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.

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 .

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.

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.

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.

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.

Smoked cannabis reduces peak cocaine plasma levels and subjective effects in a controlled drug administration study of polysubstance use in men.

BACKGROUND: Despite the high prevalence of polysubstance use, outcomes and potential risks associated with common drug combinations are not well characterized. Many individuals who use cocaine also use cannabis, yet little is known about how interactions between the two drugs might contribute to continued co-use. METHODS: The aim of this double-blind, placebo-controlled study was to determine the physiological and subjective effects of smoked cannabis with smoked cocaine, to identify variables that may contribute to the continued use of this drug combination. Healthy, non-treatment seeking volunteers who reported smoking both cocaine and cannabis (N = 9, all males) completed a 13-day inpatient protocol. On session days, cannabis [0.0 or 5.6 % tetrahydrocannabinol (THC)] was administered 28 min prior to cocaine (0, 12, or 25 mg). Dependent measures included pharmacokinetic assessment of THC and cocaine and their respective metabolites, in addition to subjective and cardiovascular effects. RESULTS: Active cannabis (5.6 % THC) increased plasma levels of THC and the metabolite 11-nor-9-carboxy-Δ9-THC (THCCOOH), as well as subjective ratings of cannabis effects and heart rate relative to inactive cannabis. Cocaine dose-dependently increased plasma cocaine and metabolites and subjective ratings of cocaine effects. Active cannabis pre-treatment decreased plasma levels of cocaine and metabolites. Furthermore, active cannabis attenuated cocaine-related reductions in 'Hunger' and 'Calm.' CONCLUSIONS: Cannabis pre-treatment altered the subjective experience of smoked cocaine and reduced peak plasma levels of cocaine. Future studies should explore additional doses of each drug and whether these changes also impact cocaine's reinforcing effects.

Methadone Dose, Cannabis Use, and Treatment Retention: Findings From a Community-based Sample of People Who Use Unregulated Drugs.

OBJECTIVES: Lower daily methadone dose is negatively associated with retention in methadone maintenance treatment (MMT). Cannabis use during MMT is common, with many patients reporting its use for opioid withdrawal mitigation. We sought to test whether the association between lower MMT dose and treatment retention differs by concurrent high-frequency cannabis use in a community sample of people on MMT. METHODS: We obtained data from participants initiating MMT in 2 community-recruited prospective cohorts of people who use drugs in Vancouver, Canada. We built multivariable Cox frailty models to estimate the relationships between MMT dose (<90 mg/d vs ≥90 mg/d) and time to treatment discontinuation. We included an interaction term to test whether high-frequency (≥daily) cannabis use modified the measured effect of lower treatment dose on treatment retention. RESULTS: Between December 2005 and December 2018, 829 participants (54.1%) initiated at least 1 MMT episode and were included in the analysis. Lower MMT dose was strongly positively associated with treatment discontinuation regardless of concurrent high-frequency cannabis use (interaction P > 0.05). Structural factors including homelessness and incarceration were significantly and positively associated with treatment discontinuation. CONCLUSIONS: Although we previously found the magnitude and strength of the relationship between lower MMT dose and high-frequency unregulated opioid use to be tempered during high-frequency cannabis use periods, this effect measure modification does not appear to translate to time retained in treatment. Cannabis-based interventions to promote retention in MMT are unlikely to produce long-term benefit without addressing external factors that place MMT patients at increased risk of treatment discontinuation.

The Cannabis-Dependent Relationship Between Methadone Treatment Dose and Illicit Opioid Use in a Community-Based Cohort of People Who Use Drugs.

