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Anxiety, Stress & Depression 


Best reviews

2022: A review of using CBD for stress-related disorders

Potential Utility of Cannabidiol in Stress-Related Disorders

2022: A review confirms the efficacy of CBD for social anxiety
Systematic literature review of human studies assessing the efficacy of cannabidiol for social anxiety


2022: A review of the studies on using CBD & THC for anxiety
Medicinal cannabis for the treatment of anxiety disorders

2022: A review of the evidence for CBD finds help for anxiety & anti-addiction effects
The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence


2022: A review on treating depression rapidly by targeting the endocannabinoid system

Rapid treatments for depression: Endocannabinoid system as a therapeutic target

2022: This review looks at the use of CBD for psychiatric disorders & finds the strongest evidence for psychotic symptoms & anxiety

A scoping review of the use of cannabidiol in psychiatric disorders

2022: A review of cannabis for anxiety

A Comparative Review of Cannabis-Based Medication and First-Line Pharmacotherapy Treatments for Anxiety Disorders

2021: This review looks at how the endocannabinoids regulate your metabolism, stress response & development

Lipid endocannabinoids in energy metabolism, stress and developmental programming

2021: This review looks at targeting the ECS for social anxiety disorder – with a focus on CBD

The endocannabinoid system in social anxiety disorder: from pathophysiology to novel therapeutics

2021: A review of how the cannabinoids relate to our fear & anxiety systems

Cannabinoids: revealing their complexity and role in central networks of fear and anxiety

2021: CV Sciences medical adviser Dr. Jamie Corroon on using CBD to lessen the anxiety that can be caused by THC

2021: A review of cannabinoids for the regulation of anxiety

Endocannabinoids, Cannabinoids and the Regulation of Anxiety

2021: This meta-review of 11 studies looking at using CBD for anxiety

Anxiolytic and antidepressant effects of cannabidiol: a systematic review

2021: This review highlights the many parts of the ECS that can be targeted to treat depression

Molecular Targets of Cannabinoids Associated with Depression

2021: A review of anxiety & trauma disorders focuses on how the endocannabinoid system works with the noradrenaline system to extinguish fears

In it together? The case for endocannabinoid-noradrenergic interactions in fear extinction

2021: A review finds that in all the studies examined, CBD exhibited anxiolytic & antidepressant activities

Anxiolytic and antidepressant effects of cannabidiol: a systematic review

2021: This review looks at targeting 2-AG for the treatment of depression

Targeting 2-arachidonoylglycerol (2-AG) signalling the neurobiology and treatment of depression

2021: This review looks at how targeting the endocannabinoid may help with depression via the regulation of dopamine

Discovering the Lost Reward: Critical Locations for Endocannabinoid Modulation of the Cortico–Striatal Loop That Are Implicated in Major Depression

2021: This review looks at how the endocannabinoid system positively affects neurogenesis & immune function in animal models of affective disorders (aka mood disorders such as anxiety, depression, bipolar disorder, etc)

A systematic, integrative review of the effects of the endocannabinoid system on inflammation and neurogenesis in animal models of affective disorders

2021: A review of targeting the endocannabinoid system for depression

Role and Function of Endocannabinoid System in Major Depressive Disease

2021: A review on whether we can measure the levels of endocannabinoids as a marker for clinical depression

Integrating Endocannabinoid Signalling In Depression

2021: This in-depth review looks at the mechanisms of how CBD works for anxiety & mood disorders

Cannabidiol as a Potential Treatment for Anxiety and Mood Disorders: Molecular Targets and Epigenetic Insights from Preclinical Research

2020: A review of using CBD for anxiety & mental health - includes a nice chart of the mechanism

Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders

2020: This review looks at the use of cannabinoids for anxiety - includes 14 studies

Efficacy and acceptability of cannabinoids for anxiety disorders in adults: A systematic review & meta-analysis

2020: A review of CBD for anxiety studies

Use of Cannabidiol for the Treatment of Anxiety: A Short Synthesis of Pre-Clinical and Clinical Evidence

2020: A meta-review of the ECS's effects on fear, stress & anxiety

The endocannabinoid system in modulating fear, anxiety, and stress

2020: A review of how early-life stressors change the ECS & the stress/anxiety response

Early life stress and development of the endocannabinoid system: A bidirectional process in programming future coping

2020: The ECS & fear

The endocannabinoid system in the amygdala and modulation of fear

2020: Hillard on the endocannabinoids & stress management

Meet Your Stress Management Professionals: The Endocannabinoids

2019: Endocannabinoids & stress signaling

Endocannabinoids, stress signaling, and the locus coeruleus-norepinephrine system

2019: Review on the use of CBD & oxytocin for social anxiety disorder

Modulation of the Endocannabinoid and Oxytocinergic Systems as a Potential Treatment Approach for Social Anxiety Disorder

2019: A review on the antidepressant effect of CBD in animals – looks at many mechanisms

Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms

2018: Review of ECS, stress & the HPA axis

Endocannabinoid system, stress and HPA axis

2017: CBD for panic – great chart of the brain & a table of effects in brain regions

Evidences for the Anti-panic Actions of Cannabidiol

2016: Hill on the interactions between stress & the ECS

Neurobiological Interactions Between Stress and the Endocannabinoid System

2016: CBD & anxiety related disorders

Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders

2016: The ECS & the immune system in depression

Crosstalk between endocannabinoid and immune systems: a potential dysregulation in depression?

