Research Studies Relating to CANNABIDIOL USE FOR ANXIETY & DEPRESSION

Research Summaries by Dr. Karen Hufnagl


ANXIETY

Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079847/ 

In this double blind placebo controlled study, researchers set out to determine if CBD could provide relief from symptoms of generalized Social Anxiety Disorder – one of the most common anxiety conditions.  As noted in previous research, this disorder is poorly controlled by the currently available drugs, with only about 30% of patients achieving true recovery or remission without residual symptomatology.

Participants in this study were divided into 3 groups: 

  • Anxiety patients receiving CBD
  • Anxiety patients receiving placebo
  • Healthy controls

 Each group was subjected to a Simulation Public Speaking Test – a documented experimental model for the induction of anxiety.   The results showed that the placebo group experienced a “significantly higher anxiety level and greater cognitive impairment, discomfort, and alert compared with the control group during the test.”

In contrast, “pretreatment of SAD patients with CBD significantly reduced anxiety, cognitive impairment, and discomfort in their speech performance” such that they achieved similar results to the healthy controls.

The researchers also emphasized, “another important observation of this study was that the increase of negative self-evaluation during public speaking was almost abolished by CBD.”

As discussed in this paper, other pharmaceuticals commonly used are hampered by a number of undesirable effects, including a long latency period to produce symptomatic relief, motor impairment, and dependence/withdrawal issues, among others.  “Conversely, CBD has important advantages in comparison with the currently available pharmacological agents for the treatment of SAD, such as an early onset of action and lack of important side effects both with acute and chronic administration to healthy subjects…and repeated treatment with CBD does not develop tolerance or dependence.”


Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425583/

Sixty healthy men and women aged 18-35 years were enrolled in this double blind placebo controlled study.  Previous animal research has demonstrated an inverted U-shaped dose response curve for CBD isolate – i.e., pure CBD showed a lack of effect at certain low end doses as well as certain high end doses, with a therapeutic effect in the mid-range doses. 

Researchers designed this study to evaluate whether different doses of CBD would have this same U-shaped therapeutic effect in humans.  Participants were subjected to a “Test of Public Speaking in a Real Situation” where they were required to speak in front of a group  - a known method of inducing anxiety.  Prior to the speech, participants received one of five different types of capsules:

  • 100 mg CBD
  • 300 mg CBD
  • 900 mg CBD
  • Clonazepam (a well known benzodiazepine anti-anxiety drug)
  • Placebo

The group receiving the 300 mg of CBD and the group receiving the clonazepam both saw significant reductions in anxiety as compared to placebo, while the groups receiving 100 mg CBD and 900 mg CBD did not.

Not only does this study add to the evidence that CBD reduces anxiety, but it also demonstrated an added benefit of CBD over clonazepam.  The researchers state that

“the anxiolytic dose of CBD (300 mg) induced a significantly lower sedation level than clonazepam. It is an advantage that must be highlighted, since sedation and motor coordination impairment are among the most common adverse effects of benzodiazepines, in addition to potential dependence, cognitive deficits, and withdrawal symptoms…These side-effects have not been observed with the use of CBD”.


Cannabidiol as a Potential Treatment for Anxiety Disorders   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/ 

This 2015 review paper evaluated the preclinical (animal), clinical and epidemiological studies that had been published to date looking at CBD and anxiety disorders.  In total, 49 studies were included.

In discussing the findings in their review of the medical literature, the authors conclude that “preclinical evidence conclusively demonstrates CBD’s efficacy in reducing anxiety behaviors relevant to multiple disorders, including PTSD, GAD, PD, OCD, and SAD.”  Going further, they state that “evidence from human studies strongly supports the potential for CBD as a treatment for anxiety disorders”.  

Of particular note is the conclusion that “CBD reduces experimentally induced anxiety in healthy controls, without affecting baseline anxiety levels, and reduces anxiety in patients with SAD.  Limited results in healthy subjects also support the efficacy of CBD in acutely enhancing fear extinction, suggesting potential for the treatment of PTSD, or for enhancing cognitive behavioral therapy.”


Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report.   https://www.ncbi.nlm.nih.gov/pubmed/20829306 

Expanding on their two previous studies showing that CBD has anxiolytic properties in healthy individuals, researchers designed this double blind clinical trial using functional neuroimaging (SPECT scan) to investigate the effects of CBD in patients with generalized social anxiety disorder. 

Subjects received either CBD or placebo in capsule form 110 minutes prior to undergoing the SPECT scanning procedure.  One week later, the procedure was repeated, with subjects receiving either the CBD or placebo capsule that they had not received in the first procedure.  Anxiety levels were assessed using the Visual Analog Mood Scale (VAMS), a validated and highly sensitive scale for the detection of drug effects on anxiety.

