Is Cannabis Legal? The History of Cannabis in the United States

Is Cannabis Legal? The History of Cannabis in the United States

It is believed that the Cannabis plant first originated thousands of years ago, at the Himalayan foothills in Central Asia (2). Archaeological evidence suggests that cannabis plants were used approximately 10,000 years ago in Taiwan to make rope and clothing (3). Consuming cannabis also dates back to ancient times. Chinese emperors brewed cannabis tea, Hindus drank warm spiced milk with “gunjah”, and Nomadic tribes in Morocco ate hash jam (5). Cannabis plants are believed to have been cultivated in India for medicinal purposes as early as 900 BC. Hindus offered cannabis to deities during religious ceremonies, and the plant continues to have religious associations in India (6). Cannabis was used globally for thousands of years before laws began to regulate it. The first recorded regulation of cannabis was in 1378. Soudoun Sheikouni, the Emir of the Joneima in Arabia, ordered all cannabis plants to be destroyed and enforced harsh punishment on those who disobeyed. Consumption did not dwindle, but instead began to increase over time (7). Many other cannabis restrictions continued globally throughout the following centuries.


1600s – 1900s


In 1619, King James I announced that American colonists in Jamestown needed to increase their support of England. Therefore, the Virginia Assembly passed legislation saying that all landowners were required to grow and export 100 hemp plants. After this, colonists continued to grow hemp to support America, and hemp was allowed to be exchanged as legal tender in Virginia, Pennsylvania, and Maryland. Cannabis crops were actually a big part of the establishment of the United States. Hemp had many industrial applications such as rope and fabric for clothing and ship sails, and it was one of George Washington’s primary crops. Hemp growth for these purposes continued strongly in the U.S. during the 18th and 19th centuries, and it was sold in public pharmacies as a medicinal ingredient in the mid to late 19th century (9, 10).


1900s – 1930s


In the late 19th century, pharmaceutical regulations began to appear. This legislation came at the state level, issuing penalties for mislabeled or altered drugs. One of these regulations was “poison” laws, which deemed certain ingredients such as cannabis to be harmful, and required labeling of the word “poison” or obtaining a prescription to purchase these medicines. This began the regulation of cannabis in the United States. In a 1905 USDA bulletin, eight states are mentioned as having poison laws for cannabis (11).

The first regulation on cannabis from the United States Congress was the Pure Food and Drug Act of 1906, which required pharmaceutical drugs that contained cannabis to be accurately labeled (9). As time went on, restrictions on cannabis began to increase, and it was labeled as not only a poison but a habit forming drug.

After the 1910 Mexican Revolution, Mexican immigrants began coming to the United States. During this time, many Mexicans would smoke cannabis after a long day of working in the fields (12), and this introduced the recreational use of cannabis to American culture. Unfortunately, cannabis became associated with American’s fear of and prejudice towards these Spanish speaking newcomers. Campaigns sprung up that were anti-cannabis and anti-Mexican, creating a negative stereotype (9). By 1920, individual state laws were beginning to prohibit the sale of cannabis completely.

After creating the first international drug control treaty in 1912, countries met in Geneva in 1925 to revise the International Opium Convention. The goal of the meeting was to discuss restrictions on opium, morphine, and cocaine. Although hemp was not originally on the agenda, the Egyptian delegate proposed that hemp should be considered as dangerous as opium, and some countries including the U.S. agreed. The Egyptian delegate cited instances of cannabis use leading to insanity, but these statistics turned out to be greatly exaggerated. Other countries did not necessarily agree but they did not possess the information or experience with cannabis to disagree, so no one objected strongly. A recommendation was made to outlaw cannabis wholly, but a compromise was found. The exportation of Indian hemp was banned to countries where it was outlawed, and countries that allowed it received stricter regulations. Importing countries would need to have a license approving the import of hemp and confirm that it was for medical use only (18, 19, 20).




The 1930s were a significant turning point towards outlawing cannabis completely. The Federal Bureau of Narcotics (FBN) was established in 1930, led by commissioner Harry J. Anslinger. Anslinger took a very strong stance against recreational drugs, and claimed that cannabis caused people to act extremely violent, sexual, and irrational (13).

During the Great Depression, high unemployment rates refueled American’s fear and resentment of Mexican immigrants. Since cannabis was already associated with Mexicans, this increased regulations. Research at the time linked cannabis to crimes committed by minorities. By 1931, 29 states had outlawed cannabis completely. This put pressure on the federal government to take action, who decided not to create federal legislation. Instead, the Federal Bureau of Narcotics pushed for state governments to accept responsibility of the problem by finalizing the Uniform State Narcotic Act in 1932 (9).

This Uniform State Narcotic Act was created by The National Conference of Commissioners on Uniform State Laws and had gone through several drafts in the late 1920s. It declared that the federal government should require all states to follow the same restrictions, building upon the 1914 Harrison Narcotics Act which introduced regulations on all opiates and coca imports (24). While the goal was to make uniform drug laws, it was still left up to the states whether or not they would consider cannabis to be a narcotic and apply the same regulations (22).

Some argued that these drug regulation acts were just trying to raise revenue, because they focused on collecting taxes. This was addressed within congress during the passing of the act, and the representative who introduced it rebutted. He argued that it’s impossible for that to be the case, because the acts prohibit the importation of opium, which is something that brought the U.S. a lot of revenue. He argued that the goal was strictly to regulate the use of opium in the U.S. for health and safety concerns (23).

In 1936, the propaganda film Reefer Madness was created, helping to fuel the hysteria that surrounded cannabis. The film wasn’t produced by the government, but by a church called “Tell Your Children” who originally titled it the same name. The church paid French director Louis Gasnier to create the film, but it was never released by him. Instead, it was purchased by a man named Dwain Esper, who recut the film with some additional scandalous shots and released it. The film tells a tale of horrible cannabis-fueled events such as murder, a hit-and-run, suicide, attempted rape, and descents into madness. The film was well viewed all the way through the 1950’s, and was rediscovered in the 1970’s when cannabis legislation was being debated again (25, 26).

