Daily diary study of associations between alcohol, cannabis, co-use and sleep quality in individuals with intentions to use cannabis to cope with anxiety.

INTRODUCTION: Sleep problems and anxiety conditions are common comorbidities and may be influenced by cannabis and alcohol use. This study examined daily within-person variation in subjective sleep quality among individuals with anxiety symptoms after cannabis or alcohol were used alone, and after co-use. METHODS: A total of 347 individuals with intentions to use cannabis to cope with anxiety reported their cannabis and alcohol use in the previous 24 h and their previous nights' sleep quality for 30 consecutive days. Mixed-effects models examined whether the within-person daily variation in use of cannabis and alcohol (alone and co-use) was associated with subjective sleep quality. Models also examined whether daily cannabis and alcohol use associations with sleep were moderated by frequency of cannabis, alcohol and co-use during the study period. RESULTS: Compared to non-use, participants reported better sleep after cannabis-use-only and after co-use, but not after alcohol-use-only. People who more frequently use alcohol and cannabis reported sleeping better after cannabis-use-only days compared to those who use cannabis and alcohol less frequently. DISCUSSION AND CONCLUSIONS: The study's utilisation of naturalistic data among individuals with anxiety symptoms replicated previously reported experimental findings among individuals without sleep and anxiety problems that overall, cannabis is associated with higher subjective sleep quality. The results expand upon other research to suggest that more frequent use of alcohol and cannabis may moderate daily associations of cannabis use and sleep, potentially through pharmacokinetics and cross-sensitisation.

Alcohol First, Cannabis Last: Identification of an Especially Risky Use Pattern among Individuals Who Co-Use Alcohol and Cannabis.

Background: Alcohol and cannabis co-use is common and confers increased risk for potential harms, such as negative consequences and substance dependence. The existing evidence suggests that factors such as dose of delta-9-tetrahydrocannabinol (THC) consumed and order of use of each substance (i.e., using alcohol or cannabis first or last when co-using) may impact co-use outcomes. Existing co-use research has focused primarily on college-samples or young adults, and few studies have explored these nuanced relations among community samples. Methods: We examined survey data from 87 community members (mean age 32.9 years, 49.4% female) recruited from legal market cannabis dispensaries. Using a combination of regression techniques (i.e., OLS, negative binomial, censor-inflated) we modeled relations among co-use ordering patterns, THC dose and cannabis outcomes as well as interactions with sex assigned at birth and age. Results: Individuals who endorsed co-use reported significantly higher CUDIT scores than those who had never co-used (p < 0.01). Using alcohol first and cannabis last (a pattern we refer to as "AFCL") was more common among females than males (p < 0.01). In the context of typical substance use weeks, more frequently engaging in the AFCL pattern was associated with significantly higher CUDIT scores (p < 0.001) and negatively predicted positive consequences (p < 0.001). Other patterns predicted higher CUDIT scores during heavy use weeks. Conclusions: Results indicate that co-use ordering patterns are related to substance use outcomes. Further research leveraging within-subjects, longitudinal designs is needed to test causal relations between these variables.

Addendum to "Evaluating substance use outcomes of recreational cannabis legalization using a unique co-twin control design".

An earlier version of this article was published in error. Our prior publication was missing reference to a prior study on this topic. Our prior research has not found an association between recreational cannabis legalization (RCL) and negative psychosocial and psychiatric outcomes. We reported significant associations between RCL with greater cannabis frequency and fewer alcohol use disorder symptoms. The current study expands on our previous research by using a cross-sectional design and different measures of problems from cannabis and alcohol use and including additional substance use variables. The current study found similar results to our previous research.

Examining Associations Between Cannabis Use Disorder and Measures of Weekly and Within-Day Cannabis Frequency, Quantity, and Potency in College Students.

