CBD for Anxiety

Overseen By Carol A Mathews, M.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must not be taking: Benzodiazepines, Opioids, Antihistamines, others

Disqualifiers: Pregnancy, Suicidal behavior, Liver disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a hemp-derived CBD product can reduce anxiety and improve sleep quality. Participants will take either the CBD or a placebo for four weeks to assess the safety and effectiveness of CBD at different doses. The trial will also explore whether improved sleep precedes the easing of anxiety symptoms. Individuals with moderate to severe anxiety and sleep disturbances may be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you've changed your SSRI, SNRI, or other non-benzo anxiolytic medication within six weeks of the baseline visit. You also need to refrain from using certain medications like benzodiazepines, opioids, and antihistamines, among others, during the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that cannabidiol (CBD), often derived from hemp, is usually well-tolerated. Studies have found that side effects can include reduced appetite and weight loss, especially at higher doses. One study noted that CBD might raise liver enzymes, signaling potential liver stress, but this occurred mostly at doses much higher than those used in this trial. The FDA has approved a CBD product for treating seizures, indicating some confidence in its safety at certain doses. While CBD isn't completely risk-free, the doses in this trial (50 to 150 mg/day) are lower than those linked to more serious side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for anxiety?

Unlike traditional treatments for anxiety, which often include medications like SSRIs or benzodiazepines, the new option on the block is a hemp-derived cannabidiol (CBD) extract. This treatment is unique because it offers a natural approach by using CBD, an active ingredient known for its calming effects without the psychoactive properties associated with THC. Researchers are excited about this treatment because it could provide anxiety relief with potentially fewer side effects and a lower risk of dependency compared to conventional pharmaceuticals. Additionally, CBD has a different mechanism of action, interacting with the body's endocannabinoid system, which may provide a novel pathway for alleviating anxiety symptoms.

What evidence suggests that this treatment might be an effective treatment for anxiety?

Research has shown that cannabidiol (CBD) might help reduce anxiety. In one study, a single 300 mg dose of CBD eased anxiety during public speaking. Another study found that CBD lowered anxiety and stress hormone levels in patients. Some research also suggests that CBD could improve sleep by making it easier to fall and stay asleep. This trial will test Hemp Derived Cannabidiol Extract, which participants may receive, to further explore its potential in treating anxiety and sleep problems. While more research is needed, these findings suggest that CBD could be promising for these conditions. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults aged 18-55 with moderate to severe anxiety, as indicated by a HAM-A score over 14. Participants must be willing to give informed consent, follow study procedures including blood donation, and use two effective contraception methods if of childbearing potential.

Inclusion Criteria

My anxiety level is moderate to severe, according to the HAM-A scale.

Subjects of childbearing potential should use two forms of highly effective contraception methods combined (e.g., barrier methods combined with Long-Acting Reversible Contraceptives) to be eligible for study participation

Normal clinical history and laboratory test

Exclusion Criteria

Positive drug screen for substances of abuse

Known or suspected hypersensitivity to cannabidiol or any other components in the extract

I do not have any unstable medical or neurological conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a hemp-derived CBD product for improving anxiety symptoms and sleep disturbances. The treatment period consists of a two-week titration period followed by a 2-week maintenance period.

4 weeks

Weekly visits for monitoring and dose adjustment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of adverse events and changes in anxiety and sleep quality.

8 weeks

Periodic assessments over 8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hemp Derived Cannabidiol Extract

Trial Overview

The trial is testing the safety and preliminary effectiveness of hemp-derived CBD for reducing anxiety symptoms and sleep disturbances. It's a randomized, double-blind study comparing CBD doses (50-150 mg/day) against placebo over four weeks.

How Is the Trial Designed?

Group I: Hemp Derived Cannabidiol Extract Experimental Treatment 1 Intervention

SunFlora's CBD Extract 50mg to 150mg titrated over 4 weeks

Group II: Placebo Placebo Group 1 Intervention

Placebo substance to reflect same consistency as the experimental drug

Hemp Derived Cannabidiol Extract is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cannabidiol for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Cannabidiol for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Approved in Canada as Cannabidiol for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Published Research Related to This Trial

Serious suspected adverse reactions (SARs) to unlicensed cannabidiol (CBD) products were found to be 18.9% of all adverse events, with a higher frequency in men and adults, indicating a need for careful monitoring of its use.

