What are cannabinoids? 

Cannabinoids are a diverse array of ‘cannabis like’ molecules, including phytocannabinoids, endocannabinoids and synthetic cannabinoids. Cannabinoids can be found within our bodies, within plants (especially cannabis) and can be synthesised in laboratory settings. The main cannabinoids you’ll hear about are likely to be CBD and THC, which are phytocannabinoids found in cannabis. But, there is growing evidence to suggest that minor cannabinoids – alongside other cannabis compounds – may play an equally important part in the therapeutic benefits of your cannabis plant.

There are 3 types of cannabinoids:

1. Phytocannabinoids – ‘Phyto’ meaning plant-derived, these are cannabinoids found in the cannabis plant (and many other plants).

2. Endocannabinoids – ‘Endo’ meaning internal, these are naturally occurring cannabinoids found in the human brain and bodily organs.

3. Synthetic cannabinoids – cannabinoids synthesised by chemists to mimic the actions of phytocannabinoids or to influence the body’s endocannabinoid levels.

Let’s first look at the main two types of cannabinoids you’ll encounter, endocannabinoids and phytocannabinoids:

Endocannabinoids

Endocannabinoids (or endogenous cannabinoids) are naturally occurring cannabinoids found in the brain and body. They are lipid signalling molecules which exist to mediate our normal physiological functions. This means they bind to a protein target (in this case, a cannabinoid receptor) to create specific cellular responses in the body, such as stimulating appetite. Endocannabinoids may have evolved in the brain to maintain biological harmony while also playing a role in neuronal plasticity (how the brain adapts to change).¹

The two major endocannabinoids that have been discovered are:

• Anandamide (AEA) (ananda is the Sanskrit word for bliss)
• 2-arachidonoyl glycerol (2-AG)

Both of these endocannabinoids help our internal functions run smoothly, and a healthy human body produces them as needed. When there is a deficiency or imbalance in our endocannabinoid production, then we may need to look at external ways to upregulate our endocannabinoid levels.

Endocannabinoids, cannabinoid receptors (which both endocannabinoids and phytocannabinoids interact with) and enzymes are the three components which make up the endocannabinoid system (ECS). The ECS is the molecular system located throughout our brains and bodies which helps regulate our immune responses, cell communication, sleep, pain, appetite, hormone levels, metabolism, memory, and more. 

Learn more about the ECS here.

Phytocannabinoids

Phytocannabinoids are cannabinoids derived from the cannabis plant which can also be found in other plants, including cloves, carrots and broccoli, in smaller quantities. Research has found that the cannabis plant produces between 80 and 100 cannabinoids and about 300 non-cannabinoid chemicals.² Like endocannabinoids, phytocannabinoids also interact with our endocannabinoid system and cannabinoid receptors to produce certain effects within the brain and body.

The two most well-known cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Both CBD and THC as well as numerous other cannabinoids are used in medicinal cannabis for their therapeutic potential. We’ll explore some of these cannabinoids and their properties below.

What do cannabinoids do? 

Both endocannabinoids and phytocannabinoids interact with the body’s endocannabinoid system (ECS) to produce varying effects. Each of us – whether we consume cannabis or not – has an ECS which helps regulate and balance many processes in the body.

The endocannabinoid system is made up of:

1. Endogenous cannabinoids (endocannabinoids)
2. Cannabinoid receptors
3. Enzymes responsible for the synthesis and degradation of the endocannabinoids 

Unlike the nervous system or cardiovascular system, the endocannabinoid system is not an isolated structural system located in a specific region of the body. Instead, the ECS is a receptor system broadly distributed throughout the body which is acted upon by cannabinoids and enzymes. Endocannabinoids and cannabinoid receptors can be found throughout the brain, organs, connective tissues, glands, and immune cells.
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Endocannabinoids and the ECS

A typical endocannabinoid system function works when the body’s naturally produced endocannabinoids (which are present in various organs and tissues) become active by binding with a cannabinoid receptor (also located all throughout the body) to regulate a bodily function, such as digestion or sleep. Essentially, when a system or function in the body is out of balance, receptors bind to cannabinoids to help correct the problem. Once the endocannabinoid system brings the body back into balance, enzymes will break down the cannabinoids to prevent overcorrecting the problem.
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Phytocannabinoids and the ECS