2015: a review of 49 studies of CBD for anxiety

Cannabidiol as a Potential Treatment for Anxiety Disorders.

2014: Hillard on the ECS & major depression

Endocannabinoid signaling in the etiology and treatment of major depressive illness

2014: A review of animal studies finding CBD’s help for depression & anxiety

Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa

Chart Gallery

Timeline of Research

2023: In mice, a single dose of CBD reduced obsessive-compulsive symptoms & object memory in males but not females while it lessened anxiety behavior in both, probably via the potassium channels

Single cannabidiol administration affects anxiety-, obsessive compulsive-, object memory-, and attention-like behaviors in mice in a sex and concentration dependent manner

2022: Among patients taking CBD for a month, it significantly improved well-being, anxiety, sleep disturbance & pain
The Safety and Effectiveness of Commercially Available Cannabidiol Products for Health and Well-Being: A Randomized, Multi-Arm, Open-Label Waitlist-Controlled Trial

2022: In young people with treatment-resistant anxiety, CBD (up to 800 mg per day) significantly reduced their depression scores
Cannabidiol for Treatment-Resistant Anxiety Disorders in Young People: An Open-Label Trial

2022: In a survey of medical cannabis patients in Oklahoma, they found cannabis to provide ‘extreme relief’ from anxiety, sleep problems, nausea & depression
Characteristics of adults with a medical cannabis license, reasons for use, and perceptions of benefit following medical cannabis legalization in Oklahoma

2022: In people with moderate to severe anxiety, a sublingual CBD solution for four weeks improved anxiety, mood, sleep, quality of life & cognition
Clinical and cognitive improvement following full-spectrum, high-cannabidiol treatment for anxiety: open-label data from a two-stage, phase 2 clinical trial

2022: A survey of women’s cannabis use around menopause reported that many found it helpful for sleep & anxiety
A survey of medical cannabis use during perimenopause and postmenopause

2022: A survey of singers finds that they use CBD for stress, anxiety or chronic pain
Alternative and Complimentary Medication Use in Singers: A Pilot Survey

2022: A series of case studies on using CBD for anxiety (with an especially well-done chart on the many biochemical actions of CBD)
Cannabidiol as a personalized treatment for anxiety: clinical cases in Mexico

2022: Among patients with fibromyalgia, part of the ability of medical cannabis to help with pain results from their ability to help with sleep, anxiety & depression
Predictors of pain reduction among fibromyalgia patients using medical cannabis: a long-term prospective cohort study

2022: Another survey of CBD users (young adults this time) that list the tops uses of CBD as pain, sleep & anxiety
Cannabidiol Knowledge, Perceptions, and Use Among Young Adults in 6 U.S. Metropolitan Areas

2022: In male vs female cancer patients, cannabis helped both groups with pain, sleep, anxiety & well-being – but in females, it helped with nausea, lack of appetite & shortness of breath while in males it helped more with pain
Sex differences exist in the perceived relief of cancer symptoms with medical cannabis: results from the Quebec Cannabis Registry

2022: A survey of Canadian cannabis users found these conditions at the top of the list: anxiety (70%), insomnia (56%), pain (53%), depression (37%)
A description of self-medication with cannabis among adults with legal access to cannabis in Quebec, Canada

2022: In stress-related psychiatric disorders such as anxiety, schizophrenia & depression, a review of how CBD’s ability to methylate (turn off) genes in the DNA can help regulate enzymes that help with these disorders
Regulation of DNA Methylation by Cannabidiol and Its Implications for Psychiatry: New Insights from In Vivo and In Silico Models

2022: In older rats, 7 days of CBD treatment caused an antidepressant effect
Dose-Dependent Antidepressant-Like Effects of Cannabidiol in Aged Rats

2022: In a mouse model of depression, inhibiting the FAAH enzyme helped reverse depression caused by early life stress
FAAH Inhibition Restores Early Life Stress-Induced Alterations in PFC microRNAs Associated with Depressive-Like Behavior in Male and Female Rats

2022: Hair analysis suggests that low anandamide levels are correlated with symptoms of depression
Depressive symptoms are negatively associated with hair N-arachidonoylethanolamine (anandamide) levels: A cross-lagged panel analysis of four annual assessment waves examining hair endocannabinoids and cortisol

2022: In a mouse model of anxiety, the ability of CBD to lower anxiety seemed to have gender differences based on the hormone cycle of the females
Sex-dependent differences in the anxiolytic-like effect of cannabidiol in the elevated plus-maze

2022: In mice being fed high-carb ultra-processed food, CBD lowered the anxiety-inducing nature & compulsive behaviors caused by that diet
Cannabidiol ameliorates the anxiogenic and compulsive-like behaviors induced by chronic consumption of a high-carbohydrate diet in male mice

2022: A case report of cannabis helping with generalized anxiety disorder
A Case Report on Generalized Anxiety Disorder through Medical Cannabis

2022: In a mouse model of anxiety & depression, CBD seemed to help via the CB1 receptor as well as by increasing the genetic expression of GABA & cannabinoid receptors
Cannabinoid CB1 Receptor Involvement in the Actions of CBD on Anxiety and Coping Behaviors in Mice

2022: A review of the reasons for medical cannabis use in Ontario
Declared Rationale for Cannabis Use Before and After Legalization for Nonmedical Use: A Longitudinal Study of Community Adults in Ontario

2022: An analysis of medical cannabis patients finds that it helps them with generalized anxiety disorder

