Alcohol and cannabis co-use: Probing subjective response in eliciting cross-substance craving.

The co-use of alcohol and cannabis is rising in prevalence, yet the mechanisms driving individuals to co-use are not well understood. Subjective response to alcohol or cannabis may predict the desire to use either substance. However, which specific facets of subjective response predict cross-substance craving remains unclear. The present study investigated whether acute administration of alcohol or cannabis facilitates cue-induced craving for the other substance, with an emphasis on the underlying subjective response mechanisms contributing to co-use. This is a secondary analysis of a behavioral pharmacology study that combined alcohol/cannabis administration with a cross-substance cue-reactivity paradigm in individuals who were heavy alcohol and heavy cannabis co-users. Over two sessions, twenty-nine individuals (17M/12F) self-administered alcohol or cannabis (in a crossover design), and then completed a cue-reactivity exercise with the other substance. Analyses tested how changes in subjective response variables following substance administration predicted cross-substance cue-induced craving. Following alcohol administration, greater subjective ratings of positive mood predicted significantly greater cue-induced cannabis craving (ß = 1.14, SE = 0.41, t = 2.80, p = 0.010). Following cannabis administration, lower subjective effects ratings of positive mood/arousal predicted significantly greater cue-induced alcohol craving (ß = -1.08, SE = 0.38, t = -2.85, p = 0.009; ß = -2.38, SE = 1.13, t = -2.10, p = 0.047). This study identified subject response mechanisms contributing to cross-substance cue induced craving. These mechanisms include increases in positive mood following alcohol use and decreases in positive mood and arousal, akin to increases in relaxation, following cannabis use.

Exploring Novel Pharmacotherapy Candidates for Cannabis Use Disorder: Uncovering Promising Agents on the Horizon by Mechanism of Action.

With rapid expansion of cannabis legalization worldwide, rates of cannabis use and cannabis use disorder (CUD) are increasing; the need for safe and effective medications to treat CUD is urgent. This narrative review evaluates evidence for promising pharmacotherapies to treat CUD from randomized, placebo-controlled trials. Pharmacotherapies for CUD are categorized based on compound targets (e.g., cannabinoid receptor 1 [CB1] agonists such as nabilone, serotonergic compounds such as bupropion, GABAergic compounds such as zolpidem) and outcomes are organized by predetermined withdrawal symptoms, cannabis craving, and cannabis relapse/use. Most promising pharmacotherapies for CUD are drugs that act on the endocannabinoid system and specifically at the CB1 receptor. Priority populations such as females, certain racial/ethnic groups, and age groups experience a different course of CUD progression, symptoms, and drug effects that are important to consider when evaluating outcomes related to CUD. Possible explanations for these disparities are explored, along with the clinical trials that explore these demographics in treating CUD with pharmacotherapies.

Altered neurobehavioral reward response predicts psychotic-like experiences in youth exposed to cannabis prenatally.

Importance: Rates of prenatal cannabis exposure (PCE) are rising with increasingly permissive legislation regarding cannabis use, which may be a risk factor for psychosis. Disrupted reward-related neural circuitry may underlie this relationship. Objective: To elucidate neural mechanisms involved in the association between PCE and youth-onset psychotic-like experiences by probing correlates of reward anticipation, a neurobehavioral marker of endocannabinoid-mediated dopaminergic function. Design setting and participants: This longitudinal, prospective study analyzed task-related functional neuroimaging data from baseline (n=11,368), 2-year follow-up (n=7,928), and 4-year follow-up (n=2,982) of the ongoing Adolescent Brain and Cognitive Development (ABCD) Study, which recruited children aged 9 to 10 years old at baseline from 22 sites across the United States. Results: PCE (n=652 exposed youth) is longitudinally associated with psychotic-like experiences. Blunted neural response to reward anticipation is associated with psychotic-like experiences, with stronger effects observed in PCE youth (all |ß| > 0.5; false discovery rate [FDR]-corrected P < .05). This hypoactivation at baseline predicts psychosis symptomatology in middle adolescence (4-year follow-up visit; ß=-.004; FDR-corrected P < .05). Dampened behavioral reward sensitivity is associated with psychotic-like experiences across baseline, 2-year follow-up visit, and 4-year follow-up visit (|ß| = .21; FDR-corrected P < .001). Psychotic-like experiences are positively associated with trait-level measures of reward motivation and impulsivity, with stronger effects for PCE youth (all |ß| > 0.1; all FDR-corrected P < .05). Conclusions and Relevance: Blunted activation in reward-related brain regions may serve as a biomarker for disrupted reward processing and increased psychosis risk during development. PCE may affect childhood behaviors and traits related to altered reward sensitivity.

