Acute effects of naturalistic THC vs. CBD use on recognition memory: a preliminary study
The ratio of ∆9-tetrahydrocannabinol (THC) to cannabidiol (CBD) varies widely across cannabis strains. CBD has opposite effects to THC on a variety of cognitive functions, including acute THC-induced memory impairments. However, additional data are needed, especially under naturalistic conditions with higher potency forms of cannabis, commonly available in legal markets. The goal of this study was to collect preliminary data on the acute effects of different THC:CBD ratios on memory testing in a brief verbal recognition task under naturalistic conditions, using legal-market Colorado dispensary products. Thirty-two regular cannabis users consumed cannabis of differing THC and CBD levels purchased from a dispensary and were assessed via blood draw and a verbal recognition memory test both before (pretest) and after (posttest) ad libitum home administration in a mobile laboratory. Memory accuracy decreased as post-use THC blood levels increased (n = 29), whereas performance showed no relationship to CBD blood levels. When controlling for post-use THC blood levels as a covariate, participants using primarily THC-based strains showed significantly worse memory accuracy post-use, whereas subjects using strains containing both THC and CBD showed no differences between pre- and post-use memory performance. Using a brief and sensitive verbal recognition task, our study demonstrated that naturalistic, acute THC use impairs memory in a dose dependent manner, whereas the combination of CBD and THC was not associated with impairment.
Cannabis produces acute memory impairment during intoxication (Bossong et al. 2014; Broyd et al. 2016; Lundqvist 2005; Ranganathan and D’Souza 2006), although regular users may not show these acute decrements in performance (Ranganathan and D’Souza 2006; Schoeler and Bhattacharyya 2013). Cannabis contains many cannabinoids that may have differential effects on memory. Overall, research studies have not sufficiently considered the fact that cannabis exists in different forms and have not characterized the effects of cannabis as the compound action of different cannabinoids that vary in terms of their pharmacological effects. Two of the primary cannabinoids, ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have some opposing effects (Osborne et al. 2017; Rømer Thomsen et al. 2017; Zhornitsky and Potvin 2012), and the ratio of THC to CBD varies dramatically among different strains of cannabis, with some strains in Colorado testing at greater than a 20:1 CBD to THC ratio, while other strains have a 1:1 THC to CBD ratio, and many have negligible amounts of CBD. Furthermore, most research to date has used low-strength government-grown cannabis (THC ranging from 3 to 6%) that lacks other key cannabinoids (CBD close to 0%) and has been administered in tightly controlled laboratory environments, all of which maximize internal validity, but compromise external validity. Currently, the THC strength of recreational cannabis in Colorado can exceed 25%, and the strength of CBD comes close to 25% in some strains (Vergara et al. 2017).
Recent reviews suggest that CBD has no effect on cognition in healthy individuals, but can improve cognitive processes including attention, executive function, working memory, and episodic memory in various pathological conditions including acute THC intoxication (Osborne et al. 2017; Rømer Thomsen et al. 2017; Zhornitsky and Potvin 2012). In this context, CBD has been considered as a potential treatment for cognitive impairments resulting from schizophrenia, Alzheimer’s disease, ischemia, inflammatory states, and hepatic encephalopathy (a disorder resulting from acute and chronic liver failure) (Osborne et al. 2017). Thus, a better understanding of the protective effects of CBD during THC impairment may also provide insights about CBD’s potential for improving cognitive problems with varying etiologies.
Previous episodic memory studies indicate that cannabinoids such as CBD may counteract the effects of THC. Chronic benefits of CBD were suggested in a study showing better recognition memory for words in regular cannabis users with CBD present in their hair (Morgan et al. 2012). A prior naturalistic study assessed acute effects in users who already prefer high-CBD strains (Morgan et al. 2010b). Prose recall was significantly higher after use of cannabis that was high in CBD compared to the low CBD group. Other previous studies have suggested that CBD acutely reduces THC-related learning and memory impairments in well-controlled human (Englund et al. 2013) and animal studies (Vann et al. 2008; Wright Jr. et al. 2013). In one clinical study, subjects were given an oral dose of CBD (600 mg) or a placebo 210 min ahead of an intravenous injection of THC (1.5 mg). Those in the CBD group showed better episodic memory (delayed free recall) compared to the placebo group (Englund et al. 2013). On the other hand, another prose recall study compared placebo, THC 8 mg, CBD 16 mg and THC 8 mg + CBD 16 mg in a randomized, double-blind crossover design with vaporizer inhalation (Morgan et al. 2018). Both the THC and THC + CBD conditions impaired memory, but CBD had no effects, even though the same subjects showed some protective effects of CBD in identification of facial emotions (Hindocha et al. 2015). These studies highlight that the effects of THC and CBD on memory may vary by dose, timing, and form of administration. Furthermore, they point to the need for measuring blood cannabinoid levels after cannabis administration to determine THC and CBD exposure.
The present experiment used a novel design to naturalistically assess the effects of real-world cannabis products on memory with the use of a mobile pharmacology and phlebotomy laboratory, which was driven to participants’ homes to allow assessment of participants both immediately before and after naturalistic administration of real-world cannabis. Although cannabis is legal at the state level in Colorado, researchers are not allowed to have participants use or handle state legal cannabis in any form on university property or in the presence of University staff, as this would be a violation of the federal Drug Free Schools Act. While we could have participants self-administer at home and take a taxi to the lab (a strategy we attempted in our prior work (Bidwell et al. 2018)), there are two major disadvantages of this approach: 1) We are unable to take a baseline assessment immediately prior to administration of an acute dose of cannabis, and 2) There is a high degree of variability in when participants actually arrive at the lab, meaning it is difficult to standardize assessments as a function of time since consumption. Using our mobile pharmacology and phlebotomy lab, we were able to draw blood to assess cannabinoid levels and collect assessments immediately before cannabis use, and at more precise time points post use. This innovative approach allows us to conduct cutting edge research on the acute effects of cannabis strains legally available in our state, but not allowed in University laboratories.
