The Cannabis Entourage Effect: Advantages & Examples

Cannabis Entourage Effect: Advantages & Examples

Words and images by @SuperFunker.

The Therapeutic Potential of Cannabis

Cannabis produces hundreds of phytochemicals (cannabinoids, terpenes and phenols). Although most of these compounds aren’t fully understood, a growing body of research has confirmed their therapeutic potential. Cannabis phytochemicals are known to influence your endocannabinoid system and induce therapeutic effects that can treat common maladies and serious diseases. Cannabis produces so many medically significant compounds that researchers often refer to it as a “phytochemical factory.”

Due to the potential health benefits, both the number and scope of Cannabis studies has greatly increased. Clinicians seek to leverage a variety of both physical and psychological healing effects to develop novel disease mitigation. An extensive list of this research can be found on Liquid Life's Scholarly Research page. We’ve sourced, described and linked more than 150 full-text studies, so you can quickly explore Cannabis science. Among the ailments considered:

  • Post-Traumatic Stress Disorder
  • Alzheimer’s Disease
  • Epilepsy
  • Liver Cirrhosis
  • Colon Cancer
  • Arthritis
  • Fibromyalgia
  • Depression
  • Multiple Sclerosis
  • Breast Cancer
  • Inflammation/Pain
  • Endometriosis
  • Insomnia
  • Gynecological Cancer
  • Inflammatory Bowel Disease
  • Social Anxiety Disorder

The Entourage Effect

Early Cannabis research assessed only a few compounds and often focused on single cannabinoids like THC (tetrahydrocannabinol) or CBD (cannabidiol). Studies examined the biological effects of individual molecules which led to the development of Epidiolex (pharmaceutical-grade CBD isolate). However, contemporary research is rapidly moving away from single-molecule assessments in favor of exploring the complex interplay of multiple compounds. When Cannabis phytochemicals are combined or when the plant integrity is maintained in a full-spectrum formula, the therapeutic effects are enhanced. This synergy is referred to as the Entourage Effect. And, compared to the utility of single-molecule extracts, the entourage synergy induces vastly superior medical outcomes. The benefits of a complex Cannabis profile are many:

  • Greater potency.
  • A smaller effective dosage.
  • Better health outcomes.
  • Fewer side effects.
  • Less severe side effects.
  • And, greater cost-effectiveness.

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Examples of the Entourage Effect

Researchers consistently validate the medical benefits of the Entourage Effect. The following are just few of the 100’s of studies that support these advantages.

THC + CBD Reduces Neuroinflammation
Al-Ghezi compared the effects of THC, CBD and a 1:1 ratio of THC + CBD on neuroinflammation associated with multiple sclerosis. Three assessments were conducted:

  • THC @ 10 mg/kg.
  • CBD @ 10 mg/kg.
  • THC + CBD @ 10 mg/kg each.

The results demonstrated that neither THC nor CBD caused a significant suppression of symptoms, but the 1:1 ratio induced a tangible reduction in neuroinflammation.

CBD + CBG Induces Neuroprotection
Mammana compared the effects of CBD, CBG (cannabigerol) and CBD + CBG on neuroprotection associated with neurodegenerative diseases. CBD and CBG are known to reduce inflammation, mitigate cell damage and control oxidative stress. And in this study, Mammana sought to establish the lower end of this effective range:

  • CBG @ 2.5 & 5 µM failed to produce significant neuroprotection.
  • CBD @ 2.5 & 5 µM induced neuroprotective effects.
  • CBD + CBG @ 2.5 & 5 µM improved upon the neuroprotective effects demonstrated by CBD alone.

The therapeutic benefits of CBD and CBG are enhanced when they are combined, creating an improved Cannabis compound that is effective even at a dose as low as 2.5 µM.

THC & CBD Combined with Co-Related Terpenoids to Treat Cancer
Namdar endeavored to explore the potential of THC and CBD to treat MDA-MB-231 (breast cancer cell line) and HCT-116 (colon cancer cell line) when combined with co-related terpenoids.

Cell death of the MDA-MB-231 breast cancer cell line:

  • THC resulted in ~10% cell death.
  • THCa co-related terpenoids exhibited no cytotoxicity,
  • THC combined with THCa co-related terpenoids resulted in ~40% cell death.
  • THC combined with CBDa co-related terpenoids exhibited no cytotoxicity.
  • CBD resulted in ~7% cell death.
  • CBDa co-related terpenoids exhibited no cytotoxicity.
  • CBD combined with CBDa co-related terpenoids resulted in ~70% cell death.
  • CBD combined with THCa co-related terpenoids exhibited no cytotoxicity.