Blunt Talk on "Blunts": The Increasingly Popular Tobacco Product That Is Potentially Exacerbating Tobacco-Related Health Disparities.

A "blunt" is a hollowed-out cigar/cigarillo from which much of the loose tobacco has been removed, and the remaining tobacco wrapper filled with cannabis. Although blunts contain significant levels of tobacco/nicotine, they are often treated as if they were exclusive cannabis products and omitted from surveys of tobacco products. Whereas the prevalence of virtually all other tobacco products is on the decline in the USA, available data suggest that the prevalence of blunt smoking is not - and in fact, it may be increasing. Blunts are most frequently used by people who self-identify as Black. As a result of misperceptions and perhaps biases, there is a dearth of scientific investigation, hence knowledge, surrounding the health effects associated with blunt smoking. Co-use of tobacco and cannabis has been reported to have additive and even synergistic adverse health effects. Lack of investigations into the health effects of tobacco products most frequently used by Black people may contribute to tobacco-related health disparities. We argue that the scientific and public health communities must treat blunts as the potentially lethal tobacco product that they are, studying their prevalence and use patterns, and investigating their adverse health effects, both short and long term.

Acute effects of cannabigerol on anxiety, stress, and mood: a double-blind, placebo-controlled, crossover, field trial.

Cannabigerol (CBG) is a phytocannabinoid increasing in popularity, with preclinical research indicating it has anxiolytic and antidepressant effects. However, there are no published clinical trials to corroborate these findings in humans. The primary objective of this study was to examine acute effects of CBG on anxiety, stress, and mood. Secondary objectives were to examine whether CBG produces subjective drug effects or motor and cognitive impairments. A double-blind, placebo-controlled cross-over field trial was conducted with 34 healthy adult participants. Participants completed two sessions (with a one-week washout period) via Zoom. In each, they provided ratings of anxiety, stress, mood, and subjective drug effects prior to double-blind administration of 20 mg hemp-derived CBG or placebo tincture (T0). These ratings were collected again after participants ingested the product and completed an online survey (T1), the Trier Social Stress Test (T2), a verbal memory test and the DRUID impairment app (T3). Relative to placebo, there was a significant main effect of CBG on overall reductions in anxiety as well as reductions in stress at T1. CBG also enhanced verbal memory relative to placebo. There was no evidence of subjective drug effects or impairment. CBG may represent a novel option to reduce stress and anxiety in healthy adults.

The Development of Cannabinoids as Therapeutic Agents in the United States.

Cannabis is one of the oldest and widely used substances in the world. Cannabinoids within the cannabis plant, known as phytocannabinoids, mediate cannabis' effects through interactions with the body's endogenous cannabinoid system. This endogenous system, the endocannabinoid system, has important roles in physical and mental health. These roles point to the potential to develop cannabinoids as therapeutic agents while underscoring the risks related to interfering with the endogenous system during nonmedical use. This scoping narrative review synthesizes the current evidence for both the therapeutic and adverse effects of the major (i.e., Δ9-tetrahydrocannabinol and cannabidiol) and lesser studied minor phytocannabinoids, from nonclinical to clinical research. We pay particular attention to the areas where evidence is well established, including analgesic effects after acute exposures and neurocognitive risks after acute and chronic use. In addition, drug development considerations for cannabinoids as therapeutic agents within the United States are reviewed. The proposed clinical study design considerations encourage methodological standards for greater scientific rigor and reproducibility to ultimately extend our knowledge of the risks and benefits of cannabinoids for patients and providers. SIGNIFICANCE STATEMENT: This work provides a review of prior research related to phytocannabinoids, including therapeutic potential and known risks in the context of drug development within the United States. We also provide study design considerations for future cannabinoid drug development.

