Cannabinoids is a “No-Go” While a Cancer Patient is on Immunotherapy; but is It Safe to Use Psychedelics During Cancer Immunotherapy?

Immunomodulation is a key mechanism by which cancers evade host immunity, and immune checkpoint inhibitors (ICIs) such as antibodies targeting PD-1/PD-L1 and CTLA-4 have become important antineoplastic therapies by releasing this inhibition to restore antitumour immune activity. At the same time, cannabinoids and classical psychedelics (serotonergic hallucinogens) are increasingly used by people with cancer for symptom relief, including anxiety, depression, pain, cachexia and inflammation. Earlier preclinical and some clinical work has raised concern that cannabinoids can diminish ICI efficacy, while in vitro studies have suggested that certain psychedelics may exert anti-cancer or anti-inflammatory effects through modulation of innate and adaptive immunity; however, evidence about how psychedelics affect tumour growth in vivo and whether they interact with ICIs during cancer therapy is lacking. Romach and colleagues set out to perform a small-scale preclinical evaluation of two psychedelic agents — lysergic acid diethylamide (LSD) and a psilocybin-containing mushroom extract — using in vitro cytotoxicity assays and an in vivo syngeneic mouse model of E0771 breast cancer, both alone and in combination with an anti-PD-1 antibody. The study aimed to test whether psychedelic exposure influences cancer cell viability and tumour growth, and whether such exposure might interfere with PD-1 inhibitor activity, given possible immunomodulatory effects mediated principally via the serotonin 5-HT2A receptor.

Two complementary experimental approaches were reported: an in vitro cytotoxicity assay using a breast cancer cell line and an in vivo syngeneic mouse model using the E0771 breast cancer model. For the cytotoxicity assay, E0771 cells were plated in 96-well plates and allowed to attach for 16–24 hours at 37°C with 5% CO2. After replacing the medium with assay medium containing test items, cells were exposed to either a psilocybin-containing mushroom extract at 103 µg/ml or LSD at 6.8 µg/ml for 48 hours. Cell viability was assessed using an XTT reagent, with optical density read at 450 nm once vehicle-treated cells reached an OD of 0.5–1.5. The extracted text does not report replicate numbers, controls beyond a vehicle, nor statistical analysis details for the in vitro assay. The in vivo component used a syngeneic E0771 breast cancer model in mice to assess anticancer activity of the same psychedelic preparations, alone and in combination with anti-PD-1 immunotherapy. Test agents were administered orally: the mushroom extract at 0.685 µg per mouse and LSD at 10.3 µg per mouse, five days per week. Anti-PD-1 antibody was given intraperitoneally twice weekly. The extraction does not clearly state mouse strain, sex, group sizes, tumour implantation details, randomisation or blinding procedures, timing of treatment relative to tumour inoculation, or the primary tumour outcome measures (for example, tumour volume endpoints or survival). Figures are referenced in the Results but were not included in the extracted text, and no detailed statistical methods or analysis plan (such as intention-to-treat or specific tests) are reported in the provided sections.

In vitro, both the psilocybin-containing extract and LSD reduced viability of E0771 breast cancer cells in the XTT assay; the text reports that each “induced cell death” in vitro and refers to figures for these data. However, numerical results, percent viability reduction, p-values and replicate numbers are not provided in the extracted material. Contrary to the in vitro cytotoxicity, both psilocybin and LSD were reported to promote tumour growth in the syngeneic E0771 mouse model in vivo; the authors state that these agents “induced tumor growth” and again point to figures for illustration. The extraction does not provide quantitative tumour growth data, statistical comparisons, time courses, or information about whether the tumour-promoting effect occurred when psychedelics were given alone or specifically in combination with anti-PD-1 therapy. Thus, while a qualitative discordance between in vitro cytotoxicity and in vivo tumour-promoting effects is the principal reported finding, the provided text lacks the detailed numerical outcomes, measures of variability and statistical inference needed to fully characterise the effects or their magnitude. Adverse events in animals, effects on immune cell populations, pharmacokinetic data or mechanistic readouts are not reported in the extracted Results section, and the interaction with anti-PD-1 therapy is not explicitly described in terms of outcome measures within the available text.

Romach and colleagues interpret their findings as indicating that psychedelics possess immunomodulatory properties that could be deleterious in the context of cancer immunotherapy. They highlight an apparent discordance: whereas LSD and psilocybin extract showed cytotoxicity against E0771 cells in vitro, both agents were associated with increased tumour growth in the syngeneic mouse model. The authors place these results alongside prior concerns about cannabinoids diminishing ICI activity and suggest that psychedelics might similarly interfere with immune-based cancer treatments. The paper frames psychedelics as generally considered physiologically safe for humans and effective for reducing anxiety and depressive symptoms in people with cancer, but cautions that serotonergic modulation via the 5-HT2A receptor — implicated in cell proliferation and immune regulation — could have unintended effects on tumour immune stroma and on responses to immune activation therapies. The extracted text does not contain a detailed discussion of limitations, but the authors note the preliminary nature of the work and call for expansion and validation of these findings in further studies. They stress the clinical relevance given increasing use of psychedelics among cancer patients and recommend caution when initiating immunotherapy or when considering psychedelic use during cancer treatment, including when ICIs are not being used. No mechanistic data, immune phenotyping, or detailed interaction analyses are presented in the extracted discussion, and the authors do not provide definitive clinical guidance beyond advising prudence and further research to validate and extend these preclinical observations.

The authors conclude that, although psychedelics are used by patients with cancer to alleviate symptoms and treatment-related side effects, their immunomodulatory properties may conflict with cancer treatments, particularly immunotherapy. Given the reported in vivo tumour-promoting signals and the absence of definitive interaction data, Romach and colleagues advise caution regarding psychedelic use in patients who are receiving or planning to receive immunotherapy and call for additional research to validate and clarify these findings.