UK Medical Cannabis Registry: an analysis of clinical outcomes of medicinal cannabis therapy for generalized anxiety disorder

2022: An analysis of the patients in the UK’s Medical Cannabis Registry, they found “treatment to be associated with a relatively low incidence of severe adverse events” & “positive changes following treatment were observed in general, as well as anxiety and sleep-specific, HRQoL [health-related quality of life] outcomes”

An Updated Analysis of Clinical Outcome Measures Across Patients From the UK Medical Cannabis Registry

2022: Endocannabinoids & endovanilloids balance each other’s actions in the release of stress hormones

Cannabinoid and vanilloid pathways mediate opposing forms of synaptic plasticity in corticotropin-releasing hormone neurons

2022: A study of anxiety in humans finds that 2-AG levels change in response to stress

Endocannabinoid system reactivity during stress processing in healthy humans

2022: In horses being transported, CBD reduced stress

Cannabidiol Supplementation and Physiological Response in Transported Horses

2022: In steers, feeding them hemp rich in CBDA helped with stress & inflammation

Short term feeding of industrial hemp with a high cannabidiolic acid (CBDA) content increases lying behavior and reduces biomarkers of stress and inflammation in Holstein steers

2022: In dairy cows, daily injections of AEA & 2-AG helped with stress & metabolism

Effects of endocannabinoids on feed intake, stress response and whole-body energy metabolism in dairy cows

2022: In a mouse model of fear and anxiety, using orexin to increase 2-AG levels in the amygdala & hippocampus led to less extinction of fearful memories

Amygdalar CB2 cannabinoid receptor mediates fear extinction deficits promoted by orexin-A/hypocretin-1

2022: In female mice with early life stress, CBD reverses their anxiety & depression behaviors via a modulation of brain energy metabolism

Early-life stress induces emotional and molecular alterations in female mice that are partially reversed by cannabidiol

2022: In female mice with early life stress, CBD reverses their anxiety & depression behaviors via a modulation of brain energy metabolism

Early-life stress induces emotional and molecular alterations in female mice that are partially reversed by cannabidiol

2022: In a mouse model of depression, LSD combined with CBD to help alleviate depression more than either substance alone

Synergistic effects of lysergic acid diethylamide (LSD) and cannabidiol (CBD)

2022: In a mouse model of depression, CBD prevented depressive behaviors by modulating the differentiation of neural stem cells into less stressful configurations

Cannabidiol prevents depressive-like behaviors through the modulation of neural stem cell differentiation

2022: In a rat model of depression, blocking the CB1 receptor at certain timeframes increased their locomotion


2021: This survey finds patients using CBG-rich products report for anxiety, chronic pain, depression & insomnia

Survey of Patients Employing Cannabigerol-Predominant Cannabis Preparations: Perceived Medical Effects, Adverse Events, and Withdrawal Symptoms

2021: In a rat model of depression, males & females showed differential antidepressant effects from CBD

Strain, Sex, and Time Dependent Antidepressant-like Effects of Cannabidiol

2021: In the hair of chronic cocaine users, they contained higher levels of the steroid cortisone (which becomes the stress hormone cortisol) & lower levels of the endocannabinoids OEA & PEA

Alterations of stress-related glucocorticoids and endocannabinoids in hair of chronic cocaine users

2021: In stressed rats, inhibiting the FAAH enzyme caused antistress effects in their brains, reduced stress hormones & promoted a return to baseline

Effects of Fatty Acid Amide Hydroxylase Inhibitor URB597 on the Catecholaminergic Activity of the Adrenal Medulla in Stressed Male and Female Rats

2021: This survey confirms that people find CBD effective for their anxiety

Expectancies about the effects of cannabidiol products on anxiety symptoms

2021: In an animal model, the antidepressant effects of rosmarinic acid (found in rosemary) is probably mediated by the endocannabinoid system

Antidepressant-like effect of rosmarinic acid during LPS-induced neuroinflammatory model: The potential role of cannabinoid receptors/PPAR-γ signaling pathway

2021: In mice with no CB1 receptors in their neurons that release stress hormones, they were more likely to be started by sudden loud sounds

CB1 receptors in corticotropin-releasing factor neurons selectively control the acoustic startle response in male mice

2021: In female rats exposed to the smell of a predator, they had lower levels of 2-AG & higher levels of AEA in the amygdala (fear center of the brain) versus male rats who showed none of these alterations

Amygdalar endocannabinoids are affected by predator odor stress in a sex-specific manner and modulate acoustic startle reactivity in female rats

2021: In a study of human using cannabis, chemovars (strains) of cannabis high in CBD reduced the plasma concentrations of THC as well as the reports of paranoia & anxiety while still reporting a similar positive mood effect

Effects of cannabidiol in cannabis flower: Implications for harm reduction

2021: In rats experiencing fear, this study looks at the interaction of adrenaline, stress hormones & the endocannabinoid system

Interactions of noradrenergic, glucocorticoid and endocannabinoid systems intensify and generalize fear memory traces

2021: In mice with depression induced by mild stress, activating the CB1 receptor reduced neuroinflammation & lessened oxidative stress injury

Cannabinoid receptor agonist WIN55212-2 reduces unpredictable mild stress-induced depressive behavior of rats

2021: In rats, mothers being fed a high-fat diet altered the CB1 levels in the brains of their sons & led to depressive symptoms in early life