Also in 1936, the Trafficking Convention concluded in Geneva, during which Harry Anslinger tried to push total criminalization of all activities related to opium, coca, and cannabis. Other countries opposed this, wanting to only criminalize illicit trafficking of drugs. The U.S. refused to sign the treaty because Anslinger felt the regulations were too weak (27). 

In 1937, Congress passed the Marihuana Tax Act, enforcing a federal excise tax on hemp growth and sales, effectively making cannabis illegal. The tax was $1-$24 per year for any person involved with cannabis, whether it was the grower, importer, buyer, or the doctor prescribing it. Doctors also had to provide detailed sales logs, including their patient’s information. Not only would this annual tax be up to $637 today after adjusting for inflation, but the penalties for selling to someone who had not paid the tax included a fee of over $2000, adjusted for inflation, and five years of jail time (14).

The use of recreational cannabis did not decrease, so Anslinger started running campaigns against it. William Randolph Hearst owned a newspaper empire at the time and contributed to demonizing cannabis and encouraging the connection between cannabis and violence. Hearst had also helped Anslinger get the Uniform State Narcotic Act passed in 1934 by endorsing it in his newspapers (21). It is theorized that the Marihuana Tax Act was created not only due to misconceptions about cannabis versus hemp, poorly attended hearings, and unreliable research, but also because certain politicians stood to profit off the decrease in hemp production. Some scholars believe that since Hearst and other prominent men had invested in nylon and other replacements for hemp, this was motivation to outlaw hemp. Other scholars, however, disagree with this theory (15).


1940s – 1960s


Hemp began to make a comeback during World War II. Before the war, the U.S. navy had been using hemp from other countries to make rope and other materials for their ships, but the supply lines were cut off when the Philippines fell to Japanese forces in 1942. This forced the U.S. to enact a program to ask local farmers to grow hemp again, and the U.S. Department of Agriculture lifted the hemp tax for these growers. A film was created called Hemp For Victory, which encouraged farmers to grow hemp for the war. Hemp production increased rapidly, with millions of acres being grown until the war ended. After the war, the hemp tax was reinstated and the film was hidden (28). In the 1950s, regulations and punishments got even more strict. The Boggs Act of 1952 and the Narcotics Control Act of 1956 introduced mandatory sentencing and increased punishments for cannabis. First-time cannabis possession was punished with a minimum of two to ten years in jail and a fine up to $20,000 (9).

The 1960s brought a change in political and cultural climate. America began to have more lenient attitudes towards cannabis, and it began to be used by the white upper middle class. Presidents Kennedy and Johnson commissioned reports which found that cannabis use did not lead to violence and was not a gateway for harder drugs. Because of this, politicians began to consider changes in cannabis policy.


1970s – 1980s


In 1969, a U.S. Supreme Court case decided that the Marihuana Tax Act was unconstitutional because it violated the fifth amendment right of self-incrimination (16). Therefore, Congress repealed the act and in its place passed the Controlled Substances Act in 1970. Cannabis was still illegal under this legislation, however it repealed mandatory sentencing and reduced crimes from a felony to a misdemeanor (17). Part of this act established five classifications of drugs to categorize all legal and illegal drugs. Cannabis was categorized as a schedule I drug, meaning it has no medical use. Schedule I drugs also have a tendency to be abused, and users are more likely to establish psychological and physical dependencies (29). The Controlled Substances Act grouped all types of cannabis together even though hemp can’t be used as a drug, since the differences were still not understood. This meant that cannabis was outlawed completely, even for medical use. In 1973, a few bureaus merged to form the Drug Enforcement Administration (30).

During the Reagan Administration, the Comprehensive Crime Control Act of 1984 and the Anti-Drug Abuse Act of 1986 reinstated mandatory sentencing. It was decided that mandatory prison sentences would be administered, such as 25 years for repeated drug crimes and even potential death penalty for criminals running large scale drug operations (9, 31).


1990s – 2000s


Arguably one of the most famous people in the history of cannabis is “Mary Jane” or “Brownie Mary” as many called her. Mary Jane Rathbun was a waitress in San Francisco who became famous for selling pot brownies (8). Mary ran an illegal kitchen out of her house in the 1980s and 90s to provide pot brownies to her friends who had AIDS. She became very politically involved in the fight for legalization, and was arrested a few times (5). Despite the arrests, Brownie Mary continued baking, motivated by the fact that the pot brownies helped decrease nausea and low appetites suffered by AIDS and cancer patients (8). Brownie Mary became a leader of the medical cannabis movement, helping pave the way for new laws. In 1991, Mary successfully campaigned to help pass Prop P in San Francisco, which asked California to restore cannabis to a list of available medications. She opened the first medical dispensary with a friend and sold the brownies to anyone who was sick. She also helped fight for Proposition 215, the Compassionate Use Act, which passed in 1996 (5). This law gave critical patients in California, including those with cancer, AIDS, arthritis, and chronic pain, the right to obtain and use cannabis medically if recommended by a physician (8).

After California passed Proposition 215, other states began to legalize medical cannabis in the late 1990s and early 2000s. In 2012, Colorado and Washington became the first two states to legalize recreational cannabis. Currently, in some states it is still considered completely illegal, in some it is completely legal, and others fall somewhere in between with decriminalization and/or legal medical use. Cannabis is still federally regulated (32).

u.s. legal cannabis

There are many arguments for why cannabis should be legalized on a federal level. Some argue that if cannabis is legalized for recreational use, it would reduce violence. Other reasons in support of legalization include that a legal market would eliminate a black market, and ensure safer cannabis. Being one the largest agricultural crops would certainly provide an economic boost in various facets and create jobs. It would also save law enforcement time and money, allowing them to focus on more important legal issues in the United States.





