Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions.

Background: One in five individuals live with chronic pain globally, which often co-occurs with sleep problems, anxiety, depression, and substance use disorders. Although these conditions are commonly managed with cannabinoid-based medicines (CBM), health care providers report lack of information on the risks, benefits, and appropriate use of CBM for therapeutic purposes. Aims: We present these clinical practice guidelines to help clinicians and patients navigate appropriate CBM use in the management of chronic pain and co-occurring conditions. Materials and Methods: We conducted a systematic review of studies investigating the use of CBM for the treatment of chronic pain. Articles were dually reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical recommendations were developed based on available evidence from the review. Values and preferences and practical tips have also been provided to support clinical application. The GRADE system was used to rate the strength of recommendations and quality of evidence. Results: From our literature search, 70 articles met inclusion criteria and were utilized in guideline development, including 19 systematic reviews and 51 original research studies. Research typically demonstrates moderate benefit of CBM in chronic pain management. There is also evidence for efficacy of CBM in the management of comorbidities, including sleep problems, anxiety, appetite suppression, and for managing symptoms in some chronic conditions associated with pain including HIV, multiple sclerosis, fibromyalgia, and arthritis. Conclusions: All patients considering CBM should be educated on risks and adverse events. Patients and clinicians should work collaboratively to identify appropriate dosing, titration, and administration routes for each individual. Systematic Review Registration: PROSPERO no. 135886.

Stigma-related barriers to medical cannabis as harm reduction for substance use disorder: Obstacles and opportunities for improvement.

Emerging evidence on substituting cannabis for more harmful drugs has led to cannabis becoming a novel harm-reduction strategy for combating the current drug poisoning crisis. However, the authorization of medical cannabis as part of a harm-reduction approach and recovery strategy has significant implementation barriers rooted in longstanding stigma towards cannabis. Through a multi-discipline collaboration of Canadian clinicians and academic researchers, we highlighted stigma barriers and opportunities to address these barriers to elicit improved delivery of medical cannabis as a harm-reduction therapy within existing therapeutic frameworks. Evidence from existing literature and real-world experiences converged on three key themes related to stigma barriers: (1) Lack of medical cannabis education within the healthcare community, (2) lack of consensus and coordination among harm-reduction services and (3) access to medical cannabis. We highlight potential solutions to these issues, including improved healthcare education, better coordination between care teams and suggestions for improving access. Through this discussion, we hope to contribute to reducing the stigma around using medical cannabis as a harm-reduction strategy for individuals with a substance use disorder and consider new perspectives in policy development surrounding recovery services.

Cannabis use to manage stimulant cravings among people who use unregulated drugs.

BACKGROUND: We sought to analyze the association between cannabis use to manage stimulant cravings and self-reported changes in stimulant use among structurally marginalized people who use unregulated drugs (PWUD). METHODS: The data for this secondary analysis was collected from a cross-sectional questionnaire administered to people who concurrently use cannabis and unregulated stimulants in Vancouver, Canada. We used logistic regression models to analyze the association between cannabis use to manage stimulant cravings and self-reported changes in the frequency of stimulant use. RESULTS: In total, 297 individuals were included in the present study. Cannabis use to manage stimulant cravings was reported by 134 (45.1 %) participants and 104 (77.6 %) of these participants reported decreasing their stimulant use during periods of cannabis use. In the multivariable logistic regression analysis, cannabis use to manage stimulant cravings (adjusted Odds Ratio [aOR] = 0.24, 95 % confidence interval [CI]: 0.10, 0.56) was significantly associated with self-reported reductions in stimulant use. In the sub-analyses, cannabis use to manage stimulant cravings was significantly associated with reduced stimulant use among people who used crystal methamphetamine daily (aOR = 0.08, 95 % CI: 0.02-0.37) and was not significantly associated with reduced stimulant use among people who used crack/cocaine daily (aOR = 0.33, 95 % CI: 0.04-2.86). CONCLUSIONS: These findings indicate that cannabis use to manage stimulant cravings is a common harm reduction strategy and suggest that this may be an effective strategy to reduce stimulant use among some PWUD.

