CBD vs. THC
By Dr. Victor Chou
From nearly 70 cannabinoids isolated to date, cannabidiol (CBD) and tetrahydrocannabinol (THC) are the two most popular and most well-researched.
Currently, several other cannabinoids are being researched, including cannabigerol (CBG) and tetrahydrocannabivarin (THCV).
Aside from these active ingredients, it is estimated that cannabis possesses over 120 active compounds, serving as a powerful combination for treating various conditions. 
Also known as phytocannabinoids, THC and CBD are two naturally occurring compounds in the cannabis plant that possess various differences and similarities. There is an ongoing debate about which component offers greater healing powers, so we will try to provide a through answer to cover this topic of discussion.
However, as we are entering the scientific world of these two cannabinoids, it will becomes more and more clear that there is no CBD vs. THC in the true sense of the word, but two components with different healing properties, each unique on their own.
Let’s take a look at their chemical structure, psychoactive components, health benefits, legal status, interaction with the endocannabinoid system, entourage effect, side-effects, benefits for chronic pain, and more.
Cannabidiol (CBD) and tetrahydrocannabinol (THC) are the two major components present naturally in the hemp plant. These two phytocannabinoids interact directly or indirectly with specific cannabinoid receptors found in the body — mainly in the brain — causing various effects in the human body. 
These two components are fundamentally different because of the manifestation of their distinctive psychological effects. While THC classifies as a psychotropic drug, CBD is the compound that doesn’t elicit a “high” but has gained ground thanks to the growing list of medicinal benefits it offers. 
The most well-known cannabinoid, THC (the full scientific name is delta-9-tetrahydrocannabinol) is the principal, mind-altering proactive molecule in cannabis sativa that reduces nausea, relieves pain, and suppresses muscle spasm, among others health benefits.
The isolation of this psychoactive ingredient was achieved in the 1960s and 1970s, whilst CBD was first isolated in 1940. The understanding of THC’s intoxicating properties came to light in 1965, when the Israeli scientist Raphael Mechoulam synthesized the molecule.
CBD and THC have lots of similarities. They both share the exact same molecular formula C21H30O2, are compounds from a family of around 113 bi – and tri – cyclic cannabinoid compounds found in cannabis, contain 21 atoms of carbon, 30 atoms of hydrogen and 2 of oxygen.
Besides, THC and CBD have a nearly identical molecular mass with 314.469 g/mol and 314.464 g/mol, respectively.
Also, both components are chemically similar to the endocannabinoids present in the body, which is why CBD and THC can interact with the cannabinoid receptors and release neurotransmitters in the brain. The neurotransmitters relay messages between cells in the human body.
In addition, the biosynthesis of these two components follows a similar pathway, with one important difference. In the part where THC contains a cyclic ring, CBD has a hydroxyl group. This seemingly small difference in the molecular structure brings the entirely different pharmacological properties.
And although the exact mechanism of both components is not fully understood, the analgesic, anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, antioxidant, and antipsychotic activity of CBD is likely due to the component’s complex pharmacological mechanisms. 
Another study found that CBD might be useful as a protective agent against external stresses such as ultraviolet irradiation and oxidative stressors, due to its effects on melanogenesis. 
Cannabinoids and the Endocannabinoid System
Patients across the US use cannabis as an open door to treating a growing number of medical conditions.
For example, in Colorado, the medical card qualifies nine different conditions addressed by cannabis, including cancer, glaucoma, persistent muscle spasms, seizures, nausea, severe pain, PTSD, HIV or AIDS and cachexia.
A vital question many people ask when looking at this list of conditions, is how cannabis interact with the body to address all of these and many more conditions in an effective way?
The answer to that complex question lays in the even more complex system found in the human body, the endocannabinoid system.
The Endocannabinoid System Maintains Homeostasis
Each year, scientist dive into the partly unknown mechanisms of the endocannabinoid system to discover more about this important part of the human body.
The endocannabinoid system is responsible for maintaining homeostasis in the body.
