Cannabis sativa is one of the world’s oldest cultivated plants, with written records dating back to the 6th century B.C.
Closer in time, many practitioners during the 1800s ascribed medicinal properties to cannabis after the drug found its way to Europe during a period of colonial expansion into Africa and Asia. During this time period cannabis was first introduced to Western medicine as a treatment for tetanus and other convulsive diseases, as well as in the treatment of mental disorders.
In 1851, cannabis was included in the 3rd edition of the Pharmacopoeia of the United States (USP), with later revisions describing in detail how to prepare extracts and tinctures of dried cannabis flowers to be used as analgesic, hypnotic, and anticonvulsant.
However, concerns about cannabis resulted in the outlawing of cannabis in several US states in the early 1900s and prohibition in 1937, at the Federal level, with the passage of the Marihuana Tax Act. In response to these concerns, in 1942 the American Medical Association removed cannabis from the 12th edition of US Pharmacopeia.
For a more detailed account of cannabis look here.
Chemical Constituents of Cannabis
- At least 104 different cannabinoids have been identified in cannabis.
- Other compounds include:
- Nitrogenous compounds; and
- More common plant molecules.
Two of the most quantitatively important constituents of cannabis sativa are CBD and THC.
What is CBD?
Cannabidiol, or CBD, is one of the main cannabinoids found in cannabis sativa plants, and is the most abundant cannabinoid in hemp.
CBD lacks the cannabis-like intoxicating properties of THC and, for this reason, has been traditionally considered non-psychoactive.
A cannabis sativa plant can be classified according to its CBD and THC production potentials
- Type I cannabis sativa contains more than 0.3% THC and less than 0.5% CBD.
- Type II cannabis sativa contains more than 0.3% THC and 0.5% CBD.
- Type III cannabis sativa contains less than 0.3% THC and more than 0.5% CBD.
Type I and type II cannabis sativa are considered marijuana while type III is classified as hemp.
CBD can be derived from any type of cannabis sativa plant, but it is legal throughout the US only when it comes from hemp specifically – an important distinction explained in greater detail below.
What is THC?
THC or Delta-9-tetrahydrocannabinol is another main cannabinoid found in cannabis sativa plants. THC is the compound that produces the intoxicating, psychoactive “high” often associated with cannabis.
THC has received the most attention for being responsible for the intoxicated state sought after by recreational cannabis users, owing to its ability to act as a partial agonist2 for type-1 cannabinoid (CB1) receptors.
Synthetic vs Natural Product Derived Compounds
Cannabinoid-Based Medications (US, as at 2017)
|Substance||Route of Administration||Description|
|Natural Product Derived Compounds||Cannabidiol (CBD)||Oral capsule Oromucosal spray||Cannabinoid extracted from Cannabis plant|
|Cannabis||Multiple||Multiple active cannabinoids|
|Cannador||Oral capsule||THC and CBD from Cannabis extract|
(FDA Fast Track)
|Oil||Concentrated CBD from Cannabis extract|
(FDA Fast Track)
|Oromucosal spray||THC and CBD extract from two Cannabis plant varieties|
|Tetrahydrocannabinol (THC)||Oral capsule Smoked Oromucosal spray||Active cannabinoid of Cannabis plant|
|THC/CBD||Oral capsule||Combination of cannabinoids|
|Synthetic Compounds||Ajulemic acid (AjA)|
(FDA PHASE II Active)
|Oral capsule||Synthetic non-psychoactive cannabinoid|
|Dronabinol (Marinol®; Syndros®) (FDA approved)||Oral capsule||Synthetic THC|
|Oral capsule||Synthetic cannabinoid – THC analogue|
In the US, cannabis-derived products are consumed for both medical and recreational purposes in a variety of ways, including:
- Smoking or inhaling from cigarettes (joints).
- Pipes (bowls).
- Water pipes (bongs, hookahs).
- Blunts (cigars filled with cannabis).
- Eating food products and snack items.
- Drinking beverages.
- Vaporising the product.
- Cannabinoids can also be absorbed through the skin and mucosal tissues, so topical creams, patches, vaginal sprays, and rectal suppositories are sometimes employed and used as a form of administering THC.
These different modes are used to consume different cannabis products, including:
- Cannabis “buds” (dried cannabis flowers);
- Cannabis resin (hashish, bubble hash); and
- Cannabis oil (butane honey oil, shatter, wax, crumble).
- The oil, which may contain up to 75% THC – versus 5 to 20% in the herb or resin – is extracted from plant material using organic solvents, such as ethanol, hexane, butane, or supercritical (or subcritical) CO2, and can be either smoked or vaporised by pressing the extracted oil against the heated surface of an oil rig pipe (dabbing).
