Conditions: Memory
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 57
Healthy volunteers: yes

Brief summary:
The main objectives of this study were to test if a singular dose of Cannabidiol (1) enhances the learning and memory of healthy human subjects, (2) test if Cannabidiol has negative effects on Retroactive and Proactive Interference during learning, (3) and test if demographic factors will influence CBD's modulation of human learning and memory.

Detailed description:
Using a randomized, double-blind, placebo-controlled two-arm case-crossover trial, this study investigates the effect of 246 milligrams (mg) of Cannabidiol (CBD) on the learning and memory scores of human subjects, as well as the effect of Cannabidiol on Proactive and Retroactive Interference. This study also investigated the influence of demographic factors on CBD's modulation of human learning and memory.

This study was conducted at Colorado State University-Pueblo (CSU Pueblo) with volunteers recruited from CSU Pueblo and the local Pueblo community. Fifty-seven subjects were randomized in a double-blind manner to receive either CBD or placebo before completing two versions of learning and memory assessments. Each version of the learning and memory assessment included the Montreal Cognitive Assessment (MOCA), the Rey Auditory Verbal Learning Task-Revised (RAVLT-R), and the Logical Memory Subject of the Weschler Memory Scale. Several components of the RAVLT-R were evaluated including the Sum of Trials (Trials I-V) score, Proactive Interference Ratio (PI Ratio), and Retroactive Interference (RI Ratio).

Arms:
arm 1: Participants first received a Placebo 246 mg press pill during visit 1. After a washout period of 1 week, subjects received a Cannabidiol press pill during visit 2. arm 2: Participants first received a Cannabidiol 246 mg press pill during visit 1. After a washout period of 1 week, subjects received a Placebo press pill during visit 2.

Interventions: intervention 1: Cannabidiol (246mg press pill) intervention 2: Placebo (246mg press pill)
Intervention descriptions: intervention 1: Cannabidiol press pills provided by Steve Goods CBD (Longmont, Colorado). CBD pills were tested by the chemistry lab at CSU Pueblo and by Botanacor in Denver, CO. Both laboratories determined CBD pills to be 99.98% pure with no THC, heavy metals, bacteria, and pesticides detected. intervention 2: Placebo press pills were provided by Steve Goods CBD (Longmont, Colorado). Placebo pills were tested by the chemistry lab at CSU Pueblo and by Botanacar in Denver, CO. Both laboratories determined placebo pills to be pure with no heavy metals, bacteria, and pesticides detected.

Protocol document:
Prot_SAP_002.pdf: 
 
 
 
 
 
The Effect of Cannabidiol on Human Learning and 
Memory 
 
Protocol and Statistical Analysis Plan 
(SAP) 
 
 
Colorado State University-Pueblo 
V2.0 
28Aug2024 
 


 
 
1. Protocol 
The broad objective of our study was to examine the potential effect of Cannabidiol (CBD) on 
human learning and memory (L&M) in relatively small scale surveys, and with consideration of 
other confounding factors (i.e., other drugs being specifically combined with CBD or particular 
preexisting medical conditions). Our study design aimed to determine whether CBD, when 
administered alone to healthy human subjects is a modulator of human L&M. We also aimed to 
determine whether particular demographic factors present in the general population (e.g., age, 
sex, history of CBD use, and urine THC) would affect the modulatory effect of CBD on L&M. 
a. Design and Participants 
57  human volunteers were recruited from the Front Range communities in Colorado 
(Pueblo, Colorado Springs and Denver). Subjects were randomized to two treatment arms: 1) 
to receive CBD First; 2) to receive placebo first. Each applicant signed an informed consent 
form and filled out a demographics questionnaire. The L&M for each subject was tested after 
administration of 246 mg CBD absolutely or placebo. Testers were blinded as to whether 
someone is getting CBD or Placebo. The principal investigator remained unblinded, and was 
not be involved in data collection nor analysis to prevent any bias. Generation of the 
randomization list was performed by the principal investigator. 
After administration of CBD or placebo the participants waited 2hrs before taking the 
learning and memory tests. The experiment was repeated one week later, by reversing the 
CBD and control groups, in order to eliminate (or minimize) the placebo effect. 


