannabinoid Receptors

Cannabinoid receptors are G protein-coupled receptors activated by both exogenous and endogenous cannabinoid systems. The two main receptor types are the CB1 and CB2 receptors. Anandamide and 2-AG bind to both, modulating bodily systems and functions.

CB1 and CB2 have some structural and functional similarities, but their pharmacological characteristics and signaling routes differ. Some exogenous cannabinoids, like THC, have a high affinity for the CB1 receptor but a much lower affinity for the CB2 receptor, whereas others, like CBD, have a low affinity for both CB1 and CB2 receptors.

Endocannabinoid receptors. Source: https://www.health.harvard.edu/blog/the-endocannabinoid-system-essential-and-mysterious-202108112569

CB1 Receptors

Cannabinoid CB1 receptors are present mainly in the brain and the central nervous system (CNS), in brain areas that help regulate pain, mood, hunger, and memory. A small number of CB1 receptors can be found in peripheral tissues such as the immune system and the digestive tract.

CB1 activation can limit the release of neurotransmitters (e.g., GABA, glutamate, and dopamine) that control many physiological and behavioral processes.

...the endocannabinoid system serves as an important filter of afferent input that acts locally at midbrain and terminal regions to shape how incoming information is conveyed onto dopaminergic neurons and to output targets. (Covey, et. al.)

This modulation of CB1 receptors can result in changes in perception, mood, and appetite, among other things.

CB1 receptors may invoke neuroprotective effects by reducing oxidative stress and inflammation. Researchers found that CB1 receptors mediate 2-AG neuroprotection after a closed head injury (CHI) in animal models. The study concluded that “CB1 receptor-mediated mechanisms…involve inhibition of intracellular inflammatory signaling pathways”

By lowering inflammation and oxidative stress, CB1 cannabinoid receptors might also help decrease neurotoxicity. In neurodegenerative diseases like Huntington’s or Parkinson’s, mutant proteins accumulate in the brain and glial cells. This downregulates the function of CB1 receptors, which leads to neuronal damage.

According to a 2023 study, “the downregulation of CB1 may also aggravate cytotoxicity such as oxidative stress.” One way to alleviate neurotoxicity, oxidative stress, and inflammation is with low doses of cannabinoids such as THC and CBD that bind to CB1 receptors and improve the symptoms of neurodegeneration.

CB2 Receptors

CB2 receptors are found primarily in the immune system and peripheral organs, including bone marrow and skin. CB2 activation has the potential to regulate immunological responses and inflammation.

Activation of CB2 receptors can reduce inflammation, pain, and tissue damage associated with inflammatory responses. Endocannabinoids may protect against traumatic brain injury and modulate inflammatory activities and microglial activation following it, mainly by binding to and activating CB2 receptors.

Infections, damage, and oxidative stress can cause microglia—the brain and spinal cord’s immune cells—to become activated. While short-term microglial activation is beneficial, prolonged or excessive activation can cause chronic inflammation, which contributes to neurodegenerative diseases like Parkinson’s disease or Alzheimer’s disease.

An injection of a specific CB2 agonist seems to reduce microglial activation in a mouse model of Alzheimer’s disease.

CB2 activation appears to prevent or decrease microglial activation. In a rodent model of Alzheimer’s disease microglial activation was completely prevented by administration of a selective CB2 agonist… We conclude that the administration of CB2 agonists and antagonists may differentially alter microglia-dependent neuroinflammation. (Ashton, et. al.)

The results imply that cannabinoid CB2 receptors in human Alzheimer’s disease brain microglia can be a potential target for lowering neuroinflammation and treating a wide range of neuropathologies.

A 2016 study confirms the anti-inflammatory role of CB2 receptors.

CB2 receptor was shown to modulate immune cell functions, both in cellulo and in animal models of inflammatory diseases. In this regard, numerous studies have reported that mice lacking the CB2 receptor have an exacerbated inflammatory phenotype.

The study suggests that therapeutic techniques that target CB2 cannabinoid signaling may be beneficial in treating inflammatory diseases. Both studies on CB2 receptors and inflammation hint at the ability of CB2 receptors to regulate immune cell activity.

CB2 receptors are involved in modulating immunological function. Since CB2 receptors are found in all immune cells, they are vital in influencing processes like cell migration, proliferation, and antibody effector functions. According to research, CB2 has the ability to affect the function of all immune cell types.

