Progesterone

For an informed discussion with your doctor or pharmacist. This information collection is not a clinically validated interaction checker. Missing data do not establish safety. Do not change or stop prescribed medicines on the basis of this information. The findings apply to the specific conditions studied; laboratory and animal studies cannot be directly extrapolated to humans.

Active substance: Progesterone

Examples of brand names: Utrogest [DE]

ATC code: G03DA04

Main use (for orientation): Hormone therapy

Documented research summary

Direct animal findings for progesterone/THC and THC/CBD inhibition of progesterone-induced CatSper responses in human sperm in vitro. Not a clinical progesterone-treatment interaction or fertility prediction. Progesterone studies in cannabis use disorder in 2026 (n=148) and 2019 (n=8) investigate abstinence/withdrawal, not acute co-administration.

Uncertainties and limitations

Not a complete safety conclusion. Animal, cell or withdrawal models cannot be extrapolated to a longer-term clinical combination. Distinguish preparations, administration routes and cannabinoid material actually used. PMID 16272754 concerns 7β-hydroxy-Δ8-THC in monkey microsomes (CYP3A8), not unchanged Δ9-THC. PMID 42429926 available only as original abstract; full-text retrieval unsuccessful. Sperm findings are not a clinical interaction with oral or vaginal progesterone. Documented individual title/abstract assessment with selected relevant full texts; not an exhaustive worldwide systematic review or independent human specialist approval. Missing data do not establish safety. All 28 cannabinoids are within the search scope, not 28 clinically investigated pairs per drug.

Separately recorded findings

5 separately recorded findings. Each statement applies to its documented study context.

THC – laboratory and animal studies

Finding ID: B0513

Type of result: Context-specific finding

Observation: The cannabinoid inhibited progesterone-induced calcium responses; this does not establish classical progesterone-receptor antagonism.

Mechanism: Inhibition of CatSper-mediated responses to progesterone and other activation conditions.

Study type: Human sperm in vitro; electrophysiological/calcium endpoints

Context studied: Ex-vivo sperm from several donors; relevant methods and results of PMC12046078 read.

Clinical interpretation: Applicability to humans is unresolved; preclinical endpoint, not clinical evidence of treatment efficacy or safety.

Limitations and uncertainties: Not a clinical interaction with oral/vaginal progesterone or a fertility prediction. Do not equate THC/CBD endpoints indiscriminately; CatSper inhibition also tested independently of progesterone.

Original sources for this finding: The major phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), affect the function of CatSper calcium channels in human sperm. [VF_P_40078063]

CBD – laboratory and animal studies

Finding ID: B0514

Type of result: Context-specific finding

Observation: The cannabinoid inhibited progesterone-induced calcium responses; this does not establish classical progesterone-receptor antagonism.

Mechanism: Inhibition of CatSper-mediated responses to progesterone and other activation conditions.

Study type: Human sperm in vitro; electrophysiological/calcium endpoints

Context studied: Ex-vivo sperm from several donors; relevant methods and results of PMC12046078 read.

Clinical interpretation: Applicability to humans is unresolved; preclinical endpoint, not clinical evidence of treatment efficacy or safety.

Limitations and uncertainties: Not a clinical interaction with oral/vaginal progesterone or a fertility prediction. Do not equate THC/CBD endpoints indiscriminately; CatSper inhibition also tested independently of progesterone.

Original sources for this finding: The major phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), affect the function of CatSper calcium channels in human sperm. [VF_P_40078063]

THC – laboratory and animal studies

Finding ID: B0515

Type of result: Context-specific finding

Observation: Progesterone reduced THC potency in one systemic study; combined oestradiol/progesterone context with intracerebral THC showed other endpoint-specific responses.

Mechanism: Progesterone alters selected THC antinociception endpoints.

Study type: Rat models with experimental hormone replacement, pharmacodynamics

Context studied: Different hormone-replacement and THC administration regimens.

Clinical interpretation: Applicability to humans is unresolved; preclinical endpoint, not clinical evidence of treatment efficacy or safety.

Limitations and uncertainties: No uniform direction or clinical analgesia/hormone-treatment recommendation. Do not present multi-hormone regimens as an isolated progesterone effect.

Original sources for this finding: Cyclic ovarian hormone modulation of supraspinal Δ9-tetrahydrocannabinol-induced antinociception and cannabinoid receptor binding in the female rat. [VF_P_24951841]; Gonadal hormones do not alter the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol in adult rats. [VF_P_25863271]

Cannabis abstinence; no standardised acute cannabinoid administration – insufficient evidence

Finding ID: B0516

Type of result: Not an isolated acute pair assessment

Observation: The larger study reported a sex-dependent craving finding; the older pilot with eight women showed only a non-significant trend.

Mechanism: Progesterone as experimental treatment for cannabis craving during abstinence.

Study type: Human studies in an abstinence/craving context

Context studied: 2026: 148 people (82 men, 66 women), progesterone 200 mg twice daily for one week. 2019: eight women, five days.

Clinical interpretation: No isolated investigation of the pair; clinical relevance as a medicine–cannabinoid interaction cannot be determined.

Limitations and uncertainties: No acute progesterone–cannabinoid interaction or measured hormone pharmacokinetics. 2026 full text unavailable; no general treatment recommendation.

