Glossary

CannaKeys Databank Glossary

Acetylcholine (neurotransmitter) Acetylcholine is a multi-function communication molecule that can transmit central and peripheral nerve impulses, for example. (See Ligand)

Affinity: This measure describes the degree of interest a specific ligand has to bind with a particular receptor (this measure is typically expressed in Ki values).

Agonism: The action of combining or binding a compound (e.g., THC) with a specific receptor site (e.g., CB2), thus producing the same or similar effect that an endogenous compound or agonist (e.g., anandamide) would have. The binding potential is typically measured in nM=nano Molar (a factor of one billionth or 0.000 000 001 or 10^-9). To provide the reader with some context, here are a few examples:

1. Strong or Full Agonism (1-9nM): Synthetic HU-210 (Ki) ~0.25nM =100 x the efficacy of THC at CB1
2. Moderate Agonism (10-99nM): THC (Ki) 25nM at CB1
3. Weak Agonism (100-999nM): Anandamide (Ki) 239nM at CB1 =1/10 the efficacy of THC at CB1
4. Very Weak Agonism(1000+nM): CBD 1459nM  =1/58 x the efficacy of THC at CB1

Agonist: Interacts with a receptor site to produce a specific effect (positive affinity). 

Allosteric modulator (+ or -): Allosteric binding sites are indirect binding sites (at or around a receptor) that can influence the agonist or antagonist effect. 

Allosteric binding sites are indirect binding sites that can influence an agonist and inverse agonist of a target ligand.

Anandamide (endocannabinoid/neurotransmitter): Anandamide is a naturally occurring communication molecule that is at once an endocannabinoid and neurotransmitter. (See Ligand)

Animal trials (in vivo testing) are experiments conducted on animals. 

Antagonist: Interacts to block or reduce the expected effect (partial positive affinity). 

Cannabis Chemotypes (aka chemovars): These are valuable designations for predicting specific medicinal properties or adverse effects potentials. As the last four decades of research discovered, three basic numbers are the primary key (but not the only variables) to realizing specific therapeutic effects for any cannabis plant. One, the amount of the primary psychoactive cannabis constituent tetrahydrocannabinol (THC for short); two, the amount of the non-psychoactive cannabis constituent cannabidiol (CBD); and third, the ratio of THC to CBD. It is these three numbers that discern the three basic chemotypes of cannabis. The Roman numerals I, II, and III are used to distinguish them. Chemotype I contains more THC than CBD. Chemotype II contains relatively equal amounts, and chemotype III contains more CBD than THC. 

Cannabis Species: The genus cannabis is divided into three species; sativa, indica, and ruderalis.

Cannabinoid: A chemical compound that interacts with the human body, producing a measurable effect in the body, mind, and emotion, such as relaxation, improved resilience to stress, neuroprotection, or analgesia. Cannabinoids come in three types: those made by plants (primarily cannabis), those made by the human body itself, and synthetic versions (human-made).

Cannabinoid Receptor Sites: Cannabinoids bind to several unique receptor sites—which, once engaged, produce a particular signal that, in turn, creates a specific physiological and mental/emotional response. 

CB1 is an endogenous receptor site in the brain and central nervous system.

CB2 is an endogenous receptor site abundantly present in the periphery and cells of the immune system.

Clinical trials are conducted on humans.

Cortisol (steroidal hormone) Cortisol is a steroid made by the adrenal glands that functions like other glandular-produced hormones in producing several specific physiological and psychological effects (e.g., stress management).

Cytokines (pro- and anti-inflammatory) Cytokines are a group of small signaling proteins involved in modulating inflammation. (See Ligand)

Dopamine (neurotransmitter/hormone) Dopamine is a communication molecule involved in various functions relevant to biological survival and mental-emotional well-being. (See Ligand)

Double-blind placebo-controlled trials are considered the “gold” standard for intervention-based scientific investigations. A vital characteristic of this type of study is that neither the investigator nor the subject knows who gets the drug to be tested or the placebo. 

