Endoctrination Series vol. 2: Cannabis and Anxiety

Welcome to the second report in our Endoctrination Series—a series of reports on the Endocannabinoid System (ECS) created by our in-house product education team to investigate the most common personal care concerns, how the ECS is involved, and what technologies can be used to address them. The Cannabis and Anxiety report dissects the available literature on the ECS and its relationship with stress and anxiety, ending with tips on toning the ECS to achieve daily calm and resilience with cannabis.

Highlights.

• Many people report using marijuana to cope with anxiety, especially those with social anxiety disorder.
• THC appears to decrease anxiety at lower doses and increase anxiety at higher doses.
• CBD appears to decrease anxiety at all doses that have been tested.
• CBD has shown anxiolytic efficacy both acutely and following chronic treatment in people with clinical anxiety.
• There are individual differences in responses to marijuana that are affected by a variety of factors.

Introduction.

Anxiety- and trauma-related disorders are the most common psychiatric conditions. Despite that, they are associated with inadequate treatment options, which can thus have a substantial negative impact on quality of life.

Psychological treatments are often limited or temporary in their effectiveness, while medications can lack efficacy or have unwanted side effects in a considerable number of patients. Psychological therapies can also be combined with medications to enhance treatment synergistically, but some medications can interfere with these therapies. Better options are therefore urgently needed for treating these disorders.

In this vein, an increasing number of people struggling with anxiety and/or depression are trying cannabis products for symptom management. With the legalization of cannabis, increasing availability of cannabinoid technologies, and proliferating anecdotal evidence for the anxiolytic potential of cannabinoids, it is important to take stock of the empirical evidence to determine if cannabinoids can live up to their hype as an option for treating anxiety-related disorders in the future.

In this narrative report, we begin by describing the underlying causes of anxiety. We then review the role of the ECS and the preclinical and clinical studies that have investigated cannabinoid regulation of fear and anxiety. We conclude by outlining two major targets for the treatment of anxiety caused by prolonged stress.

What causes anxiety?

While there are several causes, stress is the prevailing trigger for anxiety. Signs and symptoms include:

• Feeling nervous, restless or tense.
• Having a sense of impending danger, panic or doom.
• Having an increased heart rate.
• Breathing rapidly (hyperventilation).
• Sweating.
• Trembling.
• Feeling weak or tired.
• Trouble concentrating or thinking about anything other than the present worry.
• Having trouble sleeping.
• Experiencing gastrointestinal (GI) problems.
• Having difficulty controlling worry.
• Having the urge to avoid things that trigger anxiety.

Anxiety disorders are forged over years. They have a genetic component, psychological component, and environmental component. All of them present a form of stress to the systems reacting to them, so we’ll review the physiological changes stress causes that lead to anxiety and the tools that target them.

The best way to understand your anxiety is to break it down into the two main causes:

• Biology
• Environment

However, the fact remains that simply having a biological predisposition, or a heightened sensitivity to stress, is not enough to develop an anxiety disorder. A person is more likely to develop an anxiety disorder if they are biologically predisposed to anxiety, in conjunction with psychological vulnerabilities exacerbated by stress and stressful experiences.

Which highlights the criticality of a holistic approach to treating anxiety.

It bears reminding that, while the tips and tools in the report’s conclusion can help build resilience to stress so you can better manage, alleviate, and in some cases completely neutralize symptoms of anxiety, you have to do the work in order to see lasting, sustained results. However, due to the scope of this report and the direct impact that the environment and psychological vulnerabilities have on body and brain chemistry, the remainder of this report will focus on the biology of stress, anxiety, and the tools to manage and treat its symptoms.

The role of the Endocannabinoid System (ECS) in anxiety.

The ECS is expressed in all brain regions that are important for the processing of anxiety, fear, and stress and has been identified as playing an important role in these responses. That's because the ECS's primary role is to regulate stress, inflammation, and homeostasis (biological balance).

Both for anxiety and fear memory processing, the ECS is thought to ensure an appropriate reaction to stressful events and to serve as a regulatory buffer system for emotional responses.

Endocannabinoids like Anandamide (AEA) and 2-AG appear to modulate highly interactive stress and reward networks, consisting of the endocannabinoid system (ECS), dopamine system, and hypothalamic-pituitary-adrenocortical (HPA) axis. These networks establish the balance between distress and well-being.

Like social interaction and exercise, marijuana intoxication produces a sought-after state of calmness or contentedness, mediated by the anxiolytic effects of increased cannabinoid and oxytocin receptor activation and the rewarding effects of elevated dopamine.

Let’s take a look at the two most common cannabinoids and their studied effects on anxiety.

Stress and anxiety.

