Antidepressant and Anxiolytic Effects of Medicinal Cannabis Use in an Observational Trial

Archive of "Frontiers in Psychiatry".“Anxiety and depressive disorders are highly prevalent. Patients are increasingly using medicinal cannabis products to treat these disorders, but little is known about the effects of medicinal cannabis use on symptoms of anxiety and depression.

The aim of the present observational study was to assess general health in medicinal cannabis users and non-using controls with anxiety and/or depression. 

 

Results: Medicinal cannabis use was associated with lower self-reported depression, but not anxiety, at baseline. Medicinal cannabis users also reported superior sleep, quality of life, and less pain on average. Initiation of medicinal cannabis during the follow-up period was associated with significantly decreased anxiety and depressive symptoms, an effect that was not observed in Controls that never initiated cannabis use. 

Conclusions: Medicinal cannabis use may reduce anxiety and depressive symptoms in clinically anxious and depressed populations. Future placebo-controlled studies are necessary to replicate these findings and to determine the route of administration, dose, and product formulation characteristics to optimize clinical outcomes.”

https://pubmed.ncbi.nlm.nih.gov/34566726/

https://www.frontiersin.org/articles/10.3389/fpsyt.2021.729800/full

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Efficacy and Safety of Cannabidiol Plus Standard Care vs Standard Care Alone for the Treatment of Emotional Exhaustion and Burnout Among Frontline Health Care Workers During the COVID-19 Pandemic: A Randomized Clinical Trial

Free Download JAMA Network Logo Vector from Tukuz.Com“Importance: Frontline health care professionals who work with patients with COVID-19 have an increased incidence of burnout symptoms. Cannabidiol (CBD) has anxiolytic and antidepressant properties and may be capable of reducing emotional exhaustion and burnout symptoms.

Objective: To investigate the safety and efficacy of CBD therapy for the reduction of emotional exhaustion and burnout symptoms among frontline health care professionals working with patients with COVID-19.

Interventions: Cannabidiol, 300 mg (150 mg twice per day), plus standard care or standard care alone for 28 days.

Main outcomes and measures: The primary outcome was emotional exhaustion and burnout symptoms, which were assessed for 28 days using the emotional exhaustion subscale of the Brazilian version of the Maslach Burnout Inventory-Human Services Survey for Medical Personnel.

Results: A total of 120 participants were randomized to receive either CBD, 300 mg, plus standard care (treatment arm; n = 61) or standard care alone (control arm; n = 59) for 28 days. Of those, 118 participants (59 participants in each arm; 79 women [66.9%]; mean age, 33.6 years [95% CI, 32.3-34.9 years]) received the intervention and were included in the efficacy analysis. In the treatment arm, scores on the emotional exhaustion subscale of the Maslach Burnout Inventory significantly decreased at day 14 (mean difference, 4.14 points; 95% CI, 1.47-6.80 points; partial eta squared [ηp2] = 0.08), day 21 (mean difference, 4.34 points; 95% CI, 0.94-7.73 points; ηp2 = 0.05), and day 28 (mean difference, 4.01 points; 95% CI, 0.43-7.59 points; ηp2 = 0.04). However, 5 participants, all of whom were in the treatment group, experienced serious adverse events: 4 cases of elevated liver enzymes (1 critical and 3 mild, with the mild elevations reported at the final 28-day assessment) and 1 case of severe pharmacodermia. In 2 of those cases (1 with critical elevation of liver enzymes and 1 with severe pharmacodermia), CBD therapy was discontinued, and the participants had a full recovery.

Conclusions and relevance: In this study, CBD therapy reduced symptoms of burnout and emotional exhaustion among health care professionals working with patients during the COVID-19 pandemic. However, it is necessary to balance the benefits of CBD therapy with potential undesired or adverse effects. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings.”

https://pubmed.ncbi.nlm.nih.gov/34387679/

“Daily administration of CBD, 300 mg, combined with standard care reduced the symptoms and diagnoses of anxiety, depression, and emotional exhaustion among frontline health care professionals working with patients with COVID-19. Cannabidiol may act as an effective agent for the reduction of burnout symptoms among a population with important mental health needs worldwide.”

