INL Article - How can CBD help Anxiety?
How can CBD help Anxiety?
If you are still a little new to Cannabidiol (CBD) and how it relates back to cannabis, then here is a short introduction. CBD is one of the main phytocannabinoid constituents within cannabis that has garnered a lot of attention due to its pleiotropic actions within the endocannabinoid system, the nervous system and the immune system. (1)
CBD and its relationship with CB2 receptors in the endocannabinoid system is considered to be especially important, due to the role that internal cannabinoids or “endocannabinoids” play in the pathology of many disorders, where it can serve at minimum, a “protective role”.
Several diseases like enesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating the endocannabinoid system. (2)
Do we know everything about how CBD may help with anxiety?
The answer is no. But we can now draw some important ideas about how it can help via analysing the multiple therapeutic targets that CBD works on within the brain along with the modulation of multiple different disease processes such as neuroinflammation.
Anxiety disorders affected 284 million people worldwide in 2017, making it the most prevalent mental illness. (3) Furthermore, the median age of onset for anxiety in its varying presentations (11 years old) is significantly earlier in life in comparison to other mental conditions such as disorders of mood (30 years). (4)
One of the key mechanisms being investigated regarding anxiety is the presence of higher levels of inflammation within the brain, or what’s commonly referred to as “neuroinflammation.” This can often be related back to treatment resistance when using antidepressants with increased inflammatory markers both in anxiety patients and those with major depressive disorder. (5)
Neuroinflammation may be the key to understanding how CBD can help with anxiety
Interestingly within neuroinflammation, one of the first cell groups to respond are the microglial cells that release proinflammatory cytokines such as IL-6, TNFα and IL-1β. (6), (7) Microglia regulate the initiation and progression of immune responses in the central nervous system and evidence is now showing that microglia frequently alter levels of gene expression when stimulated.
Investigations on the role of the endocannabinoid system in this process came to the fore when CB2 receptor induction was found in the spinal cord with concomitant microglial activation in mouse models. (8) The interaction with the endocannabinoid system within this model now suggests that neurons or astrocytes produce endocannabinoids such as anandamide as a means of recruiting microglia. (9), (10) The recruited microglia are then able to play important roles in pathogen recognition and inflammation via the activation of Toll-like receptors (TLRs). The problems start though when this microglial system becomes dysregulated.
This interaction with anandamide brings CBD into the discussion. Exogenous cannabinoids such as CBD have been shown to increase intracellular levels of anandamide – the result being a positive modulation of the microglial activation that can lead to not only depression and anxiety but other mental health conditions as well.
Another way this neuroinflammatory process could be attenuated is via CBD’s inhibition of adenosine reuptake leading to increased adenosine which can have both a neuroprotective effect as well as decreasing inflammation in the brain after brain trauma. (11)
Important interactions between CBD and receptors in the brain may also contribute to understanding its role in anxiety
CBD has key research showing that high concentrations directly activate the 5-HT1A (hydroxytryptamine) serotonin receptor. (12) This interaction was one of the pioneering discoveries that lead to its proposed anti-anxiety effect as well as suggesting that CBD could attenuate acute responses to stress as well as the delayed effects of it via the interaction with 5-HT1A. (13)
The hydroxytrptamine receptor is implicated in a diverse range of neuropharmacological effects ranging from mood, appetite, sleep, sex and temperature amongst peripheral actions within the cardiovascular and gastrointestinal system.
Early research also suggested that 5-HT1A receptors play a key role within the hippocampus to moderate adaptive or coping responses to adverse events, a dysfunction of which is related to depression. (14) Interestingly in these early studies 5-HT1A agonists like CBD improved this dysfunction leading to more recent studies investigating its role as a “fast antidepressant drug” potentially leading to a new therapy for anxiety also. (15)
Finally, pilot studies have also been investigating CBD role as a positive allosteric modulator of the GABA-A. (16) This receptor interaction can enhance its affinity for GABA amplifying its anxiolytic effect offering an effect similar to that of benzodiazepines but potentially longer lasting. (17)
Higher doses of CBD have had good results in different presentations of anxiety, but more research is required
In anxiety, numerous studies have been conducted on the differing applications CBD may have and some notable studies have used higher doses in order to achieve these results. This has led to further discussion and research around how high doses can be delivered to get the types of potential results we are seeing in the aforementioned studies.
A good example of this is the now famous public speaking study using 600mg of CBD. Subjects were either given CBD or placebo and asked to perform a simulated public speaking course; one group of healthy controls and another with a generalized social anxiety disorder. Whilst effects did not differ between the anxiety group and the healthy controls, both groups saw a positive change with pretreatment of CBD significantly decreasing anxiety, cognitive impairment and discomfort during the speech performance, along with a marked decrease of alertness in anticipatory speech. (18)
Current animal studies are suggesting that higher doses (100mg/kg) have been ineffective and lower doses (10mg/kg) were more effective at treating anxiety - leading to a bell-shaped dose response curve. (19) This reinforces the “start low, go slow” mantra regarding clinical dosing for CBD with patients but also may suggest that higher doses offering better more consistent therapeutic potential is possible as the research evolves.
CBD has potential in preventative strategies for stress-related neuropsychiatric disorders such as PTSD
This though doesn’t mean that lower doses can’t still affect the neuroinflammatory pathways the CB2 receptor modulates suggesting its additive effects when it comes to a more prevention-oriented strategy for the treatment of anxiety over the long term.
A good example of this comes from CBD’s potential to have a positive effect on PTSD fear memory acquisition as well as its proposed attenuation of contextual memories associated with past experiences in murine experiments, showing CBD’s ability to disrupt harmful memories. (20)
So, can CBD help with anxiety?
Based on preliminary research the answer is yes. CBD’s ability to affect multiple different therapeutic targets is very clear. More answers on how we can continue to help patients increase their doses to achieve these benefits consistently is on the way as more human studies come. With CBD’s good safety and toxicity profile we may want to start increasing our patient’s dosage profiles steadily to some of higher doses such as 80-100mg daily after beginning at lower doses, especially for anxiety. Definitely a space to keep an eye on.
MedLab NanoCBD Oral SprayNanoCBD is a formulation containing 16.67 mg/mL cannabidiol (CBD) as active ingredient, in a sub-micron spray applied to the oro-buccal membrane.