September 3, 2019

What Is Tetrahydrocannabinol (THC)?

The cannabis plant is may very well be the most famous plant in the world. It’s also commonly referred to as marijuana and it has played an integral role in human culture for millenia. In fact, there is evidence of cannabis/marijuana cultivation in Ancient China dating as far back as 6000 years ago. Over the ages, it’s been used for medicine, religion, and just plain fun.

But when you say the words “cannabis” or “marijuana”, what are you actually referring to? What is the active chemical constituent of this amazing plant? Ladies and gentlemen, allow me to introduce you to tetrahydrocannabinol (THC). This is the chemical compound found in cannabis or marijuna that is responsible for the various effects and benefits of the plant.

What Are Cannabinoids?

So let’s dive right in! The full chemical name of THC is trans-Δ⁹-tetrahydrocannabinol and it has the chemical formula C₂₁H₃₀O₂. It belongs to a group of compounds known as cannabinoids that can be broken down into three primary groups:

  1. Endocannabinoids or endogenous cannabinoids – These are naturally produced in the mammalian body.
  2. Phytocannabinoids – These are extracted from the famous cannabis plant.
  3. Synthetic cannabinoids – These are created in a laboratory.

As an extract of the cannabis plant, tetrahydrocannabinol is a phytocannabinoid. The cannabis plant is complex however, with approximately 483 compounds present in its internal structure. Furthermore, there is ongoing research into identifying its exact number of phytocannabinoids, with recent studies indicating that there are over 120 different cannabinoids. THC is the most widely known phytocannabinoid, followed closely by cannabidiol (CBD). Both have extensive health benefits when used properly, although they do have different effects on users.

Furthermore, for the purposes of this article, the terms “cannabis”, “marijuana”, and “THC” will be used interchangeably.

Sativa and Indica – What’s the Difference?

There are two primary types of cannabis plants, which can be classified as separate strains or subspecies:

  1. Cannabis indica (monotypic classification) or cannabis sativa indica (polytypic classification). The indica variant has short, wide leaves and buds that are dense, bulky, and wide. With lower THC and higher CBD content, its intoxicating effects are commonly referred to as more of a “body buzz” and it is effective for insomnia, pain relief, and anxiety.
  2. Cannabis sativa – The sativa variant has long leaves with thin blades and buds that are long, sausage-shaped flowers. With higher THC and lower CBD content, the anecdotal evidence suggests that it has a more energetic, cerebral, and/or creative intoxicating effect.

Whether indica and sativa are considered to be separate strains or subspecies, both have been used extensively over the years. Furthermore, when people use the words “cannabis” or “marijuana”, they are almost always referring to THC as this is the active constituent that causes the intoxicating effects of cannabis consumption. In other words, THC is the phytocannabinoid that gets you high.

Why Do People Use Tetrahydrocannabinol (THC)?

THC has three primary purposes for consumption:

  1. Entheogen – This refers to the history of cannabis consumption for spiritual or religious purposes. Current research indicates that there has been entheogenic use of cannabis amongst ancient Hindus on the Indian subcontinent dating as far back as 1500 BCE or even 2000 BCE. In Sanskrit, it is known as ganja or ganjika. It has also been used religiously in:
    a. Ancient China
    b. Ancient Central Asia
    c. Africa
    d. Amongst the Germanic peoples and Celts
    e. Modern-day Jamaica (as a holy sacrament in the Rastafari religion/movement).
  2. Recreational use – Cannabis is the most widely used recreational drug in the world by several orders of magnitude. It is officially known as a euphoriant (as opposed to a stimulant or hallucinogen, for example), which just means it makes people feel really good. Luckily, it has few serious side effects and is not highly addictive.
  3. Medicinal use – Various phytocannabinoids found in cannabis (including THC) have a wide variety of health benefits with relatively few side effects. This makes them highly attractive as potential medicines. Medicinal cannabis use in the United States legal began with Proposition 215 in California in the year 1996; voters decided that cannabis should be legal for medicinal purposes in their state. This is widely recognized to be the first step towards widespread legalization and/or decriminalization nationwide.

As tetrahydrocannabinol use has continued throughout history, it has taken on an ever growing place in popular culture. Simply put, it is extremely popular and integral to peoples’ lives. It is also unique. For example, it is the only known psychoactive compound that does not have nitrogen (N) in its chemical formula.

Furthermore, as the most widely researched, consumed, and known member of the cannabinoid class, it has a unique mechanism of action within the human body. Let’s examine why that is.

THC and the Riddle of Cannabinoid Receptors

The human body is complex, with plenty of moving parts and integrated mechanisms. Take a moment and consider just how these different cells, tissues, and organs have to work together efficiently and effectively. How do our bodies govern these differing processes? How do these systems get integrated efficiently? Ladies and gentlemen, I present to you the endocannabinoid system (ECS)!

