Role of CBD in Improving Alexithymia

Study Overview
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Brief Summary
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Given the treatments that are available today for HIV disease, people living with HIV (PLWH) can generally expect good medical outcomes. However, HIV is still a chronic disease and there are remaining barriers to achieving ideal health status and quality of life. One barrier may be a condition that is common among PLWH, called alexithymia, which can make it difficult for a person to name and describe the emotions that they are feeling. As a result, it is difficult to resolve negative emotional states, which can then lead to worse outcomes over time due to ongoing stress and related problems such as inflammation. In this study we will try to find out whether taking cannabidiol (CBD) helps PLWH who have alexithymia to resolve those negative emotional states, which may then reduce inflammation in the body as a result. CBD may work by enhancing the body's own chemical messengers that can help to regulate emotions and encourage emotional benefits. We will compare a group of people who take CBD for 4 weeks to those who take a placebo, which is a substance that will closely resemble the CBD but will not contain any active drug. Study participants and the researchers who are working directly with the participants will not be able to tell which is the CBD and which is the placebo. We will evaluate participants before and after the 4-week study period. We will also collect samples, such as blood, so that we can measure inflammation. We will compare the two groups to see if those who took CBD have lower alexithymia and lower inflammation compared to those who took the placebo. The potential benefit of this study is that CBD may be an effective treatment for alexithymia in PLWH, which may then improve both their emotional and physical health outcomes. This can help to address a remaining barrier to good medical outcomes for PLWH.

Detailed Description
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Although HIV disease can be medically well-managed, the chronicity of the disease nevertheless takes a toll on persistent inflammation, comorbid medical and mental health conditions, and poor psychosocial functioning. Therefore, it is necessary to identify barriers to optimal health-related outcomes and quality of life. One such barrier may be alexithymia, which is poor internal emotional awareness that is elevated in the context of many chronic conditions, including HIV. Subsequent persistent dysregulation of negative emotional states and stress has been linked to worse HIV disease progression and management, and poor psychosocial functioning. The present study will evaluate whether treatment with cannabidiol (CBD) will reduce or compensate for elevated alexithymia among people living with HIV (PLWH), and whether targeting alexithymia with CBD treatment twill be associated with improved health-related outcomes in this population. Prior studies suggest that alexithymia can indeed be improved with behavioral intervention, with subsequent benefits for health outcomes. Limited evidence is available for pharmacological intervention. CBD may be a useful therapeutic tool due to its proposed role in enhancing circulating anandamide (AEA), an endogenous cannabinoid associated with social-emotional benefits. The proposed study is a phase II, double-blind, placebo-controlled clinical trial of CBD for alexithymia and health-related outcomes. The study will enroll 15 HIV+ individuals in each treatment arm (drug vs placebo), and participants will be eligible for the study if they screen positive for elevated alexithymia and are not current cannabis users. They will be evaluated at two time points, five weeks apart, to compare the study outcomes pre- and post-treatment. For one week they will titrate up to the maintenance dose of 600 mg/day of Purysis, a synthetic, liquid form of CBD, which they will continue for 4 weeks. Upon completion of the 4-week trial, they will be re-assessed, followed by one week of titrating down to discontinuation. The pre- and post-treatment assessments will measure alexithymia and health-related outcomes, and samples will be collected (i.e., plasma, cerebrospinal fluid) to measure central and peripheral levels of AEA. With this approach we will test our hypothesis that treatment with CBD will decrease alexithymia, which will be associated with better organic disease outcomes (e.g., lower inflammation), reduced physical and mental health symptom reporting, and improvement in maladaptive behaviors (e.g., psychosocial functioning). We will also determine whether AEA is indeed associated with alexithymia, and investigate the possibility that CBD reduces alexithymia via increasing circulating AEA.

Official Title
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The Role of Cannabidiol in Anandamide-Related Improvement in Alexithymia and Health Outcomes

Conditions
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Alexithymia, HIV

Intervention / Treatment
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* Drug: Synthetic CBD
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV+ and on stable ART adults aged 21-65, due to the inherent complication of providing a cannabis product to individuals under the legal age for cannabis use (i.e., 21 years of age) and the potential for greater sensitivity to CBD in older individuals possess the ability to provide consent possess the ability to read and write in English (given that translations are not available for all tests) screen positive for clinically elevated alexithymia. Exclusion Criteria: history of psychosis, bipolar disorder, or substance use disorder within 6 months (irregular drug/alcohol use not meeting criteria for a substance use disorder will not be exclusionary) history of a significant neurological condition that might affect the central nervous system (e.g., severe head trauma with loss of consciousness, epilepsy) other than HIV current psychiatric treatment or symptoms (i.e., severe distress and/or active suicidality) that may confound results or introduce risk as determined by the PI or study physician medical contraindication for CBD treatment as determined by the study physician's review of potential participants' medical screen and bloodwork, (e.g., cardiovascular, hepatic or renal disease) current cannabis use in the last 3 months given that it may confound the effect of the study drug and alter AEA levels pregnancy

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, placebo-controlled trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Synthetic CBD 4-Week Trial Arm<br>For one week they will titrate up to the maintenance dose of 600 mg/day of Purysis, a synthetic, liquid form of CBD, which they will continue for 4 weeks. Upon completion of the 4-week trial, they will be re-assessed, followed by one week of titrating down to discontinuation. | Drug: Synthetic CBD<br>* Participants will receive Purysis, or synthetic CBD, which will be compared to placebo<br>* Other names: Purysis CBD;|
| Placebo Comparator: Placebo 4-Week Trial Arm<br>For one week they will titrate up to the maintenance dose of 600 mg/day of placebo for Purysis, a synthetic, liquid form of CBD, which they will continue for 4 weeks. Upon completion of the 4-week trial, they will be re-assessed, followed by one week of titrating down to discontinuation. | Drug: Placebo<br>* Placebo for Purysis<br>* Other names: Purysis Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alexithymia | Measured by score on Toronto Alexithymia Scale-20 Item Version | 5 weeks |