The effects of cannabidiol on subjective states, cognition, and psychomotor function in healthy adults: A randomized clinical trial

Abstract

Background:

Despite being added to numerous products, little is known about cannabidiol. Drowsiness is a self-reported side effect, which could impact cognitive functioning.

Objectives:

To determine whether cannabidiol impacts cognition and psychomotor function.

Methods:

A volunteer sample of healthy, college students were recruited for this randomized, parallel-group, double-blind, feasibility trial from April-November 2021. Participants completed a baseline survey, the Stanford Sleepiness Scale, Visual Analog Mood Scale, Digit Symbol Substitution Test, Trail Making Test, Psychomotor Vigilance Test, and Simple Reaction Time tests. Participants were then randomized and allocated to receive 300mg cannabidiol oil (N=21) or placebo (N=19). After 120 minutes, participants retook the tests. Performance between groups was compared using Analysis of Covariance and multi-level Negative Binomial regression.

Results:

Participants averaged 21 ± 3 years of age and 52% were female. Self-reported anxiety did not change post-treatment. Performances on the Stanford Sleepiness Scale, Visual Analog Mood Scale, and Psychomotor Vigilance test increased for both groups. After accounting for baseline scores, attention lapse duration significantly increased for those receiving cannabidiol compared to placebo in the Psychomotor Vigilance Test (76 msec vs. 66 msec; p=0.02). Auditory reaction time improved in the cannabidiol group versus placebo for one sound emitted during the Simple Reaction Time test (241 vs. 245 msec; p=0.02), but the number of early responses increased from 0.3 to 0.8 for those receiving cannabidiol.

Conclusions:

While performance on most tests were similar between those receiving cannabidiol or placebo, cannabidiol might affect certain aspects of vigilance. More research and larger trials are needed.

1. INTRODUCTION

Hemp-derived chemicals, such as cannabidiol (CBD), are being added to a multitude of foods, tobacco/vaping, and hygiene products after the passage of the 2018 United States (US) Agriculture Improvement Act which changed hemp’s legality [1–4]. Despite CBD’s widespread availability, peer-reviewed, placebo-controlled, randomized clinical trials (RCT) investigating the effects of CBD in healthy adult populations are limited [5–33]. Studies conducted in clinical populations determined that CBD is well-tolerated amongst participants with few adverse events reported [18, 34, 35]. Some of the most common self-reported side effects included gastrointestinal issues, drowsiness, and/or sedation [18, 34, 35]. Increased drowsiness/sedation is concerning as each could negatively impact cognition and/or psychomotor function, which are necessary for the completion of most daily activities including driving a motor vehicle. Drivers with impaired cognition and/or psychomotor function could experience delayed reaction times, incur more errors, experience diminished vehicle control, and/or decreased vigilance which could put them and others at risk of collision.

Several (N=12) peer-reviewed, placebo-controlled, RCTs investigated the effects of CBD on cognition and/or psychomotor function in healthy adults and only two studies investigated CBD’s effects on driving performance [5, 7–10, 15, 19, 21, 22, 25, 36, 37]. While the types of psychological tests utilized between studies were heterogenous, the most commonly used (60%) was the Digit Symbol Substitution Test (DSST), which measures motor speed, attention, and visuoperceptual function [5, 8, 19, 21, 22, 25, 36–38]. No statistically significant differences in DSST performance were observed between those receiving placebo or CBD in any of the studies [5, 7–10, 15, 19, 21, 22, 25, 36, 37].

In addition to the DSST, one double-blind, crossover, RCT of 26 healthy cannabis users conducted by Arkel et al [5] investigated the effects of inhaled THC-dominant, CBD-dominant, THC/CBD-equivalent, and placebo cannabis on driving performance. The main study outcome was the standard deviation of lateral position (SDLP), which measures how much a driver is swerving within the lane, and is an indicator of driver impairment [39, 40]. Participants completed 100-kilometer driving assessments at two time points post-inhalation and their performance was monitored by an instrumented vehicle. This particular study found that SDLP was not significantly different between CBD and placebo study arms [5]. A recently published study by McCartney et al investigated the effects of placebo, 15 mg, 300 mg, and 1500 mg of CBD on simulated driving performance using a cross-over RCT design among 17 participants [37]. Participants completed two simulation drives at 45–75 and 210–240 minutes post-treatment. The main outcome was SDLP. No differences in SDLP were detected among placebo or CBD; however, the authors reported that the treatment effects of CBD were inconclusive given complications with recruitment due to the SARS-Cov2 pandemic [37]. Thus, the effects of CBD on cognition, psychomotor function, and driving performance in healthy adults are still unclear.