California Cannabis Research Briefing, April 2023: Meeting Summary.

On April 28, 2023, the University of California Office of the President, in partnership with the California Department of Cannabis Control (DCC), hosted the California Cannabis Research Briefing. The California Cannabis Research Briefing brought together researchers and state agencies/policymakers to discuss pertinent policy issues on cannabis within the state. Researchers across six different topic areas (environment, cannabis markets, social equity matters, public health, medicinal cannabis use, and public safety) provided brief explanations of their research and its policy implications. A moderated discussion with stakeholders followed these presentations. The goals of this event were to highlight research that can inform policy issues relevant to the state, and to discuss how research can be incorporated into the cannabis policy landscape.

Associations of U.S. state-level COVID-19 policies intensity with cannabis sharing behaviors in 2020.

BACKGROUND: Cannabis use before the COVID-19 pandemic for many involved sharing prepared cannabis for inhalation, practices that were less prevalent during the pandemic. State-level COVID-19 containment policies may have influenced this decrease. This study examined the extent to which the intensity of state-level COVID-19 policies were associated with individual-level cannabis sharing. Findings have the potential to guide harm reduction policies for future respiratory pandemics and seasonal respiratory virus waves. METHODS: This study used cross-sectional individual-level data from the COVID-19 Cannabis Study, an anonymous U.S.-based web survey on cannabis use disseminated during the early phase of the pandemic (Full sample N = 1,883). We combined individual-level data with state-level policy data from Kaiser Family Foundation's State COVID-19 Data and Policy Actions for three time-points from June to August 2020 that overlapped with the survey period. Cannabis sharing was dichotomized as any versus no sharing. We adapted a previously published coding framework to score the intensity of COVID-19 policies implemented in each U.S. state and averaged the policy score across the time period. We then used Poisson regression models to quantify the associations of the average state-level COVID-19 policy score with cannabis sharing during the pandemic. RESULTS: Participants (n = 925) reporting using inhalation as a mode for cannabis use were included in this analysis. Most respondents were male (64.1%), non-Hispanic White (54.3%), with a mean age of 33.7 years (SD 8.8). A large proportion (74.9%) reported sharing cannabis during the pandemic. Those who shared cannabis more commonly lived in states with a lower average policy score (16.7, IQR 12.3-21.5) compared to those who did not share (18.6, IQR 15.3-25.3). In adjusted models, the prevalence ratio of any cannabis sharing per every 5-unit increase in the average COVID-19 policy score was 0.97 (95% CI 0.93, 1.01). CONCLUSIONS: Fewer individuals shared cannabis in states with more intense COVID-19 containment policies compared to those in states with less intense policies. Individuals who use cannabis may be willing to make changes to their behavior and may further benefit from specific and directed public health messaging to avoid sharing during respiratory infection outbreaks.

Assessing evidence supporting cannabis harm reduction practices for adolescents at clinical high-risk for psychosis: a review and clinical implementation tool.