Background: College student cannabis use has increased significantly in recent years, and individuals aged 18-25 are at elevated risk for development of cannabis use disorder (CUD). While weekly cannabis use frequency is a commonly used measure of cannabis consumption, there is increasing scientific interest in exploring more nuanced measures of cannabis use. Currently, limited research exists examining the clinical utility of cannabis quantity, within-day frequency, and potency variables. Methods: We used cross-sectional survey data from a sample of 617 undergraduate students in the state of Colorado. A two-part model-building approach was leveraged to examine whether within-session cannabis quantity and within-day cannabis use frequency were associated with odds of experiencing any CUD symptoms and total number of CUD symptoms endorsed. We also examined whether cannabis flower potency was associated with odds of experiencing any CUD symptoms and total number of CUD symptoms endorsed among a subset (N=288) of the sample who reported knowledge of the cannabinoid content of their most frequently used products. Results: Weekly flower use frequency (odds ratio [OR]=1.27, p<0.001) and weekly concentrate use frequency (OR=1.10, p=0.044) were positively associated with increased odds of experiencing any CUD symptoms, but cannabis quantity and within-day frequency variables were not. In addition, no association was found between flower potency and odds of endorsing any CUD symptoms. Among individuals endorsing at least one symptom, weekly flower use frequency (incident rate ratio [IRR]=1.06, p<0.001) was positively associated with total symptom count, but weekly concentrate use frequency, cannabis quantity variables, and within-day frequency variables were not. Among individuals endorsing symptoms, a positive association was found between flower potency and total symptom count (IRR=1.01, p=0.008). Conclusion: Current methods of assessing within-session cannabis quantity and within-day cannabis use frequency may lack clinical utility in examining college student CUD symptoms over and above weekly cannabis use frequency. Cannabis flower potency may prove useful in assessment of CUD symptom severity, but further research is warranted.

Baseline affective symptomatology moderates acute subjective effects of high potency THC and CBD cannabis concentrates.

Highly potent cannabis concentrates are widely available and associated with affective disturbance and cannabis use disorder. Little is known about the effects of concentrated Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) and their relationship to long-term affect. We explored how baseline affective symptoms (anxiety and depression) relate to acute (i.e., immediate or short-term) subjective mood and intoxication effects during naturalistic use of cannabis concentrates. Fifty-four cannabis users (48% female; Mage = 29.87) were assigned to ad libitum use of either a THC-dominant (84.99% THC and THCa, < 1% CBD) or CBD-dominant (74.7% CBD, 4.1% CBDa, 4.5% THC and THCa) concentrate. Individuals were assessed at baseline and before, immediately after, and 1 hr after naturalistic use of their assigned product. Models regressed each outcome on time, product condition, baseline affective symptoms, and their interactions. An interaction emerged between condition and baseline depression symptoms on positive mood (F = 9.47, p < .005); higher depression symptom level was associated with higher positive mood with THC-dominant product use. There was an interaction between condition, baseline depression symptoms, and time on negative mood (F = 5.55, p < .01); negative mood decreased with CBD-dominant product use for all depression symptom levels but increased with THC-dominant product use at high levels. Finally, there was an interaction between condition and time on intoxication (F = 3.72, p = .03); the THC-dominant condition was more intoxicated postuse than the CBD-dominant condition. This novel exploratory study suggests that baseline affect moderates the acute effects of ad libitum use of THC and CBD concentrates such that preexisting affective symptoms modulate the intensity of subjective drug experiences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Evaluating substance use outcomes of recreational cannabis legalization using a unique co-twin control design.