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2782994

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Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders

biomolecules-logo“The potential therapeutic use of some Cannabis sativa plant compounds has been attracting great interest, especially for managing neuropsychiatric disorders due to the relative lack of efficacy of the current treatments.

Numerous studies have been carried out using the main phytocannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD displays an interesting pharmacological profile without the potential for becoming a drug of abuse, unlike THC.

In this review, we focused on the anxiolytic, antidepressant, and antipsychotic effects of CBD found in animal and human studies. In rodents, results suggest that the effects of CBD depend on the dose, the strain, the administration time course (acute vs. chronic), and the route of administration. In addition, certain key targets have been related with these CBD pharmacological actions, including cannabinoid receptors (CB1r and CB2r), 5-HT1A receptor and neurogenesis factors.

Preliminary clinical trials also support the efficacy of CBD as an anxiolytic, antipsychotic, and antidepressant, and more importantly, a positive risk-benefit profile. These promising results support the development of large-scale studies to further evaluate CBD as a potential new drug for the treatment of these psychiatric disorders.”

https://pubmed.ncbi.nlm.nih.gov/33228239/

https://www.mdpi.com/2218-273X/10/11/1575

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Molecular Targets of Cannabidiol in Experimental Models of Neurological Disease

molecules-logo“Cannabidiol (CBD) is a non-psychoactive phytocannabinoid known for its beneficial effects including antioxidant and anti-inflammatory properties. Moreover, CBD is a compound with antidepressant, anxiolytic, anticonvulsant and antipsychotic effects. Thanks to all these properties, the interest of the scientific community for it has grown.

Indeed, CBD is a great candidate for the management of neurological diseases. The purpose of our review is to summarize the in vitro and in vivo studies published in the last 15 years that describe the biochemical and molecular mechanisms underlying the effects of CBD and its therapeutic application in neurological diseases.

CBD exerts its neuroprotective effects through three G protein coupled-receptors (adenosine receptor subtype 2A, serotonin receptor subtype 1A and G protein-coupled receptor 55), one ligand-gated ion channel (transient receptor potential vanilloid channel-1) and one nuclear factor (peroxisome proliferator-activated receptor γ). Moreover, the therapeutical properties of CBD are also due to GABAergic modulation.

In conclusion, CBD, through multi-target mechanisms, represents a valid therapeutic tool for the management of epilepsy, Alzheimer’s disease, multiple sclerosis and Parkinson’s disease.”

https://pubmed.ncbi.nlm.nih.gov/33171772/

https://www.mdpi.com/1420-3049/25/21/5186

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The Effectiveness of Cannabis Flower for Immediate Relief From Symptoms of Depression

 Logo of yjbm“Scientific research on how consumption of whole, natural Cannabis flower affects low mood and behavioral motivations more generally is largely nonexistent, and few studies to date have measured how common and commercially available Cannabis flower used in vivo may affect the experience of “depression” in real-time.

Results: On average, 95.8% of users experienced symptom relief following consumption with an average symptom intensity reduction of -3.76 points on a 0-10 visual analogue scale (SD = 2.64, d = 1.71, p <.001). Symptom relief did not differ by labeled plant phenotypes (“C. indica,” “C. sativa,” or “hybrid”) or combustion method. Across cannabinoid levels, tetrahydrocannabinol (THC) levels were the strongest independent predictors of symptom relief, while cannabidiol (CBD) levels, instead, were generally unrelated to real-time changes in symptom intensity levels. Cannabis use was associated with some negative side effects that correspond to increased depression (e.g. feeling unmotivated) in up to 20% of users, as well as positive side effects that correspond to decreased depression (e.g. feeling happy, optimistic, peaceful, or relaxed) in up to 64% of users.

