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  • 6 min read

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    I'm writing this article as I've recently heard about conolidine through a client of mine. Oddly enough, it's touted as having been used in traditional Chinese medicine (TCM) and I've never heard of it. As a TCM herbalist and acupuncturist, I was trained in classical traditional Chinese medicine and I don't recall ever coming across this natural anti-nociceptive compound and the associated herb. I've decided to do a deeper dive into the rabbit hole of the internet. Below, I'll try to compile what information I've accumulated on conolidine for pain.


    Conolidine molecule for plant based pain relief analgesic

    What is Conolidine?

    Conolidine is a plant alkaloid that was first found in the tropical flowering crepe jasmine plant (tabernaemontana divaricata), mainly in the bark and root. Scientists have recently isolated the analgesic alkaloid, though traditional Chinese medicine (gou ya hua; 狗牙花), Ayurveda (chandni jasmine plant), and Thai herbal medicine have known of the associated plant's pain relieving effects for centuries.

    Native to Asia, the crepe jasmine is also known as: pinwheel flower, east Indian rosebay, moon beam, ceylon jasmine, susun kelapa, susoh ayam, crape jasmine, crepe gardenia, adam's apple, Nero's crown, coffee rose, jelutong badak.(1)


      Alkaloids contain nitrogen

    What is an Alkaloid?

    Alkaloids are organic nitrogen compounds found in plants and animals. Plant alkaloids are found in, you guessed it, plants. Most alkaloids in plants are concentrated in the leaves, seeds, roots, and fruits. Alkaloids have varying physiological effects on humans. Some alkaloid effects are recreational, others are medicinal, and some can be downright deadly, i.e. ricinine from the castor oil plant. When ingested, alkaloids tend to be bitter. Medicinally, alkaloids can have a wide range of uses. The major use that we are discussing here is that of analgesia, or pain relief.


      Crepe jasmine conolidine plant based pain relief compound with potential

    What Makes Conolidine Special?

    It's been called nature's morphine by some. The reason for this novel name is that thus far, conolidine has provided significant pain relief with very few side effects that are typical of opioids like morphine and codeine. This is because the molecular structure is not quite like that of an opioid. It, therefore, behaves a little differently in the body. Early testing has shown that conolidine doesn't show the GI distress or addictive qualities that the opioid family of pain relievers have. It has potential to be a very promising alternative to traditional opioids in treating chronic pain. 

    No longer limited to plant extraction, conolidine has been successfully synthesized in a laboratory environment, first in 2011 (Micalizio route)(2) and multiple times afterwards. This synthesis isolates the alkaloid for specific testing and allows for purity, control, larger dosing, and higher quantities.

    Research into conolidine has led to discovery of an opioid receptor in the body called ACKR3/CXCR7. ACKR3 seems to be the most sought after target for conolidine, which also disregards the other four classical opioid receptors(3). What's even more interesting is that researchers Andy Chevigné and his team have developed a variant (RTI-5152-12) of conolidine that binds to ACKR3 with higher affinity.


    Crepe Jasmine Flower is a source of conolidine

    What Makes Conolidine not so Special?

    The crepe jasmine bark only contains 0.00014% conolidine(4).  In my opinion, there must be other active compounds acting synergistically to produce the analgesic effect that traditional herbal medicine suggests. Further research will be necessary to understand the crepe jasmine's complete mechanism of action, but for now the focus is on the isolated alkaloid.

    There have been some patents initiated in the synthesis of conolidine, which may be why there has not been much freely distributed information. Companies may be working on a way to profitize conolidine for pain relief since the preliminary test data are extremely promising.

    Also, note that conolidine testing has been limited to mice at this point. Research data on conolidine and humans is very limited at this time. I imagine that the synthesis of conolidine will provide broader clinical testing opportunities.


    Conclusion - Could Conolidine be an Ingredient for Battle Balm?

    At this time, I am very interested in understanding the complete mechanism of action for conolidine. From what I've gathered, there's no definitive MOA that anyone has been comfortable with. 

    As an herbalist, I believe there's great value in the synergistic effect of medicinal plant compounds when taken together. I'm not sure what will result when conolidine is removed from it's system. Isolated conolidine may not have as impactful of a pain relieving punch when taken without supporting alkaloids. Or even worse, the conolidine could have a very small therapeutic index when not modulated by the rest of the herbal alkaloids. We don't quite know. This is definitely one of the limitations of isolate testing in laboratory environments.

