Cannabis 411

What is Cannabis?

Cannabis is a genus of annual flowering herb plants in the family “Cannabaceae.” The number of species within the genus is disputed but usually three particular species are commonly recognized: Cannabis sativa, Cannabis indica, and Cannabis ruderalis.  The genus is widely accepted as being indigenous to and originating from Central Asia, with some researchers also including upper South Asia in its origin.

Is Cannabis the Same as Marijauna?

Cannabis is also known as hemp, although this term is often used to refer only to varieties of Cannabis cultivated for non-drug use.  In the US, “industrial hemp” is classified by the federal government as cannabis containing no more than 0.3% THC by dry weight. This classification was established in the 2018 Farm Bill and was refined to include hemp-sourced extracts, cannabinoids, and derivatives in the definition of hemp.  Cannabis that contains levels of THC higher than 0.3% is now listed as “marijuana” and remains a Schedule I drug. So, some cannabis is marijuana and some is not.

Hemp			Marijuana
CBD	Yes		CBD	Yes
Non-Psychoactive	Yes		Non-Psychoactive	No
Federally Legal	Yes		Federally Legal	No
Available OTC	Yes		Available OTC	No

What is a Cannabinoid?

Cannabinoids are molecules that act upon certain receptors within the body and alter the production of various neurotransmitters, thus intensifying certain physiological and pathophysiological processes. The Cannabis plant contains 483 identifiable chemical constituents and included in these are over 113 different types of phytocannabinoids (i.e. plant derived cannabinoids).  Many of the cannabinoids are found in relatively small concentrations and most have yet to be studied in any real degree to determine their potential therapeutic benefit. What is known is that cannabinoids produce mental and physical effects when consumed. When you hear the term CBD, that is referring to a type of cannabinoid called “cannabidiol” (more on that below).  

Researchers still don’t understand what all of the cannabinoids do, but there are two produced in the greatest abundance — tetrahydrocannabinol (THC) and cannabidiol (CBD).  THC is the main psychoactive compound in cannabis plants. It’s responsible for the “high” or state of euphoria associated with cannabis use. Levels of THC have been increasing as growers try to create hybrids with a greater concentration of the compound.  CBD is non-psychoactive. It doesn’t cause a “high.” However, it may produce many physical benefits, such as reducing pain and nausea, preventing seizures, and easing migraine.

Scientists have identified several other less common cannabinoid compounds. These include:

• CBN – Cannabinol (CBN) is used to ease symptoms and side effects of neurological conditions, including epilepsy, seizures, and uncontrollable muscle stiffness.
• THCA – Tetrahydrocannabinol acid (THCA) is similar to THC, but it doesn’t cause any psychoactive effects. Its potential benefits include reducing inflammation from arthritis and autoimmune diseases. It may also help reduce symptoms of neurological conditions like Parkinson’s disease and ALS.
• CBG – Cannabigerol (CBG) is thought to help reduce anxiety and symptoms of obsessive-compulsive disorder, post-traumatic stress disorder, and depression.

What is Cannabidiol (CBD)?

Cannabidiol (CBD) is a major phytocannabinoid produced with Cannabis. CBD has become very popular within the scientific and medical community due to its low affinity for CB1 receptors, which renders it non-psychoactive, in addition to acting upon several receptors outside of the traditional Endocannabinoid System. The result produces broad spectrum effects coordinated by several mechanisms and physiological pathways. This accounts for a plethora of pharmacological effects and conditions capable of being treated, such as anxiety, psychosis, addiction, neuropathic pain, movement disorders, and much more. 

The presence of CBD counteracts the psychoactive properties of THC, allowing for extracts containing both cannabinoids to have greater systemic effects without producing as great of a “high” effect associated with THC alone.

How Do CBD and THC Relate to Each Other?

