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Psychosis & Schizophrenia

Best reviews

2021: This reviews looks at using CBD for the early stages of psychosis

Cannabidiol (CBD) as a novel treatment in the early phases of psychosis

https://pubmed.ncbi.nlm.nih.gov/34255100/

2021: A review of 11 studies looks at THC & CBD for schizophrenia

The Impact of THC and CBD in Schizophrenia: A Systematic Review

https://pubmed.ncbi.nlm.nih.gov/34366924/

2021: A review of targeting the ECS for treating schizophrenia

The endocannabinoid system as a therapeutic target for schizophrenia: Failures and potentials

https://pubmed.ncbi.nlm.nih.gov/34146641/

2021: This review of clinical trials looks at CBD's reducing psychotic symptoms of THC as well as effects on schizophrenia & cannabis addiction (10 trials)

Efficacy of Cannabidiol for Δ-9-Tetrahydrocannabinol-Induced Psychotic Symptoms, Schizophrenia, and Cannabis Use Disorders: A Narrative Review

https://www.mdpi.com/2077-0383/10/6/1303/htm

2021: This review of cannabinoids & psychosis suggests CBD as protective of THC-induced psychotic symptoms via the modulation of dopamine

Cannabinoids, reward processing, and psychosis

https://pubmed.ncbi.nlm.nih.gov/33644820/

2020: CB2 receptors as a target for schizophrenia

Are CB2 Receptors a New Target for Schizophrenia Treatment?

https://pubmed.ncbi.nlm.nih.gov/33329132/

2020: A review of CBD & schizophrenia

The role of cannabidiol oil in schizophrenia treatment. a systematic review and meta-analysis

https://pubmed.ncbi.nlm.nih.gov/32599446/

2020: Modulating the ECS & schizophrenia

Impact of Endocannabinoid System Manipulation on Neurodevelopmental Processes Relevant to Schizophrenia

https://pubmed.ncbi.nlm.nih.gov/32855107/

2020: The CB1 receptors & & schizophrenia

The Cannabinoid CB1 Receptor in Schizophrenia

https://www.sciencedirect.com/science/article/abs/pii/S2451902220301737

2020: A review of the studies on CBD & schizophrenia

Cannabidiol as a treatment option for schizophrenia: recent evidence and current studies

https://www.ncbi.nlm.nih.gov/pubmed/32073423

2020: A review of 8 studies using CBD for schizophrenia

Cannabidiol for the treatment of psychosis among patients with schizophrenia and other primary psychotic disorders: A systematic review with a risk of bias assessment

https://pubmed.ncbi.nlm.nih.gov/32126328/

2020: In animal models, the contribution of CB2 to schizophrenia symptoms

Contribution of CB2 receptors in schizophrenia-related symptoms in various animal models: Short review

https://pubmed.ncbi.nlm.nih.gov/32437746/

2019: A review of the clinical studies suggests CBD as a potential treatment for psychosis & addiction

The Potential of Cannabidiol as a Treatment for Psychosis and Addiction: Who Benefits Most? A Systematic Review

https://www.ncbi.nlm.nih.gov/pubmed/31330972

2019: CBD & psychosis

Cannabidiol as a potential treatment for psychosis

https://www.ncbi.nlm.nih.gov/pubmed/31741731

2018: A review of glial cells & the cannabinoids in schizophrenia

Cannabinoids and glial cells: possible mechanism to understand schizophrenia

https://www.ncbi.nlm.nih.gov/pubmed/29392440

2018: CBD & recent-onset psychosis

The Potential of Cannabidiol Treatment for Cannabis Users With Recent-Onset Psychosis

https://www.ncbi.nlm.nih.gov/pubmed/29083450

2018: in primates, CBD can be tested on prepulse inhibition of acustic startle reflex to model its effects on schizophrenia

Cannabidiol effects on prepulse inhibition in nonhuman primates

https://pubmed.ncbi.nlm.nih.gov/29794254/

2017: CBD & psychosis

The Efficacy of Cannabidiol (CBD) as Potential Antipsychotic Medication

https://openjournals.maastrichtuniversity.nl/index.php/msjpn/article/view/278

2017: CBD & the dopamine system in regards to schizophrenia

Neuronal and molecular effects of cannabidiol on the mesolimbic dopamine system: Implications for novel schizophrenia treatments

https://www.ncbi.nlm.nih.gov/pubmed/28185872

2017: CBD & schizophrenia

A systematic review of the effect of cannabidiol on cognitive function: Relevance to schizophrenia

https://www.ncbi.nlm.nih.gov/pubmed/27884751

2017: The ECS & schizophrenia

Role of the Endocannabinoid System in the Pathophysiology of Schizophrenia

https://www.ncbi.nlm.nih.gov/pubmed/26768595

Chart Gallery

THC vs CBD for psychotic symptoms
THC vs CBD for psychotic symptoms

2017: Neuronal and molecular effects of cannabidiol on the mesolimbic dopamine system: Implications for novel schizophrenia treatments

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Hypothetical circuits of CBD & psychosis  psychosis
Hypothetical circuits of CBD & psychosis psychosis

2012: A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation

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ECS in healthy & schizophrenic neurons
ECS in healthy & schizophrenic neurons

2016: The Role of Endocannabinoid Signaling in Cortical Inhibitory Neuron Dysfunction in Schizophrenia

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THC vs CBD for psychotic symptoms
THC vs CBD for psychotic symptoms

2017: Neuronal and molecular effects of cannabidiol on the mesolimbic dopamine system: Implications for novel schizophrenia treatments

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Timeline of Research

2021: In rats, the movement problems from long-term use of the antipsychotic haloperidol could be protected against by increasing endocannabinoid levels

Protective role of endocannabinoid signaling in an animal model of haloperidol-induced tardive dyskinesia

https://pubmed.ncbi.nlm.nih.gov/33933537/

2021: In a mouse model of schizpohrenia, the ability of CBD to methylate DNA (deactivate it) may underly some of its antipsychotic effects

Cannabidiol prevents disruptions in sensorimotor gating induced by psychotomimetic drugs that last for 24-h with probable involvement of epigenetic changes in the ventral striatum

https://pubmed.ncbi.nlm.nih.gov/34015384/

2021: In humans with psychosis, a single dose of 600 mg of CBD increased levels of glutamate in the hippocampus & significantly decreased symptom severity

Cannabidiol modulation of hippocampal glutamate in early psychosis

https://pubmed.ncbi.nlm.nih.gov/33860709/

2021: In humans with acute schizophrenia, CBD worked as well as amisulpride for the improvement of neurocognitive parameters in young acutely ill patients

Cannabidiol and Amisulpride Improve Cognition in Acute Schizophrenia in an Explorative, Double-Blind, Active-Controlled, Randomized Clinical Trial

https://www.frontiersin.org/articles/10.3389/fphar.2021.614811/full

2021: In a case study of a man with schizophrenia & substance use disorder, high CBD-low THC cigarettes helped lessen his cannabis use & stop his cocaine use

Case Report: CBD Cigarettes for Harm Reduction and Adjunctive Therapy in a Patient With Schizophrenia and Substance Use Disorder

https://pubmed.ncbi.nlm.nih.gov/34366942/

2021: Wellcome is funding a clinical trial to test CBD in youth at risk for psychosis

Cannabidiol for at risk for psychosis youth: A randomized controlled trial

https://pubmed.ncbi.nlm.nih.gov/34190422/

2021: In rats, the administration of second-generation antipsychotics altered the endocannabinoid system & this may be related to the adverse metabolic effects of these drugs

Protein level alteration of endocannabinoid system components after chronic, oral self-administration of three second-generation antipsychotics in rat

https://ojs.actamedicamarisiensis.ro/index.php/amm/article/view/57

2020: In humans with a high risk for psychosis, one dose of 600 mg of CBD modulated brain areas related to emotional processing (34 participants in a randomised, double-blind, parallel-group design)

