Review Articles Open Access Efficacy and Safety of Cannabidiol for Anxiety: A Bibliometric Analysis and Systematic Review Putu Ayu Putri Fajaryani1.
I Made Agus Gelgel Wirasuta1,3.
Pande Made Nova Armita Sari1.
Dyah Kanya Wati2.
Putu Indah Budi Apsari4.
Made Ary Sarasmita1* Department of Pharmacy.
Faculty of Mathematics and Natural Sciences.
Udayana University.
Badung.
Bali.
Indonesia Pediatric Consultant.
Critical Care Medicine Udayana University.
Sanglah Hospital.
Denpasar.
Bali.
Indonesia Forensic Sciences Laboratory.
Institute of Forensic Sciences and Criminology.
Udayana University.
Badung.
Bali.
Indonesia Departmen of Parasitology.
Faculty of Medicine and Health Sciences.
Warmadewa University.
Denpasar Bali.
Indonesia *Corresponding Author: E-mail: arysarasmita@unud.
ARTICLE INFO
Manuscript Received: 06 Nov, 2024 Revised: 13 Feb, 2025 Accepted: 23 Feb, 2025 Date of publication: 02 Oct, 2025 Volume: 5 Issue: 3 DOI: 10.
56338/jphp.
KEYWORDS
Anxiety.
Anxiolytic.
Cannabidiol.
Pharmacology ABSTRACT Introduction: A non-psychoactive substance present in the cannabis plant, cannabidiol (CBD), seems to have potential as an anxiolytic agent.
This study systematically reviews the efficacy, safety, dosage, mechanisms, and adverse effects of CBD in treating anxiety.
Methods: The PRISMA guideline was used to conduct the review.
Results: A total of 64 articles were included in the study.
It showed that CBD works at the endocannabinoid receptors CB1 and 5-HT1A, which regulate mood and reduce anxiety.
In animal models, a range dosage of 5 Ae 10 mg/kg showed a significant anxiolytic effect in behavioral tests, while in humans, 300 mg/day was proven to be effective in treating various types of anxiety However, individual responses to CBD showed varying results, and demographic characteristics affect the efficacy of animal and human studies.
CBD was also considered safer to be used in the short term compared to diazepam, although the long-term effect remains lacking Conclusion: This study concludes that CBD has potential as an alternative choice for anxiety.
Further research is needed in larger populations with rigorous study design and longer study durations to evaluate its effectiveness and ensure its safety.
Recommendations for Future Research: It is hoped that future research can examine the effects of fly resistance and killing on non-target organisms and control environmental conditions.
Publisher: Pusat Pengembangan Teknologi Informasi dan Jurnal Universitas Muhammadiyah Palu
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Efficacy and Safety of Cannabidiol for Anxiety: A Bibliometric Analysis and Systematic Review
INTRODUCTION
Cannabidiol (CBD) has been known as a Phyto cannabinoid compound that is non-psychoactive, meaning it has not caused a high effect or dependence like Tetrahydrocannabinol (THC) .
CBD has featured a dibenzopyran ring with a phenol group, a hydroxyl group, a pentyl side chain, and a chiral center, see Figure 1.
In addition to its chemical structure, the pharmacokinetic profile of CBD, including parameters such as Tmax.
Cmax, and half-life .
, is summarized in Table 1.
Previous research proved that CBD was able to relieve anxiety .
CBD interacts with the body's endocannabinoid system, especially at Cannabinoid 1 Receptor (CB.
, that regulates mood .
CBD also interacts with receptors from neurotransmitters such as serotonin .
HT1A receptor.
that regulate mood .
Its interaction with these receptors led to anxiolytic effects.
Figure 1.
Chemical Structure of Cannabidiol Research on its anxiolytic effect has grown rapidly, starting from animal studies to clinical trials.
Animal studies involved a variety of animals and diverse study designs that were to measure anxiety levels in animals, such as elevated plus maze test and open field test .
