Clinical and Cognitive Improvement Following Treatment with a Hemp-Derived, Full-Spectrum, High-Cannabidiol Product in Patients with Anxiety: An Open-Label Pilot Study

Posted on August 28, 2025 by David

“Background/Objectives: Cannabidiol (CBD) is a non-intoxicating cannabinoid touted for a variety of medical benefits, including alleviation of anxiety. While legalization of hemp-derived products in the United States (containing ≤0.3% delta-9-tetrahydrocannabinol [d9-THC] by weight) has led to a rapid increase in the commercialization of hemp-derived CBD products, most therapeutic claims have not been substantiated using clinical trials. This trial aimed to assess the impact of 6 weeks of treatment with a proprietary hemp-derived, full-spectrum, high-CBD sublingual solution similar to those available in the marketplace in patients with anxiety.

Methods: An open-label pilot clinical trial (NCT04286594) was conducted in 12 patients with at least moderate levels of anxiety. Patients self-administered a hemp-derived, high-CBD sublingual solution twice daily during the 6-week trial (target daily dose: 30 mg/day CBD). Clinical change over time relative to baseline was assessed for anxiety, mood, sleep, and quality of life, as well as changes in cognitive performance on measures of executive function and memory. Safety and tolerability of the study product were also evaluated.

Results: Patients reported significant reductions in anxiety symptoms over time. Concurrent improvements in mood, sleep, and relevant quality of life domains were also observed, along with stable or improved performance on all neurocognitive measures. Few side effects were reported, and no serious adverse events occurred.

Conclusions: These pilot findings provide initial support for the efficacy and tolerability of the hemp-derived, high-CBD product in patients with moderate-to-severe levels of anxiety. Double-blind, placebo-controlled studies are indicated to obtain robust data regarding efficacy and tolerability of these types of products for anxiety.”

https://pubmed.ncbi.nlm.nih.gov/40868129/

“Results from this open-label clinical trial provide evidence that a hemp-derived, full-spectrum, high-CBD product similar to those currently available in the marketplace may be both safe and efficacious for the treatment of anxiety. Given the potential benefits observed in this trial, double-blind, placebo-controlled studies of hemp-derived high-CBD products are warranted to obtain robust data regarding the safety and efficacy of CBD-containing products for anxiety.”

https://www.mdpi.com/2227-9059/13/8/1874

A novel cannabidiol:tetramethylpyrazine cocrystal (CBD:TMP, ART12.11) improves the efficacy and bioavailability of cannabidiol in reducing stress-induced depressive and anxiety symptoms

Posted on August 27, 2025 by David

“Clinical and pre-clinical research has reported promising outcomes for cannabidiol (CBD) in treating mood and anxiety disorder symptoms. However, the pharmacokinetic properties of CBD, such as low and variable bioavailability and low aqueous solubility, limit its therapeutic applications.

This study investigated the effects of ART12.11, a novel cannabidiol:tetramethylpyrazine (CBD:TMP) cocrystal, that aims to improve the pharmacotherapeutic potential of CBD by combining it with the co-former tetramethylpyrazine (TMP) to improve CBD’s pharmaceutical properties.

We used an integrative combination of translational behavioural pharmacology alongside targeted gene and protein expression analyses to characterize the potential anti-depressant and anxiolytic-like effects of ART12.11 in male Sprague Dawley rats, following exposure to chronic stress. In addition, we investigated blood plasma concentrations of CBD and TMP following oral administration of ART12.11 to examine bioavailability.

We report that oral administration of ART12.11 reversed stress-induced behavioural deficits and produced significant anti-depressant and anxiolytic-like behavioural effects, which were superior to oral administration of CBD alone, TMP alone, or the co-administration of a non-crystalline mixture of CBD and TMP. Further, we report that ART12.11 resulted in higher blood plasma levels of CBD and its major metabolite, indicating superior bioavailability. Finally, we demonstrate that ART12.11 increased activation of the endocannabinoid and serotonergic systems directly in the prefrontal cortex, ventral hippocampus, and nucleus accumbens.

