A Double-Blind,Randomized,Placebo-Controlled Test of the Effects of Cannabidiol on Experiences of Test Anxiety Among College Students

Abstract

Introduction:

Oral administration of cannabidiol (CBD) has shown to yield a variety of therapeutic benefits among humans, particularly regarding symptoms of anxiety. This study tested single oral administration doses of CBD (150, 300, or 600 mg), compared to placebo, for reducing test anxiety (TA) in a researcher-derived experimental analog.

Method:

Our sample included 32 healthy college students who self-reported moderate-to-severe levels of TA. Participants attended an experimental session, and received a dose of CBD or placebo, in a double-blind procedure. After administration of CBD, participants completed a statistics examination and measures of TA and general anxiety during examination administration.

Results:

Results indicated no effect of CBD dose on self-reported TA or general anxiety; however, results indicated efficacy of our experimental manipulation for inducing TA in vivo.

Discussion:

This is the first study to demonstrate that CBD does not reduce experiences of TA, and future work may examine the underlying mechanisms and affective states related to anxiety for which CBD may offer anxiolytic benefits, and for whom.

Introduction

Many college students report examination- and grade-related stressors as their greatest sources of anxiety, while enrolled in school.¹ Test anxiety (TA) refers to the set of phenomenological, physiological, and behavioral experiences that accompany concern about possible negative consequences associated with evaluative situations.² Previous research suggests that 10–40% of university students experience functionally impairing levels of TA.^3–6 Indeed, TA is a contributing factor to student withdrawal from universities,¹⁰ and is associated with poor grades,^7,8 lower Grade Point Averages (GPAs), difficulty engaging in instructional content,⁹ and low test performance.^10,11 Past research has demonstrated relationships between TA and various negative mental and physical health outcomes, such as increased risk for subsequent anxiety and depression, and dysregulated sleep and poor sleep quality.^12,13

Available interventions for TA have focused largely on therapeutic procedures such as individual and group counseling, systematic desensitization, and study skills training.¹⁴ To date, no study of acute pharmacological intervention for TA symptoms has been conducted. One promising pharmacological intervention to reduce symptoms of acute TA is cannabidiol (CBD). CBD is a nonintoxicating constituent of Cannabis sativa L., which has demonstrated anxiolytic effects in both human and nonhuman animal studies.^15–17 For example, a double-blind study assigned randomly healthy subjects to receive a single dose of placebo, 1 mg of clonazepam, or 1 of 3 doses of CBD (150, 300, or 900 mg) before performing a speech.¹⁸ Findings suggested that 300 mg of CBD reduced anxiety post-speech, but not 150 or 900 mg.¹⁸

In another investigation, researchers assigned randomly male participants (N=57) to receive a single CBD dose of 150, 300, 600 mg, or placebo before a simulation public speaking test (SPST).¹⁹ Findings revealed reductions in anxiety among those who received 300 mg of CBD, but no difference between or among the 150, 600, or placebo groups.¹⁹ Consistent with animal studies, results indicate that moderate, but not necessarily low or high, doses of CBD are anxiolytic.^20,21

Although past research has shown efficacy of a single dose of CBD in acutely reducing anxiety during a public speaking task,^18,19–22 no study to date has examined the potential utility of CBD for reducing TA, a conceptually similar experience. The purpose of this study is to examine the effect of a single dose of CBD on TA among college students. Given that studies suggest acute doses between 300 and 600 mg of CBD reduce anxiety, this study included similar dosing.^14,19,22,23 Specifically, we examined differences between doses of orally administered hemp-derived CBD (placebo and 150, 300, and 600 mg) in reducing symptoms of experimentally induced TA.

Methods

Participants

Participants were 32 students (M_age=20.48, SD_age=1.74) enrolled at a large mid-Atlantic University who met all eligibility criteria detailed in Table 1. Sample characteristics by treatment condition are described in Table 2. Randomization was accomplished by an unblinded research team, who was not involved in participant screening, enrollment, or data collection (Fig. 1). This study received Institutional Review Board approval.

FIG. 1.

CONSORT flowchart of participants. CBD, cannabidiol.

Table 1.

