Agonistic properties of cannabidiol at 5-HT1a receptors
Abstract
Cannabidiol (CBD) is a major, biologically active, but psycho-inactive component of cannabis. In this cell culture-based report, CBD is shown to displace the agonist, [3H]8-OH-DPAT from the cloned human 5-HT1a receptor in a concentration-dependent manner. In contrast, the major psychoactive component of cannabis, tetrahydrocannabinol (THC) does not displace agonist from the receptor in the same micromolar concentration range. In signal transduction studies, CBD acts as an agonist at the human 5-HT1a receptor as demonstrated in two related approaches. First, CBD increases [35S]GTPgammaS binding in this G protein coupled receptor system, as does the known agonist serotonin. Second, in this GPCR system, that is negatively coupled to cAMP production, both CBD and 5-HT decrease cAMP concentration at similar apparent levels of receptor occupancy, based upon displacement data. Preliminary comparative data is also presented from the cloned rat 5-HT2a receptor suggesting that CBD is active, but less so, relative to the human 5-HT1a receptor, in binding analyses. Overall, these studies demonstrate that CBD is a modest affinity agonist at the human 5-HT1a receptor. Additional work is required to compare CBD's potential at other serotonin receptors and in other species. Finally, the results indicate that cannabidiol may have interesting and useful potential beyond the realm of cannabinoid receptors.
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CBD displaces the agonist [3H]8-OHDPAT from the cloned human 5-HT1A receptor in a concentration-dependent manner.
“The anxiolytic action of CBD may be mediated by 5-HT1A receptors, as it displaces the agonist [3H]8-OHDPAT from the cloned human 5-HT1A receptor in a concentration-dependent manner and exerts an effect as an agonist at the human 5-HT1A receptor in signal-transduction studies (Russo et al, 2005).”
From Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients (2011) · cites this paper as Russo et al, 2005
CBD exerts an effect as an agonist at the human 5-HT1A receptor in signal-transduction studies.
“The anxiolytic action of CBD may be mediated by 5-HT1A receptors, as it displaces the agonist [3H]8-OHDPAT from the cloned human 5-HT1A receptor in a concentration-dependent manner and exerts an effect as an agonist at the human 5-HT1A receptor in signal-transduction studies (Russo et al, 2005).”
From Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients (2011) · cites this paper as Russo et al, 2005
The anxiolytic action of CBD may be mediated by 5-HT1A receptors.
“The anxiolytic action of CBD may be mediated by 5-HT1A receptors, as it displaces the agonist [3H]8-OHDPAT from the cloned human 5-HT1A receptor in a concentration-dependent manner and exerts an effect as an agonist at the human 5-HT1A receptor in signal-transduction studies (Russo et al, 2005).”
From Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients (2011) · cites this paper as Russo et al, 2005
CBD has neuromodulatory and neuroprotective effects through mechanisms including blocking neuroinflammation, potentiating anti-inflammatory pathways, improving mitochondrial function, GABAA agonist potentiation, stimulation of 5HT1A receptors, and enhancing levels of anandamide.
“CBD has both neuromodulatory and neuroprotective effects through a number of mechanisms including blocking neuroinflammation and potentiating anti-inflammatory pathways, improving mitochondrial function, GABAA agonist potentiation, stimulation of 5HT1A receptors, and enhancing levels of anandamide (AEA) [116–119].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [119]
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References 43 · Cited by 878
- Authors
- Russo, E. B., Burnett, A., Hall, B., & Parker, K. K.
- Affiliations
- University of Montana (US)
- Corresponding author
- Parker, Keith K.
- Venue
- Neurochemical Research
- Published
- 2005-08
- Volume
- 30
- Issue
- 8
- Pages
- 1037-1043
- ISSN
- 0364-3190 (ISSN-L)
- 1573-6903
- OpenAlex
- W2149110258
- Cited by
- 878
- References
- 43
- Citations by year
- 2026: 36 · 2025: 45 · 2024: 71 · 2023: 74 · 2022: 105 · 2021: 101 · 2020: 100 · 2019: 50 · 2018: 51 · 2017: 44 · 2016: 32 · 2015: 28 · 2014: 12 · 2013: 18 · 2012: 23
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurochemical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM/OD54302-01)
- National Center for Research Resources (P20RR15583, P20RR015583)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- cannabidiol, 5-HT1A receptor, serotonin receptors, tetrahydrocannabinol, agonist affinity, G protein-coupled receptor signaling, cAMP production, 5-HT2A receptor, receptor occupancy
- MeSH terms
- Animals, Binding, Competitive, Cannabidiol, Cricetinae, Humans, Receptors, Cell Surface, Guanosine 5'-O-(3-Thiotriphosphate), CHO Cells, Serotonin Receptor Agonists, 8-Hydroxy-2-(di-n-propylamino)tetralin, GTP-Binding Proteins, Rats, Serotonin 5-HT1 Receptor Agonists
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