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CBD (Cannabidiol)

The non-intoxicating cannabinoid studied for epilepsy, anxiety, and inflammation, with a pharmacology distinct from THC.

State of the evidence

Synthesized

Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for CBD, cannabidiol, epidiolex, then ranked by relevance.

CBD appears to reduce anxiety and mitigate some THC-induced psychotic symptoms and cognitive impairment in healthy volunteers, but its effects are dose-dependent (e.g., 300 mg but not 100 or 900 mg) and may not extend to improving cognition in schizophrenia or preventing THC-induced driving impairment. Evidence is mixed on whether CBD reduces negative mood in underrepresented groups, but it does not show clear benefit for PTSD. The main caveat is that most human studies are small, acute-dosing trials, and long-term or clinical population data are limited.

Evidence by study

Direction is which way each study's own result points, not our rating of the study.

What the directions mean
Supports:
the study found the intervention worked, or its hypothesis held.
Opposes:
it found the opposite, no benefit or a harm.
No effect:
no significant difference either way.
Mixed:
effects in both directions within the same study.
Unclear:
the abstract does not report a direction.
Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment 2012
Supports

Pre-treatment with 600 mg CBD reduced THC-elicited paranoia and odds of clinically significant positive psychotic symptoms, and mitigated THC-induced memory impairment.

randomized controlled trial Sample size: 48

Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing 2009
Supports

CBD reduced anxiety and dampened limbic brain activation during emotional processing, correlating with an anxiolytic trend.

double-blind, randomized, placebo-controlled crossover trial Sample size: 15

Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug 2006
Supports

CBD shows anxiolytic and antipsychotic-like properties and may be a safe alternative treatment for schizophrenia.

review

Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life 2017
Mixed

CBD 300 mg significantly reduced anxiety scores compared to placebo in the post-speech phase, but 100 mg and 900 mg did not, showing an inverted U-shaped dose-response curve.

randomized controlled trial Sample size: 60

Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers 2012
No effect

CBD showed no differences from placebo on any symptomatic or physiological variable, while THC produced anxiety, dysphoria, and positive psychotic symptoms.

randomized controlled trial Sample size: 16

Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol 2009
No effect

CBD had no significant effects on psychotic symptoms, anxiety, intoxication, or sedation, while THC increased these measures.

randomized controlled trial Sample size: 15

The neuropsychopharmacology of cannabis: A review of human imaging studies 2018
Supports

CBD may offset some of the acute effects of THC on neurocognitive systems.

review

Neuroimaging in cannabis use: a systematic review of the literature 2009
Unclear

The review included studies on CBD but did not provide a specific finding on CBD's effects.

systematic review

Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition 2019
Opposes

Cannabis containing equivalent CBD and THC was no less impairing than THC-dominant cannabis, and CBD may exacerbate THC-induced impairment in some circumstances.

randomized, double-blind, within-subjects crossover Sample size: 14

Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis ‘amotivational’ hypotheses 2016
Mixed

THC-only cannabis reduced high-effort choices, but adding CBD did not significantly affect effort-related decision-making compared to placebo.

randomized controlled trial Sample size: 17

Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users 2010
No effect

CBD was not studied; the study focused on THC and alcohol tolerance.

double-blind, placebo-controlled, three-way study Sample size: 21

Modulation of effective connectivity during emotional processing by Δ9-tetrahydrocannabinol and cannabidiol 2009
Supports

CBD disrupted forward connectivity between the amygdala and anterior cingulate cortex during the neural response to fearful faces, which may represent neurophysiological correlates of its anxiolytic properties.

randomized controlled trial Sample size: 15

Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids 2005
No effect

Varying concentrations of CBD did not change subjective, behavioral, or neurophysiological responses to smoked marijuana.

randomized controlled trial Sample size: 23

Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties 2020
Supports

CBD reduces anxiety without anxiogenic effects at higher doses.

