Seven days of CBD at high doses produced antidepressant effects in mice by increasing serotonin and noradrenaline | Research

The takeaway

Chronic CBD at 100 mg/kg for 7 days produced antidepressant-like effects in mice, accompanied by increased serotonin and noradrenaline levels and decreased NF-kB expression in the hippocampus.

Psychiatrists considering CBD for depression, neuroscientists studying CBD mechanisms, and researchers developing cannabinoid-based mood treatments.

CBD increased both serotonin and noradrenaline in hippocampus

What the researchers found

Only the high dose (100 mg/kg) produced antidepressant effects in the forced swim test after 7 days of administration. This dose significantly increased serotonin (5-HT) and noradrenaline (NA) in the hippocampus. Both 30 mg/kg and 100 mg/kg decreased NF-kB expression. No locomotor effects were observed at any dose, ruling out non-specific activity changes.

Why it matters

While acute CBD effects have been studied, chronic administration is more clinically relevant. Finding that CBD increases serotonin and noradrenaline, the same targets as conventional antidepressants, provides a mechanistic rationale for CBD in depression.

The numbers in context

100 mg/kg CBD for 7 days produced antidepressant effect. Significant increase in hippocampal serotonin and noradrenaline. NF-kB decreased at both 30 and 100 mg/kg. No locomotor effects at any dose.

How the study worked

Male mice received synthetic CBD (30 or 100 mg/kg) or vehicle daily for 7 days. Behavioral assessment via forced swim test and open field test. Hippocampal serotonin and noradrenaline measured by HPLC-ECD. NF-kB, BDNF, and other proteins measured by RT-PCR and Western blot.

What this study cannot tell us

Animal study with high CBD doses (100 mg/kg) that may not be achievable in humans. Only 7 days of treatment. Forced swim test is a simplified depression model. Synthetic CBD may differ from plant-derived CBD in some respects.

How to read the evidence

Controlled preclinical study with neurochemical measurements, but high doses and simplified depression model.

When this study was published

2021 animal study. Adds mechanistic detail to the emerging evidence for CBD antidepressant effects.

The bigger picture

If CBD works through the same neurotransmitter systems as established antidepressants, it could potentially be an alternative or adjunct for patients who do not respond to or tolerate conventional medications.

Questions still open

Would lower chronic CBD doses produce antidepressant effects over longer treatment periods? Does the serotonergic mechanism predict which patients might respond to CBD? How does CBD compare to standard antidepressants at equivalent serotonin-enhancing doses?

Common questions

How does CBD's antidepressant mechanism compare to SSRIs?

Like SSRIs, CBD increased serotonin levels in the hippocampus. But CBD also increased noradrenaline, making its profile more similar to SNRIs (serotonin-noradrenaline reuptake inhibitors).

Why did only the high dose work?

Only 100 mg/kg produced behavioral antidepressant effects, while 30 mg/kg reduced NF-kB but did not change behavior or neurotransmitter levels. This suggests a threshold dose may be needed for mood effects.

Read the original research

Chronic administration of synthetic cannabidiol induces antidepressant effects involving modulation of serotonin and noradrenaline levels in the hippocampus.

Neuroscience letters, 744, 135594

View on PubMed ↗Publisher’s paper ↗

Citation

Abame, Melkamu Alemu; He, Yang; Wu, Song; Xie, Zhifei; Zhang, Jian; Gong, Xudong; Wu, Chunhui; Shen, Jingshan. (2021). Chronic administration of synthetic cannabidiol induces antidepressant effects involving modulation of serotonin and noradrenaline levels in the hippocampus.. Neuroscience letters, 744, 135594. https://doi.org/10.1016/j.neulet.2020.135594