The Secret of Cannabinoids and Their Medical Benefits (18 Studies)

The Secret of Cannabinoids and Their Medical Benefits (18 Studies)

Cannabis is a complex and powerful plant and it produces a large number of exceptional compounds that can’t be found anywhere else in the plant world.

It’s simply mind boggling that all those tiny little chemicals inside the trichomes have their own evolutionary roles as well as having great therapeutic potential for us humans.

The centre of this story is that cannabis produces cannabinoids, chemical compounds that bind to certain receptors in our body. There are more than 100 of these compounds in each cannabis plant.

The best known is, of course, the notorious and psychoactive THC. However, over the past few years, a new superstar among cannabinoids rose to fame, and because it’s not psychoactive it is completely stealing the spotlight — that cannabinoid is called CBD.

Besides THC and CBD, there are many other cannabinoids which are present in the plant in varying quantities. Most of the time THC is the most prevalent cannabinoid with CBD coming in second.

The other cannabinoids are present in small quantities, totaling at usually less than 1%, but that doesn’t mean we should ignore them.

Even though they aren’t the chemical majority in the plant, they all contribute to pot’s many health benefits in something called the “entourage effect”, which we’ll discuss later on in the article.

3 types of cannabinoids explained

Cannabinoids are a class of chemical compounds that bind to the cannabinoid receptors in our brain and immune system, known as the CB1 and CB2 receptors.

Cannabinoids can be divided into three groups:

The research on cannabinoids began back in the 1940s, even though they were first found several decades before. It was actually Cannabinol (CBN), not THC, that was the first compound to be isolated from the plant at the end of the 19th century.

Cannabidiol (CBD) was the second cannabinoid to be identified, followed by the discovery of tetrahydrocannabinol (THC). But it wasn’t until the 1960s that science made a huge leap forward and began to isolate and synthesize these substances. (1)

Shortly after we isolated THC and CBD, we realized that humans produce cannabinoids on their own, these compounds are named endocannabinoids (endo meaning produced by the body).

After this, our knowledge of cannabis grew rapidly as it was fueled by the discovery of what has been called the most ancient lipid signaling network in existence — both endocannabinoids and phytocannabinoids are actually messaging molecules that fit beautifully into the endocannabinoid system.

To understand why cannabinoids are so important and how they can improve our health, we’ll need to dive in deeper into the endocannabinoid system and how our body uses cannabinoids to communicate between cells.

Cannabinoids receptors

Besides being one of the most important biological discoveries ever (deserving of a Nobel Prize) the discovery of cannabinoid receptors has solved many mysteries and relieved doubts around medical cannabis use, and has also had a major impact on research.

We have found two groups of cannabinoid receptors, present in all mammals. They are called cannabinoid receptor type 1 (or CB1) and cannabinoid receptor type 2 (CB2).

There have been hints and evidence of more receptors, but this is yet to be proven.

CB1 receptors are mainly located in the brain

Cannabinoid receptors type 1 are located mainly in the brain: in the cerebellum, the basal ganglia, the limbic system, the hippocampus, and the striatum. They are also found in female and male reproductive systems. (2)

What is particularly interesting is that these receptors are also present in the retina and anterior eye in humans. (3)

CB1 receptors are activated by all types of cannabinoids mentioned before. However, THC is particularly prone to binding to these receptors.

CB2 receptors are located in the CNS and the immune system

Cannabinoid receptors type 2 can also be found in some parts of the brain, but unlike the CB1 receptors, they are mainly located in microglia — neuronal support cells usually present in the central nervous system that function as immune cells.

CB2 receptors are also found in the peripheral tissues of the immune system (spleen, tonsils, thymus gland), and throughout the gastrointestinal and peripheral nervous system.

Endocannabinoid system and endocannabinoids

The endocannabinoid system is a signaling network which modulates neurological functions, inflammatory processes and is involved in the creation of certain diseases (Crohn’s, atherosclerosis and osteoarthritis).

It consists of cannabinoid receptors (mentioned above) and endocannabinoids that are produced by our bodies.

