If you’ve been suffering with anxiety, then I’ll bet you’re highly motivated to find ways of managing, and alleviating it.
I don’t have to tell you how much of a drain it is to feel anxious about things your logical self knows aren’t a big deal. Nonetheless, that fails to stop the pervasive worry.
Whether you find it difficult to drop into a state of harmony in social interactions, are worried about your health, or just feel the weight of the world more than the next person, anxiety sucks.
Im no stranger to anxiety. Ive come to know it very well in fact, not as an enemy, but as a friend. Sometimes it can be a powerful ally, illuminating my fears so I may work on them and grow as a result. Other times, its a force that seeks to undermine my best self and challenge the trust I hold within myself.
Thats when I find CBD to be a powerful ally. Unlike conventional pharmacological means, Ive found CBD to provide a soothing escape which makes the light of life shine just a little brighter. Whilst I would consider it more of a helping hand than a solution, it has provided a boost in quality of life that facilitates further improvements through continual growth.
Take social anxiety for example; CBD enabled me, and I bet a few others, to loosen up a little and see social situations in a different light. A less threatening light. Its this space that CBD provides which allows a different narrative to shine through – one that isn’t so scary.
With a little mindfulness and reframing practice thrown in (cognitive behavioural therapy tekkers), this combo can really help enable positive change in perceptions of threat and danger for the future.
CBD Helps Alleviate The Physical Manifestation Of Anxiety
Hitching a ride with the mental anguish are the physical symptoms of anxiety. Everyday experiences are consciously processed through the cerebral cortex, and filter through the limbic system in the brain, radiating throughout the autonomic nervous system via the hypothalamus.
This particular branch of the nervous system is divided into sympathetic and parasympathetic nervous activity. But you may know them as fight or flight aka get the hell out of here response, or rest, digest and relax.
Anxiety is typically driven through sympathetic nervous system activation (over activation in chronic cases). This has profound physical implications, as nervous activity controls many physiologic processes throughout the body such as:
- Muscle contraction
- Enzyme activity
- Heart rate
- Blood pressure
- Water/ion balance
- Breathing rate
- Digestion (muscle contraction and hormonal secretions)
- Immune activity
- Energy metabolism
- Hormonal secretions
Digestion & Gut Function
Whilst sympathetic nervous system overactivity is common in anxiety, and conditions affected by anxiety (IBS), irregularities in parasympathetic nervous system activity can also be trouble.
For instance – Acetylcholine signalling within the enteric nervous system (in the gut) mediates the smooth muscle contraction in the small and large intestine, controlling the movement of food through them.
The vagus nerve (parasympathetic) can over express Acetylcholine, resulting in hyper motility (food moving too fast through the GI tract).
This is what commonly presents as an irritable bowel, especially in diarrhoea predominant IBS, and can lead to fluid loss, poor digestion and nutrient absorption.
Interestingly, indirect elevation of your bodies own cannabinoids could be used to inhibit hyper motility states. CBD has been found to increase circulating levels of Anandamide (endocannabinoid) in the gut. Increasing Anandamide reduces excessive acetylcholine signalling by activating the CB1 receptor, slowing the transit of food, having an anti-diarrhoea effect.
THC is an agonist of CB1, activating the receptors effects directly in the same way Anandamide does (via CBD). They both inhibit hyper motility, in both the small and large intestine – a potentially useful therapy for IBS-D.
Where IBS-D is a case of hyper motility, IBS-C presents with reduced motility and transit throughout the gut causing constipation. In an opposing manor, CB1 antagonists have been found to increase contractility within the smooth muscle of the gut. CBD works on its own here, as an antagonist (blocks the effects of the receptor). This increases Acetylcholine signalling, stimulating contraction in both the small and large intestine, stimulating clearance (and maybe a little relief) within the bowels.
Its worth noting that the gut is also under sympathetic nervous system control. However, it appears that cannabinoids mediate their effects mainly through the vagus nerve in terms of motility. But thats not to say that there might be some crosstalk between the two systems.