As Encyclopedia Britannica defines it, homeostasis is, “any self-regulating process by which biological systems tend to maintain stability while adjusting to conditions that are optimal for survival. If homeostasis is successful, life continues; if unsuccessful, disaster or death ensues.”
The first part of the endocannabinoid system is the endocannabinoid receptor. These receptors are found throughout the body, on the surface of cells in the brain, organs, tissues, and glands. Embedded in cell membranes, endocannabinoid receptors provide different reactions when stimulated by cannabinoids.
There are two cannabinoid receptors discovered by researchers, the CB1 and CB2 receptors. The CB1 receptors are found in the brain and the peripheral nervous system and are the receptors that THC interacts with, producing a high in the user.
CB2 receptors can be found in the immune system and the gastrointestinal system and are responsible for regulating inflammatory responses in the bowels, cardiovascular activity, appetite, mood, memory, and pain. CB2 receptors are a large part of the endocannabinoid system and are also found in the brain.
The role of the CB1 receptor in the human body. First discovered in 1990, the CB1 receptor can be found in the brain, the central nervous system, connective tissue, and other glands. By activating the CB1 receptor with medical marijuana or hemp, the user gets the following benefits:
- Relieved symptoms of depression 
- Increased formation of myelin formation 
- Decreased intestinal permeability (Leaky Gut Syndrome) 
- Lowered blood pressure 
- Reduced GPR55 signaling  
- Reduced anxiety 
- Reduced paranoia 
- Lowered prolactin 
- Increased BDNF levels  
- Increased PPARy expression  
There are some risks included with the activation of the CB1 receptor from an agonist such as THC, including lowered thyroid hormones,  decreased cognitive function,  constipation,  increased anxiety,  and others.
The role of the CB2 receptor in the human body. First discovered in 1993, the CB2 receptor is mostly found in the spleen, tonsils, thymus, and immune cells, with only a small number found in the brain. This receptor plays a role in any type of human disease from cardiovascular and gastrointestinal, to neurodegenerative, psychiatric and even autoimmune. It has a role in regulating liver and kidney function, bone and skin health, and pain. 
The second part of the endocannabinoid system is the endocannabinoid, naturally present in the body. The two primary endocannabinoids are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). THC and CBD are cannabinoids that come from another place, the cannabis plant, and are known as phytocannabinoids.
Anandamide is a high-affinity, partial agonist of the CB1 receptor, and almost inactive at the CB2 receptor. 2-AG acts as a full agonist at both CBRs with moderate-to-low affinity. 
The third part of the endocannabinoid system is the metabolic enzyme. Enzymes destroy the endocannabinoids once used, ensuring the interaction only happens when needed.
As we’ve established so far, CBD is a non-psychoactive component, while THC produces a high. This is one of the main reasons why CBD is the common, main ingredient in many dietary and natural supplements.
CB1 is a G protein-coupled cannabinoid receptor that is activated by the endogenous transmitters anandamide and 2-arachidonoylglycerol. THC is a potential partial agonist of CB1, stimulating the receptor to cause psychotropic effects experienced when consuming marijuana.
CBD is a negative allosteric modulator of CB1, which means that it effectively alters the shape of the receptor.  In addition, CBD’s effect makes it difficult for THC to stimulate the receptor, which is the reason why it doesn’t produce the psychotropic effects associated with THC.
THC and the Endocannabinoid System
How does THC work and why does it produce high
THC produces the euphoric effect of marijuana because it is an agonist or an activator that binds well with CB1 receptors. The CB1 receptors are present in very high levels in the brain and lower amounts throughout the entire body.
Although the exact mechanisms of how the process happens are not entirely clear, it is believed that the CB1 receptor is the critical target in the brain the produces a state of intoxication. To support those claims, a study conducted in people who have had their CB1 receptor blocked by a different antagonist drug, showed no results to cannabis, simply it didn’t get them high. 
