5-HT1a is a serotonin receptor. 5-HT1a is not a classic cannabinoid receptor but its activity is modulated by cannabinoids. Since cannabinoids have a physiological effect on 5-HT1a it is effectively a cannabinoid receptor.

Chemical Name: 
5-HT1A receptor
IUPHAR entry: 
Wikipedia entry: 

The 5-HT1a receptor is the most widespread of all the 5-HT receptors. In the central nervous system, 5-HT1a receptors exist in the cerebral cortex, hippocampus, septum, amygdala, and raphe nucleus in high densities, while low amounts also exist in the basal ganglia and thalamus.[3][4][5] The 5-HT1a receptors in the raphe nucleus are largely somatodendritic autoreceptors, whereas those in other areas such as the hippocampus are postsynaptic receptors.

Literature Discussion: 


CBD interacts with 5-HT1a (Russo, Burnett & Parker, 2005).


The anxiolytic action of CBD may be mediated by the 5-HT1A receptor (Russo et al., 2005)


CBG can activate α2 receptors and block CB1 and 5-HT1A receptors (Cascio et al., 2010), suggesting CBG does have therapeutic potential in the treatment of depression.

Hypoxic-Ischemic Encephalopathy

CBD mechanisms would involve the modulation of excitotoxicity, oxidative stress and inflammation through CB2, 5HT1A, Adenosine A2A and PPAR-γ receptors (Castillo et al., 2010; Hind et al., 2015; Pazos et al., 2012, 2013).

Psychosis and Schizophrenia

In an animal study, THCV was found to have anti-psychotic effects through activation of the 5-HT1a receptor (Cascio et al., 2014)


Castillo, A., Tolón, M.R., Fernández-Ruiz, J., Romero, J., and Martinez-Orgado, J. (2010). The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic-ischemic brain damage in mice is mediated by CB(2) and adenosine receptors. Neurobiol. Dis. 37, 434–440.

Cascio, M.G., Gauson, L.A., Stevenson, L.A., Ross, R.A., and Pertwee, R.G. (2010). Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. Br. J. Pharmacol. 159, 129–141.

Cascio, M.G., Zamberletti, E., Marini, P., Parolaro, D., and Pertwee, R.G. (2015). The phytocannabinoid, Δ 9 -tetrahydrocannabivarin, can act through 5-HT 1 A receptors to produce antipsychotic effects. Br. J. Pharmacol. 172, 1305–1318.

Hind, W.H., England, T.J., and O’Sullivan, S.E. (2015). Cannabidiol protects an in vitro model of the blood brain barrier (BBB) from oxygen-glucose deprivation via PPARγ and 5-HT1a. Br. J. Pharmacol.

Pazos, M.R., Cinquina, V., Gómez, A., Layunta, R., Santos, M., Fernández-Ruiz, J., and Martínez-Orgado, J. (2012). Cannabidiol administration after hypoxia-ischemia to newborn rats reduces long-term brain injury and restores neurobehavioral function. Neuropharmacology 63, 776–783.

Pazos, M.R., Mohammed, N., Lafuente, H., Santos, M., Martínez-Pinilla, E., Moreno, E., Valdizan, E., Romero, J., Pazos, A., Franco, R., et al. (2013). Mechanisms of cannabidiol neuroprotection in hypoxic–ischemic newborn pigs: Role of 5HT1A and CB2 receptors. Neuropharmacology 71, 282–291.

Russo, E.B., Burnett, A., Hall, B., and Parker, K.K. (2005). Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem. Res. 30, 1037–1043.

Clinical Trials: 


Several clinical trials have tested the therapeutic potential of cannabinoids after Stroke. Meta-analysis revealed that both endocannabinoids like AEA, OEA or PEA and plant cannabinoids like THC or CBD can significantly reduce neuronal degeneration after Stroke (England et al., 2015). Specifically activating CB1 and/or CB2 receptors had the strongest protective effect but other receptors such as 5-TH1a and PPARα are also likely to be involved.


England, T.J., Hind, W.H., Rasid, N.A., and O’Sullivan, S.E. (2015). cannabinoids in experimental Stroke: a systematic review and meta-analysis. J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab. 35, 348–358.