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  • Writer's pictureTravis Cesarone

Does CBD protect the human endocannabinoid system?

We frequently hear that CBD can protect the endocannabinoid system. The idea, derived primarily from preclinical research, is supported by one clinical trial with schizophrenic patients using 800 milligrams of CBD. But caution must be taken when translating cellular and rodent research into human medicine, according to a new clinical trial published in the journal Translational Psychiatry. (1)

How a cannabinoid affects the human body is complex and depends largely on each individual and their state of health. Cannabidiol (CBD), a compound naturally unique to the cannabis plant, targets numerous receptors and channels. Plus, its immediate properties entwine further with a diverse network of mechanisms.

Splitting criteria across two clinical trials

Earlier, The University of Cologne conducted a clinical trial with CBD and endocannabinoid levels on schizophrenia patients. But the trial rejected cannabis consumers. (2) Opposing these conditions, the new trial results published by Translational Psychiatry, which was conducted by the University College, London, rejected non-cannabis consumers. And a lack of psychological abnormality was an important addition to their criteria. (1)

Disregarding propaganda, cannabis use disorder in a clinical context defines participants who consume enough cannabis to retain an acute quantity of THC metabolites (THCCOOH) in their urine. Thirty-four heavy cannabis consumers endured a 28-tolerance break, with eleven participants blindly consuming a placebo for the trial’s duration. But another eleven consumers were blindly given 400 mg of CBD, whereas the remaining twelve participants took 800 mg of the cannabinoid daily.

The newly published results support the former trial, although it revealed unique responses to CBD in cannabis consumers compared to patients with schizophrenia.

Breaking a preclinical myth about low-dose CBD

Chronic THC consumption activates CB1 receptors. But the body compensates for excessive cannabinoid receptor activity by turning off some receptors. A natural transmitter, which exists in vertebrate animals, binds to cannabinoid one receptors. And that transmitter, known as anandamide, temporarily depletes after a heavy THC consumer quits cold turkey.

Endocannabinoid depletion during a THC tolerance break occurs due to the interment cannabinoid receptor loss. But preclinical research suggests that CBD inhibits FAAH, which is a special type of enzyme that breaks down anandamide. So researchers often connect the dots and assume that CBD protects anandamide from enzymatic degradation.

In reality, the human system might not be sensitive to CBD, which failed to protect the endocannabinoids at low doses. The latest study revealed that anandamide was still depleted in participants who took 400mg of CBD a day during their tolerance break from high-THC cannabis products.

A CBD dose that protects the endocannabinoid system

Only 800 milligrams of CBD a day protected the endocannabinoid system from intermittent depletion after quitting regular THC consumption. In patients with schizophrenia who don’t consume cannabis, though, 200mg of CBD taken four times a day led to elevated anandamide levels. (2) Whereas CBD only maintained the endocannabinoid systems of chronic cannabis consumers at high doses. (1)

CBD, at high doses, matched 7.5 milligrams of amisulpride as a treatment for schizophrenia in the earlier trial by The University of Cologne. Yet, despite clear improvement of psychiatric symptoms in non-cannabis users, CBD failed to regulate or improve mood in chronic THC consumers. The body must be under stress to produce anandamide. This author, therefore, suggests that CBD at moderate doses can reduce our need for endocannabinoid deployment because it simultaneously turns down inflammatory signals. Effects might cancel each other out, which might explain why it takes such a large dose of CBD to protect the endocannabinoid system.

Let us know in the comments if and how you benefit from CBD.


  1. Hua, D. Y., Hindocha, C., Baio, G., Lees, R., Shaban, N., Morgan, C. J., Mofeez, A., Curran, H. V., & Freeman, T. P. (2023). Effects of cannabidiol on anandamide levels in individuals with cannabis use disorder: findings from a randomised clinical trial for the treatment of cannabis use disorder. Translational psychiatry13(1), 131.

  2. Leweke, F. M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C. W., Hoyer, C., Klosterkötter, J., Hellmich, M., & Koethe, D. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational psychiatry2(3), e94.

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