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

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.

Zufferey, Fanny et al.·Biochemical and biophysical research communications·2026·Preliminary EvidenceAnimal StudyAnimal Study
RTHC-08746Animal StudyPreliminary Evidence2026RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Animal Study
Evidence
Preliminary Evidence
Sample
Not reported

What This Study 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.

Key Numbers

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 They Did This

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.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

  • ?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?

Trust & Context

Key Stat:
THC and CBD reduced testosterone in cells, contradicting higher levels seen in cannabis users
Evidence Grade:
Preliminary: in vitro study with a single cell line. While the mechanistic findings are clear, the contradiction with human data limits direct clinical application.
Study Age:
2026 in vitro publication following up on observations from a Swiss male cohort.
Original Title:
Tetrahydrocannabinol (THC) and cannabidiol (CBD) inhibit androgen biosynthesis in H295R cells.
Published In:
Biochemical and biophysical research communications, 797, 153179 (2026)
Database ID:
RTHC-08746

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / Observational
Case Report / Animal StudyOne case or non-human subjects
This study

Tests effects in animals (usually mice or rats), not humans.

What do these levels mean? →

Frequently Asked 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 More on RethinkTHC

Cite This Study

RTHC-08746·https://rethinkthc.com/research/RTHC-08746

APA

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

MLA

Zufferey, Fanny, et al. "Tetrahydrocannabinol (THC) and cannabidiol (CBD) inhibit androgen biosynthesis in H295R cells.." Biochemical and biophysical research communications, 2026. https://doi.org/10.1016/j.bbrc.2025.153179

RethinkTHC

RethinkTHC Research Database. "Tetrahydrocannabinol (THC) and cannabidiol (CBD) inhibit and..." RTHC-08746. Retrieved from https://rethinkthc.com/research/zufferey-2026-tetrahydrocannabinol-thc-and-cannabidiol

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.