Progesterone
Fatal overdose may occur when GABAergic substances are combined with other depressants such as opiates, benzodiazepines, barbiturates, gabapentinoids, thienodiazepines or alcohol.[1]
It is strongly discouraged to combine these substances, particularly in common to heavy doses.
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| Chemical Nomenclature | |||||||||||||||||||||||||||||||||||||||||||||||||
| Common names | P4, Pregnenedione | ||||||||||||||||||||||||||||||||||||||||||||||||
| Substitutive name | Pregn-4-ene-3,20-dione | ||||||||||||||||||||||||||||||||||||||||||||||||
| Systematic name | (1S,3aS,3bS,9aR,9bS,11aS)-1-Acetyl-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9a,9b,10,11,11a-tetradecahydro-7H-cyclopenta[a]phenanthren-7-one | ||||||||||||||||||||||||||||||||||||||||||||||||
| Class Membership | |||||||||||||||||||||||||||||||||||||||||||||||||
| Psychoactive class | Depressant | ||||||||||||||||||||||||||||||||||||||||||||||||
| Chemical class | Steroid | ||||||||||||||||||||||||||||||||||||||||||||||||
| Routes of Administration | |||||||||||||||||||||||||||||||||||||||||||||||||
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| Summary sheet: Progesterone |
Pregn-4-ene-3,20-dione, also known as Progesterone or P4 is a steroid sex hormone of the progestogen class. It occurs naturally and is the bodies major progestogen.
Progesterone can be taken orally, vaginal, rectal and by subcutaneous or intramuscular injection.
Progesterone is commonly used as a part of trans-feminising hormone therapy or post menopausal Hormone replacement therapy.
History and culture
Progesterone was first discovered in 1929 by George W. Corner and Willard M. Allen. By 1934 pure crystalline material was achieved by Adolf Butenandt at the Chemisches Institut of Technical University in wikipedia:Gdańsk. Synthesis was accomplished later that year. [2]
In a 2012 study higher levels of progesterone were linked to lower affinity to competitive behavior in women.[3][4]
Chemistry
Progesterone is a naturally occurring pregnane steroid and is also known as pregn-4-ene-3,20-dione. It has a double bond (4-ene) between the C4 and C5 positions and two ketone groups (3,20-dione), one at the C3 position and the other at the C20 position.[5]
Pharmacology
Progesterone on it's own acts as a antagonist on the σ2 receptor and as a negative allosteric modulator on nicotinic acetylcholine receptors. However most of the psychoactive effects of progesterone are induced by it's metabolites.[6]
Metabolism
Progesterone is mainly metabolised in the liver, therefore the route of administration significantly influences the intensity of experienced effects. The most important metabolites are allopregnanolone, pregnanolone, isopregnanolone and epipregnanolone.[7] Allopregnanolone and Pregnanolone are documented to have antidepressant, anxiolytic, stress reducing, antiagressive, sedative, sleep aiding, analgesic, amnesic, anesthetic, anticonvulsant & neuroprotective effects.[8][9]Allopregnanolone and Pregnanolone act as positive allosteric modulators of GABAA whereas isopregnanolone and epipregnanolone selectively counteract GABAA as well as the sedative and anesthetic effects.[7]
Subjective effects
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
Physical effects 
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- Increased bodily temperature - at high concentration progesterone elevates body temperature for ~1°C
- Sedation
- Pain relief
- Motor control loss
Cognitive effects 
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After effects 
Experience reports
There are currently 0 experience reports which describe the effects of this substance in our experience index.
Toxicity and harm potential
Warning: Progesterone is a naturally occuring sex hormone, changing its levels might induce gender dysphoria or premenstrual syndrome.
Progesterone has relatively low toxicity relative to dose.
It is strongly recommended that one use harm reduction practices when using this substance.
Lethal dosage
The observed LD50 in mice was 100mg/kg via intravenous, 327mg/kg intraperitoneal and > 200mg/kg orally, anasthetic effects were observed at 16mg/kg intraperitoneal.[10]
Tolerance and addiction potential
Dependence potential of Progesterone has been sparsely reported by transfeminine people. There is one case report of a women on post menopausal HRT that documents addiction.[11]
Tolerance to the offects of Progesterone metabolites on GABA will build within a few years and return to baseline within a few months after cessation.[citation needed]
Interactions
Combining oral progesterone with food leads to a two fold increase in absorptions. [12] Since oral progesterone is a oil soluable reports of increased effects when combined with fatty foods do seem plausible.