Maternal High-Fat Diet Modulates Cnr1 Gene Expression in Male Rat Offspring

2021: In a mouse model of depression, CBD was suggested as an antidepressant

The effects of cannabidiol, Δ9-tetrahydrocannabinol, and combinations of cannabidiol and Δ9-tetrahydrocannabinol in the open field test and forced swim test

2021: In a fruit fly model of depression, an extract made from hemp seeds alleviated depression symptoms & modulated the circadian rhythm

Anti-depressant effects of ethanol extract from Cannabis sativa (hemp) seed in chlorpromazine-induced Drosophila melanogaster depression model

2021: In rats with depression from traumatic nerve pain, the injury seems to lower the levels of cannabinoids & lead to behavioral depression

Dynamic Change of Endocannabinoid Signaling in the Medial Prefrontal Cortex Controls the Development of Depression after Neuropathic Pain

2021: In rats with nerve injuries, CBD helped with pain & symptoms of depression via the serotonin receptors & CB1 receptors

Cannabidiol in the prelimbic cortex modulates the comorbid condition between the chronic neuropathic pain and depression-like behaviour in rats: The role of medial prefrontal cortex 5-HT 1A and CB 1 receptors

2021: In a rodent model of depression, CBD prevented “both behavioral & neuro-immunological changes associated” with depression as well as modulating neuroinflammation

Cannabidiol prevents lipopolysaccharide-induced sickness behavior and alters cytokine and neurotrophic factor levels in the brain

2021: In mice, ketamine & CBD combined to increase their antidepressant effects

Co-administration of cannabidiol and ketamine induces antidepressant-like effects devoid of hyperlocomotor side-effects

2021: In rats, the lateral hypothalamus (brain area involved with the body’s response to emotional stress) modulated their cardiovascular response to stress via the CB1 receptors & GABA

Lateral hypothalamus involvement in control of stress response by bed nucleus of the stria terminalis endocannabinoid neurotransmission in male rats

2021: In frontline healthcare professionals working with COVID-19 patients, 1 month of CBD reduced symptoms of burnout & emotional exhaustion

Efficacy and Safety of Cannabidiol Plus Standard Care vs Standard Care Alone for the Treatment of Emotional Exhaustion and Burnout Among Frontline Health Care Workers During the COVID-19 Pandemic: A Randomized Clinical Trial

2021: In a mouse model of chronic unpredictable stress, the analgesic drug dipyrone may exert its effects via the ECS & the TRPV1 receptor (which is activated by anandamide)

The role of endocannabinoid system and TRPV1 receptors in the antidepressant and anxiolytic effects of dipyrone in chronic unpredictable mild stress in mice

2021: This survey of Canadian cannabis clinics found CBD helped for pain, anxiety & depression in moderate & severe cases but not mild cases

Cannabidiol use and effectiveness: real-world evidence from a Canadian medical cannabis clinic

2021: In rats exposed to THC, CBD blocked the anxiety-producing effects & enhanced the anxiety-reliving effects

Female but not male rats show biphasic effects of low doses of Δ 9-tetrahydrocannabinol on anxiety: can cannabidiol interfere with these effects?

2021: In rats, the ability of 2-AG to reduce fear & stress behaviors is mediated by CB1 & CB2

Anti-aversive effect of 2-arachidonoylglycerol in the dorsolateral periaqueductal gray of male rats in contextual fear conditioning and Vogel tests

2021: This study from Brazil suggests using CBD to prevent burnout for health care workers on the frontline of the COVID pandemic

Cannabidiol as a Treatment for Mental Health Outcomes Among Health Care Workers During the Coronavirus Disease Pandemic

2021: In mice, an analysis of CBD's effect on brain activity confirms that "CBD reduces autonomic arousal under conditions of emotional and physical stress"

Cannabidiol Has a Unique Effect on Global Brain Activity: A Pharmacological, Functional MRI Study in Awake Mice

2021: In a rat model of depression, CBD modulated neuroinflammation & produced antidepressant-like effects

Cannabidiol antidepressant-like effect in the lipopolysaccharide model in mice: modulation of inflammatory pathways

2021: In mice, CBD caused antidepressant effects via the serotonin & noradrenaline in the hippocampus

Chronic administration of synthetic cannabidiol induces antidepressant effects involving modulation of serotonin and noradrenaline levels in the hippocampus

2021: In diabetic animals, CBD caused antidepressant & anxiolytic effects

Cannabidiol induces antidepressant and anxiolytic-like effects in experimental type-1 diabetic animals by multiple sites of action

2020: For people stressed out about COVID, this paper suggests CBD

Could Cannabidiol Be a Treatment for Coronavirus Disease-19-Related Anxiety Disorders?