Traumatic life events can cause anxiety disorders, but it doesn’t usually come to that. Simple life stress is one of the prevailing reasons people develop anxiety. Stress — especially long term stress, like one would experience in a job they disliked or in a relationship that was emotionally damaging — appears to create anxiety disorders. When stress is prolonged, it overwhelms the ECS's ability to regulate the stress response. When your ECS is dysfunctional, stress runs amock, which in turn leaves your systems out of whack.

The link between stress and anxiety is extensive. Those who feel stress for any reason tend to be significantly more likely to struggle with anxiety than those who have not experienced long-term stress. The reason for this isn’t entirely clear but has been linked to many theories. The possible reasons stress causes anxiety include:

Stress Affects the Balance of Hormones and Neurotransmitters

Ongoing stress can trigger increased cortisol and can manifest as inflammation, exhaustion, lack of focus, irritability, and more. Increased cortisol effects time spent in REM and deep, restorative sleep, which further impairs functional connectivity in the PFC, increasing vulnerability to / inability to deal with stress while impacting cognition, memory, mood. PFC deterioration is also linked to anxiety, depression, and more.

Stress Weakens the Part of the Brain That Controls Coping or Anxiety Control

Chronic exposure to uncontrollable stress causes loss of spines and dendrites in the prefrontal cortex (PFC), a recently evolved brain region that provides top-down regulation of thought, action, and emotion.

PFC neurons generate top-down goals through recurrent excitatory connections on spines. This persistent firing is the foundation for higher cognition, including working memory, and abstract thought. However, exposure to acute uncontrollable stress rapidly weakens synaptic connectivity to reduce persistent firing. Chronic stress exposures can further exacerbate these signaling events leading to loss of spines and resulting in marked cognitive impairment.

CBD and anxiety: Science-backed benefits and how to use.

8 clinical studies on CBD for stress show that CBD significantly reduces stress and its manifestations (anxiety, depression, burnout, fear).

CBD has also shown anxiolytic efficacy both acutely and following chronic treatment in people with clinical anxiety. Preclinical evidence suggests that anxiolytic effects are produced via serotonin (5-HT1A) receptor agonism in both acute and chronic dosing models, without impacting 5-HT1A receptor expression.

Additionally, systemic CBD treatment has been shown to reduce fear memory encoding (your body’s response to an event) and expression (future manifestations, e.g. panic, anxiety, OCD, etc.).

CBD for Anxiety and Stress – Does it Work? by @MySupplyCo

A number of pharmacological mechanisms are responsible for CBD’s therapeutic effects, but its regulation of anxiety-like behaviour and learned fear processing involves serotonin (5-HT1A) receptors, TRPV1 channels, and endocannabinoid signalling.

That means the acute effects of CBD on anxiety and learned fear expression are dose-dependent, such that low and intermediate, but not high, doses are effective. These results indicate that the anxiolytic effects of lower doses of CBD involve 5-HT1A receptor activation, whereas higher doses of CBD might not affect anxiety by also activating TRPV1 channels.

In contrast to CBD’s acute anxiolytic effects, its ability to extinguish fear memory (called an extinction) involves its activation of cannabinoid receptors. However, CBD shows little affinity for CB1 or CB2 receptors. Instead, it activates the ECS by increasing endocannabinoid levels.

As is the case with CBD, anandamide has been shown to be anxiolytic at lower doses and anxiogenic at higher doses. That’s because lower levels activate CB1 receptors, while higher levels involve TRPV1 channel activation. This indicates that maintaining the balance between CB1 receptor and TRPV1 channel activation is crucial for regulating anxiety, given their opposing anxiolytic and anxiogenic effects.

How to Use CBD for Anxiety

• Start by taking 20mg CBD AM and 20mg CBD PM of Full Spec. CBD. Study the effects for a week and, if needed, increase by 5mg CBD per dose.
• If your anxiety is caused by pain or a chronic condition, we recommend combining CBD + THC by using one of our Ratios, available in a ratio of 3:1 ratio of CBD:THC and 1:1 ratio of CBD:THC, so you don't have to buy multiple CBD and THC bottles at once. Our beautiful planet thanks you for it.
• Bonus: Stack your anti-anxiety protocol with psilocybin. Microdose for 4 days on / 3 days off with Brain Stack, Energy Stack, or Vitality Stack to enhance mood, mental performance, and long-term brain health.

Commit for transformational results.

Why Use CBD for Anxiety

A microcosm of psychoneuroimmunology, CBD targets the effects of stress for daily calm, resilience, and focus by regulating the stress response, increasing anandamide and BDNF, activating serotonin receptors, and promoting neurogenesis, among other stabilizing functions. By activating and toning the ECS, committed use of CBD can help the body re-establish homeostasis and promote resilience to stress and disease.

However, note that CBD isolate's anti-anxiety effects are dose-dependent. Taking small to moderate doses is best for anxiety, while taking too much, which ranges from 50mg+ per dose depending on your biology, will not be effective.

Unlike CBD isolate, full-spectrum CBD's effects are greater when you increase your dosage. But that does not mean that you will achieve the best results by taking the max possible dose. Clinical studies show that different dosages are effective for different outcomes. We recommend using our CBD Dosage Calculator—which is based on clinical trials, pre-clinical studies, and user experience reports—to find your ideal introductory dose for reducing anxiety. You can also find the ideal introductory dose for other health goals and concerns, from inflammation and period cramps to sleep, gut health, and endometriosis.

Psilocybin supports neurogenesis and synaptogenesis by reviving serotonin 5-HT2A and increasing BDNF levels. These are neurological processes that are critical to the development, health, and maintenance of brain networks that regulate thought, action, and emotion. As a result, psilocybin helps repair functional connectivity in the PFC impaired by stress, leading to noticeable improvements in energy, mood, and focus. This also helps ensure resilience to future stress.

THC and anxiety: Research-backed benefits and how to use.

Published studies on the impact of cannabis use on anxiety and depression have shown mixed results, and often vary based on the chemotype of the product under investigation and the duration of the dosing regimen.

For example, the two studies in which THC was acutely administered to people with clinical anxiety showed limited evidence of anxiolysis, but chronic nabilone (oral synthetic THC analog) administration over 4 weeks was associated with a significant reduction in anxiety in a placebo-controlled trial.

Effects of THC treatment on depression also appear mixed, though no clinical trials have been conducted to examine a direct effect of THC on depressive symptoms. Epidemiological studies suggest that non-medicinal (“recreational”) use of cannabis, which is typically THC-dominant, may be associated with increased risk of developing a depressive disorder and greater depressive symptom severity, an association not observed for anxiety disorders.

Rather than being causative, however, non-medicinal cannabis use may instead represent an attempt at self-medication during a prodromal period. Indeed, the CB1R agonist activity of THC mimics endogenous cannabinoid signaling, which is notably downregulated in women with clinical depression, and endogenous cannabinoids appear to regulate neural serotonergic signaling. THC itself can produce feelings of euphoria, and clinical trials of a CB1R antagonist were discontinued following reported increases in depression and suicidality (THC is an agonist, the opposite of an antagonist).

How to Use THC for Anxiety

THC mimics anandamide's effects to promote bliss. Like anandamide, low doses relieve anxiety and promote well-being, while high doses can cause anxiety. However, be warned that THC is not meant for daily use. On the contrary—daily, frequent use of THC can exacerbate anxiety and other mood disorders by damaging the PFC (mood, executive function) and hippocampus (memory).

• Take 2.5mg THC and wait 60 minutes for its onset to assess its affects. Take more if needed. Available at My Supply Co. an inspiring Sativa Oil blend and relaxing Indica Oil blend.

Takeaway.

An ever-growing body of research suggests that CBD may help relieve anxiety, the most common mental health disorder. With so many constant sources of stress, people often need a more holistic approach to heal. Even medical doctors have begun suggesting that people combine traditional psychotherapy & pharmaceutical treatments with relaxation techniques like yoga & meditation.

Our products won’t necessarily fix the problem, but they can be reparative to your natural body systems by helping them become more resilient to stress—so you aren’t seized with panic or worry each time. 

If you choose to supplement with cannabis or magic mushrooms, it will work best as part of a comprehensive anxiety treatment plan. A multi-faceted approach is essential to healing and preventing an otherwise good life interrupted by anxiety. Determine the correct nutrition and hormone balance for your biochemistry. Work with trauma-informed practitioners to address any negative experiences that may be stored in your body. And for self-exploration, keep tools like Balanced High or other high-quality psilocybin products on hand.

We encourage you to speak first with a trusted medical professional about your plans, especially if you currently take prescription medications. Similar to grapefruits, CBD could interfere with your body’s ability to metabolize drugs. A doctor or integrative practitioner can also help you rule out any contributing deficiencies and other worrisome health issues.

For your psychedelic journeys, our PAT Directory is currently the most comprehensive list of psychedelic-assisted therapy practitioners in Canada.

We wish you success on your journey and deep healing for your brain and your body.

We wish you success on your journey and deep healing for your brain and your body.

Other reports in this series:

We reviewed the clinical data on some of the most commonly reported medicinal cannabis uses. Learn more about how you can use both CBD and THC to improve your mood, libido, and sleep:

Read: Cannabis and Sex

Read: Cannabis and Sleep

Read: Cannabis and Mood

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