Background: Methadone maintenance treatment (MMT) is an effective treatment for opioid use disorder. However, subtherapeutic dosing may lead to continued opioid use by failing to suppress opioid withdrawal and craving. Preclinical and pilot experimental research suggests that cannabinoids may reduce opioid withdrawal and craving. We sought to test whether the association between low methadone dose and illicit opioid use differs according to concurrent cannabis use patterns. Methods: Data for this study were derived from two community-recruited cohorts of people (≥18 years old) who use illicit drugs in Vancouver, Canada. We used generalized estimating equations to estimate the adjusted association between lower daily MMT dose (<90 mg/day) and daily illicit opioid use, testing for interaction between dose and daily cannabis use. Results: Between December 2005 and December 2018, 1389 participants reported MMT enrolment and were included in the study. We observed a significant interaction (p<0.01) between daily cannabis and lower MMT dose on concurrent daily illicit opioid use: lower MMT doses increased the odds of daily illicit opioid use by 86% (adjusted odds ratio [AOR]=1.86, 95% confidence interval [CI]=1.61-2.16) during periods of no or low-frequency cannabis use and by 30% during periods of daily cannabis use (AOR=1.30, 95% CI=1.01-1.67). Discussion: This study provides preliminary observational evidence that cannabis may mitigate some of the negative effects of subtherapeutic MMT dosing, guiding future clinical investigations into the safety and efficacy of cannabis and cannabinoids as adjunct treatment for MMT.

Selective Changes in Medical Cannabis Use Early in the COVID-19 Pandemic: Findings from a Web-Based Sample of Adults in the United States.

Background: The COVID-19 pandemic has had widespread impacts on mental health and substance use. While increases in nonmedical cannabis use during COVID-19 have been documented among people who use cannabis across a diversity of settings, changes in specific medical applications of cannabis during the COVID-19 pandemic have not been characterized. We sought to examine changes in the prevalence, frequency, and mode of use of medical cannabis for a range of commonly treated conditions and symptoms during COVID-19. Methods: Data were obtained from an online survey of a sample of adults in the United States who use cannabis (n=1886), administered in September 2020. This study was restricted to participants who self-reported past-year medical cannabis use (n=598). Using data reported in a retrospective (pre-COVID) and current assessment period, we examined changes in cannabis use prevalence, frequency, and inhalation as the primary mode of administration for 11 commonly treated conditions. Results: There were slight but statistically significant increases in weekly (from 21.4% to 23.4%) and daily (from 16.2% to 20.7%) self-reported medical cannabis use during COVID-19 (p<0.001). Anxiety was the only specific therapeutic purpose for which daily cannabis use increased statistically significantly during COVID-19 (18.5% to 25.4%; p=0.004). In multivariable logistic regression, the odds of increasing cannabis use for anxiety during COVID-19 were statistically significantly higher for women, respondents from Western states, and states with legal medical and nonmedical cannabis. Discussion: We detected slight shifts toward higher frequencies of medical cannabis use during COVID-19. Disaggregated by therapeutic indication, daily cannabis use to manage anxiety increased during the pandemic. There is a need to assess whether changes in cannabis use that coincided with the pandemic will be sustained over time, and how these changes are connected to mental health outcomes, particularly among women.

Changes in secondary substance use after the onset of the COVID-19 pandemic among people who use cannabis: Findings from a web-based sample of adults in the United States.

The coronavirus disease 2019 (COVID-19) pandemic has had widespread impacts on mental health and substance use. Increases in cannabis use have been documented in the United States, but little is known about how other substance use has changed among people who use cannabis. We sought to examine changes in alcohol, tobacco, opioid, and stimulant use during COVID-19 and explore how these changes relate to patterns of cannabis use. Data were obtained from a web-based survey of adults in the United States who use cannabis (n = 1,471) administered in September 2020. Using data reported in retrospective (prepandemic) and time-of-survey assessment periods, we explored changes in the prevalence of regular (≥ weekly) alcohol, tobacco, opioid, and stimulant use during COVID-19 among respondents who used medical and nonmedical cannabis. We used modified Poisson regression to examine cannabis-related correlates of increasing or decreasing secondary substance use during the pandemic. There was a slight but significant increase in ≥weekly alcohol use in the medical use group only (41.4%-47.0%, p = .034). ≥ Weekly tobacco, opioid, and stimulant use did not change significantly. Pandemic-concurrent shifts in secondary substance use depended on interacting cannabis-related factors including medical cannabis use, prepandemic cannabis frequency, and pandemic-concurrent frequency changes. For example, ≥ weekly prepandemic cannabis use was significantly and positively associated with decreasing opioid use frequency among the medical cannabis use group only. Assessments of the pandemic's effects on substance use should consider relationships between cannabis and other substances, which may differ according to cannabis-specific behaviors, motives, and contexts of use. (PsycInfo Database Record (c) 2023 APA, all rights reserved).