2021: In humans with depression, the improvements caused by transcranial magnetic stimulation (a gentle electric charge on the skull) seem to be at last partially mediated by 2-AG

Peripheral endocannabinoid serum level in association with repetitive transcranial magnetic stimulation (rTMS) treatment in patients with major depressive disorder

2021: In rats, the ability of cannabinoids to lower anxiety may be via the nitric oxide system

Interactions between the nitrergic and the endocannabinoid system in rats exposed to the elevated T maze

2021: In mice with no CB1 receptors, social stress caused increased mortality, dysregulation of the hormones & altered brain immune cell responses

Cannabinoid receptor 1 signalling modulates stress susceptibility and microglial responses to chronic social defeat stress

2021: A nicely designed clinical study of anandamide (AEA) levels & your ability to stop reacting to a negative stimulus

Fear extinction learning and anandamide: an fMRI study in healthy humans


2021: In humans who have experienced trauma, their levels of circulating endocannabinoids is impacted & may function as a clinical target for treating their depression

Circulating endocannabinoids and prospective risk for depression in trauma-injury survivors

2021: In a rat model of anxiety from colitis, the increase in the FAAH enzyme led to lower levels of AEA & more anxiety

Comorbid anxiety-like behavior in a rat model of colitis is mediated by an upregulation of corticolimbic fatty acid amide hydrolase

2021: In humans experiencing acute stress, the levels of 2-AG in their saliva increased

Endocannabinoid reactivity to acute stress: Investigation of the relationship between salivary and plasma levels

2021: A great deep-dive research in mice about how the stress response is regulated by FAAH (the enzyme that breaks down anandamide) & MAGL (the enzyme that breaks down 2-AG)

Selective inhibition of monoacylglycerol lipase is associated with passive coping behavior and attenuation of stress-induced dopamine release in the medial prefrontal cortex

2021: In rats, inhibition of the FAAH enzyme & exposure to early life stress may increase depression

Inhibition of fatty acid amide hydrolase (FAAH) during adolescence and exposure to early life stress may exacerbate depression-like behaviors in male and female rats

2021: In the amygdala of monkeys, there's a high density of CB1 receptor & hence the suggestion that targeting the endocannabinoid system will be a useful treatment for fear & anxiety in humans

Expression of the type 1 cannabinoid receptor (CB1R) in CCK-immunoreactive axon terminals in the basolateral amygdala of the rhesus monkey (Macaca mulatta)

2020: In humans with panic disorder, a look at their endocannabinoids levels

Blood endocannabinoid levels in patients with panic disorder

2020: In rats experiencing chronic unpredictable stress, a FAAH inhibitor had a marked gender difference in its effects on behavior & catecholamines (the neurotransmitter family including dopamine & adrenaline)

Inhibition of the fatty acid amide hydrolase changes behaviors and brain catecholamines in a sex-specific manner in rats exposed to chronic unpredictable stress

2020: In rats, when morphine helps alleviate the negative side effects of stress, it does so partially via the ECS

Morphine improved stress-induced amnesia and anxiety through interacting with the ventral hippocampal endocannabinoid system in rats

2020: A grad student thesis found that "CBD increases serotonin receptor activity in crayfish as seen with SSRIs, thus could be of use in treating anxiety"

From the Dinner Pot to Smoking Pot; How a Better Understanding of Cannabidiol in Crayfish could Alleviate Anxiety and Modulate Hunger

2020: In mice experiencing stress, anandamide regulates the release of noradrenaline into the amygdala

Effects of the Endocannabinoid Anandamide on the Efficiency of Noradrenergic Neurotransmission in the Amygdaloid Body in Acute Stress in Mice

2020: In young mice exposed to early childhood stress, drugs that block the FAAH enzyme or block the MAGL enzyme help prevent the later development of depression, probably via stimulation of BDNF

Antidepressant-like effects of URB597 and JZL184 in male and female rats exposed to early life stress

2020: In rat brains, the ECS contributes to long-term depression (not the mental state - but the downregulation of signals, ie. forgetting)

Endocannabinoid receptors contribute significantly to multiple forms of long-term depression in the rat dentate gyrus

2020: In an analysis of the prefrontal cortexes of humans with major depressive disorder, there's dysregulation of the endocannabinoid system, especially CB1

Regulation of cannabinoid CB 1 and CB 2 receptors, neuroprotective mTOR and pro-apoptotic JNK1/2 kinases in postmortem prefrontal cortex of subjects with major depressive disorder

2020: In rats with depression, activating the GPR55 receptor helped to reverse symptoms

O-1602, an Agonist of Atypical Cannabinoid Receptors GPR55, Reverses the Symptoms of Depression and Detrusor Overactivity in Rats Subjected to Corticosterone Treatmen

2020: In rats, the fear response is linked to the endocannabinoid system

Differential modulation of the contextual conditioned emotional response by CB1 and TRPV1 receptors in the ventromedial prefrontal cortex: Possible involvement of NMDA/nitric oxide-related mechanisms

2020: In this unique study of humans, they looked at the circulating levels of endocannabinoids in grieving adults

Circulating endocannabinoid concentrations in grieving adults

2020: In a human observation study, the efficacy of cannabis as an antidepressant

The Effectiveness of Cannabis Flower for Immediate Relief from Symptoms of Depression

2020: In mice exposed to social stress, increasing 2-AG helped to normalize activity in the nucleus accumbens brain region that modulates emotions

Endocannabinoid-Mediated Plasticity in Nucleus Accumbens Controls Vulnerability to Anxiety After Social Defeat Stress

2020: In mice, the terpene terpineol seems to cause its antidepressant effects via the CB1, CB2 & D2 dopamine receptor

Antidepressant-Like Effect of Terpineol in an Inflammatory Model of Depression: Involvement of the Cannabinoid System and D2 Dopamine Receptor

2020: In rats with depression, CBD helped to enjoy life more (prohedonic) & lowered stress levels

Effects of Chronic Cannabidiol Treatment in the Rat Chronic Unpredictable Mild Stress Model of Depression

2020: In rats, blocking TRPV1 & FAAH in a specific brain region causes increased anxiety

