Cannabigerol did not affect fear memory in mice but showed sex-dependent pain effects | Research

The takeaway

The cannabis compound CBG failed to alter fear memory acquisition, consolidation, or retrieval in mice at any dose tested, but showed a biphasic pain response in females with no motor impairment.

Cannabis pharmacology researchers, anxiety disorder researchers, CBG product developers

No fear memory effect at any dose in either sex

What the researchers found

CBG at 3, 10, and 30 mg/kg failed to significantly change acquisition, consolidation, or retrieval/expression of contextual fear memories in either male or female mice. In the tail-flick pain test, female mice showed a biphasic response: the low dose (3 mg/kg) increased pain threshold while the high dose (30 mg/kg) decreased it. No motor impairment was observed in the rotarod test at any dose or timepoint.

Why it matters

While CBD has shown promise for fear-related conditions like PTSD, CBG (another non-psychoactive cannabinoid gaining market attention) did not replicate these effects on fear memory. This negative result is important for setting realistic expectations about CBG's therapeutic potential in anxiety and trauma-related disorders.

The numbers in context

CBG tested at 3, 10, 30 mg/kg; no effect on fear memory at any dose; biphasic pain effect in females only (3 mg/kg increased threshold, 30 mg/kg decreased it); no motor impairment at any dose

How the study worked

Male and female C57BL/6J mice underwent contextual fear conditioning protocols with CBG (3, 10, or 30 mg/kg) administered at different timepoints to target acquisition, consolidation, and retrieval phases. Tail-flick test assessed nociception. Rotarod test assessed motor function.

What this study cannot tell us

Mouse fear conditioning may not fully model human anxiety or PTSD. Only three doses tested. Contextual fear conditioning is one specific paradigm; CBG might affect other anxiety-related behaviors. Biphasic pain effect in females needs replication.

How to read the evidence

Well-designed preclinical study with multiple doses, both sexes, and multiple memory phases provides clear negative result, but animal models have inherent translational limitations.

When this study was published

2025 publication

The bigger picture

CBG is increasingly marketed as a wellness product with anxiety-reducing claims. This preclinical study found no evidence supporting its use for fear or trauma-related conditions, highlighting the gap between marketing claims and scientific evidence for minor cannabinoids.

Questions still open

Would CBG affect fear in other paradigms like fear extinction or cued fear conditioning? What mechanism explains the sex-dependent biphasic pain effect?

Common questions

Can CBG help with anxiety or PTSD?

This mouse study found no evidence that CBG affects fear memory at doses of 3-30 mg/kg. While this does not rule out effects in other anxiety models or in humans, it does not support the anxiety-reducing claims sometimes made for CBG products.

What was the biphasic pain effect?

In female mice only, a low CBG dose (3 mg/kg) increased pain threshold while a high dose (30 mg/kg) decreased it. This unusual pattern suggests CBG's effects on pain may depend on both dose and sex.

Read the original research

Cannabigerol does not affect contextual fear memory in mice but modulates nociception in a sex-dependent manner.

Pharmacology, biochemistry, and behavior, 254, 174053

View on PubMed ↗Publisher’s paper ↗

Citation

Andreotti, Julia P; Iglesias, Lia P; Briânis, Rayssa C; Barra, Walace C P; Duarte, Igor D G; Stern, Cristina A J; Bertoglio, Leandro J; Crippa, José A; Aguiar, Daniele C; Moreira, Fabrício A. (2025). Cannabigerol does not affect contextual fear memory in mice but modulates nociception in a sex-dependent manner.. Pharmacology, biochemistry, and behavior, 254, 174053. https://doi.org/10.1016/j.pbb.2025.174053