Category Archives: Anxiety

Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test.

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SciELO - Scientific Electronic Library Online

“Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans.

The objective of this study was to compare the acute effects of different doses of CBD and placebo in healthy volunteers performing a simulated public speaking test (SPST), a well-tested anxiety-inducing method.

Our findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.”

https://www.europeanneuropsychopharmacology.com/article/S0924-977X(16)31702-3/abstract

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462018005007102&lng=en&tlng=en

Cannabidiol regulates the expression of hypothalamus-pituitary-adrenal axis-related genes in response to acute restraint stress.

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SAGE Journals

“Research interest has grown around the potential therapeutic use of cannabidiol in mood-related disorders, due to its anxiolytic and antidepressant-like effects.

These have been partially attributed to its action as an allosteric modulator of 5-HTR1A. However, the exact mechanism supporting cannabidiol properties remains unclear.

Taken together, these data suggest the ability of cannabidiol to regulate acute stress hypothalamus-pituitary-adrenal axis activation might be explained, at least in part, by its action on 5-HTR1A receptors.”

https://www.ncbi.nlm.nih.gov/pubmed/30324842

http://journals.sagepub.com/doi/abs/10.1177/0269881118805495?journalCode=jopa

Translational Investigation of the Therapeutic Potential of Cannabidiol (CBD): Toward a New Age.

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“Among the many cannabinoids in the cannabis plant, cannabidiol (CBD) is a compound that does not produce the typical subjective effects of marijuana.

The aim of the present review is to describe the main advances in the development of the experimental and clinical use of cannabidiol CBD in neuropsychiatry.

CBD was shown to have anxiolytic, antipsychotic and neuroprotective properties. In addition, basic and clinical investigations on the effects of CBD have been carried out in the context of many other health conditions, including its potential use in epilepsy, substance abuse and dependence, schizophrenia, social phobia, post-traumatic stress, depression, bipolar disorder, sleep disorders, and Parkinson.

CBD is an useful and promising molecule that may help patients with a number of clinical conditions. Controlled clinical trials with different neuropsychiatric populations that are currently under investigation should bring important answers in the near future and support the translation of research findings to clinical settings.”

https://www.ncbi.nlm.nih.gov/pubmed/30298064

https://www.frontiersin.org/articles/10.3389/fimmu.2018.02009/full

A systematic review on the neuroprotective perspectives of beta-caryophyllene.

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“Beta (β)-caryophyllene (BCAR) is a major sesquiterpene of various plant essential oils reported for several important pharmacological activities, including antioxidant, anti-inflammatory, anticancer, cardioprotective, hepatoprotective, gastroprotective, nephroprotective, antimicrobial, and immune-modulatory activity. Recent studies suggest that it also possesses neuroprotective effect.

This study reviews published reports pertaining to the neuropharmacological activities of BCAR. Databases such as PubMed, Scopus, MedLine Plus, and Google Scholar with keywords “beta (β)-caryophyllene” and other neurological keywords were searched. Data were extracted by referring to articles with information about the dose or concentration/route of administration, test system, results and discussion, and proposed mechanism of action.

A total of 545 research articles were recorded, and 41 experimental studies were included in this review, after application of exclusion criterion. Search results suggest that BCAR exhibits a protective role in a number of nervous system-related disorders including pain, anxiety, spasm, convulsion, depression, alcoholism, and Alzheimer’s disease.

Additionally, BCAR has local anesthetic-like activity, which could protect the nervous system from oxidative stress and inflammation and can act as an immunomodulatory agent. Most neurological activities of this natural product have been linked with the cannabinoid receptors (CBRs), especially the CB2R. This review suggests a possible application of BCAR as a neuroprotective agent.”

https://www.ncbi.nlm.nih.gov/pubmed/30281175

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934

New Perspectives on the Use of Cannabis in the Treatment of Psychiatric Disorders.

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“Following the discovery of the endocannabinoid system and its potential as a therapeutic target for various pathological conditions, growing interest led researchers to investigate the role of cannabis and its derivatives for medical purposes. The compounds Δ9-tetrahydrocannabinol and cannabidiol are the most abundant phytocannabinoids found in cannabis extracts, as well as the most studied. The present review aims to provide an overview of the current evidence for their beneficial effects in treating psychiatric disorders, including schizophrenia, anxiety, and depression. Nevertheless, further investigations are required to clarify many pending issues, especially those relative to the assessment of benefits and risks when using cannabis for therapeutic purposes, thereby also helping national and federal jurisdictions to remain updated.”

https://www.ncbi.nlm.nih.gov/pubmed/30279403

https://www.mdpi.com/2305-6320/5/4/107

Cannabidiol modulates serotonergic transmission and prevents allodynia and anxiety-like behavior in a model of neuropathic pain.

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“Clinical studies indicate that cannabidiol (CBD), the primary non-addictive component of cannabis that interacts with the serotonin (5-HT) 1A receptor, may possess analgesic and anxiolytic effects. However, its effects on 5-HT neuronal activity, as well as its impact in models of neuropathic pain are unknown.

Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity. Anti-allodynic effects of CBD were fully prevented by capsazepine (10 mg/kg/day, s.c., for 7 days) and partially prevented by WAY 100635 (2 mg/kg/day, s.c., for 7 days), while the anxiolytic effect was blocked only by WAY.