Since the early 1970s, Cannabis plants have been categorized by their chemical phenotype or “chemotype,” based on the overall amount of THC produced, and on the ratio of THC to CBD.  Although overall cannabinoid production is influenced by environmental factors, the THC:CBD ratio is genetically determined and remains fixed throughout the life of a plant. Non-drug plants produce relatively low levels of THC and high levels of CBD, while drug plants produce high levels of THC and low levels of CBD. 

CBD	VS	THC
Non-Psychoactive		The compound that elicits the high in marijauna
Will not (and cannot) get you high		Highly-regulated
Therapeutic Potential:  anti-inflammatory, pain relieving, immunomodulating, anti-anxiety		Therapeutic Potential: blocks perception of pain > anti-inflammatory, anti-proliferative
Risks: Minimal; drug-interactions, hepatic toxicity		Risks: Can induce anxiety & psychosis, drug interactions, hepatic toxicity
Low affinity for CB1 & CB2 receptors – “potent antagonist”		Binds to both CB1 and CB2 receptors – partial agonist

How do Cannabinoids Work?  ECBs, CB Receptors and Enzymes

Cannabinoids operate within the body via the Endocannabinoid System (ECS).  Discovered just in 1993, the ECS was a remarkable discovery for humanity as it is the largest neurotransmitter system in the human body. The ECS takes the form of a matrix all over the body that regulates bodily functions such as anxiety, mood, pain, memory, appetite, depression, digestion, metabolism, bone development, sleep, pain, fertility, temperature regulation and immune function. The ECS consists of: 1) endo- (aka endogenous) cannabinoids (those made by us in our own bodies), 2) cannabinoid receptors (primarily CB1 and CB2), and 3) the enzymes that synthesize and degrade endogenous cannabinoids. Cannabinoids generally, whether endogenously (internally) produced OR from exogenous (outside) sources like phyto-cannabinoids, work by either up or down-regulating the ECS.

What are Endo-cannabinoids (ECBs)?

Neurotransmitters like serotonin and dopamine are chemical messengers of the nervous system. Similarly, endocannabinoids (ECBs) are the messengers of the ECS, and are produced throughout our bodies. The two key ECBs circulating in your body are anandamide and 2-arachidonoylglycerol. Just like the phytocannabinoids in cannabis, these neurotransmitters are built from lipids (fats or oils). This lipid-based structure of cannabinoids is the reason why THC and CBD are fat-soluble…and why your typical cannabis or hemp extract is delivered in an oil base like coconut, avocado, or butter.

What are Cannabinoid (CB) Receptors?

If ECBs are the messengers of the ECS, then cannabinoid receptors are the guards posted at the city wall, waiting for the messengers. Receptors sit on cell surfaces, waiting for specific neurotransmitters to bind to them. Depending on the type of cell that the receptor is on, the downstream effect will rapidly impact immunity, sensation, mood, and even consciousness. We have CB receptors throughout our bodies, guarding a wide variety of cell types & responses. Different cell types have different receptors, which are sensitive to different types of ECBs. The two main receptors of the ECS are CB1 and CB2.

CB1 receptors are one of the most common receptors in our entire nervous system. They are essential for a healthy functioning brain depending on what region of the brain they are located in, they can be moderators of your memory, mood, motor function, or your perception of pain (“nocioception”). The CB1 receptor is the one that is associated with producing both the (sometimes unwanted) psychoactive properties of THC (the “high” effect) and an increase in appetite.  

CB2 receptors are most often found on the cells of our immune system and do not produce the psychoactive effects like CB1 bound to THC does. They act on pathways that actually suppress acute pain, chronic inflammatory pain, and neuropathic pain by helping moderate inflammation and our immune response to pathogens. When cannabis is used to combat conditions of an overactive immune system (i.e. arthritis, asthma, allergies, autoimmune disorders or digestive issues like inflammatory bowel disease) it is because of the targeting of CB2 receptors.

Why Are Enzymes Important in the ECS?