Blockade of the endovanilloid receptor, TRPV1, and of the endocannabinoid enzyme, FAAH, within the nucleus accumbens shell elicits anxiolytic-like effects in male rats

2020: In rats scared of predators, the ability of MAGL inhibitors (which raise 2-AG levels) to lessen anxiety is mediated by the CB2 receptor

Cannabinoid CB2 receptors mediate the anxiolytic-like effects of monoacylglycerol lipase inhibition in a rat model of predator-induced fear

2020: In an animal model, the CB1 receptors and the mu-opioid receptors work together to regulate the fear response in the periaqueductal gray matter (PAG) region of the brain

Mu-opioid and CB1 cannabinoid receptors of the dorsal periaqueductal gray interplay in the regulation of fear response, but not antinociception

2020: In this forced-swim test of mice, CBD showed antidepressant effects by its ability to methylate DNA (block its transcription)

CBD modulates DNA methylation in mice prefrontal cortex and hippocampus of mice exposed to forced swim

2020: In mice, this fascinating preclinical work determined that the ability of the ECS to end an acute stress response is based on a genetic downregulation of two enzymes that cut up 2-AG (ABHD6 & MAGL)

Termination of acute stress response by the endocannabinoid system is regulated through lysine-specific demethylase 1-mediated transcriptional repression of 2-AG hydrolases ABHD6 and MAGL

2020: In humans, it turns out that you can measure someone's level of endocannabinoids by testing their hair and then correlate it to depression, anxiety & burnout

Determination of endocannabinoids and N-acylethanolamines in human hair with LC-MS/MS and their relation to symptoms of depression, burnout, and anxiety

2020: In mice, two widely used antidepressant drugs seem to work partially via the CB1 receptor

Influence of the endocannabinoid system on the antidepressant activity of bupropion and moclobemide in the behavioural tests in mice

2020: In a survey of older patients, cannabis found helpful for anxiety


2020: In mice, this study finds that the raising of anxiety by a Candida infection is because of changes in the ECS

Colonization with the commensal fungus Candida albicans perturbs the gut-brain axis through dysregulation of endocannabinoid signaling


2020: In depressed rats, CBD did not work as well in adolescents as in adults

Decreased sensitivity in adolescent versus adult rats to the antidepressant-like effects of cannabidiol

2020: In a human case study, CBD found helpful for a teen with depression & drug abuse - after taking high levels of CBD, they quit their depression medication & stopped abusing illegal drugs

Cannabidiol treatment in an adolescent with multiple substance abuse, social anxiety and depression

2020: In human teens who use cannabis experience higher rates of depression than those who don't use it - but a higher frequency of use was associated with lower rates of depression

Relationship between cannabis use frequency and major depressive disorder in adolescents: Findings from the National Survey on Drug Use and Health 2012–2017

2020: In mice, 2-AG signaling mediate stress response between brain regions

Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening

2020: In rats, activating CB1 helped with anxiety - but not with conditioned fear

Endocannabinoid modulating drugs improve anxiety but not the expression of conditioned fear in a rodent model of post-traumatic stress disorder

2020: In animal model, the CB1 receptor helps to modulate the cardiovascular response to stress

Cannabinoid receptor type 1 in the bed nucleus of the stria terminalis modulates cardiovascular responses to stress via local N-methyl-D-aspartate receptor/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling

2020: When inducing panic in rats, CBD lessens the fear effects via CB1 receptors in the ventromedial hypothalamus

Cannabidiol-induced panicolytic-like effects and fear-induced antinociception impairment: the role of the CB 1 receptor in the ventromedial hypothalamus

2020: In a double-blind study of humans with Parkinson’s, 300 mg of CBD decreased anxiety and tremors during a simulation of public speaking

Effects of acute cannabidiol administration on anxiety and tremors induced by a Simulated Public Speaking Test in patients with Parkinson's disease

2020: In rats, inhibiting FAAH & MAGL helped with depression

Dual pharmacological inhibitor of endocannabinoid degrading enzymes reduces depressive-like behavior in female rats

2019: In rodents, CBD caused a rapid and sustained antidepressant effect via BDNF & increased synaptogenesis

Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex

2019: In mice, they look at how the activation and inhibition of CB1 & CB2 can help antidepressants work better

Influence of the CB 1 and CB 2 cannabinoid receptor ligands on the activity of atypical antidepressant drugs in the behavioural tests in mice

2019: In mice, the activation of the CB2 receptor may increase the efficacy of antidepressants

Ligands of the CB2 cannabinoid receptors augment activity of the conventional antidepressant drugs in the behavioural tests in mice

2019: In two different rat models of depression, CBD increased hedonic enjoyment of sugar & caused more mobility in the forced swim test

Effects of cannabidiol in males and females in two different rat models of depression

2019: In humans using benzodiazapenes, almost half of them could stop using them after starting medical cannabis (146 patients in retrospective analysis)

Reduction of Benzodiazepine Use in Patients Prescribed Medical Cannabis

2019: In humans, "there was no significant association between marijuana use and experiencing [a major depressive episode], and no association between marijuana use and suicidal ideation"

Exploring the association between cannabis use and depression

2019: In rats, the ability of transcranial magnets to reverse depression & proteins in the hippocampus is partially via enhanced ECS signaling

Repetitive high-frequency transcranial magnetic stimulation reverses depressive-like behaviors and protein expression at hippocampal synapses in chronic unpredictable stress-treated rats by enhancing endocannabinoid signaling