Ae.
These positive findings were then followed by early clinical trials in humans with anxiety disorders .
Ae.
It has been demonstrated that CBD decreased the level of anxiety in animals and humans.
The legality of CBD as an anxiolytic remains limited due to inconsistent clinical results and varying individual responses.
While it has the potential to reduce anxiety, the FDA has only approved EpidiolexA for epilepsy .
, with limitations in standardized dosing and large-scale clinical trials.
Some studies indicate that the effects of CBD depend on dosage, but its optimal dose and comparative effectiveness with conventional therapies have not been clearly established.
Therefore, this study aims to explore its mechanism of action, optimal dosage, long-term safety, and genetic factors influencing individual responses to assess the evidence-based potential of CBD as an anxiety treatment.
Table 1.
Pharmacokinetics profile of cannabidiol (CBD) Parameters Value Reference Cmax 5 ng/mL .
5 ng/mL .
8 ng/mL .
Tmax 3 ng/mL .
5 ng/mL .
2 ng/mL .
T1/2 00 h .
86 h .
3 h .
32L/kg .
13 Ae 19% .
1111Ae1909 L/h .
Cl: clearance.
Cmax: maximum concentration.
F: bioavailability.
Tmax: maximum time.
T1/2: half-life.
Vd: volume of METHOD Search Strategy This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for systematic review .
Some databases used in the literature search included PubMed.
ScienceDirect, and Scopus.
The search was conducted using the following keywords (AuCBDAy OR AuCannabidiolA.
AND (AuAnxietyAy Page | 646 J.
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OR AuAnxiolyticA.
and there were no initial year limits.
The reliance on specific databases may limit the inclusion of relevant studies, affecting the completeness of this review.
Inclusion Criteria The chosen study articles concentrated on the mechanisms of CBD in treating anxiety, appropriate dosage form, dosage or strange, and adverse effects.
The main source of this research was in vivo studies written in English.
We included animal and human studies written in English.
The chosen studies assessed a minimum of two significant points, including cannabidiol and anxiety.
Exclusion Criteria Conference papers, thesis dissertations, review articles, papers published in conference proceedings, manuscripts without abstracts, gray literature or unpublished studies and those that did not fit the inclusion criteria were all disqualified to proceed with our review.
Articles discussing the association of CBD with the diseases not covered in this review were also excluded from the analysis.
These exclusion criteria may introduce selection bias, potentially limiting the generalizability of the findings Data extraction and management Bibliometric Analysis We used VOSviewer .
CWTS.
Leiden Universit.
to visualize term relationships in scientific literature, aiding conceptual understanding and study selection.
By analyzing co-occurring keywords from titles and abstracts, with a minimum threshold of two occurrences, we generated impactful network, overlay, and density visualizations to highlight key interconnections.
Systematic Review We utilized Zotero (AGPL.
USA) to collect and manage relevant articles, ensuring alignment with inclusion criteria for analysis.
Studies were categorized into two groups: .
animal studies and .
human studies.
Key data extracted from animal studies included animal type, intervention, dosage, study design, and outcomes (Table 2 and Table .
RESULTS
Figure 2.
PRISMA diagram .
Page | 647 Efficacy and Safety of Cannabidiol for Anxiety: A Bibliometric Analysis and Systematic Review Relevant articles for treating anxiety using cannabidiol were identified through a systematic search according to the PRISMA guidelines.
Figure 3.
Network Visualization The network visualization of the studies is shown in Figure 3.
Based on the color of the nodes, the VOS viewer groups the keywords into seven distinct clusters.
Figure 4.
Overlay Visualization Figure 4 depicts research trends on CBD and anxiety .
2Ae2.
using an overlay visualization.
Keywords are color-coded by publication year in the VOS viewer.
Notably, "anxiety" showed peak activity in 2018.
Figure 5.
Density Visualization Page | 648 J.
