Cannabinoids, Terpenes, and the Entourage Effect

Published June 27, 2019

Cannabis has long been a banned and regulated substance in the United States. A global prohibition on medicinal and recreational use halted product sales and related medical research for many years. Somewhat shockingly, the US Government filed for a cannabis-related patent on “cannabinoids as antioxidants and neuroprotectants” in 1999 which was subsequently issued in 2001. By 2012, we saw the first states legalize the recreational use of cannabis, and in 2016 several of the states had legalized medical cannabis.

This is all largely due to the fact that cannabis has been at the center of one of the most exciting developments in modern science with the discovery of the endocannabinoid system, a previously unknown communication system in the human body.

While the scientific community still has much to learn about cannabinoids, the endocannabinoid system, and how the two interact, our understanding of what happens when our bodies use and ingest cannabinoids is appropriately advanced.


The Endocannabinoid System

The endocannabinoid system (ECS) is found in all complex animals and is crucial for regulating our everyday experience. It is responsible for regulating a variety of functions including appetite, blood pressure, bone growth, digestion, immune response, inflammation, memory, motor function, pain, and the protection of neural tissues.

The ECS is made up of three components; endocannabinoid receptors, endocannabinoids, and the enzymes that synthesize or metabolize endocannabinoids.

One of the roles that endocannabinoids play is as a modulator, or messenger between neurons. Cannabinoids are the chemical messengers for the ECS. They are produced and transmitted by neurons and are responsible for effectively moderating and controlling the release of neurotransmitters across the synapse. Because neurotransmitter synapses are a 1-way communication path on their own, cannabinoids play the critical role in communicating information backward, creating a 2-way communication path and modulating homeostasis, a key element in the biology of all living things.

Ingesting phytocannabinoids, or any chemical that interacts with the ECS, allows patients to support their ECS in the same manner that patients use dietary supplements and prescription medications. A deficiency in the ECS, stress, injury or illness are all instances that may benefit from supplementation. By supplementing the ECS, the goal is to support physiological balance and homeostasis.


Endocannabinoid Receptors

There are two primary types of endocannabinoids receptors; CB1 and CB2. There are also further CB-type and related receptors that appear to play an important role in overall ECS function and health, which you can read more about here. The research on these CB-type and related receptors is just emerging, but if the history of medicinal cannabis research is any guide, we have much to learn and much good will hopefully come of it.


CB1 Receptors

CB1 receptors are found primarily in the brain and are responsible for influencing behaviors in this region. These receptors, with their cannabinoid partners, function as a modulator of inhibitory and excitatory neurotransmitters across the synapse. THC is able to bind to and activate these receptors, resulting in the psychoactive effects of cannabis products that include THC.

While CB1 receptors are found primarily in the brain, CB2 receptors are found throughout the body - as well as in the brain. Brain functions that are affected by the CB1 and CB2 receptors are extensive, including; anxiety, appetite, blood-brain permeability, body temperature, cognition, decision making, emotions, fear, learning, memory, motor control, pain, regulation of bodily movement, sense of reinforcement or reward, and stress.


CB2 Receptors

CB2 receptors are primarily found in the gastrointestinal system, immune and blood cells, microglia brain tissues, peripheral nervous system, spleen, and tonsils. In fact, the CB2 receptors in the brain were only recently identified - and it may be that we have yet to learn of additional CB2 receptor locations in the body. CB2 receptors may even regulate activity and information flow between brain networks. If proven, this suggests that CB2 receptors modulate the inputs that various brain functions receive from other neural networks which may ultimately guide complex behavior.

Cannabis plant



Throughout recent history of scientific understanding of the cannabis plant, it had been thought that a relatively small number of cannabinoids were pharmacologically active. As the scientific community learns more about the endocannabinoid system and its complexities, other questions about the cannabis plant beg answers. Specifically, researchers have begun to try to understand why users of medical cannabis claim that different cannabis varieties lead to different medicinal or psychoactive effects.

Research has revealed a likely answer. Instead of looking at the cannabis plant as a source of single ‘hero’ compound like THC or CBD, we should instead look at all of the compounds produced by the plant and seek to better understand how and why different combinations of compounds result in differing medicinal benefits. For this, we must look to the other major set of compounds produced by the cannabis plant called terpenes.


What are Terpenes and What Do They Do?

Terpenes are the aromatic elements of plant-based essential oils. They are found in all vegetables, fruits, and spices, and are recognized by the FDA as safe food additives. Terpenes produced by the cannabis plant are the same as terpenes produced by other non-cannabis related plants. It is now believed that terpenes are an integral part of determining how cannabinoids interact with the ECS.

Terpenes interact with a variety of receptors in the body, not just the ECS. They are pharmacologically active and work synergistically with cannabinoids when ingested, even at concentrations as low as .05% by weight. The mechanism by which terpenes interact with and alter the effects of cannabinoids is not yet well understood, and is undergoing extensive research around the world.


The Entourage Effect

The benefits of cannabinoids and terpenes, which are both pharmacologically active, combine to affect the ECS in ways that appear to go beyond the action of either molecule on its own. Their interaction is commonly referred to as the entourage effect - a critical concept to understanding how to best take advantage of the natural benefits the Cannabis plant offers.