CB2 has been shown to regulate immunity by a number of mechanisms including development, migration, proliferation and effector functions. In addition, CB2 has been shown to modulate the function of all immune cell types examined to date.

By lowering inflammation, CB2 has been shown to play a role in “maintaining homeostatic immune balance.”.

…these studies suggest that the CB2 may serve as a selective molecular target for therapeutic manipulation of untoward immune responses including those associated with a variety of neuropathies that exhibit a hyperinflammatory component.

Endocannabinoid Enzymes

Endocannabinoid enzymes are involved in the production and breakdown of endocannabinoids. Once endocannabinoids have served their role, enzymes break them down to prevent excessive signaling. This maintains equilibrium in the endocannabinoid system and prevents cannabinoid receptor overstimulation. Excessive signaling and overstimulation of cannabinoid receptors can lead to anxiety, paranoia, and cognitive impairment.

The process of endocannabinoid breakdown is mediated by two primary endocannabinoid enzymes: fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). FAAH is responsible for the breakdown of anandamide, while MAGL breaks down 2-AG.

Fatty acid amide hydrolase is a membrane-bound enzyme that breaks the amide link between arachidonic acid and ethanolamine. This enzyme is found throughout the body, including the brain and immune cells, and is involved in pain regulation, mood changes, and inflammation. According to studies, “FAAH is a key enzyme involved in the catabolism of AEA… in vivo and suggests that pain pathways are under the influence of a FAAH-regulated endocannabinoid tone.”

Monoacylglycerol lipase is a cytosolic enzyme (the liquid components of cells). It hydrolyzes the glycerol-arachidonic acid ester link to produce 2-AG and free arachidonic acid. MAGL is widely expressed in the brain, which makes it important for hunger, mood, and pain regulation.

Is the Endocannabinoid System Real?

Scientific consensus is that the endocannabinoid system is real and important in all humans and animals.

Dr. Raphael Mechoulam, an Israeli scientist, postulated the ECS in 1988. A growing body of evidence continues to substantiate its existence and therapeutic potential.

Dr. Mechoulam first isolated and identified tetrahydrocannabinol (THC), the main compound in cannabis, in the 1960s. This discovery led to the realization that the human body produces its own cannabinoids, known as endocannabinoids, which interact with cannabinoid receptors in a similar way to THC. The ECS has been studied extensively since its discovery, establishing its role in a variety of physiological processes.

What Does Research on the ECS Say?

The discovery of the ECS was regarded with suspicion at first. The concept of this sophisticated and complex cell-signaling system specifically engineered to maintain homeostasis and interact with substances from the cannabis plant seemed far-fetched. Today, a substantial body of evidence confirms the existence of the ECS.

The discovery of depolarization-induced suppression of inhibition (DSI)/excitation (DSE) provided the first clinical evidence of the ECS.

The first conclusive evidence supporting retrograde endocannabinoid signaling came from the observation of depolarization-induced suppression of inhibition (DSI)/excitation (DSE). Later, it was discovered that the endocannabinoid system is involved not only in short-term depression, but also in long-term depression (LTD) at both excitatory and inhibitory synapses. Since then, the endocannabinoid system has become the most-studied retrograde signaling system in the brain.

The ECS plays a significant role as a messenger, delivering signals between neurons. Endocannabinoids have a major role in so-called synaptic transmission: they control how neurons connect and communicate with one another.

Retrograde signaling is the principal mode by which endocannabinoids mediate short- and long-term forms of plasticity at both excitatory and inhibitory synapses. However, growing evidence suggests that endocannabinoids can also signal in a non-retrograde manner. In addition to mediating synaptic plasticity, the endocannabinoid system is itself subject to plastic changes. Multiple points of interaction with other neuromodulatory and signaling systems have now been identified. Synaptic endocannabinoid signaling is thus mechanistically more complex and diverse than originally thought. (Castillo, et. al.)

The ECS seems to be involved in mental illnesses such as depression, anxiety, and schizophrenia. Human studies have revealed that the ECS is critical for emotional and cognitive function and that abnormalities in the endocannabinoid system may contribute to mental diseases.