systematic review

Performance of schizophrenic patients in the Stroop Color Word Test and electrodermal responsiveness after acute administration of cannabidiol (CBD) 2010
No effect

Single acute doses of CBD did not improve Stroop test performance in schizophrenic patients, and 600 mg was associated with worse performance compared to placebo or 300 mg.

randomized controlled trial Sample size: 28

Prophylactic efficacy of cannabidiol and sodium nitroprusside in a ketamine model of schizophrenia: sex-dependent effects on positive-like and cognitive impairments 2026
Supports

The combination of CBD and sodium nitroprusside reduced hyperlocomotion and prevented novel object recognition deficits in a ketamine rodent model of schizophrenia.

animal study

Psychedelic-Assisted Psychotherapy for the Treatment of PTSD: A Systematic Review and Meta-Analysis 2026
No effect

A single cannabidiol trial showed no clear benefit for PTSD symptom reduction.

systematic review and meta-analysis Sample size: 358

Effects of THC, CBD, and Their Combination on EEG Dynamics in Rats. 2026
Mixed

CBD alone yielded fewer and smaller clusters of increased low-frequency EEG power compared to THC and THC+CBD, but still produced some effects.

experimental study

Cannabidiol Mitigates Ketamine-Induced Hyperlocomotion Via Allosteric Potentiation of Ventral Tegmental Glycine Receptor α1 Signaling. 2026
Supports

CBD blocked ketamine-induced hyperlocomotion by reversing glycine receptor dysfunction in the ventral tegmental area.

experimental study

Acute cannabidiol (CBD), tetrahydrocannabinol (THC) and their mixture (THC:CBD) exert differential effects on brain activity and blood flow in rats: A translational neuroimaging study. 2026
Mixed

CBD decreased brain functional connectivity without affecting cerebral blood flow, while THC increased both; CBD moderated THC's effects when combined.

randomized controlled trial

Is Cannabidiol (CBD) a Non-Psychoactive Phytocannabinoid? 2026
Unclear

The opinion piece argues that CBD may be misclassified as non-psychoactive given its clinical effects on psychiatric conditions.

opinion piece

A Systematic Review of Therapeutic Potential of Illicit Drugs: A Narrative Overview of How Cannabinoids and Psychedelics Can be Used in Medicine 2025
Unclear

There is a lack of research on cannabis' medicinal use regarding treatments and diseases, its standardization, routes of administration, and doses.

integrative literature review

Effect of caffeine and cannabidiol (CBD) co-administration on Δ9-tetrahydrocannabinol (Δ9-THC) subjective effects, performance impairment, and pharmacokinetics. 2025
Opposes

CBD, when co-administered with THC and caffeine, increased outcomes associated with abuse liability and performance impairment, and increased plasma THC and 11-OH-THC concentrations.

double-blind, randomized, placebo-controlled, within-subject crossover study Sample size: 20

Effects of Cannabinoids on Emotional States and Alcohol Use Among Underrepresented Groups: Moderation by Perceived Discrimination. 2025
Supports

CBD use led to greater decreases in negative mood symptoms than THC use, especially at average and high levels of perceived discrimination.

randomized controlled trial Sample size: 172

Astrogliosis Occurs Selectively in Amygdala of Adolescent Primate and Rodent Following Daily Δ9-Tetrahydrocannabinol, Prevented by Cannabidiol Co-Treatment. 2025
Supports

Co-administered CBD prevented THC-induced astrogliosis in the adolescent amygdala.

preclinical study

Points of agreement

  • CBD reduces anxiety in healthy volunteers, particularly at moderate doses (e.g., 300 mg).
  • CBD mitigates some THC-induced psychotic symptoms and cognitive impairment in acute settings.
  • CBD alone has minimal psychoactive or impairing effects compared to THC.
  • Preclinical studies suggest CBD has neuroprotective and anti-inflammatory properties.