Background: As more states pass recreational cannabis legalization (RCL), we must understand how RCL affects substance use.Objectives: The current study aims to examine the effect of RCL on lifetime and past-year use of cannabis, alcohol, tobacco, and other drugs, frequency of cannabis, alcohol, and tobacco use, co-use of cannabis with alcohol and tobacco, and consequences from cannabis and alcohol use.Methods: We used a unique, co-twin control design of twin pairs who were discordant for living in a state with RCL between 2018 and 2021. The sample consisted of 3,830 adult twins (41% male), including 232 twin pairs discordant for RCL. Problems from alcohol and cannabis use were assessed via the Brief Marijuana Consequences Questionnaire and the Brief Young Adult Alcohol Consequences Questionnaire.Results: Results indicated that the twin living in an RCL state was more likely to endorse past-year cannabis use (OR = 1.56, p = .009), greater number of cannabis use days in the past 6 months (ß = 0.47, p = .019), but not more negative consequences from cannabis use (ß = 0.21, p = .456) compared to their co-twin in a non-RCL state. There were no differences within-twin pairs in frequency of alcohol use (ß=-0.05, p = .601), but the RCL twin reported fewer negative consequences from alcohol use (ß=-0.29, p = .016) compared to their co-twin in a non-RCL state. We did not observe any other differences within-twin pairs on other outcomes.Conclusion: These results suggest that living in an RCL state is associated with greater cannabis frequency but not more negative consequences from cannabis use than living in a non-RCL state.

Comparing the Efficacy of Mindfulness-Based Relapse Prevention Versus Relapse Prevention for Alcohol Use Disorder: A Randomized Control Trial.

OBJECTIVE: This study compared the efficacy of mindfulness-based relapse prevention (MBRP) with relapse prevention (RP) on reducing alcohol consumption. Secondary, exploratory aims assessed moderation of treatment effects by sex and cannabis use. METHOD: A total of 182 individuals (48.4% female; 21-60 years old) who reported drinking more than 14/21 drinks/week (for women and men, respectively) in the past 3 months but who wished to quit/reduce their drinking were recruited from Denver and Boulder, Colorado. Individuals were randomly assigned to 8 weeks of individual-based MBRP or RP treatment. Participants completed substance use assessments at baseline, halfway through and at the end of treatment, and 20 and 32 weeks after treatment. Primary outcomes were Alcohol Use Disorders Identification Test-consumption questions (AUDIT-C) scores, heavy drinking days (HDD), and drinks per drinking day (DDD). RESULTS: Across treatments, drinking decreased over time (ps < .001), with a significant time-by-treatment interaction found for HDD (F = 3.50, p < .01). HDD initially decreased in both treatments but remained stable or increased after treatment for MBRP and RP participants, respectively. At follow-up, MBRP participants had significantly less HDD than RP participants. Sex did not moderate treatment effects (ps > .17), whereas cannabis use moderated treatment effects on DDD and HDD (F = 4.89, p < .001, and F = 4.30, p < .005, respectively). High cannabis use frequency was associated with continued posttreatment decreases in HDD/DDD for MBRP participants but increased HDD for RP participants. At low cannabis use frequency levels, HDD/DDD remained stable after treatment across groups. CONCLUSIONS: Drinking decreases were comparable across treatments, but HDD improvements diminished for RP participants after treatment. In addition, cannabis use moderated treatment efficacy for HDD/DDD.

Consuming oral cannabidiol prior to a standard alcohol dose has minimal effect on breath alcohol level and subjective effects of alcohol.

RATIONALE: Cannabidiol (CBD) is found in the cannabis plant and has garnered attention as a potential treatment for alcohol use disorder (AUD). CBD reduces alcohol consumption and other markers of alcohol dependence in rodents, but human research on CBD and alcohol is limited. It is unknown whether CBD reduces drinking in humans, and mechanisms through which CBD could impact behavioral AUD phenotypes are unknown. OBJECTIVES: This study explores effects of oral CBD on breath alcohol level (BrAC), and subjective effects of alcohol in human participants who report heavy drinking. METHODS: In this placebo-controlled, crossover study, participants consumed 30 mg CBD, 200 mg CBD, or placebo CBD before receiving a standardized alcohol dose. Participants were blind to which CBD dose they received at each session and completed sessions in random order. Thirty-six individuals completed at least one session and were included in analyses. RESULTS: Differences in outcomes across the three conditions and by sex were explored using multilevel structural equation models. BrAC fell fastest in the placebo condition, followed by 30 mg and 200 mg CBD. Stimulation decreased more slowly in the 200 mg CBD condition than in placebo (b = - 2.38, BCI [- 4.46, - .03]). Sedation decreased more slowly in the 30 mg CBD condition than in placebo (b = - 2.41, BCI [- 4.61, - .09]). However, the magnitude of condition differences in BrAC and subjective effects was trivial. CONCLUSIONS: CBD has minimal influence on BrAC and subjective effects of alcohol. Further research is needed to test whether CBD impacts alcohol consumption in humans, and if so, what mechanism(s) may explain this effect.

