The Entourage Effect: Maca, Cacao, Terpenes and the Endocannabinoid System

By Dr Corin Storkey, co-founder of Seleno Health · Updated November 2026

New studies are showing that synergy occurs between molecules with full-plant forms or extracts compared to isolating out single compounds. This 'entourage' approach is now commonly accepted as the ideal way to regulate our own cannabinoids.

Key takeaways

• The endocannabinoid system (ECS) helps keep the body in balance and responds to stress, inflammation and injury.
• It can be influenced directly (for example by THC) or indirectly, by helping the body's own endocannabinoids work better. The indirect approach is often called the entourage effect.
• Maca's macamides inhibit FAAH, the enzyme that breaks down anandamide, in lab studies. Our University of Otago research confirmed this for our maca products.
• Cacao and terpenes may also support the entourage effect, although much of the evidence is still early-stage.

For thousands of years, plants have been used to activate the natural cannabinoid responses of the body and nervous system by native and indigenous healers. In all cases, these so-called “master plants” have been taken in a full or whole plant form. The more recent Western approach with master plants like cannabis Sativa has focused on isolating and consuming pure extracts of single components – for example, CBD (cannabidiol) isolate (1). So the question begs, is there any benefit to taking a full-spectrum array from a cannabinoid regulator, or is it best to use a standardised single component isolates? New research has pointed in the direction of full-plant forms of cannabinoid regulators as these have demonstrated an “entourage effect” (2) in which a variety of “inactive” metabolites and closely related molecules markedly increased the activity of the primary endogenous cannabinoids in our bodies – anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Below we discuss what we now know about the endocannabinoid system and important information in using it therapeutically. We also evidence the entourage effect and discuss the pros and cons of different cannabinoid activators.

The Endocannabinoid System (ECS)

The endocannabinoid system (ECS) is a security and defence system that seeks to maintain internal harmony and balance within the body. It is linked with and can regulate the nervous, immune, hormonal or the endocrine systems (3) and the enteric nervous system (ENS) (4) of the gut sometimes called the “second brain”. The ECS acts like a master switch to control all other systems.

The role of the ECS is to relay important and timely information between these systems, but also prepare the body to adapt to external or internal stressors (3). Acting as an inbuilt thermostat the ECS seeks out and maintains the homeostatic balance point for each of the body’s systems and responses to the external environment. Think of it like a thermostat on a heater set to maintaining the room at a desired temperature that is comfortable for all.

The ECS responds to various stimuli, like injury, chronic inflammation, different forms of pain and infections (3). It protects cells and cell components, like the mitochondria and nerve cells, which are highly sensitive and prone to damage. In addition, the ECS attempts to re-balance and remove other toxic insults, like carcinogens, solvents, UV light, pesticides, and more (3).

Because the ECS is involved in so many body systems, researchers are studying it in relation to pain, inflammation, mood, sleep, gut health, hormonal health and neurological conditions. Much of this research is still at an early stage.

Anandamide and the ECS – How it Works

The ECS is all throughout the body and consists of signalling molecules called endocannabinoids (ECBs – keys) and receptors (locks). The main cannabinoid receptors are called CB1 and CB2, while the signalling molecules that unlock them are called anandamide (AEA), and 2-acyl glycerol (2-AG), collectively known as ECBs (6). Research has also discovered other receptors linked to the ECS including GPR55, GPR119, the ion channel receptor TRPV1 through which pain is mediated, and PPAR-alpha receptors, located in the nucleus of cells, that take part in regulating genes associated with pain and inflammation (7).

When harmful triggers like inflammation and injury act on the body, the ECS activates the production of ECBs like AEA or 2-AG from the membranes of cells in the vicinity of the injury. ECBs are produced on demand whenever the body requires their services. AEA for example can respond to external stimuli by activating the CB1 receptor in the brain and influence the production of serotonin and regulation of the HPA response of the body – our body’s main stress response system (8). Through this approach, the nervous system can rapidly adapt the body’s physiological response to the original stimuli and return balance and harmony.

Figure 1. Anandamide regulates the nervous system by feeding back messages to the CB1 receptor allowing adaption to external or internal stimuli.