Dangerous interactions
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This dangerous interactions section is a stub. As such, it may contain incomplete or invalid information. You can help by expanding upon or correcting it. |
Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
- Depressants Taking oral progesterone together with alcohol or barbiturates will increase absorption rates and peak potentially leading to black out intervals or loss of motor control, anesthetic levels in humans are not documented, but might be reachable. Other dangerous depressants are benzodiazepines and opioids since their absorption can be increased, resulting in a higher risk of overdose.[13]
Legal status
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This legality section is a stub. As such, it may contain incomplete or wrong information. You can help by expanding it. |
Progesterone is widely available as prescription medication or in some cases over the counter and generally not controlled. Taking transgender HRT is not as widely accepted and may be prosecuted. [14]
See also
External links
References
- ↑ Risks of Combining Depressants - TripSit
- ↑ Josimovich, J.B. (11 November 2013). Gynecologic Endocrinology. Springer Science & Business Media. pp. 9, 25–29. ISBN 978-1-4613-2157-6. Archived from the original on 14 January 2023. Retrieved 1 February 2016.
- ↑ Buser, Thomas. "The impact of the menstrual cycle and hormonal contraceptives on competitiveness" (PDF). Journal of Economic Behavior & Organization. Gender Differences in Risk Aversion and Competition. 83 (1): 1–10. doi:10.1016/j.jebo.2011.06.006. ISSN 0167-2681. Archived from the original (PDF) on 2 February 2024. Retrieved 2 February 2024.
- ↑ Piosik, Romuald (2003). "Adolf Butenandt und sein Wirken an der Technischen Hochschule Danzig". CHEMKON. 10 (3): 135–138. doi:10.1002/ckon.200390038. ISSN 0944-5846.
- ↑ "Compound Summary Progesterone". National Library of Medicine. 12 March 2024. Retrieved 12 March 2024.
- ↑ Gonzalez, Susana Laura (2020). "Progesterone for the treatment of central nervous system disorders: the many signaling roads for a single molecule". Neural Regeneration Research. 15 (10): 1846. doi:10.4103/1673-5374.280314
. ISSN 1673-5374. PMC 7513974 . PMID 32246629.
- ↑ 7.0 7.1 Kolatorova, Lucie; Vitku, Jana; Suchopar, Josef; Hill, Martin; Parizek, Antonin (2022-07-20). "Progesterone: A Steroid with Wide Range of Effects in Physiology as Well as Human Medicine". International Journal of Molecular Sciences. 23 (14): 7989. doi:10.3390/ijms23147989 . ISSN 1422-0067. PMID 35887338.
- ↑ Diviccaro, Silvia; Cioffi, Lucia; Falvo, Eva; Giatti, Silvia; Melcangi, Roberto Cosimo (2022). "Allopregnanolone: An overview on its synthesis and effects". Journal of Neuroendocrinology. 34 (2). doi:10.1111/jne.12996. ISSN 0953-8194. PMID 34189791.
- ↑ "Brexanolone". PubChem. Retrieved 2024-03-12.
- ↑ "EVIDENCE ON THE DEVELOPMENTAL AND REPRODUCTIVE TOXICITY OF Progesterone" (PDF). Office of Environmental Health Hazard Assessment California Environmental Protection Agency. Retrieved 2024-03-12.
- ↑ &Na; (1996). "Progesterone abuse Adverse effects: case report". Reactions Weekly. &NA; (599): 9. doi:10.2165/00128415-199605990-00031. ISSN 0114-9954.
- ↑ Simon, James A.; Robinson, Denise E.; Andrews, Mason C.; Hildebrand, James R.; Rocci, Mario L.; Blake, Richard E.; Hodgen, Gary D. (1993). "The absorption of oral micronized progesterone: the effect of food, dose proportionality, and comparison with intramuscular progesterone". Fertility and Sterility. 60 (1): 26–33. doi:10.1016/S0015-0282(16)56031-2.
- ↑ "Progesterone: Uses, Interactions, Mechanism of Action". DrugBank Online. 2016-04-13. Retrieved 2024-03-12.
- ↑ "Progesterone (International database)". Drugs.com. 2024-03-03. Retrieved 2024-03-12.