Also, during brain imaging, the prefrontal cortex region of the brain showed increased blood flow during THC intoxication.  The prefrontal cortex region in the brain is responsible for attention, decision-making, and executive functions, including motor skills, all affected by THC intoxication to a certain degree. A well-known fact is that cannabis also activates the reward pathway in the human brain, which makes the intoxicated individual feel good and euphoric. 
THC is also known to partially mimic the effects of anandamide, aka the ‘bliss molecule,’ a naturally occurring endocannabinoid. The resemblance to anandamide means that during activation of CB1 receptors, THC helps to produce the blissful feeling experienced when consuming weed.
CBD and the Endocannabinoid System
How does CBD work and why it doesn’t produce high
CBD, on the other hand, does not bind directly to the CB1 or CB2 receptors but works to inhibit the Fatty Acid Amide Hydrolase (FAAH enzyme) that breaks down anandamide, making anandamide available for longer periods of time in the body.
Anandamide is also known as the “bliss molecule,” and for its role in the neural generation of pleasure and motivation. Anandamide also affects the immune system, eating and sleeping patterns, anxiety and nervous thought patterns, as well as pain. 
CBD also activates the Transient Receptor Potential Vanilloid 1 (TRPV1) receptors, involved in regulating pain, body temperature, and inflammation. 
Working as an antagonist of CB1 receptors, CBD suppresses the CB1-activating qualities of THC. So, when working together, CBD goes against the effects of THC, and instead of feeling “high,” the person is less stressed, anxious, and doesn’t experience the common negative feelings, like when taking pure THC.
While THC affects the CB1 receptor, CBD is a negative allosteric modulator of the CB1 receptor. This means that although the CBD molecule is almost identical to the THC molecule, CBD counteracts the effects of THC.  The psychoactive effects are reduced, and person has much lower chances of experiencing paranoia, as when using only THC. 
For example, if combined, CBD and THC work great for treating chronic pain. If THC alleviates the pain, CBD reduces the psychotic effects. They both work towards reducing symptoms of depression, anxiety, arthritis, migraines, and other chronic non-cancer pain. 
Although THC is the main component in marijuana, and alters the mood and perception, it shows strong anti-inflammatory  and analgesic properties,  successfully relieving pain caused by arthritis and cancer. It also helps reduce symptoms and pain in participants with treatment-resistant spasticity in multiple sclerosis. 
In conclusion, choosing between these two components shouldn’t be a question. According to research, both compounds work in synergy and interact with each other in the best way possible, creating a balance in the body. It is important to remember that THC still causes mind alterations and should be consumed under certain circumstances, medical and legal, which brings us to the next point.
Legality of CBD vs. THC in the United States
In the United States, all forms of cannabis are prohibited under federal law, but, are legal for medicinal use in 20 states. In addition, nine states plus Washington, D.C., have legalized the use of marijuana with high levels of THC for recreational purposes.
In the states where marijuana is legal for both medical or recreational purposes, it is possible for a person to buy CBD legally. Some states have passed laws to make CBD for medical purposes legal. It is important to be aware of the state’s laws  before buying CBD products because you might face legal penalties if buying in a state where it isn’t legalized.
In 2014, Uruguay legalized weed for recreational use and become the first country in the world, followed by Canada in 2018. CBD is also a subject to the same Schedule I Drug classification, but it is legal for medicinal use in 46 states, only if it comes from industrial hemp. The industrial hemp must have a THC level below 0.3%.
A progress has been made in the US with the 2014 Farm Bill that semi-legalized hemp production for academic and research purposes.
As of June 25th, 2018, FDA approved the use of an epilepsy medication called Epidolex.  The drug is a CBD oral solution for the treatment of seizures associated with two rare and severe forms of epilepsy, Dravet and Lennox-Gastaut syndrome. Epidiolex is the first FDA approved drug that can be used for children two years of age and older.
