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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.

Confidence in the evidence

Low-Moderate
  • Multiple small RCTs (n=15-60) show CBD reduces anxiety and THC-induced paranoia, but results are not always statistically significant.
  • One RCT in schizophrenia (n=28) found no cognitive benefit from acute CBD, and a systematic review found no clear benefit for PTSD.
  • A driving simulation study (n=14) found CBD did not prevent THC-induced impairment and may worsen it.
  • Evidence is limited by small sample sizes, mostly acute dosing, and lack of long-term or large-scale trials.
  • Preclinical studies suggest mechanisms, but human data are insufficient for strong conclusions.
How we rate confidence

Confidence reflects the strength of the underlying evidence, not whether the result is favorable. It weighs the number and size of studies, their design (randomized trials count for more than observational or single-case work), how consistently they point the same way, and their risk of bias.

Tiers run from Insufficient to High. High is rare in this field: small, early, or open-label studies land lower even when their direction is encouraging.

Evidence by study

Direction is each study's finding relative to your question: Supports, Opposes, No effect, Mixed, or Unclear.

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

147 articles · 37 from the last two years · 17,102 participants across 73 studies reporting sample size

Common study designs

review 31 systematic review 8 experimental study 8 observational cohort 8 randomized controlled trial 24

Research

Synthesize the evidence → Search all →

The FDA Backdoor to MDMA Rescheduling

SSRN Electronic Journal Vincent Joralemon

The Drug Enforcement Administration (DEA) classifies MDMA as a Schedule I controlled substance, the most restrictive category under the Controlled Substances Act. However, Lykos Therapeutics (formerly MAPS PBC) has submitted a New Drug Application for MDMA-assisted therapy for PTSD. If the FDA approves this drug, it would provide the 'accepted medical use' that Schedule I drugs are statutorily denied, triggering a rescheduling process. Based on precedents like XYWAV and cannabis-derived medications, the DEA would likely reschedule only the specific FDA-approved drug product—likely to be marketed as RENSANSE—to Schedule II or III, while raw MDMA remains on Schedule I. This mechanism offers a model for incrementally relaxing federal restrictions on psychedelic substances and expanding research access.

DOI: 10.2139/ssrn.6960838

Regulating Psilocybin as Food, Not Drugs

Julia Etkin, Vincent Joralemon

Psilocybin, currently a Schedule I controlled substance with no accepted medical use and high abuse potential, is actually among the safest psychoactive compounds by comparative-harm metrics—far safer than alcohol and tobacco, which are exempt from the Controlled Substances Act and regulated as adult-use commodities. This essay argues that psilocybin should be regulated under food law, specifically the dietary-supplement framework of the Dietary Supplement Health and Education Act of 1994, rather than drug law.

DOI: 10.2139/ssrn.6960858

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 Full text Ketamine Cannabidiol Schizophrenia Sex +1

Psychedelic-Assisted Psychotherapy for the Treatment of PTSD: A Systematic Review and Meta-Analysis

Psychoactives June 8, 2026 Fizza Mitter, Anton Sheptooha, Janni Leung et al.

Post-traumatic stress disorder (PTSD) is often not well treated by current medications or talk therapies, leading to interest in psychedelic-assisted psychotherapy. A systematic review and meta-analysis of 11 randomized controlled trials with 358 participants examined MDMA, ketamine, and cannabidiol. MDMA-assisted psychotherapy produced a moderate-to-large reduction in PTSD symptoms, with more participants achieving clinical response and loss of PTSD diagnosis. Ketamine showed a small, non-significant effect, and one trial of cannabidiol found no clear benefit. All agents were generally well tolerated. The evidence is dominated by MDMA trials, and safety data remain insufficient for strong comparisons. More studies with standardized outcomes and direct comparisons are needed.

DOI: 10.3390/psychoactives5020016 MDMA Cannabidiol Systematic review Randomized controlled trial +9

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 Full text

Prevalence and Reasons for Microdosing Cannabis, Psilocybin, LSD, and MDMA Among U.S. Adults

American Journal of Preventive Medicine May 4, 2026 Kevin H. Yang, Nora Satybaldiyeva, Wayne Kepner et al. 1 citation

Cannabis is the most commonly microdosed substance among U.S. adults, with 9.4% (24.1 million) reporting lifetime use, followed by psilocybin (5.3%, 13.7 million), LSD (4.8%, 12.4 million), and MDMA (2.2%, 5.7 million). Cannabis is primarily microdosed for medical reasons such as pain management, whereas psilocybin, LSD, and MDMA are more often used recreationally. Lifetime microdosing is more prevalent among people with poorer mental health and those living in jurisdictions with fewer restrictions on cannabis and psychedelics. As policies continue to evolve, the prevalence of microdosing may increase, highlighting the need for ongoing surveillance.

DOI: 10.1016/j.amepre.2026.108381 Full text MDMA Medline Young adult Drug +4

Adolescent cannabinoid vapour exposure sex-dependently alters the relationship between vulnerability traits and ethanol self-administration and modifies naltrexone actions on ethanol intake in rats.

Neuropharmacology May 1, 2026 Jairo S Acosta-Vargas, Natalia De Las Heras-Martínez, Alberto Marcos et al.

Adolescent rats exposed to vaporized THC, alone or with CBD, showed no significant changes in behavioral traits or alcohol self-administration compared to controls. However, females exhibited a more vulnerable pattern of alcohol consumption and seeking. In THC-exposed males, a negative correlation appeared between sucrose preference and compulsive alcohol seeking; in females, THC disrupted the link between novelty preference and alcohol intake and was associated with a negative correlation between goal-tracking and compulsive seeking. Naltrexone reduced alcohol intake most effectively in THC-exposed rats versus those given a high-CBD/low-THC mixture. Adolescent cannabinoid exposure has limited effects on overall alcohol risk but may alter psychological underpinnings of alcohol-related behaviors and increase naltrexone potency, with sex differences highlighting the need for personalized interventions.

DOI: 10.1016/j.neuropharm.2026.110843 Full text

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 Full text 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 Full text 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 Cannabidiol Scientific literature Medline Mechanism biology +5

Clinical trials

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