Skip to content

Batch information on every product pageTHC < 0.3%Shipped from France10% off when you sign up

Research tools

Pregnenolone

An endogenous steroid; a signalling-specific negative allosteric modulator of CB1.

Endogenous
Level of detail

C₂₁H₃₂O₂

CAS 145-13-1

Family
ECS pharmacological toolAllosteric modulator
Molar mass
316.50 g/mol

Updated on

In plain terms

Pregnenolone is a hormone the body makes itself from cholesterol, notably in the brain. It does not exist in hemp. French researchers showed in 2014, in rodents, that the brain makes a lot of it after a dose of THC, and that it then slows part of the effects of THC, like a natural brake.

Receptors and activity

Target network

CB1Negative allosteric modulatorno measured value
  • Blocks or inhibits

The lower the cited value, the closer the target sits to Pregnenolone: one ring per factor of 100. A target with no measured value stays on the edge.

Where these targets live

Where each target has been found in humans, according to the cited studies. The map shows the target, not an effect of Pregnenolone.

Brain, side view
Body, front view
Blood

CB1CB1 found in 7 regions of the body

  1. Basal gangliadenseMost dense in basal ganglia outflow nuclei1
  2. CerebellumdenseVery dense in the cerebellum1
  3. HippocampusdenseVery high concentrations in the hippocampus2
  4. AmygdaladenseHigh concentrations in the amygdala2
  5. CortexpresentPresent throughout the neocortex2
  6. Adipose tissuepresentExpressed in adipose tissue3
  7. GutpresentColonic epithelium, smooth muscle and plexus4

Map sources

  1. Herkenham M et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A, 1990 (new tab)
  2. Glass M et al. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience, 1997 (new tab)
  3. Engeli S et al. Activation of the peripheral endocannabinoid system in human obesity. Diabetes, 2005 (new tab)
  4. Wright K et al. Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology, 2005 (new tab)

Cited values

  1. CB1Negative allosteric modulatorno measured value cited
Bar length follows the measured value (Ki, Kd, EC50 or IC50), on one scale shared by every entry, from 100 µM to 0.1 nM. A target with no cited value has no bar.

Measured effects

Not characterised. No placebo-controlled human trial has measured the effects of Pregnenolone, so no level is shown.

Levels computed from placebo-controlled human trials: difference from placebo on 100, at the dose and route stated. Read the method

Pharmacology

Pregnenolone is the first steroid derived from cholesterol and the common precursor of steroid hormones. Its interest for the endocannabinoid system comes from work published in Science in 2014 by Inserm teams in Bordeaux: in rodents, THC (3 mg/kg) raises brain pregnenolone by about 1,500% for two hours, up to about 3,000% at the maximum of the dose-response curve, by activating CB1, and pregnenolone then acts as a signalling-specific inhibitor of CB1: it blocks the ERK1/2 phosphorylation and the fall in mitochondrial respiration triggered by THC, but not the fall in cyclic AMP (Vallée et al., Science 2014, PMID 24385629). In mice it attenuates psychotic-like effects of THC without behavioural effects of its own (Busquets-Garcia et al. 2017). The limits are real: an independent team found no modulation of the 2-AG-mediated signal in autaptic neurons (Straiker et al. 2015), and human data are lacking for pregnenolone itself in this indication. A first-in-class signalling-specific CB1 inhibitor, AEF0117, was evaluated in phase 1 and 2a in volunteers and people with cannabis use disorder: it was well tolerated and reduced the positive subjective effects of cannabis and its self-administration, without precipitating withdrawal (Haney et al., Nat Med 2023, PMID 37291212).

Key sources.

History

Source
An endogenous mammalian steroid, the first steroid synthesised from cholesterol at all steroidogenic sites, brain included (Raux et al. 2022). It is not produced by hemp and so is not a phytocannabinoid.

Origin

Research tool

Pregnenolone is the first steroid formed from cholesterol, at all steroidogenic sites, brain included (Raux et al. 2022). It is regarded as the precursor of all steroid hormones (Vallée et al. 2014).

Classification

Family, origin and source verification

Family

ECS pharmacological tool › Allosteric modulator

Verification

Classification, sources and binding values checked on 20 October 2026; text read against its sources and Wikipedia.

Wikipedia (English)

Pregnenolone (new tab)

Article paired by the molecule's structure (InChIKey), revision read on 19 October 2026. Read as a second opinion, never cited as a source.

References

  1. Vallée M et al., Science 2014: pregnenolone protects the brain from cannabis intoxication (new tab)PMID 24385629
  2. Busquets-Garcia A et al., Mol Psychiatry 2017: pregnenolone blocks cannabinoid-induced acute psychotic states in mice (new tab)PMID 28220044
  3. Raux PL et al., J Neuroendocrinol 2022: pregnenolone, an endogenous regulator of CB1 (new tab)PMID 34486765
  4. Straiker A et al., Pharmacol Res 2015: CB1 allosteric modulators in a neuronal model (no effect of pregnenolone) (new tab)PMID 26211948
  5. Haney M et al., Nat Med 2023: signalling-specific CB1 inhibition in cannabis use disorder, phases 1 and 2a (new tab)PMID 37291212

Identifiers

Names

IUPAC name
1-[(3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone
Other names
3-Hydroxypregn-5-en-20-one · 5P · P5

Identifiers

Formula
C₂₁H₃₂O₂
CAS
145-13-1
PubChem CID
8955(new tab)
InChIKey
ORNBQBCIOKFOEO-QGVNFLHTSA-N
SMILES
CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H](C4)O)C)C

Machine-readable entry (JSON)

LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.