Therapeutic Potential of Psilocybin for Treating Psychological Distress among Survivors of Adverse Childhood Experiences: Evidence on Acceptability and Potential Efficacy of Psilocybin Use.

Survivors of adverse childhood experience are at elevated risk for psychological distress. In recent years, renewed interest in psychedelic medicine has highlighted the therapeutic potential of psilocybin for those who have experienced childhood adversity. However, recreational psilocybin use remains illegal and access to approved therapies is difficult. Such use provides an opportunity to explore the therapeutic potential of psilocybin for psychological distress among people with adverse childhood experiences. Therefore, we conducted an online survey to assess interest in, acceptability of, and experiences with psilocybin. We further explored whether the association between Adverse Childhood Experiences Questionnaire (ACEQ) scores and psychological distress was lower among those who had used psilocybin in the past three months. Results showed high levels of interest in and acceptability of psilocybin that did not differ across ACEQ scores. Results also showed that the effect of adverse childhood experiences on psychological distress was lower for people who had recently used psilocybin (p = .019). Taken together, these findings suggest that psilocybin therapy may be potentially acceptable and may feasibly help in supporting survivors of adverse childhood experiences with particularly strong benefits to those with more severe childhood adversity.

Physician perspectives on chronic pain management: barriers and the use of eHealth in the COVID-19 era.

BACKGROUND: Chronic pain is a highly prevalent and disabling condition which is often undertreated and poorly managed in the community. The emergence of COVID-19 has further complicated pain care, with an increased prevalence of chronic pain and mental health comorbidities, and burnout among physicians. While the pandemic has led to a dramatic increase in virtual health care visits, the uptake of a broader range of eHealth technologies remains unclear. The present study sought to better understand physicians' current needs and barriers in providing effective pain care within the context of COVID-19, as well as gauge current use, interest, and ongoing barriers to eHealth implementation. METHODS: A total of 100 practicing physicians in British Columbia, Canada, completed a brief online survey. RESULTS: The sample was comprised of physicians practicing in rural and urban areas (rural = 48%, urban = 42%; both = 10%), with the majority (72%) working in family practice. The most prominent perceived barriers to providing chronic pain care were a lack of interdisciplinary treatment and allied health care for patients, challenges related to opioid prescribing and management, and a lack of time to manage the complexities of chronic pain. Moreover, despite expressing considerable interest in eHealth for chronic pain management (82%), low adoption rates were observed for several technologies. Specifically, only a small percentage of the sample reported using eHealth for the collection of intake data (21%), patient-reported outcomes (14%), and remote patient monitoring (26%). The most common perceived barriers to implementation were cost, complexity, and unfamiliarity with available options. CONCLUSIONS: Findings provide insight into physicians' ongoing needs and barriers in providing effective pain management during the COVID-19 pandemic. Despite the potential for eHealth technologies to help address barriers in pain care, and strong interest from physicians, enhanced useability, education and training, and funding are likely required to achieve successful implementation of a broader range of eHealth technologies in the future.

"The Box Has Become an Indispensable Part of My Life": A Case Study of Victoria Cannabis Buyers Club and its Consumption Space.

Community-based models of cannabis cultivation, distribution, and consumption-such as cannabis clubs-have been documented across Europe, North America, South America, and New Zealand since the 1990s. For the most part, these models have a history of operating outside existing legislation and regulations. Jurisdictions that have legalized cannabis have approached community-based models in opposite ways (eliminate vs. regulate). Canada legalizing cannabis has resulted in more stringent enforcement and concerted efforts to close these models despite documented health and social benefits. This paper presents a case study of the Victoria Cannabis Buyers Club (VCBC) and its consumption space-The Box. We conducted a survey of VCBC members to explore four domains: demographics, cannabis consumption, access to and use of The Box, and the impact of its temporary closure due to COVID-19. From the survey data (n = 104), descriptive statistics were generated and three conceptual avenues were identified. The majority of respondents were 40 years old and older and identified as White (European descent) cisgendered men and women. The majority reported an income of $40,000 or less and a housing status that prevented them from smoking. Close to 75% of our sample consumed cannabis multidaily for therapeutic purposes primarily, but also for a mix of recreation, social, spiritual, and traditional healing purposes. Smoking was the preferred mode of consumption. Respondents accessed The Box daily or weekly. Reasons and benefits for using The Box fell into three categories: public health, harm reduction, and wellness perspectives. Conceptually, we found that The Box acted as a therapeutic space and offered a much-needed consumption space for smokers. We also identified a need to unpack the concept of safety. Overall, the survey reinforces the need for an equity-informed approach to community-based models and cannabis consumption spaces in Canada.