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Figure 5 highlights keyword frequency and intensity related to CBD and anxiety using a heat map.
Bright yellow indicates high density .
requent co-occurrenc.
, while dark blue/purple shows lower density.
Terms like "cannabidiol" and "anxiety" appeared in 100% of articles, while others, such as "open field test" .
4%) and "placebo," had lower density, reflecting limited research or emerging topics.
Table 2 shows that CBD has significant anxiolytic effects, particularly in rats, as evidenced by behavioral tests like the elevated plus maze and open field test.
Effective doses range from 0.
3 to 30 mg/kg, with optimal effects at 5 Ae 10 mg/kg.
Some studies report a biphasic response, where very low or high doses are less effective, suggesting dose-dependent effects influenced by species and experimental conditions.
Table 2.
Overview of the search for Cannabidiol (CBD) in Animal Models.
Study Animal
Test
Intervention Doses and Administration Uribe
- Mice
CBD
3, 3 and 30 mg/kg.
Mariyo et (Male , 2012 Swis.
Guimaryes et al.
, 1990
Elbatsh et
, 2012
Rat (Male Wista.
Rat (Male Listerhoode.
Rat (Male Wista.
EPM
CBD vs Diazepam vs Vehicle CER CBD vs Vehicle EPM CBD vs HU-219 vs HU-252 vs HU-261 vs Diazepam Moreira, 2006 .
Rat (Male Wista.
Zieba
, 2019
Mice
(Male Fmr1
and WT) CBD vs Diazepam
CBD
Flumazenil Diazepam Flumazenil CBD vs vehicle EPM CBD vs vehicle 5 and 20 mg/kg.
Rat (Male Wista.
CBD vs Vehicle 3, 3, 10, 30 mg/kg.
Rat (Male Wista.
Mice (Male ICR) CBD 1, 5, 15, 30, 60 mg/kg.
CBD .
mg/k.
increased passive social interactions.
SIH
CBD vs Diazepam
CBD
WAY100635
WAY100635 .
,1, 0,3, 1
mg/k.
, diazepam .
mg/k.
CBD .
, 3, 10 mg/k.
CBD reduces SIH by 55% and 51% at 3 and 10 mg/kg but diazepam at 3 mg/kg shows a stronger 86% reduction.
Guimaryes et al.
, 1994
SilvaCardoso et
, 2021
Almeida et
, 2013
Shu et al.
CBD: 2.
5, 5.
0, 10 and 20 mg/kg Diazepam: 2 mg/kg.
For 14 days, 10 mg/kg.
Results CBD behavioral index, explosive fleeing, and total fleeing CBD .
mg/k.
increased open-arm entries but was weaker than diazepam.
Repeated CBD administration freezing behavior duration.
CBD .
mg/k.
HU-219 .
0 mg/k.
HU252 .
2-5 mg/k.
HU-261 .
310 mg/k.
and Diazepam .
5 mg/k.
CBD .
5, 5 or 10 mg/k.
Flumazenil .
mg/k.
Diazepam .
0 mg/k.
CBD and HU-219 .
03Ae1 mg/k.
increased open-arm entries but were less potent than diazepam.
5 and 20 mg/kg.
CBD .
mg/kg or 10 mg/k.
showed no significant effect on anxiety parameters compared to controls.
CBD
effects in both mice, with no CBD .
mg/k.
effectively reduced anxiety caused by chronic pain.
Flumazenil did not block CBD's anxiolytic effects.
CBD
mg/k.
increased both penalized and total licks.
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Efficacy and Safety of Cannabidiol for Anxiety: A Bibliometric Analysis and Systematic Review
Study Kaplan et
, 2021
Wanner et
, 2021
Chaves et
, 2021
Chaves et
, 2023
Grogerio et
, 2019
AlegreZurano et
, 2021
AustrichOlivares et
, 2022
Hsiao
,2012
Chesworth et al.
, 2022
Rock et al.