Associations between alcohol and cannabis use order, frequency, quantity, and consequences in a college sample of individuals who co-use alcohol and cannabis.

BACKGROUND AND OBJECTIVES: Using both alcohol and cannabis (either at the same time or at different times) is common among college students, and is called "co-use." Using these substances simultaneously, such that their effects overlap, is thought to be an especially risky co-use pattern. Gaining a better understanding of how co-use patterns relate to substance use and consequences could aid prevention and intervention efforts. METHODS: We examined college students (N = 401) who reported using both alcohol and cannabis at least once in the past 30 days. Path analysis was used to explore relations among co-use patterns (number of days in a typical week that participants used both alcohol and cannabis; the number of days using alcohol first, cannabis first, alcohol last, and cannabis last; the number of days of simultaneous use), past-30-day alcohol and cannabis consequences, use frequency, and typical quantities used. RESULTS: Each additional day of using alcohol first was associated with fewer past-30-day cannabis consequences. Each additional day of using cannabis first was associated with fewer alcohol-related consequences. Each additional day of using alcohol and cannabis on the same day and each additional day of simultaneous use were both associated with less cannabis used and alcohol consumed in a typical week. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This study is among the first to identify associations between alcohol and cannabis order and outcomes (i.e., consequences and consumption). Results suggest that modifying which substance is used first on a given day could be a practical intervention strategy for individuals who co-use alcohol and cannabis.

Protocol for a mobile laboratory study of co-administration of cannabis concentrates with a standard alcohol dose in humans.

Cannabis is commonly used among people who drink alcohol, yet evidence on acute effects of co-use is conflicting. Two important variables that may influence the effects of cannabis and alcohol are cannabinoid content (i.e., the ratio of cannabidiol [CBD] and 9-tetrahydrocannabinol [THC]) as well as the order of use (i.e., cannabis before alcohol vs. alcohol before cannabis). Research is mixed regarding the acute imapct of cannabis on alcohol consumption and intoxication, with some studies suggesting additive effects of alcohol and cannabis, and others demonstrating negligible effects of combining these substances. Further complicating this, high-THC-content cannabis concentrates are increasingly popular on the legal-market, but to our knowledge, no studies have explored concentrate and alcohol co-use. In addition to cannabinoid content, order of use may influence intoxication and other acute effects, but is also understudied. Co-use studies typically administer a fixed dose of alcohol before cannabis, and there is a lack of data on the acute effects of cannabis before alcohol. Thus, there is a need for experimental co-use studies exploring the impact of cannabinoid content (particularly of highly potent cannabis concentrates) and order effects on intoxication. This study uses a federally-compliant mobile laboratory procedure to explore the effects of co-administration of legal-market cannabis concentrates with a moderate alcohol dose (.8g/kg) in a sample of community participants who regularly use alcohol and cannabis. The study will also explore alcohol and cannabis order effects (cannabis before alcohol vs. alcohol before cannabis). Outcomes are objective intoxication (measured using blood cannabinoid level, heart rate, psychomotor performance and breath alcohol level [BrAC]) and subjective intoxication (assessed via self-report measures). Overall, this study may influence harm-reduction recommendations for individuals who drink alcohol and use cannabis.

Effects of High-Potency Cannabis on Psychomotor Performance in Frequent Cannabis Users.

