By Dr. Benjamin Caplan, MD | Board-Certified Family Physician, CMO at CED Clinic | Evidence Watch
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Book a consultation →A 2025 narrative review proposes that CBD may influence colorectal cancer development through the serotonin signaling system, potentially acting as both protective and harmful depending on biological context. However, every piece of evidence cited comes from laboratory and animal studies, with no human clinical trial data available. This means CBD should not be used to prevent or treat colorectal cancer based on current science.
CBD and Colon Cancer: A Promising Hypothesis Built on Preclinical Ground
A new review maps how cannabidiol might both fight and fuel colorectal cancer through the serotonin system, but all supporting evidence comes from cell and animal studies, and human clinical validation remains entirely absent, leaving the hypothesis intriguing but far from actionable.
#28
Limited Direct Relevance
Entirely preclinical evidence base with no human trial data precludes any clinical application at this time.
Colorectal Cancer
Serotonergic Pathway
Preclinical Evidence
Endocannabinoid System
Colorectal cancer remains the second leading cause of cancer death in the United States, and millions of Americans now use CBD products that were legalized before their health effects were rigorously studied. The question of whether CBD helps, harms, or is neutral in the context of gastrointestinal malignancy is not merely academic. Patients with colorectal cancer or those at elevated risk are already using CBD for symptom management, often without disclosing it to oncologists, making the gap between public consumption and scientific understanding a genuine clinical concern.
Colorectal cancer biology involves numerous interacting signaling pathways, including the Wnt/beta-catenin axis and, as increasingly recognized, the serotonergic system. Serotonin, produced in large quantities by gut enterochromaffin cells, participates in both normal intestinal physiology and tumor development. CBD, a non-intoxicating cannabinoid with a complex pharmacological profile, has limited direct affinity for the classical CB1 and CB2 cannabinoid receptors but instead modulates a broader range of targets, including serotonin 5-HT1A receptors. This 2025 narrative review, authored by a single investigator affiliated with the University of Massachusetts, synthesizes preclinical evidence to build the hypothesis that CBD may influence colorectal cancer through its effects on serotonergic signaling.
The review cites preclinical studies showing that CBD can inhibit cancer cell proliferation, promote apoptosis, and modulate inflammation in cell line and animal models. Its most original contribution is the argument that the serotonergic pathway itself has dual roles in colorectal cancer, meaning CBD’s modulation of this system could theoretically be protective in some contexts and deleterious in others. Importantly, the review does not cite a single human clinical trial supporting CBD’s anticancer efficacy in colorectal cancer. The author appropriately acknowledges this gap and calls for further research, but the absence of clinical data means the hypothesis, however plausible mechanistically, remains speculative. No systematic search methodology was reported, and the review does not declare funding sources, further limiting the strength of its conclusions.
I appreciate that this review is honest about its own limitations. The dual-modulatory framing is the most intellectually responsible part of the paper: it resists the temptation to simply declare CBD anticancer and instead acknowledges that the same serotonergic machinery could cut both ways. That honesty matters because it counters a growing tide of claims online that CBD fights cancer, claims that routinely cite exactly this type of preclinical mechanistic work as though it were established clinical fact. The gap between a plausible molecular hypothesis and a proven therapy remains enormous here.
In my practice, I see patients with gastrointestinal cancers using CBD for nausea, appetite, anxiety, and sleep, and I support those uses when the evidence and the clinical picture warrant it. What I do not do is encourage CBD as an anticancer agent, because the evidence simply is not there. When patients bring studies like this one to me, I explain that laboratory findings in cell dishes do not translate automatically to the human body, and that the very pathway being discussed here could theoretically work against them. Until human trials address this question directly, the appropriate clinical posture is supportive curiosity, not therapeutic recommendation.
This review sits at the very earliest stage of the research arc: hypothesis generation from preclinical evidence. It is not a systematic review, not a meta-analysis, and does not contain original experimental data. For clinicians tracking the cannabinoid oncology literature, the paper’s contribution is a conceptual framework rather than actionable findings. The serotonergic pathway as a node of CBD activity in colorectal cancer is scientifically interesting and may help design future preclinical experiments, but it does not yet offer a basis for clinical decision-making. Clinicians should recognize that the 2018 Farm Bill context the review describes is a regulatory, not a scientific, milestone, and that legalization of hemp-derived CBD did not constitute any endorsement of safety in cancer contexts.
From a pharmacological standpoint, clinicians should remain alert to potential interactions between CBD and chemotherapeutic agents, many of which are metabolized through CYP3A4 and CYP2C19 pathways that CBD is known to inhibit. This is a practical concern that the review does not address. Patients using CBD alongside oncologic treatment should be counseled about these interactions, and providers should document CBD use as part of medication reconciliation. The one concrete recommendation this paper supports is not a treatment change but a research agenda: well-designed clinical trials are needed before any evidence-based statement about CBD and colorectal cancer can be made.