Animal Mice (Male Female C57BL/6 Mice (Male Female Agouti (Av.
Rat (Male Wista.
Test
EPM
Intervention CBD Doses and Administration 5, 10 mg/kg.
Results CBD at 5 mg/kg increased time spent in open vs.
closed arms.
CBD
20 mg/kg/day.
F1 female mice treated with CBD during development buried twice as many marbles as controls.
EPM
Experimental design I: vehicle vs CBD vs CBD with WAY100635 Experimental design II: Vehicle vs CBD.
vs CBD with AM251.
vs CBD with AM630 CBD vs Vehicle WAY 100635: 0.
1 mg/kg CBD: 30 mg/kg.
WAY100635 partially reduced CBDAos anxiolytic effect.
CBD: 30 mg/kg AM251: 1 mg/kg AM630: 1 mg/kg.
CBD reduces anxiety by increasing time and frequency in open arms, but AM251 diminishes this effect.
30, 60 mg/kg.
CBD increasing open-arm entries, duration, and overall exploratory activity .
< 0.
CBD increased open-arm duration, but its anxiolytic effects were inhibited by WAY100635.
Mice given MDPV and CBD spent extra time in the open Rat (Male Wista.
Rat (Male Wista.
EPM NSF and EPM CBD vs CBD with WAY100635.
CBD with Capsazepine CBD: 5 mg/kg.
WAY100635:
2 mg/kg.
Capsazepine: 10 mg/kg.
Mice (Male CD.
EPM Vehicle vs CBD vs CBD with MDPV CBD: 20 mg/kg.
MDPV: 3 Ae 4 mg/kg.
Mice
(Male WT) LDB
CBD
10, 20, 30 mg/kg.
EPM
CBD
10, 20, 30 mg/kg.
NSFT
CBD
10, 20, 30 mg/kg.
EPM
CBD
0,5 and 1 mg/kg.
inject to CeA
EPM
CBD
20 mg/kg.
LDB
CBD vs CBDA 5 mg/kg.
Rat (Male Wista.
Mice (Female WT) and APPxPS Rat (Male CBD at 10 and 20 mg/kg increased time spent in the light box.
CBD .
, 20 mg/k.
increased open-arm percentage, peaking at 20 mg/kg.
CBD at 10 mg/kg improved motivation and feeding, while 20 mg/kg showed strong anxiolytic effects.
CBD .
mg/k.
increased exploration in the OF and time spent in the open arm.
CBD showed no effect in both mouse groups.
CBD .
mg/k.
reversed FS stress-induced anxiety and Page | 650 J.
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Study Melkumny an et al.
Marinho et
, 2015
Animal SpragueDawle.
Mice (Male Female C57Bl/.
Rat
(Male Test
with foot
EPM
Intervention Doses and Administration CBDA.
CBD.
THC CBDA: 1 AAg/mL.
CBD: 5 mg/kg.
THC: 1 mg/kg.
CBD :10 mg/kg.
CBD : THC
: 7,5:2,5 mg/kg CBD vs CBD: THC CBD vs CBD with WAY100635 CBD: 15, 30, and 60 nmol.
WAY100635: 0,37 nmol.
microinjection to intrainfralimbic EPM CBD vs CBD with WAY100635 Restrain stress and EPM CBD vs CBD with WAY100635vs Metyrapone CBD: 15, 30, and 60 nmol.
WAY100635: 0,37 nmol.
microinjection to intraprelimbic CBD: 15, 30, and 60 nmol.
WAY100635: 0,37 nmol.
microinjection to intraprelimbic.
Metyrapone: 75 mg/kg.
30 nmol
Restrain
stress and EPM
Fogaya et
, 2014
Rat (Male Wista.
Granjeiro et al.
, 2011
Campos Guimaryes, 2009 .
Rat (Male Wista.
Rat (Male Wista.
EPM
CBD
EPM
CBD vs CBD with Capsazepine WIN 55,212-2 vs WIN 55,212-2 with Capsazepine CBD: 30 and 60 nmol.
