Within humans and other animals, there is a conserved regulatory system of endogenous cannabinoids and receptors call the endocannabinoid system. The most common cannabinoid receptors found in humans and many animals are cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). However, there are other receptors that may also play a role in the essential functioning of the endocannabinoid system. One recent study aimed to assess the potential of one of these receptors – GPR55 (sometimes referred to as the CB3 receptor) – in reducing symptoms of depression in mice.
Depression is a mood disorder that is thought to affect over 322 million people worldwide. As such, the condition poses a major global health issue. Current treatment options are often found to be not sufficiently effective as well as having a delayed onset of biological action and a high potential to cause adverse effects. This highlights the need for new treatment options for depressive conditions – an area where cannabinoid receptors such as GPR55 could be of particular interest.
What are GPR55 Receptors?
Although CB1 and CB2 receptors may be the most researched and most prevalent cannabinoid receptors, atypical receptors, such as GPR55, are also thought to play a role in some of the major and minor effects of cannabinoids.
GPR55 receptors are modulated by both cannabinoid and non-cannabinoid ligands. They are found in a number of cells and organs including cancer cells, liver, spleen, small intestine, lungs, and kidneys. The function of GPR55 receptors has been indicated in bone formation, inflammatory response, neuropathic pain, and fetoplacental development, amongst other mechanisms. GPR55 receptors have also been detected in parts of the brain responsible for pain perception, motor coordination, anxiety, substance abuse, and neuroprotection.
The Aims of the Study
GPR55 receptors are localised in brain areas that are implicated in the physiology of depression and, in addition, the GPR55 gene expression is reduced in the dorsolateral prefrontal cortex of suicide victims. Stimulation of the GPR55 receptor has also been found to have some anti-anxiety effects.
This study aimed to build upon the current body of evidence by assessing the effects of O-1602 – a phytocannabinoid-like analogue of cannabidiol (CBD) – as an agonist of GPR55 receptors. Researchers monitored depressive-like behaviour in female Wistar rats.
What methods were used for the Study?
This study aimed to assess the effects of GPR55 stimulation on depressive-like behaviour. To do this, 60 female Wistar rats were divided into four groups. The control groups received saline and/or methyl acetate for 14 days, whilst the experimental arm received corticosterone treatment for the same length of time. Half of each group then went on to receive saline and/or methyl acetate or O-1602 for 7 days forming four study arms. The control group (group one) received saline and/or methyl acetate for both drug periods.
The study animals underwent a behavioural study, which involved measuring spontaneous locomotor activity and a forced swim test.
The researchers found that rats that had received a 14-day administration of corticosterone-treatment reduced their swimming time when compared to rats receiving saline and/or methyl acetate. However, this was reduced in animals treated with O-1602 following corticosterone. These results indicate that O-1602 may present positive effects in an animal model of depression which may be replicated in humans. Previous studies have demonstrated similar findings, whereby O-1602 reduced anxious activity in both normal rodents and those exposed to acute stress.
However, the study’s researchers also admit that much more research is needed to understand the mechanisms of the observed effects of O-1602. Although it is assumed that the antidepressant-like effects of the drug are probably due to its interaction with the GPR55 receptors as O-1602 does not bind with CB1 and CB2 receptors more evidence is required to confirm that the effects are not derived form off-target effects. These results are promising in helping to further understand the endocannabinoid system and how we can better design treatments for the wide spectrum of diseases where cannabis is reported to be of benefit.