Given the limited number of studies and gaps in the extant literature, the purpose of this study was to 1) conduct a feasibility trial investigating the effects of orally ingested CBD oil on driving performance as no peer-reviewed studies existed on this topic when this study was conceptualized/designed and, 2) determine CBD’s effects on psychomotor function, cognition, and self-reported subjective states, which include sleepiness, calmness/tranquility, physical and mental sedation, in healthy adults aged 18–30 years. Due to the sheer amount of data collected, this manuscript will focus solely on the results of the self-reported subjective states, cognitive and psychomotor testing. This study’s hypothesis was that participants randomized to CBD would show greater changes consistent with sedation, increased drowsiness, and decreased cognitive and psychomotor performance relative to the placebo group.

2. MATIERALS AND METHODS

2.1. Study design

This was a randomized, double-blind, parallel-group, two-arm trial with a 1:1 allocation ratio.

2.2. Study participants

Participants were healthy, adult volunteers, and the eligibility criteria were as follows: 1) current enrollment as a student (≥ 1 credit hour), 2) 18–30 years of age at time of study, 3) possessed a current drivers’ license, 4) driven a motor vehicle at least once in the past 30 days, 5) able to read English, 6) willing to take a urine drug test and complete a test drive to ensure the absence of simulation sickness, 7) not taking any daily prescription medications (excluding birth control), 8) not diagnosed with any serious chronic disease by a licensed healthcare provider, and 9) had an individual willing to drive them home after testing. Participants were excluded if they currently smoked or used tobacco products, used CBD in the past 7 days, or used illegal drugs in the past 30 days (e.g., cocaine/crack, heroin, methamphetamine, 3,4-methylenedioxy-methamphetamine, inhalants, phencyclidine, LSD, mushrooms, or marijuana), or were pregnant or lactating at time of study. These time frames (i.e., 7 days for CBD and 30 days for illicit drugs) were chosen to ensure that these drugs would have time to potentially clear from participants’ systems if they were used. The study took place at the West Virginia University Health Sciences Center located in Morgantown, West Virginia between April 2021-January 2022. The study was registered on www.clinicaltrials.gov (NCT04590495) and approved by the university’s Institutional Review Board (ID# 2007073792).

2.3. Sample Size

GPower 3.1 was used to estimate the required sample size prior to recruitment [41]. As one of the primary outcomes was to assess differences in mean SDLP between the placebo and CBD groups, an omnibus one-way analysis of variance (ANOVA) test was chosen to estimate sample size. An ANOVA was chosen over a T-test in case the model had to be adjusted for covariates. No published studies concerning the effects of CBD on driving performance existed at the time this study was conceptualized/designed. Because several previous studies found that participants receiving 300 mg of CBD experienced anxiolytic effects [20, 21, 42], it was assumed that the effect size would be on the larger side of the spectrum especially since sedation and drowsiness are positively correlated with increased SDLP.[43, 44] For an ANOVA, with an effect size of 0.50, alpha=0.05, and 80% power between 2 groups, a total sample size of 34 participants was needed. To accommodate a 15% attrition rate, 40 participants were targeted for enrollment.