A small clinical trial of vaporized cannabis for PTSD: suggestive results and directions for future study.

The last few decades have seen increasing interest in the use of cannabis for post-traumatic stress disorder (PTSD). Recent attempts to evaluate the clinical efficacy of cannabis for PTSD were inconclusive and generalizability was limited by undesirable features of the study drug. The present clinical trial evaluated the effects of a commercially available chemovar that was delivered by vaporization. The study was designed as a randomized placebo-controlled cross-over study with three conditions; however, only five individuals completed the trial, and analysis of the placebo effect was not possible. Results identified positive changes consistent with medium-sized within-subject effects for cannabis in the treatment of PTSD. Positive trending results and high patient need mandate future studies of cannabis for the treatment of PTSD.

A Pilot Study Comparing a Community of Practice Program with and without Concurrent Ketamine-Assisted Therapy.

The prevalence of depression, anxiety, and post-traumatic stress disorder (PTSD) has increased among healthcare providers, while the effectiveness of conventional treatments remains limited. Ketamine-assisted therapy offers a promising alternative; however, few have integrated ketamine with a group-based therapeutic modality. We report a retrospective, secondary analysis of a 12-week pilot of a Community of Practice (CoP) oriented group therapy program with optional, adjunct ketamine for depression, anxiety, and PTSD in a sample of 57 healthcare providers. All participants moved through the treatment as one group, with 38 electing to also receive three adjunct ketamine sessions in addition to the weekly CoP. Symptoms were assessed at baseline and pilot completion with the PHQ-9 for depression, GAD-7 for anxiety, and PCL-5 for PTSD. We observed significant reductions in the mean change among all participants, suggesting that benefit was derived from the CoP component, with or without ketamine as an adjunct. PHQ-9 scores decreased by 6.79 (95% CI: 5.09-8.49, p < .001), GAD-7 scores decreased by 5.57 (CI: 4.12-7.00, p < .001), and PCL-5 scores decreased by 14.83 (CI: 10.27-19.38, p < .001). Reductions were larger, but statistically nonsignificant, among those receiving ketamine. Further research is required to assess the impact of ketamine as an adjunct in group-based therapies.

Why a distinct medical stream is necessary to support patients using cannabis for medical purposes.

BACKGROUND: Since 2001, Canadians have been able to obtain cannabis for medical purposes, initially through the Access to Cannabis for Medical Purposes Regulations (ACMPR). The Cannabis Act (Bill C-45) came into force on October 17, 2018, replacing the ACMPR. The Cannabis Act enables Canadians to possess cannabis purchased from a licensed retailer without authorization for either medical or nonmedical purposes. The Cannabis Act is currently the guiding legislation which governs both medical and nonmedical access. The Cannabis Act contains some improvements for patients but is essentially the same as its previous legislation. Beginning in October 2022, the federal government is conducting a review of the Cannabis Act and is questioning whether a distinct medical cannabis stream is still required, given the ease of access to cannabis and cannabis products. Although there is overlap in the reasons for medical and recreational cannabis use, the distinct legislation of medical versus recreational use of cannabis in Canada may be under threat. MAIN BODY: A large segment of the medical, academic, research, and lay communities agree that there is a need for distinct medical and recreational cannabis streams. Perhaps most importantly, separation of these streams is necessary to ensure that both medical cannabis patients and healthcare providers receive the required support needed to optimize benefits while minimizing risks associated with medical cannabis use. Preservation of distinct medical and recreational streams can help to ensure that needs of different stakeholders are met. For example, patients require guidance in the form of assessing the appropriateness of cannabis use, selection of appropriate products and dosage forms, dosing titration, screening for drug interactions, and safety monitoring. Healthcare providers require access to undergraduate and continuing health education as well as support from their professional organizations to ensure medical cannabis is appropriately prescribed. Although there are challenges in conducing research, as motives for cannabis use frequently straddle boundaries between medical versus recreational cannabis use, maintenance of a distinct medical stream is also necessary to ensure adequate supply of cannabis products appropriate for medical use, to reduce stigma associated with cannabis in both patients and providers, to help enable reimbursement for patients, to facilitate removal of taxation on cannabis used for medical purposes, and to promote research on all aspects of medical cannabis. CONCLUSION: Cannabis products for medical and recreational purposes have different objectives and needs, requiring different methods of distribution, access, and monitoring. HCPs, patients, and the commercial cannabis industry would serve Canadians well to continue to advocate to policy makers to ensure the continued existence of two distinct streams and must strive to make ongoing improvements to the current programs.

Cannabis use to manage opioid cravings among people who use unregulated opioids during a drug toxicity crisis.

BACKGROUND: Accumulating evidence has indicated that cannabis substitution is often used as a harm reduction strategy among people who use unregulated opioids (PWUO) and people living with chronic pain. We sought to investigate the association between cannabis use to manage opioid cravings and self-reported changes in opioid use among structurally marginalized PWUO. METHODS: The data were collected from a cross-sectional questionnaire administered to PWUO in Vancouver, Canada. Binary logistic regression was used to analyze the association between cannabis use to manage opioid cravings and self-reported changes in unregulated opioid use. RESULTS: A total of 205 people who use cannabis and opioids were enrolled in the present study from December 2019 to November 2021. Cannabis use to manage opioid cravings was reported by 118 (57.6%) participants. In the multivariable analysis, cannabis use to manage opioid cravings (adjusted Odds Ratio [aOR] = 2.13, 95% confidence interval [CI]: 1.07, 4.27) was significantly associated with self-reported reductions in opioid use. In the sub-analyses of pain, cannabis use to manage opioid cravings was only associated with self-assessed reductions in opioid use among people living with moderate to severe pain (aOR = 4.44, 95% CI: 1.52, 12.97). In the sub-analyses of males and females, cannabis use to manage opioid cravings was only associated with self-assessed reductions in opioid use among females (aOR = 8.19, 95% CI: 1.20, 55.81). CONCLUSIONS: These findings indicate that cannabis use to manage opioid cravings is a prevalent motivation for cannabis use among PWUO and is associated with self-assessed reductions in opioid use during periods of cannabis use. Increasing the accessibility of cannabis products for therapeutic use may be a useful supplementary strategy to mitigate exposure to unregulated opioids and associated harm during the ongoing drug toxicity crisis.

Cannabidiol as a Harm Reduction Strategy for People Who Use Drugs: A Rapid Review.

OBJECTIVE: The drug poisoning crisis throughout North America necessitates novel harm reduction approaches. Emerging evidence suggests that cannabidiol (CBD) may have some utility as a harm reduction modality for those with problematic substance use. This rapid review aimed to synthesize available evidence on CBD as a potential harm reduction tool for people who use drugs while providing clinical and research insights. METHOD: A systematic search in EMBASE, MEDLINE, CENTRAL, and CINAHL was completed in July 2022. For inclusion, studies had to meet the following criteria: (1) drawn from an adult population of people who use drugs; (2) investigates CBD as an intervention for problematic substance use or harm reduction-related outcomes; (3) be published after the year 2000 and in English; and (4) be primary research or a review article. A narrative synthesis was used to group outcomes relevant to harm reduction and provide clinical and research insights. RESULTS: We screened 3,134 records, of which 27 studies (5 randomized trials) were included. The evidence remains limited, but available studies support the potential utility of CBD to reduce drug-induced craving and anxiety in opioid use disorder. There were low-quality studies suggesting that CBD may improve mood and general well-being of people who use drugs. Evidence suggests that CBD monotherapy may not be an adequate harm reduction strategy for problematic substance use but rather an adjunct to the standard of care. CONCLUSION: Low-quality evidence suggests that CBD may reduce drug cravings and other addiction-related symptoms and that CBD may have utility as an adjunct harm reduction strategy for people who use drugs. However, there is a significant need for more research that accurately reflects CBD dosing and administration regimens used in a real-world context.

