cannabidiol and Panic-Disorder

Panic disorder (PD) is a disabling psychiatry condition that affects approximately 5% of the worldwide population. Currently, long-term selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PD; however, the common side-effect profiles and drug interactions may provoke patients to abandon the treatment, leading to PD symptoms relapse. Cannabidiol (CBD) is the major non-psychotomimetic constituent of the Cannabis sativa plant with antianxiety properties that has been suggested as an alternative for treating anxiety disorders. The aim of the present review was to discuss the effects and mechanisms involved in the putative anti-panic effects of CBD.. electronic database was used as source of the studies selected selected based on the studies found by crossing the following keywords: cannabidiol and panic disorder; canabidiol and anxiety, cannabidiol and 5-HT1A receptor).. In the present review, we included both experimental laboratory animal and human studies that have investigated the putative anti-panic properties of CBD. Taken together, the studies assessed clearly suggest an anxiolytic-like effect of CBD in both animal models and healthy volunteers.. CBD seems to be a promising drug for the treatment of PD. However, novel clinical trials involving patients with the PD diagnosis are clearly needed to clarify the specific mechanism of action of CBD and the safe and ideal therapeutic doses of this compound.

Topics: Animals; Antioxidants; Cannabidiol; Databases, Bibliographic; Disease Models, Animal; Humans; Panic Disorder; Receptor, Serotonin, 5-HT1A

Preclinical research suggests that enhancing CB1 receptor agonism may improve fear extinction. In order to translate this knowledge into a clinical application we examined whether cannabidiol (CBD), a hydrolysis inhibitor of the endogenous CB1 receptor agonist anandamide (AEA), would enhance the effects of exposure therapy in treatment refractory patients with anxiety disorders. Patients with panic disorder with agoraphobia or social anxiety disorder were recruited for a double-blind parallel randomised controlled trial at three mental health care centres in the Netherlands. Eight therapist-assisted exposure in vivo sessions (weekly, outpatient) were augmented with 300 mg oral CBD (n = 39) or placebo (n = 41). The Fear Questionnaire (FQ) was assessed at baseline, mid- and post-treatment, and at 3 and 6 months follow-up. Primary analyses were on an intent-to-treat basis. No differences were found in treatment outcome over time between CBD and placebo on FQ scores, neither across (β = 0.32, 95% CI [-0.60; 1.25]) nor within diagnosis groups (β = -0.11, 95% CI [-1.62; 1.40]). In contrast to our hypotheses, CBD augmentation did not enhance early treatment response, within-session fear extinction or extinction learning. Incidence of adverse effects was equal in the CBD (n = 4, 10.3%) and placebo condition (n = 6, 15.4%). In this first clinical trial examining CBD as an adjunctive therapy in anxiety disorders, CBD did not improve treatment outcome. Future clinical trials may investigate different dosage regimens.

Topics: Agoraphobia; Cannabidiol; Extinction, Psychological; Fear; Humans; Implosive Therapy; Panic Disorder; Phobia, Social; Receptor, Cannabinoid, CB1

The behavioural effects elicited by chemical constituents of Cannabis sativa, such as cannabidiol (CBD), on the ventromedial hypothalamus (VMH) are not well understood. There is evidence that VMH neurons play a relevant role in the modulation of unconditioned fear-related defensive behavioural reactions displayed by laboratory animals.. This study was designed to explore the specific pattern of distribution of the CB. A panic attack-like state was triggered in Wistar rats by intra-VMH microinjections of N-methyl-D-aspartate (NMDA). One of three different doses of CBD was microinjected into the VMH prior to local administration of NMDA. In addition, the most effective dose of CBD was used after pre-treatment with the CB. The morphological procedures demonstrated distribution of labelled CB. These findings suggest that CBD causes panicolytic-like effects and reduces unconditioned fear-induced antinociception when administered in the VMH, and these effects are mediated by the CB

Topics: Animals; Cannabidiol; Fear; Injections, Intraventricular; Male; N-Methylaspartate; Pain Measurement; Panic Disorder; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Ventromedial Hypothalamic Nucleus