More scientific evidence confirms the importance of a functional endocannabinoid system for mental health. Researchers examined the cerebrospinal fluid of ten people with schizophrenia and eleven people without. The cerebrospinal fluid levels of two endogenous cannabinoids (anandamide and palmitoylethanolamide) were elevated in schizophrenic patients compared to those of healthy participants. The findings imply that “elevated anandamide and palmitoylethanolamide levels in the cerebrospinal fluid of schizophrenic patients may reflect an imbalance in endogenous cannabinoid signaling, which may contribute to the pathogenesis of schizophrenia.”

Endocannabinoid Deficiency

Endocannabinoid deficiency, or clinical endocannabinoid deficiency (CED), is a theory that suggests that certain medical conditions may result from low endocannabinoid levels in our bodies. There are several possible indicators that you’re low on endocannabinoids:

Chronic pain
Stress
Anxiety
Depression
Irritable bowel syndrome (IBS)
Chronic migraines
Sleep disorders
Mood changes
Immune system dysfunction

What Causes Endocannabinoid Deficiency?

The exact causes of CED are unknown, but genetics, diet, and environmental toxins may play a role. Chronic stress and a lack of exercise are also considered possible underlying causes of endocannabinoid deficiency. All these factors may impair the ECS's regular functioning, resulting in low endocannabinoid levels.

What Disorders May Be Caused by Deficiencies in the Endocannabinoid System?

Certain disorders may be connected to clinical endocannabinoid deficiency.

Chronic pain
Fibromyalgia
Migraines
IBS
Post-traumatic stress disorder (PTSD)

A 2016 study reviewed over 10 years' worth of research on CED and found that some people develop migraines, fibromyalgia, and irritable bowel syndrome due to low levels of endocannabinoids. People who suffer from migraines have decreased levels of anandamide. Cerebrospinal fluid surrounds the brain and spinal cord of all vertebrates. It’s kind of important since it provides protection and nourishment for the brain.

According to the study, “statistically significant differences in cerebrospinal fluid anandamide levels have been documented in migraineurs, and advanced imaging studies have demonstrated ECS hypofunction in post-traumatic stress disorder.”

What is Good for the Endocannabinoid System?

There are ways you can boost the levels of endocannabinoids and improve the ECS’s function.

A nutritious and balanced diet rich in omega-3 fatty acids can increase endocannabinoid synthesis.
Regular exercise can also boost endocannabinoid levels in the body and improve cannabis receptor sensitivity. According to a study, “the increase in endocannabinoid levels during exercise can also be a key element in incrementing brain-derived neurotrophic factor, mediating benefits in cognition, as in neurogenesis and plasticity synaptic and antidepressant effects.” That means exercise is good for your body, your brain, and your endocannabinoids.
Getting enough sleep is necessary for a healthy ECS, as endocannabinoid levels fluctuate during the sleep-wake cycle.
Dysregulation of the ECS plays a crucial role in increasing stress, depression, and psychiatric disorders. According to Lutz, et. al., “endocannabinoid signaling seems to determine the value of fear-evoking stimuli and to tune appropriate behavioral responses, which are essential for the organism’s long-term viability.” If you want your ECS to function like a well-oiled machine, try to reduce stress and engage in activities that promote relaxation of the body and the mind.
Phytocannabinoid supplements, or exogenous cannabinoids, may help sustain important roles of the ECS and treat symptoms of endocannabinoid deficiency.

Investigating the causes of fibromyalgia, IBS, and migraines, a study confirmed that CED might be responsible for developing these and many other medical disorders. The study also proposed that treating the endocannabinoid system therapeutically could be a way to treat these disorders. Cannabinoids and cannabinoid-based medications seem to be a viable and natural way to help support the normal levels and function of the ECS.

Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator. THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is now conceived as a central sensitization state with secondary hyperalgesia. Cannabinoids have similarly demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS and related disorders. (Russo)

Exogenous cannabinoids—THC, CBD, and other cannabinoids—can interact with the ECS to restore balance and relieve symptoms associated with many disorders. Let’s examine the benefits of taking small amounts of THC and CBD to support our endocannabinoid system.

Cannabinoids and the Endocannabinoid System

The cannabis plant contains exogenous cannabinoids, also called phytocannabinoids. There have been more than 100 phytocannabinoids discovered, but the best-known and most researched are tetrahydrocannabinol (THC) and cannabidiol (CBD).

The effects of cannabis on our bodies are delivered via the endocannabinoid system. Cannabinoids interact with endocannabinoid receptors to signal biochemical changes in our bodies. THC and CBD bind to CB1 and CB2 to relieve pain, alter mood and perception, influence sleep, hunger, and other important bodily functions. While THC has a strong affinity for the CB1 receptor, CBD has a weak affinity for both CB1 and CB2.