2.4. Recruitment, screening, and enrollment

Study advertisements were sent to all students at West Virginia University via email list serves. Flyers were hung around campus and at businesses located near campus where students frequented. Using a standardized screening checklist, 96 individuals were pre-screened, and 58 were scheduled for a study visit. Prior to their visit, participants were given a list of instructions both verbally and over email. They were told to abstain from taking any types of medications including nutraceuticals, over-the-counter medications, vitamins, or supplements 24 hours before their appointment. They were also instructed to not consume alcohol or caffeine within 10 hours of their appointment. This was to ensure that other substances would not interact with the CBD and/or alter their driving performance. They were also advised to get at least 6 hours of sleep the night prior. All study visits were scheduled at the same time in the morning (i.e., ~9:00 AM) to avoid differences in driving behavior due to biorhythms. Study personnel re-screened the participant; if participants did not follow the pre-visit instructions, their appointment was rescheduled. Written consent was then obtained. After consenting, the participant was asked to provide a urine sample, which was analyzed immediately onsite for potentially impairing drugs, which included amphetamines, barbiturates, benzodiazepines, buprenorphine, cocaine, heroin, marijuana, methadone, methamphetamine, methylenedioxymethamphetamine (MDMA), morphine, opiates, morphine, oxycodone, phencyclidine. If the individual tested positive for any of these substances, they were not able to participate. If a participant’s sample tested negative, they then completed a 10-minute practice drive on the driving simulator which provided practice and served as a screen for simulation sickness [45]. If there was evidence of simulation sickness observed by study staff and/or reported by the participant, such as nausea, dizziness, sweating, disorientation, etc. the individual was not eligible to participate. Forty individuals completed the consent process and were enrolled in the study.

2.5. Study Overview

An overview of the study procedures is shown in Figure 1. After enrollment, all participants were administered a, standardized, internet-based, pilot-tested, baseline survey which inquired about their demographics, gaming habits, and behaviors. After completing the survey, all participants took a series of tests (N=6) which assessed sleepiness, calmness/tranquility, physical and mental sedation, psychomotor function, and cognition. This included the Stanford Sleepiness Scale (SSS), the Visual Analog Mood Scale (VAMS), Digit Symbol Substitution Test (DSST), Trail Making Test Parts A and B (TMT-A, TMT-B), Psychomotor Vigilance Test (PVT), and Simple Reaction Time (SRT). After testing, participants were provided a standardized breakfast and then waited 120 minutes for absorption. This time frame was chosen based on the pharmacokinetics of CBD along with the consideration of participant burden [24, 46]. Participants then completed the driving simulation and re-took all the psychological tests in the same order ~2.5 hours post-treatment. Lastly, participants completed a questionnaire which inquired about blinding and the acceptability of study procedures. All individuals completing the study received $50 gift card, and the entire procedure lasted 4–4.5 hours.

Figure 1.

Overview of study design and flow.

2.6. Randomization, treatment allocation, and blinding

Using a 1:1 stratified randomly varying block technique [47], participants were randomized to receive either CBD (N=21) or placebo (N=19). As driving behaviors and/or risk tolerances differ between males and females, participants’ sex served as the stratification variable [48, 49]. The randomization schedule was prepared by the study statistician, who had no contact with participants. Following this randomization schedule, study staff sequentially placed small cards labeled A or B into opaque envelopes, sealed, and stacked them by sex. When a participant was enrolled into the study, the top envelope was removed from the corresponding sexes’ stack. The Principal Investigator, the staff collecting data, the staff delivering the treatment, and participants were all blinded to treatment assignment.

2.7. Intervention

2.7.1. Study drugs

Treatment A (e.g., placebo), consisted of avocado oil, while Treatment B was 300 mg of CBD. Both treatments were flavored with mint oil immediately prior to dispensing to mask taste. This dosage of CBD was chosen as it has been used in other studies and was well-tolerated with no major adverse events [21, 25, 42, 50]. The CBD for this study was purchased from Zatural (Eden, Idaho). As previous studies have shown that CBD products are often mislabeled [51], the product was tested by an independent third-party lab prior to use to ensure safety. Samples of the CBD were sent to Botanacor Laboratories located in Denver, Colorado. Testing revealed that the labeling was accurate with virtually no THC present (i.e., 0.006% detected). Both CBD and placebo were dispensed via oral syringe.

2.7.2. Driving simulation

After the 120-minute waiting period, all participants (N=40) underwent an identical driving simulation to assess performance. The simulator used in this study was the STISIM Drive M1000, which is equipped with screens, a steering wheel, signals, and pedals. Participants completed a second practice drive (i.e., ~5 minutes), brake reaction test (i.e., ~5 minutes), and then the primary study drive (i.e., ~25 minutes), which included both urban, suburban, and rural highway segments that required turns, changes in speed, and avoidance of objects.

2.8. Data collection and outcomes

All collected data were entered directly into a secure, electronic database by staff. As this manuscript is focused strictly on psychological testing outcomes, these data are described in more detail below.