Original sources for this finding: Sex differences in stress responding in a randomized, placebo-controlled clinical trial of progesterone in cannabis use disorder. [VF_P_42429926]; Exogenous progesterone for cannabis withdrawal in women: Feasibility trial of a novel multimodal methodology. [VF_P_30711528]

7β-hydroxy-Δ8-THC; metabolite – laboratory and animal studies

Finding ID: B0517

Type of result: Context-specific finding

Observation: Progesterone stimulated conversion of 7β-hydroxy-Δ8-THC to 7-oxo-Δ8-THC.

Mechanism: Substrate-dependent activation of THC-metabolite oxidation.

Study type: Monkey liver microsomes, mechanistic assay

Context studied: CYP3A8/microsomal context; original abstract.

Clinical interpretation: Mechanistic metabolite finding; not direct evidence for parent THC or clinical hormone therapy.

Limitations and uncertainties: Metabolite, not unchanged Δ8/Δ9-THC; not a clinical progesterone interaction.

Original sources for this finding: Stimulatory effects of testosterone and progesterone on the NADH- and NADPH-dependent oxidation of 7beta-hydroxy-delta8-tetrahydrocannabinol to 7-oxo-delta8-tetrahydrocannabinol in monkey liver microsomes. [VF_P_16272754]

References and access status

[VF_L_D0435] PROMETRIUM (PROGESTERONE) CAPSULE [ACERTIS PHARMACEUTICALS, LLC]

Original source / bibliographic reference

Authors: Marketing authorisation holder; official product information via DailyMed

Year: 2026

Source type: Official medicine information; relevant identity, PK, PD and DDI sections read individually

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

[VF_P_16272754] Stimulatory effects of testosterone and progesterone on the NADH- and NADPH-dependent oxidation of 7beta-hydroxy-delta8-tetrahydrocannabinol to 7-oxo-delta8-tetrahydrocannabinol in monkey liver microsomes.

Original source / bibliographic reference

Authors: Funahashi T, Tanaka Y, Yamaori S, Kimura T, Matsunaga T, Ohmori S, Kageyama T, Yamamoto I, Watanabe K.

Year: 2005

Source type: Scientific publication; precise study type and suitability described in the finding or individual review

DOI: 10.2133/dmpk.20.358

PMID: 16272754

Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[VF_P_24951841] Cyclic ovarian hormone modulation of supraspinal Δ9-tetrahydrocannabinol-induced antinociception and cannabinoid receptor binding in the female rat.

Original source / bibliographic reference

Authors: Wakley AA, McBride AA, Vaughn LK, Craft RM.

Year: 2014

Source type: Scientific publication; precise study type and suitability described in the finding or individual review

DOI: 10.1016/j.pbb.2014.06.007

PMID: 24951841

Source access – 23 October 2026: Automated direct retrieval was restricted; this does not establish that the link is broken.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[VF_P_25863271] Gonadal hormones do not alter the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol in adult rats.

Original source / bibliographic reference

Authors: Wakley AA, Wiley JL, Craft RM.

Year: 2015

Source type: Scientific publication; precise study type and suitability described in the finding or individual review

DOI: 10.1016/j.pbb.2015.03.021

PMID: 25863271

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

PubMed Central – full-text access according to the literature database – Archive attribution confirmed by Europe PMC metadata. Direct retrieval was not fully verified here; access may require a browser check.

Europe PMC – full-text access according to the literature database – Listed as freely available HTML full text in the official Europe PMC metadata. Direct retrieval was not fully verified here.

[VF_P_30711528] Exogenous progesterone for cannabis withdrawal in women: Feasibility trial of a novel multimodal methodology.

Original source / bibliographic reference

Authors: Sherman BJ, Caruso MA, McRae-Clark AL.

Year: 2019

Source type: Scientific publication; precise study type and suitability described in the finding or individual review

DOI: 10.1016/j.pbb.2019.01.008

PMID: 30711528

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

PubMed Central – full-text access according to the literature database – Archive attribution confirmed by Europe PMC metadata. Direct retrieval was not fully verified here; access may require a browser check.

Europe PMC – full-text access according to the literature database – Listed as freely available HTML full text in the official Europe PMC metadata. Direct retrieval was not fully verified here.

[VF_P_40078063] The major phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), affect the function of CatSper calcium channels in human sperm.

Original source / bibliographic reference

Authors: Wehrli L, Altevogt H, Brenker C, Zufferey F, Rossier MF, Strünker T, Nef S, Rahban R.

Year: 2025

Source type: Scientific publication; precise study type and suitability described in the finding or individual review

DOI: 10.1093/humrep/deaf020

PMID: 40078063

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[VF_P_42429926] Sex differences in stress responding in a randomized, placebo-controlled clinical trial of progesterone in cannabis use disorder.

Original source / bibliographic reference

Authors: Martin EL, Baker NL, Neelon B, Saladin ME, Gray KM, Watson Z, McRae-Clark AL.

Year: 2026

Source type: Scientific publication; precise study type and suitability described in the finding or individual review

DOI: 10.1007/s00213-026-07128-2

PMID: 42429926

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

Research as of 23 October 2026. Not all original full texts could be reviewed in full. Source accessibility and the strength of scientific evidence must be assessed separately. An accessible link does not establish medical approval; a bibliographic record with an abstract does not replace the original full text.

Drug search and explanation of the evidence · Guide: cannabinoids and medicines · Author and responsibility