If you’ve never heard of CBD before, this is your chance to learn everything about the effects, benefits, and uses of CBD.

Let’s see exactly how CBD and THC affect the endocannabinoid system.

How Does THC Affect the Endocannabinoid System?

THC seems to be a “partial agonist” of CB1 and CB2 receptors.

Δ9-THC, the main psychotropic constituent of cannabis, is a CB1 and CB2 receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by the expression level and signaling efficiency of cannabinoid receptors and by ongoing endogenous cannabinoid release. (Pertwee, et. al.)

THC’s interaction with CB1 receptors boosts the release of dopamine in the brain, which is “responsible” for euphoria and the “high” typically associated with cannabis use. When THC binds to CB2 receptors, it produces anti-inflammatory and immunomodulatory effects.

THC and CB1 Receptors

We mentioned its strong affinity for CB1 receptors; when THC binds to this receptor type, it can cause changes in mood, appetite, pain perception, and more. THC produces the following effects when it binds to cannabinoid CB1 receptors.

Pain relief: THC is a potent analgesic. Its pain-soothing effects are mediated primarily through CB1 receptors. THC can treat chronic pain conditions, such as neuropathy, fibromyalgia, arthritic pain, and cancer pain.
Appetite stimulation: THC has been shown to stimulate appetite. This effect is believed to be mediated through the CB1 receptors in the hypothalamus. As an agonist of cannabinoid receptors, THC “raises the possibility of improved therapies for disorders of eating and body weight [and for] the treatment of conditions that involve reduced appetite and weight loss.” (Kirkham)
Sedation: by affecting CB1 receptors in the basal ganglia (brain structures that form important connections), THC can produce sedative effects.
Relaxation: THC is known to produce a sense of relaxation in cannabis users, another effect mediated through the CB1 receptors in the amygdala.

THC and CB2 Receptors

The effects of Delta 9 THC on CB2 receptors are somewhat less researched than those of CB1. CB2 receptors are predominantly found in the immune system and peripheral tissues; by binding to them, THC seems to stimulate anti-inflammatory and immunomodulatory effects.

Because of its interaction with CB2 receptors, THC has potent anti-inflammatory properties. THC was found to significantly reduce inflammation in mice with acute lung injury. According to the study, “THC treatment significantly suppressed the inflammatory cytokines, IFN-γ and TNF-α. Additionally, THC elevated the induction of regulatory T cells (Tregs) and their associated cytokines, IL-10 and TGF-β… THC acted through CB2 receptor…” (Mohammed, et. al.)
THC’s activation of CB2 receptors has also been shown to relieve pain, although more research is needed to provide more substantial evidence.

THC's activation of CB2 receptors has been investigated for its potential in cancer treatment. Cannabis research suggests that THC may suppress breast cancer cell proliferation by triggering apoptosis (cell death) in cancer cells. Its main course of action was to activate cannabinoid CB2 receptors.
THC’s interaction with CB2 receptors might have neuroprotective effects. Although a “weak agonist” of CB2 receptors, THC may reduce brain inflammation and protect against cognitive impairment.

The CB2 receptor has been shown to have potential as a therapeutic target in models of diseases with limited or no currently approved therapies, such as neuropathic pain and neurodegenerative conditions such as Alzheimer’s disease. (Bie, et. al.)

That’s why many people diagnosed with dementia turn to microdosing THC as a natural way to reduce the symptoms and improve cognitive function. With our pink lemonade Euphoria gummies, THC has never tasted better. These refreshing vegan gummies contain 10 mg of Delta 9 THC, perfect for days when you need to give your brain a break from the daily grind.

How Does CBD Affect the Endocannabinoid System?

Cannabidiol is another major phytocannabinoid. Unlike THC, CBD can’t make you high, probably because its interaction with the endocannabinoid system is a bit more complex. As mentioned before, CBD has a low affinity for CB1 and CB2 receptors; it doesn’t bind to them directly. It regulates the activation of these receptors in a more indirect way.

CBD has been shown to slow anandamide breakdown. This causes an increase in anandamide levels, which may aid in mood regulation, anxiety reduction, and stress response. A medically reviewed study confirms that, by boosting anandamide, CBD may even help treat schizophrenia.

…cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol…

The results of this study show that CBD is a great way to fight stress and anxiety. If you’re struggling with chronic stress or want to reduce the symptoms of anxiety disorders, our collection of CBD gummies is at your disposal.

Have you heard of our Relax gummies with CBD and ashwagandha? These watermelon-flavored edibles are packed with premium cannabidiol and ashwagandha, a powerful stress-reducing adaptogen, and will make stressful situations (like dinners with your in-laws) a walk in the park.

CBD has also been shown to activate the TRPV1 receptor, which is involved in pain, inflammation, and body temperature regulation. A 2020 study shows how effective CBD is in reducing inflammation and chronic pain.

CBD at low doses corresponding to plasma concentrations observed physiologically inhibits or desensitizes neuronal TRPV1 signalling by inhibiting the adenylyl cyclase – cAMP pathway, which is essential for maintaining TRPV1 phosphorylation and sensitization. CBD also facilitated calcineurin-mediated TRPV1 inhibition. These mechanisms may underlie nociceptor desensitization and the therapeutic effect of CBD in animal models and patients with acute and chronic pain. (Anand, et. al.)

We’ve covered the main cannabinoid receptors in great detail, but there are more receptors in the ECS that cannabis interacts with. CBD has been shown in studies to activate the GPR55 receptor, which helps regulate blood pressure, motor control, and bone density, among other things. As a GPR55 antagonist, CBD was found to improve motor impairment in rats with hemiparkinsonism, a secondary form of Parkinson’s disease.

Taking low doses of CBD-rich cannabis extracts seems to ease the symptoms of Parkinson’s disease and even prevent the onset of many neurodegenerative disorders. To produce even greater health benefits, some of our CBD gummies also contain low doses of THC.

Like we mentioned before, CBD doesn’t interact directly with CB1 and CB2 receptors. Instead, it seems to downregulate the function of cannabinoid receptors in the presence of THC. According to Vučković, et. al., “CBD has little binding affinity for either CB1 or CB2 receptors, but it is capable of antagonizing them in the presence of THC.” In other words, when THC and CBD are taken together, CBD acts as a safety engineer, improving the safety and tolerability of Delta 9 THC and downregulating THC’s possible adverse effects (e.g., increased anxiety and heart rate, and sedation).

CBD and THC might have more health benefits when taken together than in isolation. A study reveals that “the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids…exert additional effects of therapeutic interest.”

THC and CBD in the Entourage Effect

The entourage effect is a proposed theory in which THC, CBD, and other cannabinoids multiply each other’s benefits. In the entourage effect, cannabis components work together to provide a more potent and positive effect than any of the individual compounds could produce alone. Through mechanisms that are still being researched, compounds derived from cannabis plants appear to act synergistically with each other.

The beneficial effect of cannabidiol becomes more pronounced when you take CBD and THC together, and vice versa.

When phytocannabinoids interact with endocannabinoids, receptors, and enzymes, the entourage effect has an indirect impact on our endocannabinoid system. Different cannabis compounds affect the ECS in different ways, amplifying or regulating each other’s effects.

It has been proven that CBD softens the effects of THC when both cannabinoids are taken together. Similarly, beta-caryophyllene, a cannabis terpene, has been shown to bind directly to CB2 receptors and potentially increase the effects of other cannabinoids. According to Giacomo, et. al., terpenes like beta-caryophyllene and cannabichromene interacted together to boost the efficiency of cannabis extracts in treating breast cancer in animal models.

While the entourage effect is not something you can feel, you might start to sleep better or notice reduced symptoms of anxiety.

Is the Entourage Effect Real?

For some people, the idea of cannabinoids working together to enhance each other’s benefits seems too far-fetched. Yet, several studies have demonstrated that the entourage effect can help treat a variety of medical disorders, such as pain, inflammation, anxiety, and epilepsy.

A 2018 study's analysis discovered that a CBD-rich extract (which contained other cannabinoids in lower doses) was more efficient than pure CBD in reducing the frequency of seizures in two-thirds of participants with refractory epilepsy. According to the researchers, “the roots of this difference is likely due to synergistic effects of CBD with other phytocompounds (aka Entourage effect)...”

While CBD isolate (pure CBD) gets you some benefit, the ultimate entourage effect is best achieved with full spectrum cannabis products. You can find additional information on the differences between pure CBD and full spectrum CBD right here.