The inhibition and activation of these cannabinoid receptors makes up the endocannabinoid system which mediates the following physiological actions:

  • Antinociception (reduction of pain sensitivity);
  • Cognition and memory;
  • Locomotor activity;
  • Endocrine functions;
  • Temperature control and heart rate;
  • Nausea and vomiting;
  • Intraocular pressure;
  • Inflammation;
  • Immune recognition and antitumor effects.

Endogenous cannabinoids, or just endocannabinoids, are cannabinoids produced within our body.

In layman terms, endocannabinoids have a binding affinity for CB1 and CB2 receptors, which enables our body to communicate on a cellular level. Our body produces an endocannabinoid, which travels and binds to the nearest CB receptor, thus initiating whatever process our body requires.

An example of this would be in a way that our body regulates appetite. When we eat and process food, our small intestine releases a hormone called NAPE in our bloodstream. NAPE travels to the hypothalamus, is synthesized into anandamide (an endocannabinoid), which then attaches itself to corresponding receptors, thus reducing our appetite.

There are six endocannabinoids, but only two have been researched thoroughly — anandamide and 2-AG. We produce them ourselves but only in times of need.

Anandamide (AEA)

They call it the human THC, a natural antidepressant, but its most famous nickname is the bliss molecule. Anandamide is a compound that we produce in our own body but the FAAH (fatty acid amide hydrolase) enzyme breaks it down very fast.

So, those who produce less FAAH (which is actually a genetic mutation) have larger concentrations of this endocannabinoid which plays a great role in our mental health.

Anandamide is actually very important for maintaining our inner bliss and happiness. A 2014 rodent study found that preventing the breakdown of AEA reduced anxiety while also improving mood. (4)

Our natural THC not only acts like a pain reliever, but also regulates our appetite, helps you forget bad memories, and induces the famous “runner’s high” effect.

2-AG

2-Arachidonoylglycerol (2-AG) is another endocannabinoid and a neurotransmitter. This endocannabinoid is present in the human brain in concentrations up to 170 times higher than anandamide.

Cannabinoids from cannabis affect those that we make on our own, especially 2-AG. THC may inhibit the role of 2-AG, because it primarily binds to the same group of receptors. CBD does not bind to the receptors directly, but rather increases the endocannabinoids’ lifespan by inhibiting enzymes in charge of degrading them.

2-AG is particularly important for balancing our metabolism, regulating sleep, pain, and reproduction. It also has some neuroprotective properties. A 2016 study suggests that 2-AG may also help in treating conditions such as PTSD, Parkinson’s disease, autism, motion sickness, and many others. (5)

13 cannabinoids from cannabis explained

The cannabis plant itself produces a bunch of different substances from which we can benefit from. Besides terpenes, which are aromatic chemicals with great medical value, there are some 113 different phytocannabinoids (6) in this powerful plant.

Cannabinoids found in cannabis are produced in trichomes, tiny little hairlike outgrowths on the flowers, leaves and stems of the cannabis plant. Together with terpenes, cannabinoids protect the plant from UV rays, heat and predators.

What makes pot so popular is the fact that cannabinoids from cannabis have a binding affinity towards the same CB receptors as endocannabinoids, which allows us to produce a wide variety of effects depending on the dosage taken.

Simply put, THC can mimic the effects of anandamide provided we get the dosage right, and CBD can delay its degradation by inhibiting an enzyme in charge of shutting down anandamide.

This means that, for each condition, there should be a strain that works best that has just the right cannabinoid levels. There are a few tricks that pot growers use to manipulate the cannabinoid levels, like tweaking the lighting, temperature and humidity while the plant is growing.

For example, when we expose the plant to UV rays or high temperatures, it thinks it needs to protect itself, so it starts to produce more trichomes. Since trichomes contain cannabinoids (among other things) this allows us to produce a high potency flower with upwards of 20% THC.

Cannabinoid acids

Before we start exploring cannabinoids one by one, we need to make something clear. Cannabis does not produce cannabinoids in the form that we all know them. Instead, it synthesizes acids which have to be activated with heat (in a process called decarboxylation) to turn into cannabinoids.