Sympathetic activity is generally inhibitory for muscle contraction in the small intestine (slows it down), and excitatory in the large intestine. That means that sympathetic over activation could result in both diarrhoea and constipation, depending on the individual.
Effects of cannabinoid receptor activity throughout the gut (with special attention to motility in the small and large intestine).
Nausea & Vomiting
A common effect of feeling incredibly anxious is the imminent possibility that you might throw up, or even faint.
In an opposing manor to which a ‘whitey’ occurs (having smoked a very large dose of cannabis very quickly), termed hyperemisis; CBD can actually help counteract emesis (nausea and vomiting).
This was found to be the case when CBD was combined with THC in a preparation called Sativex (1:1 ratio). In chemotherapy patients, Sativex reduced the delayed nausea and vomiting induced by chemo by 71% in the group given the combination, compared with 22% in the placebo group. Its worth noting that all participants were also receiving an adjunct anti-emetic therapy (5-HT3 Antagonist).
Learned Fears And Responses
Fear, and anxiety stem from the amygdala within the limbic system – our emotional processing centre as well as our fear database. Also within the limbic system is the hippocampus, our centre for learning and memory.
Before information passes through the limbic system, it is first gathered by a higher brain centre – the cerebral cortex. Whilst the information gathered in the cerebral cortex is neutral, when filtered through the limbic system (where fears and memories reside), a threat may then be associated with a certain situation, environment or stimuli.
Essentially what the limbic system does is screen this new information based on passed experiences and attaches a (often false) perception of danger.
So, past experiences go on to shape how we react to future stimuli. These learned fears are what constitute PTSD and anxiety from traumatic memories and events.
So, how exactly does CBD (and cannabis) help?
Im glad you asked…..
Housed within the limbic system is also the hypothalamus, which is essentially the messenger connecting the brain to the body. As part of the limbic crew, it takes what its neighbours (amygdala, hippocampus) have told it, and radiates that message throughout the body via the Hypothalamic Pituitary Adrenal (HPA) axis.
The HPA axis is effectively a communication network which sends messages via hormones, like corticosteroids (cortisol), to cells, tissues and organ systems throughout the body. Mental anguish can begin to take its toll physiologically overtime, and manifest as physical symptoms. Its common to see muscle wasting, impaired immunity and mitochondrial disruption (fatigue) as a result of chronic stress, anxiety and PTSD via HPA over activation (cortisol).
This is why its important to tell your hypothalamus to chill out, due to these deleterious downstream effects. This is where Cannabis comes in, effectively acting as a pacifier for the screaming baby that is your limbic system.
In a double blind, placebo controlled crossover trial, CBD was found to significantly decrease subjective anxiety, measured by VAMS (Visual analog mood scales). CBD was dosed at 400mg, and brain activity was measured using SPECT (Single-photon emission computed tomography). Interestingly, CBD actually changed brain activity within the limbic areas, inclusive of the amygdala and hippocampus. A later study by the same author showed a decreased activity in these areas of the brain, again with 400mg CBD, which also reduced subjective anxiety scores.
Endocannabinoid signalling is actually centrally involved in the production of stress. The activity of endocannabinoids can actually modulate the activity of the HPA axis (via the limbic system).
Illustrated below are the effects of stress on the activity and degradation of the two endocannabinoids – Anandamide (AEA) and 2-Arachadonylglycerol (2-AG). Stress induces increased release of Corticotropic releasing hormone (CRH), which increases the enzyme Fatty acid amide hydrolase (FAAH), subsequently speeding the degradation of Anandamide (the ‘bliss’ molecule). In addition, stress also elevates cortisol, further affecting endocannabinoid tone and balance.
Get this – CBD actually inhibits the activity of the enzyme FAAH (Fatty acid amide hydrolase) which degrades the endocannabinoid Anandamide. It also inhibits the action of a fatty acid binding protein, which transports Anandamide to FAAH for degradation.
Therefore, CBD enables increased binding of Anandamide to CB1 and CB2 receptors, which in part accounts for the reduction in fear expression, fear memory disruption and enhanced fear extinction.