Enzymes in the ECS are the molecules devoted to controlling when & where ECBs are synthesized and produced, and how quickly they get sequestered or broken down. Think of the role of enzymes in the ECS as the administrative system, making sure the messenger is sent exactly when and only when desired. Accordingly, when your body gets the signal to produce ECBs (anandamide and 2-AG) and deliver them to their receptors (CB1 and CB2), these enzymes are put to work in order to prevent the process from stimulating the ECS indefinitely by either using transport proteins to move the ECBs into storage sites OR to enzymes that degrade and therefore lower the level of them in our system.  The two most-studied enzymes in the ECS are FAAH (which degrades anandamide) and MAGL (which breaks down 2-AG). 

What about CBD and the ECS?

Most cannabinoids – whether the ECBs anandamide and 2-AG OR certain exogenous phytocannabinoids like THC – can bind to both types of receptors, CB1 & CB2. The phytocannabinoid CBD, however, doesn’t directly trigger either the CB1 or CB2 receptors; instead, it modifies the receptors’ ability to bind to the ECBs by occupying the FAAH and MAGL enzymes and diminishing their effects.  In other words, because CBD inhibits ECS enzymes, it tends to increase the body’s levels of the feel-good ECBs of anandamide and 2-AG thereby decreasing anxiety, inflammation, and pain.  

Are CBD and THC the Only Things That Matter?

No. A great deal of attention is paid to the amount of THC and CBD, but newer research suggests that there are other naturally occurring compounds in the cannabis plant, specifically terpenes, that may be just as impactful. Terpenes are the fragrant oils found in cannabis (as well as fruits, plants, and other herbs) that give each strain its unique smell and flavor.  The terpenes present may also influence the effects produced by specific strains. 

Common terpenes include:

• Bisabolol. With notes of chamomile and tea tree oil, the terpene bisabolol is thought to reduce inflammation and irritation. It may also have microbial and pain-reducing effects.
• Caryophyllene. The peppery, spicy molecule may reduce anxiety, ease symptoms of depression, and improve ulcers.
• Linalool. Linalool is said to help improve relaxation and boost mood with its floral notes.
• Myrcene. The most common terpene, this earthy, herbal molecule may help reduce anxiety and insomnia so you can sleep better. 
• Ocimene. This terpene produces notes of basil, mango, and parsley. Its primary effects may include easing congestion and warding off viruses and bacteria. 
• Pinene. As the name suggests, this terpene produces an intense pine aroma. It may help boost memory, reduce pain, and ease some of the not-so-pleasant symptoms of THC, such as nausea and coordination problems.
• Terpinolene. Cannabis with this compound may smell like apples, cumin, and conifers. It may have sedative, antibacterial, and antifungal properties.
• Limonene. Bright, zippy citrus notes come from this terpene. It’s said to improve mood and reduce stress.
• Humulene. This terpene is deeply earthy and woody, like hops or cloves. Cannabis strains with this molecule may reduce inflammation.
• Eucalyptol. With notes of eucalyptus and tea tree oil, this molecule is refreshing and invigorating. It may also reduce inflammation and fight bacteria.

Different terpenes have different uses.  Here are some common conditions and suggested terpenes:  

• Pain Management: Linalool, Caryophyllene, Limonene, Myrcene, a-Pinene, Eucalyptol
• Anxiety Reduction: Linalool, Caryophyllene, Limonene, a-Pinene, Borneol
• Inflammation Reduction: Linalool, Limonene, Myrcene, Humulene
• Insomnia Reduction: Linalool, Myrcene, Terpineol
• Neurodegeneration Management: Linalool, Carene, Eucalyptol, Geraniol

Are There Different Types of CBD?

Yes, when looking at CBD products, it is extremely important that you understand the different types of CBD available.  Most commonly, you will see either CBD Isolate, Full-Spectrum CBD, or Broad-Spectrum CBD. Each type is a result of various extraction and refinement processes, all of which impact the amount needed for dosing in order to achieve different effects over different lengths of time.

What is CBD Isolate?