A single dose of cannabidiol modulates medial temporal and striatal function during fear processing in people at clinical high risk for psychosis

https://pubmed.ncbi.nlm.nih.gov/32921794/

2020: A case report of using CBD for anxiety & psychosis

Treatment of social anxiety disorder and attenuated psychotic symptoms with cannabidiol

https://casereports.bmj.com/content/13/10/e235307.abstract

2020: This imaging study of patients with first episode psychosis find a relationship between the ECS & glutamate

Association between cannabinoid 1 receptor availability and glutamate levels in healthy controls and drug-free patients with first episode psychosis: a multi-modal PET and 1H-MRS study

https://link.springer.com/article/10.1007/s00406-020-01191-2

2020: In mice, heteromer complexes of CB1 & dopamine 2 are altered by treatment with cannabinoids & antipsychotics

Heteromer formation between cannabinoid type 1 and dopamine type 2 receptors is altered by combination cannabinoid and antipsychotic treatments

https://onlinelibrary.wiley.com/doi/abs/10.1002/jnr.24716

2020: In this clinical trial of 33 people liable to psychosis, brain scans showed that 600 mg of CBD helped with emotional processing 

A SINGLE DOSE OF CANNABIDIOL MODULATES MEDIAL TEMPORAL & STRIATAL FUNCTION DURING FEAR PROCESSING IN PEOPLE AT CLINICAL HIGH RISK FOR PSYCHOSIS

https://kclpure.kcl.ac.uk/portal/files/127906449/Davies_FacesCBD_Manuscript_FinalRevised_AAM_Pure_Apr28.pdf

2020: In a mouse model of schizophrenia, CBD helped as a preventative treatment

CANNABIDIOL AS A POTENTIAL PREVENTATIVE TREATMENT IN A NEUREGULIN-1 MOUSE MODEL OF SCHIZOPHRENIA

https://academic.oup.com/schizophreniabulletin/article/46/Supplement_1/S298/5839394

2020: In humans with schizophrenia, this analysis shows links to dysregulated CB1 receptors and to certain variants of the CNRN1 gene which encodes CB1

Cannabinoid receptor CNR1 expression and DNA methylation in human prefrontal cortex, hippocampus and caudate in brain development and schizophrenia

https://www.nature.com/articles/s41398-020-0832-8

2020: In mice with a tendency towards schizophrenia, early treatment with CBD altered the transcription of a dopamine gene, suggesting CBD as a potential treatment

Altered dopamine D3 receptor gene expression in MAM model of schizophrenia is reversed by peripubertal cannabidiol treatment

https://pubmed.ncbi.nlm.nih.gov/32360362/

2020: In rats treated with haloperidol (a medication for schizophrenia), CBD reduced the motor impairments and other negative side effects

Investigation of the Effects of Cannabidiol on Vacuous Chewing Movements, Locomotion, Oxidative Stress and Blood Glucose in Rats Treated with Oral Haloperidol

https://www.ncbi.nlm.nih.gov/pubmed/32264772

2020: In a mouse model of schizophrenia, CBD helped with behavioral changes not through the CB1 or CB2 receptors but via a serotonin receptor (5-HT1A)

Cannabidiol attenuates behavioral changes in a rodent model of schizophrenia through 5-HT1A, but not CB1 and CB2 receptors

https://www.sciencedirect.com/science/article/abs/pii/S1043661819315439

2020: In humans, a brain imaging study shows how 600 mg of CBD causes its antipsychotic effects (34 participants in a double-blind, randomized, PLB-controlled, repeated-measures, within-subject cross-over design)

Normalization of mediotemporal and prefrontal activity, and mediotemporal-striatal connectivity, may underlie antipsychotic effects of cannabidiol in psychosis

https://www.ncbi.nlm.nih.gov/pubmed/31994476

2020: In humans with a high risk for psychosis, CBD helped in the social stress response to public speaking (58 participants)