Eligibility Criteria

Inclusion criteria

1. Person is between 18 and 55 years old (inclusive)

2. Person is willing and able to provide informed consent and attend a 2.5-h, in-person session

3. Student self-reports completing a college-level introductory level statistics class with a grade of “C” or better

4. Student scores a 3.0 or higher on the Westside Test Anxiety Scale (indicating moderately high test anxiety)

5. Female student of childbearing potential must not be pregnant or currently breastfeeding

6. If student uses medication, the person has maintained a stable dose and regimen on existing medications for at least 30 days before participation in the study and throughout the study

7. Person agrees to abide by all study restrictions and comply with all study procedures

Exclusion criteria

1. Student has a known history of significant allergic condition, significant hypersensitivity to the IP, or allergic reaction to cannabis, cannabinoid medications, hemp products, or excipients of the IP

2. Student has been exposed to any investigational drug or device <30 days before screening or plans to take an investigational drug in the near future (within 30 days)

3. Student has used cannabis, synthetic cannabinoid or cannabinoid analog (e.g., dronabinol, nabilone), synthetic cannabinoid receptor agonist (e.g., spice, K2), or any CBD- or THC-containing product within 30 days of screening or during the study

4. Student has a current or past DSM-5 diagnosis other than an anxiety disorder that the Investigator deems would interfere in testing or interfere in evaluation of the study testing (e.g., current psychotic disorder)

5. Student has a total score of 16 or higher on the Alcohol Use Disorders Identification Test

6. Student has a total score of 12 or higher on the Drug Abuse Screening Test

7. Student has an acute or progressive disease that is likely to require changes in drug therapy during the study, or interfere with objectives of the study, or the ability to adhere to protocol requirements

8. Student is currently prescribed medications with likely THC or CBD interactions (e.g., warfarin, clobazam, valproic acid, phenobarbital, mTOR inhibitors, oral tacrolimus, St. John's wort; Epidiolex)

9. Student has history of suicide attempt in the last year

10. Student endorses current suicidal intent during the baseline assessment

11. Student has a positive drug screen for THC, barbiturates, amphetamines, benzodiazepines, and/or opiates at baseline assessment

12. Student has any clinically significant condition or abnormal findings during screening or the baseline assessment that would, in the opinion of the Investigator, preclude study participation or interfere with evaluation of the study testing

13. Student demonstrates behavior indicating unreliability or inability to comply with the requirements of the protocol

14. Female student of childbearing potential, unless willing to ensure that they or their partner uses effective contraception (e.g., oral contraception, double barrier, intrauterine device) during the study and for 3 months thereafter (however, a male condom should not be used in conjunction with a female condom)

15. Male student whose partner is of childbearing potential, unless willing to ensure that they or their partner uses effective contraception (e.g., oral contraception, double barrier, intrauterine device) during the study and 3 months thereafter (however, a male condom should not be used in conjunction with a female condom)

16. Any other significant disease or disorder which, in the opinion of the investigator, may put the person at risk because of participation in the study, confound the results of the study, or affect the student's ability to participate in the study

17. Student has history of diagnosis related to hepatic function and/or significantly impaired hepatic function (ALT >5′ ULN or TBL >2′ ULN) OR the ALT or AST >3′ ULN and TBL >2′ ULN (or INR >1.5)

18. Student has a BMI of underweight (18 kg/m² and below) or obese (30 kg/m² and above), or waist:hip ratio that is considered high health risk (0.86 and higher for females and 1.0 and higher for males)

ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CBD, cannabidiol; DSM-5, Diagnostic and Statistical Manual of Mental Disorders-5; INR, international normalized ratio; IP, investigational product; mTOR, mechanistic target of rapamycin; TBL, total bilirubin; THC, delta-9-tetrahydrocannabinol; ULN, upper limit of normal.

Table 2.

Descriptive Statistics of Demographic Variables by Treatment Condition

	Placebo	150 mg	300 mg	600 mg
Age	21.25 (0.96)	20.30 (1.16)	21.14 (2.85)	20.14 (1.06)
GPA	3.33 (0.50)	3.21 (0.54)	2.94 (1.02)	3.09 (0.51)
WTAS total	3.35 (0.24)	3.47 (0.43)	3.37 (0.60)	3.71 (0.38)
AUDIT total	6.75 (0.50)	4.90 (2.28)	3.14 (2.85)	3.14 (1.95)
DAST total	1.25 (0.50)	0.50 (0.53)	1.29 (0.95)	1.00 (1.15)
Gender
Male	1	1	2	1
Female	5	11	5	6
Ethnicity
Hispanic/Latinx	0	2	0	0
Not Hispanic/Latinx	6	10	7	6
School year
Freshman	1	3	1	1
Sophomore	1	2	1	2
Junior	3	2	2	3
Senior	1	4	1	1
Graduate student	1	1	2	0
Grade received in statistics course
A/A−	3	7	1	3
B+/B/B−	2	3	3	2
C+/C/C−	1	2	3	2

Note: Standard deviations of ratio variables are indicated in parentheses.