CBD isolate products are generally labeled as being 99% or more pure CBD depending on the form they come in. As the name suggests, these products have been isolated down to just the CBD molecule. They have no other active ingredients and just aim to deliver therapeutic doses of CBD, isolated from the other cannabinoids, terpenes and flavonoids.  CBD isolate itself is a white powder, which may be available to consumers. More often, isolates are mixed with a carrier oil to become tinctures, or placed in capsules, edible products like gummies, topical salves, and so on. One issue with CBD isolate is that you need higher doses in order to achieve a peak response that ultimately is a lower peak than what you could get with other CBD products.  

What is Full-Spectrum CBD?

Full spectrum CBD or “whole-plant” hemp products means the full plant extract is included so that they contain not only CBD but also other plant molecules as well, including THC. This version of CBD is minimally refined, leaving most of the cannabinoids and terpenes intact. Full spectrum provides more of the plant’s molecules in ratios and amounts that nature intended and therefore acts at lower doses with a higher peak potential.

What is Broad Spectrum CBD?

Broad spectrum products represent a middle ground between CBD Isolate and Full Spectrum CBD. A true broad spectrum product is high in CBD, contains absolutely 0% THC, but retains some of the other cannabinoids, terpenes, and similar potentially beneficial compounds which an isolate does not.  In other words, broad spectrum CBD has all of the components of full spectrum CBD without any THC, thereby making it the best choice for people who cannot have ANY trace of THC in their system (for personal or professional reasons).

What is the Entourage Effect?

The “entourage effect” is important to understand as it impacts the effectiveness of cannabinoid products. The entourage effect refers to cannabis compounds working in synergy with one another. Whether CBD and THC or CBD and terpenes (such as in a “full spectrum” product) or other cannabinoid combinations, when appearing together, these compounds produce a stronger influence than any individual single cannabinoid on its own – this synergy is the “entourage effect.”  This interaction is why terpenes that are found in other plants as well as in cannabis do not have the same effects on your body alone as a terpene that is combined with other cannabinoid compounds. For example, limonene is a terpene also commonly found in citrus fruits, but consuming a citrus fruit won’t produce the same benefits as consuming cannabis with limonene.

Is CBD Regulated?

No, not presently – CBD is a totally unregulated market with misleading claims and lots of gimmicky products. CBD only comes from the whole flower thus any real product must be labeled “hemp-extract” or “whole leaf extract” – anything that says “hemp oil” or “hemp seed oil” or “cannabis-infused” then they have no CBD in them at all.

Are CBD Products Drugs?

For decades, the US Drug Enforcement Administration (DEA) treated Cannabis plants and their products all the same, however that has now changed.  To keep it simple: if a CBD product comes from a hemp plant (<0.3% THC), it’s legal; if it comes from a marijuana plant (>0.3% THC), it’s federally illegal, despite local laws. And even if it does come from a hemp plant, there’s often no guarantee it won’t contain some THC, thanks to things like cross-pollination and the absence of industry regulation.  For this reason, experts recommend buying CBD products from companies located in states like Kentucky, Indiana and Utah that require cannabis products to be tested for potency and purity. 

What is the Evidence for the use of CBD (Hemp) Extract?

Based on over 70 years of data, researchers have concluded that cannabinoids are very effective for pain relief, whether at the level of opioid use or just traditional non-steroidal anti-inflammatory drugs.  Specifically, cannabinoids can be used concurrently with opioids without any increased risk of respiratory depression or cardiovascular issues and even better they help reduce withdrawal symptoms from opioids enabling patients to eliminate opioids completely – in all instances without impairing or burdening the liver (when used at proper doses). What is even more impressive is that the studies showed that CBD alone was sufficient to achieve these effects, without the inclusion of any THC at all.  

After reducing or eliminating opioid use, CBD’s next two most significant impacts have been on improving chronic pain and increasing sleep quality.  The next most common reason for CBD use is mood modulation and optimizing sexual health. Other emerging areas of research include: IBD/IBS, peripheral neuropathy, degenerative diseases, autoimmune diseases, transplant patients, pediatric use, autism spectrum disorders, cognitive decline, tumor reduction and more.  Accordingly, more than THC, CBD dominates in the medical benefits category, but there are times when you will want to use them together in a set ratio.