In the present experiment, we sought to collect feasibility data that would allow us to replicate and extend prior work using a mobile laboratory (Bidwell et al. 2018), facilitate more precise timing of pre- and post- cannabis use assessments, and administer a verbal recognition memory task. These feasibility data were collected in the context of two larger studies focused on the acute effects of high potency legal market forms of concentrate (State of Colorado Marijuana Research Grant 96,947 to LCB) or flower cannabis (R01DA039707 to Kent E Hutchison). The two studies were otherwise identical regarding the tasks that subjects completed. The detailed procedures and primary outcomes of these larger studies are described and reported elsewhere (Bidwell et al. 2020). A recognition memory task, which was not part of the original aims of either study, was selected to extend our previous ISLT results (Bidwell et al. 2018) beyond free recall with a task that provides better control over memory retrieval conditions (Kahana 2012). In addition to recollection processes required for free recall, recognition engages familiarity-based memory processes (Diana et al. 2006; Malmberg 2008; Yonelinas 2002) that we plan to dissociate in future cannabis studies with event related potentials (ERPs, Curran and Doyle 2011; Rugg and Curran 2007). Regular cannabis users twice completed a verbal recognition memory task with words: Before (“pretest”) and approximately 35 min after ad libitum use (“posttest”) of their assigned cannabis strain. Several strains of flower and two concentrates were used, and each strain fell into one of two groups: THC and THC + CBD (see Table 1). We assessed the effects of each cannabis strain as the degree of memory performance decrement from the pretest to the posttest. We hypothesized that CBD should have a protective effect on THC-induced memory impairment, so we predicted that the pre/post decrement would interact with strain such that the decrement would be largest in the THC group compared to the THC + CBD group. Furthermore, a blood draw taken immediately after cannabis consumption was used to quantify peak levels of THC and CBD. We predicted that posttest memory performance would decline as THC levels increased, and THC and CBD levels would interact such that THC levels would have diminished effects as CBD levels increased.
Participants (32 cannabis users aged between 21 and 66 years) were recruited from the Boulder-Denver Metro area in Colorado using social media postings and mailed flyers. Because the goal was to collect feasibility data using a novel methodology, the recognition memory task reported here was only assessed in 32 subjects. Trained research staff screened eligible participants via telephone. Criteria for inclusion in the study were: 1) Aged between 21 and 70; 2) Used cannabis at least 4 times in the past month; 3) Experience with the highest potency of cannabis that could be assigned in the study (24% THC for flower groups and 90% THC for concentrate groups); 4) No other non-prescription drug use in the past 60 days; with a urine toxicology screen; 5) No daily tobacco use; 6) Reported drinking 2 times or fewer per week, and ≤ 3 drinks per occasion; 7) Not be pregnant, or trying to become pregnant; 8) No self-reported prior or current psychotic or bipolar disorder. Those eligible for the study completed both a baseline appointment and an experimental appointment, described in greater detail below.
Overview of Design of Feasibility Study
In an observational study, cannabis flower and concentrate users were assigned to purchase and use a legal market THC only or THC + CBD product. Participants completed a verbal recognition memory task at baseline and during an experimental mobile laboratory assessment approximately 50 min after ad libitum administration of their product. Thus, product strain was manipulated between participants and pre/post-use memory assessment was manipulated within participants.
Participants were instructed not to use cannabis on the day of their baseline appointment, which took place at the research team’s on-campus laboratory. After completing the informed consent process, a Breathalyzer (Intoximeter, Inc., St. Louis, MO) and urinalysis test was administered to ensure that participants had no alcohol, sedatives, cocaine, opiates, or amphetamines in their system. If either test was positive, the baseline appointment was rescheduled, and participants with repeated positives were terminated from the study. Female participants were required to take a urine pregnancy test, to ensure that they were not currently pregnant. Participants completed questionnaires on demographics, lifestyle, substance use, and medical history. After baseline questionnaires were completed, participants provided a blood draw.
Before leaving the baseline appointment, each participant was given a card with directions to a local dispensary in order to purchase their study product. Several strains of flower and two concentrates were used and randomly assigned in the larger studies (details on these procedures are in Bidwell et al. (2020)). In order to achieve a wide range of THC and CBD exposure for the purposes of this verbal recognition feasibility study, individuals were assigned to the full range of strains being tested in the parent studies and each strain was grouped into one of the following categories for the purposes of this feasibility study: THC or THC + CBD (see Table 1). Specifically, participants who primarily used cannabis concentrates purchased either a 70% or 90% THC concentrate which fell into the THC group. Participants who primarily used flower, instead of other cannabis products, were given instructions to purchase one of the following flower strains: 24% THC and 1% CBD, which fell into the THC group; or one of the THC + CBD group strains that contained either 14% THC and 9% CBD, 6% THC and 9% CBD, 9% THC and 10% CBD, or 24% CBD and 1% THC. The THC and CBD potency of each study product was tested and labeled consistent with State of Colorado requirements, in an International Organization for Standardization (ISO) 17,025 accredited laboratory. ISO 17025 is the highest recognized quality standard in the world for calibration and testing laboratories. Independent testing by University researchers is not permitted under federal law. Research staff were blinded to strain condition, and the blind was maintained by the dispensary and one senior member of the lab. The sample sizes of each group were: THC (n = 15) and THC + CBD (n = 17).
