Deep Dive: CBD for Mood Disorders

This Deep Dive serves two roles: First as a homework assignment for the Cannabis Foundation: Part 1 course and second as part of Higher Learning's Deep Dive Subscription.

For Deep Dive subscribers: This Deep Dive serves as a research review that summarizes four peer-reviewed research studies on the topic of CBD for mood disorders. This article is a living document that is updated regularly based on the release of new research on this topic.

For students of Cannabis Foundation: Part 1, welcome to the second homework assignment for Module 3: Cannabinoids 1 > Lesson 5: CBD. In this assignment, students will learn about the latest research about CBD for mood disorders.

Mood disorders affect tens of millions of Americans. In fact, it is estimated that social anxiety alone afflicts more than 15 million in the U.S. according to the Anxiety and Depression Association of America (ADAA).

The National Institute of Mental Health estimates that major depression strikes approximately 17 million Americans at least once during their lifetimes (a whopping seven percent of the population) and disproportionately affects women more than men, according to the ADAA.

During the past few decades, much research has been conducted, including the collection of anecdotal testimonials, regarding the role of cannabidiol (CBD) and other cannabinoids from herbs such as hemp.

Hemp and its constituent molecules have been employed in the treatment of mood disorders such as depression for centuries. In 1621, English clergyman Robert Burton employed hemp in the treatment of depression. In 1887, physician Hobart Amory Hare in the United States used the herb to control restlessness and anxiety for a terminally ill patient. "The patient, whose most painful symptom has been mental trepidation, becomes more happy," wrote Burton.

"In 1621, English clergyman Robert Burton employed hemp in the treatment of depression. In 1887, physician Hobart Amory Hare used the herb to control restlessness and anxiety."

A peer-reviewed study published in November 2022 entitled "Clinical and Cognitive Improvement Following Full-spectrum, High-cannabidiol Treatment for Anxiety: Open-label Data from a Two-stage, Phase 2 Clinical Trial" that was published in the journal Communications Medicine investigated the potential ability of the hemp-derived cannabinoid cannabidiol (CBD) to effectively treat anxiety.

"Approximately 34 percent of adults in the U.S. are diagnosed with an anxiety disorder at some point in their lifetime," reported the study. It explained that a number of "conventional pharmacotherapeutic agents" are available to treat anxiety disorders, with positive outcomes experienced by many patients.

However, the study noted some negative outcomes resulting from many conventional anxiety treatments, including delayed symptom relief (of up to 12 weeks) and "bothersome side effects" that include cognitive and sexual dysfunction. Most significant, many mainstream treatment options "do not guarantee adequate symptom alleviation" and many patients do not go into remission, noted the scientists.

The design of this research study was that of a clinical trial involving 14 subjects (11 females and three males) featuring an average age of 41, all of whom suffered from moderate to severe anxiety. Participants were recruited from "the New England area through online advertisements and social media postings."

"Four weeks of treatment with a full-spectrum, CBD-rich sublingual product is efficacious in patients with moderate-to-severe anxiety."

At the end of the four-week trial, "significant decreases were noted on all primary outcome assessments of anxiety relative to baseline on self-report measures," reported the study. It determined that the data it collected represent "evidence that four weeks of treatment with a full-spectrum, CBD-rich sublingual product is efficacious in patients with moderate-to-severe anxiety."

At the beginning of the study, participants reported average anxiety ratings that were moderate to severe. At the end of the study, average anxiety scores fell to the "minimal or mild-to-none range of severity." Most participants achieved this level of improvement after only one week, while some required three weeks. "This rapid response...is a marked improvement over the typical time course (up to 12 weeks) often required for full treatment response using conventional pharmacotherapy," observed the researchers.

The study's authors concluded their results demonstrate "significant improvement of primary outcome assessments of anxiety, providing preliminary evidence that a full-spectrum, CBD-rich product may be efficacious for treating anxiety with few side effects." They reiterated that most study participants achieved improvement after only one week, versus the typical 10-12 week improvement timeline associated with conventional pharmaceutical drugs.