b. Cognitive Assessments 
Each subject will be required to take two 30-min tests (Version 1 L&M test and Version 2 
L&M test). Each test compromised of two sessions: session A, session B, and session C. Test 
session A was an assessment of basal cognitive function, session B was a verbal declarative 
memory test, and session C was a prose recall-cognitive L&M test (Schoeler and 
Bhattacharyya 2013).  
First, participants were asked to complete the Montreal Cognitive Assessment (MOCA) as 
part of session A. The MOCA was given by a tester and took 5-10 minutes. This was a 
written non-invasive assessment of basal cognitive function. The purpose of the prose test 
was to evaluate logical memory in study subjects (Curran et al. 2002, Morgan et al. 2010, 
Hindocha et al. 2018).  
For the verbal declarative memory test (session B), we used the Rey-Auditory Verbal 
Learning Test-Revised (RAVLT-R) test (Solowij et al. 2011, Meier et al. 2012, Schoeler and 
Bhattacharyya 2013, Becker et al. 2014, Khosravi Fard et al. 2016). Participants were 
instructed to listen to a list of 12 words (List A) read to them. They were asked to recall List 
A in four trials, with the words repeated to them during each trial. The number of words the 
participants remember was expected to increase between trails 1 and 4. The purpose of the 
multiple trails was to check if list learning is enhanced. Participants were scored for the 
number of correctly repeated words for each trail and for the number of intrusions (number 
of words not on list). Participants were also be scored for clusters (number of words said 
consecutively that were in the same semantic category). Then, the participants were 
instructed to listen to another list of 12 words (List B), asked to recall List B once, and scored 


for the number of correctly repeated words. Afterward, participants were asked to recall List 
A and were scored for the number of correctly repeated words.  
Participants were instructed to listen to a short prose story (Passage I) and asked to 
immediately recall the passage as part of session C. Then, the participants were asked a series 
of questions about Passage I and given a score of 0 if they said the incorrect answer and a 
score of 1 if they got the right answer. Scores were added. Participants were distracted with 
delayed recall of list A. Afterward, participants were asked to recall passage I. 
The test sessions were conducted at CSU-Pueblo in Pueblo. 
c. L&M data collection from participants 
The learning and memory scores collected from participants included MOCA performance, 
RAVLT-R performance (List A trials: A1, A2, A3, A4, A5, A6, A7, sum of list A trials; List B trial: 
B), and prose recall performance (immediate, delayed, and total). The effects of two types of 
interference from the RAVLT-R were quantified as:  
• 1) Proactive Interference: (PI)  = 
!
"#, where B is the number of words recalled from 
List B (distractor list), and  A1 is the number of words recalled from list A on the 
1st trial 
•  2) Retroactive Interference (RI) = 
"$
"%, where A6 is the number of words recalled 
from List A after the distractor List B, and A5 is the number of words recalled from 
List A on the 5th trial.  
Assessing Proactive Interference allowed for the determination of how learning old material 
impacts learning new information. In this study, effects of proactive interference were determined 


by seeing how List B recall was impacted after List A recall. Assessing Retroactive Interference 
allowed for determination of how newly acquired information impacts the recall of previously 
learned information. In this study, effects of retroactive interference were determined by seeing 
how immediate recall is impacted after List B recall by comparing trial 5 recall (before List B) and 
immediate recall (after List B). These equations were utilized by Magalhães (et al., 2012) to 
evaluate the PI, RI, and FS Ratios and the ratios have been used in other L&M studies (Geffen et 
al., 1990; Vanderploeg et al., 2001; Kramer et al., 1991; Numan et al., 2000; Torres et al., 2001; 
Malloy-Diniz et al., 2007; Magalhães et al., 2012; Frith et al., 2018).  
 
 
 


2. Statistical Analysis Plan 
 
All statistical analyses were performed using SPSS. Linear Mixed Models (LMM) with 
Bonferroni Corrections were to examine L&M scores of placebo and CBD recipients, while also 
controlling for demographic factors. Two-tailed P < 0.05 will be considered statistically 
significant. Subject IDs were included as random effects. Treatment (CBD vs placebo) was 
included as a factor. The following were included as covariates: age, history of CBD use (user or 
non-user), sex (male or female), and urine THC result (THC positive or negative). A Linear Mixed 
model was created for each of the following dependent variables: MOCA, Sum of List A trials, 
List B, PI Ratio, RI Ratio, FS Ratio, and Total Prose Recall. 
COVID as a factor was removed from the Linear Mixed Models. Data related to COVID 
will be independently analyzed in a separate statistical model and reported later.