2.8.1. Demographics

At baseline, participants were self-administered a standardized, pilot-tested, baseline survey via RedCap software. The survey asked participants’ ages, biological sex, race, student status (undergraduate or graduate student including professional programs), the number of hours they spent playing games on their cellphone or computer, how many hours they slept the night before testing, and if they ever used CBD. As cannabis can be absorbed in body fat, participants height and weight were taken, and their subsequent body mass indices were calculated.

2.8.2. Measures of Sedation, Cognition, and Psychomotor Function

To assess current sleepiness/drowsiness, participants were administered the Stanford Sleepiness Scale (SSS), which is a 7-point Likert scale with greater scores indicating more sleepiness/drowsiness [52]. To assess tranquility, physical, and mental sedation, participants were administered the Visual Analog Mood Scale (VAMS). The VAMS consists of 16 Likert scale questions ranging from 0–100. Questions 1,4,11, and 13 on the VAMS measure mental sedation, while questions 3, 5, 6, and 16 measure physical sedation. Questions 2,7,8, and 12 measure calmness/tranquility. After combining the questions as described in previous research, higher scores equate to greater sedation and tranquility/calm (range 0–400) [53]. To assess processing speed, attention, and psychomotor function, participants were administered the Digit Symbol Substitution Test (DSST) [38, 54]. The DSST requires participants to translate numbers into symbols; the test is scored by the degree of completion and accuracy over a timed 90 second period. Higher scores indicate better performance [38, 54]. To assess executive function, cognitive flexibility, and scanning, the Trail Making Test Parts A and B (TMT-A, TMT-B) were administered. TMT-A requires participants to connect numbers in ascending order, while the TMT-B requires individuals to connect numbers and letters in alternating sequence. The test is scored by the time it takes to accurately complete each test in seconds. Increases in completion time correlate with greater impairment [55, 56]. To assess processing speed and vigilance, participants were administered the Psychomotor Vigilance Test (PVT); the PVT is a 10-minute computer-based test where a symbol appears at random intervals on the screen and the individual must press a key in response. The PVT can be used to investigate mean reaction time, number of lapses in attention during testing, and length of lapses in attention; a lapse in attention is considered any reaction >500 milliseconds [57]. The length of lapse duration was the time after a lapse was identified (i.e., at 500 milliseconds) to the time the participant reacted. To assess auditory processing speed, participants were administered a Simple Reaction Time (SRT). The SRT is a 5-minute test administered on a laptop. Two different auditory sounds are emitted at random, and the participant must hit a particular key in response. The test measures reaction time (in milliseconds) and early responses to assess performance [58]. These tests have all been used in drug impairment research and deemed valid and reliable instruments [59–65].

2.9. Statistical analyses

As no enrolled participants failed to complete the study and there were no missing data, only an intent-to-treat analysis was performed. Demographic characteristics were compared between groups via descriptive statistics. For demographic categorical variables, characteristics were compared using Chi Square tests or Fisher’s exact tests for small cell counts. For continuous or ordinal variables, Student’s T tests (for normally distributed variables), or Mann Whitney U Tests (non-normally distributed variables) were utilized. All count data (e.g., numbers of correct symbols, number of lapses, and number of early responses) were analyzed using a multi-level Negative Binomial regression where the subject was treated as a random effect with an autoregressive correlation matrix to account for repeated measurements. Because all other outcome measures were continuous repeated measures, group differences were assessed using Analysis of Covariance (i.e., Paired T-test equivalent) for normally distributed variables or Wilcoxon Signed Rank for non-normally distributed variables; these tests compared the post-treatment scores between the CBD and placebo groups while adjusting for baseline performances. Effect sizes were calculated using Cohen’s D for Welch test which accounted for the dependence of observations using the difference between post and pretreatment assessments [66]. All analyses utilized two tailed hypothesis tests with α=0.05. All analyses were performed using SAS version 9.4 (Cary, NC).

3. RESULTS

Ninety-six individuals were pre-screened by research personnel to participate in this study. Among these individuals, 58 were eligible and initially scheduled a testing date. All enrolled participants (N=40) completed the study. There were no missing data, and no adverse events were reported by study participants. (Figure 1).