The other part of this anxiolytic magic is mediated through activation of the 5-HT1A receptor by CBD. These are serotonin binding receptors which increases the activity of the vagus nerve (parasympathetic nervous system – rest and digest, remember?). 5-HT1A are densely populated in the brain, and modulate emotion in the limbic system. Other neuromodulatory effects of 5-HT1A activation include sympathoinbihition (cool it flight or flight system).
Social Anxiety & Public Speaking
One of the most ubiquitous fears is that of public speaking, which stems from a fear of being judged.
Interestingly, the fear of public speaking is actually very similar to social anxiety. It is in fact a form of state social anxiety. However, the fundamental difference is that fear typically disappears after being faced with speaking in front of a crowd.
In social anxiety, the fear is pervasive when faced with everyday social situations which most of us would consider normal.
The good news is that CBD is here to help, and has demonstrated some promising evidence for the treatment of social anxiety conditions.
In a double blind protocol, CBD (300mg), ipsapirone (5 mg), diazepam (10 mg), or placebo were administered before a simulated public speaking test. Bar the placebo, all the interventions significantly reduced the anxiety induced by the test. This is encouraging, as CBD demonstrates equal efficacy for alleviating social anxiety, only without the risks and side effects associated with pharmaceuticals such as diazepam.
In another study, participants with Social Anxiety Disorder were given CBD (600mg) or placebo in a double blind, randomised fashion. Again, they were tested using a simulated public speaking test. Healthy participants were also subjected to the same test, only without the use of medication. The Visual Analogue Mood Scale (VAMS) and Negative Self-Statement scale (SSPS-N) were used to assess subjective anxiety, as well as physiological markers of anxiety – blood pressure, heart rate and skin conductance.
Participants treated with CBD significantly reduced anxiety, cognitive impairment and discomfort during their speech. As a result, SAD participants given CBD showed a similar response to public speaking as the healthy controls. This indicates a strong potential for CBD to reduce any excessive fear that would be otherwise considered as an anxiety disorder.
Effects On Mood
Depression is a common passenger that hitches a ride with anxiety. The fact that one experiences anxiety (especially chronically) is enough to produce a bleak outlook on life.
Disturbances in mood and depression are famously associated with serotonin signalling (although more contemporary evidence suggests there is more to it than that). As we have seen above, CBD activates the 5-HT1A receptor, which stimulates serotonergic neurones affecting mood.
Mood disorders are complex, and involve a range of neurotransmitter and signalling pathways. At the root of many signalling pathways are the endocannabinoids. Your endocannabinoid system is a homeostatic regulator of neurotransmitter systems, and just about every other physiologic system in the body.
As we have seen, CBD can influence endocannabinoid signalling and therefore other neurotransmitters, such as glutamate. This is excitatory in nature, and is closely associated with anxiety responses. An indirect inhibition of glutamate signalling (via endocannabinoid activity) might also contribute to the anti-anxiety effects of CBD.
When we talk about neurotransmitters binding receptors, we have to look at a given molecules affinity for that receptor. Take CB receptors for example; CBD is an antagonist of the CB receptors, with a fairly weak affinity. It also influences endocannabinoid biosynthesis and subsequently CB receptor binding. THC however is a partial agonist with strong affinity (its more attracted to that receptor), which may explain some of CBD’s subtle effects on mood when compared to THC, which has full blown psychoactive effects.
Thats why the addition of THC is often synergistic with CBD, as an even more effective means of treating depression and anxiety. In the right ratios, they can be a power couple for altering mood.
Anyway, CBD can actually change the shape of the GABA-A receptor in a way which increases its affinity for its specific target neurotransmitter – GABA. Gamma-Aminobutyric acid is an inhibitory neurotransmitter which produces states of calm and balance throughout the nervous system, and is what accounts for the sedating and relaxing qualities of alcohol. Through a greater affinity for GABA-A receptors, the relaxing qualities of GABA are more pronounced, alleviating anxiety.
In addition, a more recent understanding of mood disorders, such as depression and anxiety has emerged. These share a common underpinning which you may be familiar with – inflammation.