Understanding the ECS and its role in the human body will help you understand just how tetrahydrocannabinol (THC) works on the human body. Other cannabinoids (like CBD) also exert profound effects on the ECS, but THC has a different mechanism of action.

The ECS is a regulatory system that governs a variety of processes in the human body. It has revolutionized our understanding of human physiology, and, like many scientific advances, its discovery was a happy accident.

For a number of years, THC was the only known cannabinoid. However, a landmark paper in 1988 identified G-protein coupled cannabinoid receptors (GPCR) in the mammalian brain. The presence of these cannabinoid receptors was puzzling to the scientific community. Why would our brains have receptors designed for a compound derived from a plant (in this case, cannabis)?

In 1990, a research team at the National Institute of Health (NIH) cloned the cannabinoid receptor, taking its existence from a hypothetical construct to an actual protein molecule. However, researchers were still pondering why the brain would have these cannabinoid receptors. Was the body anticipating that humans would consume cannabis? Or were there natural compounds in the body that were similar in structure and effect to tetrahydrocannabinol?

We now know that the latter is true. An endocannabinoid known as anandamide was discovered in 1992 by a team of researchers that included the renowned Dr. Mechoulam and Dr. Hanus. They had solved the riddle; our brains have cannabinoid receptors as well as natural compounds that interact with these receptors. This eventually led to the discovery of the ECS and its complex set of interlinked structures.

The Structure and Function of the Endocannabinoid System

The ECS can be broken down into three fundamental components:

  1. Cannabinoid receptors – These are known as (usually referred to as CB1 and CB2 receptors). Though they are spread all over our bodies, CB1 receptors are largely located in the central nervous system (CNS) while CB2 receptors are largely located on immune cells and in the gut.
  2. Endocannabinoids – These cannabinoids are produced within the human body and bind to CB1/CB2 receptors. The two most notable endocannabinoids are N-arachidonoylethanolamine (widely referred to as anandamide or AEA) and 2-arachidonoylglycerol (2-AG for short).
  3. Enzymes – These compounds produce and/or break down both phytocannabinoids and endocannabinoids. AEA is produced by NAPE-PLD and broken down by fatty acid amide hydrolase (FAAH) while 2-AG is broken down by monoacylglycerol lipase (MAGL).

So what does this system do? What’s the big deal? Well, researcher Vincenzo Di Marzo summarized its primary functions as: “relax, eat, sleep, forget, and protect.” This is a useful shortcut for understanding the ECS and distilling its essence down to the most basic concepts. However, to put it in fancier terms, the ECS is responsible for:

  1. Pain and inflammation
  2. Reward and motivation
  3. Appetite, digestion, and metabolism
  4. Proper functioning of the Immune system
  5. Memory and learning
  6. Pleasure and reward
  7. Regulating body temperature
  8. Emotional states and mood

Clearly, the ECS is an important system as those are all crucial functions in our bodies. If it were to break down or cease functioning, your entire body would go absolutely haywire. Imagine as if your body is an advanced supercomputer, then the ECS is kind of like the central processing unit (CPU).

What Does Tetrahydrocannabinol Do

The most noticeable (and desirable) effect of tetrahydrocannabinol is euphoria. This is the feeling of being high and is the result of THC triggering massive increases in the neurotransmitter dopamine within the brain. This is also where THC gets its fun reputation and is the primary reason for its use as a recreational drug. However, tetrahydrocannabinol can also cause the following:

  1. Increase in heart rate
  2. Problems with coordination
  3. Dry mouth
  4. Reaction times that are slowed down
  5. Memory loss
  6. Red eyes

All of this is caused by THC’s interaction with the ECS. How exactly does this happen? By activating the CB1/CB2 receptors. As a quick side note, it’s important to understand that there are two primary ways by which a compound can interact with a receptor:

  1. Agonist – This compound activates the receptor it binds to.
  2. Antagonist – This compound binds to a receptor but does not activate it. It may also block the action of surrounding agonists.

Furthermore, agonists can be further broken down as follows

  1. Partial agonists – These only partially activate a given receptor (as opposed to a full agonist).
  2. Inverse agonists – These are a type of agonist that bind to the same receptors but initiate a physiological response that is the opposite of the other agonists.

Don’t be overwhelmed by all this terminology; it’s important to simply know that THC is a partial agonist to CB1/CB2 receptors.

THC and the Brain

Remember anandamide (AEA) mentioned above? Well, tetrahydrocannabinol most closely mimics this endocannabinoid. This is most prevalent in the central nervous system (CNS). It’s also important to know that CB1 receptors are the primary type of cannabinoid receptors found in the CNS.