After participants obtained the study product, they were asked to use it exclusively, and ad libitum, for the 5 days leading up to the experimental appointment, which took place in a mobile laboratory outside of the participants’ place of residence. Participants were asked to abstain from using cannabis on the day of the appointment, prior to the experiment. At the first assessment of the day (pre-use), participants completed a blood draw and the primary outcome measures, followed by the first administration of the recognition task. Footnote 1 Then they returned home to use their study cannabis ad libitum with their normally preferred method of administration. The THC group used 6 different administration methods: oil rig (n = 6), bong (n = 4), vaporizer (n = 1), glass straw (n = 2), joint (n = 1) and bubbler (n = 1). The THC + CBD group used 4 different administration methods: pipe (n = 7), bong (n = 5), vaporizer (n = 2) and joint (n = 2). Shortly thereafter, they returned to the mobile lab to complete the blood draw to estimate peak cannabinoid exposure, the primary outcome measures, and the recognition memory task again, while acutely intoxicated (acute post-use). The post-use recognition memory task took place 35 min after participants returned to the van. Footnote 2
Past-month use of cannabis
To report on their typical use of cannabis at the baseline appointment, participants completed a calendar-assisted, researcher administered Timeline Followback that queried their use of alcohol, nicotine/tobacco, cannabis, prescription drugs, and illicit drugs over a 30-day retrospective timeframe (Dennis et al. 2004).
Because University research staff are not permitted to handle legal market cannabis, we asked participants to weigh their product with a study-provided scale [American Weigh Scale, Gemini Series Precision Digital Milligram Scale (GEMINI-20)] at the experimental appointment both before and after ab libitum use. Although blood THC, CBD, and metabolite measures remain our primary measure of individual cannabinoid exposure, the weight that each participant provided (mg) was used to further estimate the amount of each cannabinoid consumed based on the percentages of THC and CBD contained in their specific study strain. While these mg estimates are not considered a primary measurement of cannabinoid dose, we include these data in order to facilitate integration and interpretation of our findings with prior controlled laboratory studies.
A certified phlebotomist collected 32 mL (2 tablespoons) of blood through venipuncture of a peripheral arm vein using standard, sterile phlebotomy techniques in order to assess plasma cannabinoids. Plasma was separated from erythrocytes by centrifugation at 400 xg for 15 min, transferred to a fresh microcentrifuge tube, and stored at − 80 °C. Plasma samples were sent to iC42 Clinical Research and Development (Department of Anesthesiology) on the Anschutz Medical Campus at the University of Colorado Denver. Four cannabinoids were quantified in the blood (THC and its primary metabolites THC-COOH and 11-OH-THC, and CBD) using validated high performance liquid chromatography/mass-spectroscopy (HPLC-MS/MS) (API5500) in MRM mode (Klawitter et al. 2017).
Recognition memory task
Figure 1 provides an overview of the recognition memory task procedures. In each of the two runs of the recognition memory task, subjects studied 20 words followed by a recognition memory test with 20 old (studied) and 20 new (non-studied) concrete nouns. The pretest and posttest tasks included different words, and the exact same lists were used for each participant to minimize variability. The four lists (2 old × 2 new) were matched on word length and Kucera-Francis written frequency (Kucera and Francis 1967). The study lists also included 2-word, non-tested buffer items at the beginning and end of the list to reduce primacy and recency effects. Each study trial started with a 500–700 ms fixation cross, followed by a word for 1000 ms, and ending with a 1000 ms blank screen. Participants were instructed to try to remember each word in preparation for the upcoming test. Participants played Sudoku for 3 min between each of the study and test lists to provide a distracting stimulus that would minimize active rehearsal during the delay. Each test trial started with a 500–1000 ms fixation cross, followed by a word for 2000 ms, and ending with a 1000 ms blank screen. Subjects were instructed to judge each word as old or new as quickly and accurately as possible, by pressing either a leftward (R or F) or a rightward (U or J) key on the keyboard. Assignment of response keys and left/right to old/new responses was counterbalanced across subjects.
Time course of one trial during the study phase and the test phase
Cannabinoid plasma biomarker levels taken immediately post-use were our primary assessment of the strength of the effects of each cannabinoid, but cannabinoid content weight is also reported to facilitate comparison with other studies. The total weight of the product that each participant used was measured as the difference between pre- and post-use weight (mg Total, Table 2). The amount of each cannabinoid consumed by each participant was estimated by multiplying the total weight used by the percentage of THC and CBD in that subject’s strain (mg THC and mg CBD, Table 2). To examine differences in cannabinoid content across groups, analyses were performed in a mixed-design ANOVA with cannabinoid type (CBD, THC) as a within-subject factor and strain group (THC, THC + CBD) as a between-subject factor.
Table 2 Participant characteristics and blood biomarkers by strain group. Means are reported with 95% confidence intervals in brackets
Cannabinoid plasma biomarker levels
Given that our observational study involved ad libitum use of various cannabis products, cannabinoid plasma biomarker levels obtained from blood taken immediately after cannabis administration were our primary quantitative assessment of individual exposure to each relevant cannabinoid. As shown in Table 2, four cannabinoids were quantified in the blood (THC and its primary metabolites THC-COOH and 11-OH-THC, and CBD). Analysis of THC levels were performed with a composite THC + metabolites measure, which is the sum of the three THC levels. These measurements were analyzed in a mixed-design ANOVA with session (pretest, posttest) and cannabinoid type (CBD, sum THC + metabolites) as within-subject factors and strain group (THC, THC + CBD) as a between-subject factor.
Estimated cannabis dose and strain effects on memory
As is typical in recognition memory research (Macmillan and Creelman 2005; Malmberg 2008; Neath and Surprenant 2003; Wixted 2007) and consistent with previous studies on the effects of THC and CBD on recognition memory (Morgan et al. 2012; Morgan et al. 2010b), d’ (accuracy in discriminating old vs. new words) was used as the primary measure of memory performance. The hit rate (H, proportion of correct “old” responses to studied words) and false alarm rate (FA, proportion of incorrect “old” responses to non-studied words) are used to calculate d’ (d′ = zH − zFA, where z is the standard normal distribution). Given the distribution of the metabolites, we performed a log transformation of the metabolite data.
For d’ we first ran a regression model to examine how cannabinoid levels (sum THC + metabolites and CBD) were associated with accuracy (d’).