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What is CBD Oil and How is it Made?

What is CBD Oil and How is it Made?

Whether one is already a CBD user or a potential user, the question may arise – how is CBD oil made? What exactly is CBD oil and what is it used for? Before addressing those questions, it is important to understand the different terms related to cannabis.

The term cannabis refers to a genus of plants within the Cannabaceae family, consisting of three primary species: Cannabis sativa, Cannabis indica, and Cannabis ruderalis (1).


Cannabis Plant

There are two main categories of cannabis plants. Hemp plants are categorized as those containing less than 0.3% of the cannabinoid THC, whereas other varieties contain more.

Hemp plants are incredibly easy to grow, and it is believed that hemp was the first crop ever cultivated by humans (1). Hemp fibers have been used for centuries to make a large variety of things, from sails for ships, to rope, to clothing and concrete. Hemp flower, hemp seeds, stalks, and leaves are all parts of the hemp plant that get used (18). The hemp seed is used for many foods and nutritional benefits (2, 18).

Other varieties of cannabis contain more than 0.3% THC (1), sometimes up to 30% (2). These plants are much harder to grow than hemp, and require strict conditions and maintenance. They have also been utilized for centuries for their psychoactive properties and medicinal benefits (31, 32).



Cannabinoids are specialized compounds produced by cannabis plants (9).

Named after them, endocannabinoids are similar compounds that are produced by the human body. Endocannabinoids are part of a complex system located throughout the body, but they essentially work to maintain internal health by facilitating communication between cells. When cannabis is consumed, cannabinoids bind to receptor sites in the body and brain, with different cannabinoids providing different effects (26).

Cannabis plants produce hundreds of cannabinoids, over one hundred of which have been identified (14, 21). When the cannabis plant is still in the ground, it produces what are called acid cannabinoids. The cannabinoids that are most abundant are THC (tetrahydrocannabinol) and CBD (cannabidiol), but in their original forms they are THCA and CBDA, with the “a” standing for acid (9). When heat is applied to these cannabinoids, a process known as decarboxylation, the chemical structure changes and they become the THC and CBD that are familiar to users (9).



CBD can be extracted from any cannabis flower, and is exactly the same molecularly from either type of plant (1, 2, 23). Only small quantities of THC are found in hemp. Both CBD and THC are cannabinoids, but have different properties and effects. THC causes psychoactive effects, or the feeling of being “high”, while CBD does not.

Like all cannabinoids, THC and CBD interact with the body’s endocannabinoid system. These two cannabinoids actually have the exact same molecular structure, but due to the way the atoms are arranged, they cause different effects (25). THC binds with the CB1 or cannabinoid 1 receptor in the brain, whereas CBD does not. CBD can actually interfere with the binding of THC, which decreases the psychoactive effects (25).

Terpenes are similar to cannabinoids in that they are chemicals produced by cannabis plants and there are many different kinds (27). Terpenes are aromatic oils that are secreted from the cannabis plant, as well as many other plants. Terpenes give different strains of cannabis particular aromas, which also causes different looks and flavors (15). It is thought that terpenes may play a role in the entourage effect by interacting with cannabinoids to cause a variety of different effects (27).

The entourage effect is the term for the anecdotal reaction that different combinations of cannabinoids produce different effects, and that CBD may have more successful effects when combined with THC (11). In addition, it has been reported that CBD may help combat negative psychological effects from THC (22).


How to Make CBD oil

cbd oil

There are a few ways to extract CBD from the cannabis plant.


The most popular method is using CO2, in which carbon dioxide is used to extract CBD oil from the plant. The specific type of CO2 used is called supercritical CO2, which means that it can function as both a liquid and a gas (29). Two pressurized chambers are used for the process, one containing CO2 and the other containing the plant (28). The CO2 is pumped from its chamber into the plant chamber, where it turns into liquid due to the pressure (29). The CO2 extraction method uses high pressure and extremely low temperatures which is the best environment to isolate and preserve the purity of CBD oil (30, 24). In the chamber, the liquid CO2 breaks down the plant and causes the oil to separate, absorbing it (16, 29). Then the CO2 containing CBD is pumped into a third chamber, where it turns into a gas state and leaves behind the oil (29). The CO2 extracts with 90% efficiency, creating a high concentration of CBD from this method (24). This process requires the proper machinery, which is very expensive, but is the preferred extraction method for CBD oil. It is safe, efficient, and free of bad-tasting chlorophyll (30). This process also allows for creating oil with varying amounts of CBD concentration (16). 


Solvent extraction is another method and has many risks, but has some benefits as well. This process can be achieved through either hydrocarbon extraction or by using a natural solvent like ethanol. The hydrocarbon method involves solvents such as butane, propane or petroleum (16). The benefit of this method is that it is incredibly effective at separating the wanted materials like cannabinoids and terpenes from unwanted materials like chlorophyll. This process creates wax or potent cannabis concentrates called shatter, which look like brittle candy. These products are consumed through inhalation with a dab rig or vaporizer (30). The major risk with this method is that if the toxic solvents are not completely evaporated from the CBD extract, traces could remain in the resulting products, which has occurred (16). Hydrocarbons are also highly flammable, so not only are they harmful to consume, but have been known to explode during the manufacturing process (30).


Ethanol is a good solvent option, because it is a high grain alcohol and safe for consumption. One benefit of using ethanol is that it can create very concentrated and potent CBD oil. The cannabis flower is soaked in ethanal and strained, which produces an oil that is then heated. The result is a highly concentrated goo texture, just like with hydrocarbon solvents. When using ethanol, there is a risk of also extracting chlorophyll, which gives the resulting product a bad taste (16).