    Cell death of the HCT-116 colon cancer cell line:

    • THC exhibited no cytotoxicity.
    • THCa co-related terpenoids exhibited no cytotoxicity.
    • THC combined with THCa co-related terpenoids resulted in ~15% cell death.
    • THC combined with CBDa co-related terpenoids exhibited no cytotoxicity.
      • CBD resulted in ~30% cell death.
      • CBDa co-related terpenoids resulted in ~10 to 36% cell death.
      • CBD combined with CBDa co-related terpenoids resulted in ~55% cell death.
      • CBD combined with THCa co-related terpenoids resulted in ~50% cell death.

      Although Cannabis contains relatively small amounts of terpenoids, when combined with THC or CBD at naturally occurring levels, cytotoxic activity is greatly enhanced.

      CBD Isolate Compared to Clone-202/Avidekel in Reducing Inflammation & Pain
      Gallily compared the dose-response of a CBD isolate to a Clone-202/Avidekel extract (CBD-dominant Cannabis chemovar with ~18% CBD and ~1% THC). In assessing the capacity of each to control inflammation and reduce pain, the CBD isolate produced a bell-shaped dose-response characterized by a rapid reduction in efficacy with higher doses. In contrast, the full-spectrum Clone-202/Avidekel extract exhibited continued effectiveness as the dosage increased. Thus, the CBD isolate has a very narrow therapeutic window, whereas Clone-202/Avidekel has a much broader response range. It’s the synergistic effect of the naturally occurring phytochemicals within the Clone-202/Avidekel that’s thought to produce this broader application range.

      CBD-Rich Full-Spectrum Formulas Compared to CBD Isolates in Treating Epilepsy
      Pamplona compared the therapeutic capacity of purified CBD and CBD-rich full-spectrum mixtures to treat epilepsy. He highlighted critical information that suggests several advantages associated with full-spectrum cannabis therapies:

      • Without applying the clinical threshold of a 50% reduction in seizure frequency, 71% of patients reported a reduction in seizures when consuming a full-spectrum mixture. In contrast, only 46% of patients reported similar improvements when using a CBD isolate.
      • When the above clinical threshold was applied, there was little difference between the efficacy of full-spectrum blends and CBD isolates. A 50% reduction was reported by 37% of those who used a full-spectrum formula and 42% among patients who used a CBD isolate. However, as detailed below, the dosage associated with a full-spectrum therapy was significantly less.
      • Full-spectrum Cannabis tinctures are more potent than isolated extracts, therefore a smaller amount of a full-spectrum treatment is required to achieve desirable results. The average daily dosage of an isolated extract (25.3 mg/kg/day) needed to be more than four times greater than the average daily dosage of a full-spectrum blend (6.0 mg/kg/day).
      • Full-spectrum Cannabis tinctures are associated with fewer side effects. In contrast, CBD isolates tend to dramatically increase undesirable reactions. Purified CBD tripled the rate of both mild and severe side effects among seizure patients. Typical adverse effects include appetite alteration, sleepiness, diarrhea, weight changes, fatigue, and nausea.

      Full-Spectrum Cannabis Blends are “Preferable” Therapies

      Doctor Ethan Russo reviewed research with a focus on addressing clinical endocannabinoid deficiency through Cannabis therapy. He explained the importance of a well functioning endocannabinoid system and the potential of Cannabis to restart/balance associated functionality. Russo also identified numerous treatment-resistant ailments that may respond to Cannabis-based medicines: migraine, fibromyalgia, irritable bowel syndrome, Huntington’s disease, Parkinson’s disease, post-traumatic stress disorder and depression. In treating various ailments, Russo indicated that single-molecule therapies may provide some relief, but are less than ideal. Instead, “standardized whole cannabis extracts that contain additional synergistic and buffering components, such as CBD and cannabis terpenoids, are certainly preferable.”

      Whenever considering a Cannabis product, a therapeutic that contains a combination of phytochemicals is a prudent choice. And, selecting a full-spectrum formula is even better. This rationale is the foundation of several cannabis items offered by Liquid Life British Columbia. Among our full-spectrum products are tinctures, balms and Phoenix Tears.

      Liquid Life British Columbia Cannabis CBD Products


      Al-Ghezi, Zinah Zamil et al (2019). Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways.

      Gallily, Ruth et al (2015). Overcoming the Bell‐Shaped Dose‐Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol.

      Mammana, Santa et al (2019). Could the Combination of Two Non-Psychotropic Cannabinoids Counteract Neuroinflammation? Effectiveness of Cannabidiol Associated with Cannabigerol.

      Namdar, Dvora et al (2019). Terpenoids and Phytocannabinoids Co-Produced in Cannabis Sativa Strains Show Specific Interaction for Cell Cytotoxic Activity.

      Pamplona, Fabricio et al (2018). Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis.

      Russo, Ethan B. (2016). Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes.