Category Archives: Depression

Rapid treatments for depression: Endocannabinoid system as a therapeutic target

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“Current first-line treatments for major depressive disorder (MDD), i.e., antidepressant drugs and psychotherapy, show delayed onset of therapeutic effect as late as 2-3 weeks or more. In the clinic, the speed of beginning of the actions of antidepressant drugs or other interventions is vital for many reasons. Late-onset means that depression, its related disability, and the potential danger of suicide remain a threat for some patients. There are some rapid-acting antidepressant interventions, such as sleep deprivation, ketamine, acute exercise, which induce a significant response, ranging from a few hours to maximally one week, and most of them share a common characteristic that is the activation of the endocannabinoid (eCB) system. Activation of this system, i.e., augmentation of eCB signaling, appears to have anti-depressant-like actions. This article puts the idea forward that the activation of eCB signaling represents a critical mechanism of rapid-acting therapeutic interventions in MDD, and this system might contribute to the development of novel rapid-acting treatments for MDD.”

https://pubmed.ncbi.nlm.nih.gov/35351488/

Cannabidiol prevents depressive-like behaviors through the modulation of neural stem cell differentiation

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“Chronic stress impairs radial neural stem cell (rNSC) differentiation and adult hippocampal neurogenesis (AHN), whereas promoting AHN can increase stress resilience against depression. Therefore, investigating the mechanism of neural differentiation and AHN is of great importance for developing antidepressant drugs. The nonpsychoactive phytocannabinoid cannabidiol (CBD) has been shown to be effective against depression. However, whether CBD can modulate rNSC differentiation and hippocampal neurogenesis is unknown. Here, by using the chronic restraint stress (CRS) mouse model, we showed that hippocampal rNSCs mostly differentiated into astrocytes under stress conditions. Moreover, transcriptome analysis revealed that the FoxO signaling pathway was involved in the regulation of this process. The administration of CBD rescued depressive-like symptoms in CRS mice and prevented rNSCs overactivation and differentiation into astrocyte, which was partly mediated by the modulation of the FoxO signaling pathway. These results revealed a previously unknown neural mechanism for neural differentiation and AHN in depression and provided mechanistic insights into the antidepressive effects of CBD.”

https://pubmed.ncbi.nlm.nih.gov/35212887/

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

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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

“Johns Hopkins: New Study Backs Claims That Cannabis Can Reduce Anxiety And Depression”  https://finance.yahoo.com/news/johns-hopkins-study-backs-claims-145005658.html

“Report Shows Cannabis is Effective in Treating Anxiety, Depression”   https://www.legalreader.com/report-shows-cannabis-is-effective-in-treating-anxiety-depression/

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

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ijms-logo“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.

In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.

The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.

The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.

This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”

https://pubmed.ncbi.nlm.nih.gov/34502379/

https://www.mdpi.com/1422-0067/22/17/9472

 

“Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830475/

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

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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

Anti-depressant effects of ethanol extract from Cannabis sativa (hemp) seed in chlorpromazine-induced Drosophila melanogaster depression model

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Publication Cover“Context: Depression is a severe mental illness caused by a deficiency of dopamine and serotonin. Cannabis sativa L. (Cannabaceae) has long been used to treat pain, nausea, and depression.

Objective: This study investigates the anti-depressant effects of C. sativa (hemp) seed ethanol extract (HE) in chlorpromazine (CPZ)-induced Drosophila melanogaster depression model.

Results: The behavioural patterns of individual flies were significantly reduced with 0.1% CPZ treatment. In contrast, combination treatment of 1.5% HE and 0.1% CPZ significantly increased subjective daytime activity (p < 0.001) and behavioural factors (p < 0.001). These results correlate with increased transcript levels of dopamine (p < 0.001) and serotonin (p < 0.05) receptors and concentration of dopamine (p < 0.05), levodopa (p < 0.001), 5-HTP (p < 0.05), and serotonin (p < 0.001) compared to those in the control group.

Discussion and conclusions: Collectively, HE administration alleviates depression-like symptoms by modulating the circadian rhythm-related behaviours, transcript levels of neurotransmitter receptors, and neurotransmitter levels in the CPZ-induced Drosophila model. However, additional research is needed to investigate the role of HE administration in behavioural patterns, reduction of the neurotransmitter, and signalling pathways of depression in a vertebrate model system.”

https://pubmed.ncbi.nlm.nih.gov/34362287/

“CPZ induces depression-like symptoms, such as changes in behavioural patterns, transcription levels of neurotransmitter receptors, and depression-related neurotransmitter levels in the D. melanogaster depression model. However, administration of HE restores the circadian rhythms, improves locomotor activity, and significantly increases transcription levels of dopamine and serotonin receptors in the depression-induced flies. Based on these findings, we can conclude that HE alleviates depression-like symptoms by increasing the levels of serotonin and dopamine receptors and dopamine, L-DOPA, 5-HTP, and serotonin levels in the brain.”

https://www.tandfonline.com/doi/full/10.1080/13880209.2021.1949356

The effectiveness of inhaled Cannabis flower for the treatment of agitation/irritability, anxiety, and common stress

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Cognetivity publishes MS paper in BMC Neurology Journal - Cognetivity Neurosciences

“Background: An observational research design was used to evaluate which types of commonly labeled Cannabis flower product characteristics are associated with changes in momentary feelings of distress-related symptoms.