Cannabis use is consistently associated with both increased incidence of frank psychotic disorders and acute exacerbations of psychotic symptoms in healthy individuals and people with psychosis spectrum disorders. Although there is uncertainty around causality, cannabis use may be one of a few modifiable risk factors for conversion to psychotic disorders in individuals with Clinical High Risk for Psychosis (CHR-P) syndromes, characterized by functionally impairing and distressing subthreshold psychotic symptoms. To date, few recommendations beyond abstinence to reduce adverse psychiatric events associated with cannabis use have been made. This narrative review synthesizes existing scientific literature on cannabis' acute psychotomimetic effects and epidemiological associations with psychotic disorders in both CHR-P and healthy individuals to bridge the gap between scientific knowledge and practical mental health intervention. There is compelling evidence for cannabis acutely exacerbating psychotic symptoms in CHR-P, but its impact on conversion to psychotic disorder is unclear. Current evidence supports a harm reduction approach in reducing frequency of acute psychotic-like experiences, though whether such interventions decrease CHR-P individuals' risk of conversion to psychotic disorder remains unknown. Specific recommendations include reducing frequency of use, lowering delta-9-tetrahydrocannabinol content in favor of cannabidiol-only products, avoiding products with inconsistent potency like edibles, enhancing patient-provider communication about cannabis use and psychotic-like experiences, and utilizing a collaborative and individualized therapeutic approach. Despite uncertainty surrounding cannabis' causal association with psychotic disorders, cautious attempts to reduce acute psychosis risk may benefit CHR-P individuals uninterested in abstinence. Further research is needed to clarify practices associated with minimization of cannabis-related psychosis risk.

Marijuana and Cannabidiol Use Prevalence and Symptom Management Among Patients with Cancer.

Symptoms such as pain, nausea, and anxiety are common in individuals with cancer. Treatment of these issues is often challenging. Cannabis products may be helpful in reducing the severity of these symptoms. While some studies include data on the prevalence of cannabis use among patients with cancer, detailed data remain limited, and none have reported the prevalence of cannabidiol (CBD) use in this population. Adult patients with cancer attending eight clinics at a large, NCI-designated Comprehensive Cancer Center completed a detailed, cannabis-focused questionnaire between 2021 and 2022. Eligible participants were diagnosed with invasive cancer and treated in the past 12 months. Summary statistics were calculated to describe the sample regarding cannabis use. Approximately 15% (n = 142) of consented patients (n = 934) reported current cannabis use (defined as use within the past 12 months). Among which, 75% reported cannabis use in the past week. Among current cannabis users, 39% (n = 56; 6% overall) used CBD products. Current users reported using cannabis a median of 4.5 (interquartile range: 0.6­7.0) days/week, 2.0 (1.0­3.0) times per use/day, and for 3 years (0.8­30.0). Use patterns varied by route of administration. Patients reported moderate to high relief of symptoms with cannabis use. This study is the most detailed to date in terms of cannabis measurement and provides information about the current state of cannabis use in active cancer. Future studies should include complete assessments of cannabis product use, multiple recruitment sites, and diverse patient populations. SIGNIFICANCE: Clinicians should be aware that patients are using cannabis products and perceive symptom relief with its use.

Associations of U.S. state-level COVID-19 policies intensity with cannabis sharing behaviors in 2020.

Background: Cannabis use before the COVID-19 pandemic for many involved sharing prepared cannabis for inhalation, practices that were less prevalent during the pandemic. State-level COVID-19 containment policies may have influenced this decrease. This study examined the extent to which the intensity of state-level COVID-19 policies were associated with individual-level cannabis sharing. Findings have the potential to guide harm reduction policies for future respiratory pandemics and seasonal respiratory virus waves. Methods: This study used cross-sectional individual-level data from the COVID-19 Cannabis Study, an anonymous U.S.-based web survey on cannabis use disseminated during the early phase of the pandemic (Full sample N = 1,883). We combined individual-level data with state-level policy data from Kaiser Family Foundation's State COVID-19 Data and Policy Actions for three time-points from June to August 2020 that overlapped with the survey period. Cannabis sharing was dichotomized as any versus no sharing. We adapted a previously published coding framework to score the intensity of COVID-19 policies implemented in each U.S. state and averaged the policy score across the time period. We then used logistic regression models to quantify the associations of the average state-level COVID-19 policy score with cannabis sharing during the pandemic. Results: Participants (n = 975) reporting using inhalation as a mode for cannabis use were included in this analysis. Most respondents were male (64.1%), non-Hispanic White (54.3%), with a mean age of 33.7 years (SD 8.8). A large proportion (75.1%) reported sharing cannabis during the pandemic. Those who shared cannabis more commonly lived in states with a lower average policy score (15.3, IQR 11.3-19.0) compared to those who did not share (16.3, IQR 13.7-22.7). In adjusted models, the odds of any cannabis sharing per every 5-unit increase in the average COVID-19 policy score were 0.78 (95% CI 0.58, 1.04). Conclusions: Fewer individuals shared cannabis in states with more intense COVID-19 containment policies compared to those in states with less intense policies. Individuals who use cannabis may be willing to make changes to their behavior and may further benefit from specific and directed public health messaging to avoid sharing during respiratory infection outbreaks.

Kratom Alkaloids, Cannabinoids, and Chronic Pain: Basis of Potential Utility and Role in Therapy.

Introduction: Chronic neuropathic pain is as a severe detriment to overall quality of life for millions of Americans. Current pharmacological treatment options for chronic neuropathic pain are generally limited in efficacy and may pose serious adverse effects such as risk of abuse, nausea, dizziness, and cardiovascular events. Therefore, many individuals have resorted to methods of pharmacological self-treatment. This narrative review summarizes the existing literature on the utilization of two novel approaches for the treatment of chronic pain, cannabinoid constituents of Cannabis sativa and alkaloid constituents of Mitragyna speciosa (kratom), and speculates on the potential therapeutic benefits of co-administration of these two classes of compounds. Methods: We conducted a narrative review summarizing the primary motivations for use of both kratom and cannabis products based on epidemiological data and summarize the pre-clinical evidence supporting the application of both kratom alkaloids and cannabinoids for the treatment of chronic pain. Data collection was performed using the PubMed electronic database. The following word combinations were used: kratom and cannabis, kratom and pain, cannabis and pain, kratom and chronic pain, and cannabis and chronic pain. Results: Epidemiological evidence reports that the self-treatment of pain is a primary motivator for use of both kratom and cannabinoid products among adult Americans. Further evidence shows that use of cannabinoid products may precede kratom use, and that a subset of individuals concurrently uses both kratom and cannabinoid products. Despite its growing popularity as a form of self-treatment of pain, there remains an immense gap in knowledge of the therapeutic efficacy of kratom alkaloids for chronic pain in comparison to that of cannabis-based products, with only three pre-clinical studies having been conducted to date. Conclusion: There is sufficient epidemiological evidence to suggest that both kratom and cannabis products are used to self-treat pain, and that some individuals actively use both drugs, which may produce potential additive or synergistic therapeutic benefits that have not yet been characterized. Given the lack of pre-clinical investigation into the potential therapeutic benefits of kratom alkaloids against forms of chronic pain, further research is warranted to better understand its application as a treatment alternative.

Sex differences in the subjective and reinforcing effects of smoked cannabis.

Preclinical studies have shown sex-based differences in the reinforcing effects of cannabinoid 1 receptor agonists such as delta-9-tetrahydrocannabinol (THC). This study sought to test whether these sex differences translate to humans by assessing the subjective and reinforcing effects of smoked cannabis in male and female volunteers. We pooled data (n = 68; 55M, 13F) from two within-subject randomized controlled trials of healthy, ≥weekly cannabis users comparing the subjective and reinforcing effects of smoked active (~25 mg THC) versus placebo cannabis (0-mg THC). Subjective ratings of drug effects and mood were measured using visual analogue scales, and reinforcing effects were measured with a cannabis self-administration task. Sex-dependent outcomes were explored using generalized linear mixed models. Under active cannabis conditions, female participants reported greater reductions from baseline in cannabis craving and significantly higher cannabis-specific ratings of strength, liking, willingness to take again and good effect, compared with males (interaction p < 0.05). Placebo and active cannabis were self-administered by 22% and 36% of male participants, respectively, and by 15% and 54% of female participants, respectively. Receipt of active cannabis significantly increased likelihood of self-administration (p = 0.011), but a sex difference was not detected (p = 0.176). Although females were more sensitive to certain positive subjective effects of active cannabis, they were not more likely than males to self-administer it. These findings highlight the need to test sex differences as a primary objective in experimental studies and may shed light on accelerated trajectories from initiation to cannabis use disorder observed among women.

Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials.

Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB1-SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ9-tetrahydrocannabinol (THC) binding without modifying behavior per se. In mice and non-human primates, AEF0117 decreased cannabinoid self-administration and THC-related behavioral impairment without producing significant adverse effects. In single-ascending-dose (0.2 mg, 0.6 mg, 2 mg and 6 mg; n = 40) and multiple-ascending-dose (0.6 mg, 2 mg and 6 mg; n = 24) phase 1 trials, healthy volunteers were randomized to ascending-dose cohorts (n = 8 per cohort; 6:2 AEF0117 to placebo randomization). In both studies, AEF0117 was safe and well tolerated (primary outcome measurements). In a double-blind, placebo-controlled, crossover phase 2a trial, volunteers with CUD were randomized to two ascending-dose cohorts (0.06 mg, n = 14; 1 mg, n = 15). AEF0117 significantly reduced cannabis' positive subjective effects (primary outcome measurement, assessed by visual analog scales) by 19% (0.06 mg) and 38% (1 mg) compared to placebo (P < 0.04). AEF0117 (1 mg) also reduced cannabis self-administration (P < 0.05). In volunteers with CUD, AEF0117 was well tolerated and did not precipitate cannabis withdrawal. These data suggest that AEF0117 is a safe and potentially efficacious treatment for CUD.ClinicalTrials.gov identifiers: NCT03325595 , NCT03443895 and NCT03717272 .

Cannabis Use and Sharing Practices Among Sexual Minority and Heterosexual Individuals During the COVID-19 Pandemic.

Purpose: Cannabis behaviors during the COVID-19 pandemic among sexual minority (SM) individuals in the United States remain understudied. This study assessed the prevalence and correlates of cannabis use and cannabis sharing, a potential risk for COVID-19 transmission, among SM and heterosexual-identified individuals in the United States during the COVID-19 pandemic. Methods: This cross-sectional study used data from an anonymous, US-based web survey on cannabis-related behaviors from August to September 2020. Included participants reported past-year nonmedical cannabis use. Associations between frequency of cannabis use and sharing behaviors by sexual orientation were evaluated using logistic regression analysis. Results: Overall, 1112 respondents reported past-year cannabis use; mean age 33 years (standard deviation = 9.4), 66% male identified (n = 723), and 31% SM identified adults (n = 340). Increased cannabis use during the pandemic was similar among SM (24.7%; n = 84) and heterosexual (24.9%; n = 187) respondents. Any sharing during the pandemic was 81% for SM adults (n = 237) and 73% for heterosexual adults (n = 486). In the fully adjusted models, the odds of daily/weekly cannabis use and the odds of any cannabis sharing among SM respondents were 0.56 (95% confidence interval [CI] = 0.42-0.74) and 1.60 (95% CI = 1.13-2.26), respectively, compared with heterosexual respondents. Conclusions: SM respondents were less likely to use cannabis with high frequency during the pandemic but more likely to share cannabis compared with heterosexual respondents. Sharing cannabis was high overall, which may increase COVID-19 risk. Public health messaging around sharing may be important during COVID-19 surges and respiratory pandemics especially as cannabis becomes more widely available in the United States.

Adolescent Cannabis Misuse Scale: Longitudinal Associations with Substance Use, Mental Health, and Social Determinants of Health in Early Adulthood.

BACKGROUND: Some patterns of cannabis use may presage risk for long-term negative effects. We examined associations between a novel adolescent cannabis misuse scale and early-adult life course outcomes. METHODS: We performed a secondary data analysis of a cohort of Los Angeles, CA high school students from grade 9 through age 21. Participants reported baseline individual demographic and family characteristics at grade 9, adolescent cannabis misuse (8-items) and alcohol misuse (12-items) at grade 10, and outcomes at age 21. We used multivariable regression to model the associations of cannabis misuse scale score with problem substance use (defined as any of: 30-day illegal drug use, 30-day use of another's prescription to get high, hazardous drinking) and several secondary outcomes (behavioral, mental health, academic, social determinants of health), adjusting for covariates. Parallel analyses were conducted for alcohol misuse. RESULTS: The 1,148 participants (86% retention) were 47% male, 90% Latinx, 87% US born, and 40% native English speakers. Approximately 11.4% and 15.9% of participants reported at least one item on the cannabis and alcohol misuse scales, respectively. At age 21, approximately 6.7% of participants reported problem substance use, which was associated with both Cannabis and Alcohol Misuse Scales (OR 1.31, 95%CI[1.16, 1.49] and OR 1.33, 95%CI[1.18, 1.49], respectively). Both scales were similarly associated with outcomes in all four categories. CONCLUSIONS: The Adolescent Cannabis Misuse Scale is a promising tool for identifying early patterns of substance use that predict future negative outcomes and enabling early intervention at a critical period in youth development.

Changes in Immune-Related Biomarkers and Endocannabinoids as a Function of Frequency of Cannabis Use in People Living With and Without HIV.

Background: Cannabis use is common among people living with HIV (PLWH). Some observational studies of PLWH have linked cannabis use to lower immune markers; however, this is yet to be confirmed. In addition, whether HIV affects the endogenous cannabinoid system has not been studied. Our objective was to examine changes in immune-related biomarkers and endocannabinoids as a function of cannabis use frequency in people living with and without HIV. Materials and Methods: Data were obtained from a longitudinal study of men who have sex with men living in Los Angeles with, or at risk for, HIV. By design, half were PLWH. Those eligible for the parent study were willing and able to return for follow-up every 6 months. Those eligible for inclusion in this study reported varying levels of current cannabis use at follow-up. Specifically, one visit corresponded to a period of daily use and another to a period of infrequent use (weekly, monthly, or less than monthly). Banked serum from all eligible participants was analyzed for immune-related biomarkers, endocannabinoids, and paracannabinoids. Results: The analysis included 36 men, 19 of whom were PLWH. PLWH reported greater lifetime methamphetamine or amphetamine use (68% vs. 0%) and current cigarette use (55% vs. 20%) than people without HIV. Serum levels of HIV-related immune biomarkers including tumor necrosis factor receptor 2 (TNFR2; p=0.013) and CD27 (p=0.004) were greater in PLWH, alongside lower anandamide (AEA) (F1,34=5.337, p=0.027) and oleoylethanolamide (OEA) (F1,34=8.222, p=0.007) levels relative to people without HIV. Frequency of cannabis use did not impact the serum analytes in our study. Conclusions: Higher levels of TNFR2 and CD27 and lower levels of AEA and OEA in PLWH underscore the role of the TNF/TNFR superfamily in HIV, while highlighting a new role for the enzymatic activity of fatty acid amide hydrolase (the enzyme that hydrolyzes AEA and OEA) in HIV. Findings that cannabis frequency did not impact the immune phenotype may not generalize to other populations of PLWH. Additional work is required to further clarify the relationship between immune markers and endocannabinoids as a function of cannabis use frequency in PLWH. ClinicalTrials.gov ID: NCT01201083.

Shifts in medical cannabis use in Canada during the COVID-19 pandemic. / Changements observés au Canada dans la consommation de cannabis à des fins médicales pendant la pandémie de COVID-19.