A broad selection of cannabis-derived products are also available in the form of clothing, and health and beauty aid products.
Does CBD have Therapeutic Effects?
CBD can also enhance adenosine receptor signalling by inhibiting adenosine inactivation, suggesting a potential therapeutic role in pain and inflammation. The antioxidant and anti-inflammatory properties of this compound may explain its potential neuroprotective actions. Irrespective of the mechanism of action, there is evidence that CBD could potentially be exploited in the treatment and symptom relief of various neurological disorders such as:
- Epilepsy and seizures;
- Movement disorders (e.g. Huntington’s disease and amyotrophic lateral sclerosis); and
- Multiple sclerosis.
Consumers with diagnosable conditions such as psychiatric (e.g. anxiety) and orthopaedic (e.g. joint pain) conditions are the most commonly reported medical reasons for using CBD, often using CBD as a substitute or adjunct for approve therapies (Leas et al., 2021).
However, unsubstantiated claims may increase use of CBD products, prolong illnesses with existing effective treatments, and expose consumers to both known and unknown health risks without conferring any of the purported beneﬁts (Leas et al., 2021). For this reason, the US Food and Drug Administration (FDA) prohibits the sale of CBD products with such marketing claims, and has already sent warning letters to some companies that have marketed CBD in this manner.
As of 2017, the FDA has licenced three drugs based on cannabinoids (refer to Table above):
- Dronabinol, the generic name for synthetic THC, is marketed under the trade name of Marinol® and is clinically indicated to counteract the nausea and vomiting associated with chemotherapy and to stimulate appetite in AIDS patients affected by wasting syndrome.
- A synthetic analogue of THC, nabilone (Cesamet®), is prescribed for similar indications.
- Both dronabinol and nabilone are given orally and have a slow onset of action.
- In July 2016 the FDA approved Syndros®, a liquid formulation of dronabinol, for the treatment of patients experiencing chemotherapy-induced nausea and vomiting who have not responded to conventional antiemetic therapies.
- The agent is also indicated for treating anorexia associated with weight loss in patients with AIDS.
- Two additional cannabinoid-based medications have been examined by the FDA.
- Nabiximols (Sativex®) is an ethanol cannabis extract composed of Δ9-THC and CBD in a one-to-one ratio.
- Nabiximols is administered as an oromucosal spray and is indicated in the symptomatic relief of multiple sclerosis and as an adjunctive analgesic treatment in cancer patients (Pertwee, 2012).
- As of September 2016, nabiximols has been launched in 15 countries, including Canada, Germany, Italy, Spain, the United Kingdom, and has been approved in a further 12, but not in the United States.
- In response to the urgent need expressed by parents of children with intractable epilepsy, in 2013 the FDA allowed investigational new drug studies of Epidiolex®, a concentrated CBD oil (>98 percent CBD), also developed by GW Pharmaceuticals, as an anti-seizure medication for Dravet and Lennox-Gastaut syndromes.
What are the Differences
CBD and THC may come from the same plant, but their unique chemical structures affect how they interact with the body. Because of these inherent differences, they are also treated differently in the US legal system.
“From a chemistry standpoint, THC and CBD are isomers, meaning they share the same chemical formula (C21H30O2) with different chemical structures,” say Nick Jackowetz and Soheil Hajirahimkhan, chief scientific officer and head of research and development at Cirona Labs, a cannabinoid product developer. “While the structure of CBD consists of two 6-membered rings, THC has an additional 6-membered ring that is formed via the attachment of a carbon and an oxygen atom (called an ether bond).”
Therefore, CBD and THC bind differently with the receptors in the body’s endocannabinoid system, which helps modulate the central nervous system, synaptic plasticity (how neurons communicate with each other) and the body’s response to external stressors.
The two main receptors in the endocannabinoid system are CB1, which is largely found in the brain and central nervous system, and CB2, which is mostly found in the immune system (and in much lower levels in the central nervous system). THC tends to bind with both receptors while CBD has little affinity for either.
THC is the compound most commonly associated with psychoactive effects while CBD is not. However, this understanding is “a huge misconception,” says Monique McHenry, Ph.D., director of the Medical Cannabis Centre for Research and Education at the University of Vermont Medical School.
Lauren Rudick, partner of the cannabis practice at Hiller, PC, a law firm in New York, agrees with McHenry. “It’s an important distinction,” she says. CBD is still psychoactive, meaning it affects the mind – it is just not intoxicating and does not impair function.
