cannabidiol and Stress-Disorders--Post-Traumatic

Cannabidiol (CBD) is a non-intoxicating cannabinoid compound with diverse molecular targets and potential therapeutic effects, including effects relevant to the treatment of psychiatric disorders. In this scoping review, we sought to determine the extent to which sex and gender have been considered as potential moderators of the neuropsychiatric effects and pharmacokinetics of CBD. In this case, 300 articles were screened, retrieved from searches in PubMed/Medline, Scopus, Google Scholar, PsycInfo and CINAHL, though only 12 met our eligibility criteria: eight studies in preclinical models and four studies in humans. Among the preclinical studies, three suggested that sex may influence long-term effects of gestational or adolescent exposure to CBD; two found no impact of sex on CBD modulation of addiction-relevant effects of Δ⁹-tetrahydrocannabinol (THC); two found antidepressant-like effects of CBD in males only; and one found greater plasma and liver CBD concentrations in females compared to males. Among the human studies, two found no sex difference in CBD pharmacokinetics in patient samples, one found greater plasma CBD concentrations in healthy females compared to males, and one found no evidence of sex differences in the effects of CBD on responses to trauma recall in patients with post-traumatic stress disorder (PTSD). No studies were identified that considered the role of gender in CBD treatment effects. We discuss potential implications and current limitations of the existing literature.

Topics: Adolescent; Cannabidiol; Cannabinoids; Dronabinol; Female; Humans; Male; Sex Characteristics; Stress Disorders, Post-Traumatic

Two primary compounds of the cannabis plant (. A keyword search of eight online literature databases identified eight randomized controlled trials of defined CBD or THC doses for the target populations.. A 1-month trial of daily THC (up to 3 mg per day) for. With only eight very small studies, insufficient evidence was found for efficacy of CBD and THC to manage affective disorders, anxiety disorders, or PTSD. Therefore, medical cannabis should not be recommended for treating patients with these disorders. Further research should investigate the safety and efficacy of managing psychiatric disorders with cannabinoids.

Topics: Adolescent; Anxiety Disorders; Cannabidiol; Cannabinoids; Humans; Mood Disorders; Stress Disorders, Post-Traumatic

Post-traumatic Stress Disorder (PTSD) is a diagnosis of extreme anxiety caused by a traumatic event. Less than 10% of individuals who have experienced severe trauma will develop this disorder. Treatment options include various psychotherapies, but not all patients respond to them. Different pharmacological approaches have been explored as potential adjuvants, including using cannabinoids to target the endocannabinoid system to reduce the symptoms and enhance extinction training over the associated fear memories. This review was aimed to determine the effects of using cannabinoids for treatment of PTSD.. For this review, four cohort studies, four randomized clinical trials, one case report, and one case series were obtained from PubMed within the last 10 years. Cannabis extracts, tetrahydrocannabinol (THC) and cannabidiol (CBD), and synthetic cannabinoids were used in the studies to target the cannabinoid receptors 1 and 2. Cannabinoids were shown to improve overall PTSD symptoms, including sleep quality and quantity, hyperarousal, and treatment-resistant nightmares. When participants were undergoing extinction training, cannabinoids given within the same time interval enhanced consolidation and retention.. Cannabinoids have been shown to be an effective treatment option for patients with PTSD. Besides aiding to relieve the symptoms and enhance extinction training, they also are relatively well tolerated. Common adverse effects included light-headedness, forgetfulness, dizziness, and headaches.

Topics: Anxiety; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Humans; Stress Disorders, Post-Traumatic

Studies with cannabidiol (CBD) suggest that this compound has anxiolytic properties and may mediate the reconsolidation and extinction of aversive memories. The objective of this study was to test whether the administration of CBD 300 mg before the recall of traumatic events attenuated symptoms usually induced by recall in subjects diagnosed with posttraumatic stress disorder (PTSD) and if its potential effects interfere with the reconsolidation of aversive memories. The double-blind trial included 33 participants of both sexes, aged between 18 and 60 years, diagnosed with PTSD according to the SCID-5 and randomly allocated to two groups treated with CBD (n = 17) and placebo (n = 16). In the first experimental section, participants were matched by sex, age, body mass index (BMI), and PTSD symptoms as assessed with the Posttraumatic Stress Disorder Checklist (PCL-5). On the same day, participants prepared the behavior test, recording accounts of their traumas in digital audio for a minute and a half and then imagining the trauma for 30 s. After 7 days, participants received CBD (300 mg) or placebo and performed the behavioral test, listening to the trauma account and imagining themselves in that situation. Before and after the behavioral test, subjective changes in mood and anxiety were recorded (Visual and Analogical Mood Scale - VAMS and STAI-state), along with physiological correlates of anxiety blood pressure (BP), heart rate (HR), and salivary cortisol (SC). Seven days later, participants underwent the same procedures as the previous session, but without the pharmacological intervention, to assess the effect on reconsolidation of traumatic memories. We found that CBD significantly attenuated the increase in the VAMS scale cognitive impairment factor scores, under the CBD's effect, with this effect remaining 1 week after drug administration. No significant differences between the effects of CBD and placebo on anxiety, alertness, and discomfort induced by the recall of the traumatic event during the pharmacological intervention and in the subsequent week, in the absence of it. There were no significant differences between the CBD and placebo groups regarding physiological data (BP, HR, and SC). The attenuation of cognitive impairments during trauma recall under the effect of CBD may have interfered with the reconsolidation of traumatic memories concerning its association with cognitive impairments.

Topics: Adolescent; Adult; Anxiety; Anxiety Disorders; Cannabidiol; Female; Humans; Male; Mental Recall; Middle Aged; Stress Disorders, Post-Traumatic; Young Adult

The burden of illness for PTSD is staggering and confers significant interference in work, social functioning, as well as increased risk for other physical and mental health problems. Recently, there's been considerable attention paid to the potential therapeutic use of cannabidiol (CBD) products in the treatment of a variety of physical and mental health problems. The endocannabinoid system (ECS) is a logical therapeutic target for combating PTSD and other fear-based disorders given that cannabinoid receptors and other molecular mediators crucial for ECS signaling are richly expressed in a variety of brain regions that govern the regulation of learned fear and defensive behavior.. This is an 8-week single-site Phase II randomized double-blind placebo-controlled fixed dose clinical trial. Participants recruited throughout the United States (N = 150) meeting DSM-5 criteria for posttraumatic stress disorder are randomly assigned to one of three treatment arms: (a) 300 mg CBD Isolate; (b) 300 mg CBD Broad Spectrum; and (c) Placebo oil. The primary outcome is PTSD symptom severity as indexed by the PTSD Checklist for DSM-5 (PCL-5) assessed at post treatment (Week 9) and follow-up (Week 13). Secondary outcomes including patient-rated depression, overall disability, anxiety, quality of life, and alcohol use are assessed weekly throughout the trial. Safety and CBD adherence are assessed daily throughout the trial.. This is the first placebo-controlled clinical trial investigating (a) CBD for the treatment of PTSD; and (b) the first study to test the relative efficacy of CBD Isolate vs CBD Broad Spectrum. Trial registration ClinicalTrials.gov registered (12/12/2019), trial identifier NCT04197102.. issued 08/04/2022, protocol amendment number #2019-05-0123.

Topics: Anxiety; Cannabidiol; Double-Blind Method; Humans; Quality of Life; Stress Disorders, Post-Traumatic; Treatment Outcome

Post-traumatic stress disorder (PTSD), which normally follows psychological trauma, has been increasingly studied as a brain disease. However, the blood-brain barrier (BBB) prevents conventional drugs for PTSD from entering the brain. Our previous studies proved the effectiveness of cannabidiol (CBD) against PTSD, but low water solubility, low brain targeting efficiency and poor bioavailability restricted its applications. Here, a bionic delivery system, camouflage CBD-loaded macrophage-membrane nanovesicles (CMNVs), was constructed via co-extrusion of CBD with macrophage membranes, which had inflammatory and immune escape properties. In vitro anti-inflammatory, cellular uptake and pharmacokinetic experiments respectively verified the anti-inflammatory, inflammatory targeting and immune escape properties of CMNVs. Brain targeting and excellent anti-PTSD effects of CMNVs had been validated in vivo by imaging and pharmacodynamics studies. In our study, the potential of ultrasound to open BBBs and improve the brain-targeted delivery of CBD was evaluated. In conclusion, this cell membrane bionic delivery system assisted with ultrasound had good therapeutic effect against PTSD mice, which is expected to help convey CBD to inflammatory areas within the brain and alleviate the symptoms of PTSD.

Topics: Animals; Anti-Inflammatory Agents; Biomimetics; Cannabidiol; Macrophages; Mice; Stress Disorders, Post-Traumatic

The development of anxiety disorders and post-traumatic stress disorder (PTSD) is complex. Both delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are of potential therapeutic use. Evidence suggests that cannabis has a beneficial effect on neural circuitry involved in fear regulation. In the United States, cannabis is considered either medical or recreational and can contain pure THC or CBD or any combination thereof. The numerous cannabis compounds of various administration routes, with variable pharmacokinetics, further affect the cannabis conundrum. Despite being federally unregulated, medical cannabis has received increased attention socially, and at present, 37 states, four territories, and the District of Columbia have legalized medical cannabis for use in specific health conditions. Patients are increasingly inquiring about cannabis, and clinicians must educate themselves with reliable cannabinoid information for patient education. In adults with anxiety disorders and PTSD, evidence supports a relatively safe profile for medical cannabis; however, conclusive scientific evidential support of its therapeutic properties is limited, resulting in a lack of standardization and Food and Drug Administration approval.

Topics: Adult; Anxiety Disorders; Cannabidiol; Cannabis; Dronabinol; Humans; Medical Marijuana; Stress Disorders, Post-Traumatic

Post-traumatic stress disorder (PTSD) is characterized by poor adaptation to a traumatic experience and disturbances in fear memory regulation, and currently lacks effective medication. Cannabidiol is a main constituent of Cannabis sativa; it has no psychotomimetic effects and has been implicated in modulating fear learning in mammals. Using a mouse PTSD model, we investigated the effects of CBD on PTSD-like behaviors and the modulation of trauma-related fear memory, a crucial process leading to core symptoms of PTSD.. We applied the modified pre-shock model to evaluated PTSD-like behaviors from days 3 to 26. The measures included the freezing time to the conditioned context, open field test, elevated plus maze test, and social interaction test. CBD and sertraline were administered at different stages of fear memory.. CBD (10 mg/kg, i.p.) administration alleviated main PTSD-like symptoms in the mouse pre-shock model by attenuating trauma-related fear memory and anxiety-like behavior, and increasing social interaction behavior. The effects of CBD were apparent irrespective of whether it was administered before, during, or after re-exposure to the aversive context. However, sertraline (15 mg/kg, p.o.) was only effective when administered before the behavioral test. CBD also reduced the consolidation, retrieval, and reconsolidation of trauma-related fear memory, whereas sertraline only reduced fear-memory retrieval.. CBD produced anti-PTSD-like actions in mice and disrupted trauma-related fear memory by interfering with multiple aspects of fear memory processing. These findings indicate that CBD may be a promising candidate for treating PTSD.

Topics: Animals; Cannabidiol; Fear; Mammals; Memory; Sertraline; Stress Disorders, Post-Traumatic

Topics: Cannabidiol; Humans; Research Design; Stress Disorders, Post-Traumatic

Topics: Cannabidiol; Humans; Research Design; Stress Disorders, Post-Traumatic

Topics: Analgesics; Cannabidiol; Cannabis; Humans; Knowledge; Stress Disorders, Post-Traumatic

Patients with psychiatric conditions are increasingly using cannabinoids, particularly cannabidiol (CBD), to treat their own symptoms. After reviewing the mechanism of action of CBD, the current article examines the existing evidence for CBD in the treatment of schizophrenia, anxiety, autism, posttraumatic stress disorder, and insomnia, and discusses the challenges in translating these studies, often using very high doses of CBD, into clinical practice. Until additional, well-designed studies that examine the more common practice of lower doses of CBD are performed, a harm-reduction, patient-centered, empiric approach is encouraged to optimize symptom reduction while at the same time avoiding the known risks of cannabis. [Journal of Psychosocial Nursing and Mental Health Services, 57(10), 7-11.].

Topics: Anxiety Disorders; Cannabidiol; Cannabis; Humans; Mental Health; Schizophrenia; Sleep Initiation and Maintenance Disorders; Stress Disorders, Post-Traumatic

Previous studies have shown attenuated cortisol awakening response in patients with posttraumatic stress disorder (PTSD).. A 15-year-old girl, a survivor of acute sexual violence, received a 7-day oral treatment with cannabidiol. She was followed-up from the first 24 hours after the event for 6 months, for assessment of the effects of this treatment on the reconsolidation of memories related to the traumatic event.. Cannabidiol treatment did not prevent the onset of PTSD. Cortisol awakening responses after the onset of the disorder were attenuated compared with those observed in the same individual before the onset of PTSD, in line with previous evidence from studies comparing groups with and without PTSD.

