Endoctrination Series vol. 3: Cannabis and Mood

Welcome to the third report in our Endoctrenation 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 Mood report dissects the available literature on the ECS and its relationship with everyday mood regulation, ending with tips for toning the ECS to improve mood with cannabis technologies. We also include tips on using psilocybin to improve mood.

Highlights.

• Studies have discovered that chronic stress may suppress the brain’s production of endocannabinoids, which can lead to depression-like behavior.
• The ECS regulates brain homeostasis throughout development. Consequently, loss of ECS control might affect mood disorders and impact neurodegenerative and neurodevelopmental disorders.
• Since CBD interacts with a wide variety of molecular targets in the brain, its therapeutic potential is being investigated in a number of neuropsychiatric diseases, including anxiety and mood disorders.
• CBD improves sleep quality, promotes neurogenesis, increases endocannabinoid signalling, and activates serotonin receptors to establish balance and confer its mood-regulating benefits.
• THC binds with CB1 receptors and activates the pleasure center to calm and brighten mood in low doses.
• Psilocybin activates serotonin receptors and dampens the Default Mode Network to confer its anxiolytic and anti-depressant benefits while while promoting neurogenesis and synaptogenesis to repair functional brain connectivity that can cause or exacerbate anxiety, depression, irritability, OCD, and more.

Introduction.

Cannabinoids, namely CBD and THC, have received much attention in recent years because of their ability to ease pain and induce relaxation. They have become widely popular as a treatment for anxiety, and recent research suggests that they may be options for treating depression, along with the active compound in magic mushrooms, psilocybin.

Cannabidiol (CBD) in particular, the most abundant non-intoxicating component of cannabis, is touted for its anxiolytic and antidepressant properties. Since CBD interacts with a wide variety of molecular targets in the brain, its therapeutic potential is being investigated in a number of neuropsychiatric diseases, including anxiety and mood disorders.

Consequently, and given its safety profile, CBD is considered a promising new agent in the treatment of anxiety and mood disorders. However, the exact molecular mechanism of action of CBD still remains unknown.

In the first part of this report, we consider the ECS’s role in mood regulation, including a review of pre-clinical and clinical studies, to identify potential therapeutic targets. Next, we discuss the CBD’s, THC’s, and Psilocybin’s benefits for mood, along with tips on how to include them in your personal care regimen.

If you’re interested in using cannabinoids to support and balance your mood, read on. We also include a section on psilocybin due to its proven ability to improve mood, brain function, and long-term brain health.

The Endocannabinoid System’s role in mood and mood disorders.

Responsible for homeostasis, the ECS (Endocannabinoid System) is a widely distributed network of receptors in the brain and body that modulates many physiological and cognitive functions. It is involved in innumerable mood disorders and its activity may be modified by cannabinoids, from phytocannabinoids like CBD and THC to endocannabinoids (eCB) like Anandamide (AEA) and 2-AG.

What many are unaware of is that the ECS is unlike any other system in your body, supreme to and in control of all major systems and organs. From childhood to death, it regulates brain homeostasis throughout development, from neurogenesis and synaptogenesis, brain plasticity, and circuit repair to learning, memory, fear, and protection. It is also a major player in the regulation of food intake, energy storage, nutritional status, and adipose tissue (body fat) mass, which implicates it as a treatment for obesity and other weight-related conditions.

Consequently, loss of ECS control might affect mood disorders (anxiety, hyperactivity, psychosis, and depression), lead to drug abuse, and impact neurodegenerative (Alzheimer's, Parkinson, Huntington, Multiple, and Amyotrophic Lateral Sclerosis) and neurodevelopmental (autism spectrum) disorders.

It’s important to focus on maintaining a healthy ECS to combat this. To live a better life is to vigilantly maintain your ECS, which can be done through:

• healthy diet selection based on a balanced omega-3 and -6 polyunsaturated fatty acids, which are essential endocannabinoid (eCB) building blocks
• weekly practice of physical and/or mind-body mindfulness and meditative activities, all of which regulate eCBs levels
• surrounding yourself with a constructive social network
• taking CBD, a diet supplement with anti-inflammatory, anxiolytic, antidepressant, and antioxidant benefits and a major player in toning the ECS

As therapeutically concerned, the ECS is essential for maintaining homeostasis and cannabinoids are promising tools to regulate and balance countless targets.

CBD and mood: Evidence from pre-clinical and clinical studies.

Due to the availability of data and CBD’s safety profile—it is safe for daily use up to 1,500mg with no recorded adverse side effects—this section of the report will focus on CBD.

CBD’s multi-depth calming effects are perhaps its most popular and the reason its use is so widespread. Various independent studies support the view that CBD could represent a new approach to treating anxiety and mood disorders. In this regard, CBD has been tested in several animal models of anxiety and depression, showing promising results in decreasing anxiety and improving depressive-like behaviors. However, the molecular mechanisms underlying these therapeutic-like effects are just beginning to be understood.

In this section of the report, we provide a summary of pre-clinical studies that support the use CBD as an anxiolytic- and antidepressant-like compound. We also describe neuropharmacological evidence that links the molecular pharmacology of CBD to its behavioral effects. Finally, we elaborate on CBD’s putative epigenetic mechanism of action that mediate its therapeutic outcomes. Epigenetics is the study of how your behaviours and environment can change the way your genes work without altering your DNA sequence.

CBD and Mood Disorders: Pre-clinical Rodent Models

The anxiolytic effects of CBD have been highlighted in several rodent models of anxiety (Table 1). The EPM is a widely used experimental method to test anxiety-related behaviors in rodents. In the EPM, CBD has been found to elicit, in both rats and mice, anxiolytic effects at doses of 2.5, 5, 10 mg/kg, and 0.50, 1, 2.5, 5, 10, 50 mg/kg, respectively. The lowest effective acute dose of 1 mg/kg of CBD also exhibited anxiolytic properties in the social interaction (SI) test, in which rats are placed in pairs to measure their sociability, e.g., sniffing and grooming.

Table 1

CBD effects in animal models of anxiety.

Animal Model	Animal	Dose/Route of Administration	Effect	Mechanism	Reference
EPM	Rats	2.5, 5, 10 mg/kg, acute, i.p.	Anxiolytic	Not investigated	PubMed
EPM	Mice	2.5, 5, 10, 50 mg/kg, acute, i.p.	Anxiolytic	Not investigated	PubMed
SI	Mice	1 mg/kg, acute, i.p.	Anxiolytic	Not investigated	PubMed
VCT	Rats	10 mg/kg, acute, i.p.	Anxiolytic	Not investigated	PubMed
Restrain stress	Rats	10 mg/kg, acute, i.p.	Anxiolytic	5-HT1A receptors	PubMed
Light- dark test	Rats	5 mg/kg, acute, i.p.	Anxiolytic	Not investigated	PubMed
EPM	Rats	30 nmol/µL; intra-dPAG	Anxiolytic	5-HT1A receptors	PubMed
ETM	Rats	30 and 60 nmol/µL; intra-dPAG	Anxiolytic	5-HT1A receptors	PubMed
EPM/VCT	Rats	1 µg/µL; intra-CeA	Anxiolytic	Not investigated	PubMed
EPM/VCT	Rats	30 nmol/µL; intra-BNST	Anxiolytic	5-HT1A receptors	PubMed
CFC	Rats	30 and 60 nmol/µL; intra-BNST	Anxiolytic	5-HT1A receptors	PubMed
Restrain stress	Rats	30 nmol/µL; intracisternal	Anxiolytic	Not investigated	PubMed
CFC	Rats	30 nmol/µL; intra-PL	Anxiolytic	5-HT1A receptors	PubMed
EPM	Rats	30 nmol/µL; intra-PL	Anxiogenic	5-HT1A receptors	PubMed
EPM	Rats	60 nmol/µL; intra-dPAG + Capsazepine	Anxiolytic	TRPV1 receptors	PubMed
ETM	Rats	5 mg/kg/daily/21 days; i.p.	Anxiolytic	5-HT1A receptors	PubMed
Chronic Stress	Mice	30 mg/kg; /daily/14days; i.p.	Anxiolytic	Hippocampal Neurogenesis; CB1 receptors	PubMed
CER	Rats	10 mg/kg/daily/14 days; i.p.	Anxiogenic	BDNF ↓ Trk B ↓	PubMed

CBD and Mood: Human Studies

In a review of 8 clinical studies on CBD for stress, researchers showed that 150mg - 300mg of CBD taken twice daily (300 - 600mg per day) significantly reduced stress and its manifestations (anxiety, depression, burnout, fear).

In humans, CBD’s therapeutic profile is complex since it acts on various molecular targets, including cannabinoid, TRPV1, and 5-HT1A (serotonin) receptors. Moreover, CBD facilitates endocannabinoid signaling by increasing AEA and 2-AG levels. All these molecular targets have been studied for their involvement in the anxiolytic effects of CBD. For instance, the activation of the 5-HT1A serotonin receptors underlies CBD’s acute anxiolytic effects. The 5-HT1A receptors are widely distributed in brain areas related to stress and anxiety, such as the prefrontal cortex, hippocampus, and amygdala.

On the other hand, high doses of CBD activate TRPV1 receptors, which may be responsible for either no effects or anxiogenic effects, meaning it can actually cause anxiety. That’s because TRPV1 receptors are expressed in various brain regions related to anxiety. Note that this only applies to CBD isolate, which only works within a specific dosage range and has dose-dependent effects. Taking higher doses of full-spectrum CBD typically lead to increased effects.

Read: Full-spectrum CBD vs. CBD Isolate: What You Need to Know

CBD and Mood: The Role of Epigenetics

Although the exact mechanisms responsible for CBD’s anxiolytic effects remain poorly understood, it has been hypothesized that epigenetic modifications may mediate CBD’s effects. Epigenetics refers to mechanisms that can alter gene expression without altering the underlying DNA sequence.

Epigenetic changes have been found to contribute to psychiatric disorders, including anxiety and mood disorders. Moreover, commonly used pharmacological agents for depression, bipolar disorder, and anxiety have been shown to induce epigenetic changes that are associated with remission. Epigenetic mechanisms also represent a way by which the environment can affect gene activity independently of the underlying DNA sequence. This is illustrated by early-life stress, a common risk factor for anxiety and mood disorders, which has been linked to aberrant epigenetic changes in key genes involved in regulating the hypothalamic–pituitary–adrenal axis response.

CBD and mood: Benefits and how to use it.

Benefits of CBD for Mood

Experts believe that CBD’s potential benefits for mood, anxiety, and depression are related to its positive effect on serotonin receptors in the brain.

Low serotonin levels are likely connected to depression, but CBD doesn’t necessarily boost serotonin levels. Instead, affects how your brain’s chemical receptors respond to the serotonin that’s already in your system. It may be that your body is producing enough serotonin, but isn’t necessarily effective at processing it. But by inhibiting serotonin’s breakdown, CBD allows serotonin levels to accumulate in the brain.

A 2017 review of CBD’s potential benefits for panic disorder found some positive results. According to the authors, panic disorder affects approximately 5 percent of the worldwide population and causes unexpected and recurring panic attacks. A more recent 2018 review of existing studies concluded that CBD has anti-stress effects, which may reduce anxiety and depression related to stress.

Alternatively, studies also show that inadequate sleep or experiencing sleep disturbances significantly effects mood. Sometimes a simple nap can help you bounce back. But what if you experience sleeplessness, or wake up a lot at night?

Research has shown that CBD improves sleep quality by helping you fall asleep faster and keeping you asleep longer. It does so not only by relieving anxiety and regulating cortisol, which interfere with sleep, but by also enhancing the effects of melatonin, the hormone that controls the sleep-wake cycle.

As mentioned, this is an area that’s still being actively studied, and new research and reviews are published every year. As researchers begin to better understand CBD and its potential benefits or concerns, information about how to most effectively use the product will continue to change.

How does CBD compare to anxiolytic and antidepressant medications?

When it comes to treating anxiety and depression, CBD does appear to have some benefits over medications.

Most medications, particularly antidepressants, take weeks to start working. However, a 2019 animal study found that CBD has a fast and sustained antidepressant-like effect.

There are also two clinical trials on humans showing that CBD was as good as benzodiazepines and anti-depressants at reducing the effects of stress and its manifestations (anxiety, depression, burnout, fear).

CBD may also result in fewer side effects than antidepressant medication. Insomnia, sexual dysfunction, mood swings, and agitation are common side effects of antidepressants. CBD has not shown similar issues.

How to Use CBD for Mood

Our CBD Dosage Calculator was designed to help you find an optimal starting CBD dosage for a range of mood concerns, from stress, anxiety, and burnout to depression. You can also use it to find the optimal CBD dosage for other health goals and concerns, such as gut health, pain, and sleep.

But if you'd like a quick reference guide to using our products for sleep:

1. Take 100mg of Full Spectrum CBD oil two times daily, once with breakfast and once with dinner. We recommend taking your doses with meals that are rich in healthy fats, which can increase the bioavailability (absorption) of CBD by four to five times. If you are sensitive to THC or unable to consume it, CBD isolate oil is a strong alternative.
2. Assess your mood after 1 week—if you aren’t noticeably more calm, focused, and energized, increase by 5mg per dose.
3. Assess your mood after 1 week, repeating steps 2 and 3 until you find your perfect dose.
4. If your mood prevents you from sleeping: Layer with CBD Sleep Solution or CBN Sleep Solution, our herbal nightcaps for calm, relaxation, and deep, tranquil sleep.

Read: What to Know About CBD Isolate

THC and mood: Benefits, risks, and how to use it.

Benefits of THC for Mood

THC—it’s why most people try cannabis. The main intoxicating ingredient, THC stimulates the part of your brain that responds to pleasure, like food and sex. That unleashes a chemical called dopamine, which gives you a euphoric, relaxed feeling.

The evaluation of cannabis for mood-related disorders like depression is still in its early stages. Right now, researchers share that benefits may include the restoration of “normal” endocannabinoid function and mood stabilization.

Scientists at the University at Buffalo have begun looking into medicinal cannabis as a possible treatment for depression caused by chronic stress. The school’s Research Institute on Addictions (RIA) has been focusing specifically on brain chemicals called endocannabinoids (eCB).

These are naturally produced chemical compounds. They play a role in motor control, cognition, emotions, and behavior. They also have a chemical makeup like that of cannabis.

Despite performing their studies on animals and not humans, they have discovered that chronic stress may suppress the brain’s production of endocannabinoids. They found that this can lead to depression-like behavior.

So, introducing cannabis into the system may help restore normal levels and function, which in turn can ease symptoms of depression.

As it stands, more studies are needed to assess the true benefits and disadvantages of cannabis as a potential therapy for people with depression. However, what we do know is, thanks to THC’s potent pain-killing and anti-inflammatory mechanisms, those with chronic and inflammatory conditions can live better, happier, more meaningful lives. It also helps those with stubborn sleep issues fall asleep faster and stay asleep.

So, if you’re not sure that THC is for you, but suffer from poor sleep or pain/inflammation, THC may be the perfect add-on to your personal care regimen.

How to Use THC for Mood

1. Starting with 2.5mg per dose, take Uplift THC Oil in the AM or early PM and Unwind THC Oil in the PM. Drop the oil under your tongue for at least 60 seconds before swallowing.
2. Wait 60 minutes to assess effects and take more if needed. Note that THC is anxiolytic (calming) in low doses, but can be anxiogenic (causes anxiety) for some in high doses.
3. For optimal results: Layer Full Spectrum CBD oil during breakfast and dinner for multi-depth calm, focus, and resilience.

Psilocybin and mood: Benefits and how to use it.

Benefits of Psilocybin for Mood

In a small study of adults with major depression, Johns Hopkins Medicine researchers report that two doses of the psychedelic substance psilocybin, given with supportive psychotherapy, produced rapid and large reductions in depressive symptoms, with most participants showing improvement and half of study participants achieving remission through the four-week follow-up.

Psilocybin works by reviving serotonin receptors; more specifically, 5-HT2A receptors, dysfunctions of which are associated with mental health issues. Psilocybin mostly acts on 5-HT2A receptors in the prefrontal cortex (PFC), the part of the brain that regulates mood, cognition, and perception and is highly susceptible to stress. Prolonged exposure to stress leads to loss of functional connectivity in the PFC, leading to anxious and depressive symptoms among other mood disorders.

People often take full doses of mushrooms specifically for the “trip” they produce, which might include hallucinations and other changes in perception, including:

• enhanced senses
• expanded emotional or cognitive insight
• meaningful or spiritually significant experiences

While both microdosing and macrodosing can produce these feelings, there are massive differences between the two. For one, microdosing is subperceptual (no visuals or hallucinations), while macrodosing is not. For another, each method produces different outcomes.

For example, there's ample anecdotal evidence and a small amount of research suggesting that microdosing may be the best way to use magic mushrooms for depression and enhancing brain function, while macrodosing occasionally might be best for anxiety and traumatic brain injuries.

That’s because microdosing psilocybin lightly activates serotonin receptors and optimizes brain chemistry to sharpen focus, brighten mood, and bring calming energy. And, by promoting neurogenesis and synaptogenesis in the PFC, microdosing psilocybin can restore functional connectivity, which reverses the effects of stress on the brain and treats depressive symptoms by re-establishing functional connectivity in the PFC.

On the other hand, macrodosing can catalyze profound, structural brain changes (called neuroplasticity) within hours, changing the way you perceive yourself, your environment, and everything in between. It also significantly decreases Default Mode Network (DMN) activity while increasing connectivity in the rest of the brain. The DMN refers to an interconnected group of brain regions that are associated with introspective functions and internally directed thought, such as self-reflection and self-criticism. It has been found to be particularly overactive in certain mental health conditions, such as depression, anxiety, and OCD, so DMN overactivity is associated with experiences of “hypercriticality,” “rigid thought patterns,” and “automatic negative thought loops” about oneself.

So, if you’re anxious, you may want to experiment with macrodosing. If you’re depressive, then microdosing might be best for you.

In 2016, Johns Hopkins Medicine researchers first reported that treatment with psilocybin under psychologically supported conditions significantly relieved existential anxiety and depression in people with a life-threatening cancer diagnosis.

Today, findings from the new study, published Nov. 4, 2020 in JAMA Psychiatry, suggest that psilocybin may be effective in the much wider population of patients who suffer from major depression than previously appreciated.

“The magnitude of the effect we saw was about four times larger than what clinical trials have shown for traditional antidepressants on the market,” says Alan Davis, Ph.D., adjunct assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “Because most other depression treatments take weeks or months to work and may have undesirable effects, this could be a game changer if these findings hold up in future ‘gold-standard’ placebo-controlled clinical trials.” The published findings cover only a four-week follow-up in 24 participants, all of whom underwent two five-hour psilocybin sessions under the direction of the researchers.

How to Use Psilocybin for Mood

1. Take 1–4 capsules of Brain Stack, Vitality Stack, or Energy Stack in the AM, 4 days on / 3 days off. Our Stacks can be taken together for synergistic effects.
2. After 4 weeks, take a 1–2 week break.
3. Repeat steps 1 and 2.
4. Macrodose (2g+) with Balanced High (aka Scooby Snacks) or Extended Release for immediate, long-lasting, and durable effects.

Read: Microdosing Cycles, Protocols, & Schedules: What You Need to Know

Takeaway.

An ever-growing body of research suggests that cannabinoids and psilocybin may help relieve mood-related disorders, particularly anxiety, depression, OCD, and trauma. 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 mood treatment plan. A multi-faceted approach is essential to healing and preventing an otherwise good life interrupted by a mood disorder. 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.

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 libido, get better sleep, and eliminate anxiety:

Read: Cannabis and Sex

Read: Cannabis and Sleep

Read: Cannabis and Anxiety

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