AUDIT, Alcohol Use Disorders Identification Test; DAST, Drug Abuse Screening Test; GPA, Grade Point Average; WTAS, Westside Test Anxiety Scale.

Materials

Online screening survey

Demographics

Information related to gender, age, race, ethnicity, year in school, body mass index (BMI), GPA, medical and psychiatric history, and medication use was collected to verify eligibility and describe the sample.

Screening assessments

The Structured Clinical Interview Screener for DSM-5—Screener was used to identify Diagnostic and Statistical Manual of Mental Disorders-5—defined mental disorders.²⁴ The Columbia-Suicide Severity Rating Scale (C-SSRS) was used to exclude participants endorsing current suicidal intent (responding “yes” to item 4 or 5).²⁵ The Drug Abuse Screening Test-28 was used to identify and exclude individuals who potentially abuse substances (score of 12 or higher).²⁶ The Alcohol Use Disorders Identification Test was used to evaluate alcohol use and experiences of alcohol-related problems (score of 16 or higher).²⁷ The Westside Test Anxiety Scale (WTAS) was used to identify self-assessed anxiety impairment and cognitions.²⁸ WTAS scores can range from one to five with higher scores reflecting more severe experiences of TA. Similar to past research,²⁹ scores of three or higher were used as an inclusion criterion.

In-person screening session materials

A tape measure was used to obtain height, weight, and waist-to-hip ratio measurements to verify BMI inclusion criteria. We used STATDIP^® One Step Drug Tests (12-panel) to qualitatively assess for drug use. Positive drug tests resulted in study exclusion. We used Clearblue^® Rapid Detection Pregnancy Tests to verify that female participants were not pregnant.

Experimental session measures and materials

Visual analog scale for TA

Participants indicated points and identified a corresponding number on a 100-point visual analog scale indicating their present subjective state-TA (100=the most intense experience of TA possible).

Visual analog mood scales

Participants indicated points and identified corresponding numbers on a series of sixteen 100-point visual analog scales (100=the most intense experience of each descriptor possible), indicating their present subjective state of general symptoms of anxiety and related mood states (e.g., discontented, withdrawn, lethargic, incompetent). The visual analog mood scales (VAMS) yields four factors: (1) anxiety, (2) sedation, (3) cognitive impairment, and (4) discomfort.²⁹ VAMS item ratings can be computed as factors, or combined to yield a single composite scale indicating overall mood.³⁰ Visual analog ratings of intensity of emotion states are commonly used in studies of the effects of CBD on acute anxiety inductions.^18,22 Internal consistency for this sample was excellent (Cronbach's α range=0.87–0.93).

State-trait anxiety inventory: state form

The state-trait anxiety inventory (STAI)-state form³¹ is a measure of present anxiety symptoms after anxiety induction.^32,33 Participants rated 20 symptoms of state anxiety on a 1 (not at all) to 4 (very much so) scale. The STAI-state yields a total score for the presence of current anxiety symptoms, with higher scores indicating more severe symptoms of state anxiety. Internal consistency for this sample was excellent (Cronbach's α range=0.86–0.94).

Somatic-symptom scale-8

The SSS-8 is an eight-item measure intended to capture the extent to which participants experienced somatic symptoms of anxiety (e.g., stomach problems, shortness of breath) on a 0 (not at all) to 4 (very much) scale. Internal consistency for this sample was good (Cronbach's α range=0.79–0.81).

Global impression of change

Participants indicated the extent to which their experiences of TA and general anxiety changed since the start of the study session on a 1 (very much improved) to 7 (very much worse) scale.