INTRODUCTION: The COVID-19 pandemic has had widespread secondary negative health impacts including loss of material security and exacerbation of mental illness in at-risk populations. While increases in the nonmedical use of certain substances, including cannabis, have been observed in samples of the Canadian population, no research has documented COVID-concurrent shifts in medical cannabis use in Canada. METHODS: Data were derived from the 2021 Canadian Cannabis Patient Survey, an online survey administered in May 2021 to people authorized to use medical cannabis recruited from one of two Canadian licensed medical cannabis producers. McNemar tests assessed for changes in past 3-month medical cannabis frequency from before to during the pandemic. We explored correlates of increasing frequency of cannabis use since before the pandemic in bivariable and multivariable logistic models. RESULTS: In total, 2697 respondents (49.1% women) completed the survey. Daily medical cannabis use increased slightly but significantly from before the pandemic (83.2%) to during the pandemic (90.3% at time of survey; p < 0.001). Factors significantly associated with increasing frequency of medical cannabis use included female gender, younger age, pandemic-related job loss, primary cannabis use to manage mental health, prescription drug use and nonmedical cannabis use (p < 0.05). CONCLUSION: There were slight shifts towards higher frequency of medical cannabis use after the onset of the COVID-19 pandemic. While short- and long-term impacts of cannabis use on pandemic-related mental distress are unknown, clinicians working with patients who use medical cannabis should be aware of possible changes in use patterns during the pandemic.

Puff, Puff, Don't Pass: harm reduction for cannabis use during a viral respiratory pandemic.

BACKGROUND: Prior to the COVID-19 pandemic, cannabis use social practices often involved sharing prepared cannabis (joints/blunts/cigarettes) and cannabis-related paraphernalia. Previous studies have demonstrated that sharing paraphernalia for cannabis, tobacco, and crack cocaine is a risk factor for respiratory viral and bacterial infections. Although COVID-19 is a respiratory viral infection that spreads through droplets and airborne transmission, it is unclear if many individuals adopted harm reduction practices around sharing cannabis. This study: quantifies the prevalence of sharing prepared non-medical cannabis and cannabis-related paraphernalia reported before and during the pandemic; assesses changes in sharing of non-medical cannabis from before to during the pandemic; assess the association between frequency of non-medical cannabis use and sharing of cannabis during the pandemic; and describes how respondents obtained their cannabis and the reasons for changing their cannabis use during the pandemic to explain differences in sharing patterns. METHODS: This cross-sectional study used data collected from an anonymous, US-based web survey on cannabis-related behaviors from August to September 2020 (n = 1833). Participants were included if they reported using a mode of inhalation for non-medical cannabis consumption. We calculated proportional changes in sharing cannabis before/during the COVID-19 pandemic. Associations between frequency of cannabis use and cannabis sharing during the COVID-19 pandemic were assessed using logistic regression analysis. RESULTS: Overall, 1,112 participants reported non-medical cannabis use; 925 (83.2%) reported a mode of cannabis inhalation. More respondents reported no sharing during (24.9%) than before the pandemic (12.4%; p < 0.01); less respondents shared most of the time (19.5% before; 11.2% during; p < 0.01) and always during the pandemic (5.2% before; 3.1% during; p < 0.01). After adjusting for covariates, the odds of any sharing during the pandemic for those who reported ≥ weekly cannabis use was 0.53 (95% CI 0.38, 0.75) compared to those who reported ≤ monthly. CONCLUSIONS: Sharing of prepared cannabis and cannabis-related paraphernalia decreased during the COVID-19 pandemic compared to before the pandemic. This finding suggests potential risk mitigation strategies taken by participants for COVID-19 prevention either directly through behavior change or indirectly through adherence to COVID-19 prevention recommendations. Harm reduction messaging around sharing of cannabis during surges of COVID-19 or other respiratory infections may provide benefit in reducing infection among those who use cannabis, especially as cannabis use in the USA continues to increase.