Efficacy: This measure describes a ligand’s ability to activate the receptor once binding has occurred (this measure is typically expressed in Ki values).

Endocannabinoid Enzymes such as FAAH and MAGL alter the bioavailability of the body’s endocannabinoids anandamide and 2-AG, respectively, and with it, the effects they engender.  

Endocannabinoidome (eCBome): The relatively new idea of an (eCBome) is used to describe the larger environment that interacts with the endocannabinoid system (ECS). In general, this includes all knowns aspects of the ECS (i.e., endocannabinoids, endocannabinoid receptor sites, their metabolizing enzymes, and endocannabinoid tone).

We can activate the eCBome with the use of cannabis constituents, food (e.g., diet), nutraceuticals (e.g., turmeric), mind-body approaches (e.g., mindfulness, exercise, acupuncture), the microbiome (e.g., probiotics), and the lipidome (e.g., omega-3, C15).

By engaging the eCBome, especially alongside the use of appropriate cannabis-based products, we can significantly and safely improve patient outcomes by:

• Inducing precision effects
• Establishing predictability of effects
• Preventing of lowering any adverse effects and potential
• Reducing total mg amounts of cannabis-based products used to achieve the same or better, and longer-lasting results

Endogenous opioids (e.g. endorphins) are ligands made by the human body for the purpose of producing effects such as analgesia, anti-anxiety, and mood improvements similar to that of opioids.(See Ligand)

Epinephrine (neurotransmitter/hormone) Epinephrine is a significant communication molecule involved in numerous necessary functions such as “fight, flight, or freeze” responses. (See Ligand)

Estrogen (hormone) Estrogen is the primary female sex hormone. (See Ligand)

Fatty Acid Amide Hydrolase (FAAH) is the enzyme produced and regulated by the human body that breaks down anandamide.

GABA (neurotransmitter) The inhibitory ligand GABA is produced by metabolizing the excitatory neurotransmitter glutamate thus reducing cellular excitement. (See Ligand)

Genotype: The plant’s genetic composition or DNA blueprint of life.

Ghrelin (hormone) Ghrelin is a hormone that is associated with the sensation of hunger. (See Ligand)

Glucagon (hormone) Glucagon is a hormone that tells the liver (or muscles) to convert glycogen into glucose for cellular energy consumption. (See Ligand)

Glutamate (neurotransmitter) Glutamate is the primary excitatory neurotransmitter. (See Ligand)

G-Protein Coupled Receptor Sites (GPR)are a vast family of receptor sites embedded in the skins (membranes) of trillions of individual cells that make up the human body. GPRs that are cannabinoid sensitive include the classical endocannabinoid receptor site 1 (CB1) and (CB2). In addition, there are GPR 3, GPR 6, GPR 18, GPR 55, and opioid receptor sites (mu/μ and delta/δ), all of which are modulated (either in part or significantly) by components of the endocannabinoid system. 

Hemp: An industrial crop usually with less than 0.3% THC.

Human trials are human subject research. 

Insulin (hormone) One of the prime functions of insulin is to stimulate the uptake of glucose. (See Ligand)

Inverse agonist: Interacts to create the opposite effect (negative affinity).

K_d stands for “disassociation constant” and simply represents ligand-receptor affinity (the concentration of ligand disassociation). 

K_i stands for “inhibitory constant” (or the concentration of competitive displacement). The use of K_i helps anticipate how potent a particular substance has to be to inhibit the action of a cannabinoid, for example. K_i is an absolute value. Whenever possible, CK will exhibit the efficacy of an agonist at a specific receptor in K_i. However, sometimes research papers only offer values in EC₅₀ or IC₅₀. The Cheng Prusoff equation can convert IC₅₀ or EC₅₀ values for a more direct comparison (see below).

