Broad-spectrum cannabis oil ameliorates reserpine-induced fibromyalgia model in mice

Biomedicine & Pharmacotherapy

“Fibromyalgia (FM) is an idiopathic disorder characterized by generalized pain and associated symptoms such as depression and anxiety.

Cannabis sativa shows different pharmacological activities, such as analgesic, anti-inflammatory, neuroprotective, and immunomodulatory. Associated with this, the use of an oil with low concentrations of THC can reduce the psychomimetic adverse effects of the plant. Therefore, the present study aimed to evaluate the analgesic effect of broad-spectrum cannabis oil with low THC concentration in an experimental model of FM.

Mechanical hyperalgesia, thermal allodynia, depressive- and anxious-related behavior, and locomotor activity were evaluated after reserpine (0.25 mg/kg; injected subcutaneously (s.c.) once daily for three consecutive days) administration.

Our results showed that oral administration of broad-spectrum cannabis oil (0.1, 1, and 3 mg/kg, p.o.) in a single dose on the 4th day inhibited mechanical hyperalgesia and thermal allodynia induced by reserpine. Relevantly, treatment during four days with broad-spectrum cannabis oil (0.1 mg/kg, p.o.) reduced mechanical hyperalgesia 1 h after reserpine administration.

Intraplantar treatment with cannabis oil significantly reversed mechanical and heat thermal nociception induced by reserpine injection. Interestingly, spinal and supraspinal administration of broad-spectrum cannabis oil completely inhibited mechanical hyperalgesia and thermal sensitivity induced by reserpine. The repeated cannabis oil administration, given daily for 14 days, markedly mitigated the mechanical and thermal sensitivity during the FM model, and its reduced depressive-like behavior induced by reserpine.

In summary, broad-spectrum cannabis oil is an effective alternative to reverse the reserpine-induced fibromyalgia model.”

“In the present study, it was possible to observe that, regardless of the route of administration, broad-spectrum cannabis oil proved to be effective in reversing the mechanical hyperalgesia effects of the reserpine-induced fibromyalgia model. Furthermore, chronic treatment with broad-spectrum cannabis oil showed analgesic effects on mechanical hyperalgesia and heat allodynia and mitigated reserpine-induced passive stress-coping behavior and lower-self-care behavior in mice. Conjointly, our results point to broad-spectrum cannabis oil as a therapeutic alternative for the disorders caused by FM.”

Dose-Dependent Antidepressant-Like Effects of Cannabidiol in Aged Rats

Frontiers - Crunchbase Company Profile & Funding

“Aging predisposes to late-life depression and since antidepressants are known to change their efficacy with age, novel treatment options are needed for our increased aged population. In this context, the goal of the present study was to evaluate the potential antidepressant-like effect of cannabidiol in aged rats.

For this purpose, 19-21-month-old Sprague-Dawley rats were treated for 7 days with cannabidiol (dose range: 3-30 mg/kg) and scored under the stress of the forced-swim test. Hippocampal cannabinoid receptors and cell proliferation were evaluated as potential molecular markers underlying cannabidiol’s actions.

The main results of the present study demonstrated that cannabidiol exerted a dose-dependent antidepressant-like effect in aged rats (U-shaped, effective at the intermediate dose of 10 mg/kg as compared to the other doses tested), without affecting body weight. None of the molecular markers analyzed in the hippocampus were altered by cannabidiol’s treatment.

Overall, this study demonstrated a dose-dependent antidepressant-like response for cannabidiol at this age-window (aged rats up to 21 months old) and in line with other studies suggesting a beneficial role for this drug in age-related behavioral deficits.”

“In conclusion, this study increased the age-window at which cannabidiol exerted dose-dependent responses in this behavioral test, to include aged rats (up to 21 months old), at which it could be considered as a potential antidepressant, and in line with other studies suggesting a beneficial role for this drug in age-related behavioral deficits.”

Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions


“Combination tetrahydrocannabinol (THC)/cannabidiol (CBD) medicines or CBD-only medicines are prospective treatments for chronic pain, stress, anxiety, depression, and insomnia. THC and CBD increase signaling from cannabinoid receptors, which reduces synaptic transmission in parts of the central and peripheral nervous systems and reduces the secretion of inflammatory factors from immune and glial cells.

The overall effect of adding CBD to THC medicines is to enhance the analgesic effect but counteract some of the adverse effects. There is substantial evidence for the effectiveness of THC/CBD combination medicines for chronic pain, especially neuropathic and nociplastic pain or pain with an inflammatory component. For CBD-only medication, there is substantial evidence for stress, moderate evidence for anxiety and insomnia, and minimal evidence for depression and pain.