There are two main cannabinoid acids — cannabigerolic acid (CBGA) and cannabigerovarinic acid (CBGVA) and from them, other acids are produced like THCA (delta 9-tetrahydrocannabinolic acid), CBDA (Cannabidiolic acid), CBCA (Cannabichromenic acid), and many others.

So for example, when we expose THCA to heat, we transform it into psychoactive THC. THCA is not psychoactive at all, which is why we need to either smoke or decarboxylate cannabis if we’d like to activate its psychoactive properties and get high.

Some would say that we can also benefit from raw cannabis, too. Apparently, raw pot has anti-anxiety, antioxidant properties and may improve neural functions, however there is still not enough research to completely prove this.

Now that we’re familiar with cannabinoid basics, which may sound rather complicated at first, let’s explore the most important cannabinoids in cannabis.

Have in mind, though, that the medical benefits of cannabis come from all of the different cannabinoids playing together, and not so much from isolated compounds.

However, to fully understand the complexity of the plant and all of its key players, we must first look at each of the main cannabinoids individually, and only then can we grasp the big picture.

So let’s get started.

THC (Tetrahydrocannabinol)

The principal substance in most cannabis strains, THC (also known as delta-9 THC) is the most abundant and the only psychoactive cannabinoid in cannabis.

I bet that anyone who has ever had anything to do with pot has heard of THC. It’s the THC that produces that high effect in our head and body, and it’s basically why cannabis is still prohibited in most parts of the world.

In the majority of strains it is the most abundant cannabinoid, although nowadays with cross-breeding and other growing methods we are seeing more and more high CBD strains, which produce many health benefits with very few side effects.

Despite the “undesirable” high it produces, THC has a lot to offer medically. THC binds primarily to CB1 receptors, thus producing effects similar to that of anandamide. Although THC’s binding affinity to these receptors is not of the same quality as anandamide, meaning that you’d need more of it to achieve similar effects.

The trick (as it usually is when it comes to cannabis) is in the dosage, because the adequate stimulation of these receptors produces one effect, but overstimulation produces the opposite effect.

With that in mind, in proper medical dosages THC can be used as an antiemetic alternative by patients fighting cancer and as an appetite stimulant by people living with HIV/AIDS.

THC has also been shown to relieve symptoms of conditions such as insomnia, chronic pain, arthritis, migraines, and it even helps us forget traumatic memories that cause PTSD.

Although THC is probably the most explored cannabinoid of them all, there’s still a lot of research to be done.

CBD (Cannabidiol)

Cannabidiol or just CBD for short, is a rising star in the cannabis world. You might’ve noticed yourself that it seems like everyone is talking about CBD and its benefits.

CBD is the second most prevalent cannabinoid in the plant, although in recent years budtenders managed to create new high CBD strains by cross-breeding plants with different genetics.

What’s so special about CBD is that it’s a non-intoxicating compound with great medical potential. That means that it does not make people “high” like THC does, which is why it has become very popular among medical users who’d like to stay clear headed.

CBD was discovered and synthesized at about the same time as THC (by Dr Mechoulam in the 1960s), which means the modern science has had its hands on it for quite some time.

Consequently, there are tons of studies on CBD and its medical effects, and we can confidently say that it reduces seizure frequency in epilepsy patients, relieves inflammation, and reduces anxiety and neuropathic pain.

CBD does all of this through several molecular pathways, but primarily through these three:

  • It inhibits the enzyme that degrades anandamide, making you feel less anxious and depressed, and relieving pain.
  • It activates 5-HT1A receptors, which help you secrete more “feel good” hormones, like endorphin, serotonin and oxytocin.
  • It blocks GPR55 signaling, which might slow down the growth and migration of certain cancers.

Since this rounds up the two primary cannabinoids of the cannabis plant, we’ll now discuss several of the minor ones.

CBG (Cannabigerol)

Cannabigerol is a scarcer cannabinoid in the cannabis plant since it’s usually present in concentrations of less than 1%. Just like CBD, it’s completely non-psychoactive.