Steam distillation is a method that uses steam to separate CBD oil from the plant. The steam actually extracts CBD vapors, which float up and are captured in a vessel where they are condensed into oil and water. Then the liquid is distilled, and the CBD oil is extracted from the water. This method works well, but is more difficult, less efficient, and requires more plants. There is also a risk of the hot steam damaging or altering the cannabinoids (16).


One of the oldest methods, which is also used for making THC edibles, is oil infusion. In this process, the cannabis flower is decarboxylated by heating it at a particular temperature for a particular length of time. This changes the acid form of CBDA into CBD, which is the desired form of the cannabinoid. Then the plant is infused into a carrier oil like olive oil or hemp seed oil. The downside is that carrier oils do not evaporate, so the end product has a big oil to CBD ratio (29).

If a cannabis plant with THC is being used for the extraction, a full spectrum CBD oil will be produced, meaning it contains all of the cannabinoids including THC. If wishing to create broad spectrum CBD, which does not contain THC, a hemp plant should be used for extraction. Some users prefer full spectrum CBD due to the entourage effect, while others prefer broad spectrum, since THC is not legal everywhere and not every user wants psychoactive effects.


Winterization is the process used to create CBD isolate (29). This method is used to further purify the oil after its extracted and remove unwanted materials (24). The extract is combined with 200 proof alcohol and frozen overnight. The next day, the mixture is run through a filter to remove extra fats. It then gets boiled until the alcohol evaporates, which is effective because the alcohol has a lower boiling point than the oil (29, 24). You can also repeat this process and continue to boil off different compounds at various boiling points to further refine the oil (29). The resulting product is a flavorless, odorless powder containing only CBD (16). Many users report that CBD isolates are not as effective as oil, due to the lack of other cannabinoids and terpenes needed for the entourage effect (24).



How to Consume CBD oil

sublingual cbd oil

CBD oil is consumed sublingually, meaning under the tongue. Using a dropper allows for a fairly precise dose, and also allows for experimentation with dosage.

CBD tinctures are similar to CBD oils but differ in ingredients. The major difference is that tinctures by definition contain alcohol. To create tinctures, cannabis is soaked in alcohol or watered down alcohol, which breaks it down and extracts the CBD. Tinctures also contain more ingredients than just CBD. These additions could be vitamins, herbs, or essential oils (12). Not all tinctures are the same, but they must either contain alcohol or additional ingredients to be classified as tinctures. There are also products sold called CBD oil tinctures, which usually contain a carrier oil and no alcohol, but do contain additional ingredients. Tinctures and oil tinctures often have a better flavor due to the extra ingredients added (12), but because of the alcohol content, not every consumer will want to or be able to consume tinctures. CBD oil can be purchased in its natural flavor, but also in a variety of other flavors. Natural additives like flavorful essential oils can be added for a more pleasing taste.

Both CBD oil and tinctures are consumed sublingually or can be added to foods and beverages. 


Why CBD oil instead of other consumption methods?

There are many other types of CBD products available for purchase and consumption. In addition to CBD oil, CBD can be consumed in the form of flower for smoking, concentrated oil for vaping, topical creams, edibles, and oral sprays. There are some benefits of consuming CBD in the form of CBD oil.

Consuming CBD sublingually provides more bioavailability than edibles, and the effects are fast acting (17). Bioavailability refers to how potent a drug or ingredient is by the time it reaches the treatment site (20). CBD oil takes around 30-90 minutes for effects to kick in, and tends to last for at least four hours (19).

Consuming CBD in oil form has far reduced health risks compared to smoking or vaping. Unlike those methods, CBD oil does not damage the lungs, and no studies have yet to show health effects from consuming CBD oil. It is also easy to carry around a CBD oil bottle and consume it on the go.


Health benefits of CBD oil

There is plenty of anecdotal evidence regarding successful use of CBD to treat health problems (3). CBD research has been minimal in the past, but recently some studies have emerged that show successful results. CBD may be useful in treating pain (7), psychosis (5), and anxiety (4). There is also now an FDA approved CBD medication, which is prescribed for treating extreme cases of epilepsy (6).

The only reported side effects of CBD have been changes in appetite, changes in weight, drowsiness, diarrhea, and mood change (13). In addition, it is important to keep in mind that certain combinations of medications should not be consumed, so users should check with a doctor before taking CBD with other medicine. 




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The Endocannabinoid System

The Endocannabinoid System

The endocannabinoid system is an intricate and complicated biological system that is found in all vertebrate species (8). It was discovered in the late 1980s to early 1990s when researchers were trying to understand the effects of cannabis on humans. They realized that the body produces its own cannabinoids, which is why they earned the name endogenous cannabinoids, or endocannabinoids (5, 11). Many functions of the endocannabinoid system are still unknown. What scientists do know is that the main role of this system appears to be maintaining homeostasis, which is the stability of our internal environment. When external factors disrupt the body’s status quo, such as temperature or blood sugar levels, the body needs to internally coordinate to keep everything balanced and functioning (1). The endocannabinoid system sends messages throughout the body to help regulate functions such as sleep, appetite, stress, memory, and mood (9). This complex system consists of three main components: endocannabinoids, receptors, and metabolic enzymes (8).


Endocannabinoids are molecules produced by cells in the body. The two major endocannabinoids are Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG). AEA is a fatty acid neurotransmitter that is also referred to as the bliss molecule, named after the Sanskrit word ‘ananda’ which means ‘bliss.’ This is because it has mood enhancing properties, in addition to helping regulate inflammation and neuron signaling (5). AEA contributes to homeostasis by binding to receptors and encouraging the development of nerve cells in the brain. The development of these new cells is called neurogenesis, and aids learning and memory.