The most common adverse effects associated with unlicensed CBD included mental disorders, hepatic disorders, and worsening of pre-existing epilepsy, particularly in patients also taking antiepileptic medications like clobazam and valproic acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. Calapai, F., Esposito, E., Ammendolia, I., et al.[2023]

About 31.3% of parents surveyed reported giving unlicensed cannabidiol (CBD) products to their children diagnosed with ADHD, autism spectrum disorder (ASD), or generalized anxiety disorder (GAD), indicating a significant prevalence of CBD use in this population.

Parents who used CBD products generally perceived them as safer and felt more community support for their use, suggesting a need for healthcare providers to discuss the safety and implications of CBD use with families.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parental Perceptions and Usage of Unlicensed Cannabidiol Products in Children With Anxiety and Neurodevelopmental Disorders. Schwaller, K., Krauss, Z., Chen, AMH., et al.[2023]

A 28-day treatment with 300 mg of Cannabidiol (CBD) significantly reduced anxiety levels in frontline healthcare workers during the COVID-19 pandemic, with effects observed up to one month after stopping the treatment.

The study suggests that CBD may provide lasting anxiolytic benefits, but further double-blind placebo-controlled trials are necessary to confirm these findings and assess any potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintained anxiolytic effects of cannabidiol after treatment discontinuation in healthcare workers during the COVID-19 pandemic. Souza, JDS., Zuardi, AW., Guimarães, FS., et al.[2022]

A systematic review of eight studies, including six randomized controlled trials, suggests that cannabidiol (CBD) may be effective in reducing anxiety symptoms in various anxiety disorders, with doses ranging from 6 mg to 400 mg.

CBD was generally well-tolerated with minimal side effects, primarily fatigue and sedation, indicating its potential as a safe alternative therapy for anxiety management, although further research is needed for standardized dosing and efficacy assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of cannabidiol in anxiety and anxiety-related disorders. Skelley, JW., Deas, CM., Curren, Z., et al.[2022]

In a 12-week open-label trial involving 31 young people aged 12-25 with treatment-resistant anxiety disorders, cannabidiol (CBD) significantly reduced anxiety severity by 42.6%, as measured by the Overall Anxiety Severity and Impairment Scale (OASIS).

CBD was found to have an adequate safety profile, with 80.6% of participants reporting mild adverse events like fatigue and low mood, but no serious or unexpected adverse events were noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol for Treatment-Resistant Anxiety Disorders in Young People: An Open-Label Trial. Berger, M., Li, E., Rice, S., et al.[2022]

In a study involving 63 individuals with high levels of worry, a single acute dose of 300mg of cannabidiol (CBD) did not significantly reduce worry severity or anxiety symptoms, indicating that CBD may not effectively target cognitive aspects of anxiety.

However, after a 2-week period of repeated administration, the 300mg dose of CBD did show a reduction in physical anxiety symptoms compared to placebo, suggesting that CBD may have modest effects on the physical manifestations of anxiety rather than cognitive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of cannabidiol on worry and anxiety among high trait worriers: a double-blind, randomized placebo controlled trial. Gournay, LR., Ferretti, ML., Bilsky, S., et al.[2023]

A systematic review of 4186 studies on cannabidiol (CBD) revealed that most research focuses on neurological outcomes, with significant adverse events reported in this area, highlighting the need for careful assessment of CBD's safety.

There is a notable gap in research regarding the reproductive and developmental toxicity of CBD, suggesting that future studies should prioritize these areas to establish safe intake levels for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Safety Data: A Systematic Mapping Study. Henderson, RG., Franke, KS., Payne, LE., et al.[2023]

In a study comparing the effects of cannabidiol (CBD) on anxiety in male and female rats, it was found that female rats showed a significant response to CBD only during the late diestrus phase of their estrous cycle, requiring a much lower dose than males.

Both sexes exhibited anxiolytic-like effects from CBD, but the differences in responsiveness suggest that hormonal fluctuations in females may influence the drug's effectiveness, highlighting the need for sex-specific considerations in CBD treatment for anxiety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex-dependent differences in the anxiolytic-like effect of cannabidiol in the elevated plus-maze. Fabris, D., Carvalho, MC., Brandão, ML., et al.[2023]

In a large survey of over 45,000 participants from the U.S. and Canada, CBD product use was more common in the U.S. (26.1%) compared to Canada (16.2%), with a variety of products being used for managing pain, anxiety, and depression.