Surprisingly, CBG is the “parent cannabinoid” of both THC and CBD. The marijuana plant produces cannabigerolic acid (CBGA) which later develops into three essential cannabinoid acids and then into THC, CBD and CBC.

CBG has some very promising medical potential as the cannabinoid has shown to be very effective in lowering ocular pressure. (7)

Also, it works as an antibacterial agent, appetite stimulant and muscle spasm inhibitor. It has also shown some promising cancer-fighting properties by blocking the growth of cancer cells. (8)

CBN (Cannabinol)

Cannabinol is the most sedative cannabinoid of all, producing the couch-lock effect in conjunction with the famous THC and a terpene called myrcene.

When THC ages and is exposed to too much oxygen it transforms into CBN. That usually happens with the buds that are stored for too long.

CBN produces little-to-no psychoactive effects. Although this is a less researched cannabinoid, early findings suggest that it has great potential, especially in combination with other cannabinoids.

Besides its sedative effect and its use as a sleeping aid, this cannabinoid when used alongside CBD and CBG is an effective treatment for psoriasis, by decreasing the proliferation of keratinocytes. (9)

Early research has shown that CBN instigates the growth of stem cells in the bone marrow, helping the bones to form and grow. (10) It has also shown promising antibacterial, anti-inflammatory and pain killing properties.

CBC (Cannabichromene)

Cannabichromene is another non-psychoactive cannabinoid, which has low binding affinity for CB1 receptors, but it has more affinity towards other receptors in our body that are connected with pain regulation.

Although CBC has a lot of potential on its own, it seems that it works best in synergy with other cannabinoids, in the so-called the entourage effect, helping other cannabinoids reach their full potential.

A 2013 study by the Italian Institute of Biomolecular Chemistry suggests that CBC may boost neurogenesis (the production of neurons in stem cells) by improving their function. (11)

In one animal study, rats who were treated with CBC performed better in stressful situations.(12)

Besides its antifungal and antibacterial effects, a recent study suggested that this cannabinoid may perform better than other medications used for treating the MRSA virus. (13)

THCV (Tetrahydrocannabivarin)

Similar to THC in its molecular structure, THCV is a psychoactive compound with great medical potential. But, unlike its “cannabinoid sibling”, it suppresses the appetite, which makes it great for keeping your weight in check.

It is of interest to diabetes patients as one study found that it regulates blood sugar and insulin levels. (14)

THCV helps improve tremors and brain lesions connected to Alzheimer’s disease. Along with other cannabinoids, it reduces panic attacks caused by anxiety or PTSD, and there are some indications that it stimulates bone growth as well.

CBDV (Cannabidivarin)

Structurally similar to CBD, cannabidivarin will not make you high like THC-related compounds. Since it’s not very common in the majority of strains, it’s hard to find a strain that has it in more than just traces.

This does not mean that CBDV doesn’t have a lot to offer, especially to medical users. A few studies confirmed CBDV helps in reducing epileptic seizures, and there is evidence of its ability to relieve nausea. (15)

This just goes to show how powerful CBD homologs are.

CBL (Cannabicyclol)

Cannabicyclol is another non-psychoactive phytocannabinoid but still not studied or understood nearly enough.

CBL is formed in the degradation process of CBC. It’s typically found in Pakistani hash strains which have been stored for at least six months. It’s really hard to decarboxylate it, making it the most heat-resistant cannabinoid.

There aren’t many studies on the medical benefits of CBL. Instead, most of the research done so far has focused on its chemical structure.

The few studies done on CBL have concluded that it does not have the same medical potential as THC and CBD or other cannabinoids.

CBV (Cannabivarin)

Cannabivarin is another compound in the cannabis plant that is derived from THC but does not make people high. It’s pharmacological potential has not yet been explored.

CBCV (Cannabichromevarin)

Another lesser known cannabinoid, CBCV does not produce mind altering effects. It was discovered back in 1975 when Japanese researchers isolated it for the first time from the cannabis plant.