The regression allows us to assess how memory accuracy was affected by differences in the strength of neurophysiological exposure to each cannabinoid alone and in combination. Second, the effect of strain group on memory accuracy (d’) was analyzed in a mixed-design analysis of variance (ANOVA) with session (pretest, posttest) as a within-subject factor and strain group (THC and THC + CBD) as a between-subject factor. Because the THC content was lower in the product consumed by the THC + CBD group, we ran a second ANOVA with log (THC + metabolites) as a covariate in this ANOVA.
Our primary measure of recognition memory performance was d’, but Table 3 shows other performance measures for completeness, including the hit and false alarm rates used to calculate d’. Table 3 shows a measure of response bias (c = − 1/2 * [zH − zFA]), where negative values indicate a liberal bias to respond “old” and positive values indicate a conservative bias to respond “new”. Table 3 also shows response time (RT). Each of these performance measures were separately analyzed in a mixed-design analysis of variance (ANOVA) with session (pretest, posttest) as a within-subject factor, strain group (THC and THC + CBD) as a between-subject factor, and THC + metabolite levels as a covariate.
Table 3 d’, hit rate, FA (false alarm) rate, c (response bias) and reaction time (RT) for pre- and posttest, for the two strain groups, THC and THC + CBD. Means are reported with 95% within subject confidence intervals in brackets. The right columns indicate significant differences from the t-test on group differences (*: p < .05, **: p < .01)
Multiple comparisons were assessed with Bonferroni post-hoc tests (with corresponding p-values reported as pbf) for all analyses.
One of the 32 participants was excluded from analyses because their pretest blood levels exceeded mean + 3 standard deviation over all participants, when considering the combination of THC + metabolites level (sum of THC, THC-COOH and 11-OH-THC) and CBD level. Footnote 3 This reduced the THC + CBD strain group from 17 to 16 participants (see Table 1).
As seen in Table 2, the strain groups did not significantly differ in age, first age of regular cannabis use, or time away from the van. We did observe a significant difference in cannabis consumption for the past 30 days, showing more cannabis use in the THC group compared to the THC + CBD group.
One participant did not weigh her or his product, so dosage results are based on only 14 subjects in the THC group. As reported in Table 2, the groups did not differ significantly in the total amount (mg) of product they consumed during at-home administration. However, they did differ in the amount (mg) of CBD and THC. As expected based on product content and group assignment, and as shown in Table 2, results indicated that each group differed on THC and CBD dosages in the expected directions. The THC group had the highest THC doses and the CBD group had the highest CBD doses.
Cannabinoid plasma biomarker levels
Cannabinoid plasma biomarker levels (Table 2) were analyzed in a mixed-design ANOVA with 2 sessions (pretest, posttest) and 2 cannabinoid types (CBD, sum THC + metabolites) as within-subject factors, and strain (THC, THC + CBD) as a between-subject factor. Pre-test THC levels fell < 10 ng/mL on average across both groups, supporting that participants complied with day of abstinence procedures prior to their mobile laboratory study appointment.
Analysis of cannabinoid plasma biomarker levels revealed a main effect of session, F(1,29) = 11.44, p < .001, ( _p^2 ) = 0.28, and a significant main effect of cannabinoid type, F(1,29) = 16.12, p < .001, ( _p^2 ) = 0.36. Cannabinoid type interacted with strain group, F(1,29) = 5.25, p < .05, ( _p^2 ) = 0.15, showing that sum THC + metabolite levels were higher for the THC group compared to the THC + CBD group (pbf < .05). Cannabinoid type interacted with session, F(1,29) = 7.69, p < .01, ( _p^2 ) = 0.21, showing that the level of sum THC + metabolites was higher at posttest (i.e., after cannabis use) compared to pretest (pbf < .001). There was a significant 3-way interaction between cannabinoid type, strain group, and session, F(1,29) = 5.42, p < .05, ( _p^2 ) = 0.16. When this interaction was decomposed with Bonferroni-corrected post hoc tests, they indicated that the strain groups did not differ on any pretest levels, but posttest sum THC + metabolites levels were higher for the THC group than the THC + CBD group (pbf < .001). When testing each measure separately (Table 2), we only observed a significant difference for THC levels at pretest. Posttest CBD levels were higher for the THC + CBD group than the THC group, whereas posttest THC levels and sum THC + metabolites were higher for the THC group than the THC + CBD group.
Cannabis dose and strain effects on memory
First, we ran a regression model (Eq. 1) to examine how cannabinoid levels (THC + metabolites and CBD) were associated with accuracy (d’). The model revealed that the level of THC + metabolites was significantly negatively correlated to accuracy (p < .05, ( _p^2 ) = 0.28) (Fig. 2a), but neither the effect of CBD (Fig. 2b) nor the THC × CBD interaction was significant. This result was observed across the two strain groups, and neither THC nor CBD blood levels were significantly correlated with d′ within each strain group.
Accuracy d’ according to blood biomarkers log (THC + metabolites) (a) and log (CBD) (b) during posttest, for the two strain groups: THC and THC + CBD. The black lines represent the correlation between accuracy and blood biomakers with R 2 reported
Second, accuracy (d′, Fig. 3) was analyzed in a mixed-design analysis of variance (ANOVA) with session (pretest, posttest) as a within-subject factor, and strain group (THC, THC + CBD) as a between-subject factor. d′ significantly decreased between pre- and post-test, F(1, 29) = 5.84, p < .05, ( _p^2 ) = 0.17, and d ′ was significantly higher for the THC + CBD group compared to the THC group, F(1, 29) = 6.05, p < .05, ( _p^2 ) = 0.17. The significant session × strain group interaction, F(1,29) = 7.90, p < .01, ( _p^2 ) = 0.21, showed that accuracy was lower at posttest than pretest for the THC group (pbf < .01), but not for the THC + CBD group. We also observed that the accuracy at posttest was lower for the THC group than for the THC + CBD group (pbf < 0.01). Additionally, sum THC + metabolite blood plasma levels were included as a covariate since it significantly predicted memory accuracy in the regression analysis and because the THC content of the product consumed by the THC + CBD group was lower in THC. As performed in previous analyses, we used the log transform of metabolite data. The covariate log (THC) was significant, F(1,28) = 7.79, p < .01, ( _p^2 ) = 0.22. The significant session × strain group interaction, F(1,28) = 6.18, p < .05, ( _p^2 ) = 0.18, showed similar results as before, with lower accuracy at posttest compared to pretest for the THC group (pbf < .01), but not for the THC + CBD group. Also, the accuracy at posttest for the THC group was lower than for the THC + CBD group (pbf < 0.01).