Medical Benefits of THC and CBD
Side Effects: CBD vs. THC
It is interesting how the side effects of CBD tend to be minimal to non-existent in people consuming CBD products on a day-to-day basis. Some side effects include dry mouth, low blood pressure, and drowsiness, but nothing serious.
According to research, the side-effects that occur in the body with CBD intake are likely a result of interactions between CBD and other medications the user is taking. 
The problem lays in the inability of the liver to break down most of the pharmaceuticals because of a CBD inhibition.
This makes taking medicine for conditions such as arrhythmia or high blood pressure ineffective, causing complications in the body. And makes a strong reason to talk to your doctor before using a CBD product.
While CBD is known for its mild side effects, THC causes an entire list of temporary side effects, including:
- Reduced cognitive functions
- Slower reaction times
- Coordination problems
- Increased heart rate
- Dry mouth
- Red eyes
- Memory loss
Although nothing fatal, high THC is likely to cause long-term psychiatric effects. According to a 2017 study, cannabis abuse in adolescence is associated with an increased risk of psychotic disorders, like schizophrenia. 
How THC Works for Chronic Pain
As research suggests, THC is likely to help patients with spasticity and cramp-related pain, more effectively than CBD.  High doses of THC should be avoided because they can exacerbate the symptoms. 
THC resembles the two cannabinoid chemicals naturally occurring in the body, so when consumed, it stimulates the cannabinoid receptors of the brain (CB1 and CB2).
The CB2 receptor is associated with lymphoid and immune tissues, serving as an important mediator for surprising pain and inflammatory processes.
Additionally, THC activates the brain’s reward system, stimulating neurons to release dopamine at high levels. 
Also, it interferes with the glutamatergic system which is, “integral to development and maintenance of neuropathic pain, and is responsible for generating secondary and tertiary hyperalgesia in migraine and fibromyalgia via NMDA mechanisms.” 
THC inhibits glutamate release, producing 30%-40% glutamate reduction in NMDA responses. In addition to THC being a neuroprotective antioxidant, it reduces pain sensitivity via calcitonin gene-related peptide.
Also, THC blocks capsaicin-induced hyperalgesia at sub-psychoactive doses in animals. THC also stimulates beta-endorphin production, which prevents development of tolerance to and withdrawal from opiates.
How CBD Works for Chronic Pain
Cannabidiol shares neuroprotective effects with THC, also inhibits glutamate neurotoxicity and displays antioxidant activity greater that vitamin C or vitamin E.
But, “while THC has no activity at vanilloid receptors, CBD, like AEA, is a TRPV1 (vanilloid receptor) agonist that inhibits fatty acid amidohydrolase (FAAH), AEA’s hydrolytic enzyme, and also weakly inhibits AEA reuptake”.
The continuous activation of TRPV1 receptor causes analgesia, which has made this receptor a viable drug target for clinical use in management of pain. 
Together with endorphin and inflammatory, the vanilloid/transient receptor potential are some of the major endogenous pain control systems which also interact with the endocannabinoid system.
This means that CBD is an endocannabinoid modulator, additionally affecting THC’s function and reducing associated intoxication, panic, anxiety, and tachycardia.
Hemp CBD vs. Marijuana CBD
The two most prominent cannabinoids are produced by both marijuana and hemp, with a major difference. Namely, marijuana has a higher concentration of THC, while hemp has a higher concentration of CBD, which makes hemp ideal for CBD oil production.
On average, a marijuana strain contains about 12 percent THC, while the CBD oil may contain small amounts of THC because the component is present in the hemp plant. 
High-CBD Cannabis Strains
Although CBD is the second most abundant cannabinoid in the cannabis plant, a strain may have a higher or lower THC vs. CBD ratio:
- High THC, low CBD (e.g.,10-30% THC, trace amounts of CBD)
- Balanced CBD/THC (e.g., 5-15% THC and CBD)
- High CBD, low THC (e.g., 5-20% CBD, THC under 5%)
High-CBD strains are typically consumed by people who are extremely sensitive to the side effects of THC, such as anxiety, dizziness, and paranoia.