Conflicts

  • Some studies find CBD reduces anxiety (e.g., 300 mg), while others find no effect on anxiety or other symptoms.
  • CBD's effect on THC-induced impairment is inconsistent: some studies show mitigation, while others show no benefit or even exacerbation.
  • CBD shows no cognitive benefit in schizophrenia patients in acute dosing, but preclinical models suggest potential prophylactic effects.

Gaps

  • Lack of large-scale, long-term clinical trials in patient populations (e.g., anxiety disorders, schizophrenia, PTSD).
  • Durability of CBD effects beyond acute dosing is unknown.
  • Optimal dosing and route of administration are not established.
  • Limited research on CBD in diverse populations and with chronic use.
  • Few studies directly compare CBD to standard treatments (e.g., anxiolytics, antipsychotics).
Browse these studies in the library
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is CBD, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when CBD or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

Ask your own question in the Research Synthesis Tool

167 articles · 42 from the last two years · 18,081 participants across 81 studies reporting sample size

Common study designs

review 37 systematic review 9 experimental study 9 observational cohort 13 randomized controlled trial 26

Research

Synthesize the evidence → Search all →

Prophylactic efficacy of cannabidiol and sodium nitroprusside in a ketamine model of schizophrenia: sex-dependent effects on positive-like and cognitive impairments

Brazilian Journal of Psychiatry June 16, 2026 Daniel B.a. Prado, Matheus T. Rossignoli, Rafael N. Ruggiero et al.

In a rat model of schizophrenia-like symptoms induced by ketamine, the combination of cannabidiol and sodium nitroprusside given during brain development prevented hyperactivity and memory problems in both sexes, while each drug alone had limited effects. The model produced different symptoms in males and females: females showed greater hyperactivity and long-term memory deficits, whereas males showed reduced pleasure-seeking and short-term memory impairments. The combined treatment was more effective in females, and distinct behavioral patterns were seen between sexes. This suggests that a combination of these two compounds may offer a sex-specific preventive strategy for schizophrenia symptoms.

DOI: 10.47626/1516-4446-2025-4301 (opens in new tab) Full text (opens in new tab) Ketamine Cannabidiol Schizophrenia Sex +1

Effects of THC, CBD, and Their Combination on EEG Dynamics in Rats.

Physiological research May 12, 2026 M Bochin, Č Vejmola, V Koudelka et al.

Acute oral administration of THC (10 mg/kg), CBD (10 mg/kg), or their combination in freely moving rats alters resting-state EEG dynamics. THC and THC+CBD produced the strongest and most spatially extensive increases in low-frequency spectral power, with significant delta-beta clusters in prefrontal, cingulate, hippocampal, and striatal regions. CBD yielded fewer and smaller clusters. Connectivity analyses revealed altered functional coupling within overlapping CB1 receptor-rich regions. The combination treatment closely resembled THC alone, suggesting a dominant THC-driven contribution. These findings identify a cannabinoid-specific EEG signature of enhanced low-frequency oscillatory activity and altered large-scale network organization.

DOI: 10.33549/physiolres.935771 (opens in new tab) Full text (opens in new tab)

Effect of cannabinol, tetrahydrocannabivarin and cannabidiol on voluntary alcohol consumption.

Alcohol and alcoholism (Oxford, Oxfordshire) March 17, 2026 Ieva Poceviciute, Martynas Arbaciauskas, Rokas Buisas et al.

Three non-psychoactive phytocannabinoids—cannabinol (CBN), tetrahydrocannabivarin (THCV), and cannabidiol (CBD)—all reduced voluntary alcohol consumption in male Wistar rats that had been drinking alcohol long-term. CBN and THCV lowered alcohol intake and preference with mild sedation; CBD had a minor effect on consumption, did not affect preference, reduced activity, and lowered positive emotional states. None caused discomfort or distress. CBN and THCV may be promising for treating alcohol use disorder.

