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Synthetic

HU-308

Highly selective synthetic agonist of the CB2 receptor, non-psychoactive, used as a research tool.

Unscheduled
Level of detail

Harm-reduction warning

No characterised human dose: animal / in vitro data only. Effect profile, safety margin and acute toxicity are not documented in human clinical practice. Extremely potent compound: severe effects, seizures and deaths reported in the literature.

C₂₇H₄₂O₃

CAS 256934-39-1

Family
Synthetic CB receptor agonistResearch ligand or medicine
Molar mass
414.60 g/mol

Updated on

In plain terms

HU-308 is a molecule made in the laboratory, related to cannabidiol but absent from hemp. It acts almost solely on the CB2 receptor, the one on immune cells, and produced none of the effects of THC in a behavioural test in mice. It serves above all as a laboratory tool: it is neither an authorised medicine nor an ingredient of any consumer product.

Receptors and activity

Target network

CB2AgonistKi = 22.7 nMradioligand displacement; inhibition of forskolin-stimulated cAMP
  • Activates
  • Binds or modulates

The lower the cited value, the closer the target sits to HU-308: 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 HU-308.

Brain, side view
Body, front view
Blood

CB2CB2 found in 5 regions of the body

  1. SpleendenseHighly abundant in the spleen1
  2. Immune cellspresentMainly B cells and natural killer cells1
  3. SkinpresentKeratinocytes, mast cells and nerve fibres2
  4. GutpresentImmune cells of the colonic mucosa3
  5. BonepresentPresent on osteoclasts4

Map sources

  1. Galiègue S et al. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem, 1995 (new tab)
  2. Ständer S et al. Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci, 2005 (new tab)
  3. Wright K et al. Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology, 2005 (new tab)
  4. Rossi F et al. The endovanilloid/endocannabinoid system in human osteoclasts: possible involvement in bone formation and resorption. Bone, 2009 (new tab)

Cited values

  1. CB2AgonistKi = 22.7 nM61 out of 100

    Hanuš et al., Proc Natl Acad Sci USA 1999 (new tab) · radioligand displacement; inhibition of forskolin-stimulated cAMP

  2. CB1Binding (function not established)no 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.

Pharmacology

HU-308 is a highly selective synthetic agonist of the cannabinoid CB2 receptor. The original study reports an inhibition constant of 22.7 nM at CB2 and no binding to CB1 up to more than 10 µM, a selectivity of at least about 440-fold; the molecule inhibits cyclic AMP production in cells transfected with CB2, much less in cells transfected with CB1 (Hanuš et al., PNAS 1999, PMID 10588688). In mice it produced no effect in the battery of four behavioural tests specific to THC-type, CB1-mediated effects; it lowered blood pressure, blocked defecation and produced anti-inflammatory and peripheral analgesic effects, effects blocked or partly blocked by the CB2 antagonist SR 144528 but not by the CB1 antagonist SR 141716A (Hanuš et al. 1999). Since then it has served as a pharmacological probe in animal models of arthritis (Tian et al. 2025), acute lung injury (Hall et al. 2022), retinopathy (Young et al. 2024) and trigeminal neuropathic pain (Ma et al. 2024). No published clinical study was found, no human pharmacokinetic profile is described, and the therapeutic reach remains undetermined.

Key sources.

History

Source
An entirely synthetic molecule. It exists in no known plant and has never been detected in hemp or in Cannabis sativa extracts. It derives formally from cannabidiol, whose two phenol functions are methylated, combined with a pinene-type bicyclic ring and an extended dimethylheptyl side chain.

Origin

Laboratory synthesis

No known biosynthetic pathway: a synthetic molecule (a dimethyl ether of a cannabidiol analogue carrying a pinene-type bicyclic ring). No living organism produces it.

Classification

Family, origin and source verification

Family

Synthetic CB receptor agonist › Research ligand or medicine

Class

non-classical

Verification

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

Wikipedia (English)

Onternabez (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. Hanuš L, Breuer A, Tchilibon S, et al. HU-308: a specific agonist for CB2, a peripheral cannabinoid receptor. PNAS, 1999 (new tab)PMID 10588688
  2. Ma S, Nakamura Y, Uemoto S, et al. Intranasal treatment with cannabinoid 2 receptor agonist HU-308 ameliorates cold sensitivity in mice with traumatic trigeminal neuropathic pain. Cells, 2024 (new tab)PMID 39682692
  3. Hall S, Faridi S, Trivedi P, et al. Selective CB2 receptor agonist, HU-308, reduces systemic inflammation in endotoxin model of pneumonia-induced acute lung injury. Int J Mol Sci, 2022 (new tab)PMID 36555499
  4. Tian N, Yang C, Du Y, et al. Cannabinoid receptor 2 selective agonist ameliorates adjuvant-induced arthritis by modulating the balance between Treg and Th17 cells. Front Pharmacol, 2025 (new tab)PMID 39959429
  5. Young AP et al., Enantiomeric Agonists of the Type 2 Cannabinoid Receptor Reduce Retinal Damage during Proliferative Vitreoretinopathy (HU-308 and HU-433), ACS Pharmacol Transl Sci 2024 (new tab)PMID 38751621
  6. PubChem, compound record for HU-308 (CID 11553430) (new tab)
  7. Ganzoni RLZ et al., Single-position ligand modifications tune CB2R activity by targeting the toggle switch, Chem Sci 2026 (new tab)PMID 41859514
  8. Pertwee et al., Pharmacol Rev 2010 (IUPHAR): HU-308, non-classical cannabinoid; Ki CB1 > 10,000 nM, CB2 22.7 nM (new tab)PMID 21079038

Identifiers

Names

IUPAC name
[(1S,4S,5S)-4-[2,6-dimethoxy-4-(2-methyloctan-2-yl)phenyl]-6,6-dimethyl-2-bicyclo[3.1.1]hept-2-enyl]methanol
Other names
HU 308 · onternabez · HU308 · PPP-003 · ARDS-003

Identifiers

Formula
C₂₇H₄₂O₃
CAS
256934-39-1
PubChem CID
11553430(new tab)
InChIKey
CFMRIVODIXTERW-BDTNDASRSA-N
SMILES
CCCCCCC(C)(C)C1=CC(=C(C(=C1)OC)[C@H]2C=C([C@H]3C[C@@H]2C3(C)C)CO)OC

Machine-readable entry (JSON)

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