Background: Recently increased access to cannabis products in the United States has been associated with increased rates of driving after cannabis use. Although numerous studies indicate that cannabis impairs psychomotor and neurocognitive functions that can affect driving ability, the determination of cannabis-impaired driving risk is complicated by the extent to which frequent cannabis users develop tolerance to THC's subjective, cognitive, and psychomotor effects, and by the fact that there is no validated behavioral or biological marker of recent cannabis use or cannabis-related impairment. This study examined the psychomotor impairment-related effects experienced by frequent cannabis users in Colorado after naturalistic consumption of smoked cannabis, both immediately and 1 h postuse. Results were then validated in a smaller replication sample from Washington state. Methods: In the primary Colorado study, participants (n=70) used the DRUID® mobile app, a brief measure of psychomotor and cognitive domains that are sensitive to the effects of cannabis. First, participants used DRUID to establish a sober baseline impairment score. During a second appointment, they used DRUID at three time points: preuse, immediately after acutely using cannabis, and 1 h postuse. In the Washington replication sample, participants (n=39) used DRUID before acute cannabis consumption and then every half hour for 2.5 h. Results: In both studies, peak DRUID impairment effects were seen immediately after cannabis use, with recovery of performance at 1 h postuse. Specifically, significant quadratic effects of time emerged for both studies (Colorado study: (ß=-0.935, SE=0.204, p<0.001); Washington study: ß=3.0299, SE=1.3085, p<0.01). Domain-specific effects were tested in the larger Colorado study and were observed for reaction time within a complex divided attention task and a postural-stability balance task. Conclusions: These findings demonstrate that psychomotor impairment emerges immediately after acute cannabis use even in regular users, but decreases significantly 1 h postuse. These results underscore the potential utility of the DRUID app for assessing acute cannabis-related psychomotor impairment. Further research is needed to explore whether the DRUID app and/or the specific psychomotor functions it assesses might serve as a tool for measuring cannabis-related driving impairment. Clinical trials registration number for the Colorado Study: NCT03522103.

Effects of cannabidiol in cannabis flower: Implications for harm reduction.

Using a federally compatible, naturalistic at-home administration procedure, the present study examined the acute effects of three cannabis flower chemovars with different tetrahydrocannabinol (THC) to cannabidiol (CBD) ratios, in order to test whether chemovars with a higher CBD content produce different effects. Participants were randomly assigned to ad libitum administration of one of three chemovars (THC-dominant: 24% THC, 1% CBD; THC+CBD: 9% THC, 10% CBD; CBD-dominant: 1% THC, 23% CBD); 159 regular cannabis users (male = 94, female = 65) were assessed in a mobile pharmacology lab before, immediately after, and 1 h after ad libitum administration of their assigned chemovar. Plasma cannabinoids as well as positive (e.g., high, elation) and negative (e.g., paranoia and anxiety) subjective effects were assessed at each time points. Participants who used the CBD-dominant and THC + CBD chemovars had significantly less THC and more CBD in plasma samples compared to participants who used the THC-dominant chemovar. Further, the THC + CBD chemovar was associated with similar levels of positive subjective effects, but significantly less paranoia and anxiety, as compared to the THC-dominant chemovar. This is one of the first studies to examine the differential effects of various THC to CBD ratios using chemovars that are widely available in state-regulated markets. Individuals using a THC + CBD chemovar had significantly lower plasma THC concentrations and reported less paranoia and anxiety while also reporting similar positive mood effects as compared to individuals using THC only, which is intriguing from a harm reduction perspective. Further research is needed to clarify the harm reduction potential of CBD in cannabis products.

A naturalistic study of orally administered vs. inhaled legal market cannabis: cannabinoids exposure, intoxication, and impairment.