Results: In total, a decrease in symptom intensity levels was reported in 95.51% of Cannabis usage sessions, an increase in 2.32% of sessions, and no change in 2.16% of sessions. Fixed effects models showed, on average, respondents recorded a maximum symptom intensity reduction of 4.33 points for agitation/irritability (SE = 0.20, p < 0.01), 3.47 points for anxiety (SE = 0.13, p < 0.01), and 3.98 for stress (SE = 0.12, p < 0.01) on an 11-point visual analog scale. Fixed effects regressions showed that, controlling for time-invariant user characteristics, mid and high tetrahydrocannabinol (THC) levels were the primary independent predictor of increased symptom relief, and that when broken out by symptom type, this effect was only statistically significant for our largest sample of users, those reporting anxiety rather than agitation/irritability or stress. Cannabidiol (CBD) levels were generally not associated with changes in symptom intensity levels. In a minority of cannabis use sessions (< 13%), cannabis users reported anxiogenic-related negative side effects (e.g., feeling anxious, irritable, paranoid, rapid pulse, or restless), whereas in a majority of sessions (about 66%), users reported positive anxiolytic side effects (e.g., feeling chill, comfy, happy, optimistic, peaceful, or relaxed).

Conclusions: The findings suggest the majority of patients in our sample experienced relief from distress-related symptoms following consumption of Cannabis flower, and that among product characteristics, higher THC levels were the strongest predictors of relief.”

https://pubmed.ncbi.nlm.nih.gov/33526145/

“Our findings suggest that self-directed use of Cannabis flower, especially that with higher THC levels, is associated with significant improvements in at least short-term feelings of distress in many users, likely a contributing factor to its widespread popularity and consumption in the U.S.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-00051-z

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

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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

Treatment of social anxiety disorder and attenuated psychotic symptoms with cannabidiol

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See the source image “Anxiety disorders in young people are frequently comorbid with other mental disorders and respond unsatisfactorily to first-line treatment in many cases.

Here, we report the case of a 20-year-old man with severe social anxiety disorder, major depressive disorder, insomnia and attenuated psychotic symptoms despite ongoing treatment with cognitive behavioural therapy and mirtazapine who was treated with adjunctive cannabidiol (CBD) in doses between 200 and 800 mg/day for 6 months.

During treatment with CBD, he experienced subjective benefits to his anxiety, depression and positive symptoms during treatment that were confirmed by clinicians and by standardised research instruments.

Findings from this case study add to existing evidence in support of the safety of CBD and suggest that it may be useful for young people with treatment refractory anxiety and for attenuated psychotic symptoms.”

https://pubmed.ncbi.nlm.nih.gov/33028567/

https://casereports.bmj.com/content/13/10/e235307

Cannabis: An Emerging Treatment for Common Symptoms in Older Adults

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Journal of the American Geriatrics Society “Background/objectives: Use of cannabis is increasing in a variety of populations in the United States; however, few investigations about how and for what reasons cannabis is used in older populations exist.

Design: Anonymous survey.

Setting: Geriatrics clinic.

Participants: A total of 568 adults 65 years and older.

Intervention: Not applicable.

Measurements: Survey assessing characteristics of cannabis use.

Results: Approximately 15% (N = 83) of survey responders reported using cannabis within the past 3 years. Half (53%) reported using cannabis regularly on a daily or weekly basis, and reported using cannabidiol-only products (46%).

The majority (78%) used cannabis for medical purposes only, with the most common targeted conditions/symptoms being pain/arthritis (73%), sleep disturbance (29%), anxiety (24%), and depression (17%). Just over three-quarters reported cannabis “somewhat” or “extremely” helpful in managing one of these conditions, with few adverse effects.

Just over half obtained cannabis via a dispensary, and lotions (35%), tinctures (35%), and smoking (30%) were the most common administration forms. Most indicated family members (94%) knew about their cannabis use, about half reported their friends knew, and 41% reported their healthcare provider knowing. Sixty-one percent used cannabis for the first time as older adults (aged ≥61 years), and these users overall engaged in less risky use patterns (e.g., more likely to use for medical purposes, less likely to consume via smoking).

Conclusion: Most older adults in the sample initiated cannabis use after the age of 60 years and used it primarily for medical purposes to treat pain, sleep disturbance, anxiety, and/or depression. Cannabis use by older adults is likely to increase due to medical need, favorable legalization, and attitudes.”

https://pubmed.ncbi.nlm.nih.gov/33026117/

https://onlinelibrary.wiley.com/doi/10.1111/jgs.16833

“Study Finds Older Adults Using Cannabis to Treat Common Health Conditions”  https://health.ucsd.edu/news/releases/Pages/2020-10-07-study-finds-older-adults-using-cannabis-to-treat-common-health-conditions.aspx