The endocannabinoid system (ECS) is a signaling system interwoven in the central nervous system that acts peripherally in many areas of the body, including modulating mood. There are three main constituents of the ECS: the endocannabinoid signaling molecules (simply endocannabinoids), the G-protein-coupled cannabinoid receptors, and the enzymes that play a role in endocannabinoid biosynthesis and inactivation. Endocannabinoids include anandamide and 2-arachidonoylglycerol. The main receptors in the ECS are cannabinoid (CB) receptor types 1 and 2 (CB1 and CB2). Endocannabinoids may also interact with other receptors, such as transient receptor potential cation channel subfamily V member: 1/vanilloid receptor 1 and orphan G-coupled protein receptor 55.

Studies have demonstrated the potential for the ECS, especially CB1, to play a role in mood and related disorders, including depression, anxiety, post-traumatic stress disorder (PTSD), and bipolar disorder. Animal studies have demonstrated the role of CB1 as a mood regulator. Activating CB1 may help regulate mood, with additional studies demonstrating that CB1 agonists have antidepressant and anxiolytic effects. Alterations to the ECS have also been found to be associated with depression and other psychiatric disorders. The ECS may also help regulate the stress response and neuroinflammation, which may mitigate the effect that stress and inflammation may have on the development of psychiatric disorders and mood alterations.

Phytocannabinoids bind to the ECS receptors, including CB1 and CB2. As such, they may modulate the ECS system. Studies have found the potential for anxiolytic and antidepressant properties, likely through their modulation of CB1 and CB2. Phytocannabinoids may also promote a healthy inflammatory response, which may also support a healthy mood. Researchers have found many potential benefits of phytocannabinoids for mental health disorders, including depression, anxiety, and PTSD.

Animal models have demonstrated the potential for phytocannabinoids to help support mood disorders, including anxiety, depression, and PTSD. Human studies are starting to emerge, but additional research remains necessary.

One systematic review of clinical studies assessed the potential for phytocannabinoids to help psychiatric disorders. The researchers found few clinical studies on phytocannabinoids, especially randomized controlled trials, but they determined that the findings were promising for schizophrenia, social anxiety, PTSD, and attention deficit hyperactivity disorder.

Secondary metabolites, such as the terpenes found in cannabis plants, may also support mood regulation. Full-spectrum phytocannabinoids that also include terpenes may act synergistically to promote a healthy mood. Research on phytocannabinoids remains in the early stages, but there are promising results that have demonstrated their potential to support mood and occasional anxiety.

By Kendra Whitmire, MS, CNS