Statistics exam

A 40-item multiple-choice statistics test was developed by an expert in statistics pedagogy. Questions were intended to be challenging for undergraduates, as many items required mathematical calculation. This examination was used as part of the TA induction procedure (see TA induction).

Investigational product

Hemp-derived CBD isolate (<0.3% delta-9-tetrahydrocannabinol w/w) in medium-chain triglyceride oil with two percent peppermint oil (100 mg CBD/1 mL) was combined with inert oral solution such that each participant ingested orally 12 mL of a combination of investigational product (IP) and inert oral solution through opaque syringe. CBD and inert oral solution ratios differed to achieve desired dose for respective groups (e.g., the 150 mg CBD group received 1.50 mL of IP with 10.50 mL inert oral solution, the placebo group received 0 mL of CBD and 12 mL of inert oral solution). Product was manufactured at Best Formulations Inc. in California and was provided by the study sponsor.

Procedure

Online screening

Study advertisements, including the electronic screening survey, were distributed through university bulk email to currently enrolled university students. Students deemed eligible based on survey responses were contacted through email to schedule a 1 h in-person screening appointment.

In-person screening

At the in-person screening appointment (60 min), participants signed informed consent and were re-screened on C-SSRS items 4 and 5, and other eligibility criteria were verified verbally. Researchers also obtained height, weight, and waist-to-hip ratio measurements to verify BMI inclusion criteria. Participants who no longer met inclusion criteria were given $15 and dismissed. Participants also provided urine samples to test for illicit drug use. Participants who could not produce urine (n=2) or were detected as positive for drug use (n=1) were paid $15 and dismissed. Female participants' urine samples were pregnancy tested (n_positive=0). Participants who met all screening criteria received $15 and were invited to attend a single experimental session.

Experimental session

Experimental sessions lasted ∼2.5 h and each session was completed within specific timing parameters; participants completed experimental sessions held in groups across 4 days of data collection. Participants completed baseline measures and practice statistics questions, consumed a provided snack (with ≥20 mg fat to maximize bioavailability; minutes 0–34), and ingested IP (minutes 34–39). After IP administration, participants watched a 60-min, affectively neutral documentary (minutes 40–99). Following the documentary, researchers implemented experimental inductions of TA (see below), and participants completed pre-test measures (minutes 100–105). After completing pre-test measures, participants completed the first half of the statistics test (minutes 106–120), completed mid-test measures (minutes 120–123), and then completed the second half of the statistics test (minutes 124–137).

After submitting test materials, participants completed post-test measures (minutes 138–143), and researchers provided information regarding commercial purchase of CBD and provided instructions to pick up remaining study payment. See Table 3 for the schedule of measures during the experimental session.

Table 3.

Schedule of Measures During Experimental Session

Measures	Time points of testing session
Measures	Baseline 0–100 min	Pre-test 100–105 min	Mid-test 120–123 min	Post-test 138–143 min
VAS state test anxiety	X	X	X	X
VAMS	X	X	X	X
STAI–state form	X	X		X
Somatic symptom scale-8	X	X		X
Global impression of severity	X
Global impression of change		X		X
Statistics exam			X

VAMS, visual analog mood scales; VAS, visual analog scale.

TA induction

To induce TA experimentally, a series of strategies were employed. First, three “practice” questions were included with baseline measures—these questions were particularly challenging and designed to heighten worry about the pending test. Second, just before the onset of testing, an acute loud noxious noise (a recording of microphone feedback) was presented without warning. Third, students were told that data suggest that those who receive scores of 80% or higher on the test were more likely than others to get into graduate school, attain employment, and/or earn more money in entry-level jobs. Fourth, students were told they will receive monetary incentives for test performance such that the more questions answered correctly, the more money all questions will be worth; however, this incentive is a cover story to promote higher stakes for performance (all participants received full compensation, regardless of test performance).

Finally, students were told that if they were caught cheating on the test, they would be dismissed from the study without compensation and that an academic dishonesty report would be filed to the University Honor Council. To maintain the cover story, several teaching assistants monitored for cheating. Participants were told that remaining payment would be determined and made available after test scoring. Unbeknownst to participants, all participants were provided full payment ($70) regardless of test performance.

Statistical analyses

Initial sample size was determined to ensure adequate statistical power of changes in state-TA from baseline to post-test from past research on a single dose administration of 600 mg of CBD for social anxiety (SA).^17,22 The onset of the COVID-19 pandemic resulted in study discontinuation. While we were not able to recruit the target sample size (N=200), most analyses yielded adequate statistical power (see below).