The scientists also stressed that their study found such improvement "at a much lower dosage than a previous clinical trial using a single extracted CBD isolate product," providing additional insight into the different outcomes associated with both isolate and full-spectrum products.

"Improvements on measures of mood, sleep disturbance, quality of life, and executive functioning following treatment" with full-spectrum, CBD-rich product.

Their data demonstrated "improvements on measures of mood, sleep disturbance, quality of life, and executive functioning following treatment" with full-spectrum, CBD-rich product for four weeks. This study is a precursor to a forthcoming double-blind, placebo-controlled study designed to gather additional data.

Lack of motivation and energy are often symptoms of depression. A 2016 study entitled "Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?" that was published in the Annual Review of Neuroscience explored preclinical and clinical data regarding the therapeutic efficacy of CBD in the treatment of motivational disorders such as "drug addiction, anxiety, and depression."

Concluded the study's authors, "Across studies, findings suggest promising treatment effects and potentially overlapping mechanisms of action for CBD in these disorders."

A 2012 research study entitled "The Endocannabinoid System in the Regulation of Emotions Throughout Lifespan: A Discussion on Therapeutic Perspectives" that was published in the Oxford-based Journal of Psychopharmacology researched the role of the endocannabinoid system (ECS)—the complex network of cellular receptors located throughout the body with which cannabinoids from hemp, such as CBD, interact and bind—in modulating emotional responses and its effect on depression and anxiety.

Reported the researchers, "The [ECS] has emerged as a major neuromodulatory system critically involved in the control of emotional homeostasis and stress responsiveness." The study's authors concluded, "The pharmacological modulation of the [ECS] system has recently arisen as a promising strategy in the management of anxiety and mood disorders."

"The [ECS] system has recently arisen as a promising strategy in the management of anxiety and mood disorders."

Sometimes severe mood disorders manifest as psychotic disorders. A research study conducted in 2012 entitled "Multiple Mechanisms Involved in the Large-spectrum Therapeutic Potential of Cannabidiol in Psychiatric Disorders" that was published in the journal Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences investigated the ability of CBD to treat both non-psychiatric and psychiatric disorders, including anxiety, depression, and psychosis.

Reported the researchers, "It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis." The study pointed out how CBD exhibits a "bell-shaped dose-response curve," observing how this molecule delivers different efficacy, depending on dose administered. The study's authors concluded, "Activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD."

A 2011 research study entitled "Endocannabinoid System Dysfunction in Mood and Related Disorders" that was published in the journal Acta Psychiatrica Scandinavica "examined the therapeutic potential of cannabinoids in psychiatric disorders."

The study's authors concluded the study by hypothesizing that dysfunction in the ECS leads to mood disorders. "Anandamide...and cannabidiol (CBD) variously combine antidepressant, antipsychotic, anxiolytic, analgesic, [and] anticonvulsant actions, suggesting a therapeutic potential in mood and related disorders," summarized the scientists.

"Anandamide and CBD combine antidepressant, antipsychotic, analgesic, [and] anticonvulsant actions, suggesting a therapeutic potential in mood disorders."

A 2009 research study entitled "The Endocannabinoid System and the Treatment of Mood and Anxiety Disorders" that was published in the journal CNS and Neurological Disorders Drug Targets also investigated the role of the ECS in the regulation of mood states and responses and prevention of mood disorders.

Reported the study, "A growing body of evidence unequivocally demonstrates that deficits in endocannabinoid signalling may result in depressive and anxiogenic behavioral responses, while pharmacological augmentation of endocannabinoid signalling can produce both antidepressive and anxiolytic behavioral responses."

Concluded the study's authors, "Collectively, both clinical and preclinical data argue that cannabinoid receptor signalling may be a realistic target in the development of a novel class of agent for the pharmacotherapy of mood and anxiety disorders."