Enhancing Endocannabinoid Control of Stress with Cannabidiol

The stress response is a well-defined physiological function activated frequently by life events. However, sometimes the stress response can be inappropriate, excessive, or prolonged; in which case, it can hinder rather than help in coping with the stressor, impair normal functioning, and increase the risk of somatic and mental health disorders. There is a need for a more effective and safe pharmacological treatment that can dampen maladaptive stress responses. The endocannabinoid system is one of the main regulators of the stress response. A basal endocannabinoid tone inhibits the stress response, modulation of this tone permits/curtails an active stress response, and chronic deficiency in the endocannabinoid tone is associated with the pathological complications of chronic stress. Cannabidiol is a safe exogenous cannabinoid enhancer of the endocannabinoid system that could be a useful treatment for stress. There have been seven double-blind placebo controlled clinical trials of CBD for stress on a combined total of 232 participants and one partially controlled study on 120 participants. All showed that CBD was effective in significantly reducing the stress response and was non-inferior to pharmaceutical comparators, when included. The clinical trial results are supported by the established mechanisms of action of CBD (including increased N-arachidonylethanolamine levels) and extensive real-world and preclinical evidence of the effectiveness of CBD for treating stress.

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Cats at the Vet: The Effect of Alpha-s1 Casozepin

Animals ◽

10.3390/ani10112047 ◽

2020 ◽

Vol 10 (11) ◽

pp. 2047

Author(s):

Adjet Makawey ◽

Christine Iben ◽

Rupert Palme

Keyword(s):

Stress Responses ◽

Clinical Signs ◽

Controlled Study ◽

High Dose ◽

Daily Routine ◽

Double Blind ◽

Fecal Cortisol ◽

Waiting Area ◽

The Impact ◽

Examination Room

The aim of this study was to evaluate the impact of α-s1 casozepin on cat stress responses at a veterinary practice. Cats feel confident in their familiar surroundings and daily routine. A visit, and transport, to the veterinarian is a stressful experience for cats and their owners. Stress can mask clinical signs and has physiological impacts. Alpha-s1 casozepin (Zylkène; Vétoquinol) could potentially minimize stress in cats with its calming and anxiolytic characteristics. A randomized, partial double-blind and placebo-controlled study was carried out with 60 adult cats. The trial was designed for three groups: low dose (15 mg/kg q24 h α-s1 casozepin for six days), high dose (75 mg/kg q24 h α-s1 casozepin for three days), and a placebo (one fructose capsule per day for three days). For the study, cats had a checkup at their trusted veterinarian without the dietary supplement, followed by a second one four weeks later. Alpha-s1 casozepin or a placebo was administered three to six days before the checkup. Fecal cortisol metabolites (FCMs) were measured to non-invasively evaluate the impact of α-s1 casozepin on adrenocortical activity. The cat owners and veterinarians also assessed the physiological reactions (respiratory rate, sweaty paws, pupils, panting, and vocalization) of the cats at home, in the waiting area, and in the examination room. The only significant effect (kappa coefficient κ = 0.007 and κ = 0.003) found in this study was the absence of sweaty paws in cats who were treated with the high dose of α-s1 casozepin over three days, observed in the waiting area and examination room of the veterinarian’s practice, respectively. Alpha-s1 casozepin also showed a small but insignificant reduction in FCM levels. Alpha-s1 casozepin influences the autonomic nervous system, and can inhibit sweaty paws during stressful situations for cats.

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A Comparative Study of Intravenous Nitroglycerin With or Without Intravenous Lignocaine for Attenuation of Stress Responses to Endotracheal Intubation

Journal of Nepalgunj Medical College ◽

10.3126/jngmc.v16i2.24872 ◽

2018 ◽

Vol 16 (2) ◽

pp. 35-39

Author(s):

Nabin Kumar Regmi ◽

Grisuna Singh

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Stress Response ◽

Tracheal Intubation ◽

Stress Responses ◽

Age Groups ◽

Rate Pressure Product ◽

Double Blind Study ◽

Double Blind ◽

Group I

Background: Laryngoscopy and tracheal intubation lead to stress response which is characterized by transient rise in blood pressure and heart rate. This response is tolerated well in normal individuals but can lead to significant morbidity and mortality in patients with cardiovascular and cerebrovascular diseases. Search for the better drugs to suppress these responses is going on through decades. Aim of Study: To compare the effects of IV nitroglycerin alone and in combination with IV lignocaine, on attenuation of stress response to end tracheal intubation. Material and Methods: This is a randomized, double blind study conducted in 60patients admitted for operation at NGMCTH, between June 2018 to November 2018. Patients were of 16- 60 years age groups and belonging to ASA group I and II. Patients were divided into two groups: Group I IV Nitroglycerin 500 mcg+ NS 3 ml. (n=30) and Group IIIV Nitroglycerin 500 mcg+ IV Lignocaine 63 mg (n=30). Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP) and Heart rate (HR) were measured and Rate Pressure Product (RPP) calculated. Results: Baseline values were comparable in both groups. Post Intubation, there was significant decrease in SBP at 0,1,3 and 5 minutes while DBP and MAP significantly decreased at 1, 3 and 5 minutes, in both groups. Significant tachycardia was noted in both groups at 0,1and 3 minutes, and RPP remained unchanged in both groups. Conclusion: Nitroglycerin significantly decreases blood pressure, prevents rise in RPP but does not attenuate heart rate after end tracheal intubation. There is no benefit of adding IV lignocaine to IV nitroglycerin for attenuation of stress response to end tracheal intubation.

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Enteroviral Meningitis: Natural History and Outcome of Pleconaril Therapy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00227-06 ◽

2006 ◽

Vol 50 (7) ◽

pp. 2409-2414 ◽

Cited By ~ 87

Author(s):

R. A. Desmond ◽

N. A. Accortt ◽

L. Talley ◽

S. A. Villano ◽

S.-J. Soong ◽

...

Keyword(s):

Clinical Trials ◽

Natural History ◽

Cox Regression ◽

Severe Disease ◽

Controlled Study ◽

Controlled Clinical Trials ◽

Severe Nausea ◽

Double Blind ◽

Course Of Illness ◽

Enteroviral Meningitis

ABSTRACT Enteroviral meningitis causes appreciable morbidity in adults, including hospitalization, decreased activity, and headache. Limited data define the natural history of disease. No antiviral therapeutic agent has demonstrated improved outcome in controlled clinical trials. Pleconaril, an inhibitor of enterovirus replication, was tested in two placebo-controlled clinical trials. Of 607 randomized patients in a multicenter, double-blind placebo-controlled study of pleconaril (200 mg three times daily versus an identical-appearing placebo), 240 patients were confirmed to have enterovirus infection. The time to headache resolution was evaluated by using Kaplan-Meier survival methodology. A Cox regression model evaluated multivariate factors associated with disease resolution. Resolution of headache in patients with concomitant moderate to severe nausea at baseline occurred at a median of 9.5 days in the absence of therapy and was reduced to 7.0 days for pleconaril recipients (P = 0.009). For a headache score of >5 alone, treated patients resolved headache significantly more rapidly (P = 0.005). Males resolved headache 50% faster than females. Regardless of randomization group, patients with a baseline headache score of 5 or greater resolved headache 50% more slowly than patients with a baseline headache score of 4. No differences in either clinical or laboratory adverse events were noted. Over 50% of untreated patients had a persistent headache that was greater than 1 week in duration. Pleconaril shortened the course of illness compared to placebo recipients, especially in the early disease course. However, the benefit was achieved only modestly in a subgroup analysis of patients with more severe disease after adjusting for confounding variables.

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