An animal study on chemotherapy-induced neuropathic pain showed similar entourage effect-like results. The study experiments “demonstrate quantitatively for the first time that CBD and THC work synergistically to prevent the development of neuropathic pain using a mouse model of chemotherapy‐induced peripheral neuropathy.”

For all those doubting Thomases out there, read our article on what makes the entourage effect real.

How to Produce the Entourage Effect

You can experience the entourage effect with full-spectrum cannabis products. They contain a wide range of cannabinoids and terpenes, ideal for creating that sweet cannabis synergy.

Our full spectrum Energy gummies are the way to go. Only 2.5 mg of Delta 9 is balanced perfectly by 5 mg of CBD. If you’re looking for a boost in energy and focus, the combination of these powerful cannabinoids in low doses can be exactly what you need.

Some cannabis users prefer not to take THC, so our broad spectrum CBD gummies are the obvious choice.

For additional information, read our comparison of full spectrum CBD and broad spectrum CBD.

Benefits of Microdosing Cannabis

Microdosing cannabis involves taking very small doses, usually with a concentration of THC below the psychoactive threshold. Low doses of cannabis seem to stimulate the endocannabinoid system and reduce the symptoms associated with many health issues, such as pain, anxiety, and inflammation.

Surprisingly, smaller doses of THC may provide more health benefits than higher ones. Large concentrations of THC can actually desensitize CB1 receptors, lowering their overall efficacy and perhaps causing unpleasant side effects like anxiety or paranoia. As a result, microdosing THC may be a more effective and safer strategy to harness the therapeutic potential of cannabis while avoiding unwanted side effects.

Scientific research confirms that microdosing cannabis can have greater medical and therapeutic benefits. In a case study, THC-rich microdoses relieved the symptoms of Alzheimer's disease without causing severe adverse effects. Low THC doses also counteracted the effects of brain aging by improving the cognitive performance and mental health of the participants. The findings of the study showed that “the primary beneficial effect on memory/cognition is provoked by compensatory low doses of THC for an aging-impaired endocannabinoid system.”

Here are some potential benefits of microdosing cannabis.

Microdosing cannabis has been shown to reduce anxiety and stress. The University of Washington found that small amounts of THC reduced anxiety and improved mood, while higher doses had the opposite effect on mental health. Low THC edibles can be beneficial for people struggling with depression.
At low doses, THC can boost creativity and focus. That’s why many people with ADHD microdose cannabis.
Microdosing cannabis may provide relief from symptoms of multiple sclerosis, such as muscle spasticity, pain, and tremors. A 2022 study found that cannabis-based medicine was effective in reducing and managing “MS outcomes such as spasticity, pain, tremors, ataxia, bladder functions, sleep, quality of life, and adverse effects.”
Low doses of cannabis have been found to boost serotonin. Serotonin is an important neurotransmitter that regulates mood, appetite, and sleep.
At low doses, THC and CBD have anti-cancer properties, particularly in the treatment of prostate cancer. A medically reviewed study found that THC and CBD can inhibit the growth of prostate cancer cells. According to the results of the study, “cannabinoids were shown to reduce the size of prostate cancer tumors in animal models.”
Microdosing cannabis may provide relief from the symptoms of irritable bowel syndrome (IBS). Microdosing cannabis could potentially modulate the ECS and alleviate symptoms of IBS, such as abdominal pain, spasms, and altered bowel movements, according to research.

Are you looking for a natural way to improve your health and help your endocannabinoid system work for you? Microdosing cannabis is the way to go. Our quality THC gummies have the most exquisite flavor profiles and are the perfect way to reap the benefits of cannabis.

If you’re a beginner, you should probably start small: Sleep Plus gummies contain only 2 mg of THC, 25 mg of CBD, and 3 mg of melatonin. With the juicy blackberry lavender flavor, improving sleep has never tasted so fresh.

Check out this detailed guide to melatonin for more information on this nighttime hormone.

Endocannabinoid System FAQ

What are the benefits of activating the endocannabinoid system?

The activation of the endocannabinoid system has been linked to a variety of potential health benefits. The main role of the endocannabinoid system is to regulate vital physiological functions—sleep, appetite, pain, and immunological response—and maintain homeostasis. Endocannabinoid receptors, endocannabinoids, and the enzymes that break them down help activate the ECS and keep our bodies in balance. Activating the ECS has been associated with improved sleep, chronic pain reduction, and overall improved quality of life.