Accuracy d′ for pretest and posttest, for the two strain groups: THC and THC + CBD. Colored regions represent the 95% within subject confidence intervals (Morey 2008). Thick black lines represent the mean. Individual data points represent the mean d’ for each participant. Thin black lines connect individuals across conditions. Asterisks show results of the Bonferroni post-hoc tests (* pbf < 0.05)
Consistent with our approach for d’, each of the other performance measures was separately analyzed in a mixed-design analysis of variance (ANOVA) with session (pretest, posttest) as a within-subject factor, and strain (THC, THC + CBD) as a between-subject factor. Results are presented without a covariate. When adding log (THC) as a covariate, no significant effects were observed for the 4 measures. Analysis of false alarm (FA) rate indicated a significant main effect of session, F(1, 29) = 18.45, p < .001, ( _p^2 ) = 0.39, showing a higher rate of FA at posttest compared to pretest. Session also interacted with strain for FA, F(1, 29) = 4.86, p < .05, ( _p^2 ) = 0.14, such that only the posttest FA rate was higher for the THC group than for the THC + CBD group (Table 3). Analysis of response bias (c) indicated a significant effect of session, F(1, 29) = 5.79, p < .05, ( _p^2 ) = 0.17, such that subjects were somewhat conservative pretest (tended to respond “no” more than “yes”) but somewhat liberal posttest (tended to respond “yes” more than “no”). Analysis of hit rate and reaction time revealed no significant effects. The presence of significant posttest hit rate effects in the t tests (Table 3), but not in the ANOVA, suggests that ANOVA did not have sufficient power to detect the session × strain interaction for this outcome.
This study demonstrates the feasibility of a brief and mobile verbal recognition memory task for naturalistic and experimental studies of the acute effects of cannabis. Participants completed a recognition memory task before (pretest) and shortly after (posttest) ad libitum acute administration of cannabis products with varying THC:CBD ratios. Participants using products containing primarily THC showed significantly worse memory accuracy (d’) after use than before use, whereas subjects using strains containing both THC and CBD showed no differences between pre- and posttest memory performance. When blood cannabinoid levels were considered, d’ was negatively correlated with THC levels, whereas performance showed no association with CBD levels. Thus, acute THC use was associated with impaired memory in a dose dependent manner, whereas the combination of THC and CBD was not associated with impaired memory.
Compared to other recent studies examining the acute effects of THC on episodic memory, the present study included more naturalistic methods of cannabis use and higher dosage. Recognition accuracy was better before than after THC consumption and decreased as THC blood levels increased. Our participants self-administered their assigned products ad libitum using their normally preferred methods at home. The mean estimated THC dosage across both the THC and THC + CBD strain groups was 58.61 mg (range = 1.92–235.8 mg). In a broad review of studies of cannabis use on human cognition from 2004 to 2015, Broyd et al. (2016) identified 11 studies investigating acute effects on verbal episodic memory. Of those demonstrating acute memory deficits, five administered intravenous (IV) THC (D’Souza et al. 2004; D’Souza et al. 2008; Englund et al. 2013; Morrison et al. 2009; Ranganathan et al. 2012), two administered vaporized cannabis (Liem-Moolenaar et al. 2010; Theunissen et al. 2015), and one administered oral THC (nabilone) (Wesnes et al. 2009). Dosage in these studies ranged from 2 to 12 mg of THC. More recent studies have documented episodic memory impairments after acute use of 8 mg of THC with a vaporizer (Morgan et al. 2018) and 10.73 mg of THC with experimenter-regimented joint smoking (Hindocha et al. 2015). Thus, we have replicated prior work under more naturalistic conditions and higher doses, as well as replicating our previous free recall results in a separate sample of participants with a recognition memory task (Bidwell et al. 2018).
As predicted, the deleterious effects of THC on recognition memory accuracy were not present when CBD was co-self-administered. Because THC levels were negatively correlated with posttest memory accuracy and THC levels differed between strain groups, we controlled for THC levels as a covariate and found a significant interaction between strain group and pre/posttest sessions. Participants using products that contained only THC showed memory accuracy decrements from pre- to posttest. No such decrements were observed in subjects using both THC and CBD. While preliminary, this finding is generally consistent with other suggestions that CBD and THC can have opposing effects on a variety of outcomes (Bidwell et al. 2018; Osborne et al. 2017; Rømer Thomsen et al. 2017; Zhornitsky and Potvin 2012) as well as other recent episodic memory studies suggesting that CBD can counteract memory impairments caused by acute THC use (Bidwell et al. 2018; Englund et al. 2013; Morgan et al. 2010a; Morgan et al. 2010b). These prior studies have all used free recall measures of memory, which the present results extend to recognition memory. Both recollection and familiarity processes are thought to contribute to recognition memory, whereas only recollection is relevant to free recall (Diana et al. 2006; Malmberg 2008; Yonelinas 2002). Some older studies have suggested that acute cannabis use impairs recollection more than familiarity (Fletcher and Honey 2006; Ilan et al. 2004), but none have examined differential acute effects of THC vs. CBD. ERPs have proven useful for discriminating these processes (Curran and Doyle 2011; Rugg and Curran 2007) and we plan to use ERPs in future research examining THC and CBD effects on recognition memory.
