An extensive review catalogued the individual medicinal properties of major and minor cannabinoids, terpenes, and flavonoids that contribute to the entourage effect, with accumulating evidence for pain and potential in opioid reduction.
Read this if you want to understand why different cannabis strains have different effects and what specific compounds contribute to pain relief.
Over 100 cannabinoids plus terpenes and flavonoids work synergistically in the entourage effect
What the researchers found
This comprehensive review examined the medicinal properties of individual components in cannabis well beyond the usual focus on THC and CBD. The author catalogued the therapeutic potential of major and minor cannabinoids, primary and secondary terpenes, and flavonoids, explaining how these work synergistically to produce what is called the entourage effect.
For pain and migraine specifically, the review found accumulating evidence for therapeutic benefits, though most evidence comes from studies of general chronic pain rather than headache-specific trials. The review also identified supporting evidence that cannabis may assist in opioid detoxification and weaning, positioning it as a potential tool against the opioid epidemic.
The detailed profiling of individual compounds enables understanding of why different cannabis strains produce different effects. For example, the terpene beta-caryophyllene activates CB2 receptors and has anti-inflammatory properties, while myrcene has analgesic and sedative effects. Knowledge of these individual properties is necessary for developing strain-specific treatments targeted at specific conditions.
Why it matters
Most cannabis research and clinical discussion focuses narrowly on THC and CBD, but cannabis contains over 100 cannabinoids plus numerous terpenes and flavonoids. Understanding the individual and synergistic properties of these compounds is essential for developing standardized, condition-specific cannabis medicines rather than treating all cannabis as a single drug.
The numbers in context
Cannabis contains over 100 cannabinoids, numerous terpenes, and various flavonoids. The review covered major cannabinoids (THC, CBD, CBG, CBN, CBC, THCV), primary terpenes (myrcene, limonene, linalool, alpha-pinene, beta-caryophyllene), secondary terpenes, and multiple flavonoids with individual medicinal property profiles.
How the study worked
This was a comprehensive narrative review of the medical literature covering the use of cannabis and cannabinoids in pain, migraine, headache, and facial pain, combined with a detailed examination of the pharmacological properties of individual cannabinoids, terpenes, and flavonoids.
What this study cannot tell us
Much of the evidence for individual compounds comes from preclinical or in vitro studies rather than human clinical trials. The entourage effect, while plausible, has limited direct clinical evidence. The review necessarily covers a vast amount of pharmacological data, and the depth of evidence varies widely across compounds.
How to read the evidence
This is a comprehensive narrative review synthesizing evidence across many compounds, with evidence quality varying from preclinical to clinical across different components.
When this study was published
Published in 2018. Cannabis science, particularly around minor cannabinoids and terpenes, has continued to advance rapidly.
The bigger picture
Cannabis science is moving from a THC/CBD binary toward precision medicine that considers the full chemical profile of cannabis products. This review provides the foundation for that approach by systematically documenting what each component does. As production standards become more regulated, this knowledge enables breeding and formulation of strain-specific therapeutic products.
Questions still open
- Can the entourage effect be quantified and optimized for specific conditions? Will strain-specific clinical trials produce better outcomes than studies using single-compound preparations? How should the terpene and flavonoid profiles of cannabis products be regulated and labeled?
Common questions
What is the entourage effect?
Can cannabis help with the opioid crisis?
Read the original research
Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science.
Headache, 58(7), 1139-1186
Citation
Baron, Eric P. (2018). Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science.. Headache, 58(7), 1139-1186. https://doi.org/10.1111/head.13345
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