2019: In mice, CBD shows anti-depressant effect

Pharmacokinetics of oral and intravenous cannabidiol and its antidepressant-like effects in chronic mild stress mouse model

2019: In rats with PTSD, CBD reduced anxiety but not freezing

The Divergent Effects of CDPPB and Cannabidiol on Fear Extinction and Anxiety in a Predator Scent Stress Model of PTSD in Rats

2019: In mice who were isolated and therefore more aggressive, CBD reduced their aggression via CB1 & serotonin

Cannabidiol attenuates aggressive behavior induced by social isolation in mice: Involvement of 5-HT1A and CB1 receptors

2019: In humans with depression, the mood boost of exercise may be caused by endocannabinoids

Serum Endocannabinoid and Mood Changes after Exercise in Major Depressive Disorder

2019: In mice, the depressant effects of ketamine may involve the endocannabinoid system

Ketamine-induced antidepressant like effects in mice: A possible involvement of cannabinoid system

2019: In a rat model of depression, lower levels of endocannabinoids in the cortex & hippocampus

Hemisphere-dependent endocannabinoid system activity in prefrontal cortex and hippocampus of the Flinders Sensitive Line rodent model of depression

2019: Shannon’s case series on anxiety & sleep in humans using CBD-rich hemp extracts

Cannabidiol in Anxiety and Sleep: A Large Case Series

2019: In a double-blind study of human teens with anxiety, 300 mg of CBD helped significantly

Anxiolytic Effects of Repeated Cannabidiol Treatment in Teenagers With Social Anxiety Disorders

2019: In a human study, U shaped curve found for CBD’s help for public speaking anxiety

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

2019: In rats, CBD upregulates serotonin sensitivity similar to an SSRI

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

2019: This genome-wide association study in humans, found one variant associated with depression but not the other

The association of endocannabinoid receptor genes (CNR1 and CNR2) polymorphisms with depression

2019: In mice, how stress alters ECS levels

Chronic Psychosocial Stress Causes Increased Anxiety-Like Behavior and Alters Endocannabinoid Levels in the Brain of C57Bl/6J Mice

2019: In rats, how antidepressant drugs change the expression of ECS enzymes in brain regions

Brain region-dependent changes in the expression of endocannabinoid-metabolizing enzymes in rats following antidepressant drugs

2018: In stressed mice, CBD lowers anxiety via neurogenesis & dendritic remodeling

The anxiolytic effects of cannabidiol in chronically stressed mice are mediated by the endocannabinoid system: Role of neurogenesis and dendritic remodeling

2018: In two rat models of depression, CBDA (HU580) reduced depression symptoms

Acute oral cannabidiolic acid methyl ester reduces depression-like behavior in two genetic animal models of depression

2018: In mice, the antidepressant effects of CBD are caused by serotonin

Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels

2018: In rats, boosting ECS tone helps maintain the HPA axis in a basal state & inhibits corticosterone release from the adrenal gland

Pharmacological augmentation of endocannabinoid signaling reduces the neuroendocrine response to stress

2017: In humans, shock therapy enhanced endocannabinoids & helped their depression

Electroconvulsive therapy enhances endocannabinoids in the cerebrospinal fluid of patients with major depression: a preliminary prospective study

2017: In rats experiencing foot shock, CBD & CBDA decreased the stress

Effect of prior foot shock stress and Δ 9-tetrahydrocannabinol, cannabidiolic acid, and cannabidiol on anxiety-like responding in the light-dark emergence test in rats

2017: In postmortem human brains, the ECS dysregulated oppositely in schizophrenics & depressed people

Schizophrenia and depression, two poles of endocannabinoid system deregulation

2017: In mice, 2-AG helps to promote resilience against stress

Endocannabinoid signalling modulates susceptibility to traumatic stress exposure

2016: In mice, role of serotonin receptors in CBD’s antidepressant effects

Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors

2016: In rats, injections of CBD into the ventral medial prefrontal cortex caused antidepressant effects perhaps via CB1 & serotonin receptors

Antidepressant-like effect of cannabidiol injection into the ventral medial prefrontal cortex-Possible involvement of 5-HT1A and CB1 receptors

2016: In mice, CBD lowered anxiety & increased neurogenesis

Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice

2016: In rats, CBD caused a prohedonic (enjoyment) effect

Prohedonic Effect of Cannabidiol in a Rat Model of Depression

2015: In rats, injection of CBD into limbic regions of the frontal cortex lessened anxiety in stressful tests via serotonin receptors

Effects of intra-infralimbic prefrontal cortex injections of cannabidiol in the modulation of emotional behaviors in rats: contribution of 5HT₁A receptors and stressful experiences

2015: In an animal model, microinjection of CBD mediated panic response via CB1

Dissociation between the panicolytic effect of cannabidiol microinjected into the substantia nigra, pars reticulata, and fear-induced antinociception elicited by bicuculline administration in deep layers of the superior colliculus: The role of CB1-cannabinoid receptor in the ventral mesencephalon

2014: In rats, injection of CBD lessens expression of anxiety behaviors via 5HT1A receptors

Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: Involvement of 5HT1A receptors and previous stressful experience

2014: In stressed mice, importance of neurogenesis & autophagy via CB1 receptor activation for stress and neuroprotection

Behavioural effects of cannabidiol in chronically stressed mice is mediated by neurogenesis and autophagy through CB1 receptor activation

2014: In stressed mice, the ECS works with the HPA for recovery with a focus on key gender differences