In addition to being a small feasibility study that needs to be replicated, there are three primary limitations of the present study. First, like Morgan et al. (2010a, 2010b), assignment of subjects to strains was not completely random, so pre-existing differences between participants could have influenced the results. For example, regular users of high potency THC concentrates may be more or less susceptible to its acute effects than other subjects. Bidwell et al. (2018) and Englund et al. (2013) used random assignment, but only Bidwell et al. (2018) used naturalistic administration. Second, the 50 min that elapsed after consumption prior to the memory assessment (which occurred ~ 35 min after blood draw to assess peak cannabinoid levels) may have limited the observed effects of THC and CBD. On the other hand, we have found the effects of THC on verbal recall memory to be relatively persistent when international shopping list test (ISLT) performance was compared between 15 and 30 min after use versus 60–75 min after use (Bidwell et al. 2020). Third, given the nature of this observational pilot study we were not powered to include all relevant covariates or ethically able to match the groups on important characteristics such as cannabis use history, preferred form of cannabis (e.g. flower vs. concentrate), or preferred route of inhaled administration (e.g. bong, pipe, etc.). Furthermore, compared to the THC group, the THC + CBD group tended to be older (with age also ranging more widely), started regular cannabis use later, used less cannabis in the past month, and consumed significantly less THC in their assigned strain. Although the first three demographic trends were not significant, that may be attributable to the small sample size, so these factors could have contributed to group differences on memory. Despite these concerns, our strongest memory effects were shown in the THC group, which had the heaviest levels of use prior to the study sessions mitigating a concern that our findings are driven by tolerance effects in heavy users. Typically, heavier users are less likely to show acute decrements in memory performance (Ranganathan and D’Souza 2006; Schoeler and Bhattacharyya 2013).
This study puts forward novel, naturalistic data on the feasibility of a brief and mobile recognition memory task that can assess the impacts of higher potency legal market forms of cannabis that vary in levels of THC and CBD. With an emphasis on external validity, we demonstrate the feasibility of a method for assessing cannabis-related memory impairment after the use of legal market forms of cannabis either in the field or in clinical settings. Very few studies have examined the cognitive effects of legal market cannabis, which leaves a gap in the current literature in regards to real world consumption patterns when legal market access as well as medical and recreational use is rapidly increasing. These findings contribute naturalistic data to the public health sphere on the impact of THC and CBD on memory function and are relevant to patients, medical providers, policy makers, and law enforcement.
Availability of data and materials
Because the recognition task was added onto another ongoing protocol, it was always run after the primary outcome measures for the main study which included assessments of other memory tasks, attention, inhibitory control, balance, and subjective drug effects. These tasks are unlikely to interfere with recognition memory results. The only other verbal memory test included was the International Shopping List Task (ISLT), which used different words than the recognition task. Our larger study found that THC administration was negatively associated with ISLT performance, but CBD results await ongoing data collection and analysis (Bidwell et al. 2020).
We do not have the specific time point for the memory assessment for each participant, so the time given here is an estimate based on the general flow of the protocol. The timing of the protocol should not differ between participants.
Results obtained without excluding the outlier were similar and are not presented in detail. In particular, d′ negatively correlated with THC blood levels (p < .05), but not CBD blood levels. The session × strain interaction on d′ was significant, with or without the log(THC) covariate (both p < .01).
CBD and Memory: Can Hemp Oil Enhance Memory?
Cannabis users have long been thought of as people with short-term memory problems due to an alleged negative impact of cannabinoids — the active ingredients in cannabis plants — on the brain cells.
Ironically, the infamous THC has been recently shown to have neuroprotective effects on brain cells during studies. This means that cannabis, instead of killing healthy brain cells, protects them against damage. This fairly recent discovery sheds new light on the potential use of cannabinoids in the treatment of memory issues.
And as for CBD, neuroprotection is believed to be one of the compound’s major roles.
So, have we been misinformed all that time?
Apparently yes, but this isn’t the subject of our article.
Today, we’re going to cover CBD’s potential in fighting Cognitive Decline (CD), the scientific term used to diagnose memory loss. The condition is more likely to occur with aging; that’s why learning more about CBD, including its effects on catabolic processes in the brain, is essential to understand how it can help with memory issues.
Does CBD Help with Memory?
In recent years, CBD has been found to alleviate certain symptoms of memory loss conditions, including different types of dementia. People are turning to CBD oil to treat Alzheimer’s disease as well as to improve focus and enhance the daily performance of their brains.
We have all experienced temporary memory glitches, but if memory loss becomes chronic and compromises your daily functioning, it may be time to seek out treatment.
CBD interacts with the master regulatory network known as the endocannabinoid system (ECS). From there, it operates on over 65 molecular pathways, ensuring the balanced functioning of ECS and the maintenance of homeostasis (1). Homeostasis is a biological term describing the harmony between all biological functions in the human body.
The interaction between CBD and the central nervous system (CNS) is where the cannabinoid manifests its benefits for memory.
In the next section, we cover the most common memory issues CBD is known to help with, and back it up with scientific research.
CBD and Memory Issues: The Benefits
Perhaps the most important benefit of CBD for people with memory problems is that the compound is non-intoxicating. Unlike THC, CBD won’t get you high because it doesn’t have a direct affinity to any of the cannabinoid receptors in the brain. CBD can even negate the psychotropic potential of CBD by blocking the sites of these receptors when THC tries to bind to them.
THC can help enhance memory in people with neurodegenerative disorders, but as we said, this article focuses specifically on CBD. And if you’re reading this, you’re probably interested in achieving memory improvements without the psychoactive buzz.
CBD has been established as a potential remedy for people who struggle with a variety of cognitive disorders. However, because the research is in its early stages, more studies in this regard are needed to confirm preclinical findings.