A series of 4 (treatment condition)×4 (time) mixed analyses of variance (ANOVAs) was conducted to examine potential effects of state-TA and VAMS factors. A series of 4×3 mixed ANOVAs was conducted to examine potential effects of state anxiety and bodily symptoms of anxiety. A 4×2 mixed ANOVA was conducted to examine potential effects of changes in global impression of anxiety from pre- to post-test. Finally, differences in test scores across CBD dosage and placebo were evaluated using a one-way ANOVA. All data were analyzed in SPSS Version 27.0.

Results

Visual analog scale for TA

A 4×4 mixed ANOVA revealed a main effect of time on state-TA, F(3, 28)=4.38, p=0.007, η_p² = 0.14, observed power=0.86, such that participants, regardless of treatment condition, reported higher state-TA at mid-test (M=57.48, SD=25.88) compared to baseline (M=47.71, SD=30.25, p=0.03), and pre-test (M=42.35, SD=28.95, p=0.005). No other effect was observed (Fig. 2; Table 4).

FIG. 2.

Data represent mean VAS state test anxiety scores across treatment condition at measured time points. Error bars represent standard error. VAS, Visual Analog Scale.

Table 4.

Means and Standard Deviations of Primary Outcomes by Treatment Condition

	Baseline	Pre-test	Mid-test	Post-test
VAS state test anxiety
150 mg CBD	31.67 (27.66)	37.50 (27.83)	53.92 (25.96)	51.91 (25.00)
300 mg CBD	36.43 (33.13)	35.00 (36.52)	47.86 (35.69)	42.86 (36.27)
600 mg CBD	53.57 (53.57)	33.57 (17.25)	56.43 (16.76)	52.14 (20.59)
Placebo	69.17 (19.60)	63.33 (27.87)	71.67 (20.17)	67.50 (26.79)
VAMS (total)
150 mg CBD	609.25 (235.60)	661.50 (154.31)	686.53 (178.37)	717.33 (175.58)
300 mg CBD	448.14 (165.23)	460.00 (192.25)	529.29 (305.44)	531.43 (311.54)
600 mg CBD	624.29 (217.01)	633.43 (263.21)	768.57 (262.05)	665.14 (235.29)
Placebo	641.17 (208.76)	690.00 (139.18)	761.67 (112.90)	780.00 (228.23)
STAI–state form
150 mg CBD	46.00 (4.15)	45.92 (5.60)	—	42.08 (5.84)
300 mg CBD	47.86 (3.19)	44.71 (4.96)	—	46.43 (7.79)
600 mg CBD	47.71 (5.06)	44.29 (3.90)	—	44.00 (5.10)
Placebo	48.17 (3.96)	45.75 (1.08)	—	46.00 (6.69)
SSS-8
150 mg CBD	9.17 (7.26)	6.75 (5.51)	—	4.83 (4.22)
300 mg CBD	4.71 (2.87)	3.57 (2.51)	—	3.57 (2.88)
600 mg CBD	9.43 (4.20)	9.57 (3.46)	—	10.57 (5.16)
Placebo	6.17 (5.53)	5.00 (4.47)	—	5.50 (4.98)
Global impression of change
150 mg CBD	—	3.46 (0.69)	—	3.90 (0.94)
300 mg CBD	—	3.57 (0.53)	—	4.57 (0.54)
600 mg CBD	—	2.83 (1.17)	—	3.50 (1.64)
Placebo	—	2.60 (0.89)	—	3.40 (1.11)

Note: Values in parentheses indicate standard deviations. VAMS subscores were summed to create a composite score.

SSS-8, somatic symptom scale-8; STAI, state trait anxiety inventory.

Visual analog mood scales

A series of 4×4 mixed ANOVAs revealed main effects of time on anxiety, F(3, 84)=6.369, p<0.001, η_p²=0.19, observed power=0.96, sedation, F(3, 84)=6.39, p<0.001, η_p²=0.19, observed power=0.96, cognitive impairment, F(3, 84)=3.39, p=0.02, η_p²=0.12, observed power=0.75, and discomfort factors of the VAMS, F(3, 84)=12.21, p<0.001, η_p²=0.30, observed power=1.00. For all VAMS factors, subjective ratings increased from baseline, to pre-test, to mid-test. No other effect was observed (Table 4).