Despite widespread use, over half of the consumers reported benefits from CBD oil, highlighting a need for clearer public health messaging about its therapeutic effects, especially since many reported conditions lack strong evidence for CBD efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use and Perceptions of Cannabidiol Products in Canada and in the United States. Goodman, S., Wadsworth, E., Schauer, G., et al.[2023]

Chronic administration of cannabidiol (CBD) in rats led to increased anxiety-like behavior, as indicated by more time spent freezing in a conditioned emotional response test, contrasting with previous findings of acute anxiolytic effects.

CBD also decreased the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the hippocampus, suggesting that chronic CBD treatment may negatively impact brain protein levels associated with anxiety and depression, which is opposite to the effects seen with traditional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anxiogenic-like effects of chronic cannabidiol administration in rats. ElBatsh, MM., Assareh, N., Marsden, CA., et al.[2021]

Repeated administration of cannabidiol (CBD) over 21 days significantly reduces panic-like escape responses in rats, indicating its potential as an anti-panic treatment.

The anti-panic effects of CBD are mediated through the activation of 5-HT1A receptors in the dorsal periaqueductal gray (DPAG), as blocking these receptors prevents CBD's effects, although CBD does not alter serotonin levels or receptor expression in this brain region.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats. Campos, AC., de Paula Soares, V., Carvalho, MC., et al.[2021]

Cannabidiol (CBD) has shown greater anxiolytic effects in healthy individuals and certain clinical populations, but it does not significantly impact sleep, indicating its potential as an anxiety treatment.

The effectiveness of CBD appears to be influenced by dosage and its ratio to THC in combined treatments, with its action primarily modulating the endocannabinoid system and regulating neuroendocrine function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoid treatments for anxiety: A systematic review and consideration of the impact of sleep disturbance. Narayan, AJ., Downey, LA., Manning, B., et al.[2022]

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/pii/S0165178124003342

Therapeutic potential of cannabidiol (CBD) in anxiety ...

A randomized clinical trial (RCT) demonstrated that CBD reduced drug-induced anxiety and salivary cortisol levels in patients (Hurd et al., 2019). Moreover, ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06672666

NCT06672666 | Use of CBD in the Treatment of Anxiety

This study will examine the doses, safety, and test the preliminary efficacy of hemp-derived CBD product for improving anxiety symptoms and sleep ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11595441/

The Impact of Cannabidiol Treatment on Anxiety Disorders

A single dose of 300 mg of CBD proved effective in alleviating anxiety induced by public speech, as indicated in the studies by Zuardi et al. ( ...

4.

health.harvard.edu

health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-201808242496

Cannabidiol (CBD): What we know and what we don't

Insomnia: Studies suggest that CBD may help with both falling asleep and staying asleep, in part by helping address chronic pain and anxiety.

5.

rally.massgeneralbrigham.org

rally.massgeneralbrigham.org/study/hemp_cbd_anxiety

Clinical Trial of a Hemp-Derived, High Cannabidiol (CBD) ...

This is a clinical trial designed to examine the impact of 6 weeks of treatment with a hemp-derived, high cannabidiol (CBD) sublingual product on individuals ...

6.

library.samhsa.gov

library.samhsa.gov/sites/default/files/pep22-06-04-003.pdf

Cannabidiol (CBD) – Potential Harms, Side Effects, and ...

CBD is typically derived from hemp because of its low THC concentration, and THC is typically derived from marijuana plants. There is currently only one FDA- ...

7.

cdc.gov

cdc.gov/cannabis/about/about-cbd.html

About CBD | Cannabis and Public Health

Using CBD products is not risk free. The FDA has limited data on CBD safety. Please consider these possible side effects and risks before ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5569602/

An Update on Safety and Side Effects of Cannabidiol

The only observed side effects were reduced sucrose preference, reduced food consumption and body weight in the nonoperated animals treated with CBD (50 mg/kg).

9.

fda.gov

fda.gov/drugs/regulatory-science-action/cder-investigators-address-safety-cbd-randomized-trial

CDER Investigators Address the Safety of CBD in a ...

At labeled doses up to 25 mg/kg/day, an increased risk of liver enzyme elevation was observed., Liver enzyme elevations typically occurred after ...

10.

mayoclinic.org

mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700

CBD: Safe and effective?

A prescription cannabidiol (CBD) oil is considered an effective anti-seizure medication. ... FDA approves first drug compromised of an active ingredient derived ...