For now, let’s focus on the most important studies investigating the efficacy of CBD for common memory ailments.
CBD for Alzheimer’s and Dementia Memory Loss
Memory loss triggered by degenerative conditions, such as dementia and Alzheimer’s disease, is a significant area that CBD oil has been shown to alleviate inflammation of the brain, reduce oxidative stress, and improve the regeneration of neurons, all of which can help improve cognitive performance.
Patients with Alzheimer’s disease experience progressive cognitive decline due to the degeneration of neurons in the brain, which further destroys neural pathways. Numerous studies have shown that CBD oil not only prevents the destruction of these neurons, but it also aids the body in creating new ones (neurogenesis). (2)
CBD for Memory Loss Caused by Stress and Anxiety
While analyzing the impact of CBD on the brain cells, researchers have discovered that it can actually mitigate brain damage caused by physical trauma and severe stress.
Studies have shown that the body starts to release endocannabinoids (the body’s version of plant-based cannabinoids) to defend the brain and repair it (3). When phytocannabinoids like CBD are administered to the endocannabinoid system, it strengthens the defensive response, therefore strengthening the memory.
Moreover, there is a large body of evidence supporting the use of CBD in the treatment of traumatic brain injury that derives from neuroinflammation (4). Since CBD is such a potent anti-inflammatory compound, it could help you after memory loss caused by an injury that brought inflammation to your brain.
CBD for Memory Loss Due to Lack of Focus
If your memory issues are caused by an inability to focus, CBD oil may come in handy, as shown by studies that tested the efficacy of CBD as a potential treatment for ADHD, including children.
In a review published in the Journal of Pediatric Pharmacology and Therapeutics, the authors reported that CBD oil had been shown to support people with a range of medical conditions, including the behavioral symptoms of ADHD, such as a short attention span (5). Another study mentions anxiolytic (anti-anxiety) and sleep-regulating properties of CBD, both of which contribute to better memory retention (6).
However, it is unclear whether CBD oil can improve your cognitive function if your memory loss doesn’t stem from a diagnosed condition or disease. A comprehensive review of 27 previously conducted studies found that apart from improving the mental health of patients with schizophrenia, CBD oil didn’t have significant effects on memory functioning in otherwise healthy subjects (7).
So, whether the therapeutic effects of CBD on the brain are universal is still up to debate; that’s why we need more longitudinal human trials to draw definitive conclusions on CBD as a memory booster.
CBD, Memory, and Addiction
In addition to the aforementioned publications, an additional study suggests that CBD may be a promising treatment for people recovering from addiction due to its effect on memory (8).
The study introduces the idea of CBD having “a disruptive effect on reconsolidation of contextual drug-related memories.” It also highlights CBD’s potential to “attenuate contextual memories” from drug abuse, reducing the risk of relapse.
In simple words, the study concludes that CBD can help with addiction by altering memories linked to substance use.
The research team used cue exposure to tempt mice with a rewarding drug (morphine) and observed that taking CBD disrupted the cue. In a perfect world, this would mean that human cravings in addicts can be curbed with CBD too.
Long story short, the effects of CBD on memory may help addicts unlearn the habits of addiction. These habits give rise to cravings and pose a risk of relapse, long after withdrawal symptoms are gone. Some research also suggests that since CBD affects the memory in such a fashion, it may be able to help addicts in recovery by dissociating experiences with substance abuse.
What Else Does the Research Say About Taking CBD for Memory Enhancement?
Some studies suggest that even chronic low doses of THC can help to improve cognitive function — at least in animal models (9). As far as humans are concerned, there is growing data suggesting its positive effects on memory (as mentioned above).
Here’s a summary of the current research:
- A study from the Frontiers in pharmacology has found that CBD promotes neurogenesis — the growth and development of new cells in the brain. Neurogenesis prevents further cognitive deterioration. This specific study analyzed the effects of mice with induced Alzheimer’s condition prior to being treated with CBD. The CBD effectively reversed the cognitive impairments of the mice (10).
- A separate study indicates that an 8-month CBD treatment can prevent the development of social recognition memory deficits. Similar to the previous study, this one was conducted on mice in a controlled laboratory environment (11).
- According to a study from the American Journal of Psychiatry, CBD has a beneficial effect on schizophrenia. The authors claim that CBD’s activity is independent of dopamine receptor antagonism, which makes it a promising treatment for the condition (12).
- The aforementioned Australian review suggested similar health benefits of CBD. After covering 27 publications in peer-reviewed journals, researchers concluded that CBD enhances cognition in “preclinical models of cognitive impairment.” Cognitive impairment examined in the study included disorders such as schizophrenia, Alzheimer’s disease, meningitis, sepsis, malaria, hepatic encephalopathy, and brain ischemia (13).
That being said, we are still lacking clinical evidence on CBD for memory loss, and until more data is collected, we can only theorize about these effects and experiment with CBD on our own. The good news is that all animals share the same endocannabinoid system that responds to plant-based cannabinoids in a similar manner. This means that studies using animal models show a high degree of relevance, and positive results from such research usually give green light to human trials.
Can CBD Cause Short Term Memory Loss?
Perhaps one of the biggest stereotypes surrounding cannabis is that the long-term use of the plant may cause problems with short-term memory due to alleged brain damage.
Now that we’ve established CBD and THC are both antioxidants and neuroprotectants, you may be wondering whether those alleged problems are caused by some other properties of these cannabinoids.
The truth is, CBD doesn’t cause short term memory loss, and as the current evidence suggests, it can actually improve memory and focus, aiding people with cognitive disorders.
It’s the THC that May Cause Short Term Memory Loss… But Here’s The Catch!
When it comes to THC, this issue is less obvious. THC has been shown to cause short-term memory loss directly after use. The results came from adolescents and indicated problems with the ability to recall things. However, these results weren’t replicated in population studies, nor did they carry over to adult samples.