    I do believe that conolidine has opened the door to a new physiological pathway for pain relief. This could lead us to healthier alternatives to opioid use and reduce the opioid abuse that has run rampant worldwide. The importance of finding safer, cleaner, & more natural ways to mitigate pain is paramount.

    One day, when conolidine has been better understood, I may consider adding it to Battle Balm in some way, shape, or form. But, for now, I will wait for more clinical results and research data on the benefits/consequences of conolidine.

    Until then, I think Battle Balm can be used as an opioid alternative in many cases of pain. If one is looking for a top-notch, clean, effective, non-addictive, over-the-counter topical analgesic, you've come to the right place.

     If you have questions, just drop us a line. Otherwise...

    Buy Battle Balm Now!

    Commonly Asked Questions about Conolidine

    What is conolidine good for?

    Conolidine has the potential to be a powerful, natural pain reliever without significant side effects. Found in nature, conolidine is showing the ability to treat chronic pain without the harmful side effects of opioids. Further testing is still necessary to confirm efficacy and safety.

    Is conolidine an opioid?

    Conolidine is not an opioid, though conolidine does exhibit pain relieving effects similar to opioids. From a receptor standpoint, conolidine does not interact with the MOP, DOP, KOP or NOP receptors like the opioid family. Conolidine targets the chemokine receptor, ACKR3, instead. This difference may be one of the reasons why conolidine does not have the same side effects that opioids exhibit.

    Is corydalis the same as conolidine?

    Corydalis is the genus of a perennial flowering plant in the poppy family with over 400 species. The tubers of corydalis (corydalis yanhusuo yan hu suo; 延胡索)  have been used in TCM for pain relief and blood disorders.

    Conolidine has been found in the tabernaemontana divaricata plant, which is in the Apocynaceae family. It is an evergreen shrub that also goes by many names, one of which is crepe jasmine.

    Corydalis and crepe jasmine are two different plants both used for pain relief. They most likely have different mechanisms of action on the body, given the information that I've gathered. Please note that there may be multiple active compounds in either plant that may synergistically produce similar pain relieving effects.

    What is the pinwheel flower for pain?

    The pinwheel flower is another name for the pinwheel jasmine, crepe jasmine, etc. (see above). The genus and species name is tabernaemontana divaricata. This is the same plant that have been linked to conolidine, a promising alkaloid for pain relief.

    What is gou ya hua painkiller?

    Gou ya hua is the pinyin name for tabernaemontana divaricata that has been used for centuries in traditional herbal medicine for pain relief. Gou ya hua (gouyahua) was recently found to contain conolidine, which has some promising value as a potential opioid alternative with fewer side effects.

    What is the MOA of conolidine?

    The mechanism of action of conolidine has not been completely sorted out. Thus far, it seems that conolidine only binds to the ACKR3 receptor and none of the other classical opioid receptors. It is interesting to note that testing was limited to approximately 240 potential receptors.(7) A comparison of drug effects to conolidine in multi-electrode array (MEA) cultures identified that it was most similar to that of ω-conotoxin CVIE, a Cav2.2 calcium channel blocker.(2)

    What is RTI-5152-12?

    RTI-5152-12 is a laboratory modified structure based on conolidine. This compound binds to the same ACKR3 receptor, but with much higher affinity than conolidine. Whether or not this higher affinity is valuable, is still under research & testing.


    1. NParks | Tabernaemontana divaricata

    2. Conolidine: A Novel Plant Extract for Chronic Pain - PMC (nih.gov) Edinoff AN, Patel AS, Baker MW, et al. Conolidine: A Novel Plant Extract for Chronic Pain. Anesth Pain Med. 2021;11(6):e121438. Published 2021 Dec 8. doi:10.5812/aapm.121438

    3. Pain-killing molecule developed with enhanced pharmaco properties - (biotechnologycommunity.com)

    4. Conolidine - Wikipedia

    5. A Natural Treatment for Chronic Pain - Neuroscience News

    6. The natural analgesic conolidine targets the newly identified opioid scavenger ACKR3/CXCR7

    7. New Study Further Advances the Treatment of Chronic Pain

    8. Definition of alkaloid

    9. Synthesis of conolidine and discovery of a potent non-opioid analgesic for pain

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