Baseline characteristics of the study population by treatment group are shown in Table 1. Demographic characteristics were similar between CBD and placebo groups. Overall, the participants were approximately 21 +/− 3 years of age, 52% female, and of white race. Though not statistically different, those in the placebo group gamed slightly more than those in the CBD group (8.6 vs. 5.6 hours, respectively). Most participants were CBD-naïve.

Table 1.

Demographics of study participants by treatment group (N=40)

Characteristic	CBD (N=21)	Placebo (N=19)	Total (N=40)	P
Age in years, mean (SD)a	21.4 (2.8)	21.0 (2.7)	21.2 (2.7)	0.57
Male, N (%)b	10 (47.6)	9 (47.4)	19 (47.5)	0.99
White, N (%)c	18 (85.7)	16 (84.2)	34 (85.0)	1.00
BMI, mean (SD)d	26.3 (6.3)	25.6 (3.6)	26.0 (5.2)	0.70
Weight in pounds, mean (SD)d	171.9 (47.2)	166.2 (30.7)	169.2 (39.8)	0.66
Undergraduate student, N (%)b	13 (61.9)	15 (79.0)	28 (70.0)	0.24
Hours gaming per week, mean (SD)a	5.6 (5.1)	8.6 (13.8)	7.1 (10.2)	0.66
Hours sleep previous night, mean (SD)a	7.3 (1.0)	7.1(1.2)	7.2 (1.1)	0.64
Ever used CBD, N (%)c	4 (19.1)	5 (27.8)	9 (23.1)	0.71

Abbreviations: N=total; P=probability value; SD=standard deviation

^a:P-value calculated via Mann Whitney U Test comparing CBD to placebo group

^b:P-value calculated via Chi-square test comparing CBD to placebo group

^c:P-value calculated via Fisher’s Exact test due to small cell counts comparing CBD to placebo group

^d:P-value calculated via Student’s T-test comparing CBD to placebo group

Both groups were more physically and mentally tired after treatment as their SSS and VAMS scores dramatically increased (Table 2). However, tranquility scores did not change for either group between pre and post treatment. Both groups saw improvements in their DSST and TMT parts A and B. In fact, after adjusting for baseline performance, CBD group performed better in TMT part B than placebo (30 vs. 37 seconds; p=0.03). The findings concerning reaction times were mixed. In regard to the PVT, which is a 10-minute test, increases in reaction time were observed for both groups. Conversely, for the SRT, which is a 5-minute test, auditory reaction time improved in the CBD group compared to placebo for sound 1 after accounting for baseline performance (241 vs. 245 msec; p=0.02). However, after accounting for baseline scores on the PVT, attention lapse duration significantly increased for those receiving CBD compared to placebo (76 msec vs. 66 msec; p=0.01). Additionally, the number of early responses for sound #2 increased from 0.3 to 0.8 for those receiving CBD whereas there was no difference seen for those receiving placebo. Effect sizes ranged from 0.1–0.64, with an average of 0.24.

Table 2.

Mean participant scores at baseline and post-treatment for cognitive and psychomotor tests, sleepiness, and mood stratified by group^a