Collectively, our findings indicate that ART12.11 may offer significant advantages over delivering CBD by more traditional approaches in the treatment of mood and anxiety disorders.”

https://pubmed.ncbi.nlm.nih.gov/40854502/

https://www.sciencedirect.com/science/article/abs/pii/S0278584625002325?via%3Dihub

Acute and chronic effects of medicinal cannabis use on anxiety and depression in a prospective cohort of patients new to cannabis

Posted on July 8, 2025 by David

“Introduction: Medicinal cannabis has mixed evidence for treating anxiety and depression, yet patients frequently use it as a treatment. This observational study evaluated the effects of medicinal cannabis initiation in adults with clinically significant anxiety and/or depression over a 6-month period.

Methods: Adults with clinically significant anxiety and/or depression initiating medicinal cannabis use in Maryland, USA completed ecological momentary assessment (EMA) and longitudinal follow-up evaluations. Hospital Anxiety and Depression Scale (HADS) assessments were completed at baseline and 1, 3, and 6 months after medicinal cannabis initiation. EMA measures were completed at baseline and daily for 8 weeks after cannabis initiation with measures collected before each cannabis use and at time of expected peak effect. Changes in anxiety and depression were evaluated using linear mixed effect models.

Results: Significant decreases from baseline in anxiety and depression were observed, with mean scores dropping below clinically significant levels within three months of initiation. EMA data indicated that most participants selected THC-dominant cannabis and acute reductions in anxiety, depression, and perceived driving ability along with increased ratings of feeling “high”. Acute effects were dose-dependent: 10-15 mg of oral THC and at least 3 puffs of vaporized cannabis yielded the most robust reductions in anxiety and depression.

Conclusions: Initiation of THC-dominant medicinal cannabis was associated with acute reductions in anxiety and depression, and sustained reductions in overall symptom severity over a 6-month period. Controlled clinical trials are needed to further investigate the efficacy and safety of medicinal cannabis for acute anxiety and depression symptom management.”

https://pubmed.ncbi.nlm.nih.gov/40623642/

“In this prospective, observational study, medicinal cannabis use was associated with significant decreases in self-reported anxiety and depression compared with pre-cannabis use initiation baseline assessments among individuals with clinically significant anxiety and/or depression. Reductions in anxiety and depression were observed acutely following individual episodes of cannabis use and overall symptom reductions were sustained over the six-month period of observation.”

https://www.sciencedirect.com/science/article/abs/pii/S0165032725012716?via%3Dihub

Medicinal cannabis in the management of anxiety disorders: A systematic review

Posted on May 27, 2025 by David

“Background: With rising anxiety disorder diagnoses, many individuals are seeking alternatives to standard pharmacotherapies, like medicinal cannabis. This systematic review focuses exclusively on anxiety-related disorders and examines a wide range of cannabis-based preparations and interventions.

Method: We searched MEDLINE, EMBASE, CINAHL, and PsycInfo (October-December 2023) for peer-reviewed empirical studies, excluding case series, case studies, and review papers. Inclusion criteria were studies on adults (18+ years) diagnosed with anxiety-related disorders, examining the efficacy or effectiveness of medicinal cannabis. Studies on recreational cannabis or cannabis-use-disorder were excluded. The MASTER and QualSyst tools were used to assess bias.

Results: Fifty-seven studies met the inclusion criteria: 40 % cohort (n = 23), 30 % randomised controlled trials (n = 17), 18 % cross-sectional (n = 10), 12 % qualitative or other designs (n = 7). The MASTER scale revealed a high risk of bias, with a mean score of 62.9 (out of 100) due to inadequate reporting. Among the 13 highest-quality studies, 70 % (n = 9) reported a positive improvement for disorders including generalised anxiety disorder (GAD), social anxiety disorder (SAD), and post-traumatic stress disorder (PTSD). 30 % (n = 4) reported a negative result for conditions like obsessive-compulsive disorder, trichotillomania, test anxiety and SAD. Over 90 % of all studies, including lower quality studies, reported positive outcomes for CBD and THC-based cannabis. However, 53 % (n = 30) either omitted, or included self-reported data on either form and/or dosage.

