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Basic & Clinical Pharmacology &... Apr 2022Cannabidiol (CBD) is an abundant non-psychoactive phytocannabinoid in cannabis extracts which has high affinity on a series of receptors, including Type 1 cannabinoid... (Review)
Review
Cannabidiol (CBD) is an abundant non-psychoactive phytocannabinoid in cannabis extracts which has high affinity on a series of receptors, including Type 1 cannabinoid receptor (CB1), Type 2 cannabinoid receptor (CB2), GPR55, transient receptor potential vanilloid (TRPV) and peroxisome proliferator-activated receptor gamma (PPARγ). By modulating the activities of these receptors, CBD exhibits multiple therapeutic effects, including neuroprotective, antiepileptic, anxiolytic, antipsychotic, anti-inflammatory, analgesic and anticancer properties. CBD could also be applied to treat or prevent COVID-19 and its complications. Here, we provide a narrative review of CBD's applications in human diseases: from mechanism of action to clinical trials.
Topics: Animals; Anti-Anxiety Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; COVID-19; Cannabidiol; Endocannabinoids; Humans; Receptors, Cannabinoid; COVID-19 Drug Treatment
PubMed: 35083862
DOI: 10.1111/bcpt.13710 -
Nutrients Dec 2020Stress is a natural response of the body, induced by factors of a physical (hunger, thirst, and infection) and/or psychological (perceived threat, anxiety, or concern)...
BACKGROUND
Stress is a natural response of the body, induced by factors of a physical (hunger, thirst, and infection) and/or psychological (perceived threat, anxiety, or concern) nature. Chronic, long-term stress may cause problems with sleep, concentration, and memory, as well as affective disorders. The passionflower () is a perennial plant with documented therapeutic properties. The literature data suggest that the passionflower itself, as well as its preparations, helps reduce stress and can therefore be helpful in the treatment of insomnia, anxiety, and depression. The objective of this systematic review was to evaluate in terms of its neuropsychiatric effects.
METHODS
The scientific databases PubMed, ClinTrials.gov, and Embase were searched up to 22 October 2019. The search identified randomized clinical trials describing the effects of in neuropsychiatric disorders.
RESULTS
The systematic review included nine clinical trials. The duration of the studies included in the analysis varied widely, from one day up to 30 days. Study participants were no less than 18 years old. In each of the papers, the effects of passionflower were measured by using a number of different tests and scales. The majority of studies reported reduced anxiety levels following the administration of preparations, with the effect less evident in people with mild anxiety symptoms. No adverse effects, including memory loss or collapse of psychometric functions, were observed.
CONCLUSION
may be helpful in treating some symptoms in neuropsychiatric patients.
Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Female; Humans; Male; Memory; Passiflora; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Sleep; Sleep Initiation and Maintenance Disorders; Stress, Physiological; Young Adult
PubMed: 33352740
DOI: 10.3390/nu12123894 -
Medicine Sep 2019Ashwagandha (Withania somnifera (L.) Dunal) is a herb traditionally used to reduce stress and enhance wellbeing. The aim of this study was to investigate its anxiolytic... (Randomized Controlled Trial)
Randomized Controlled Trial
An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study.
BACKGROUND
Ashwagandha (Withania somnifera (L.) Dunal) is a herb traditionally used to reduce stress and enhance wellbeing. The aim of this study was to investigate its anxiolytic effects on adults with self-reported high stress and to examine potential mechanisms associated with its therapeutic effects.
METHODS
In this 60-day, randomized, double-blind, placebo-controlled study the stress-relieving and pharmacological activity of an ashwagandha extract was investigated in stressed, healthy adults. Sixty adults were randomly allocated to take either a placebo or 240 mg of a standardized ashwagandha extract (Shoden) once daily. Outcomes were measured using the Hamilton Anxiety Rating Scale (HAM-A), Depression, Anxiety, and Stress Scale -21 (DASS-21), and hormonal changes in cortisol, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone.
RESULTS
All participants completed the trial with no adverse events reported. In comparison with the placebo, ashwagandha supplementation was associated with a statistically significant reduction in the HAM-A (P = .040) and a near-significant reduction in the DASS-21 (P = .096). Ashwagandha intake was also associated with greater reductions in morning cortisol (P < .001), and DHEA-S (P = .004) compared with the placebo. Testosterone levels increased in males (P = .038) but not females (P = .989) over time, although this change was not statistically significant compared with the placebo (P = .158).
CONCLUSIONS
These findings suggest that ashwagandha's stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis. However, further investigation utilizing larger sample sizes, diverse clinical and cultural populations, and varying treatment dosages are needed to substantiate these findings.
TRIAL REGISTRATION
Clinical Trials Registry-India (CTRI registration number: CTRI/2017/08/009449; date of registration 22/08/2017).
Topics: Adult; Anti-Anxiety Agents; Anxiety; Dehydroepiandrosterone Sulfate; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Phytotherapy; Plant Extracts; Stress, Psychological; Testosterone; Treatment Outcome
PubMed: 31517876
DOI: 10.1097/MD.0000000000017186 -
Medicina (Kaunas, Lithuania) Dec 2019Invasive dental procedures can be performed only with local anesthesia; in some cases, it may be useful to combine the administration of drugs to obtain anxiolysis with...
Invasive dental procedures can be performed only with local anesthesia; in some cases, it may be useful to combine the administration of drugs to obtain anxiolysis with local anesthesia. Sedation required level should be individually adjusted to achieve a proper balance between the needs of the patient, the operator, and the safety of the procedure. Surgical time is an important factor for post-operative phases, and this could be greatly increased by whether the patient interrupts the surgeon or if it is not collaborative. In this manuscript some dentistry-used methods to practice conscious sedation have been evaluated. This manuscript could be a useful reading on the current state of conscious sedation in dentistry and an important starting point for future perspectives. Surely the search for safer drugs for our patients could have beneficial effects for them and for the clinicians.
Topics: Administration, Oral; Adult; Ambulatory Care; Anesthesia, Dental; Anesthesia, Local; Anesthetics, Inhalation; Anti-Anxiety Agents; Benzodiazepines; Central Nervous System; Child; Conscious Sedation; Dental Anxiety; Dental Care; Dentistry; Humans; Nitrous Oxide; Operative Time; Postoperative Period; Safety
PubMed: 31817931
DOI: 10.3390/medicina55120778 -
British Journal of Clinical Pharmacology Oct 2022There is a growing interest in the psychiatric properties of the dissociative anaesthetic ketamine, as single doses have been shown to have fast-acting mood-enhancing... (Review)
Review
There is a growing interest in the psychiatric properties of the dissociative anaesthetic ketamine, as single doses have been shown to have fast-acting mood-enhancing and anxiolytic effects, which persist for up to a week after the main psychoactive symptoms have diminished. Therefore, ketamine poses potential beneficial effects in patients with refractory anxiety disorders, where other conventional anxiolytics have been ineffective. Ketamine is a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) glutamate receptor, which underlies its induction of pain relief and anaesthesia. However, the role of NMDA receptors in anxiety reduction is still relatively unknown. To fill this paucity in the literature, this systematic review assesses the evidence that ketamine significantly reduces refractory anxiety and discusses to what extent this may be mediated by NMDA receptor antagonism and other receptors. We highlight the temporary nature of the anxiolytic effects and discuss the high discrepancy among the study designs regarding many fundamental factors such as administration routes, complementary treatments and other treatments.
Topics: Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Humans; Ketamine; Receptors, N-Methyl-D-Aspartate
PubMed: 35510346
DOI: 10.1111/bcp.15374 -
International Journal of Molecular... Dec 2022Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of... (Review)
Review
Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of somatic diseases. The pathophysiology of anxiety development is complex and involves alterations in stress hormone production, neurosignaling pathways or free radical production. The various manifestations of anxiety, its complex pathophysiological background and the side effects of available treatments underlie the quest for constantly seeking therapies for these conditions. Melatonin, an indolamine produced in the pineal gland and released into the blood on a nightly basis, has been demonstrated to exert anxiolytic action in animal experiments and different clinical conditions. This hormone influences a number of physiological actions either via specific melatonin receptors or by receptor-independent pleiotropic effects. The underlying pathomechanism of melatonin's benefit in anxiety may reside in its sympatholytic action, interaction with the renin-angiotensin and glucocorticoid systems, modulation of interneuronal signaling and its extraordinary antioxidant and radical scavenging nature. Of importance, the concentration of this indolamine is significantly higher in cerebrospinal fluid than in the blood. Thus, ensuring sufficient melatonin production by reducing light pollution, which suppresses melatonin levels, may represent an endogenous neuroprotective and anxiolytic treatment. Since melatonin is freely available, economically undemanding and has limited side effects, it may be considered an additional or alternative treatment for various conditions associated with anxiety.
Topics: Animals; Melatonin; Anti-Anxiety Agents; Antioxidants; Free Radicals; Anxiety
PubMed: 36555831
DOI: 10.3390/ijms232416187 -
Pharmacology & Therapeutics Dec 2019Current medication for anxiety disorders is suboptimal in terms of efficiency and tolerability, highlighting the need for improved drug treatments. In this review an... (Review)
Review
Current medication for anxiety disorders is suboptimal in terms of efficiency and tolerability, highlighting the need for improved drug treatments. In this review an overview of drugs being studied in different phases of clinical trials for their potential in the treatment of fear-, anxiety- and trauma-related disorders is presented. One strategy followed in drug development is refining and improving compounds interacting with existing anxiolytic drug targets, such as serotonergic and prototypical GABAergic benzodiazepines. A more innovative approach involves the search for compounds with novel mechanisms of anxiolytic action using the growing knowledge base concerning the relevant neurocircuitries and neurobiological mechanisms underlying pathological fear and anxiety. The target systems evaluated in clinical trials include glutamate, endocannabinoid and neuropeptide systems, as well as ion channels and targets derived from phytochemicals. Examples of promising novel candidates currently in clinical development for generalised anxiety disorder, social anxiety disorder, panic disorder, obsessive compulsive disorder or post-traumatic stress disorder include ketamine, riluzole, xenon with one common pharmacological action of modulation of glutamatergic neurotransmission, as well as the neurosteroid aloradine. Finally, compounds such as D-cycloserine, MDMA, L-DOPA and cannabinoids have shown efficacy in enhancing fear-extinction learning in humans. They are thus investigated in clinical trials as an augmentative strategy for speeding up and enhancing the long-term effectiveness of exposure-based psychotherapy, which could render chronic anxiolytic drug treatment dispensable for many patients. These efforts are indicative of a rekindled interest and renewed optimism in the anxiety drug discovery field, after decades of relative stagnation.
Topics: Animals; Anti-Anxiety Agents; Anxiety Disorders; Humans; Molecular Targeted Therapy
PubMed: 31470029
DOI: 10.1016/j.pharmthera.2019.107402 -
Psychopharmacology Jul 2021Cannabidiol (CBD) has been reported to attenuate stress and anxiety, but little is known about the extent to which such effects result from pharmacological versus... (Randomized Controlled Trial)
Randomized Controlled Trial
RATIONALE
Cannabidiol (CBD) has been reported to attenuate stress and anxiety, but little is known about the extent to which such effects result from pharmacological versus expectancy factors.
OBJECTIVES
We evaluated whether CBD expectancy alone could influence stress, anxiety, and mood, and the extent to which beliefs regarding CBD effects predicted these responses.
METHODS
In this randomized crossover study, 43 health adults (23 women) attended two experimental laboratory sessions, where they self-administered CBD-free hempseed oil sublingually. During one session, they were (incorrectly) informed that the oil contained CBD and in the other session, that the oil was CBD-free. Following administration, participants engaged in the Maastricht Acute Stress Test (MAST). Heart rate variability (HRV) was assessed continuously, and subjective state was assessed at baseline, 90-min following oil administration, immediately following the MAST, and after a 10-min recovery period.