Because of its structure, it has effects similar to CBC.

There is still a lot of research to be done on this cannabinoid, but because of its similarity with CBC, medical experts speculate that it acts as a painkiller and antidepressant.

CBE (Cannabielsoin)

Researchers from the University of Ohio discovered cannabielsoin back in 1983, and this cannabinoid is classified as a metabolite of CBD. (16) CBE can be found only in trace amounts in majority of strains.

Because it’s present in such small amounts, it has not been explored in detail in clinical research and is barely mentioned in scientific literature.

CBT (Cannabitriol)

Cannabitriol has the same structure as THC, but it has two more alcohol groups added. It was discovered, isolated and described in 1966 by Yataro Obata and Yoshinori Ishikawa.

Scientists don’t yet know if this is a psychoactive compound or if it has any medical value.

Delta(8)-THC

This cannabinoid is very similar to THC but with some slight differences, primarily that delta(8)-THC is less psychoactive.

Early research has shown some promising properties: First of all, it seems to be a great appetite stimulant, by some accounts boosting appetite even better than THC. In one study delta(8)-THC increased the appetite in rodents much more than THC. (17)

Back in 1995, delta(8)-THC was introduced into nausea therapy for children with cancer between the ages of 2 and 13. It was surprising to see how well the children responded to treatment, with no reported psychoactive effects. (18)

Synthetic cannabinoids

Synthetic cannabinoids entered the market in the early 2000s in an attempt to avoid legal restrictions that follow cannabis around the world. They are of course made artificially to bind to the same receptors as phytocannabinoids and endocannabinoids, however they are much more potent and dangerous.

They have been on the black market for a while under the names like K2, Spice or Synthetic marijuana, and sold like herbal smoking blends. The problem with this is that synthetic cannabinoids can be life-threatening and there are number of deaths associated with them.

Pharmaceutical companies have designed artificial cannabinoids to treat nausea, vomiting, loss of appetite and, most recently, epilepsy. These are not to be mistaken with black market synthetic cannabinoids such as K2 and Spice.

Summary

As you’ve had a chance to see, there are more than a hundred cannabinoids in the plant, but only few are psychoactive and even fewer have been thoroughly researched. They play a very important role in every plants life, while making a major impact in our endocannabinoid system, too.

The cannabis plant is like a half-explored mine of medical benefits, however we must never forget the fact that cannabinoids work best when combined in adequate amounts. Only then they can play off each other and, with the help of terpenes, produce a multitude of medical benefits.

References:

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  3. Straiker AJ, Maguire G, Mackie K, Lindsey J; Localization of cannabinoid CB1 receptors in the human anterior eye and retina; Investigative Ophthalmology and Visual Science; September 1999; 40(10):2442-2448
  4. Bluett RJ, Gamble-George JC, Hermanson DJ, Hartley ND, Marnett LJ, Patel S; Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation; Translational Psychiatry; July 2014; 4:e408
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  7. Nadolska K, Goś R; Possibilities of applying cannabinoids’ in the treatment of glaucoma; Klinika Oczna; 2008; 110(7-9):314-317
  8. Borrelli F, Pagano E, Romano B, Panzera S, Maiello F, Coppola D, Petrocellis LD, Buono L, Orlando P, Izzo AA; Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid; Carcinogenesis; December 2014; 35(12): 2787–2797
  9. Wilkinson JD, Williamson EM; Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis; Journal of Dermatological Science; February 2005; 45(2):87-92
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  13. Appendino G, Gibbons S, Giana A, Pagani A, Grassi G, Stavri M, Smith E, Rahman MM; Antibacterial cannabinoids from Cannabis sativa: a structure-activity study; Journal of Natural Products; August 2008; 71(8):1427-1430
  14. Jadoon KA, Ratcliffe SH, Barrett DA, Thomas EL, Stott C, Bell JD, O’Sullivan SE, Tan GD; Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study; October 2016; 39(10):1777-1786
  15. Amada N, Yamasaki Y, Williams CM, Whalley BJ; Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression; PeerJ; November 2013 ; 1:e214
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