Studies have shown that high levels of AEA cause enhanced mood and reduced fear. High levels of AEA have also been found in people right after completing vigorous exercise, which could explain the ‘endorphin high’ that many athletes experience. Additional research shows that AEA plays a role in ovulation and embryo development. It seems that increased AEA is beneficial for becoming pregnant, and changes in these levels during pregnancy can affect fetal development (5, 8).

2-AG is a compound that is found primarily in the central nervous system. It is the most prevalent endocannabinoid in the human body, and appears to play a bigger role in endocannabinoid signaling than AEA (7). Because of its appearance in immune cells, it is believed to play a role in anti-inflammation through immune suppression (10). It can also be found in maternal milk of humans and cows (8).

Endocannabinoids bind to cannabinoid receptors found throughout the body to signal that help is needed in a particular area (9). Unlike other molecules, they are produced on demand when needed, so the body only creates as much as is required. This differs from classic neurotransmitters which are synthesized in advance and stored until needed (11). 



Cannabinoid receptors are G protein-coupled receptors (GPCRs). These are proteins found on the surface of cells, in the membrane, and listen to what’s happening in the body. When they detect an issue, they send important information to a molecule in the cell called a G protein, so that the cell can respond accordingly (8). One example of a GPCR is rhodopsin, which responds to light signals detected by rod cells in the eye. The cell will provide an appropriate response to the situation, such as adjusting vision due to dim lighting (12). Cannabinoid receptors are actually one of the most abundant GPCRs (11).

GPCRs are directly involved in human diseases, and therefore, are also the target of many pharmaceutical drugs used to treat those diseases. Because of their role in cell communication, mutations in GPCRs can cause diseases such as retinitis pigmentosa, hypo and hyperthyroidism, nephrogenic diabetes insipidus, and some fertility disorders. Research has found that more than 30 human diseases are caused by GPCR mutations (15). To treat these diseases, many drugs are used that block specific GPCRs. For example, clozapine and olanzapine, which are used to treat psychosis, work by blocking the GPCRs that bind dopamine or serotonin. This interrupts the neural pathways that cause symptoms of schizophrenia. Additionally, some drugs work the opposite way by stimulating GPCR activity. For example, Albuterol activates beta-adrenergic GPCRs, causing airway openings in the lungs to treat asthma (12).

The two main cannabinoid receptors are Cannabinoid receptor type 1 (CB1) and Cannabinoid receptor type 2 (CB2). CB1 receptors are found throughout the central nervous system, with many found inside the brain in areas like the cerebellum, hippocampus, and basal ganglia. They also exist in organs such as the heart, lungs, uterus, and prostate (16). CB2 receptors are located mostly in the immune system. This location coupled with research studies suggests that CB2 receptors have potential therapeutic applications for treating inflammation and allergies (16). 

Endocannabinoids bind to these cannabinoid receptors and activate them (8). The effects of this binding is dependent on the endocannabinoid type, the receptor type, and where the receptor is located in the body. Additionally, the efficacy differs between the two endocannabinoids. 2-AG binds well to both CB1 and CB2 receptors, while AEA has low affinity for CB1 receptors and even lower for CB2 receptors (6, 16).


cannabinoid receptors


Metabolic Enzymes

The third component of the endocannabinoid system is enzymes. The role of these enzymes is to quickly destroy endocannabinoids once they are done with their task (10). The two main enzymes involved are called FAAH (fatty acid amide hydrolase) and MAGL (monoacylglycerol lipase). FAAH breaks down AEA, while MAGL and FAAH both break down 2-AG (17). Their job is to make sure that the endocannabinoids get used when they are needed, but not for any longer. This quick destruction is a unique process that does not occur with other molecules in the body. Because cannabinoids are quickly synthesized and destroyed, fewer long-term side effects are created (10).


More on the Endocannabinoid System

The endocannabinoid system seems to only engage when it’s needed to obtain homeostasis, and not otherwise. Research so far has shown that this system regulates various central neural activities (3) like brain firing (8), inflammation (1), anxiety, depression (3), digestion, metabolism, chronic pain, mood, memory, liver function, and much more (9).

Inflammation in particular has been studied as it relates to the endocannabinoid system. The immune system responds to physical damage or infection with inflammation, by sending cells to the affected area to remove damaged tissue or germs. Some diseases involve chronic inflammation, or autoimmunity which is when the cells cause inflammation in the wrong part of the body. Research shows that endocannabinoids appear to be produced by the immune system response, and help aid with anti-inflammation. Therefore, manipulating the levels of endocannabinoid production may be useful in the treatment of inflammatory diseases (8).

Every human possesses a different “endocannabinoid tone”, which essentially refers to how well the endocannabinoid system is working. Some researchers believe in a theory called CECD, or clinical endocannabinoid deficiency. This theory states that dysfunctional endocannabinoid systems or low endocannabinoid tones may contribute to conditions like migraines or IBS (9). Initial research has found evidence of different AEA levels in patients with migraines, as well as evidence of endocannabinoid system dysfunction in patients with PTSD. Additionally, cannabinoids have been found to help treat some of the associated symptoms (14).


What does this have to do with Cannabis?


Cannabinoids are the same thing as endocannabinoids, but are produced by cannabis plants as opposed to the body. When cannabis is consumed, the cannabinoids bind to receptors in the brain and body just like endocannabinoids, which is why effects from cannabis occur (9).

THC is the cannabinoid that has psychoactive effects, causing a ‘high’ feeling when consumed. THC activates the CB1 receptors in the brain, causing the brain to produce a sensation of being ‘high’ (8). Although endocannabinoids also bind with the CB1 receptor, psychoactive effects are not produced by endocannabinoids. This is because they don’t interact with CB1 receptors in the same way as THC, but also because the metabolic enzymes don’t quickly break down THC like they do with endocannabinoids, so THC lingers (8). In addition to being used recreationally, studies have found THC to help mitigate symptoms of various illnesses such as anorexia and vomiting caused by chemotherapy treatment (3).

