spec sheet8 rows
HU-308 is a synthetic cannabinoid that acts as a highly selective agonist of the type-2 cannabinoid receptor (CB2), the peripheral and immune-cell arm of the endocannabinoid system. First reported in 1999 by Raphael Mechoulam's group at the Hebrew University of Jerusalem, it was designed as a nonpsychotropic probe: it binds CB2 with nanomolar affinity (Ki ~22.7 nM) while showing essentially no affinity for the centrally expressed CB1 receptor (Ki > 10 microM), so it produces none of the tetrahydrocannabinol-type behavioral effects mediated by CB1. Through CB2 activation it lowers blood pressure, blocks defecation, and exerts anti-inflammatory and peripheral analgesic activity, effects reversed by the CB2 antagonist SR-144528 but not by the CB1 antagonist rimonabant. Across preclinical models it dampens pro-inflammatory cytokine release from macrophages and microglia, and it has been studied in acute lung injury, collagen-induced arthritis, endothelial activation, Parkinsonian neuroinflammation, and proliferative vitreoretinopathy. HU-308 remains an investigational research compound and is not an approved drug.
- Highly selective CB2 activation delivers anti-inflammatory effects without CB1-mediated psychoactivity
- Suppresses pro-inflammatory cytokine release (TNF-alpha, IL-6, nitric oxide) from macrophages and microglia
- Reduces microglial activation and neuroinflammation in preclinical CNS models
- Lowers endothelial adhesion-molecule expression and monocyte migration relevant to vascular inflammation
- Shows peripheral analgesic and anti-inflammatory activity in animal models
- Protective effects in preclinical arthritis, acute lung injury, and retinal-damage models
- Can lower blood pressure (hypotension) via CB2 activation in animal studies
- Inhibits gastrointestinal motility (blocks defecation) in preclinical models
Overview
HU-308 is pretty much the textbook selective CB2 agonist; it is the tool compound Mechoulam's lab built to prove you could get the anti-inflammatory and analgesic upside of cannabinoids without touching CB1, so there is essentially no high, no head-change, no THC tetrad. What stands out on paper is how clean the selectivity is; nanomolar at CB2 and basically silent at CB1, which is why it keeps showing up in immune and neuroinflammation work from lung injury to arthritis to microglia in the retina. It leans on the endocannabinoid system's "calm the immune cells down" side, quieting TNF-alpha and IL-6 release. Honest framing though; this is an investigational research chemical, not a supplement and not an approved drug, so it lives in the lab-tool bucket for now. Hands down one of the most useful CB2 probes out there for understanding where cannabinoids help inflammation.
Mechanism
HU-308 is a selective at the cannabinoid CB2 receptor, a Gi/o-protein-coupled receptor expressed mainly on immune cells (macrophages, monocytes, ) and peripheral tissues rather than in the central nervous system.
On binding CB2 (Ki ~22.7 nM) it activates the Gi/o pathway, inhibiting adenylyl cyclase and lowering intracellular cyclic AMP (the second messenger that drives many pro-inflammatory programs), and it also recruits beta-arrestin2 and G-alpha-i. Downstream this suppresses NF-kappaB and RhoA signaling and reduces the release of pro-inflammatory mediators including TNF-alpha, IL-6, , and inducible nitric oxide synthase, while also blunting endothelial adhesion-molecule expression (ICAM-1, VCAM-1) and monocyte migration.
Because its affinity for the centrally expressed CB1 receptor is negligible (Ki > 10 microM), it does not trigger the CB1-mediated psychoactive tetrad, so its actions are essentially peripheral and immunomodulatory. Its effects are pharmacologically confirmed by reversal with the CB2 SR-144528 and their absence in CB2-knockout tissue.
receptor fingerprint
CB2 receptor (cannabinoid receptor 2)Agonist (activates)
Adenylyl cyclase / (via Gi/o)Inhibits
beta-arrestin2Recruits
NF-kappaB / TNF-alpha / IL-6 signalingSuppresses (downstream)
CB1 receptor (cannabinoid receptor 1)Negligible binding
Safetyrisks and cautions, not medical advice
HU-308 is an investigational synthetic cannabinoid used as a research tool; it is not an approved medicine and has no established human dosing or safety profile. In animal studies CB2 activation by HU-308 can produce hypotension and inhibit gastrointestinal motility. Because it is a highly selective CB2 agonist, it lacks the psychoactive CB1-mediated effects of THC, but its human pharmacokinetics, chronic-use safety, and interactions remain uncharacterized. It should be treated as an experimental compound, not a supplement.
Subjective profileweighing the evidence above
A landmark, cleanly selective CB2 agonist and one of the most valuable pharmacological tools for probing the anti-inflammatory, non-psychoactive side of the endocannabinoid system; strong and consistent preclinical anti-inflammatory data, but it remains an investigational research chemical with no approved human use.
Resources
This entry is here for reference.
Research
- 1999first citedHU-308: a specific agonist for CB(2), a peripheral cannabinoid receptor
- 2024most recentEnantiomeric Agonists of the Type 2 Cannabinoid Receptor Reduce Retinal Damage during Prolifera…
- 1.HU-308: a specific agonist for CB(2), a peripheral cannabinoid receptor
- 2.CB2-receptor stimulation attenuates TNF-alpha-induced human endothelial cell activation, transendothelial migration of monocytes, and monocyte-endothelial adhesion
- 3.Activation of cannabinoid receptor 2 attenuates synovitis and joint distruction in collagen-induced arthritis.
- 4.Potential of the cannabinoid CB(2) receptor as a pharmacological target against inflammation in Parkinson's disease
- 5.Selective CB2 Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury
- 6.Enantiomeric Agonists of the Type 2 Cannabinoid Receptor Reduce Retinal Damage during Proliferative Vitreoretinopathy and Inhibit Hyperactive Microglia In Vitro.
6 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
What is HU-308 used for?
It is a research compound used to study the CB2 cannabinoid receptor, especially its anti-inflammatory, immunomodulatory, and peripheral analgesic effects. It is not an approved drug or supplement.
Does HU-308 get you high?
No. HU-308 is highly selective for CB2 and has negligible affinity for CB1 (Ki > 10 microM), the receptor responsible for THC's psychoactive effects, so it produces no THC-type behavioral or psychoactive effects in the standard tetrad tests.
How does HU-308 work?
It activates the CB2 receptor on immune cells, engaging Gi/o signaling that lowers cAMP and beta-arrestin2 recruitment, which suppresses NF-kappaB signaling and the release of pro-inflammatory mediators like TNF-alpha, IL-6, and nitric oxide.
Is HU-308 well-researched?
It is well-characterized as a preclinical tool since 1999, with consistent anti-inflammatory findings across lung injury, arthritis, endothelial, Parkinsonian, and retinal models, but there are no approved human clinical uses; it remains investigational.
What are the main side effects of HU-308?
In animal studies CB2 activation can cause hypotension and inhibit gastrointestinal motility. As an investigational research chemical it has no established human safety profile.
Limitations of the evidence
- Investigational research chemical with no approved human use and no established human safety profile
- Human dosing, long-term safety, and drug interactions are not characterized
Adverse effects
- Can lower blood pressure (hypotension) via CB2 activation in animal studies
- Inhibits gastrointestinal motility (blocks defecation) in preclinical models