RATIONALE: Published studies examining the effects of cannabis have largely utilized forms of cannabis that are not representative of the legal market products currently available. OBJECTIVES: The present study aimed to characterize naturalistic use of legal market flower and edible products by examining associations among blood cannabinoids and amount of THC consumed as well as physiological, cognitive, and subjective effects in users of edible and flower forms. METHOD: Eighty-four participants who used cannabis at least 1 × /week (55 flower cannabis using participants; 29 edible cannabis using participants mean age = 31.95 years, 44% female) participated. At the experimental appointment in our mobile laboratory, participants completed a blood draw to assess plasma cannabinoids, measures of heart rate, subjective drug effects, and cognition both before and after ad libitum use of legal market flower or edible cannabis. RESULTS: Average self-reported THC consumed was 15.97 mg (SD = 22.40) in edible users and 51.25 mg (SD = 45.23) in flower users. In the edible group, but not the flower group, strong correlations emerged between self-reported ad libitum THC consumed and plasma THC. Plasma THC was significantly higher after use of inhaled cannabis, but similar levels of plasma THC metabolites and similar levels of subjective intoxication and verbal memory impairment were observed in both flower and edible users. CONCLUSIONS: Findings support strong correlations among ad libitum THC consumed and THC plasma levels after edible cannabis use and suggest few differences in intoxication and impairment between edible and flower cannabis users after ad libitum use. This novel study provides important preliminary data on the pharmacology and effects of legal market edible cannabis.

Investigating Associations Between Inflammatory Biomarkers, Gray Matter, Neurofilament Light and Cognitive Performance in Healthy Older Adults.

Background: Exploring biological variables that may serve as indicators of the development and progression of cognitive decline is currently a high-priority research area. Recent studies have demonstrated that during normal aging, individuals experience increased inflammation throughout the brain and body, which may be linked to cognitive impairment and reduced gray matter volume in the brain. Neurofilament light polypeptide (NfL), which is released into the circulation following neuronal damage, has been proposed as a biomarker for neurodegenerative diseases, and may also have utility in the context of normal aging. The present study tested associations between age, peripheral levels of the pro-inflammatory cytokine IL-6, peripheral NfL, brain volume, and cognitive performance in a sample of healthy adults over 60 years old. Methods: Of the 273 individuals who participated in this study, 173 had useable neuroimaging data, a subset of whom had useable blood data (used for quantifying IL-6 and NfL) and completed a cognitive task. Gray matter (GM) thickness values were extracted from brain areas of interest using Freesurfer. Regression models were used to test relationships between IL-6, NfL, GM, and cognitive performance. To test putative functional relationships between these variables, exploratory path analytic models were estimated, in which the relationship between age, IL-6, and working memory performance were linked via four different operationalizations of brain health: (1) a latent GM variable composed of several regions linked to cognitive impairment, (2) NfL alone, (3) NfL combined with the GM latent variable, and (4) the hippocampus alone. Results: Regression models showed that IL-6 and NfL were significantly negatively associated with GM volume and that GM was positively associated with cognitive performance. The path analytic models indicated that age and cognitive performance are linked by GM in the hippocampus as well as several other regions previously associated with cognitive impairment, but not by NfL alone. Peripheral IL-6 was not associated with age in any of the path models. Conclusions: Results suggest that among healthy older adults, there are several GM regions that link age and cognitive performance. Notably, NfL alone is not a sufficient marker of brain changes associated with aging, inflammation, and cognitive performance.

Exploring relationships between alcohol consumption, inflammation, and brain structure in a heavy drinking sample.