State-trait anxiety inventory: state form

A 4×3 mixed ANOVA revealed a main effect of time on state anxiety ratings, F(2, 56)=4.98, p=0.01, η_p²=0.15, observed power=0.79. On average, state anxiety decreased from baseline (M=47.82, SD=3.96) to pre-test (M=45.27, SD=4.42, p=0.005). No other effect was observed (Table 4).

Somatic symptom scale-8

A 4×3 mixed ANOVA revealed an interaction between CBD dose and time, F(6, 56)=2.45, p=0.04, η_p²=0.21, observed power=0.78. At pre-test, participants in the 600 mg CBD group (M=9.57, SD=3.46) reported higher bodily symptom scores of anxiety compared to participants in the 300 mg CBD group (M=3.57, SD=2.51, p=0.01). At post-test, participants in the 600 mg CBD group (M=10.57, SD=5.16) reported higher bodily symptom scores of anxiety compared to participants in the 150 mg CBD group (M=4.83, SD=4.22, p=01) and 300 mg CBD group (M=3.57, SD=2.22, p=0.007; Table 4).

Global impression of change

A 4×2 mixed ANOVA revealed a main effect of time on global impression of change in anxiety such that participants, on average, reported slightly higher experiences of anxiety at post-test (M=3.90, SD=1.11) compared to pre-test (M=3.20, SD=0.86), F(1, 25)=12.31, p=0.002, η_p²=0.33, observed power=0.92 (Table 4).

Statistics exam scores

A one-way ANOVA revealed no difference in test performance across treatment conditions, F(3, 28)=0.82, p=0.50, η_p²=0.08, observed power=0.20.

Discussion

This study implemented a randomized, double-blind, placebo-controlled test of 150, 300, and 600 mg of CBD on experiences of TA among college students. Findings revealed that CBD (at any dose) did not impact self-reported TA, psychological experiences of anxiety and related mood states, impressions of change in anxiety, or examination performance (during an experimental analog of a college testing environment); however, 600 mg of CBD appeared to increase bodily symptoms of anxiety across study time points compared to 150 and 300 mg CBD. Study outcomes are inconsistent with most pre-clinical and clinical research suggesting that ∼300 and 600 mg of acutely administered CBD may be effective in reducing anxiety among humans.^15,18,19,22

The majority of past research on anxiolytic effects of acute administration of CBD among humans has focused primarily on experiences of SA.^18,19,22 The experimental induction of SA (by SPST) has been widely used in clinical research and has shown to be a valid procedure for manipulating and inducing SA among clinical and nonclinical populations.³⁴ To our knowledge, this is the first study to attempt to experimentally induce TA in a controlled, laboratory setting. Baseline TA and anxiety symptoms were generally balanced across assigned CBD dosing groups; however, findings showed that baseline levels of TA were variable across individuals, and, on average, lower than predicted based on WTAS responses from the eligibility screening survey. Interestingly, participants in the placebo group reported higher levels of TA at all points of the procedure.

Relatedly, it is possible that CBD may not impact anxiety symptoms broadly, but instead serves as an anxiolytic for specific cognitive, physiological, and/or behavioral responses related to anxiety. Experiences of TA predominantly include negative nonsocial consequences (e.g., need to repeat a class, potential loss of financial aid, etc.); however, experiences of SA predominantly involve perceptions of pending negative social evaluation (e.g., social isolation, avoidance of social situations, etc.).^24,35

In this study, participants were subjected to threat of several potential negative consequences related to examination performance; however, none of the potential consequences involved threat of negative social evaluation. Although TA and SA are related constructs in terms of symptom expression, the underlying cognitive processes from which symptoms develop differ between conditions and may contribute to differential effects of acute CBD dosing for SA relative to TA. Further supporting the probable social specificity of CBD's anxiolytic effects, a recent placebo-controlled study testing the impact of acute CBD administration (150, 300, and 600 mg) on fear responses (induced through carbon dioxide-enriched air inhalation) found that CBD did not impact subjective fear ratings or panic attack symptoms.³⁶