Effects of short-term cannabidiol treatment on response to social stress in subjects at clinical high risk of developing psychosis

https://pubmed.ncbi.nlm.nih.gov/31915861/

2020: In human double-blind study, 600 mg of CBD showed help for cortisol levels in those at risk for psychosis

Effects of short-term cannabidiol treatment on response to social stress in subjects at clinical high risk of developing psychosis

https://www.ncbi.nlm.nih.gov/pubmed/31915861

2019: In rats, the harms in a model of schizophrenia induced by repeated doses of ketamine seem to be attenuated by CBD

Cannabidiol Improves Cognitive Impairment and Reverses Cortical Transcriptional Changes Induced by Ketamine, in Schizophrenia-Like Model in Rats

https://pubmed.ncbi.nlm.nih.gov/31823199/

2019: In rat model of schizophrenia, CBD normalized muscarinic signaling

Effect of cannabidiol on muscarinic neurotransmission in the pre-frontal cortex and hippocampus of the poly I:C rat model of schizophrenia

https://pubmed.ncbi.nlm.nih.gov/31108177/

2019: In humans with psychosis, 600 mg of CBD helped with memory and connectivity in the brain as well as a decrease in symptoms (34 participants)

The neurocognitive and neurochemical effects of cannabidiol in psychosis

https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.789173

2019: Endocannabinoid levels are increased in people with high risk for psychosis

Childhood trauma and being at-risk for psychosis are associated with higher peripheral endocannabinoids

https://www.ncbi.nlm.nih.gov/pubmed/31422779

2019: In humans at high risk for psychosis, CBD attenuates dysfunction of a certain brain region (54 in a a double-blind, placebo-controlled, parallel-arm study)

Cannabidiol attenuates insular dysfunction during motivational salience processing in subjects at clinical high risk for psychosis

https://www.ncbi.nlm.nih.gov/pubmed/%2031439831

2019: In a female rat model of schizophrenia, “CBD restored recognition memory, social withdrawal and NMDAR binding deficits” & "CBD is an efficacious treatment for behavioural and neurochemical changes”

Cannabidiol improves behavioural and neurochemical deficits in adult female offspring of the maternal immune activation (poly I:C) model of neurodevelopmental disorders

https://www.sciencedirect.com/science/article/abs/pii/S0889159119302806

2019: In humans with schizophrenia, their prefrontal cortex show an imbalanced endocannabinoid system

Endocannabinoid system imbalance in the postmortem prefrontal cortex of subjects with schizophrenia

https://www.ncbi.nlm.nih.gov/pubmed/31237179

2019: In humans with psychosis, cannabis use did not alter the efficacy of their antipsychotic medication

The influence of substance use on the effectiveness of antipsychotic medication: a prospective, pragmatic study

https://pubmed.ncbi.nlm.nih.gov/31140342/

2019: In mice, the use of FAAH & MAGL inhibitors show that symptoms of schizophrenia may be regulated by the ECS

Effects of Fatty Acid Amide Hydrolase Inhibitors Acute Administration on the Positive and Cognitive Symptoms of Schizophrenia in Mice

https://pubmed.ncbi.nlm.nih.gov/31004320/

2019: In humans with schizophrenia, cannabis protected against gut disorders

Cannabis use disorders may protect against certain disorders of the digestive organs in people with schizophrenia but not in healthy controls

https://www.ncbi.nlm.nih.gov/pubmed/30880659

2019: In rat model of schizophrenia, CBD restored cannabinoid & GABA signaling deficits

Effect of cannabidiol on endocannabinoid, glutamatergic and GABAergic signalling markers in male offspring of a maternal immune activation (poly I:C) model relevant to schizophrenia

https://pubmed.ncbi.nlm.nih.gov/31202911/

2018: in humans with schizophrenia, CBD well-tolerated but did not improve scores