	CBD (N=21)				Placebo (N=19)				ES d	P
Assessment	Baseline		Post- Treatment		Baseline		Post- Treatment
	Mean	(SD)	Mean	(SD)	Mean	(SD)	Mean	(SD)
SSSb	2.0	(1.0)	2.7	(1.3)	1.9	(1.0)	2.6	(1.4)	0.02	0.99
VAMS: Physical sedationb	93.0	(49.8)	135.6	(65.3)	118.8	(69.2)	152.7	(71.0)	0.18	0.79
VAMS: Mental sedationb	84.5	(53.4)	148.7	(80.1)	111.8	(75.5)	161.3	(78.3)	0.20	0.87
VAMS: Tranquilityb	303.0	(53.9)	302.4	(50.8)	297.3	(69.6)	301.3	(66.2)	0.10	0.85
DSST: # Correct symbolsc	68.0	(10.7)	74.5	(8.1)	65.7	(11.6)	71.8	(12.1)	0.05	0.43
TMT Part A: Time (sec)b	18.8	(4.9)	14.2	(4.1)	18.7	(6.2)	15.6	(5.2)	0.29	0.26
TMT Part B: Time (sec)b	43.4	(13.2)	29.7	(8.9)	41.9	(13.5)	37.1	(15.9)	0.64	0.03
PVT: Rxn Time (msec)b	315.0	(25.8)	331.7	(37.7)	318.3	(20.8)	330.0	(32.7)	0.22	0.47
PVT: # of lapsesc	2.6	(1.6)	2.9	(1.6)	2.4	(1.3)	3.5	(1.5)	0.61	0.71
PVT: Lapse duration (msec)b	39.2	(69.7)	75.8	(82.6)	34.6	(34.9)	65.8	(71.6)	0.06	0.01
SRT: Rxn time sound 1(msec)b	245.4	(17.8)	241.4	(22.1)	252.5	(21.5)	244.6	(30.2)	0.19	0.02
SRT: # Early responses sound 1c	0.6	(0.8)	0.5	(0.8)	0.5	(0.7)	0.4	(0.7)	0.01	0.14
SRT: Rxn time sound 2 (msec)b	241.3	(19.8)	239.6	(20.8)	242.4	(23.1)	240.4	(48.0)	0.45	0.06
SRT: # Early responses sound 2c	0.3	(0.5)	0.8	(1.0)	0.3	(0.5)	0.4	(0.7)	0.34	0.14

Abbreviations: CBD=Cannabidiol; DSST= Digit Symbol Substitution Test; Msec=Millisecond; P=Probability value; PVT=Psychomotor Vigilance Test; Rxn= Reaction; SD=Standard deviation; Sec=Seconds; SRT=Simple Reaction Time; SSS=Stanford Sleepiness Scale; TMT=Trail Making Test; VAMS= Visual Analog Mood Scale

^a:Higher scores indicated worse performance for the SSS, VAMS, TMT, PVT, SRT. Higher scores for the DSST indicated improved performance

^b:Probability values were calculated via Analysis of Covariance (e.g., Paired T-test equivalent). These tests compared the post-treatment scores between the CBD and placebo groups after adjusting for baseline performances.

^c:Numbers of correct symbols, number of lapses, and number of early responses for sounds 1 and 2 were all analyzed using multi-level Negative Binomial regression which utilized autoregressive correlation matrices to account for dependence of observations

^d:Effect sizes were calculated between groups using Cohen’s D for Welch test. This measure accounted for the dependence of observations using the difference between post and pretreatment periods.

4. DISCUSSION

This study found that self-reported subjective states such as sleepiness, sedation, and tranquility/calmness along with the performance on some cognitive and psychomotor tests were similar between participants receiving CBD or placebo. Both groups experienced soporific effects, but no changes in anxiety after treatment. Both groups also displayed learning effects as their scores improved on the DSST and TMT parts A and B, which is most likely due to the fact that these are young, healthy adults. However, differences between the groups may have been elucidated in the PVT, which is designed to be a longer, more monotonous test than the SRT. While both groups experienced increased reactions times and number of lapses in attention in the PVT after treatment, the lapse duration was significantly higher in those receiving CBD vs. placebo. While the CBD group performed slightly better in terms of reaction time to one of the sounds emitted for the SRT, they may not have been as accurate as the placebo group; the CBD group’s early responses were slightly higher, but not statistically significant, than the placebo group for sound 2 in the SRT. Thus, these findings may preliminarily suggest that CBD may impact certain aspects of vigilance.

The findings of this study are similar to others conducted previously. Several RCTs conducted in both clinical and healthy populations also compared subjective states such as anxiety, drowsiness, sedation, or feeling ‘high/impaired’ between groups receiving placebo or CBD [5–8, 10, 14–17, 19, 20, 23, 25, 27, 31, 37, 67]. The findings between studies were highly variable; several studies reported that participants receiving CBD experienced more drowsiness/sedation and/or were less anxious [14, 16, 20, 23, 25, 37] than those receiving placebo, while others reported no difference in subjective states between placebo and CBD groups [5–8, 10, 15, 17, 19, 27, 31, 67]. The variability of the findings between studies may be due to factors such as the dosage of CBD given, route of administration (inhaled vs. consumed CBD), type of RCT (between group or within person comparisons), and population studied (i.e., cannabis naïve, frequent, or infrequent users; healthy or clinical populations).