CBD is the other popular cannabinoid found in cannabis. Unlike THC, CBD does not cause psychoactive effects when consumed. Initial research does show that CBD may aid with some health issues, which is why it’s being studied and consumed. CBD doesn’t appear to activate CB1 or CB2, but instead interacts with other unknown receptors (3, 9). It is also unique in that it affects overall levels of endocannabinoids in the brain, or the endocannabinoid tone (8). Research shows that CBD inhibits the FAAH enzyme which prevents it from breaking down AEA. Since increased AEA levels have been shown to treat anxiety, this may be why CBD has also been linked with anxiety reduction (8). Several studies have shown CBD to help with chronic pain (3).

It has also been found that a terpene called β-caryophyllene selectively targets the CB2 receptor (10). Studies have shown this terpene to have anti-inflammation and pain relief properties. Further research is exploring this concept as a treatment option for multiple sclerosis (13).



When THC (Delta-9-THC) is consumed, it undergoes a hydroxylation reaction. This process differs depending on what method is used to consume the cannabis. When edibles are consumed, THC enters the liver and is metabolized. This process turns most of the Delta-9 into 11-Hydroxy-THC. This 11-Hydroxy is much smaller than the Delta-9, so it has an easier time penetrating the brain. It also binds more efficiently to CB1 receptors. This is why edibles cause a more intense psychoactive effect, as well as lasting longer (2).

If inhaled, THC enters the bloodstream and circulates the body. During this circulation, some of it is metabolized into a small amount of 11-Hydroxy-THC. Then, both the Delta-9 and the 11-Hydroxy penetrate vascular tissue like the brain and muscles. When cannabis is consumed sublingually, meaning under the tongue, it dissolves and penetrates the glands and mucus membrane. THC enters the bloodstream this way and the rest of the process is the same as the inhalation process (2).


Entourage Effect

Cannabis researchers are exploring a theory called the entourage effect, which posits that multiple cannabinoids and terpenes consumed in conjunction may enhance each other’s effects. This theory came about in 1998 when two professors suggested that some inactive molecules caused an increase in endocannabinoid activity. This inspired a line of research to confirm that botanical drugs may be more effective than isolates. In the pharmaceutical industry, isolates are used for treatments, however more research is beginning to show evidence of “botanical synergy.” In cannabis, this means that other cannabinoids and terpenes in addition to THC may contribute to the overall effect (4).

One study found that a cannabis extract containing small amounts of THCA (THC in its raw state) and another cannabinoid called CBG was more effective in treating breast cancer cells than pure THC. Another study looking at epilepsy found that 71% of patients improved after using CBD-dominant cannabis extract, as opposed to 36% of patients improving from pure CBD (4).

Even though CBD doesn’t appear to interact with the CB1 or CB2 receptors, studies are finding that it seems to have an indirect effect on cannabinoid receptors, enhancing the effects of THC (3). This finding has also been confirmed anecdotally. A common report from recreational cannabis users is that CBD mitigates some of the negative effects caused by THC such as anxiety and paranoia (18). There are many other cannabinoids and terpenes that may be involved in this effect, but more research will need to be done.



It is pretty remarkable that human bodies produce their own cannabinoids, and therefore have a system in place that can utilize the cannabinoids found in cannabis. In fact, all vertebrate animals possess the endocannabinoid system, which is why some people are experimenting with using cannabis products to treat ailments in their pets as well as themselves. As research continues to grow around the subject, more will be understood about what the various cannabinoids are, what they do, and how they can be used to treat symptoms and diseases.




1) De Laurentiis, A., Araujo, H. A., & Rettori, V. (2014). Role of the endocannabinoid system in the neuroendocrine responses to inflammation. Current pharmaceutical design, 20(29), 4697–4706. 

2) Cannabis Science. (2019, May 31). Science You Can Eat – How and Why Edibles Work (and Sometimes Don’t). Periodic Edibles. Retrieved from

3) Zou, S., & Kumar, U. (2018). Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. International journal of molecular sciences, 19(3), 833. 

4) Russo E. B. (2019). The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No “Strain,” No Gain. Frontiers in plant science, 9, 1969. 

5) Bennett, P. (2019, April 17). Meet the ‘bliss molecule’ Anandamide, a cannabinoid your body produces. Leafly. Retrieved from

6) Lu, H. C., & Mackie, K. (2016). An Introduction to the Endogenous Cannabinoid System. Biological psychiatry, 79(7), 516–525. 

7) Ueda, N., Tsuboi, K. & Uyama, T. (2015). Metabolic enzymes for endocannabinoids and endocannabinoid-like mediators. In Di Marzo, V. & Wang, J. (Eds.), The endocannabinoidome: The world of endocannabinoids and related mediators. (111-135). Academic Press. Retrieved from

8) Jikomes, N. (2016, December 12). What is the endocannabinoid system and what is its role? Leafly. Retrieved from

9) Raypole, C. (2019). A simple guide to the endocannabinoid system. Healthline. Retrieved from

10) Sallaberry, C. A. & Astern, L. (2018, June 1). The endocannabinoid system, our universal regulator. Journal of Young Investigators. Retrieved from

11) Mackie, K. (2008, April 17). Cannabinoids receptors: Where they are and what they do. Journal of Neuroendocrinology.

12) Rogers, K. (2019, February 7). G protein-coupled receptor. Encyclopaedia Britannica. Retrieved from

13) Alberti, T. B., Barbosa, W. L., Vieira, J. L., Raposo, N. R., & Dutra, R. C. (2017). (-)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis. International journal of molecular sciences, 18(4), 691. 

14) Russo E. B. (2016). Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis and cannabinoid research, 1(1), 154–165. 