How do you know if you have an endocannabinoid deficiency?

Although there is no conclusive test for endocannabinoid deficiency, the condition is often accompanied by poor digestion, low energy, disrupted sleep, a bad mood, chronic pain, and other symptoms. If you experience persistent symptoms, seek medical advice from a healthcare expert who is familiar with the endocannabinoid system.

How can I get endocannabinoids naturally?

You can enhance your endocannabinoid levels by engaging in activities that increase endocannabinoid signaling, such as exercise, meditation, or eating a well-balanced diet rich in fatty acids like omega-3. If you live on the Mediterranean, you’re in luck, because the Mediterranean diet is high in all the good stuff that naturally boosts endocannabinoids: sardines, anchovies, hemp seed and hemp oil, olive oil, and walnuts.

For the rest of us mortals who don’t follow the Mediterranean diet, here are some more foods and activities that support healthy endocannabinoids:

Flaxseed and flax oil
Coffee
Green tea
Exercise
Yoga
Meditation
Tai chi
Probiotics
Dark chocolate
CBD oil

Phytocannabinoids from medical cannabis—like CBD, THC, and Delta 8 THC—may also boost endocannabinoid synthesis. Delta 8 THC is another cannabinoid found in the cannabis plant. Read more about Delta 8 and all its benefits right here.

Do all plants have endocannabinoids?

Not all plants produce endocannabinoids. Cannabinoids are unique compounds that are primarily found in the cannabis plant, but they can also be found in other plants such as:

Echinacea
Black truffles
Black pepper
Dark chocolate
Helichrysum umbraculigerum
Liverwort (Marchantiophyta)

What organ produces endocannabinoids?

Endocannabinoids are produced on-demand by cells located in various tissues and organs, such as:

Brain
Liver
Pancreas
Immune cells
Skeletal muscle
Adipose tissue

Endocannabinoid receptors CB1 and CB2 are found throughout the bodies of all animals and humans, particularly in the central and peripheral neurological systems, the immune system, and the digestive tract. The prevalence of these receptors shows that the endocannabinoid system regulates many body activities, including pain perception, mood, hunger, and immunological response.

Is THC part of the endocannabinoid system?

THC is not a component of the endocannabinoid system, but it can activate its endocannabinoid receptors (CB1 and CB2). THC is a phytocannabinoid present in cannabis plants.

How do THC and CBD impact weight loss?

THC and CBD might have contradictory effects on weight loss.

THC has been shown to increase food consumption and boost appetite, which can contribute to weight gain. These are the so-called munchies that are typically associated with medical marijuana. Strangely, THC can also trigger a decrease in overall body weight due to the control of endocannabinoid precursors and increased energy expenditure.

CBD, on the other hand, has been proven to have potential weight loss advantages by suppressing appetite and promoting fat breakdown in the body. Study results “suggest that cannabidiol has an anorexigenic effect, correlated with a decrease in body weight.”

Has the FDA approved cannabis?

The FDA has not approved cannabis for any medical use. However, the FDA has approved several drugs that contain individual cannabinoids.

Epidiolex is a CBD-based medicine used to treat seizures caused by Lennox-Gastaut syndrome and Dravet syndrome, two rare forms of epilepsy. (Abu-Sawwa, et. al.)
Marinol (dronabinol) is a synthetic cannabinoid, a version of THC, used to treat chemotherapy-induced nausea and vomiting. It also promotes appetite in patients suffering from AIDS-related wasting syndrome. (O’Donnell, et. al.)
Syndros, also called “liquid dronabinol,” is a synthetic cannabinoid used for the same purposes as marinol: to help people in chemotherapy with nausea and vomiting.

All of these cannabis-based medications have undergone comprehensive clinical trials and have been shown to be safe and effective. Patients should use these medications under the supervision and medical advice of a healthcare professional, as they may interact with other medications.

Is Delta 9 THC legal?

Delta 9 is legal on a federal level in the US. Under the 2018 Farm Bill, Delta 9 must be derived from hemp, and the THC content cannot exceed 0.3% by dry weight.

However, the legality of hemp-derived products is determined by each state individually. For example, our Delta 8 products are federally legal, but a number of US states still ban Delta 8 outright.

All our Delta 9 THC edibles are legal in compliance with the Farm Bill. To make sure they are legal in your state, read up on our state-by-state guide to Delta 9 legality.

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