Conclusions: The findings suggest that, at least in the short term, the vast majority of patients that use cannabis experience antidepressant effects, although the magnitude of the effect and extent of side effect experiences vary with chemotypic properties of the plant.”

https://pubmed.ncbi.nlm.nih.gov/32607086/

“In conclusion, almost all patients in our sample experienced symptom relief from using Cannabis to treat depression and with minimal evidence of serious side effects in the short run.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309674/

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Can Physical Activity Support the Endocannabinoid System in the Preventive and Therapeutic Approach to Neurological Disorders?

ijms-logo“The worldwide prevalence of neurological and neurodegenerative disorders, such as depression or Alzheimer’s disease, has spread extensively throughout the last decades, becoming an enormous health issue.

Numerous data indicate a distinct correlation between the altered endocannabinoid signaling and different aspects of brain physiology, such as memory or neurogenesis. Moreover, the endocannabinoid system is widely regarded as a crucial factor in the development of neuropathologies. Thus, targeting those disorders via synthetic cannabinoids, as well as phytocannabinoids, becomes a widespread research issue.

Over the last decade, the endocannabinoid system has been extensively studied for its correlation with physical activity. Recent data showed that physical activity correlates with elevated endocannabinoid serum concentrations and increased cannabinoid receptor type 1 (CB1R) expression in the brain, which results in positive neurological effects including antidepressant effect, ameliorated memory, neuroplasticity development, and reduced neuroinflammation. However, none of the prior reviews presented a comprehensive correlation between physical activity, the endocannabinoid system, and neuropathologies.

Thus, our review provides a current state of knowledge of the endocannabinoid system, its action in physical activity, as well as neuropathologies and a possible correlation between all those fields. We believe that this might contribute to finding a new preventive and therapeutic approach to both neurological and neurodegenerative disorders.”

https://pubmed.ncbi.nlm.nih.gov/32545780/

https://www.mdpi.com/1422-0067/21/12/4221

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Effects of Chronic Cannabidiol Treatment in the Rat Chronic Unpredictable Mild Stress Model of Depression

biomolecules-logo“Several neuropharmacological actions of cannabidiol (CBD) due to the modulation of the endocannabinoid system as well as direct serotonergic and gamma-aminobutyric acidergic actions have recently been identified.

The current study aimed to reveal the effect of a long-term CBD treatment in the chronic unpredictable mild stress (CUMS) model of depression.

Adult male Wistar rats (n = 24) were exposed to various stressors on a daily basis in order to induce anhedonia and anxiety-like behaviors. CBD (10 mg/kg body weight) was administered by daily intraperitoneal injections for 28 days (n = 12). The effects of the treatment were assessed on body weight, sucrose preference, and exploratory and anxiety-related behavior in the open field (OF) and elevated plus maze (EPM) tests. Hair corticosterone was also assayed by liquid chromatography-mass spectrometry.

At the end of the experiment, CBD-treated rats showed a higher rate of body weight gain (5.94% vs. 0.67%) and sucrose preference compared to controls. A significant increase in vertical exploration and a trend of increase in distance traveled in the OF test were observed in the CBD-treated group compared to the vehicle-treated group. The EPM test did not reveal any differences between the groups. Hair corticosterone levels increased in the CBD-treated group, while they decreased in controls compared to baseline (+36.01% vs. -45.91%). In conclusion, CBD exerted a prohedonic effect in rats subjected to CUMS, demonstrated by the increased sucrose preference after three weeks of treatment.

The reversal of the effect of CUMS on hair corticosterone concentrations might also point toward an anxiolytic or antidepressant-like effect of CBD, but this needs further confirmation.”

https://pubmed.ncbi.nlm.nih.gov/32455953/

https://www.mdpi.com/2218-273X/10/5/801

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Two-weeks treatment with cannabidiol improves biophysical and behavioral deficits associated with experimental type-1 diabetes.

Neuroscience Letters“The prevalence rates of depression and anxiety are at least two times higher in diabetic patients, increasing morbidity and mortality.

Cannabidiol (CBD) has been identified as a therapeutic agent viable to treat diverse psychiatric disorders. Thus, this study aimed to investigate the effect of CBD treatment (once a day for 14 days starting two weeks after diabetes induction; at doses of 0, 3, 10 or 30 mg/kg, i.p.) on depression- and anxiety-like behaviors associated with experimental diabetes induced by streptozotocin (60 mg/kg; i.p.) in rats.