Laboratory trials (in vitro testing) are experiments that operate under controlled conditions, performing careful measurement and utilizing the scientific method (e.g., observing and measuring the effect of a cannabinoid against bacteria in a Petri dish). 

Ligand(s) is derived from the Latin word “to bind or to tie.” In medicine, a ligand is a small molecule, functional group, or ion that binds with another to form a more complex or larger one. Examples of ligands include agonists or activators (initiate activity) or inhibitors (reduce an action). More specifically, cannabinoids such as THC or CBD are ligands, but so are carbon monoxide, water, ammonia, heme, or sulfides. Several ligands and their respective receptor sites are cannabinoid sensitive, i.e., are modulated either in part or significantly by the endocannabinoid system. They include in alphabetical order:

• Acetylcholine (e.g., memory, wakefulness)
• Anandamide (endocannabinoid/neurotransmitter)
• Endogenous opioids (body generated analgesic)
• Epinephrine (neurotransmitter/hormone)
• Estrogen (hormone)
• Cortisol (steroidal hormone)
• Cytokines (pro- and anti-inflammatory)
• Dopamine (neurotransmitter/hormone)
• GABA (neurotransmitter)
• Ghrelin (hormone)
• Glucagon (hormone)
• Glutamate (neurotransmitter)
• Insulin (hormone)
• Leptin (hormone)
• Norepinephrine (neurotransmitter/hormone)
• Oxytocin (hormone)
• Serotonin (neurotransmitter)
• Testosterone (hormone)
• Vasopressin (hormone)

Leptin (hormone) Leptin is a multipurpose hormone commonly associated with satiation. (See Ligand)

Lipidome: The lipidome is a full accounting of all lipids embedded in the membranes of each cell. Cellular membranes can be thought of as the skin of the cell. The skin of our trillions of individual cells is made from lipophilic compounds containing lipophilic receptor sites such as CB1 or CB2, ready to interact with lipophilic compounds such as cannabinoids. Polyunsaturated fatty acids (PUFAs) are their essential building blocks. The human body does not make its PUFAs. Thus, we must consume them to survive and thrive. PUFAs such as omega-3 and omega-6 fatty acids are primary building blocks the body uses to produce endocannabinoids and thus play a significant role in maintaining a healthy ECS. 

Lipophilic: Combining the prefix lipo- from the Greek word lipos, translated “fat,” and the other Greek word phílos, translated “love,” create the meaning and practical description of “fat-loving” and dissolves easily in fat, respectively. Cannabinoids are lipophilic.

Marijuana: A slang term borrowed from Mexican Spanish and commonly used to denigrate the plant and its users by the narrative on the war on drugs.

Meta-analyses typically include a review (statistical or qualitative) of many already published scientific studies to provide an overview, extrapolate data, or use them in innovative ways. 

Microbiome: The microbiome consists of the human body (the host) and the wide variety of microbial organisms (e.g., viruses, bacteria, fungi) that live within the body and on the skin’s surface. Some microbial members of the “superorganism” are disruptive intruders, such as dermatophytes or fungi that cause onychomycosis (foot and nail fungus), for example, while others are beneficial organisms called probiotics. 

The connection between probiotics and components of the ECS is only beginning to be understood. For instance, CBD and several probiotics, including acidophilus, have been found to share the ability to modulate PPAR-gamma, which in turn produces anti-inflammatory effects. Furthermore, oral administration of acidophilus has been shown to reduce pain by modulating the endocannabinoid receptor 2 (CB2). Additionally, THC has shown the ability to reduce signs and symptoms of acute respiratory distress syndrome (ARDS), a typically fatal infection, by changing the microbiota in the lungs and the gut of test animals. More specifically, THC significantly increased the presence of beneficial bacteria while decreasing pathogenic bacteria.

Most fermented foods such as sauerkraut, kimchi, kefir, and yogurt naturally contain an abundance of probiotic cultures. 