BACKGROUND: Chronic alcohol consumption is associated with structural brain changes and increased inflammatory signaling throughout the brain and body. Increased inflammation in the brain has been associated with structural damage. Recent studies have also shown that neurofilament light polypeptide (NfL) is released into the systemic circulation following neuronal damage. Although NfL has thus been proposed as a biomarker for neurodegenerative diseases, its connection to alcohol use disorder has not been explored. For this secondary data analysis, we proposed a conceptual model linking alcohol consumption, the pro-inflammatory cytokine IL-6, brain structure, and NfL in heavy drinking participants. METHODS: Of the 182 individuals enrolled in this study, 81 participants had usable data on gray matter (GM) thickness and 80 had usable data on white matter (WM) diffusivity. A subset of participants had NfL (n = 78) and IL-6 (n = 117) data. An estimate of GM thickness was extracted from middle frontal brain regions using FreeSurfer. Estimated mean WM diffusivity values were extracted from Tract Based Spatial Statistics. NfL and IL-6 were measured in blood. Regression models were used to test individual linkages in the conceptual model. Based on significant regression results, we created a simplified conceptual model, which we tested using path analysis. RESULTS: In regressions, negative relationships emerged between GM and both drinks per drinking day (DPDD) (p = 0.018) and NfL (p = 0.004). A positive relationship emerged between WM diffusivity and DPDD (p = 0.033). IL-6 was not significantly associated with alcohol use, GM or WM. The final path model demonstrated adequate fit to the data and showed significant, negative associations between DPDD and middle frontal gyrus (MFG) thickness, and between MFG thickness and NfL, but the association between DPDD and NfL was not significant. CONCLUSIONS: This is the first study to show that heavy drinking is associated with lower GM thickness and higher WM diffusivity and that lower GM thickness is associated with higher circulating NfL. The analyses also show that the effects of drinking do not involve the pro-inflammatory cytokine IL-6.

Advancing the science on cannabis concentrates and behavioural health.

ISSUES: The Cannabis sativa L. plant contains hundreds of phytocannabinoids, but putatively of highest importance to public health risk is the psychoactive cannabinoid delta-9-tetrahydrocannabinol (THC), which is associated with risk for cannabis use disorder, affective disturbance, cognitive harm and psychomotor impairment. Recently, there has been an increase in the use and availability of concentrated cannabis products (or 'concentrates') that are made by extracting cannabinoids from the plant to form a product with THC concentrations as high as 90-95%. These products are increasingly popular nationwide. The literature on these widely available high potency concentrates is limited and there are many unknowns about their potential harms. APPROACH: This review covers the state of the research on cannabis concentrates and behavioural health-related outcomes and makes recommendations for advancing the science with studies focused on accurately testing the risks in relation to critical public and behavioural health questions. KEY FINDINGS: Data point to unique behavioural health implications of concentrate use. However, causal, controlled and representative research on the effects of cannabis concentrates is currently limited. IMPLICATIONS: Future research is needed to explore chronic, acute and developmental effects of concentrates, as well as effects on pulmonary function. We also highlight the need to explore these relationships in diverse populations. CONCLUSION: While the literature hints at the potential for these highly potent products to increase cannabis-related behavioural health harms, it is important to carefully design studies that more comprehensively evaluate the impact of concentrates on THC exposure and short- and long-term effects across user groups.

Effects of cannabis use on alcohol consumption in a sample of treatment-engaged heavy drinkers in Colorado.

BACKGROUND AND AIMS: Cannabis is commonly used among people who drink alcohol, but evidence suggests a nuanced relationship between alcohol consumption and cannabis use. In particular, among individuals undergoing alcohol treatment the impact of cannabis on alcohol intake may depend upon cannabis use frequency. We aimed to test the effects of within-day cannabis use on total drinks consumed and likelihood of binge drinking on a given day among all participants and compare these relationships between males and females and between individuals who reported infrequent and frequent cannabis use. DESIGN: This observational study is a substudy of a larger randomized controlled trial (RCT). Individuals were included from the RCT if they reported any cannabis use and were divided into groups based on cannabis use patterns. Alcohol use was compared within and between groups. SETTING: Individuals were recruited from 2016 to 2020 from community and university settings in Denver and Boulder, CO, USA. PARTICIPANTS: Of the 182 individuals enrolled in the RCT, 96 cannabis-using subjects were included in these analyses. MEASUREMENTS: Subjects completed a time-line follow-back (TLFB) at baseline, 4, 8 (end of treatment) and 20 weeks. Daily data on alcohol and cannabis use from the TLFB at all time-points were analyzed. FINDINGS: Across the sample (n = 96), individuals drank approximately 29% fewer drinks [95% confidence interval (CI) = 18-39%, P < 0.001] and were 2.06 times (95% CI =1.37-3.08, P < 0.001) less likely to have a binge-drinking episode on days that cannabis was used compared with days that cannabis was not used. These patterns were observed in males, females and the infrequent and frequent cannabis use groups. Findings were inconclusive regarding differences in the association between cannabis use and alcohol outcomes when comparing males and females and when comparing infrequent and frequent cannabis use groups. CONCLUSIONS: Heavy drinkers engaged in treatment to reduce their alcohol consumption who also use cannabis appear to increase their cannabis use on days when they reduce their alcohol consumption.