Although these study findings contrast with previous literature, a number of strengths suggest experimental value. For example, this study implemented a randomized, placebo-controlled, double-blind design as is the “gold standard” for examining efficacy of an IP (Leen-Feldner et al. a double-blind, randomized, placebo-controlled test of the effects of cannabidiol on fear elicited by a 10% carbion-dioxide-enriched air breathing challenge; in review). Second, the highly controlled manufacturing and the documented analytic testing of the CBD product promoted precision dosing. Third, the multimethod assessment of TA, as well as general anxiety (e.g., assessing both psychological and physiological experiences of anxiety) included well-established indices of human anxiety that have been used in past CBD administration studies.^18,19,22 Fourth, standardized methods (i.e., timing and verification of both food and CBD administration) employed in a controlled environment limited the number of confounds that may have influenced results.

Finally, observed effect sizes were smaller than the recommended effect size for observing a meaningful effect in social science research,³⁷ suggesting that the failure to detect group differences was likely attributable to minimal impact of acute CBD dosing on TA rather than insufficient power to detect meaningful effects. Taken together, these methodological approaches increase confidence in the conclusion that acute administration of CBD does not appear to reduce experiences of TA among college students.

While the study had many strengths, limitations should also be noted. First, the sample included healthy, educated, primarily Caucasian female, young adults. Future research may increase sample diversity in an effort to understand generalizability of the impact of acute CBD dosing generally as well as on experiences of TA and anxiety symptoms broadly. Second, although past research has shown that 300 mg of CBD appears to have the strongest acute anxiolytic effects,^18,19,22 it is possible that effective doses related to TA are outside the range of tested doses in this study. Third, replication of methods employed to induce TA in this study is needed to validate the novel experimental analog; however, results demonstrate that the experimental analog sufficiently induced TA, as TA and VAMS ratings increased from baseline to mid-test, when participants experienced experimental manipulations of TA.

Furthermore, state anxiety did not change meaningfully during the study, suggesting the experimental manipulations were sensitive to inducing changes in TA specifically rather than anxiety symptoms broadly.

This study provides preliminary evidence suggesting that a single oral ingestion of CBD does not impact experiences of TA and general anxiety among college students in an experimental analog of testing environments. Further research aimed at understanding underlying mechanisms and affective states related to anxiety is needed to clarify instances in which CBD may offer anxiolytic benefits and for whom.

Footnotes

Authors' Contributions

T.B.S.: conceptualization, methodology, validation, investigation, formal analysis, data curation, writing—original draft, writing—review and editing, visualization, and project administration. M.L.F.: methodology, investigation, writing—original draft, and writing—review and editing. M.O.B.-M.: supervision, funding acquisition, and resources writing—review and editing. J.G.I.: conceptualization, methodology, validation, investigation, resources, writing—original draft, writing—review and editing, supervision, project administration, and funding acquisition.

Acknowledgments

Authors wish to acknowledge Caroline Prendergast and Morgan DeLong, who served as the unblinded research team for this project. In addition, we would like to acknowledge the members of the Changing Activity, Substance Use, and Health (CASH) Lab at James Madison University for their hard work and assistance with data collection. We would also like to thank Dr. Tracy Zinn for her consultation and assistance toward the project. Finally, we would like to thank Canopy Growth Corporation for donating the product for this study.

Author Disclosure Statement

Canopy Growth Corporation served as the Sponsor for this study. They assisted with the design of the study, provided financial support and IP for the study, and assisted with preparation and provided approval of the article. Canopy Growth Corporation played no part in the conduct of the study; collection, management, analysis, or interpretation of the data; or decision to submit the article for publication.

The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Ms. Stanley reports personal fees from Canopy Growth Coporation, outside the submitted work. Ms. Ferretti reports personal fees from Canopy Growth Corporation, outside the submitted work. Dr. Bonn-Miller reports personal fees, nonfinancial support, and other from Canopy Growth Corporation, personal fees and nonfinancial support from AusCann Group Ltd., personal fees and nonfinancial support from Realm of Caring Foundation, and personal fees and nonfinancial support from The Lambert Center for the Study of Medicinal Cannabis and Hemp, outside the submitted work. Dr. Irons reports a grant and nonfinancial support from Canopy Growth Corporation, outside the submitted work.

Funding Information

This project was funded by a grant from Canopy Growth Corporation.

Abbreviations Used

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