Much like endocannabinoids, phytocannabinoids (which have a similar chemical structure to our endocannabinoids) also interact with our ECS and cannabinoid receptors to produce varying effects. When taken under the guidance of a prescribing doctor, phytocannabinoids like CBD, THC and more also have the potential to aid internal processes, mediate physiological functions and create balance within the body.
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Learn more about the endocannabinoid system and how cannabinoids like THC, CBD and CBN interact with it here.
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Effects of phytocannabinoids 

Different phytocannabinoids (or combinations of cannabinoids and other cannabis compounds such as terpenes) create different effects in the mind and body, depending on how they’re used and who is using them. Some cannabinoids, like THC, are psychoactive, meaning they have an effect on the mind and can cause changes in mood, awareness, feelings, thoughts and behaviour. Psychoactive cannabinoids can be impairing for a period of time after use. Other cannabinoids, like CBD, do not produce psychoactive effects, meaning they are not likely to impact cognitive abilities like driving or memory recall.

Cannabinoids have a range of studied therapeutic benefits, from nausea and pain relief³ to anti-inflammatory⁴ and anxiolytic (anxiety relieving) capabilities⁵. In Australia, cannabinoid medicines have been prescribed to treat the symptoms of a range of chronic conditions, including anxiety, chronic pain and endometriosis. 

Continue reading to learn more about some of the main phytocannabinoids found in cannabis.

‍Types of cannabinoids in cannabis

The cannabis plant contains over 400 distinct compounds, between 80 and 100 of which are cannabinoids. Each cannabinoid has its own unique properties, many of which are still being uncovered by researchers. CBD and THC are the two major cannabinoids that you’ll probably hear about the most, but there is growing evidence to support the therapeutic effects of minor cannabinoids such as CBG and CBN. In fact, many of the proposed medical benefits originally thought to arise from CBD may actually be attributed to minor cannabinoids.⁶

Let’s look at four of the main cannabinoids you might find in cannabis and cannabinoid medicines:

Tetrahydrocannabinol (THC)

Delta-9-tetrahydrocannabinol (THC) is one of the main phytocannabinoids found in the cannabis plant. THC is a psychoactive cannabinoid which gives the ‘high’ sensation commonly associated with cannabis use. THC works directly with the ECS by binding with CB1 receptors in the brain, and may help relieve symptoms of pain while reducing chemotherapy induced nausea and vomiting, increasing appetite, improving sleep and more in some patients. 

Learn more about how THC interacts with the ECS here.

Cannabidiol (CBD)

Cannabidiol (CBD) is another of the most abundant in the long list of cannabinoids found in the cannabis plant. Unlike THC, CBD is non-impairing and won't bring on a feeling of being ‘high.’ This is because CBD does not bind with the CB1 receptor which creates the high sensation. Instead, CBD  works indirectly with the endocannabinoid system to interact with our opioid, dopamine, and serotonin receptors, giving it the potential to provide pain relief, depression and anxiety while boosting the immune system and helping with addiction. 

Learn more about how CBD interacts with the ECS here.

Cannabinol (CBN) 

Cannabinol (CBN) is a cannabinoid known to have anticonvulsant, sedative, and other pharmacological activities⁷ that are still being explored. CBN is created during the breakdown of the psychoactive cannabinoid THC⁸. Like THC, CBN also binds to the CB1 receptor, but at a much lower strength than THC. This technically makes it a psychoactive compound, but it doesn’t produce much of a ‘high’ sensation. CBN has a stronger affinity towards the CB2 receptors, which are mostly associated with immune system regulation.⁹

Cannabigerol (CBG)

Cannabigerol (CBG) is an active, non-intoxicating minor cannabinoid found in cannabis. CBG can work synergistically with CBD to mitigate the ‘high’ produced by THC while also helping to compound each cannabinoid’s therapeutic effects, depending on the ratios of each cannabinoid present. Studies indicate that CBG may have therapeutic potential in treating the symptoms of some neurological disorders and inflammatory bowel disease, as well as having antibacterial activity.¹⁰

Synthetic cannabinoids

Synthetic cannabinoids are cannabinoids that have been synthesised to mimic the actions of phytocannabinoids or influence the body’s endocannabinoid levels. Like naturally occurring cannabinoids, synthetic cannabinoids act on the cannabinoid receptors in the body to produce certain effects. The more accurate term for these compounds is ‘synthetic cannabinoid receptor agonists’ (SCRAs).