DOI: 10.1093/alcalc/agag019 (opens in new tab) Full text (opens in new tab) Alcohol use disorder Cannabidiol Cannabinol Tetrahydrocannabivarin

Cannabidiol Mitigates Ketamine-Induced Hyperlocomotion Via Allosteric Potentiation of Ventral Tegmental Glycine Receptor α1 Signaling.

Biological Psychiatry March 16, 2026 Xianglian Wang, Jing Xia, Heyi Luo et al.

Ketamine produces rapid antidepressant effects but also causes hyperlocomotion, a side effect linked to increased dopamine activity in the ventral tegmental area (VTA). Cannabidiol (CBD) blocked ketamine-induced hyperlocomotion in mice when given systemically (30 mg/kg) or directly into the VTA (10 μg per mouse). Whole-brain imaging showed that ketamine increased neuronal activity in the VTA, prefrontal cortex, and nucleus accumbens, which CBD reduced. Electrophysiology revealed that ketamine suppressed glycine receptor (GlyR) function, while CBD reversed this dysfunction by antagonizing ketamine-driven delays in GlyR activation. In GlyRα1S296A mice, CBD's effect on hyperlocomotion was abolished, indicating that VTA GlyRα1 signaling, particularly the S296 residue, is essential for CBD's dissociation of ketamine's therapeutic and adverse effects.

DOI: 10.1016/j.biopsych.2026.03.992 (opens in new tab) Full text (opens in new tab) Cannabidiol Ketamine Antidepressant Glycine receptor +2

Acute cannabidiol (CBD), tetrahydrocannabinol (THC) and their mixture (THC:CBD) exert differential effects on brain activity and blood flow in rats: A translational neuroimaging study.

Journal of psychopharmacology (Oxford, England) March 1, 2026 Eilidh Macnicol, Michelle Kokkinou, Maria Elisa Serrano Navacerrada et al. 2 citations

THC increases brain functional connectivity and blood flow in rats, while CBD decreases connectivity without affecting blood flow. When combined, CBD moderates THC's effects. Adult male rats received THC, CBD, a combination, or a placebo. Brain scans two hours later showed THC raised whole-brain connectivity and blood flow in cortical and subcortical regions. CBD lowered connectivity metrics. The combination produced moderate increases in both measures. THC specifically strengthened connections between the cortex and hippocampus and between the cortex and striatum, an effect reduced when CBD was present. These distinct neurophysiological profiles suggest cannabinoids induce different brain states, supporting the use of functional neuroimaging in developing cannabinoid-based therapies.

DOI: 10.1177/02698811251360745 (opens in new tab) Full text (opens in new tab) Cannabinoids Cerebral blood flow Neuroimaging Rat +1

Is Cannabidiol (CBD) a Non-Psychoactive Phytocannabinoid?

Psychoactives February 3, 2026 Eliana Rodrigues

Interest in psychoactive substances like psychedelics is growing in medicine and academia, but misclassifications of certain plants, animals, fungi, and their substances persist in media and scholarly circles. This opinion piece argues whether cannabidiol (CBD) is a non-psychoactive phytocannabinoid, noting that hundreds of robust studies support its clinical use for seizures, anxiety, psychosis, schizophrenia, post-traumatic stress disorder, and addiction. The text reviews historical classifications of psychoactive substances, reflects on terminology, and proposes a new classification for psychedelics.

DOI: 10.3390/psychoactives5010004 (opens in new tab) Cannabidiol Scientific literature Medline Mechanism biology +5

Effect of caffeine and cannabidiol (CBD) co-administration on Δ9-tetrahydrocannabinol (Δ9-THC) subjective effects, performance impairment, and pharmacokinetics.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology November 1, 2025 Justin C Strickland, Hayleigh E Tilton, Noah M Patton et al.