Conclusion: Medicinal cannabis demonstrates potential in reducing anxiety symptoms, but the long-term benefits and overall impact on quality of life remain unclear. Further high-quality, longitudinal research with standardised dosing is needed.”

https://pubmed.ncbi.nlm.nih.gov/40413923/

“Across a range of anxiety-related disorders, most high-quality studies found that medicinal cannabis reduced anxiety symptoms in individuals with GAD, PTSD and SAD.”

https://www.sciencedirect.com/science/article/pii/S0165178125002008?via%3Dihub

Low-dose cannabidiol treatment prevents chronic stress-induced phenotypes and is associated with multiple synaptic changes across various brain regions

Posted on May 24, 2025 by David

“Major Depressive Disorder (MDD) is a heterogeneous and debilitating mood disorder often associated with stress. Although current treatments are available, they remain ineffective for approximately 30% of affected individuals and are frequently accompanied by undesirable side effects.

Cannabidiol (CBD) has emerged as a potential and safe therapeutic option for alleviating depressive symptoms; however, the underlying molecular mechanisms through which this compound exerts its beneficial effects are not yet fully understood.

In this study, we demonstrate that a very low dose of CBD (1 mg/kg) can partially reverse some sequelae induced by chronic stress, a well-established mouse model used to simulate depressive-like symptoms. Using mass spectrometry to analyze different brain regions, we observed several improvements following CBD treatment, particularly in the medial prefrontal cortex (mPFC), across multiple neurotransmission systems (including glutamatergic and serotonergic pathways). Microstructural experiments, utilizing double-labeling of F-Actin and VGlut1-positive clusters, revealed a complete restoration of mature synapses in the mPFC of mice treated with CBD.

In conclusion, our findings indicate that a very low dose of CBD is effective in counteracting the adverse effects of chronic stress, possibly through the synaptic remodeling of excitatory synapses in the mPFC.”

https://pubmed.ncbi.nlm.nih.gov/40409535/

“We show that a very low dose of CBD is enough to correct emotional sequelae in a mouse model of chronic stress.”

https://www.sciencedirect.com/science/article/pii/S0028390825002321?via%3Dihub

Daily Impact of Medical Cannabis on Anxiety and Sleep Quality in Older Adults

Posted on May 19, 2025 by David

“Objective: Older adults represent the fastest growing demographic of cannabis users, and they endorse cannabis use for a variety of reasons including modulation of chronic pain, mental health symptoms, and sleep concerns. However, current evidence leaves questions of efficacy unanswered among these groups. Goals of the present study were to examine the hypothesis that medical cannabis (MC) use will, at the daily level, predict lower pain, depression, anxiety, and improved sleep.

Method: A final sample of 106 MC users were recruited nationwide (ages 55-74, 66.67% female, 82.86% white). A fully within-subject multilevel structural equation model was conducted with use patterns and symptomology broken into four temporal epochs. MC use, operationalized as subjective intoxication (Epoch 1), averaged across the day was used to predict subsequent pain, anxiety, and depression levels (Epoch 2), which were then used to predict sleep that night (Epoch 3), then subsequent pain, anxiety, and depression the following day (Epoch 4) prior to initiation of MC use.Results: Subjective intoxication predicted lower post-use pain, anxiety, and depression. Subjective intoxication is related to lower anxiety and better sleep the following night.

Conclusions: These findings provide evidence of momentary improvements in pain, anxiety, depression, and indirect benefits for sleep quality. In combination with other findings, the results advance our understanding of the efficacy and limitations of MC among older adults. Findings are limited by MC measurement and sample homogeneity (primarily White, non-Hispanic female). Future research should seek to further measurement of use and corresponding effects and examine expectancy effects in aging clinical populations.”

https://pubmed.ncbi.nlm.nih.gov/40372396/

https://www.tandfonline.com/doi/full/10.1080/00332747.2025.2484827

Cannabinoids: Adaptogens or Not?