While some synthetic cannabinoids (SCRAs) have been developed for medicinal use with a prescription, synthetic cannabis products obtained without a prescription are both prohibited and unregulated in Australia. These ‘synthetic cannabis’ products often have stronger and more negative effects (that are not caused by natural cannabis) and greater health risks than their prescribed or natural counterparts.¹¹

Some of the serious adverse effects seen with non-prescription synthetic cannabinoids include:

• fast and irregular heartbeat
• psychosis
• aggressive and violent behaviour
• chest pain
• vomiting
• raised blood pressure (hypertension)
• breathing difficulties
• hyperthermia (overheating)
• breakdown of muscle tissue (rhabdomyolysis)
• acute kidney injury
• seizures
• stroke
• death.¹²,¹³

Synthetic cannabinoids are usually mixed with solvents and sprayed onto herbs to be sold in colourful, branded packets. Although the contents may be described as ‘herbal’, the actual psychoactive material in these products is synthetic, and not all ingredients or their correct amounts are likely to be listed. On top of this, chemicals usually vary significantly from batch to batch, so different packets can produce different effects, even when the packaging looks the same. All of these factors can contribute to the risk of overdosing on synthetic cannabis products.

Using cannabinoids safely 

The only way to ensure you’re getting the therapeutic benefits and cannabinoid content you need from your cannabis is to get a prescription from a licensed healthcare professional. Cannabinoids can cause unwanted side effects in some people at certain doses, particularly when consumed via illegal cannabis products which are not regulated for safety, quality or ingredients (learn more about legal v. illegal cannabis here) and which often contain high levels of the cannabinoid THC. While there have not been any reported deaths in teens and adults resulting solely from cannabis use or cannabis toxicity, synthetic cannabinoids obtained without a prescription are known to be dangerous and can even cause death. 

CBD is generally well tolerated as a cannabinoid and is non-impairing, even at high doses.¹⁴ On the other hand, THC can induce the ‘high’ feeling associated with cannabis, and can be impairing or sedating in some people at certain doses. Because of this, THC is more likely to cause unwanted side effects like anxiety, confusion, dizziness, slower reaction times and increased heart rate at high doses. In rare cases and at high doses it can also cause hallucinations, paranoia, psychosis, panic attacks, nausea and vomiting.¹⁵ There may also be a link between heavy recreational cannabis use and some psychiatric disorders –  with recent research suggesting that smoking high-potency cannabis each day could increase the chances of developing psychosis by nearly five times compared to people who have never used the drug.¹⁶

Available evidence suggests that the following guidelines may help users reduce or avoid cannabis use-related health risks:¹⁷,¹⁸

1. Abstain from cannabis if it is not required to treat a medical condition, especially if you are in a higher risk group for cannabis related health problems
2. Avoid using THC-containing cannabis treatments if you have angina or a history of myocardial infarction, or a personal or family history of schizophrenia or psychotic disorders
3. Avoid early age initiation of cannabis use (particularly before the age of 16) unless benefits clearly outweigh the risks
4. Choose low-potency or balanced THC-to-CBD ratio cannabis treatments, or CBD only treatments (if appropriate for your condition)
5. Abstain from using synthetic cannabinoids
6. Avoid combustion cannabis methods (instead opt for other non smoking consumption methods)
7. Start with a low dose and slowly titrate up to your ideal dose under the guidance of your doctor
8. Do not use cannabis if you are taking any medications which are known to interact poorly with cannabis (always check with your doctor)
9. Carefully monitor any side effects and interactions with other prescription medications that you experience when taking cannabis
10. Abstain from cannabis use while pregnant

It’s important to note that driving with any amount of THC in your system is currently illegal in Australia (in every state except Tasmania) due to its potential to impair cognitive functions needed for safe driving. Always follow the dosing and administration guidelines provided to you by your doctor and monitor your symptoms and any side effects when starting a new treatment or changing your dose.