However, comparing the results of this study’s cognitive and psychomotor tests to others conducted with healthy adults is more challenging due to the differences in the types of instruments used to assess performance. The DSST is the most common test utilized by other RCTs investigating the effects of CBD on cognition and psychomotor function; other studies also found no difference in DSST performance among healthy individuals randomized to receive CBD or placebo [5, 7–10, 15, 19, 22, 25, 36, 37]. Yet, only two previous RCTs conducted in healthy adults utilized the PVT to investigate the effects of CBD compared to placebo; neither study reported differences in PVT performance between placebo or CBD groups [21, 37]. However, in one study it was unclear which aspects of the PVT were investigated [21]. It also appears that neither study investigated lapse duration. Thus, given the limited number of studies and differences in tests utilized, additional research regarding CBD’s effects on vigilance, cognition, and psychomotor function in healthy adults are clearly needed.

While statistical significance may have been achieved by chance, if CBD does impact certain aspects of vigilance, this could have public health implications. Maintaining vigilance is an essential function of driving. Previous studies have shown that hypo-vigilance can lead to driving errors and variations in drivers’ speeds [68, 69], which could lead to motor vehicle collisions. A recent study of drivers in the Washington, DC metro found that 78% of all crashes in a one-year period were due to driver inattention [70]. Studies conducted in Australia found that >30% of all fatal and injurious crashes in that country were due to driver inattention [71]. Given that hypo-vigilance is already problematic for drivers, this issue could intensify as hemp-derived products, such as CBD, become more ubiquitous among the driving population. However, more research is needed.

4.1. Limitations

While this study contributes to the limited extant literature on the effects of CBD, it is not without limitation. First, the study population consisted of 40 healthy college students. We did not collect participants medical records to ensure they were healthy; their health was self-reported which could be subject to reporting bias. Given the limited research at time of conception and design, this study was initially powered at 0.50 to assess SDLP and not cognition, psychomotor function, and subjective states specifically. This study was most likely statistically underpowered as the average effect size for the outcomes reported herein was 0.24. Moreover, the findings may not be generalizable to the general US population or other healthy adults. Because the participants were in good health, it is unknown how CBD may impact older individuals, those with preexisting medical conditions, or those taking other prescription or non-prescription drugs which may influence the effects of CBD. As mentioned previously, this study assessed subjective states, cognition, and psychomotor function via 6 tests. As the human brain is an amazingly complex organ, these tests do not encompass every facet of cognition or psychomotor function. Also, subjective states rely on self-reported instruments which are also subject to reporting biases. Also, this study used one dosage of CBD (e.g., 300mg). This may not reflect a normal dosage of CBD though a ‘normal’ dose is unknown. Also, multiple comparisons were made so statistical significance may have been achieved by chance. Lastly, a two-hour time period was chosen between treatment and retesting. Previous studies have suggested that the half-life of CBD is 2–5 hours [24, 46]. It is entirely possible that the max effect of the drug was not achieved in some participants. While a standardized high fat meal was given to participants after dosing, this should have increased absorption as CBD is fat soluble. However, the amount of food participants consumed was not recorded. It is possible that some participants ate more and absorbed more CBD.

5. CONCLUSIONS

This study found that drivers randomized to receive CBD performed similarly to those receiving placebo on some cognitive and psychomotor tests and self-reported subjective states including sleepiness, sedation, and calmness. However, those receiving CBD experienced greater lapses in attention during the PVT compared to placebo. Larger studies are needed to elucidate whether CBD does indeed impact vigilance, cognition, and/or psychomotor function in both healthy and clinical populations.

LIST OF ABBREVIATIONS:

ANOVA

Analysis of Variance

CBD

Cannabidiol

DSST

Digit Symbol Substitution Test

PVT

Psychomotor Vigilance Test

RCT

Randomized clinical trial

SDLP

Standard deviation of lateral position

SRT

Simple Reaction Time Test

SSS

Stanford Sleepiness Scale

THC

Delta-9-tetrahydrocannabinol

TMT-A

Trail Making Test Part A

TMT-B

Trail Making Test Part B

US

United States

VAMS

Visual Analog Mood Scale

Data Availability Statement:

No additional data are available.