Topics: Adolescent; Cannabidiol; Female; Humans; Hydrocortisone; Rape; Saliva; Stress Disorders, Post-Traumatic

Cannabidiol (CBD) is a non-psychotomimetic cannabinoid compound that is found in plants of the genus Cannabis. Preclinical research has suggested that CBD may have a beneficial effect in rodent models of post-traumatic stress disorder (PTSD). This effect is believed to be due to the action of CBD on the endocannabinoid system. CBD has seen a recent surge in research regarding its potential value in a number of neuro-psychiatric conditions. This is the first study to date examining the clinical benefit of CBD for patients with PTSD.. This retrospective case series examines the effect of oral CBD administration on symptoms of PTSD in a series of 11 adult patients at an outpatient psychiatry clinic. CBD was given on an open-label, flexible dosing regimen to patients diagnosed with PTSD by a mental health professional. Patients also received routine psychiatric care, including concurrent treatment with psychiatric medications and psychotherapy. The length of the study was 8 weeks. PTSD symptom severity was assessed every 4 weeks by patient-completed PTSD Checklist for the DSM-5 (PCL-5) questionnaires.. From the total sample of 11 patients, 91% (n = 10) experienced a decrease in PTSD symptom severity, as evidenced by a lower PCL-5 score at 8 weeks than at their initial baseline. The mean total PCL-5 score decreased 28%, from a mean baseline score of 51.82 down to 37.14, after eight consecutive weeks of treatment with CBD. CBD was generally well tolerated, and no patients discontinued treatment due to side effects.. Administration of oral CBD in addition to routine psychiatric care was associated with PTSD symptom reduction in adults with PTSD. CBD also appeared to offer relief in a subset of patients who reported frequent nightmares as a symptom of their PTSD. Additional clinical investigation, including double-blind, placebo-controlled trials, would be necessary to further substantiate the response to CBD that was observed in this study.

Topics: Administration, Oral; Adult; Anxiety; Cannabidiol; Dreams; Female; Humans; Male; Middle Aged; Retrospective Studies; Stress Disorders, Post-Traumatic; Treatment Outcome; Young Adult

The prefrontal cortex (PFC), amygdala and hippocampus display a coordinated activity during acquisition of associative fear memories. Evidence indicates that PFC engagement in aversive memory formation does not progress linearly as previously thought. Instead, it seems to be recruited at specific time windows after memory acquisition, which has implications for the treatment of post-traumatic stress disorders. Cannabidiol (CBD), the major non-psychotomimetic phytocannabinoid of the Cannabis sativa plant, is known to modulate contextual fear memory acquisition in rodents. However, it is still not clear how CBD interferes with PFC-dependent processes during post-training memory consolidation. Here, we tested whether intra-PFC infusions of CBD immediately after or 5h following contextual fear conditioning was able to interfere with memory consolidation. Neurochemical and cellular correlates of the CBD treatment were evaluated by the quantification of extracellular levels of dopamine (DA), serotonin, and their metabolites in the PFC and by measuring the cellular expression of activity-dependent transcription factors in cortical and limbic regions. Our results indicate that bilateral intra-PFC CBD infusion impaired contextual fear memory consolidation when applied 5h after conditioning, but had no effect when applied immediately after it. This effect was associated with a reduction in DA turnover in the PFC following retrieval 5days after training. We also observed that post-conditioning infusion of CBD reduced c-fos and zif-268 protein expression in the hippocampus, PFC, and thalamus. Our findings support that CBD interferes with contextual fear memory consolidation by reducing PFC influence on cortico-limbic circuits.

Topics: Animals; Cannabidiol; Conditioning, Psychological; Fear; Gene Expression; Hippocampus; Male; Memory Consolidation; Neurons; Prefrontal Cortex; Rats, Wistar; Stress Disorders, Post-Traumatic; Time Factors

Anxiety and sleep disorders are often the result of posttraumatic stress disorder and can contribute to an impaired ability to focus and to demonstration of oppositional behaviors.. These symptoms were present in our patient, a ten-year-old girl who was sexually abused and had minimal parental supervision as a young child under the age of five. Pharmaceutical medications provided partial relief, but results were not long-lasting, and there were major side effects. A trial of cannabidiol oil resulted in a maintained decrease in anxiety and a steady improvement in the quality and quantity of the patient's sleep.. Cannabidiol oil, an increasingly popular treatment of anxiety and sleep issues, has been documented as being an effective alternative to pharmaceutical medications. This case study provides clinical data that support the use of cannabidiol oil as a safe treatment for reducing anxiety and improving sleep in a young girl with posttraumatic stress disorder.