Talk to a doctor about safely using cannabinoids to treat the symptoms of a chronic condition by signing up as a Polln patient today.

Learn more about the differences between illegal and legal cannabis in Australia here.
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FAQs

Are terpenes cannabinoids? 

Like cannabinoids, terpenes are one of the numerous chemical compounds found within the cannabis plant which have therapeutic potential, but they are not considered cannabinoids. Terpenes are organic, aromatic compounds found in plants in the form of oils. Essentially, they are what gives a plant its unique flavour and aroma. But beyond just influencing the cannabis plant’s unique taste and smell, terpenes also play a significant role in the therapeutic effects of cannabis by interacting with cannabinoids and other cannabis compounds to create subtle differences in our experience.

Learn more about terpenes here.

Are cannabinoids addictive? 

Cannabis is known to have a low to moderate risk of dependence that is significantly lower than alcohol, nicotine, caffeine, and prescription drugs like morphine and opioid medicines.¹⁹ But there is still some potential for a dependence to develop, particularly in non-prescription users and those taking high concentrations of THC. 

In 2018, a report from the World Health Organisation found that the cannabinoid CBD exhibits no effects indicative of any abuse or dependence potential in humans and stated that to date ‘there is no evidence of public health related problems associated with the use of pure CBD.’²⁰ In fact, evidence suggests that CBD can mitigate the unwanted effects of THC and shows potential in treating symptoms of Alzheimer's disease, cancer, psychosis, Parkinson's disease, and other serious conditions. It is therefore highly unlikely that CBD is an addictive cannabinoid.

THC, on the other hand, may have the capacity to create dependence in some users. Studies show that the risk of recreational cannabis dependence is more common with high strength THC cannabis strains with a low CBD content (which are often bred illegally for this purpose), large amounts consumed, high frequency use (heavy, daily) and with starting use early in adolescence.²¹ Currently, there is very limited research looking at whether there is an association between medicinal THC and dependence, so more research is needed. With the support of a prescribing doctor, you should be able to find a treatment plan and dose that works for you while reducing the risk of dependence.

Taking tolerance breaks can reduce the amount of THC you need to feel the therapeutic benefits of your medicine and reduce the risk of dependence. Talk to your prescribing doctor if you believe you are experiencing any signs or symptoms of cannabis dependence.

Learn more about tolerance breaks here.

Chronic cannabis use can lead to what is known as Cannabis Use Disorder. Cannabis Use Disorder is categorised by a problematic pattern of cannabis use leading to clinically significant impairment or distress. This might look like taking larger amounts of cannabis over a longer period than intended, neglecting work, social or other obligations due to cannabis use, developing a tolerance or experiencing withdrawals to cannabis, experiencing strong cravings to use cannabis and more.²² Talk to your doctor if you are concerned about or believe you are showing signs of Cannabis Use Disorder. 
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How many different cannabinoids are there? 

The cannabis plant produces between 80 and 100 phytocannabinoids. In addition to CBD and THC, some of these include:

• THC-acid (THCA)
• CBD-acid (CBDA)
• Cannabigerol (CBG)
• Cannabigerolic acid (CBGA)
• Cannabichromene (CBC)
• Cannabichromenolic acid (CBCA)
• Cannabichromevarin (CBCV)
• Cannabichromevarinolic acid (CBCVA)
• Cannabidivarin (CBDV)
• Cannabidivarinolic acid (CBDVA), and
• Cannabinol (CBN)
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Do all cannabinoids get you high?

No. Not all cannabinoids are intoxicating and therefore will not produce the ‘high’ sensation that is most commonly associated with THC. This is because each cannabinoid has unique properties and interacts with the endocannabinoid system in varying ways. Cannabinoids (like THC) which interact with the CB1 receptor in our ECS are more likely to produce a psychoactive or intoxicating effect, however not all cannabinoids which interact with the CB1 receptor will produce a strong ‘high’ feeling.

Learn more about the endocannabinoid system here.