1. Directly

By using exogenous molecules not produced by the body that directly bind the CB1 or CB2 receptors known as endocannabinoids or cannabinomimetics (9). The most well-known of these is the plant cannabinoid Tetrahydrocannabinol (THC) present in some strains of cannabis (10). Beyond this, there are many other plants and cannabimimetic that have been discovered to directly bind the cannabinoid receptors, for example, Salvinorin A from the plant Salvia Divinorum (11), Yangonin from Kava Kava (12), and Perrottetinene (13) from New Zealand Liverwort (Figure 2). All four of these examples are molecules extracted from traditional medicines used by different cultures to treat and manage pain or for enhancing spiritual practices.

The benefits of using a direct cannabinomimetic are that it acts rapidly with high potency. It can offer relief for severe or chronic conditions associated with pain and can assist in the treatment of chronic inflammation. The drawbacks are that it can be difficult to dose adjust to ensure that desensitisation of CB receptors does not occur. Using cannabinomimetics like THC regularly or excessively increases the risk for developing a dependency on it and can result in an inability to manufacture sufficient natural ECBs like anandamide (14). People who develop a dependency on cannabinomimetics may find they suffer from withdrawal effects like brain fog, lethargy, and anxiety when the mimetic is withdrawn (14). In addition, some CB1 agonists like THC can be psychoactive, a property that is not ideal for everyone and often not wanted when consuming it for medicinal benefits.

Figure 2. Examples of some plants and their components that act directly on the endocannabinoid receptors.

2. Indirectly – the entourage effect

By using molecules not produced by the body that increase production or sensitivity of our natural endocannabinoids like Anandamide, but do not themselves bind the CB1 or CB2 receptors. This is known as the cannabinoid entourage effect (15). Studies in cannabis have shown that using pure THC or CBD (isolate) is not as effective as the whole plant extract as different components in the full plant work in synergy to promote enhanced healing over any one single compound (16). The entourage effect may occur through different mechanisms, e.g., preventing the breakdown of the ECB’s by enzymes that are responsible for their destruction in which case the ECB’s last longer in the body giving a prolonged and enhanced action, or improving the binding of ECB’s on various receptors, or by activating other receptors, e.g., opening up ion channels that cause a synergistic effect of the major molecule. The most commonly targeted ways to improve cannabinoid entourage are via inhibition of FAAH – the key enzyme that breaks down our ECB’s or through slowing re-uptake of ECB’s (17). Plants like Peruvian maca act as entourage enhancers through a series of FAAH inhibitors known as macamides that are produced during the traditional drying and preparation processes. In addition, quality ceremonial cacao paste can contain N-acetyl-ethanolamines (18) that also can act as FAAH inhibitors to enhance the natural production and function of ECBs. Both maca and cacao have been traditionally used for their abilities to indirectly regulate the ECS and improve resilience to stress (Figure 3). A further class of entourage enhancers called terpenes is discussed in more detail below.

Supporting the body's own endocannabinoids may have advantages over taking direct cannabinomimetics. Endocannabinoids are made on demand, where they are needed and in amounts that match the body's needs, and they are quickly broken down and recycled once their job is done. This may mean fewer issues with tolerance and dependency, although indirect approaches have been studied far less in people.

Figure 3. Examples of some plants and their components that act indirectly on the endocannabinoid system.

How to create entourage using maca and cacao

Maca is a traditional Peruvian food used to support energy, balance and resilience to stress. When traditionally dried and prepared, maca contains macamides that inhibit FAAH in laboratory studies (17). Our own research with the University of Otago confirmed that our maca products and macamides inhibit FAAH, and found that macamides bind cannabinoid receptors only weakly and do not activate them, consistent with an indirect, entourage-type effect. Macamide levels vary widely between products, so choose a traditionally prepared maca that is tested for macamide content. See which type of maca is right for you and how maca works.

Certain cacao beans and ceremonial cacao paste can contain molecules called N-acetyl-ethanolamines (18) that also can act as FAAH inhibitors. As these molecules are fat-soluble it is important to find a quality cacao paste or full cacao beans/nibs as these are the highest sources of N-acetyl-ethanolamines. Cacao powder does not contain the same levels as its full bean equivalents.

Maca and cacao both contain compounds that inhibit FAAH, which may help protect the body's own anandamide from rapid breakdown. This is a promising, but still largely pre-clinical, explanation for their traditional use for resilience and wellbeing, and it may also complement other approaches to supporting the ECS.