Safety and tolerability of intramuscular and sublingual ketamine for psychiatric treatment in the Roots To Thrive ketamine-assisted therapy program: a retrospective chart review.

Background: In the last few years, ketamine is becoming increasingly common in the treatment of mental health conditions, but there is a lack of safety data informing intramuscular and sublingual dosing in a community-focused group psychotherapy setting. The Roots To Thrive ketamine-assisted therapy (RTT-KaT) program is a unique 12-week RTT-KaT program with 12 community of practice (a form of group therapy) sessions and three ketamine medicine sessions. Objectives: This study reports on adverse effects of intramuscular and sublingual ketamine dosing in a community group psychotherapy setting among 128 participants across four cohorts. Design: Retrospective chart review. Methods: A chart review of the RTT-KaT Program was performed retrospectively on four cohorts (n = 128) that participated in 448 sessions running between September 2020 and December 2021. Baseline characteristics and adverse events were captured including medication administration before, during, and after RTT-KaT sessions. Analyses by session and by individual were conducted. Chi-square test with Yates' continuity correction was used to assess side effects in subgroups from ketamine administration. Results: RTT-KaT was well tolerated with none of the 128 participants dropping out of the program. Primarily, of the 448 sessions, 49.16% had elevated blood pressures post-KaT session by session. In terms of other adverse effects, 12.05% of participant-sessions experienced nausea, 2.52% had an episode of vomiting, 3.35% had a headache, and seven participant-sessions experienced dizziness. Analysis by individual revealed congruent findings. Conclusion: These findings suggest good safety and tolerability for RTT-KaT among individuals seeking treatment for mental health issues. The majority of participants did not experience adverse reactions and the adverse events that were recorded involved transient symptoms that were resolved with rest and/or medications. The group therapy model described provides a comprehensive approach and presents a promising model for operating a KaT program in a community setting.

Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions

One in five individuals live with chronic pain globally, which often co-occurs with sleep problems, anxiety, depression, and substance use disorders. Although these conditions are commonly managed with cannabinoid-based medicines (CBM), health care providers report lack of information on the risks, benefits, and appropriate use of CBM for therapeutic purposes. Aims: We present these clinical practice guidelines to help clinicians and patients navigate appropriate CBM use in the management of chronic pain and co-occurring conditions. Materials and Methods: We conducted a systematic review of studies investigating the use of CBM for the treatment of chronic pain. Articles were dually reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical recommendations were developed based on available evidence from the review. Values and preferences and practical tips have also been provided to support clinical application. The GRADE system was used to rate the strength of recommendations and quality of evidence. Results: From our literature search, 70 articles met inclusion criteria and were utilized in guideline development, including 19 systematic reviews and 51 original research studies. Research typically demonstrates moderate benefit of CBM in chronic pain management. There is also evidence for efficacy of CBM in the management of comorbidities, including sleep problems, anxiety, appetite suppression, and for managing symptoms in some chronic conditions associated with pain including HIV, multiple sclerosis, fibromyalgia, and arthritis. Conclusions: All patients considering CBM should be educated on risks and adverse events. Patients and clinicians should work collaboratively to identify appropriate dosing, titration, and administration routes for each individual.

Correlations of kratom (Mitragyna speciosa Korth.) use behavior and psychiatric conditions from a cross-sectional survey.

Kratom (Mitragyna speciosa Korth.) use has increased substantially over the past decade outside of its indigenous regions, especially for the self-treatment of psychiatric conditions. An anonymous, cross-sectional, online survey was completed by 4,945 people who use kratom (PWUK) between July 2019 and July 2020. A total of 2,296 respondents completed an extended survey that included clinical scales for measuring attention deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), depressive and anxiety disorders. PWUK and met criteria for ADHD, PTSD, depressive or anxiety disorders were primarily middle-aged (31-50 years), employed, college-level educated, and reported greater concurrent or prior use of kratom with cannabis, cannabidiol, and benzodiazepines. For all psychiatric conditions, PWUK reported decreased depressive and anxious moods than before kratom use. Based on this self-report study, observational and other clinical studies are warranted for kratom. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

Physician Communication and Perceived Stigma in Prenatal Cannabis Use.