Phenomenal study here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503660/ 

Overview of studies here:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277878/ 

How are CBD and THC Used Medicinally?

When it comes to medicinal uses for cannabis, in almost all instances high CBD strains are most important. If you’re using cannabis recreationally, then you will want more (or all) THC. CBD does not make you feel high, although in higher dosages it does have a slight altering of perception which is much more acute than THC. Unfortunately, because (in most places) more people use cannabis recreationally than medicinally, high THC cannabis is far more prevalent. This can make sourcing high CBD-only or low ratio strains much more difficult.  In states where marijauna is legal, you will often find a combo product listed by ratio.

What is a CBD:THC Ratio?

The CBD:THC ratio refers to the amount of CBD and THC that is contained in any form of cannabis. The optimal CBD:THC ratio will vary depending on one’s individual physiology, medical conditions, and cannabis tolerance.  Finding your most effective CBD to THC ratio will aid in maximizing the potential medicinal benefits cannabis can provide.

What Are the Most Common Ratios?

• THC dominant options (0:1) will provide varying degrees of psychoactivity.  THC also induces appetite, reduces inflammation, and can provide relaxing and/or cerebral effects.  Adverse effects may include tachycardia, anxiety, and paranoia. These can be reduced by introducing CBD into the equation.
• A 1:3 ratio of CBD to THC results in some psychoactivity while minimizing THC’s unwanted side effects, producing a calming sensation with reduced anxiety, stress relief and exhibiting anti-inflammatory properties.  This ratio can act as an advanced pain reliever with the synergistic benefits CBD and THC provide.
• A ratio of equal parts CBD to THC (1:1) is considered highly effective for pain relief, anxiety, spasticity, fibromyalgia, insomnia, nausea and appetite stimulation. This ratio shows promise in relieving symptoms associated with Multiple Sclerosis and may be able to kill certain cancer cells and inhibit tumor growth.  A 1:1 can be a good starting point for many due to the multitude of conditions it may treat with minimal impairment.
• Higher CBD options, such as 2:1 or 3:1, may be an ideal ratio for combating autoimmune disorders, gastrointestinal issues such as Crohn’s and colitis, arthritis, and psoriasis with little to no psychoactivity.  
• CBD dominant ratios of 25:1 or 1:0 (hemp-based CBD) offer no psychoactivity and may be most effective for curbing high anxiety, depression, seizures, psychosis, PTSD, and neurodegenerative conditions such as Parkinson’s and Huntington’s Disease.  

Is there a proper ratio of CBD to THC for specific conditions?

The beauty of cannabinoids is that they represent a personalized approach to an individual’s health and wellbeing. This means that there is no specific ratio or dose that works best. It is up to an individual and her/his healthcare team to determine the best efficacy. With that said, some individuals do not like the psychoactive effects produced by THC and thus may do better with ratios of higher CBD and very low THC. Others may do better with a 1:1 ratio, which actually provides the broadest range of actions. Additionally, depending on state laws, certain extracts may not be available for an individual. In summary, it is best to focus on getting a precise and consistent dose of CBD with as high of THC ratio as is comfortable and tolerable.

Extensive clinical studies have shown that THC and CBD in a 1:1 ratio is the most effective drug in the treatment of neuropathic pain.  Optimization of therapeutic doses of CBD oil can be a slow step-by-step process, where folks start off with small dosages of the drug to higher concentrations of CBD and gradually increase the dose of THC in the preparation.

The goal is to find a suitable dose of the drug in such a way that the dose of the drug enriched with CBD will contain as much THC as the person can tolerate.

What is the correct dosage of CBD?

Unlike many other drugs we are familiar with, there is not a “one dose fits all” when it comes to CBD. Every person’s metabolism and physiology is unique and will respond differently to varying amounts of CBD. Another factor that plays into CBD’s effects is the emotional and physical environment one is in when taking it, as well as one’s perceived stress levels. 