Overall, repeated treatment with low-dose CBD induces analgesia predominantly via TRPV1 activation, reduces anxiety via 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/30157131

https://insights.ovid.com/crossref?an=00006396-900000000-98870

“Cannabis pain relief without the ‘high’. Canadian researchers pinpoint the mechanism of cannabidiol for safe pain relief without side effects”  https://eurekalert.org/pub_releases/2018-10/muhc-cpr102418.php

“Effective dose of cannabidiol for safe pain relief without the typical ‘high'”  https://www.news-medical.net/news/20181025/Effective-dose-of-cannabidiol-for-safe-pain-relief-without-the-typical-high.aspx

Patient-Reported Symptom Relief Following Medical Cannabis Consumption

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“The Releaf AppTM mobile software application (app) data was used to measure self-reported effectiveness and side effects of medical cannabis used under naturalistic conditions.

Results: Releaf AppTM responders used cannabis to treat myriad health symptoms, the most frequent relating to pain, anxiety, and depressive conditions. Significant symptom severity reductions were reported for all the symptom categories, with mean reductions between 2.8 and 4.6 points (ds ranged from 1.29–2.39, ps < 0.001). On average, higher pre-dosing symptom levels were associated with greater reported symptom relief, and users treating anxiety or depression-related symptoms reported significantly more relief (ps < 0.001) than users with pain symptoms. Of the 42 possible side effects, users were more likely to indicate and showed a stronger correlation between symptom relief and experiences of positive (94% of sessions) or a context-specific side effects (76%), whereas negative side effects (60%) were associated with lessened, yet still significant symptom relief and were more common among patients treating a depressive symptom relative to patients treating anxiety and pain-related conditions.

Conclusion: Patient-managed cannabis use is associated with clinically significant improvements in self-reported symptom relief for treating a wide range of health conditions, along with frequent positive and negative side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/30210337

https://www.frontiersin.org/articles/10.3389/fphar.2018.00916/full

The endocannabinoid system in mental disorders: Evidence from human brain studies.

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Biochemical Pharmacology

“Mental disorders have a high prevalence compared with many other health conditions and are the leading cause of disability worldwide. Several studies performed in the last years support the involvement of the endocannabinoid system in the etiopathogenesis of different mental disorders.

The present review will summarize the latest information on the role of the endocannabinoid system in psychiatric disorders, specifically depression, anxiety, and schizophrenia. We will focus on the findings from human brain studies regarding alterations in endocannabinoid levels, cannabinoid receptors and endocannabinoid metabolizing enzymes in patients suffering mental disorders.

Studies carried out in humans have consistently demonstrated that the endocannabinoid system is fundamental for emotional homeostasis and cognitive function. Thus, deregulation of the different elements that are part of the endocannabinoid system may contribute to the pathophysiology of several mental disorders. However, the results reported are controversial. In this sense, different alterations in gene and/or protein expression of CB1 receptors have been shown depending on the technical approach used or the brain region studied.

Despite the current discrepancies regarding cannabinoid receptors changes in depression and schizophrenia, present findings point to the endocannabinoid system as a pivotal neuromodulatory pathway relevant in the pathophysiology of mental disorders.

https://www.ncbi.nlm.nih.gov/pubmed/30026022
https://www.sciencedirect.com/science/article/abs/pii/S0006295218302776

A Cross-Sectional Study of Cannabidiol Users.

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Cannabis and Cannabinoid Research cover image

“Introduction: Preclinical and clinical studies suggest that cannabidiol (CBD) found in Cannabis spp. has broad therapeutic value. CBD products can currently be purchased online, over the counter and at Cannabis-specific dispensaries throughout most of the country, despite the fact that CBD is generally deemed a Schedule I controlled substance by the U.S. Drug Enforcement Administration and renounced as a dietary supplement ingredient by the U.S. Food and Drug Administration. Consumer demand for CBD is high and growing, but few studies have examined the reasons for increasing CBD use.

Results: Almost 62% of CBD users reported using CBD to treat a medical condition. The top three medical conditions were pain, anxiety, and depression. Almost 36% of respondents reported that CBD treats their medical condition(s) “very well by itself,” while only 4.3% reported “not very well.” One out of every three users reported a nonserious adverse effect. The odds of using CBD to treat a medical condition were 1.44 (95% confidence interval, 1.16-1.79) times greater among nonregular users of Cannabis than among regular users.

Conclusion: Consumers are using CBD as a specific therapy for multiple diverse medical conditions-particularly pain, anxiety, depression, and sleep disorders. These data provide a compelling rationale for further research to better understand the therapeutic potential of CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/30014038
https://www.liebertpub.com/doi/10.1089/can.2018.0006

Integrating endocannabinoid signaling in the regulation of anxiety and depression

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“Brain endogenous cannabinoid (eCB) signaling seems to harmonize appropriate behavioral responses, which are essential for the organism’s long-term viability and homeostasis. Dysregulation of eCB signaling contributes to negative emotional states and increased stress responses. An understanding of the underlying neural cell populations and neural circuit regulation will enable the development of therapeutic strategies to mitigate behavioral maladaptation and provide insight into the influence of eCB on the neural circuits involved in anxiety and depression. This review focuses on recent evidence that has added a new layer of complexity to the idea of targeting the eCB system for therapeutic benefits in neuropsychiatric disease and on the future research direction of neural circuit modulation.” 

https://www.nature.com/articles/s41401-018-0051-5