RESULTS
The CBD expectancy condition was associated with increased sedation as well as with changes in HRV that were consistent with heightened anticipatory stress regulation. Overall, there were no systematic changes in subjective stress, or anxiety, according to expectancy condition. However, participants who endorsed strong a priori beliefs that CBD has anxiolytic properties reported significantly diminished anxiety in the CBD expectancy condition.
CONCLUSIONS
CBD expectancy alone impacted several subjective and physiological responses. Additionally, expectancy-related factors were implicated in anxiolytic effects of CBD for those who believed it was helpful for such purposes, emphasizing the need to measure and control for CBD-related expectancies in clinical research that involves the administration of CBD.
Topics: Administration, Sublingual; Adult; Affect; Anti-Anxiety Agents; Anxiety; Cannabidiol; Cross-Over Studies; Double-Blind Method; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Motivation; Self Administration; Stress, Psychological; Young Adult
PubMed: 33813611
DOI: 10.1007/s00213-021-05823-w -
International Journal of Molecular... Feb 2021Cannabidiol (CBD) is the most abundant non-psychoactive component of cannabis; it displays a very low affinity for cannabinoid receptors, facilitates endocannabinoid... (Review)
Review
Cannabidiol (CBD) is the most abundant non-psychoactive component of cannabis; it displays a very low affinity for cannabinoid receptors, facilitates endocannabinoid signaling by inhibiting the hydrolysis of anandamide, and stimulates both transient receptor potential vanilloid 1 and 2 and serotonin type 1A receptors. Since CBD interacts with a wide variety of molecular targets in the brain, its therapeutic potential has been investigated in a number of neuropsychiatric diseases, including anxiety and mood disorders. Specifically, CBD has received growing attention due to its anxiolytic and antidepressant properties. As a consequence, and given its safety profile, CBD is considered a promising new agent in the treatment of anxiety and mood disorders. However, the exact molecular mechanism of action of CBD still remains unknown. In the present preclinical review, we provide a summary of animal-based studies that support the use of CBD as an anxiolytic- and antidepressant-like compound. Next, we describe neuropharmacological evidence that links the molecular pharmacology of CBD to its behavioral effects. Finally, by taking into consideration the effects of CBD on DNA methylation, histone modifications, and microRNAs, we elaborate on the putative role of epigenetic mechanisms in mediating CBD's therapeutic outcomes.
Topics: Animals; Anti-Anxiety Agents; Anxiety Disorders; Cannabidiol; Epigenesis, Genetic; Humans; Mood Disorders; Receptor, Serotonin, 5-HT1A; TRPV Cation Channels
PubMed: 33668469
DOI: 10.3390/ijms22041863 -
International Journal of Molecular... Jun 2022Major depressive disorder and anxiety disorders are common and disabling conditions that affect millions of people worldwide. Despite being different disorders, symptoms... (Review)
Review
Major depressive disorder and anxiety disorders are common and disabling conditions that affect millions of people worldwide. Despite being different disorders, symptoms of depression and anxiety frequently overlap in individuals, making them difficult to diagnose and treat adequately. Therefore, compounds capable of exerting beneficial effects against both disorders are of special interest. Noteworthily, vitamin D deficiency has been associated with an increased risk of developing depression and anxiety, and individuals with these psychiatric conditions have low serum levels of this vitamin. Indeed, in the last few years, vitamin D has gained attention for its many functions that go beyond its effects on calcium-phosphorus metabolism. Particularly, antioxidant, anti-inflammatory, pro-neurogenic, and neuromodulatory properties seem to contribute to its antidepressant and anxiolytic effects. Therefore, in this review, we highlight the main mechanisms that may underlie the potential antidepressant and anxiolytic effects of vitamin D. In addition, we discuss preclinical and clinical studies that support the therapeutic potential of this vitamin for the management of these disorders.
Topics: Anti-Anxiety Agents; Antidepressive Agents; Anxiety; Anxiety Disorders; Depression; Depressive Disorder, Major; Humans; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 35806075
DOI: 10.3390/ijms23137077