These strains tend to deliver clear-headed functional effects, without the euphoric high, also perfect for people that need to medicate through the day for chronic pain, or inflammation. The hemp oil is extracted from industrial hemp, from cannabis sativa, which primarily consist of CBD and very low amounts of THC.
Some high-CBD strains are:
- Harlequin OG
- Suzzy Q
Balanced CBD/THC strains offer a more euphoric feeling than the CBD dominant, and are much less likely to induce anxiety or paranoia. These strains are effective for pain relief and can be consumed as CBD-infused edibles, oil capsules, lotions, and and tinctures.  On the other hand, high-THC strains are attractive to recreational users.
What is Pure CBD vs. Full Spectrum CBD
As the name suggests, a CBD isolate is pure, isolated CBD compound, existing all by itself without any other active compounds. Contrary to previous beliefs that the pure CBD was the “gold standard” of non-psychoactive cannabis therapy, the discovery of the entourage effect debunked each claim.
The first byproduct that manufacturers get from extracting oils from the hemp plant is a full spectrum CBD hemp oil. After getting the full-spectrum product with 20% actual CBD and 80% other elements, it is broken down until isolating other elements. The end byproduct is CBD isolate, 99% pure cannabidiol.
There are many benefits of CBD isolate, because you are getting a small, but effective dose that provides immediate relief. A CBD isolate can be used topically, orally, can be smoked, vaporized, and dabbed.
A full-spectrum oil contains other active cannabinoids, such as CBN, CBL, and CBCVA, THC, together with aromatic terpenes like limonene and pinene. The limonene can relieve stress and boost mood, while pinene increases alertness and memory.
Most CBD consumers find greater relief in full-spectrum CBD oil, rather than the isolate. One of the most important things in choosing between pure CBD and full spectrum CBD is finding a reliable supplier.
How to Dose CBD vs. THC (and vice versa) for Your Medical Issue
From the studies referred to in this article, it is safe to say that the therapeutic benefits of cannabis can be achieved at a lower dose than the one needed to produce euphoria.
It is important to remember the adage “start low, go slow,” regardless of the administration method used.
For example, the first couple of days, a 2.5 mg of only CBD or THC, once a day is a good start, and then continue to increase the dose itself, as well the number of times it is taken during the day.
A power combination, THC and CBD offer remarkable medicinal attributes. Although there is no single CBD:THC ratio that works universally, a 2.5 mg of CBD mixed with a small amount of THC can have a therapeutic effect.
THC dominant options (0:1) provide high degrees of psychoactivity and a variety of side-effects.
A 1:3 CBD:THC ratio also causes some psychoactivity, but minimizes the unwanted side effects caused by THC.
A 1:1 CBD to THC ratio is considered highly effective for pain relief, fibromyalgia, insomnia, nausea and spasticity.
A 2:1 or 3:1 now CBD vs THC ratio is great for autoimmune disorders, Crohn’s disease, arthritis, ideal for patients that want to avoid THC’s psychoactive effects.
A 2014 Review of Medical Cannabis Studies relating to Chemical Compositions and Dosages for Qualifying Medical Conditions by the Minnesota Department of Health,  summarizes clinical trials and prospective observational studies in humans in the following recommended doses for different diseases:
- Cancer pain: most effective approach is a combination of THC and CBD rather than THC alone. If used doses of THC higher than 25mg during an entire day, substantial number of patients might poorly tolerate the drug.
- Seizures: 200 to 300 mg CBD daily.
- Crohn’s Disease: THC:CBD ratio 1:10 (5 mg THC and 50 mg CBD, twice daily) and CBD only (5 mg CBD in olive oil twice daily).
- Tourette’s Syndrome: THC:CBD ratio of 1:1 (versus 2:1 or 3:1)
- Muscle spasms: average doses of 20 to 25 mg of THC alone or in combination with CBD.
- Glaucoma: 5 mg single dose of THC reduces symptoms for 4 to 5 hours.
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