Posted on May 8, 2025 by David

“Since ancient times, humanity has been exploring natural substances with the aim of increasing stress resistance, enhancing biochemical homeostasis, and treating different diseases. In this way, the objective of the present review is to compare the biological effects of cannabinoids (CNBs) with adaptogens, this exploration allows us to consider the controversy if they can be classified together considering the effects on the body.

First, the work revises different features of adaptogens such as their chemical structure, ligand-receptors properties, and homeostasis-stress capabilities. Also, this review includes an overview of preclinical and clinical studies of the effect of adaptogens considering a broad spectrum of adverse biological, chemical, and physical factors.

Then, the work does a review of the CNBs effects on the body including the principal uses for the treatment of several diseases as neurodegenerative disorders, arthritis, cancer, cardiovascular affections, diabetes, anxiety, chronic pain, among others. In addition, the different characteristics of the specific endocannabinoid system are described explaining the wide CNBs body effects.

Finally, this review presents a comparative analysis between CNBs and adaptogens properties, expecting to contribute to understanding if CNBs can be classified as adaptogens.”

https://pubmed.ncbi.nlm.nih.gov/40332769/

https://www.liebertpub.com/doi/10.1089/can.2024.0108

“Adaptogens are herbs and plant-based substances believed to help the body manage stress and restore balance after stressful situations”

“Adaptogens are active ingredients in certain plants and mushrooms that may impact how your body deals with stress, anxiety and fatigue.”

Improvements in health-related quality of life are maintained long-term in patients prescribed medicinal cannabis in Australia: The QUEST Initiative 12-month follow-up observational study

Posted on April 3, 2025 by David

“Aims: Since 2016, more than one million new patients with chronic health conditions have been prescribed medicinal cannabis in Australia. We aimed to assess overall health-related quality of life (HRQL), pain, fatigue, sleep, anxiety, depression, and motor function in a large real-world sample of patients prescribed medicinal cannabis. We previously found all patient-reported outcomes improved in the first 3-months and hypothesised that improvements would be maintained to 12-months.

Methods: The QUEST Initiative, a multicentre prospective study, recruited adult patients with any chronic health condition newly prescribed medicinal cannabis oil between November 2020 and December 2021. Participants identified by 114 clinicians across Australia completed validated questionnaires at baseline, then 2-weeks titration, and 1-,2-,3-,5-,7-,9- and 12-months follow-up.

Results: Of 2744 consenting participants who completed baseline assessments, 2353 also completed at least one follow-up questionnaire and were included in analyses, with completion rates declining to 778/2353 (38%) at 12-months. Ages ranged between 18-97 years (mean 50.4y; SD = 15.4), 62.8% were female. Chronic conditions commonly treated included musculoskeletal pain (n = 896/2353; 38.1%), neuropathic pain (n = 547/2353; 23.2%), insomnia (n = 546/2353; 23.2%), anxiety (n = 520/2353; 22.1%), and mixed depressive and anxiety disorder (n = 263/2353; 11.2%). Clinically meaningful improvements were observed in HRQL: EQ-5D-5L index (d = 0.52) and QLQ-C30 summary scores (d = 0.91), PROMIS fatigue (d = 0.51) and sleep disturbance (d = 0.76). Participants diagnosed with chronic pain experienced clinically meaningful improvement in scores on QLQ-C30 pain (d = 0.5), PROMIS pain intensity (d = 0.76), and PROMIS pain interference (d = 0.76). There was significant improvement in DASS anxiety (d = 0.69) and DASS depression (d = 0.65) for those with anxiety or depressive conditions, but no motor function improvements observed for participants with movement disorders. All observed improvements were statistically significant.