WIN 55,212-2: 3, 10, 30 nmol.
Capsazepine: 10 nmol.
intradlPAG Bitencourt et al.
, 2008
Rat (Male Wista.
EPM CBD vs AM404 vs Diazepam AM404 .
0 AAg/AA.
CBD .
0 AAg/AA.
Diazepam .
AAg/AA.
Salviato et
, 2021
Rat (Female Wista.
Rat
(Male EPM
CBD
1 mg/kg and 3 mg/kg.
EPM
THC: CBD
THC .
mg/k.
: CBD .
Ae 3 mg/k.
THC .
,075 mg/k.
CBD .
mg/k.
Mice
(Male EPM
CBD
30 mg/kg.
HUF-101
1, 3, and 10 mg/kg.
Breurer et
, 2016
Results increased time spent in the bright room.
THC induced anxiety and foot shock stress worsens anxiety.
24-hour
CBD
reduced anxiety.
CBD .
nmol increased exploration of EPM open arms.
In stress-restricted rats.
CBD treatment did not alter open arm exploration in the EPM compared to untreated groups.
CBD .
reducing openarm exploration in the EPM.
CBD's effect on EPM shifted from anxiogenic to anxiolyticlike in rats.
CBD exhibited open-arm entries.
CBD .
and WIN
55,212-2
Ae10 increased open-arm entries, while higher doses reduced the Capsazepine blocked anxiety from high doses.
AM404 and CBD increased open-arm entries in the conditioned group, while diazepam increased entries in both groups.
CBD .
mg/k.
showed increase in %OAT and %OAE compared to control.
THC's anxiogenic effects were reduced with CBD .
-3 mg/k.
Combining THC .
075 mg/k.
and CBD .
mg/k.
THC's anxiolytic effects.
Time spent in the open arm (%OAT) and entries into the open arm (%OAE) were The number of entries into the open arm (%OAE) and the Page | 651 Efficacy and Safety of Cannabidiol for Anxiety: A Bibliometric Analysis and Systematic Review Study Campos Guimaryes, 2008 .
Animal Rat (Male Wista.
Test
EPM
Intervention Doses and Administration HUF-102 1, 10 and 60 mg/kg.
HUF-103
1, 3 and 10 mg/kg.
CBD
15, 30, and 60 nmol CBD with AM251 CBD: 30 nmol.
AM251: 100
CBD
WAY100635
CBD: 30 nmol.
WAY100635:
0,37 nmol.
CBD
15, 30, dan 60 nmol Results duration in the open arm (%OAT) were increased by 3 mg/kg.
HUF-102 showed no increase in open-arm time or entries.
Significant increases in openarm time (%OAT) at 3 and 10 mg/kg.
Rats .
spent more time in the open arm, showing a bell-shaped dose-response curve with 30 nmol as the optimal dose.
Rats given 30 nmol CBD with AM251 showed similar openarm exploration as with CBD
CBD
WAY100635 didnAot increase open-arm exploration.
Rats given 30 nmol CBD drank more despite electric shocks.
Cats given CBD spent more time near their owner without Masataka, 2024 .
Cat (Male Domest.
CBD vs placebo 4 mg/kg Schleicher et al.
, 2019
Mice (Male Female C57BL/6 LDB 20 mg/kg CBD-treated mice showed no increased time in the lighted area, unlike vehicle-treated 20 mg/kg Former group showed no change, while the current group reduced time in the open Zebrafish (Male Female WT) Rat (Male Wista.
Rat (Male Sprague Dawle.
Time in the top
area of EPM
CBD
months/former grou.
vs CBD .
months/current CBD months/former grou.
vs CBD .
months/current CBD 1, 0.
5, 5.
0, and 10 mg/kg CBD showed a U-shaped doseresponse, with 0.
5 mg/kg surface time.
CBD
3, 3, 30 mg/kg.