15) Schöneberg, T., Schulz, A., Biebermann, H., Hermsdorf, T., Römpler, H., & Sangkuhl, K. (2004). Mutant G-protein-coupled receptors as a cause of human diseases. Pharmacology & therapeutics, 104(3), 173–206.

16) Reggio P. H. (2010). Endocannabinoid binding to the cannabinoid receptors: what is known and what remains unknown. Current medicinal chemistry, 17(14), 1468–1486. 

17) Basavarajappa B. S. (2007). Critical enzymes involved in endocannabinoid metabolism. Protein and peptide letters, 14(3), 237–246.

18) Rahn, B. (2016, July 3). Can CBD undo the anxious side effects of THC? Leafly. Retrieved from

CBD User Guide

CBD User Guide

CBD User Guide: How to Consume CBD

CBD, short for cannabidiol, is currently one of the most popular trends in health and wellness. There has been plenty of anecdotal evidence of CBD being used to successfully treat a variety of ailments (1). There have also been preliminary research studies showing evidence that CBD may be useful in treating anxiety (2), psychosis (3), epilepsy (4), and physical pain (5), to name a few. Whether one is curious about trying CBD or has tried it before and wants more information, this guide should provide a well-rounded overview of CBD. There are many ways to consume CBD, and it can understandably be overwhelming when choosing a preferred method of consumption.


Choosing A CBD Consumption Method



CBD oil is one of the most common forms of consumable CBD. So what is CBD oil exactly?

To make CBD oil, cannabidiol is extracted from the hemp plant and then infused with a carrier oil like hemp seed oil or MCT, which is extracted from coconut oil (6). Some may confuse CBD oil with hemp oil (also referred to as hemp seed oil), but they are not the same thing. The main difference between hemp oil and CBD oil is which part of the cannabis plant they come from. CBD is found in the leaves, flowers and stalks of hemp plants. Hemp oil is made from the seeds of the hemp plant, which contain no CBD, but are often used for hair and skin health. (7) Both CBD oil and hemp oil contain less than 0.3% THC, which is the cannabinoid with psychoactive effects (8).

CBD oil is consumed sublingually by using a dropper to place it under the tongue. The dropper allows for a fairly precise dosage, and also allows one to experiment with dose amounts. Taking CBD sublingually ensures one absorbs more CBD than one would with edibles, and the effects are fast acting (9). Unfortunately the dropper will not provide quite as accurate of a dose as something like a capsule will. One other drawback is that some users do not like the taste of natural CBD oils, but there are various flavor options available on the market. 

The onset time and duration of the CBD effects will differ depending on various factors, but typically it takes up to 45 minutes minutes for sublingual CBD to kick in, and it lasts for 2-6 hours (15).



CBD tinctures are similar to CBD oil, but differ in the ingredients and the way they are made. CBD oil is made by extracting CBD from the hemp plant using CO2 and infusing it with a carrier oil, such as MCT. That means the only two ingredients in CBD oil are CBD and oil. Tinctures are typically made by soaking the cannabis in alcohol, or a combination of alcohol and water. Alcohol is used to break down and extract the CBD, and then additional ingredients are often added such as terpenes or other cannabinoids. Many commercially sold tinctures do not contain alcohol, but the extra ingredients still classify them as tinctures (12).

As with CBD oil, tinctures are consumed sublingually, which provides fast acting effects and even higher bioavailability than oil. Another benefit of tinctures is that they often have a better flavor than oil (12). The drawback is that they can contain alcohol, so anyone with an aversion to alcohol should not consume tinctures.


CBD Edibles

CBD can be consumed in the form of food just like THC edibles. CBD treats can either be cooked at home by adding CBD oil to whatever is being made, or be purchased pre-made. If cooking with CBD flower, it will need to be decarboxylated and infused with fat just like THC edibles. The easier method would be to simply add a few drops of CBD oil to a smoothie, salad dressing, or any other edible item.

If cooking is too nerve wracking or time consuming, one can also purchase edibles. One of the most popular CBD edible options are CBD gummies, but CBD chocolate bars, cookies, drinks, and many more products are also available. 

CBD edibles are easy to consume anywhere, and can be a tasty option. One drawback to edibles is that they get partially broken down in the digestive system, and by the time they are absorbed, the user only receives 20-30% of the CBD they ingested (13).

It can take up to two hours for the effects of edibles to set in, since they must pass through the digestive system, and they last anywhere from four to eight hours (14, 15, 16). Both of these times vary per consumer and are affected by height, weight, activity, and other things consumed that day. With edibles, the CBD continues to release slowly over an extended period of time and can last for six to eight (16).


CBD Topicals

CBD creams are another option for consumption. They are made by extracting CBD oil and then infusing it with other healing ingredients like essential oils. Topicals are absorbed into the top layer of the skin, as opposed to being transdermal and infusing into the bloodstream.

Many people use CBD for rheumatoid arthritis, joint and muscle soreness (17), and chronic pain (18). As with other forms of CBD and THC, there still is not enough substantial evidence to prove these products work, however, it is easy to see why they might. CBD has the ability to increase natural endocannabinoids and desensitize pain receptors (18).

Exercise and strength training create micro-tears in muscles, and the body will feel sore until the immune cells repair the tissue. CBD is thought to limit some of the body’s inflammatory signals, helping with muscle pain but not restricting the body’s healing process.

An additional way that CBD is thought to help physical pain is through TrpV1 receptors (18). These are receptors in the body that when activated, produce heat to soothe pain (20). CBD activates these receptors, creating heat to address pain.

Topicals are best used for joint or muscular pain because they can be applied directly to the problem area. It can take 20-60 minutes for the effects to kick in (14,15), and they tend to last 2-5 hours (11,14), but vary considerably in both onset time and duration per consumer (16).