The results showed that CBD significantly decreased anxiety over placebo before, during, and after the procedure.  Researchers concluded that this study “demonstrated that acute administration of CBD, one of the main psychoactive constituents of Cannabis sativa, can reduce subjective anxiety in patients clinically diagnosed with an anxiety disorder, in this case SAD.  Furthermore, the present study indicates that this behavioral response is associated with changes in the functional activity of brain areas implicated in the processing of anxiety.”

CBD was well tolerated by all participants and no side effects were reported.


Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing.   https://jamanetwork.com/journals/jamapsychiatry/fullarticle/482939  

This double-blind, randomized, placebo-controlled study evaluated the effects of THC or CBD on emotional processing using functional MRI scanning, a tool which “provides a sensitive means of examining how cannabis acts on the brain.”

Participants were healthy men who viewed images of faces that “implicitly elicited varying levels of anxiety” following oral ingestion of THC, CBD or placebo capsules. Evaluations were performed on 3 separate occasions, and regional brain activation, electrodermal activity, and objective and subjective ratings of anxiety were recorded.  Blood levels of THC and CBD were also monitored.

The findings demonstrated that CBD reduced anxiety compared to placebo, and the researchers concluded that CBD is associated with a “reduction in the electrodermal response, consistent with behavioral evidence that it has anxiolytic effects.”  They go on to state that “the effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety.”


Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818147/ 

As defined in this 2016 review article, disorders of motivation include drug addiction, anxiety and depression.  Researchers gathered all data available on the therapeutic efficacy of CBD for the treatment of these conditions.

In evaluating the evidence for therapeutic actions of CBD, it was noted that “findings strongly implicate [serotonin]-mediated transmission in key brain areas as a potential mechanism underlying the effects of CBD on anxiety.” 

As related to depression, the authors quote research showing that CBD may reduce depressive symptoms by a similar mechanism to classical antidepressants. 

While elucidation of individual mechanistic effects is required for full understanding of any medicinal compound, the authors of this paper state that “the greatest treatment value of CBD may lie in its multitarget actions…Pharmacotherapies that target numerous receptors across neural networks may be more efficacious than those that are maximally selective for a single target…Therefore, in motivational disorders with complex etiology and underlying neural substrates, the multitarget effects of CBD may make it a highly efficacious treatment option.”

The authors conclude that “present results signify an important therapeutic role for CBD in the treatment of depression and anxiety.”


Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462012000500008&lng=en&nrm=iso&tlng=en  

Conducted in 2012, this review paper systematically analyzed all studies to date that specifically evaluated the effects of CBD on anxiety.  The researchers intentionally excluded studies using a blend of THC and CBD in order to get an accurate representation of CBD in particular.

In total, there 17 pre-clinical (animal) studies and 6 human clinical studies included in the review.  All human studies used oral CBD, with doses ranging from 1 mg/kg up to 600 mg.

The authors conclude that “studies using animal models of anxiety and involving healthy volunteers clearly suggest an anxiolytic-like effect of CBD.  Moreover, CBD was shown to reduce anxiety in patients with social anxiety disorder.”  They go on to point out that CBD “has no psychoactive effects and does not affect cognition; has an adequate safety profile, good tolerability, positive results in trials with humans, and a broad spectrum of pharmacological actions…”.


DEPRESSION

Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation? 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818147/ 

As defined in this 2016 review article, disorders of motivation include drug addiction, anxiety and depression.  Researchers gathered all data available on the therapeutic efficacy of CBD for the treatment of these conditions. 

In evaluating the evidence for therapeutic actions of CBD, it was noted that “findings strongly implicate [serotonin]-mediated transmission in key brain areas as a potential mechanism underlying the effects of CBD on anxiety.”

As related to depression, the authors quote research showing that CBD may reduce depressive symptoms by a similar mechanism to classical antidepressants. 

While elucidation of individual mechanistic effects is required for full understanding of any medicinal compound, the authors of this paper state that “the greatest treatment value of CBD may lie in its multitarget actions…Pharmacotherapies that target numerous receptors across neural networks may be more efficacious than those that are maximally selective for a single target…Therefore, in motivational disorders with complex etiology and underlying neural substrates, the multitarget effects of CBD may make it a highly efficacious treatment option.”

The authors conclude that “present results signify an important therapeutic role for CBD in the treatment of depression and anxiety.”


Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L.  

https://www.ncbi.nlm.nih.gov/pubmed/20332000 

This pre-clinical (animal) study investigated the potential of numerous cannabinoids, including CBD.

In discussing the results of this study, researchers state that “phytocannabinoids display antidepressant-like actions in established models of behavioral despair” and note that “cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis.” 

The results show that “both CBD and CBC displayed significant antidepressant-like effect in the used animal models”.


Prohedonic effect of cannabidiol in a rat model of depression

https://www.ncbi.nlm.nih.gov/pubmed/27010632 

Seeking to expand on limited knowledge of CBD and depression, researchers designed this animal study to evaluate the effects of this particular cannabinoid on depressive-like behavior.

In this genetic animal model of depression, the researchers state that their “results suggest that CBD may be beneficial for the treatment of clinical depression and other states with prominent anhedonia.”