The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial

https://www.ncbi.nlm.nih.gov/pubmed/29619533

2018: In humans, CBD did not attenuate the THC effects of memory impairment or acute psychosis

Individual and combined effects of acute delta-9-tetrahydrocannabinol and cannabidiol on psychotomimetic symptoms and memory function

https://pubmed.ncbi.nlm.nih.gov/30185793/

2019: comment

Lost in translation: an overinterpretation of the acute effects of cannabinoids

https://pubmed.ncbi.nlm.nih.gov/31852882/

2018: in humans at risk for psychosis, brain scans showed how 600 mg of CBD normalized function (52 participants in a parallel-group, double-blind, placebo-controlled randomized clinical trial)

Effect of Cannabidiol on Medial Temporal, Midbrain, and Striatal Dysfunction in People at Clinical High Risk of Psychosis: A Randomized Clinical Trial

https://pubmed.ncbi.nlm.nih.gov/30167644/

2018: In humans, double-blind study looks at CBD for schizophrenia

Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial

https://www.ncbi.nlm.nih.gov/pubmed/29241357

2018: In a rat model of schizophrenia, CBD administered during adolescence prevented behavioral abnormalities

Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia

https://www.ncbi.nlm.nih.gov/pubmed/30186164

2018: In humans, CBD increased fronto-striatal connectivity

Probing the endocannabinoid system in healthy volunteers: Cannabidiol alters fronto-striatal resting-state connectivity

https://www.ncbi.nlm.nih.gov/pubmed/29887287

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

Schizophrenia and depression, two poles of endocannabinoid system deregulation

https://pubmed.ncbi.nlm.nih.gov/29249810/

2017: In rat model of schizophrenia, CBD attenuated the social interaction and cognitive deficits

Improved Social Interaction, Recognition and Working Memory with Cannabidiol Treatment in a Prenatal Infection (poly I:C) Rat Model

https://www.ncbi.nlm.nih.gov/pubmed/28230072

2016: In rats, CBD counteracted the negative effects of amphetamine on the mesolimbic dopamine pathway

Cannabidiol Counteracts Amphetamine-Induced Neuronal and Behavioral Sensitization of the Mesolimbic Dopamine Pathway through a Novel mTOR/p70S6 Kinase Signaling Pathway

https://pubmed.ncbi.nlm.nih.gov/27147666/

2016: In a double-blind human study of 42 patients with schizophrenia, 800 mg of CBD showed significant symptom reduction after 2-4 weeks – also fewer side effects compared to amilsupride

Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence

https://www.ncbi.nlm.nih.gov/pubmed/27877130

2016: On CBD and the effect on prepulse inhibition of startle

Cannabidiol, among Other Cannabinoid Drugs, Modulates Prepulse Inhibition of Startle in the SHR Animal Model: Implications for Schizophrenia Pharmacotherapy

https://pubmed.ncbi.nlm.nih.gov/27667973/

2016: In mice, CBD attenuated the catalepsy from haloperidol via serotonin

Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice

https://pubmed.ncbi.nlm.nih.gov/27131780/

2016: In rats, the ability of CBD to occupy dopamine receptors may alter psychosis

Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose

https://www.ncbi.nlm.nih.gov/pubmed/27754480

2015: In humans, fMRI scans showed that CBD increased function connectivity while THC decreased it

Cannabinoid modulation of functional connectivity within regions processing attentional salience

https://www.ncbi.nlm.nih.gov/pubmed/25249057

2015: CBD’s reduction of glial activity could cause antipsychotic effects

Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol

https://www.ncbi.nlm.nih.gov/pubmed/25680767

2014: In mice, CBD attenuates the damage from chronic use of a NMDAR

Cannabidiol attenuates sensorimotor gating disruption and molecular changes induced by chronic antagonism of NMDA receptors in mice

https://www.ncbi.nlm.nih.gov/pubmed/25618402

2013: in humans, “pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment”

Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment

https://www.ncbi.nlm.nih.gov/pubmed/23042808

2013: In humans, they found those with psychosis had increased FAAH & MAGL levels (185 participants)