Modulator: A compound (e.g., THC, CBD, beta-caryophyllene) that affects or changes the activity of a  receptor site (e.g., CB1, CB2), an enzyme (e.g., FAAH), or a biochemical pathway (e.g., metabolism), for example.

Molar or molarity measures the amount/concentration of a dissolved substance (solute) in a solution in a given volume. For example, 1 mol/L is written as 1M. For example, both K_d and K_i affinities are measured in nM units. nM=nano Molar (a factor of one billionth or 0.000 000 001 or 10^-9)

Molecules are made up of individual atoms that are held together by chemical bonds.

Monoacylglycerol lipase (MAGL) is the enzyme produced and regulated by the human body that breaks down the endocannabinoid 2-AG.

Neurotransmitter is a molecule that transmits a signal across the synaptic cleft, a space between nerve cells.

Norepinephrine (neurotransmitter/hormone)  Like epinephrine, the general purpose of norepinephrine is to ready the brain and body for action (e.g., fight, fight, freeze). (See Ligand)

Orthosteric binding sites are direct or primary binding sites of a receptor.

Oxytocin (hormone) Oxytocin is a multipurpose ligand associated with bonding, birth, and lactation. (See Ligand)

Peroxisome Proliferator-Activated Receptors or short PPARs (pronounced “peepars”) are Nuclear Receptor Proteins (located inside a cell), some of which are modulated by cannabinoids. For example, THC is an agonist of PPAR γ (gamma).

Phenotype: This term is utilized to delineate the variable observable characteristics, such as the shape of a leaf. E.g., siblings sharing some of the same visible traits but not others.

Potency: to be precise, potency measures need specific definitions, such as 

LD₅₀ —Median Lethal Dose 

ED₅₀ —Median Effective Dose

EC₅₀ —Half Maximal Effective Concentration

LC₅₀ —Lethal Concentration 50%

IC₅₀  —Half Maximal Inhibitory Concentration

Pre-clinical trials are not conducted on humans and include laboratory and animal experiments.

Receptor Binding is the value between a cannabinoid and a receptor that inform you of the intensity and duration of the effect and the nature of the subsequent actions (e.g., anti-inflammatory, mood-enhancing).

Serotonin (neurotransmitter) Serotonin is associated with the experience of happiness and well-being. (See Ligand)

Silexan Silexan is a lavender oil preparation taken in capsule form. Released in 2010, it was developed in Germany and is approved for anxiety-related restlessness. Tests of the preparation indicated it is 36% linalool, 34% linalyl acetate, and minor quantities of eucalyptol, borneol, and camphor.

Strain: A strain is an attempt to differentiate further or create a different value ranking within one of the three prime species of cannabis.

Study Types

• Pre-clinical trials are not conducted on humans and include laboratory and animal experiments.
• Clinical trials are conducted on humans. 
• Laboratory trials (in vitro testing) are experiments that operate under controlled conditions, performing careful measurement and utilizing the scientific method (e.g., observing and measuring the effect of a cannabinoid against bacteria in a Petri dish). 
• Animal trials (in vivo testing) are experiments conducted on animals. 
• Meta-analyses typically include a review (statistical or qualitative) of many already published scientific studies to provide an overview, extrapolate data, or use them in innovative ways. 
• Human trials are human subject research. 
• Double-blind placebo-controlled trials are considered the “gold” standard for intervention-based scientific investigations. A vital characteristic of this study is that neither the investigator nor the subject knows who gets the drug to be tested or the placebo. 

Testosterone (hormone) is the primary male sex hormone. (See Ligand)

Transient Receptor Potential (TRP) Channels (pronounced “trips”) include (aka Ionic Cannabinoid Receptors): TRPA1, TRPV1, TRPV2, TRPV4, and TRPM8. (“A” stands for ankyrin), (“V” stands for vanilloid) and (“M” stands for melastatin). Vasopressin (hormone) is a multi-function hormone associated with many processes, including raising blood pressure. (See Ligand)