THC activates these CB1 receptors and increases AEA levels in the following regions of the brain:

  1. Amygdala – Regulates anxiety, emotions, and fear. THC may trigger paranoia due to its activation of these receptors.
  2. Basal ganglia – Regulates planning and executing motor actions/movements. THC causes severely slowed reaction times due to its interaction with these receptors.
  3. Brain stem – Relays information between the brain and spine as well as controls basic neural functions like breathing. THC has powerful antinausea (antiemetic) effects due to its interactions with these receptors.
  4. Cerebellum – Regulates balance and motor coordination. THC impairs these activities due to its interaction with the cannabinoid receptors.
  5. Hippocampus – Responsible for learning new information and memory formation. THC interacts with these receptors and causes impaired memory.
  6. Hypothalamus – Regulates pleasure and rewards like eating or sexual behavior. THC interacts with these receptors to increase appetite and potentially enhance sexual activity.
  7. Neocortex – Responsible for feeling, complex/abstract thought, and movement. THC interacts with these receptors and alters thought patterns, judgment, decision-making ability, and general sensations.
  8. Nucleus accumbens – Responsible for motivation and reward. Interacting with these receptors is how THC causes euphoria in users; this is the most desirable effect for recreational users.
  9. Spinal cord – Transmitting information between peripheral nervous system (the body) and central nervous system (brain/spine). THC acts as an effective painkiller due to its interactions with these cannabinoid receptors.

This is how THC works and this is why it has such profound effects on perception and consciousness. The key to THC’s appeal is its ability to induce these effects while still being fairly safe and less addictive than other psychoactive compounds.

Is THC Safe?

Researchers and health organizations have repeatedly concluded that THC has a large safety margin. Various studies have calculated the median lethal dose (LD50) to be:

  1. 800 milligrams per kilogram in rats
  2. 3000 milligrams per kilogram in dogs
  3. Up to 9000 milligrams per kilogram in monkeys

Using these metrics and incorporating human data, the lethal dose for a 70 kilogram (154 pound) human has been calculated as 4 grams (4,000 milligrams). That is a huge amount! Realistically, no human could smoke, vaporize, or orally ingest this much THC. Furthermore, the low density of CB1 receptors in the brainstem (remember, this controls breathing) means that THC does not impair respiratory function. For example, this is the mechanism by which opiates cause overdoses in humans. As a result, there is a marked absence in mortality with THC use.

Is THC Addictive?

THC is widely considered to be a “soft drug”. This means that it is not as dangerous or addictive as so-called “hard drugs”. This is based on a plethora of studies as well as millennia of anecdotal evidence (remember that cannabis use has been traced back over thousands of years). Shockingly enough, however, the Drug Enforcement Agency (DEA) has categorized THC as Schedule 1, meaning that it has no medicinal use and a high level of abuse potential. That means that THC/cannabis/marijuana is in the same category as:

  1. Heroin
  2. Lysergic acid diethylamide (LSD)
  3. 3,4-methylenedioxymethamphetamine (ecstasy)
  4. Methaqualone
  5. Peyote

Remember that cocaine and methamphetamine are not included as they are considered to be Schedule 2, meaning they have medicinal use in certain situations. Still, the idea of classifying THC with heroin is absurd! It just shows how antiquated and out of touch the DEA is in regards to cannabis use.

That is not to say that tetrahydrocannabinol does not have some unfortunate drawbacks. In fact, according to recent research, approximately 30% of cannabis users may display some degree of dependence on the substance. If you want to put it in fancy terms, this is known as marijuana use disorder. Furthermore, data also suggests that people who begin using cannabis before the age of 18 are four to seven times more likely to develop marijuana use disorder when compared to adult users.

It’s also important to differentiate between dependence and full-blown addiction. With marijuana use disorder, dependence occurs when the user exhibits withdrawal symptoms that may include:

  1. Irritability
  2. Cravings
  3. Restlessness
  4. Mood swings
  5. Insomnia
  6. Decreased appetite
  7. Overall physical discomfort

These symptoms usually hit their peak within the first week of quitting and may last up to 2 weeks.

Marijuana use disorder turns into full-blown addiction when the user cannot stop using the drug even if interferes with various aspects of their life. There is no definitive figure on the number of people addicted to marijuana (this is partially because many studies fail to differentiate between dependence and addiction – it is possible to be dependent but not addicted). However, various studies indicate that:

  1. Approximately 9% of cannabis users will become dependent on it.
  2. This figure rises to 17% if they started using in their teens.
  3. As of 2015, approximately 4.0 million Americans met the diagnostic criteria for marijuana use disorder.