The “high” from THC comes from its binding with CB1 receptors. Since CBD does not attach to CB1 or CB2 receptors like THC does, it does not produce the same intoxicating effect.
However, when CBD and THC are consumed together, CBD binds to the receptors and blocks THC from binding with them, thus mitigating some of the effects felt from the THC.
At the US Federal level, hemp-derived products – including CBD products – are legal under the 2018 Farm Bill as long as they contain no more than 0.3% THC by dry weight basis. Cannabis products, regardless of whether they are hemp derived, that contain more than 0.3% THC by dry weight are still illegal under federal law.
However, at the state level, Legality can be confusing thanks to varying state laws regarding both cannabis and hemp. As of November 2021:
- 19 states allow for adult recreational and medical use of cannabis.
- 17 states allow for medical use of cannabis.
- 11 states allow for low-THC/CBD products.
- 3 states do not allow any cannabis use.
Due to competing state and federal laws and evolving regulations, cannabis products also tend to be mislabelled, leading to further confusion. One study analysed 84 CBD products and found 69% of them either overstated or understated their concentrations of CBD. Further, 21% of the products contained THC without labelling them as such (Bonn-Miller et al., 2017).
Generally, drug tests are designed to detect THC – not CBD – in a person’s system. However, depending on who orders a test and what they use the results for, a drug test can be used to look for CBD as well.
It is also important to note that THC can still be detected on a drug test if you are using hemp-derived CBD products that contain a legal amount THC (no more than 0.3%). If you want to use CBD products without running this risk, then you might want to consider using broad spectrum CBD or CBD isolate, both of which exclude THC entirely.
You may also want to consult a medical professional about CBD use or learn more about the specific drug test you will be taking.
Potential Side Effects
THC and CBD may elicit varying side effects:
- THC use tends to lead to dry mouth and intoxication effects, such as disorientation, paranoia and dizziness.
- More serious reactions can include panic attacks and psychosis.
- High doses may even lead to hospitalisation.
- On the other hand, CBD has been determined to have no abuse potential and will not lead to hospitalisation even with high doses.
- High dosage most commonly leads to sleepiness and may lead to liver issues over the long term, although more research is needed to confirm this connection.
- Adverse digestive effects associated with CBD typically stem from other ingredients in the CBD product, such as coconut oil.
Regular users may experience withdrawal and symptoms of dependence, especially in synthetic cannabinoid-derived products.
What are the Similarities?
Given their almost identical chemical makeup, CBD and THC produce some similar effects – and can even work together to compound their benefits.
- Both CBD and THC have been shown to help manage sleep troubles and physical pain.
- CBD specifically is often used to alleviate stress and anxiety as well.
- Administered jointly, they can work together to have even more potent medical benefits. For instance, Nabiximols (known by the brand name Sativex) is a 1:1 THC and CBD mix used to relieve symptoms of multiple sclerosis and cancer-related pain.
- Nabiximols has been approved for use in 27 countries, but not in the US.
- Clinical studies have also shown THC and CBD mixes to be helpful in managing symptoms of post traumatic stress disorder (PTSD) and amyotrophic lateral sclerosis (ALS).
CBD and THC can be consumed in the same ways, which include:
- Smoke inhalation by igniting dried cannabis flower.
- Vapor inhalation via a vape pen.
- Edibles like gummies.
- Oil or extracts of the plant material.
What about Contaminants and Adulterants?
- The most frequent natural contaminants consist of degradation products, microbial contamination (e.g. fungi, bacteria), and heavy metals.
- These contaminants are usually introduced during cultivation and storage.
- Growth enhancers and pest control chemicals are the most common risks to both the producer and the consumer.
- Can be contaminated for marketing purposes.
- This usually entails adding:
- Substances (e.g. tiny glass beads, lead) to increase the weight of the cannabis product;
- Psychotropic substances (e.g. tobacco, calamus); and/or
- Cholinergic compounds to either enhance the efficacy of low-quality cannabis or to alleviate its side effects.
- Additionally, some extraction and inhalation methods used for certain dosing formulations (tinctures, butane hash oil, “dabs”) can result in substantial pesticide and solvent contamination.
Bonn-Miller, M.O., Loflin, M.J.E., Thomas, B.F., Marcu, J.P., Hyke, T., Vandrey, R. (2017) Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA. 318(17), pp.1708-1709.
Leas, E.C., Moy, N., McMenamin, S.B., Shi, Y., Benmarhnia, T., Stone, M.D., Trinidad, D.R. & White, M. (2021) Availability and Promotion of Cannabidoil (CBD) Products in Online Vape Shops. International Journal of Environmental Research and Public Health. 18:6719. doi.org/103390/ijerph18136719.