Peripheral endocannabinoid system dysregulation in first-episode psychosis

https://pubmed.ncbi.nlm.nih.gov/23822951/

2012: in human double blind study, CBD increased AEA and helped with schizophrenia – better side effects than amisulpride

Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia

https://www.ncbi.nlm.nih.gov/pubmed/22832859/

2012: THC & CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing

Induction of psychosis by Δ9-tetrahydrocannabinol reflects modulation of prefrontal and striatal function during attentional salience processing

https://www.ncbi.nlm.nih.gov/pubmed/22213786

2012: In rats on a drug model of schizophrenia, CBD normalized their social relations and lowered hyperactivity

Cannabidiol and clozapine reverse MK-801-induced deficits in social interaction and hyperactivity in Sprague-Dawley rats

https://pubmed.ncbi.nlm.nih.gov/22495620/

2012: In rat model of schizophrenia, CBD helped with the impairment of emotional processing

Antipsychotic profile of cannabidiol and rimonabant in an animal model of emotional context processing in schizophrenia

https://pubmed.ncbi.nlm.nih.gov/22716146/

2011: In rats on a drug model of schizophrenia, CBD “showed both propsychotic activity and partial antipsychotic activity”

Effect of cannabidiol in a MK-801-rodent model of aspects of schizophrenia

https://pubmed.ncbi.nlm.nih.gov/21458498/

2011: THC psychotic effects might be caused by impaired communication between right and left frontal lobes

Disruption of frontal θ coherence by Δ9-tetrahydrocannabinol is associated with positive psychotic symptoms

https://www.ncbi.nlm.nih.gov/pubmed/21150914

2011: THC may break down the synchronized neural oscillations necessary for speech

Communication breakdown: delta-9 tetrahydrocannabinol effects on pre-speech neural coherence

https://www.nature.com/articles/mp2011141

2011: On combo of CBD and ketamine for schizophrenia

The interplay of cannabinoid and NMDA glutamate receptor systems in humans: preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects

https://www.ncbi.nlm.nih.gov/pubmed/21062637

2010: in humans, a one-time dose of CBD didn’t show help for a responsiveness to auditive stimuli in patients with schizophrenia

Performance of schizophrenic patients in the Stroop Color Word Test and electrodermal responsiveness after acute administration of cannabidiol (CBD)

https://www.ncbi.nlm.nih.gov/pubmed/20339735

2009: In a mouse model of schizophrenia, chronic CBD lessened anxiety & psychosis

A behavioural comparison of acute and chronic Delta9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice

https://pubmed.ncbi.nlm.nih.gov/19785914/

2008: In humans, hair samples from schizophrenia patients saw more positive symptoms in those with only THC in their hair and no CBD

Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis

https://www.ncbi.nlm.nih.gov/pubmed/18378995

2006: In mice, CBD reverses a drug that disrupts the prepulse inhibition model of schizophrenia

Cannabidiol reverses MK-801-induced disruption of prepulse inhibition in mice

https://pubmed.ncbi.nlm.nih.gov/16052245/

2006: In three patients with schizophrenia, CBD was well tolerated but after ~30 days, only one showed minor improvement

Cannabidiol monotherapy for treatment-resistant schizophrenia

https://www.ncbi.nlm.nih.gov/pubmed/16401651

2004: In rats, CBD increased Fos in the limbic area but not the motor control area

Cannabidiol increases Fos expression in the nucleus accumbens but not in the dorsal striatum

https://www.ncbi.nlm.nih.gov/pubmed/15158372

1995: Case study saw CBD help schizophrenia

Antipsychotic effect of cannabidiol

https://pubmed.ncbi.nlm.nih.gov/7559378/

1991: early tests on rats of CBD versus haloperidol for antipsychotic activity

Effects of cannabidiol in animal models predictive of antipsychotic activity

https://www.ncbi.nlm.nih.gov/pubmed/1678894