Levels of plasma insulin, blood glucose, and weight gain were evaluated in all experimental groups, including a positive control group treated with imipramine. The rats were tested in the modified forced swimming test (mFST) and elevated plus maze (EPM) test. Besides, the levels of serotonin (5-HT), noradrenaline (NA) and dopamine (DA) in two emotion-related brain regions, the prefrontal cortex (PFC) and hippocampus (HIP) were evaluated using high-pressure liquid chromatography.

Our results showed that CBD treatment (only at the higher dose of 30 mg/kg) reduced the exaggerated depressive- and anxiogenic-like behaviors of diabetic (DBT) rats, which may be associated with altered 5-HT, NA and/or DA levels observed in the PFC and HIP. Treatment with CBD (higher dose) also induced a significant increase in weight gain and the insulin levels (and consequently reduced glycemia) in DBT rats. The long-term CBD effects gave rise to novel therapeutic strategies to limit the physiological and neurobehavioral deficits in DBT rats.

This approach provided evidence that CBD can be useful for treating psychiatry comorbidities in diabetic patients.”

https://www.ncbi.nlm.nih.gov/pubmed/32360935

“Treatment of diabetic rats with cannabidiol induced antidepressant- and anxiolytic-like behaviors.”

https://www.sciencedirect.com/science/article/abs/pii/S0304394020302901?via%3Dihub

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CBD modulates DNA methylation in mice prefrontal cortex and hippocampus of mice exposed to forced swim.

Behavioural Brain Research“Cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa plant, shows therapeutic potential in psychiatric disorders, including depression.

The molecular mechanisms underlying the antidepressant-like effects of CBD are not yet understood. Previous studies in differentiated skin cells demonstrated that CBD regulates DNA methylation, an overall repressive epigenetic mechanism. Both stress exposure and antidepressant treatment can modulate DNA methylation in the brain, and lead to gene expression changes associated with depression neurobiology.

We investigated herein if the antidepressant effect of CBD could be associated with changes in DNA methylation in the prefrontal cortex (PFC) and hippocampus (HPC) of mice submitted to the forced swimming test (FST).

Altogether, our results indicate that CBD regulates DNA methylation in brain regions relevant for depression neurobiology, suggesting that this mechanism could be related to CBD-induced antidepressant effects.”

https://www.ncbi.nlm.nih.gov/pubmed/32348868

“Cannabidiol (CBD) shows antidepressant-like properties in mice.”

https://www.sciencedirect.com/science/article/pii/S0166432820303260?via%3Dihub

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Decreased sensitivity in adolescent versus adult rats to the antidepressant-like effects of cannabidiol.

SpringerLink“Cannabidiol is a non-psychoactive phytocannabinoid with great therapeutic potential in diverse psychiatric disorders; however, its antidepressant potential has been mainly ascertained in adult rats.

OBJECTIVES:

To compare the antidepressant-like response induced by cannabidiol in adolescent and adult rats and the possible parallel modulation of hippocampal neurogenesis.

RESULTS:

Cannabidiol induced differential effects depending on the age and dose administered, with a decreased sensitivity observed in adolescent rats: (1) cannabidiol (30 mg/kg) decreased body weight only in adult rats; (2) cannabidiol ameliorated behavioral despair in adolescent and adult rats, but with a different dose sensitivity (10 vs. 30 mg/kg), and with a different extent (2 vs. 21 days post-treatment); (3) cannabidiol did not modulate anxiety-like behavior at any dose tested in adolescent or adult rats; and (4) cannabidiol increased sucrose intake in adult rats.

CONCLUSIONS:

Our findings support the notion that cannabidiol exerts antidepressant- and anorexigenic-like effects in adult rats and demonstrate a decreased potential when administered in adolescent rats. Moreover, since cannabidiol did not modulate hippocampal neurogenesis (cell proliferation and early neuronal survival) in adolescent or adult rats, the results revealed potential antidepressant-like effects induced by cannabidiol without the need of regulating hippocampal neurogenesis.”

https://www.ncbi.nlm.nih.gov/pubmed/32086540

https://link.springer.com/article/10.1007%2Fs00213-020-05481-4

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