data + articles · 6 listed
newest 2023spec sheet8 rows
PF-3845 is a highly selective, covalent fatty acid amide hydrolase (FAAH) inhibitor developed by Pfizer as a pharmacological tool to augment endocannabinoid signaling in vivo. By carbamylating the serine nucleophile of FAAH, the enzyme responsible for degrading the endocannabinoid anandamide, PF-3845 raises brain and peripheral levels of anandamide and related N-acylethanolamines for up to 24 hours after a single dose. It is widely used in preclinical neuroscience to probe endocannabinoid contributions to pain, inflammation, anxiety, and nausea, and remains an investigational research compound rather than an approved drug.
- Raises brain and peripheral anandamide for up to 24 hours after a single dose
- Produces cannabinoid receptor-dependent analgesia in inflammatory and neuropathic pain models
- Anxiolytic-like effects, including reversing anxiety from palatable-food withdrawal
- Suppresses nausea-related behavior via a ventral pallidum PPAR-alpha mechanism
- Anti-inflammatory action in microglia, lowering pro-inflammatory cytokines and PGE2
- Highly selective for FAAH over other serine hydrolases, giving clean mechanistic readouts
- FAAH inhibition as a drug class drew scrutiny after unrelated fatal trials with other molecules
- Off-target inhibition of bacterial phenylalanyl-tRNA synthetase has been reported
- Theoretical mood, cognitive, or sedative effects from sustained endocannabinoid elevation
- Irreversible mechanism means enzyme activity only returns as new FAAH is synthesized
Overview
PF-3845 is hands down one of the cleanest FAAH inhibitors in the research toolbox; it locks onto FAAH covalently and essentially leaves the enzyme shut down for the better part of a day, so anandamide climbs and stays up. The draw is the selectivity story; activity-based profiling shows it pretty much stays on FAAH instead of spraying across the serine hydrolase family, which is why so many labs reach for it when they want a clean readout on endocannabinoid tone.
The preclinical picture is genuinely broad; analgesia, anxiolysis, anti-nausea, and anti-inflammatory effects all show up, and a lot of them wash out when you block CB1 or PPAR-alpha, which is exactly what you want mechanistically. Straight framing though; this is an investigational tool compound with no established human dosing, and the FAAH class as a whole earned real scrutiny after unrelated tragedies with other molecules, so it belongs in the lab-reagent bucket, a fascinating mechanism rather than a supplement.
Mechanism
PF-3845 is an irreversible, covalent inhibitor of fatty acid amide hydrolase (FAAH), the integral membrane serine hydrolase that breaks down the endocannabinoid anandamide (AEA) and other fatty acid amides. Its aryl piperidine urea warhead carbamylates the catalytic serine nucleophile (Ser241) in FAAH's unusual Ser-Ser-Lys triad, permanently disabling the enzyme so that new protein must be synthesized to restore activity. With FAAH offline, anandamide and related N-acylethanolamines (such as palmitoylethanolamide and oleoylethanolamide) accumulate in brain and periphery, elevating anandamide levels for up to 24 hours.
The raised anandamide indirectly stimulates cannabinoid CB1 (and to a lesser extent CB2) receptors, producing analgesia, anxiolysis, and anti-inflammatory effects, while the accumulating N-acylethanolamines also engage PPAR-alpha (a nuclear transcription factor) to drive anti-nausea and anti-inflammatory signaling. Because it augments on-demand endocannabinoid tone rather than flooding receptors like a direct CB1 , it produces its effects with less of the classic cannabinoid tetrad profile than direct agonists such as THC.
receptor fingerprint
FAAH (fatty acid amide hydrolase)Inhibits (covalent, irreversible carbamylation of Ser241)
Anandamide (AEA)Raises levels (indirect, via FAAH blockade)
CB1 receptorIndirect agonism (via elevated anandamide)
PPAR-alphaIndirect activation (via elevated N-acylethanolamines PEA/OEA)
Phenylalanyl-tRNA synthetase (M. tuberculosis PheRS)Inhibits (off-target)
CB2 receptorIndirect agonism (via elevated endocannabinoids)
Safetyrisks and cautions, not medical advice
PF-3845 is an investigational research compound with no approved human use and no established human dosing or long-term safety profile; nearly all data come from rodent and cell studies. Its covalent, irreversible mechanism means FAAH stays inhibited until the enzyme is resynthesized. As a class, FAAH inhibitors received heightened safety scrutiny after the unrelated BIA 10-2474 trial catastrophe (a different molecule), so PF-3845 should be regarded as a laboratory tool rather than a therapeutic. Off-target inhibition of Mycobacterium tuberculosis phenylalanyl-tRNA synthetase has been documented, though it does not inhibit human PheRS.
Subjective profileweighing the evidence above
A gold-standard, highly selective covalent FAAH inhibitor and one of the most trusted tool compounds for probing endocannabinoid biology; broad preclinical analgesic, anxiolytic, anti-nausea, and anti-inflammatory signals, but strictly investigational with no human safety data.
Resources
This entry is here for reference.
Research
- 2009first citedDiscovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory p…
- 2023most recentAnxiety associated with palatable food withdrawal is reversed by the selective FAAH inhibitor P…
- 1.Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain
- 2.Anxiety associated with palatable food withdrawal is reversed by the selective FAAH inhibitor PF-3845: A regional analysis of the contribution of endocannabinoid signaling machinery.
- 3.The ventral pallidum as a critical region for fatty acid amide hydrolase inhibition of nausea-induced conditioned gaping in male Sprague-Dawley rats.
- 4.Anti-Inflammatory Effects by Pharmacological Inhibition or Knockdown of Fatty Acid Amide Hydrolase in BV2 Microglial Cells
- 5.Fatty acid amide hydrolase activity in the dorsal periaqueductal gray attenuates neuropathic pain and associated dysautonomia
- 6.Rediscovery of PF-3845 as a new chemical scaffold inhibiting phenylalanyl-tRNA synthetase in Mycobacterium tuberculosis
6 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
What is PF-3845 used for?
It is a research tool used to inhibit fatty acid amide hydrolase (FAAH) and raise anandamide, letting scientists study endocannabinoid roles in pain, inflammation, anxiety, and nausea. It is not an approved medicine.
How does PF-3845 work?
It covalently and irreversibly blocks FAAH by carbamylating the enzyme's catalytic serine, so anandamide and related lipids build up and indirectly activate CB1, CB2, and PPAR-alpha signaling for up to 24 hours.
Is PF-3845 well-researched?
It is extensively characterized in preclinical models, from its 2009 discovery through many rodent and cell studies, and it is a standard selective FAAH inhibitor in the literature. However, there is no approved human clinical use.
Does PF-3845 get you high like THC?
It works differently from THC; rather than directly flooding CB1 receptors it boosts the body's own on-demand anandamide, which produces a less pronounced classic cannabinoid profile in animal studies.
What are the main risks of PF-3845?
It is investigational with no human safety data, its inhibition is irreversible until new enzyme is made, and it has a reported off-target action on a bacterial enzyme. The broader FAAH-inhibitor class has also drawn safety scrutiny.
Limitations of the evidence
- Investigational tool compound; no established human safety or dosing data
Adverse effects
- FAAH inhibition as a drug class drew scrutiny after unrelated fatal trials with other molecules
- Off-target inhibition of bacterial phenylalanyl-tRNA synthetase has been reported
- Theoretical mood, cognitive, or sedative effects from sustained endocannabinoid elevation
- Irreversible mechanism means enzyme activity only returns as new FAAH is synthesized