In males.
CBD .
mg/k.
increased open-arm entries.
females, effects appeared at 0.
mg/kg in late diestrus.
LDB
CBD vs THC: CBD 30 mg/kg, 0.
3 mg/kg: 30 mg/kg.
EPM
CBD vs THC: CBD 30 mg/kg, 0.
3 mg/kg: 30 mg/kg.
CBD alone had little effect.
combined treatment reduced anxiety in stressed males.
In males, the combination significantly increased openarm duration.
Nazario et
, 2015
Fabris et
, 2022
PyrezValenzuela et al.
, 2023
EPM
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Study Huffstetler et al.
, 2023
Campos et
, 2013
Fogaya et
, 2018
Animal Mice (Male Female C57BL/6 (Kv1.
3Oe/ O.
Test Intervention CBD Doses and Administration 10 mg/kg and 20 mg/kg.
EPM
CBD
10 mg/kg and 20 mg/kg.
LDB
CBD
10 mg/kg and 20 mg/kg.
Mice (Male C57BL/6 GFAPTK Mice (Male C57BL/6 EPM CBD vs CBD with AM251 CBD: 30 mg/kg .
AM251: 1 mg/kg.
NSF
CBD vs CBD with AM251 CBD: 30 mg/kg .
AM251: 1 mg/kg.
EPM
CBD
30 mg/kg.
CBD with AM251 30 mg/kg, 0.
3 mg/kg.
CBD with AM630 30 mg/kg, 0.
3 mg/kg.
CBD
WAY100635
30 mg/kg, .
05 mg/kg and 1 mg/k.
NSF
Gomes et
, 2011
Rat (Male Wista.
EPM
CBD
30 mg/kg.
CBD with AM251 30 mg/kg 0.
3 mg/kg.
CBD with AM630 30 mg/kg, 0.
3 mg/kg.
CBD
WAY100635
CBD
30 mg/kg, .
05 mg/kg and 1 mg/k.
15, 30, or 60 nmol.
into BNST
CBD
WAY100635
CBD: 15, 30, or 60 nmol.
WAY100635: 0.
37 nmol.
injection into BNST 15, 30, or 60 nmol.
into BNST
CBD
CBD: 15, 30, or 60 nmol.
WAY100635: 0.
37 nmol.
injection into BNST 5 mg/kg.
CPPDB
30 mg/kg.
CBD
CBD
WAY100635
Shallcross et al.
, 2019
Rat (Male SpragueDawle.
EPM Results Male WT mice given CBD .
mg/k.
buried significantly fewer marbles than controls.
WT mice showed no change, but Kv1.
3Oe/Oe females .
mg/k.
spent more time in closed arms.
CBD eased anxiety in WT mice but increased it in female Kv1.
3Oe/Oe mice at 20 mg/kg.
CBD increased open-arm duration, showing anxiolytic effects in stressed WT mice.
CBD reduced eating latency in stressed WT mice.
Repeated CBD intake boosted open-arm stressed mice.
AM251 blocked the CBDAos anxiolytic effect.
AM630 blocked the CBDAos anxiolytic effect.
WAY100635 .
05 mg/k.
did not block CBDAos anxiolytic CBD decreased the latency to feed in stressed mice.
AM251
CBD's anxiolytic effect.
AM630
CBD's anxiolytic effect.
WAY100635 did not block CBD's anxiolytic effect.
CBD .
significantly increased open-arm entries and WAY100635 .
37 nmo.
blocked CBDAos anxiolytic CBD .
Ae60 nmo.
increased punished licks, resembling anxiolytic effects.
WAY100635 blocked CBD's anxiolytic effects.
Rats treated with CBD were less frequent in the open arms CPPDB did not affect openarm duration.
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Efficacy and Safety of Cannabidiol for Anxiety: A Bibliometric Analysis and Systematic Review
Study Morris et
, 2020
Animal Dog (Male Femal.