Cannabis has long been widely used throughout the prenatal period. However, motives for prenatal cannabis use (PCU) have not been comprehensively examined. Stigmatization has been identified as a barrier to therapeutic cannabis use and related physician communication. Such stigma may be particularly salient in the context of PCU. One hundred and three women who reported current or past pregnancy were recruited online. Participants completed a survey querying prenatal experiences, substance use, and attitudes toward PCU. PCU was reported by 35 (34%) respondents. Treating nausea and vomiting of pregnancy was the most frequently reported reason for PCU (89%), and 24 (69%) reported substituting cannabis for pharmaceutical drugs. Sixty-two percent of PCU participants and 31% of non-PCU participants indicated discomfort discussing PCU with their physician, and 74% of PCU participants and 27% of non-PCU participants indicated they would not disclose PCU to their physician if it occurred in future pregnancies. Our findings suggest that PCU may reflect primarily therapeutic motives of relieving symptoms of morning sickness, nausea, low appetite, pain, and substituting for other prescription medications. Respondents reported discomfort discussing PCU with physicians, which was more pronounced among respondents with lived experience of PCU. Findings suggest PCU might best be evaluated within a therapeutic framework and highlight the importance of efforts to enhance patient-caregiver communication regarding PCU.

The Naturalistic Cannabis Administration Protocol (NCAP): A Proof-of-Concept Study.

Lab-based studies examining the effects of cannabis administration on human behavior compromise ecological validity due to the influence of set and setting. Contextual factors of clinical settings have long been recognized as producing measurable changes in physiology, emotionality, and cognition. Among people who use drugs, these settings may be associated with higher levels of perceived stigma and stereotype threat which may meaningfully confound the effects of cannabis on outcomes of interest. Recent liberalization of cannabis regulation may allow novel and more ecologically valid approaches to assessing the acute effects of cannabis. The Naturalistic Cannabis Administration Protocol (NCAP) is a novel paradigm for the study of acute cannabis effects in an ecologically valid manner. Two independent studies demonstrated the safety and feasibility of the NCAP. Participants (N= 79; Mage = 25.44, SD = 5.67) self-administered the cannabis of their choice in their home and then (Study 1; n= 47) engaged in a leisure activity or (Study 2; n= 32) underwent cognitive assessment remotely via videoconference following cannabis administration. The NCAP was well tolerated across samples with no reported adverse events. These findings provide a rationale for the adoption of the NCAP to reduce research barriers and develop our research capabilities to fit the landscape of cannabis use today.

Psilocybin microdosers demonstrate greater observed improvements in mood and mental health at one month relative to non-microdosing controls.

Psilocybin microdosing involves repeated self-administration of mushrooms containing psilocybin at doses small enough to not impact regular functioning. Microdose practices are diverse and include combining psilocybin with substances such as lion's mane mushrooms (Hericium erinaceus; HE) and niacin (vitamin-B3). Public uptake of microdosing has outpaced evidence, mandating further prospective research. Using a naturalistic, observational design, we followed psilocybin microdosers (n = 953) and non-microdosing comparators (n = 180) for approximately 30 days and identified small- to medium-sized improvements in mood and mental health that were generally consistent across gender, age and presence of mental health concerns, as we all as improvements in psychomotor performance that were specific to older adults. Supplementary analyses indicated that combining psilocybin with HE and B3 did not impact changes in mood and mental health. However, among older microdosers combining psilocybin, HE and B3 was associated with psychomotor improvements relative to psilocybin alone and psilocybin and HE. Our findings of mood and mental health improvements associated with psilocybin microdosing add to previous studies of psychedelic microdosing by using a comparator group and by examining the consistency of effects across age, gender, and mental health. Findings regarding the combination of psilocybin, HE and B3 are novel and highlight the need for further research to confirm and elucidate these apparent effects.