THC has a very similar structure to anandamide, which is one of the two major cannabinoids produced by the body. Anandamide comes from Sanskrit and means “ananda,” which translates to “bliss,” “joy,” and “happiness.”
Aren’t these the feelings you experience after hitting a vape pen with cannabis oil?
Anandamide also plays an important role in the formation and processing of memories. Anandamide deficits are associated with a faster onset of PTSD in people who have gone through trauma; it also causes a person to experience more severe flash-backs from traumatic events. THC happens to alleviate the symptoms of PTSD because it makes the memory more selective.
Now, when the user gets a bit too high for their tolerance, the brain takes it as if there was more anandamide than it actually needs to function on the optimal level. This is when the brain may become more selective than it should.
Ever found yourself in a situation where in the middle of telling a story, you lose a thought and need a few seconds to recall the message you’ve been trying to convey?
That’s the backfiring selectivity of your memory.
It’s not chronic and it stops once your body gets flushed from THC.
How Much CBD Should I Take?
There are no officially established standards for CBD oil when it comes to dosage. All people are different, so the optimal CBD dosage may vary between individuals who are going to take it for a memory boost.
Currently, the U.S. Food and Drug Administration (FDA) doesn’t regulate the safety and purity of dietary supplements. As you may guess, hemp-derived CBD products are categorized as supplements, so you also need to pay attention to the quality of your CBD oil. There are many products out there that contain less CBD than advertised.
But, when you have a high-quality product in your hand, looking for advice on the dosage, here’s one simple advice: start low and go slow.
Different studies recommend starting with 1–50 mg of CBD daily. While 1 mg is rather considered a microdose, most people start with 5–10 mg twice a day. For some people, CBD may provide fast relief, whereas others will need to give it some time to work in the endocannabinoid system. Still, if you don’t feel any difference after a week of testing your dose, increase it by another 5 mg, and monitor the results for next week.
Once you’ve found the amount of CBD that boosts your focus and memory, you can stick to it, as people don’t build a tolerance to CBD. The cannabinoid is even known to induce “reverse tolerance,” where users take less CBD over time due to feeling better.
Final Verdict: Does CBD Oil Really Improve Memory?
CBD oil may be a natural and safe alternative for those seeking help for memory loss. CBD has remarkable antioxidant and neuroprotective effects on the brain, and unlike traditional treatments, its use doesn’t raise safety concerns among patients.
Research from animal models and preliminary human studies has yielded promising results when it comes to the memory-boosting properties of CBD, although we’re still waiting for clinical trials to investigate its efficacy on a large scale. So far, we know that CBD reduces inflammation, curbs oxidative stress, and contributes to neurogenesis in the brain — all of which are essential for memory preservation.
If you’re thinking of adding CBD oil to your supplementation plan, make sure to consult with your doctor to avoid any adverse interactions that CBD may have with your current medication. A visit to a knowledgeable professional will also help you establish an effective dosage range for your individual situation.
Do you take CBD to boost memory? Let us know in the comments below!
- Ibeas Bih, Clementino et al. “Molecular Targets of Cannabidiol in Neurological Disorders.” Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics vol. 12,4 (2015): 699-730. doi:10.1007/s13311-015-0377-3
- Watt, Georgia, and Tim Karl. “In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer’s Disease.” Frontiers in pharmacology vol. 8 20. 3 Feb. 2017, doi:10.3389/fphar.2017.00020
- Panikashvili, D et al. “An endogenous cannabinoid (2-AG) is neuroprotective after brain injury.” Nature vol. 413,6855 (2001): 527-31. doi:10.1038/35097089
- Walter, Lisa, and Nephi Stella. “Cannabinoids and neuroinflammation.” British journal of pharmacology vol. 141,5 (2004): 775-85. doi:10.1038/sj.bjp.0705667
- Campbell, Christopher T et al. “Cannabinoids in Pediatrics.” The journal of pediatric pharmacology and therapeutics: JPPT: the official journal of PPAGvol. 22,3 (2017): 176-185. doi:10.5863/1551-6776-22.3.176
- Bériault, Maxime et al. “Comorbidity of ADHD and Anxiety Disorders in School-Age Children: Impact on Sleep and Response to a Cognitive-Behavioral Treatment.” Journal of attention disorders vol. 22,5 (2018): 414-424. doi:10.1177/1087054715605914
- Osborne, Ashleigh L et al. “A systematic review of the effect of cannabidiol on cognitive function: Relevance to schizophrenia.” Neuroscience and biobehavioral reviews vol. 72 (2017): 310-324. doi:10.1016/j.neubiorev.2016.11.012
- de Carvalho, Cristiane Ribeiro, and Reinaldo Naoto Takahashi. “Cannabidiol disrupts the reconsolidation of contextual drug-associated memories in Wistar rats.” Addiction biology vol. 22,3 (2017): 742-751. doi:10.1111/adb.12366
- Bilkei-Gorzo, Andras et al. “A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice.” Nature medicine vol. 23,6 (2017): 782-787. doi:10.1038/nm.4311
- Watt, Georgia, and Tim Karl. Op. Cit.
- Cheng, David et al. “Long-term cannabidiol treatment prevent the development of social recognition memory deficits in Alzheimer’s disease transgenic mice.” Journal of Alzheimer’s disease: JAD vol. 42,4 (2014): 1383-96. doi:10.3233/JAD-140921
- McGuire, Philip et al. “Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial.” The American journal of psychiatry vol. 175,3 (2018): 225-231. doi:10.1176/appi.ajp.2017.17030325
- Osborne, Ashleigh L et al. Op. Cit.
Livvy is a registered nurse (RN) and board-certified nurse midwife (CNM) in the state of New Jersey. After giving birth to her newborn daughter, Livvy stepped down from her full-time position at the Children’s Hospital of New Jersey. This gave her the opportunity to spend more time writing articles on all topics related to pregnancy and prenatal care.
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