Test
LDB
Noiseinduced Intervention CBD Doses and Administration 5 mg/kg.
CPPDB
30 mg/kg.
CBD
4 mg/kg body CBD Trazodone Stern et al.
Rat (Male Wista.
EPM Results CBD reduced dark box time and sped up light entry.
CPPDB had no effect on dark box time or light box latency.
CBD doesn't significantly decrease anxiety.
CBD: 1.
4 mg/kg.
Trazodone:
100 mg for dogs 10-20 kg, 200 mg for dogs 20.
1-40 kg 1, 3 mg/kg.
No added benefit over trazodone alone.
may reduce its cortisol-lowering effect.
CBD showed no significant effect on open-arm duration or entries versus controls.
THC with CBD THC .
1 mg/k.
and CBD .
0 mg/k.
CBD
1, 3 mg/kg.
THC .
1 mg/k.
and CBD .
0 mg/k.
reduced freezing open-arm CBD .
0 or 3.
0 mg/k.
did not affect center duration in the OF test versus controls.
THC with CBD THC .
1 mg/k.
and CBD .
0 mg/k.
CBD
The combination treatment increased center duration in the OF test.
BNST: Bed Nucleus of the Stria Terminalis.
CBD: Cannabidiol.
CBDA: Cannabidiol Acid.
CeA: Central Amygdala.
CER: Conditioned Emotional Response.
CPPDB: 3-Cyano-N-.
,3-diphenyl-1H-pyrazol-5-y.
dlPAG: Dorsolateral Periaqueductal Gray.
EPM: Elevated Plus Maze.
v: intracerebroventricular.
Intraperitoneal.
LDB: Light Dark Box.
MB: Marble Burying.
MDPV: Methylenedioxy pyrovalerone.
MP: Mock Predatory.
NSF: Novelty-Suppressed Feeding.
OF: Open Field.
c: Subcutaneous.
SB: Secure Base.
SI: Social Interaction.
SIH: Stress-Induced Hyperthermia.
THC: Tetrahydrocannabinol.
VC: Vogel Conflict.
VH: Ventral Hippocampus.
vs: versus.
WT: Wild Type.
Table 3 presents that CBD reduces anxiety across diverse populations, including individuals with social anxiety disorder and PTSD at doses ranging from 150 to 800 mg/day.
It has been found that combining CBD with THC or antidepressants could balance the anxiogenic effects of THC and improved therapeutic outcomes.
Table 3.
Overview of the search for Cannabidiol (CBD) Study N Participant Age Drug .
Stanley et al.
, 32 (Test Anxiety 18 Ae 25 CBD vs placebo Inductio.
Zuardi et al.
20 - 38 Doses and 150, 300, 600 mg.
CBD
1 mg/kg.
CBD: THC
1 mg/kg: 0.
5 mg/kg.
Results Patients on 600 mg CBD showed more physical anxiety signs than placebo and lowerdose groups.
CBD had mild anxiolytic effects, weaker than diazepam.
The THC-CBD combination psychological anxiety.
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Study Martin et al.
N Participant .
Age .
Ou 18 Drug Medical cannabis (CBD dominant 82 %) Masataka, 2019 .
37 (SAD) Medical cannabis .
alanced THC:
CBD 7%)
CBD vs placebo Hurd et al.
eroin use CBD vs placebo Berger et al.
12 - 25
CBD
Antidepressants with CBD Doses and 61 mg.
Results CBD consistently reduced anxiety in both acute and longterm psychoactive effects.
CBD can reduce the anxietyincreasing THCAos effect.
300 mg/day for 4 400 mg.
oral once consecutive days 800 mg.
oral once consecutive days Starting at 200 mg/day, titrated to max 800 mg/day over 12 weeks.
Significant decrease in social anxiety scores (FNE & LSAS) compared to placebo Moderate anxiety and craving reductions lasted up to 7 days post-dose.