The potential anxiolytic and antipanic properties of cannabidiol have been shown; however, its mechanism of action seems to recruit other receptors than those involved in the endocannabinoid-mediated system. It was recently shown that the model of panic-like behaviors elicited by the encounters between mice and snakes is a good tool to investigate innate fear-related responses, and cannabidiol causes a panicolytic-like effect in this model. The aim of the present study was to investigate the 5-hydroxytryptamine (5-HT) co-participation in the panicolytic-like effects of cannabidiol on the innate fear-related behaviors evoked by a prey versus predator interaction-based paradigm. Male Swiss mice were treated with intraperitoneal (i.p.) administrations of cannabidiol (3 mg/kg, i.p.) and its vehicle and the effects of the peripheral pre-treatment with increasing doses of the 5-HT1A receptor antagonist WAY-100635 (0.1, 0.3 and 0.9 mg/kg, i.p.) on instinctive fear-induced responses evoked by the presence of a wild snake were evaluated. The present results showed that the panicolytic-like effects of cannabidiol were blocked by the pre-treatment with WAY-100635 at different doses. These findings demonstrate that cannabidiol modulates the defensive behaviors evoked by the presence of threatening stimuli, and the effects of cannabidiol are at least partially dependent on the recruitment of 5-HT1A receptors.

Topics: Animals; Anti-Anxiety Agents; Behavior, Animal; Boidae; Cannabidiol; Disease Models, Animal; Dose-Response Relationship, Drug; Fear; Injections, Intraperitoneal; Male; Mice; Panic; Panic Disorder; Piperazines; Predatory Behavior; Pyridines; Receptor, Serotonin, 5-HT1A; Serotonin Antagonists

Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that promotes antianxiety and anti-panic effects in animal models after acute systemic or intra-dorsal periaqueductal gray (DPAG) administration. However, the effects of CBD repeated administration, and the possible mechanisms involved, in animal models of anxiety- and panic-related responses remain poorly understood.. The present study evaluates the role of the serotonergic neurotransmission within the DPAG in the modulation of escape responses of rats chronically treated with CBD.. Male Wistar rats received acute or repeated (5 mg/Kg/daily/21 days) administration of CBD and were submitted to the elevated T-maze (ETM). We also investigated if CBD effects on the ETM depend on facilitation of 5-HT1A-mediated neurotransmission in the DPAG. To this latter aim, we verified if these effects would be prevented by intra-DPAG injection of the 5-HT1A receptor antagonist WAY100635 (0.37 nmol/0.2 μL). Also, we verified, by in vivo microdialysis, if CBD chronic treatment increases serotonin (5-HT) release and, by quantitative polymerase chain reaction, if there are changes in 5HT-1A or 5HT-2C mRNA expression in DPAG.. The results showed that repeated but not acute peripheral administration of CBD decreases escape responses in the ETM, suggesting a panicolytic effect. This treatment did not change 5HT-1A or 5-HT-2C receptor mRNA expression nor modify serotonin extracellular concentrations in the DPAG. CBD effects were prevented by DPAG injection of the 5-HT1A receptor antagonist.. Together, these findings suggest that repeated treatment with CBD induces anti-panic effects by acting on 5-HT1A receptors in DPAG.

Topics: Animals; Behavior, Animal; Brain Mapping; Cannabidiol; Dose-Response Relationship, Drug; Male; Maze Learning; Microdialysis; Panic Disorder; Periaqueductal Gray; Polymerase Chain Reaction; Rats, Wistar; Receptor, Serotonin, 5-HT1A; Serotonin; Synaptic Transmission

Several pharmacological targets have been proposed as modulators of panic-like reactions. However, interest should be given to other potential therapeutic neurochemical agents. Recent attention has been given to the potential anxiolytic properties of cannabidiol, because of its complex actions on the endocannabinoid system together with its effects on other neurotransmitter systems. The aim of this study was to investigate the effects of cannabidiol on innate fear-related behaviors evoked by a prey vs predator paradigm. Male Swiss mice were submitted to habituation in an arena containing a burrow and subsequently pre-treated with intraperitoneal administrations of vehicle or cannabidiol. A constrictor snake was placed inside the arena, and defensive and non-defensive behaviors were recorded. Cannabidiol caused a clear anti-aversive effect, decreasing explosive escape and defensive immobility behaviors outside and inside the burrow. These results show that cannabidiol modulates defensive behaviors evoked by the presence of threatening stimuli, even in a potentially safe environment following a fear response, suggesting a panicolytic effect.

Topics: Animals; Anti-Anxiety Agents; Cannabidiol; Disease Models, Animal; Fear; Humans; Instinct; Male; Mice; Panic Disorder; Snakes