Endocannabinoid signaling in hypothalamic-pituitary-adrenocortical axis recovery following stress: effects of indirect agonists and comparison of male and female mice

2014: In rats, the anti-depressive effects of transcranial magnetic stimulation mediated by the ECS

Anti-depressive mechanism of repetitive transcranial magnetic stimulation in rat: the role of the endocannabinoid system

2013: In humans, CBD helped with the conditioning, extinction & recall of fear

Cannabidiol enhances consolidation of explicit fear extinction in humans

2013: In mice, the anxiety-lessening power of CBD depends on neurogenesis in the hippocampus

The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system

2013: In rats, the panic responses reduced by CBD involves serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter

Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats

2013: In mice & tissue culture, COX2 inhibition decreases anxiety via activation of the endocannabinoids

Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation

2013: In mice next to a snake, CBD helped to calm their panic response via serotonin

The role of 5-HT1A receptors in the anti-aversive effects of cannabidiol on panic attack-like behaviors evoked in the presence of the wild snake Epicrates cenchria crassus (Reptilia, Boidae)

2013: In a restrained animal, CBD lessened the stress via serotonin

Cannabidiol administration into the bed nucleus of the stria terminalis alters cardiovascular responses induced by acute restraint stress through 5-HT₁A receptor

2012: In rats, injection of CBD lessens expression of contextual fear conditioning via 5HT1A receptors

Cannabidiol injected into the bed nucleus of the stria terminalis reduces the expression of contextual fear conditioning via 5-HT1A receptors

2012: In rats exposed to a cat, CBD reduced their anxiety via serotonin

Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors

2012: In tissue culture, mechanisms of how CBD protects the oligodendrocyte progenitor cells (OPCs) which can differentiate into myelinating cells to reduce cell death & free radical production

Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress

2012: In mice next to a snake, CBD reduced their panic response

Anti-aversive effects of cannabidiol on innate fear-induced behaviors evoked by an ethological model of panic attacks based on a prey vs the wild snake Epicrates cenchria crassus confrontation paradigm

2011: In a double-blind study of humans with anxiety, 400 mg of CBD reduced anxiety - scans showed decreased activity in left parahippocampal gyrus, hippocampus, and inferior temporal gyrus (anxiety mediating centers) & increased activity in right posterior cingulate gyrus (an emotional processing center)

Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report

2011: In an animal model, CBD decreased the anxiety of being restrained

Effects of intracisternal administration of cannabidiol on the cardiovascular and behavioral responses to acute restraint stress

2011: In humans, CBD helps with public speaking anxiety

Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients

2011: In an animal model, the role of MAGL in coping with chronic stress

Reversible gating of endocannabinoid plasticity in the amygdala by chronic stress: a potential role for monoacylglycerol lipase inhibition in the prevention of stress-induced behavioral adaptation

2011: In rats, CBD injected into the brain causes anti-anxiety effects via 5HT1A receptors

The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors

2011: In mice, raising AEA or 2-AG levels by inhibiting FAAH or MAGL helped with stress

Inhibition of endocannabinoid catabolic enzymes elicits anxiolytic-like effects in the marble burying assay

2010: In mice, possible involvement of serotonin receptors for CBD’s antidepressant effects

Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors

2010: In rats, injection of CBD lessens the panic response via 5HT1A receptors

Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors

2010: In humans, CBD can block fear response of THC because they seem to have opposite effects on regional brain function

Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology

2009: In humans, brain scans showed how CBD altered anxiety when shown fearful faces

Modulation of effective connectivity during emotional processing by Delta 9-tetrahydrocannabinol and cannabidiol

2009: In a tissue culture, THC & CBD help to inhibit tryptophan degradation & allow for more serotonin synthesis

Delta9-tetrahydrocannabinol and cannabidiol modulate mitogen-induced tryptophan degradation and neopterin formation in peripheral blood mononuclear cells in vitro

2009: In rats, stress relief occurs by CBD facilitating 5HT1A receptor-mediated neurotransmission

5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats

2008: In rats, this important paper confirmed that the anti-anxiety effects of CBD are mediated by 5HT1A serotonin receptor

Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats

2006: In rats, CBD reduced anxiety – confirmed that it didn’t so via benzodiazepine receptors

Anxiolytic-like effect of cannabidiol in the rat Vogel conflict test

1997: In rats, CB1 antagonism causes anxiety

Acute administration of the CB1 cannabinoid receptor antagonist SR 141716A induces anxiety-like responses in the rat

1994: In an animal model, synthetic cannabinoids derived from CBD help with anxiety in elevated plus-maze test

Anxiolytic effect of cannabidiol derivatives in the elevated plus-maze

1993: In humans, CBD helped for public speaking

Effects of ipsapirone and cannabidiol on human experimental anxiety

1990: In rats, CBD caused less stress in the elevated plus-maze test

Antianxiety effect of cannabidiol in the elevated plus-maze

1984: In rats, interactions between CBD, THC & corticosterone levels

Pharmacological interaction of the effects of delta 9-trans-tetrahydrocannabinol and cannabidiol on serum corticosterone levels in rats

1982: In a double-blind human study, CBD blocked the anxiety caused by THC

Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects

1974: In a double-blind human study, CBD at 60 mg caused no side effects – but it did block many of the effects of THC, including anxiety

Cannabidiol interferes with the effects of delta 9 - tetrahydrocannabinol in man

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