THC/CBD combination medicines have a good tolerability and safety profile relative to opioid analgesics and have negligible dependence and abuse potential; however, should be avoided in patients predisposed to depression, psychosis and suicide as these conditions appear to be exacerbated. Non-serious adverse events are usually dose-proportional, subject to tachyphylaxis and are rarely dose limiting when patients are commenced on a low dose with gradual up-titration. THC and CBD inhibit several Phase I and II metabolism enzymes, which increases the exposure to a wide range of drugs and appropriate care needs to be taken. Low-dose CBD that appears effective for chronic pain and mental health has good tolerability and safety, with few adverse effects and is appropriate as an initial treatment.”

“Tetrahydrocannabinol (THC) and cannabidiol (CBD) combination medicines and CBD-only medicines are prospective new treatments for chronic pain, stress, anxiety, depression, and insomnia, which are all medical conditions in need of better therapeutics. Both THC/CBD combination and CBD-only medicines could provide effective new treatment options for pain and mental health, respectively, and both have good safety and tolerability profiles relative to the current treatments.

THC and CBD combination medicines have a good safety and tolerability profile that is appropriate for opioid stage (stage 2–3) treatment of chronic pain. Low-dose CBD could be used as an initial treatment for chronic pain and for stress, anxiety, depression, and insomnia. High quality efficacy evidence is best for THC/CBD combination medicines for chronic pain and CBD-only medicines for stress and anxiety. “

Cannabis: Chemistry, extraction and therapeutic applications


“Cannabis, a genus of perennial indigenous plants is well known for its recreational and medicinal activities. Cannabis and its derivatives have potential therapeutic activities to treat epilepsy, anxiety, depression, tumors, cancer, Alzheimer’s disease, Parkinson’s disease, to name a few.

This article reviews some recent literature on the bioactive constituents of Cannabis, commonly known as phytocannabinoids, their interactions with the different cannabinoids and non-cannabinoid receptors as well as the significances of these interactions in treating various diseases and syndromes.

The biochemistry of some notable cannabinoids such as tetrahydrocannabinol, cannabidiol, cannabinol, cannabigerol, cannabichromene and their carboxylic acid derivatives is explained in the context of therapeutic activities.

The medicinal features of Cannabis-derived terpenes are elucidated for treating several neuro and non-neuro disorders. Different extraction techniques to recover cannabinoids are systematically discussed. Besides the medicinal activities, the traditional and recreational utilities of Cannabis and its derivatives are presented. A brief note on the legalization of Cannabis-derived products is provided.

This review provides comprehensive knowledge about the medicinal properties, recreational usage, extraction techniques, legalization and some prospects of cannabinoids and terpenes extracted from Cannabis.”

“Cannabinoids have therapeutic effects against various health disorders.•

Medicinal effects are due to the interactions of cannabinoids with bio-receptors.•

Cannabinoids can be extracted from Cannabis plant products by eco-friendly extraction methods.”

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The antidepressant and anxiolytic effects of cannabinoids in chronic unpredictable stress: a preclinical systematic review and meta-analysis

Translational Psychiatry

“Neuroscience research presents contradictory evidence in support of both the protective and destructive effects of cannabinoids in depression. Therefore, this systematic review and meta-analysis summarizes the existing preclinical literature on the effects of cannabinoid administration in the chronic unpredictable stress model of depression in order to evaluate the effects of cannabinoids and identify gaps in the literature. After protocol registration (PROSPERO #CRD42020219986), we systematically searched Scopus, Embase, Psychology & Behavioral Sciences Collection, APA PsychINFO, PubMed, CINAHL Complete, and ProQuest Dissertations & Theses Global from the earliest record of the databases, February 1964, to November 2020 for articles that met inclusion criteria (e.g., rodent subjects and administration of a cannabinoid. A total of 26 articles were included representing a sample size estimate of 1132 rodents with the majority of articles administering daily intraperitoneal injections during chronic unpredictable stress. These articles were evaluated using a modified SYRCLE’s risk-of-bias tool. For each continuous behavioral measure, the standardized mean difference was calculated between cannabinoid and vehicle groups in rodents subjected to chronic unpredictable stress. The effects of cannabinoids on depressive-like behavior was evaluated using a multilevel mixed-effects model with effect size weights nested within control groups. Cannabinoid administration moderately improved the pooled negative effects of chronic unpredictable stress on anhedonia, learned helplessness, novelty suppressed feeding, time in the anxiogenic context, and entries into the anxiogenic context. Although the interpretations are limited, these findings suggest that with further investigation, cannabinoids may be a viable long-term treatment for stress-related psychopathologies such as depression.”