Figure 4. The ECS response with FAAH inhibitors – protecting our natural anandamide (left). FAAH inhibitors enhance natural anandamide function and build resilience fluctuations during stress. This can improve our total body health and well-being, especially when dealing with chronic health conditions (right).

Mood elevation and entourage with terpenes

Terpenes are a large and diverse class of organic compounds produced by a variety of plants. Terpenes are what give each flower, herb, and fruit its unique scent and flavour. Every day, everywhere you go, you encounter terpenes. When you zest a lemon, you smell terpenes. Open a jar full of herbs; what you sense is the terpenes. Stop and smell the roses? More like stop and smell the terpenes. Terpenes are aromatic compounds that, when inhaled, applied to the skin or consumed, enhance our sensory experience and greatly influence flavours and aromas.

The cannabis plant is known to contain more than 100 terpenes (15), and most plants contain only a handful of terpenes, the different terpenes in cannabis are dependent upon a variety of factors such as the strain of cannabis, growing methods i.e., indoor/outdoor or environmental factors (19). Terpenes have been shown to work in synergy with both exogenous and endogenous cannabinoids to promote the entourage effect’ (20).

Early research (21) suggests that combining specific terpenes (such as limonene, pinene, myrcene and linalool) with cannabinoids may influence their effects on mood and anxiety, although more clinical research is needed. When it comes to cannabis, all the constituents combine to create the experience. Think of it like flying a plane: cannabinoids such as THC and CBD control the altitude and speed, while terpenes act like the rudder, steering the experience towards feeling calm and relaxed, or focused and alert. Read more in terpenes and the entourage effect.

Summary

• The endocannabinoid system (ECS) is a key part of how the body maintains balance and responds to stress, injury and inflammation.
• It can be influenced directly or indirectly by plant compounds, each approach with its own pros and cons.
• Direct cannabinomimetics act quickly and potently, but need careful dosing to avoid desensitisation.
• Indirect regulators help the body's own endocannabinoids work better, for example by slowing their breakdown. This is known as the entourage effect.
• Common entourage compounds include macamides (from maca), N-acylethanolamines (from cacao) and terpenes (from cannabis and many other plants).
• Quality matters: choose traditionally prepared, tested products.

Frequently asked questions

What is the entourage effect?

The entourage effect describes how different plant compounds can work together, or help the body's own endocannabinoids work better, producing a greater effect than single isolated compounds.

Does maca affect the endocannabinoid system?

In lab studies, maca's macamides inhibit FAAH, the enzyme that breaks down the endocannabinoid anandamide. Our University of Otago research confirmed this for our maca products and found macamides do not directly activate cannabinoid receptors.

Is maca a cannabinoid?

No. Maca contains no THC or CBD and is not psychoactive. Its macamides appear to act indirectly on the endocannabinoid system.

Can maca and cacao be taken together?

Yes, maca and cacao are traditionally combined in Peru, and both contain compounds that may support the endocannabinoid system indirectly.

Watch the full webinar for free

Video Key Timestamps:

0:00 Introduction

0:59 What is the ECS?

3:09 How does the ECS work?

7:41 How do we activate our ECS?

8:28 Directly – cannabimimetics

13:08 Indirectly – “entourage effect”

21.59 Cannabinoids in cannabis sativa

24:58 Cannabidiol – CBD

26:38 THC and cannabis addiction

31:48 Cacao and entourage

34:57 Maca and entourage

39:04 How to use maca for entourage

42:21 Meet Good Herb Soda

43:09 Therapeutic composition of cannabis

44:59 Cannabis vs Hemp

47:07 What are terpenes

48:34 The entourage effect with terpenes

50:59 Cannabis regulations in New Zealand 2020

53:24 The 6 main terpenes found in cannabis

54:14 1. Myrcene

59:36 2. Limonene

105:40 3. Pinene

109:47 4. Beta-Caryophyllene

112:58 5. Linalool

116:20 6. Terpinolene

119:36 What is Good Herb Soda?

120:53 How do you use Good Herb Soda?

125:18 Where can you buy Good Herb Soda? 

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Written by Dr Corin Storkey Founder and Director of Seleno Health.