Topics: Anxiety; Cannabidiol; Cannabis; Child; Child Abuse, Sexual; Female; Humans; Phytotherapy; Plant Oils; Sleep; Sleep Initiation and Maintenance Disorders; Stress Disorders, Post-Traumatic

Topics: Animals; Biomedical Research; Cannabidiol; Cannabis; Child; Clinical Trials, Phase II as Topic; Craniocerebral Trauma; Crohn Disease; Drug Industry; Female; Humans; Israel; Medical Marijuana; Mice; Stress Disorders, Post-Traumatic

Traumatic memories have been resilient to therapeutic approaches targeting their permanent attenuation. One of the potentially promising pharmacological strategies under investigation is the search for safe reconsolidation blockers. However, preclinical studies focusing on this matter have scarcely addressed abnormal aversive memories and related outcomes.. By mimicking the enhanced noradrenergic activity reported after traumatic events in humans, here we sought to generate a suitable condition to establish whether some clinically approved drugs able to disrupt the reconsolidation of conditioned fear memories in rodents would still be effective.. We report that the α2-adrenoceptor antagonist yohimbine was able to induce an inability to restrict behavioral (fear) and cardiovascular (increased systolic blood pressure) responses to the paired context when administered immediately after acquisition, but not 6h later, indicating the formation of a generalized fear memory, which endured for over 29 days and was less susceptible to suppression by extinction. It was also resistant to reconsolidation disruption by the α2-adrenoceptor agonist clonidine or cannabidiol, the major non-psychotomimetic component of Cannabis sativa. Since signaling at N-methyl-D-aspartate (NMDA) receptors is important for memory labilization and because a dysfunctional memory may be less labile than is necessary to trigger reconsolidation on its brief retrieval and reactivation, we then investigated and demonstrated that pre-retrieval administration of the partial NMDA agonist D-cycloserine allowed the disrupting effects of clonidine and cannabidiol on reconsolidation.. These findings highlight the effectiveness of a dual-step pharmacological intervention to mitigate an aberrant and enduring aversive memory similar to that underlying the post-traumatic stress disorder.

Topics: Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Animals; Blood Pressure; Cannabidiol; Clonidine; Cycloserine; Excitatory Amino Acid Agents; Extinction, Psychological; Fear; Male; Memory; Psychotropic Drugs; Random Allocation; Rats, Wistar; Stress Disorders, Post-Traumatic; Yohimbine

Posttraumatic stress disorder (PTSD) is an incapacitating syndrome that follows a traumatic experience. Predator exposure promotes long-lasting anxiogenic effect in rodents, an effect related to symptoms found in PTSD patients. Cannabidiol (CBD) is a non-psychotomimetic component of Cannabis sativa with anxiolytic effects. The present study investigated the anti-anxiety actions of CBD administration in a model of PTSD. Male Wistar rats exposed to a predator (cat) received, 1 h later, singled or repeated i.p. administration of vehicle or CBD. Seven days after the stress animals were submitted to the elevated plus maze. To investigate the involvement of 5HT1A receptors in CBD effects animals were pre-treated with WAY100635, a 5HT1A receptor antagonist. To explore possible neurobiological mechanisms involved in these effects, 5HT1A receptor mRNA and BDNF protein expression were measured in the hippocampus, frontal cortex, amygdaloid complex and dorsal periaqueductal gray. Repeated administration of CBD prevented long-lasting anxiogenic effects promoted by a single predator exposure. Pretreatment with WAY100635 attenuated CBD effects. Seven days after predator exposure 5HT1A mRNA expression was up regulated in the frontal cortex and hippocampus. CBD and paroxetine failed to prevent this effect. No change in BDNF expression was found. In conclusion, predator exposure promotes long-lasting up-regulation of 5HT1A receptor gene expression in the hippocampus and frontal cortex. Repeated CBD administration prevents the long-lasting anxiogenic effects observed after predator exposure probably by facilitating 5HT1A receptors neurotransmission. Our results suggest that CBD has beneficial potential for PTSD treatment and that 5HT1A receptors could be a therapeutic target in this disorder.

Topics: Animals; Behavior, Animal; Cannabidiol; Disease Models, Animal; Male; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1A; Serotonin 5-HT1 Receptor Antagonists; Stress Disorders, Post-Traumatic; Stress, Psychological; Time Factors