Conclusions: Statistically significant and clinically meaningful improvements in overall HRQL, fatigue, and sleep disturbance were maintained over 12-months in patients prescribed medical cannabis for chronic health conditions. Anxiety, depression, insomnia, and pain also improved over time for those with corresponding health conditions.”

https://pubmed.ncbi.nlm.nih.gov/40173146/

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0320756

Cannabidiol alters psychophysiological, craving and anxiety responses in an alcohol cue reactivity task: A cross-over randomized controlled trial

Posted on February 2, 2025 by David

“Background: Preclinical studies have demonstrated that cannabidiol (CBD) reduces alcohol-seeking behaviors and may have potential for managing alcohol use disorder (AUD). In this study, we examined the effects of CBD versus placebo on (i) psychophysiological, craving and anxiety responses to alcohol and appetitive cues; (ii) tolerability measures including cognitive functioning.

Methods: Twenty-two non-treatment-seeking individuals with AUD (DSM-5) participated in a cross-over, double-blind, randomized trial, receiving either 800 mg of CBD or matched placebo over 3 days. A laboratory alcohol cue reactivity task with appetitive control (juice) and alcohol exposures, and subsequent recovery periods to examine regulation of cue-elicited responses after cue-offset (recovery) was completed, with psychophysiological indices of autonomic nervous system activity (skin conductance, high-frequency heart rate variability [HF-HRV]) and self-reported measures (alcohol craving and anxiety). Self-reported scales of sedation and neuropsychological executive function tasks were also completed.

Results: CBD sessions were significantly associated with elevated parasympathetic nervous system (PNS) activity across the task, as indicated by increased HF-HRV. Reductions in self-reported anxiety during cue exposure stages compared to placebo sessions were also evidenced. Reductions in self-reported alcohol craving after cue exposure were seen during CBD sessions only. There were no significant differences between CBD and placebo on executive functioning performance.

Conclusions: In a short-term regimen, CBD appears to modulate PNS activity, reduce cue-elicited anxiety during cue exposure and reduce alcohol craving after cue exposure while not significantly impairing cognition. Large, parallel clinical trials with longer term regimens are now needed to determine the therapeutic potential of CBD in the management of AUD.”

https://pubmed.ncbi.nlm.nih.gov/39891614/

https://onlinelibrary.wiley.com/doi/10.1111/acer.15514

Bridging the gap: The endocannabinoid system as a functional fulcrum for benzodiazepines in a novel frontier of anxiety pharmacotherapy

Posted on January 29, 2025 by David

“While benzodiazepines have been a mainstay of the pharmacotherapy of anxiety disorders, their short-term efficacy and risk of abuse have driven the exploration of alternative treatment approaches.

The endocannabinoid (eCB) system has emerged as a key modulator of anxiety-related processes, with evidence suggesting dynamic interactions between the eCB system and the GABAergic system, the primary target of benzodiazepines.

According to the existing literature, the activation of the cannabinoid receptors has been shown to exert anxiolytic effects, while their blockade or genetic deletion results in heightened anxiety-like responses. Moreover, studies have provided evidence of interactions between the eCB system and benzodiazepines in anxiety modulation. For instance, the attenuation of benzodiazepine-induced anxiolysis by cannabinoid receptor antagonism or genetic variations in the eCB system components in animal studies, have been associated with variations in benzodiazepine response and susceptibility to anxiety disorders.

The combined use of cannabinoid-based medications, such as cannabinoid receptor agonists and benzodiazepine co-administration, has shown promise in augmenting anxiolytic effects and reducing benzodiazepine dosage requirements.

This article aims to comprehensively review and discuss the current evidence on the involvement of the eCB system as a key modulator of benzodiazepine-related anxiolytic effects, and further, the possible mechanisms by which the region-specific eCB system-GABAergic connectivity modulates the neuro-endocrine/behavioral stress response, providing an inclusive understanding of the complex interplay between the eCB system and benzodiazepines in the context of anxiety regulation, to inform future research and clinical practice.”

https://pubmed.ncbi.nlm.nih.gov/39862927/

https://www.sciencedirect.com/science/article/abs/pii/S0163725825000117?via%3Dihub

www.thctotalhealthcare.com

Category Archives: Anxiety