Despite this, marijuana use disorder can be effectively treated. It is also not considered to be as serious as other substance abuse disorders.

What Is the Legal Status of THC?

This is a simple question with a complex answer. First, let’s take a look at something that astronomer Carl Sagan once wrote: “The illegality of cannabis is outrageous, an impediment to full utilization of a drug which helps produce the serenity and insight, sensitivity and fellowship so desperately needed in this increasingly mad and dangerous world.” Those are some strong words, but given the utter inefficiency and horrific damage caused by the War on Drugs, we can all see where Dr. Sagan is coming from. Most experts agree that the United States is moving towards full legalization in all 50 states and territories. Until this happens, however, the laws vary on a state-by-state basis.

Remember, the term “THC” is virtually synonymous with “marijuana” or “cannabis” and these terms are used interchangeably in this article. For the entire duration of the federal government’s ban on cannabis products, they were targeting THC to the exclusion of any other cannabinoids present in the plant. This is because tetrahydrocannabinol is the active constituent that causes intoxication and euphoria. In other words, THC is the fun cannabinoid!

Currently, cannabis/marijuana/THC is illegal under federal laws. However, there is a growing movement of legalizing or decriminalizing the substance throughout the United States. What that means, though, is that marijuana levels are kind of a mess. This is because it is determined on a state-by-state basis, and each state can have different exemptions or legislative details.

As of August 2019, the following states allow recreational marijuana use:

  1. Washington
  2. Oregon
  3. California
  4. Nevada
  5. Colorado
  6. Michigan
  7. Vermont
  8. Massachusetts
  9. Maine
  10. District of Columbia
  11. Alaska

Furthermore, some states allow for medicinal marijuana use. These include all the states with recreational laws on the books as well as:

  1. Hawaii
  2. Montana
  3. Utah
  4. Arizona
  5. New Mexico
  6. Texas (only for CBD oil)
  7. Oklahoma
  8. North Dakota
  9. Minnesota
  10. Iowa (only for CBD oil)
  11. Missouri
  12. Arkansas
  13. Louisiana
  14. Illinois (recreational is decriminalized)
  15. Indiana (only for CBD oil)
  16. Ohio
  17. Florida
  18. Georgia (only for CBD oil)
  19. Virginia (only for CBD oil)
  20. West Virginia
  21. Maryland
  22. Pennsylvania
  23. Delaware
  24. New Jersey
  25. New York (recreational is decriminalized)
  26. Connecticut
  27. Rhode Island
  28. New Hampshire
  29. Tennessee
  30. Mississippi
  31. Alabama (only for CBD oil)
  32. Kentucky (only for CBD oil)
  33. South Carolina
  34. North Carolina
  35. Wisconsin (only for CBD oil)
  36. Kansas (only for CBD oil)

Finally, we arrive at the states in which THC/marijuana is fully illegal:

  1. Idaho
  2. Wyoming
  3. South Dakota
  4. Nebraska (although the first offense has been decriminalized)

Generally, the most liberal parts of the country (West Coast and New England) have the highest percentage of highly decriminalized or entirely legal state laws. As you move towards the more conservative areas (Midwest and South), then the laws generally become stricter. However, it’s important to remember that there is still a great deal of variation from state to state; although recreational use may be illegal in some states, it may also be highly decriminalized and treated as nothing more than a misdemeanor. Ultimately, it’s best to do your research before traveling somewhere to ensure that you are operating within the bounds of the law.

Furthermore, federal laws around hemp/CBD has changed. In 2018, Congress passed a bipartisan piece of legislation called the Farm Bill. This bill effectively differentiates between hemp (low or no THC content) and marijuana (THC is present in significant concentrations). Furthermore, the Farm Bill allows farmers to grow hemp plants as well as sell hemp-derived products. Hemp or hemp-derived products are explicitly defined as cannabis plants with less than 0.3% THC; if they maintain this level of tetrahydrocannabinol concentration, then they are fully excluded from the Controlled Substances Act (CSA). It also requires farmers to adhere to a permitting and licensing process.

In other words, the DEA has codified the two primary cannabinoids in cannabis as follows:

  1. THC – Schedule 1. This means that the DEA considers THC to be a highly addictive drug with no medicinal benefits.
  2. CBD – Schedule 5. This means that the DEA considers CBD to not be habit-forming and that it has extensive medicinal benefits as well as fewer restrictions on research and development.

As anyone can see, this is just ridiculous. Treating THC as a highly dangerous and addictive drug is just plain inaccurate. However, it appears as if widespread decriminalization or even outright legalization is imminent. Of course, once this occurs on the federal level, then any and all cannabis products, regardless of THC content, will be legal everywhere in the United States.  

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