THC and CBD both reduced testosterone production in lab-grown adrenal cells, contradicting findings from human cannabis users | Research

The takeaway

Both THC and CBD significantly reduced DHEA, androstenedione, and testosterone production in H295R adrenal cells in a dose-dependent manner, contradicting the researchers' own prior finding that cannabis users had higher testosterone levels.

Endocrinologists, male fertility researchers, cannabinoid pharmacologists

THC and CBD reduced testosterone in cells, contradicting higher levels seen in cannabis users

What the researchers found

THC and CBD both reduced DHEA, androstenedione, and testosterone production in H295R cells dose-dependently. The effect was rapid and primarily affected late steps of steroidogenesis. It was not blocked by rimonabant (CB1 antagonist), indicating a non-CB1 mechanism. CBD additionally appeared to affect the CYP17A1 enzyme step. These in vitro results contradict the researchers' prior finding of higher testosterone in cannabis-using men.

Why it matters

The contradiction between lab results (cannabinoids reduce testosterone) and human observations (cannabis users have higher testosterone) highlights that the relationship between cannabis and male hormones is more complex than direct pharmacological effects suggest.

The numbers in context

Both THC and CBD reduced DHEA, androstenedione, and testosterone dose-dependently; inhibition was rapid; not blocked by rimonabant (CB1 antagonist); CBD affected CYP17A1 enzyme; prior human cohort showed higher testosterone in cannabis users

How the study worked

In vitro study using H295R adrenal cells. THC and CBD effects on steroid production measured by liquid chromatography-tandem mass spectrometry. CB1 receptor involvement tested with rimonabant. This followed the authors' earlier observation of higher serum testosterone in cannabis users from a cohort of young Swiss men.

What this study cannot tell us

In vitro system using adrenal cell line, not testicular cells which produce most testosterone. Concentrations may not reflect physiological exposure. Cannot replicate the complex hormonal feedback systems of the whole body. Single cell line.

How to read the evidence

Preliminary: in vitro study with a single cell line. While the mechanistic findings are clear, the contradiction with human data limits direct clinical application.

When this study was published

2026 in vitro publication following up on observations from a Swiss male cohort.

The bigger picture

This apparent contradiction between in vitro and in vivo findings is a reminder that cell culture results don't always translate to whole-body effects. The higher testosterone in cannabis users may be driven by indirect mechanisms, not direct cannabinoid action on steroidogenesis.

Questions still open

Why do cannabis users have higher testosterone despite cannabinoids inhibiting steroidogenesis in cells? Could compensatory hormonal feedback increase testosterone in vivo? Does route of cannabis administration affect hormonal outcomes?

Common questions

Does cannabis raise or lower testosterone?

It is complicated. In lab-grown adrenal cells, both THC and CBD reduced testosterone production. But the same researchers previously found that cannabis-using men had higher testosterone in their blood. The direct cellular effect and whole-body outcome appear opposite.

Why might the lab and real-world results disagree?

The researchers suggest that indirect mechanisms in the body, such as hormonal feedback loops or effects on other organs, may override the direct inhibitory effect on steroid-producing cells. The body is more complex than a cell culture.

Read the original research

Tetrahydrocannabinol (THC) and cannabidiol (CBD) inhibit androgen biosynthesis in H295R cells.

Biochemical and biophysical research communications, 797, 153179

View on PubMed ↗Publisher’s paper ↗

Citation

Zufferey, Fanny; Hebinger, Doriane; Brossaud, Anne-Claire; Millius, Laura; Rossier, Michel F. (2026). Tetrahydrocannabinol (THC) and cannabidiol (CBD) inhibit androgen biosynthesis in H295R cells.. Biochemical and biophysical research communications, 797, 153179. https://doi.org/10.1016/j.bbrc.2025.153179