In general, researchers have observed an inverted U-shaped dose response curve for optimal CBD dosing. This means that at relatively low and high doses there are no physiological effects, while a middle range dose is most efficacious. When determining an effective dose, the general rule of thumb is “start low, go slow” and then gradually increase the dose every couple of days. When you feel your symptoms return (or new symptoms arise), stop and note that your last dose is your correct dose – this is referred to as “finding the peak.” Most people’s peak is between 10-40mg, however CBD is safe and has been well tolerated at doses up to 1,500mg/day. 

What is the Best or Most Effective Form of CBD?

CBD can be taken as a sublingual oil, as oral gelcaps or edible, or as a topical lotion or cream.  Sublingual products deliver the quickest hit (in 20-40 mins) but last the shortest duration (2-4 hrs). Oral products that you swallow take longer to kick in (2-3 hrs) but last the longest (6-8 hrs). Topical products provide only a local effect wherever they are placed.

What about Side Effects of CBD?

CBD interacts with CYP450 in the liver (similar to grapefruit juice) and therefore may inhibit the actions of certain prescription medications.  Any interaction with other drugs, however, has been at clinically significant – in other words, very high – doses and often involves an already compromised liver.  Otherwise, CBD used at regular, therapeutic doses, optimized for an individual’s peak needs, has no known side effects.

What about Drug Tests?

If you are subject to drug testing for any reason, know that THC use will be identified in a drug screen. With respect to hemp products, whether full-spectrum CBD which has negligible (<0.3% THC) and broad-spectrum CBD which is technically 100% THC free, the vast majority of labs that conduct drug screens in the United States cannot distinguish between THC and other cannabinoids. Most work-place drug screens and tests target delta9-tetrahydrocannabinol (THC) and do not detect the presence of Cannabidiol (CBD) or other legal natural hemp-based constituents. However, studies have shown that eating hemp foods and oils can cause confirmed positive results when screening urine and blood specimens. Accordingly, if you are subject to any form of drug testing or screening, it is recommended (even by the United States Armed Services) that you DO-NOT ingest hemp/cannabis products. Prior to consuming these products, consult with your healthcare practitioner, drug screening\testing company or employer.

What Else to Know?

Even before understanding and choosing from the variables of dose, delivery, type, and ratios, the most important consideration when choosing a cannabis product is quality assurance and transparency provided by the provider.  You will want to make sure that the product has 3rd party validation by a certified lab and is checked for potency and purity. Also you should check to see whether a batch or lot-specific Certificate of Analysis is provided. Due to the lack of regulation of this market, without these assurances, you cannot be certain of the quality or validity of the product you are choosing.  

How to Proceed

Knowing what type of product you are seeking and what is legal in your state are the first places to start when determining whether CBD is right for you.  If you live in a state where marijuana has been legalized for “adult-use” (aka, more than just for medicinal marijauna card holders) and you therefore have access to CBD:THC combo products, I encourage you to seek out a reputable dispensary and talk with one of their agents.  While the great preponderance of customers in the dispensary will be recreational drug users, the employees are incredibly knowledgeable and well-prepared to help you with whatever your pain management and health goals are. 

Know that due to the variety of products available as well as the range of effects any one cannabinoid combo can have, your solution may be multifactorial.  While I do not under any circumstances recommend smoking or vaping cannabis products, I do believe there is sound use for other forms of THC and CBD. Specifically, oil tinctures (under-the-tongue oil drops), mouth sprays, edibles  and even topicals (balm/lotion) can be amazing for pain management, and optimally you may end up using/needing a combination of each! That being said, whether you even “need” or want a CBD product with or without THC is a very personal decision.

Finally, as with anything that we put in or on our body, respect your bio-individuality. What “works” for any one of us can be dependent upon our pain level, digestion, liver function, skin absorption, stress level, sleep quality, environment and mindset – and even know that what works for you one day may change on another day based on those same things.