CBD sharply reduced anxiety and craving, lasting 7 days, beating 400 mg and placebo.
Anxiety dropped 42.
6% in 12 weeks, with 40% seeing a 50% CBD with antidepressants reduced anxiety more than CBD alone.
CBD significantly reduced CBD reduced anxiety and depressive symptoms from moderate to minimal in 8 Bergamaschi et al.
, 2011
Laczkovics et , 2021 .
24 (SAD) and 12 .
CBD vs Placebo 600 mg.
1 (SAD)
CBD
Hutten et al.
annabis THC-dominant CBD-dominant THC/CBDequivalent Cannabidiol (CBD), mg/day .
ver 8 week.
Sertraline .
mg/day, discontinued after 3 weeks of CBD).
75 mg THC, 75 mg THC, 75 mg THC 75 mg CBD.
Dahlgren et , 2022 .
22 - 64
18 - 50
1 mL sublingually 3x/day .
otal: 30 mg
CBD,
THC/da.
CBD:30, mg/day.
L-theanine:
175Ae185 mg.
Anxiety dropped significantly by week 4, evident by week 1.
Ramani et al.
CBD
ontains mg/mL CBD, 0.
mg/mL THC) CBD with L theanine Crippa et al.
25 - 42
CBD
400 mg.
Reduced anxiety .
< 0.
compared to placebo Significant increase in state anxiety compared to placebo.
No significant increase in anxiety compared to placebo.
CBD reduced THC-induced Anxiety, cognitive function, exhaustion, and BDNF levels did not significantly change.
Page | 655 Efficacy and Safety of Cannabidiol for Anxiety: A Bibliometric Analysis and Systematic Review Study N Participant .
69 (SAD) Age .
ntidepressants 178 .
Zuardi et al.
18 - 35
CBD
Souza et al.
rontline workers during COVID-.
CBD 150 mg twice daily .
mg/da.
for 28 CBD group demonstrates significant reduction in anxiety (GAD-7 score.
compared to Crippa et al.
10 (SAD)
CBD
600 mg.
CBD significantly reduced anxiety during public speaking tests versus placebo.
Bloomfield et , 2022 .
18 Ae 27
CBD
600 mg.
Bolsoni et al.
tressinducing arithmetic tas.
14 (PTSD.
18 Ae 60 CBD and Placebo 300 mg.
Stack et al.
(PTSD.
nxiety 18 Ae 70
CBD
0 Ae 100 mg/day.
between CBD and placeboAos CBD did not significantly reduce anxiety compared to CBD significantly reduced 50% of participants improved Significant reductions in anxiety .
< 0.
0-100mg/day.
18 Ae 50 CBD .
THC
THC .
CBD
CBD:
THC(Balanc.
CBD
18 Ae 25
CBD
50, 600mg .
wice daily for a wee.
Kwee et al.
Gundugurti et , 2024 .
Hundal et al.
Gournay , 2023 .
igh 63 .
levated trait
Drug
CBD
CBD
Nano-dispersible CBD and Placebo Doses and 300 mg, 2 hours before therapy.
CBD,
150 mg/mL .
600 mg/da.
for 12 100 mg, 300 mg, 900 mg.
0-38mg/day.
0-100mg/day.
Results CBD reduced subjective shock mild/unknown threat.
CBD impaired fear reextinction Significant reduction in GAD7 and HAM-A score.
CBD .
reduced anxiety in the post-speech phase .
nverted U-shaped curv.
Significant reduction in fatigue and anxiety .
< 0.
improved anxiety .
= 0.
Significant anxiety reduction .
< 0.
CBD increased anxiety slightly .
on-significan.
CBD symptoms in 2 weeks but did not affect worry severity.
CBD: Cannabidiol.
PTSD: Post Traumatic Stress Disorder.
SAD: Social Anxiety Disorder.
VS: Versus Page | 656 J.
Public Heal.
Pharm.
: 645-663
DISCUSSION