Modulation of Endocannabinoid System Components in Depression: Pre-Clinical and Clinical Evidence


“Depression is characterized by continuous low mood and loss of interest or pleasure in enjoyable activities. First-line medications for mood disorders mostly target the monoaminergic system; however, many patients do not find relief with these medications, and those who do suffer from negative side effects and a discouragingly low rate of remission.

Studies suggest that the endocannabinoid system (ECS) may be involved in the etiology of depression and that targeting the ECS has the potential to alleviate depression.

ECS components (such as receptors, endocannabinoid ligands, and degrading enzymes) are key neuromodulators in motivation and cognition as well as in the regulation of stress and emotions. Studies in depressed patients and in animal models for depression have reported deficits in ECS components, which is motivating researchers to identify potential diagnostic and therapeutic biomarkers within the ECS. By understanding the effects of cannabinoids on ECS components in depression, we enhance our understanding of which brain targets they hit, what biological processes they alter, and eventually how to use this information to design better therapeutic options.

In this article, we discuss the literature on the effects of cannabinoids on ECS components of specific depression-like behaviors and phenotypes in rodents and then describe the findings in depressed patients. A better understanding of the effects of cannabinoids on ECS components in depression may direct future research efforts to enhance diagnosis and treatment.”

Medical cannabis use in Canada and its impact on anxiety and depression: A retrospective study

Psychiatry Research

“This was a retrospective study of patients utilizing medical cannabis who received their medical cannabis documentation and allotment from a Harvest Medicine clinic in Canada to determine the impact of medical cannabis on anxiety and depression outcomes. Patients included in the study were at least 18 years of age with completed validated questionnaires for anxiety (GAD-7) and depression (PHQ-9) at their initial evaluation and at least one follow-up visit. There were 7,362 patients included in the sample, of which the average age was 49.8 years, and 53.1% were female.

There were statistically significant improvements between baseline and follow-up scores for both the GAD-7 and PHQ-9, with larger improvements seen for patients who were actively seeking medical cannabis to treat anxiety or depression. From 12 months on, those reporting anxiety had an average decrease in GAD-7 scores that was greater than the minimum clinically important difference of 4, and the same was seen for patients reporting depression from 18 months on, with the average decrease in PHQ-9 scores more than the MCID minimum clinically important difference of 5. This study provides some evidence to support the effectiveness of medical cannabis as a treatment for anxiety and depression.”

Role and Function of Endocannabinoid System in Major Depressive Disease

“The endocannabinoid system (ECS) is a neuromodulator system with a crucial role in CNS and the reaction to endogenous and exogenous compounds and inflammation. Cannabidiol (CBD) is a basic part of the ECS which is the overwhelming causative and/or protective factor of major depressive disease (MDD). CBD interacts with brain-derived neurotropic factor (BDNF) that responds to inflammation, dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis, and many more imbalances in MDD patients for which the ECS is a vital part to analyze, diagnose, and reflect the treatment. The ECS and MDD appear to have strong connections and interactions, so interest in ECS and CBD use in MDD patients is developing as a rescue resort.”

An investigation of cannabis use for insomnia in depression and anxiety in a naturalistic sample

“Background: Little is known about cannabis use for insomnia in individuals with depression, anxiety, and comorbid depression and anxiety. To develop a better understanding of distinct profiles of cannabis use for insomnia management, a retrospective cohort study was conducted on a large naturalistic sample.

Methods: Data were collected using the medicinal cannabis tracking app, Strainprint®, which allows users to monitor and track cannabis use for therapeutic purposes. The current study examined users managing insomnia symptoms in depression (n = 100), anxiety (n = 463), and comorbid depression and anxiety (n = 114), for a total of 8476 recorded sessions. Inferential analyses used linear mixed effects modeling to examine self-perceived improvement across demographic variables and cannabis product variables.

Results: Overall, cannabis was perceived to be efficacious across all groups, regardless of age and gender. Dried flower and oral oil were reported as the most used and most efficacious product forms. In the depression group, all strains were perceived to be efficacious and comparisons between strains revealed indica-dominant (Mdiff = 1.81, 95% CI 1.26-2.36, Padj < .001), indica hybrid (Mdiff = 1.34, 95% CI 0.46-2.22, Padj = .045), and sativa-dominant (Mdiff = 1.83, 95% CI 0.68-2.99, Padj = .028) strains were significantly more efficacious than CBD-dominant strains. In anxiety and comorbid conditions, all strain categories were perceived to be efficacious with no significant differences between strains.

Conclusions: In terms of perceptions, individuals with depression, anxiety, and both conditions who use cannabis for insomnia report significant improvements in symptom severity after cannabis use. The current study highlights the need for placebo-controlled trials investigating symptom improvement and the safety of cannabinoids for sleep in individuals with mood and anxiety disorders.”

Rapid treatments for depression: Endocannabinoid system as a therapeutic target

“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.”