Neuroinflammation (brain) is found in a host of mental illnesses which affect mood, including depression, anxiety and even bi-polar disorder and schizophrenia. This inflammation actually effects a host of communication networks within the brain, messing with mood.
More good news – CBD is a potent anti-inflammatory and has antioxidant properties which make it an effective neuroprotective.
TPRV-1 is a receptor which is well associated with pain perception and inflammation. Capsaicin (the pungent principal in chills) actually binds this receptor, and produces the burning sensation associated with the chilli’s ‘heat’. In an opposing manor, CBD may act to desensitise you to pain, and quite possibly exert its anti-inflammatory effects through this receptor (as well as CB2 receptor activity, which ‘talks’ to the immune system).
As you’ve seen above, the limbic system is a key regulator of mood and stress. The hippocampus, as part of this system is also of great interest in anxiety. Conditions of chronic stress can impair the neural plasticity within the hippocampus, and produce symptoms of depression and anxiety. This might explain the co-existence of these two mood disorders, as stress induces depression.
What is neural plasticity?
Its basically the brains ability to adapt to new situations and environments, and respond to injury and disease through the development and maintenance of neural networks.
A key regulator of neural plasticity, Brain Derived Neutropic Factor (BDNF) can be measured as a serum and plasma reading, and is typically found to be reduced in cases of depression. BDNF is a crucial component in the growth and development of new neural networks in the brain – neurogenesis.
I bet your guessing what role Cannabis has to play here, right?
Well, its a corker, Ill tell you that.
Anandamide is actually very closely associated with BDNF. In fact when you exercise you are increasing Anandamide signalling, thereby stimulating BDNF to work its magic on the hippocampus. This is why exercise is such a powerful anti-anxiety therapy.
In a similar way to exercise, CBD prevents the metabolism and re-uptake of Anandamide, allowing increased endocannabinoid signalling and possibly BDNF presence. In this way, neurogenesis can occur in the hippocampus.
In addition, a synthetic cannabinoid which mimicked the action of THC (CB1 activation), when administered chronically showed anxiolytic and antidepressant action likely via hippocampal neurogenesis.
If you think about the similarity between THC and anandamide, they both bind to the CB1 receptor and cue its activation. CBD encourages increased binding of Anandamide to produce this effect, and exercise independently increases Anandamide signalling. Together, these could be powerful anti-anxiety treatments.
CBD And Panic Attacks
Anyone who experiences anxiety knows about the incessant background noise that seeks to undo their very being. If that wasn’t enough, sometimes it goes a step further when a tidal wave of anxiety suddenly hits at once.
Coming out of the blue, this rogue wave takes hold and unfolds into full blown panic – unpleasant to say the least. Thankfully, CBD has a helping hand to play in riding this wave out.
Moderated once again through the activation of the 5-HT1A receptor, CBD impairs escape like behaviour, which suggests that it packs an anti-panic punch. This was found by a study conducted on rats subjected to electrical stimulation whilst housed in a circular arena. Panic was defined as the threshold which prompted the rats to run around the arena in an attempt to escape.
A similar study also showed inhibition of anxiety and panic in mice, whose fear was induced by the presence of a wild snake!
These animal studies are encouraging, and can likely be supported by the anecdotal evidence of human CBD users who experience panic attacks.
Taking This Into Consideration
These studies may have a certain degree of internal validity, but when using CBD oil for yourself, doses and effects may vary. In addition, many studies showing a potentially efficacious effect of CBD are on animals, and may vary for humans.
Due to your highly personalised genetic make – up and biochemical individuality, an effective dose for you may be different from others. In addition, the tone of your endocannabinoid system may vary, which could affect your response to CBD (and cannabinoids in general).
A good starting point is to try low doses of CBD and work your way up. Anywhere from 10mg allows you space to experiment. Doses used in studies (400 & 600mg) are considered fairly high, so before you dive into the unknown or potentially waste your CBD oil (isolated CBD may have a bell shaped curve effect compared to full spectrum extract), dip your toe in.
Here’s a neat summative illustration of everything listed above: