How Does CBD Oil Help Treat Anxiety and Depression?

CBD Oil For Anxiety: How Cannabidiol Is An Effective Treatment

Cannabidiol (CBD) is just one of over 85 scientifically-identified cannabinoids (or chemical compounds) derived from the flowering plant cannabis.  Each of the cannabinoids within cannabis elicit unique neurophysiological effects.  Most people are well-aware of THC (tetrahydrocannabinol), the predominant cannabinoid within cannabis that is ingested by upwards of 230 million people per year as a psychoactive euphoriant.

Although not as abundant as THC cannabinoid content, cannabidiol accounts for approximately 40% of all cannabinoids within cannabis extract.  Unlike THC, cannabidiol is non-psychoactive and isn’t typically ingested with the intent to attain any sort of psychological euphoria.  That said, the medicinal properties associated with cannabidiol (often administered in the format of “CBD oil”) are thought to far exceed those of THC.

Preliminary evidence suggests that CBD may act as an: anticonvulsant, antipsychotic, anti-inflammatory, and neuroprotective agent.  Furthermore, some evidence suggests that CBD oil may be an effective intervention for the ongoing management of anxiety disorders.  Those with anxiety disorders who fail to derive benefit from traditional pharmacology and/or who are unable to tolerate standard pharmacological treatments may want to consider administration of CBD oil on an ongoing or “as-needed” basis.

How CBD Oil Treats Anxiety (Mechanisms of Action)

Cannabidiol offers a novel pharmacodynamic profile as an anxiolytic agent.  It is believed that administration of CBD (cannabidiol) modulates neurotransmission in a multitude of ways.  Literature shows that cannabidiol alters 5-HT1A, GPR55, CB1/CB2, and mu/delta opioid receptor sites – while simultaneously enhances hippocampal neurogenesis.  The combination of these neurophysiological effects likely contribute to its efficacy as a novel anxiolytic.

5-HT1A partial agonist: Modulation of neurotransmission at the 5-HT1A receptor is understood to provide anxiolytic, antidepressant, and neuroprotective effects.  Research has demonstrated the effect of cannabidiol as a 5-HT1A receptor partial agonist, meaning it binds to the receptor site but only stimulates the receptor partially (relative to a full agonist).  Studies with cloned human cell cultures note that cannabidiol displaces 5-HT1A agonists from 5-HT1A receptor sites in a dose-dependent manner.

In other words, the greater the amount of CBD oil administered following administration of a 5-HT1A agonist, the more significant the displacement.  Researchers mention that this mechanism differs from THC which is incapable of displacing 5-HT1A agonists from the 5-HT1A receptor.  Partial agonism of the 5-HT1A receptor site is associated with an array of therapeutic effects including: increased serotonin (or serotonergic effects), increased dopamine (in medial PFC, striatum, hippocampus), releasing acetylcholine, and hippocampal neurogenesis.

A study published in 2008 indicated that CBD injections into the dorsolateral periaqueductal gray area of rats reduced anxiety via 5-HT1A receptor interaction.  Researchers noted that the 5-HT1A receptors were more involved than cannabinoid receptors (e.g. CB1) in reducing anxiety.  The study concluded that cannabidiol interacts directly with 5-HT1A receptors to yield an anxiolytic response.

Although the 5-HT1A partial agonism exerted by CBD may not be an outright cure for anxiety, it is likely to help many individuals.  Studies conducted on humans with panic disorder note impairments in 5-HT1A receptor function and poor 5-HT1A binding.  The bottom line is that individuals with anxiety could have dysfunctional 5-HT1A activation and may resort to commercialized 5-HT1A partial agonists (e.g. Buspar) as treatments.

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Hippocampal neurogenesis: One hypothesized mechanism by which pharmaceutical anxiolytics may decrease anxiety is via hippocampal neurogenesis – or growth of new neurons within the hippocampus.  It appears as though cannabidiol administration induces hippocampal neurogenesis in animal models, and for this reason, similar outcomes may occur in humans.  A rat study involving the chronic administration of 5-HT1A partial agonist (tandospirone) increases the biomarker of doublecortin – indicating emergence of new neurons in the hippocampus.

Some researchers believe that hippocampal neurogenesis may play a critical role in attenuating symptoms of severe anxiety and/or depression.  Although not all 5-HT1A partial agonists may induce hippocampal neurogenesis, there’s evidence to suggest that cannabidiol does.  A study published in 2013 assessed the anxiolytic effects of CBD in mice exposed to chronic stress.

Results from the study indicated that CBD administration increased neuronal proliferation and neurogenesis in the hippocampal region.  It is also thought that CBD’s modest affinity for cannabinoid receptors CB1 and CB2 may contribute to hippocampal neurogenesis.  Stimulation of the CB1/CB2 receptor sites upregulates endocannabinoid signaling and leads to neuronal growth.

Regardless of how CBD oil induces hippocampal neurogenesis, the growth of new brain cells may be enough to decrease anxiety.  A report published in 2015 documented that increasing adult neurogenesis (regardless of the modality) is sufficient enough to decrease anxiety.  Therefore, it could be that CBD is an effective anxiolytic predominantly through mechanisms implicated in neurogenesis.

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CB1 + CB2 receptor (inverse agonist): Most evidence suggests that CBD oil has a low affinity for CB1 and CB2 receptor sites as an inverse agonist.  In other words, it binds to the CB1 and CB2 receptors but exerts the pharmacologically opposite effect to an agonist.  This differs from a CB1/CB2 antagonist which solely binds to these receptors and blocks stimulation from endocannabinoids.

It also is distinct from THC which acts as a CB1/CB2 partial agonist, thereby stimulating the receptor sites.  If it acted the same as THC at the CB1/CB2 receptor sites, its therapeutic potential may be reduced.  Moreover, since cannabidiol acts as an inverse agonist at the CB1/CB2 receptor sites, it doesn’t induce psychological euphoria and/or pleasure associated with downstream dopaminergic enhancement in the mesolimbic pathway (resulting from CB1/CB2 agonism).

Research has shown that administration of cannabidiol actually inhibits agonist effects at the CB1/CB2 receptor sites.  Although the effects of CB1 inverse agonism aren’t fully elucidated, many speculate that CB2 inverse agonism may contribute to cannabidiol’s anti-inflammatory effects.  Due to the fact that neuroinflammation is associated with anxiety disorders, we could hypothesize that a decrease in inflammation may yield anxiolytic responses in a subset of CBD users.

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Opioid receptor modulator: Another possible mechanism by which CBD may alleviate symptoms of anxiety is through allosteric modulation of mu-opioid receptor (MOR) and delta-opioid receptor (DOR) sites.  Though it is known that allosteric modulation of the MOR and DOR is capable of reducing anxiety, it isn’t fully understood how.  Some speculate that MOR and DOR sites affect GABAergic and dopaminergic neurotransmission.

Certain individuals may be more prone to anxiety than others as a result of mu-opioid receptor expression and/or activation.  Research indicates that mu-opioid receptors participate in the modulation of anxiety based on the specific region of the brain in which they are stimulated.  What’s more, a report published in 2015 indicated that the neural circuitry associated with the DOR (delta opioid receptor) can induce OR inhibit anxiety.

Selective delta receptor agonists have been shown (in animal studies) to reduce anxiety-like behavior and block anxiogenic effects of stressors.  Specifically, modulation of the DOR in the central amygdala may predict severity of an individual’s anxiety.  There’s reason to believe that allosteric MOR and DOR modulation provided by CBD could reduce anxiety in a subset of individuals – especially when combined with aforestated 5-HT1A and CB1/CB2 effects.

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Benefits of CBD Oil for Anxiety (Possibilities)

There are an array of speculative advantages associated with using CBD [oil] as a treatment for anxiety.  The agent appears effective for reducing many different types of anxiety and stress when administered on an acute, single-dose basis.  In addition to reducing anxiety, preliminary research suggests that CBD may enhance mood, reduce inflammation, improve sleep quality, and preserve healthy brain function.  Compared to traditional anxiolytics, CBD isn’t associated with any significant side effects nor substantial contraindications, thereby making it an appealing investigational treatment.

  • Acute “as needed” administration: Though studies haven’t examined the effects of chronic CBD administration in humans, most have documented the effects of acute administration. Acute administration is associated with a significant anxiolytic effect (as compared to a placebo).  Unlike medications such as SSRIs, CBD provides fast-acting (nearly instantaneous) anxiety relief and doesn’t require daily administration for weeks/months to attenuate symptoms.
  • Adjunctive option: Many speculate that CBD could bolster anxiolytic effects of various first-line pharmaceutical agents. Since likelihood of CBD interacting with other agents is minimal, it may serve as a novel adjunctive option for those with severe anxiety.  In other words, someone who fails to derive sufficient benefit from a first-line option may find that addition of CBD (on an “as needed” basis) fully attenuates anxious symptoms.
  • Antipsychotic: Those suffering from anxiety as a result of a condition like schizophrenia may benefit from utilization of CBD oil. While the phytocannabinoid THC may exacerbate positive symptoms of schizophrenia (due to its psychotomimetic properties), CBD is understood to have antipsychotic properties.  It isn’t fully elucidated as to how CBD reduces psychotic symptoms, but some believe its indirect modulation of dopaminergic transmission plays a role.
  • Anti-inflammatory: Many individuals with neuropsychiatric disorders have severe inflammation, particularly neuroinflammation. Neuroinflammation is associated with many causative underpinnings including: air pollution, brain injuries, viruses, and even standard aging.  This increase in inflammation can lead to glial cell and cytokine abnormalities, each of which could contribute to anxiety disorders.  CBD has been shown to reduce neuroinflammation, which in turn may directly improve anxiety, as well as cognitive function and mood.
  • Doesn’t affect cognition: A major drawback associated with anxiolytics is that many affect cognitive function. Sure it helps to take a pill and have less anxiety, but what if it compromises your cognitive abilities (e.g. critical thinking, problem solving, planning, etc.)?  Agents such as benzodiazepines are linked to memory problems and generally impair functionality despite reducing anxiety.  Research has highlighted CBD’s ability to reduce anxiety without impairing cognitive function.
  • Few interactions: Most evidence indicates that CBD is unlikely to interact with pharmaceutical drugs. However, when taken at a reasonable dosage, CBD is understood to inhibit CYP450 isoenzymes in the liver.  This may alter the pharmacokinetics of other drugs such as Warfarin which are metabolized by similar enzymes.  That said, the pharmacokinetic and pharmacodynamic contraindications associated with CBD appear minimal.
  • Efficacy: While it is impossible to confirm that CBD will effectively reduce anxiety in all users, most evidence indicates that it is likely to provide benefit when ingested at a sufficient dosage (600 mg – orally) on an acute basis. In other words, most people seeking immediate relief from anxiety will likely feel significantly less anxious after using CBD than if they had ingested a placebo.  Placebo-controlled studies have already documented the efficacy of acute CBD administration for anxiety.
  • General health improvement: Intermittent usage of CBD oil on an “as-needed” basis is understood to provide numerous general health benefits. Research suggests that CBD oil may offer anticancer, analgesic, and antiemetic properties.  There’s evidence noting that it may boost immune function, slow the growth of bacteria, reduce muscle spasms, and modulate blood sugar levels.  Literature indicates that cannabidiol may be conducive to general health.
  • Mood enhancement: While CBD isn’t known for provoking a euphoric high, there’s some evidence to suggest that it may enhance mood. Research in animal models notes that CBD yields a combination of anxiolytic and antidepressant effects.  That said, this research cannot be generalize to humans.  If you’re severely depressed, don’t expect CBD to treat your depression.  However, the fact that the drug targets the 5-HT1A receptor and CB1/CB2 receptors suggests that it could improve mood in certain individuals.
  • Multiple types of anxiety: A limitation associated with CBD research is that it hasn’t been tested extensively among patients with a specific diagnostic subtype of anxiety (e.g. generalized anxiety). That said, studies note that CBD is likely efficacious in treating symptoms of many different types of anxiety including: social phobia, PTSD, panic disorder, OCD, and generalized anxiety disorder.  Therefore, individuals may derive anxiolytic benefit from CBD – regardless of their specific type of anxiety.
  • Neuroprotective properties: There’s some evidence to suggest that CBD may act as a neuroprotective agent. In other words, it may prevent brain cell death and/or damage resulting from hypoxic-ischemic encephalopathy.  Those with hypoxic-ischemic encephalopathy tend to incur damage as a result of inadequate brain oxygenation.  Studies in pigs indicate that CBD protects the brain from hypoxic-ischemic damage.
  • Nervous system reset: When we experience a freeze-fight-flight response, activity in the autonomic nervous system (ANS) is altered. Anxiety and fear-inducing situations skew activation of the ANS so that the sympathetic branch is more active than the parasympathetic branch.  Administration of CBD has been shown to prevent overactivity in the sympathetic branch via 5-HT1A partial agonism.  This means that administration of CBD prior to or after a highly stressful event may prevent a full-blown nervous breakdown.
  • Public speaking: Those who have difficulty with public speaking due to anxiety will likely benefit from CBD. Cannabidiol administration approximately 1.5 hours prior to a simulated public speaking engagement significantly reduced anxiety compared to a placebo.  Those with social anxiety were found to derive the most benefit from its administration.  However, it is likely that cannabidiol would benefit even those without social phobia if anxiety is experienced during a public speaking task.
  • Safety: As of current, there’s zero evidence to suggest that cannabidiol is unsafe and/or intolerable. While certain individuals may experience adverse effects from its administration, these adverse effects are not common and may be a result of: poor sourcing, formatting, addition of other unwanted chemicals or cannabinoids, or contamination.  Most research indicates CBD is just as safe and well-tolerated as a placebo.
  • Side effects: There appear to be no significant unwanted side effects associated with CBD compared to a placebo. Many anxiolytics carry severe side effects such as: brain fog, drowsiness, inability to retrieve memories, impaired learning, sexual dysfunction, etc.  Individuals taking CBD are unlikely to experience severe unwanted side effects.
  • Sleep enhancement: Many individuals with anxiety disorders struggle to get proper sleep. Anxiety often causes insomnia and insomnia often causes anxiety – leading to a vicious cycle of back-and-forth reinforcement that is seemingly inescapable.  Administration of CBD has been shown to restore normal REM sleep and is thought to improve sleep quality of certain individuals.

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