Caffeine co-administered with THC produced minimal changes in subjective effects, performance, or metabolism, though signals for perceived driving impairment were observed. In contrast, CBD co-administered with THC and caffeine increased outcomes associated with abuse liability and performance impairment versus THC alone. CBD also increased plasma THC and 11-OH-THC concentrations. These data provide the first direct assessment of pharmacodynamic and pharmacokinetic effects of THC and caffeine co-administered in humans, emphasizing the importance of considering full cannabinoid profiles and drug combinations in regulatory decision-making.

DOI: 10.1038/s41386-025-02232-x (opens in new tab) Full text (opens in new tab)

Astrogliosis Occurs Selectively in Amygdala of Adolescent Primate and Rodent Following Daily Δ9-Tetrahydrocannabinol, Prevented by Cannabidiol Co-Treatment.

Biological Psychiatry Global Open Science July 1, 2025 Yalin Sun, Meenalochani Sivasubramanian, Marija Milenkovic et al.

Adolescent cannabis use increases risk for neuropsychiatric disorders, possibly through amygdala dysfunction. Chronic THC treatment in male adolescent nonhuman primates and rats disrupted sleep and increased anxiety-related behavior. THC activated proinflammatory glial cells (astrocytes) exclusively in the adolescent amygdala, upregulating GFAP and complement factor-B, effects absent in adults or other brain regions. THC also reduced synaptic plasticity markers stathmin-1 and NrCAM. Co-administered cannabidiol prevented astrocyte inflammation but did not restore plasticity markers. Astrogliosis correlated with fragmented sleep, attenuated plasticity markers with anxiety. Elevated CB1R expression in the maturing brain was astrocyte-localized in the amygdala, linking THC to unique adolescent amygdala vulnerability.

DOI: 10.1016/j.bpsgos.2025.100496 (opens in new tab) Full text (opens in new tab) Anxiety Adolescent neurodevelopment Amygdala Astrocytes +3

THC, CBD and minor cannabinoid CBDV differently modulate hippocampal neurons firing.

Neurotoxicology May 1, 2025 Giulia Tomagra, Nikita Gandlevskiy, Elena Rosso et al. 3 citations

Cannabis sativa contains many minor cannabinoids beyond THC and CBD, and their effects on neuronal activity are not fully understood. In cultured hippocampal neurons, standard THC alone or combined with CBD significantly reduced spontaneous firing and burst generation, while CBD alone had no effect. Extracts from Cannabis sativa showed that cannabidivarin (CBDV), a non-psychoactive cannabinoid, reversed the inhibition of firing caused by the THC-CBD mixture. When applied alone, CBDV increased neuronal firing. All effects returned to baseline within 24 hours. These results suggest CBDV can counteract the suppressive effect of THC and CBD on neuronal activity.

DOI: 10.1016/j.neuro.2025.04.004 (opens in new tab) Full text (opens in new tab) C. sativa Cannabidivarin Hippocampal neurons Mea

Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model.

Schizophrenia Research April 1, 2025 Sofia de Almeida Queiroz, Linério Ribeiro de Novais Junior, Anita Beatriz Pacheco de Carvalho et al. 2 citations

In a rat model of schizophrenia induced by ketamine, cannabidiol (CBD) restored rearing behavior (a measure of exploratory activity) without causing anhedonia-like behavior, whereas risperidone further reduced rearing and induced anhedonia-like effects in control rats. CBD reversed ketamine-induced increases in myeloperoxidase activity in the prefrontal cortex and striatum and protein carbonyls in the hippocampus, while risperidone reduced protein carbonyls in the prefrontal cortex and lowered the nitrite/nitrate ratio in the hypothalamus. Both compounds reduced oxidative stress and neuroinflammation in the striatum, hippocampus, and prefrontal cortex, but CBD did so more broadly and without the side effects seen with risperidone. These findings suggest CBD's antipsychotic effects may stem from its antioxidant and anti-inflammatory properties.

DOI: 10.1016/j.schres.2025.03.031 (opens in new tab) Full text (opens in new tab) Cannabidiol Ketamine Rats Risperidone +5

Clinical trials

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