Few Structural Brain Changes Associated With Moderate-Intensity Interval Training and Low-Intensity Continuous Training in a Randomized Trial of Fitness and Older Adults.

This study utilized a randomized control trial to examine whether structural changes in the precuneus, insula, caudate, hippocampus, and putamen were related to exercise. A total of 197 healthy older adults with no evidence of dementia participated in moderate-intensity interval training or low-intensity continuous training for 16 weeks. Size decreased in the right hippocampus such that the effect of time was significant but the interaction with condition was not. For the left hippocampus, size decreased in the low-intensity continuous training condition but increased in the moderate-intensity continuous training plus interval training condition at the trend level. Finally, there was a significant time-by-condition interaction such that the thickness of the left insula increased for low-intensity continuous training and decreased for moderate-intensity continuous training plus interval training. Few structural changes were associated with the exercise intervention. Future studies should examine the effects of exercise on brain structure in high-risk or clinical populations for a longer period of time.

Association of Naturalistic Administration of Cannabis Flower and Concentrates With Intoxication and Impairment.

Importance: The rapidly growing legal cannabis market includes new and highly potent products, the effects of which, to our knowledge, have not previously been examined in biobehavioral research studies because of federal restrictions on cannabis research. Objective: To use federally compatible, observational methods to study high-∆9-tetrahydrocannabinol (THC) legal market forms of cannabis. Design, Setting, and Participants: In this cohort study with a between-groups design that was conducted in a community and university setting, cannabis flower users and concentrate users were randomly assigned to higher- vs lower-THC products within user groups. Participants completed a baseline and an experimental mobile laboratory assessment that included 3 points: before, immediately after, and 1 hour after ad libitum legal market flower and concentrate use. Of the 133 individuals enrolled and assessed, 55 regular flower cannabis users (41.4%) and 66 regular concentrate cannabis users (49.6%) complied with the study's cannabis use instructions and had complete data across primary outcomes. Exposures: Flower users were randomly assigned to use either 16% or 24% THC flower and concentrate users were randomly assigned to use either 70% or 90% THC concentrate that they purchased from a dispensary. Main Outcomes and Measures: Primary outcome measures included plasma cannabinoids, subjective drug intoxication, and neurobehavioral tasks testing attention, memory, inhibitory control, and balance. Results: A total of 121 participants completed the study for analysis: 55 flower users (mean [SD] age, 28.8 [8.1] years; 25 women [46%]) and 66 concentrate users (mean [SD] age, 28.3 [10.4] years; 30 women [45%]). Concentrate users compared with flower users exhibited higher plasma THC levels and 11-hydroxyΔ9-THC (THC's active metabolite) across all points. After ad libitum cannabis administration, mean plasma THC levels were 0.32 (SE = 0.43) µg/mL in concentrate users (to convert to millimoles per liter, multiply by 3.18) and 0.14 (SE = 0.16) µg/mL in flower users. Most neurobehavioral measures were not altered by short-term cannabis consumption. However, delayed verbal memory (F1,203 = 32.31; P < .001) and balance function (F1,203 = 18.88; P < .001) were impaired after use. Differing outcomes for the type of product (flower vs concentrate) or potency within products were not observed. Conclusions and Relevance: This study provides information about the association of pharmacological and neurobehavioral outcomes with legal market cannabis. Short-term use of concentrates was associated with higher levels of THC exposure. Across forms of cannabis and potencies, users' domains of verbal memory and proprioception-focused postural stability were primarily associated with THC administration.