Smoking and Vaping

Just like cannabis containing THC, CBD flower can be smoked. Any of the regular cannabis smoking methods may be used such as a pipe, water pipe, or joint.

Vaping is similar to smoking in that the CBD is inhaled, but instead of flower, vape pens heat up CBD oil concentrate which is then vaporized and inhaled. Depending on how long and deep the inhalation is, the body will absorb 10-60% of the CBD. (13, 21).

Smoking and vaping are the fastest acting and most bioavailable methods of consumption. The CBD enters the lungs and then goes into the bloodstream, skipping the digestive system (11). It will only take a few minutes to feel the effects, up to 10 minutes at the most (14, 16). If one is trying to quit smoking nicotine, smoking or vaping CBD can be a great alternative with fewer health risks (22). Effects from these methods tend to last around 2-4 hours (11, 16).

Be aware of the health risks that come with smoking or vaping anything, such as lung injury (24).


CBD Capsules

CBD capsules or CBD softgels are pill capsules filled with CBD extract. When a capsule is consumed, CBD goes through the digestive system and ends up in the liver to be metabolized (25). Unfortunately, by the time CBD reaches the bloodstream, the concentration of compounds are reduced. This means that consuming CBD in the form of capsules has low bioavailability, roughly 13-19% (26).

A major benefit of capsules is the pre-measured dose. Capsules are also easy to bring and consume anywhere. The onset time and duration are the same as edibles; the CBD will take at least 60 minutes to take effect, depending on what else was consumed that day. It will also last 4 hours or more, slowly continuing to release throughout the day (14).

What to look for in a CBD product

cbd shopping

Full Spectrum vs. Broad Spectrum

Some terms that will appear when exploring CBD products are full spectrum or broad spectrum, so users should be aware of the difference between full and broad spectrum CBD.

As we know, the cannabis plant contains many cannabinoids, two of which are CBD and THC. Full Spectrum CBD contains all of the cannabinoids, including THC. It has been reported that this type of CBD relieves pain better by interacting with the THC, but not everyone can legally consume THC or wants the psychoactive effects (10). Broad Spectrum CBD contains all cannabinoids except THC. Any THC is removed, making these products legal in the U.S. (28).

Quality CBD products will specify which CBD spectrum was used, or the THC to CBD ratio of the product.



When it comes to cannabis products, one of the most important things to look at is the ingredients. Depending on the type of product, one should make sure that it only has CBD (and THC if that is okay) and other natural additives.


Lab tested

Quality CBD products go through third-party lab tests to ensure their quality and confirm the exact amounts of ingredients. Since CBD isn’t currently regulated by the FDA, this is the best way to ensure that the products consumed are safe and contain what they claim to. Lab testing provides customers with an unbiased scientific analysis of cannabinoid profiles, meaning which cannabinoids and how much are in the product (29).


Where and when was it grown

Look for CBD products that are U.S. grown. This ensures that it falls under strict U.S. guidelines and agricultural regulations (30).

It is also important to check when the product was manufactured and when it expires.


CBD Dosage

cbd dose

Determining CBD dosage differs per person, and will take some trial and error. Obviously it is better to start small and increase from there, which could mean starting with 20 or 40 mg a day (23). Try and keep track of how much CBD is taken and what effects are felt, to determine if that dosage is right for the user. Do not ramp it up too quickly, because small doses of cannabis tend to provide stimulation while too much can cause sedation (11). Dosage will differ per consumption method.

CBD capsules or gummies are the easiest forms of CBD to track dosage. Generally each individual capsule or gummy is one dosage, but be sure to read the bottle for dose instructions.

Smoking or vaping is another easy method to monitor dosage. Because inhaling CBD is so fast acting, the effects (or lack of effects) should be felt within minutes. Try waiting 20 minutes just to be safe, and if no effects are felt, take another puff.

CBD edibles can be a little tricky to dose, but if the edible was purchased, the amount of CBD and/or THC will be on the label. If the edibles were made at home, be careful. The tricky aspect of dosing edibles is that they are slow acting, so the user will not know for up to a few hours. Many people have made the mistake of assuming it did not work and consuming more, but it is best to wait a few hours and determine whether the effects are felt.

For CBD cream, it is important to rub a very small amount on the skin to start. 24 hours should be enough time to check for a rash or other negative reaction. Once the user can confirm no adverse effects, they can apply more to the skin. More can always be added so starting with a small dose is best.

CBD oils and tinctures will list the amount of CBD in milligrams on the bottle, but will probably not list the amount per drop. One will need to look at the amount of total CBD in milligrams on the bottle and do the math. If a 20 milliliter bottle of CBD oil contains 400 drops, and the label says there are 2000 milligrams of CBD total, that means each drop contains 5 milligrams. Again, a nice low dosage to start with is 20 milligrams, so in this scenario the user would take 4 drops. A drop is literally that – just one drop – not the entire dropper.


Entourage Effect

The entourage effect is a common phrase used in relation to CBD products. As mentioned earlier, CBD and THC are two cannabinoids found within the cannabis plant. There are also many other cannabinoids, and they may support the effects of the main two. It is theorized that different combinations of these cannabinoids produce different effects. The entourage effect is based on a very small amount of research and mostly anecdotal evidence, but some preliminary research has shown that CBD may be more effective when taken in combination with THC (10). Terpenes are aromatic oils that are secreted from the same glands as CBD and THC. These are what give certain strains of cannabis particular looks, odors, and tastes (19). Terpenes may also be involved in producing entourage effects.


Are there any side effects of CBD?

While there are no reported long-term side effects of consuming CBD, one thing to be aware of is mixing medications. If on medication, talk to a doctor about the combination of substances and make sure it is safe. Other than that, reported side effects have included change in appetite, change in weight, diarrhea, drowsiness or fatigue, and mood change (27).





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