Cannabis and Cannabinoids in Adults With Cancer: ASCO Guideline.

PURPOSE: To guide clinicians, adults with cancer, caregivers, researchers, and oncology institutions on the medical use of cannabis and cannabinoids, including synthetic cannabinoids and herbal cannabis derivatives; single, purified cannabinoids; combinations of cannabis ingredients; and full-spectrum cannabis. METHODS: A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and cohort studies on the efficacy and safety of cannabis and cannabinoids when used by adults with cancer. Outcomes of interest included antineoplastic effects, cancer treatment toxicity, symptoms, and quality of life. PubMed and the Cochrane Library were searched from database inception to January 27, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: The evidence base consisted of 13 systematic reviews and five additional primary studies (four RCTs and one cohort study). The certainty of evidence for most outcomes was low or very low. RECOMMENDATIONS: Cannabis and/or cannabinoid access and use by adults with cancer has outpaced the science supporting their clinical use. This guideline provides strategies for open, nonjudgmental communication between clinicians and adults with cancer about the use of cannabis and/or cannabinoids. Clinicians should recommend against using cannabis or cannabinoids as a cancer-directed treatment unless within the context of a clinical trial. Cannabis and/or cannabinoids may improve refractory, chemotherapy-induced nausea and vomiting when added to guideline-concordant antiemetic regimens. Whether cannabis and/or cannabinoids can improve other supportive care outcomes remains uncertain. This guideline also highlights the critical need for more cannabis and/or cannabinoid research.Additional information is available at www.asco.org/supportive-care-guidelines.

The Dairy and Cancer Controversy: Milking the Evidence.

PURPOSE OF REVIEW: Cancer risk reduction remains a significant concern for both individuals with a cancer diagnosis and those aiming to prevent it. Dairy products, a source of beneficial dietary nutrients, have sparked controversy regarding their impact on cancer risk. RECENT FINDINGS: Evidence indicates that dairy consumption, particularly milk, can decrease colorectal cancer risk. However, cow's milk, a key dairy product, exposes individuals to growth hormones, notably insulin-like growth factor-1, potentially elevating cancer risk. Extensive research supports the link between dairy intake and heightened prostate cancer risk. Nonetheless, investigations into dairy's association with breast, ovarian, and other cancers yield mixed results. The overall data on dairy and cancer remains inconclusive. Available data suggests that a diet emphasizing fiber-rich foods such as whole grains, fruits, and vegetables, while restricting milk and dairy intake-similar to the Mediterranean dietary pattern-might mitigate cancer incidence. However, further research is crucial to elucidate the precise role of dairy products in overall cancer risk.

Patients Receiving Integrative Medicine Effectiveness Registry (PRIMIER) of the BraveNet practice-based research network: Outcomes of the PRIMIER cohort.

OBJECTIVE: To evaluate the real-world effectiveness of integrative medicine treatment on quality of life using the Patients Receiving Integrative Medicine Effectiveness Registry (PRIMIER). DESIGN: A prospective, longitudinal, observational evaluation of patient reported outcomes for quality of life. SETTING: Participants were patients from 17 integrative medicine clinics who received personalized, integrative medicine treatments between August 2013 and October 2017. MAIN OUTCOME MEASURES: Participants completed the Patient Reported Outcomes Measurement Information System (PROMIS)- 29, Perceived Stress Scale-4 (PSS-4), and the Patient Activation Measure (PAM) at index (baseline) visit and at 2, 4, 6, and 12 month follow-up assessments. Electronic health record data included diagnostic and billing codes/descriptions. A linear mixed-effects model was used to test whether outcomes changed from index through 12 months RESULTS: During enrollment, 4883 participants began the assessment, 3658 completed the index measures, and 2374 (65 %) completed at least 1 follow-up assessment, had electronic health record data and at least 1 integrative medicine visit. Most participants (mean age=51.4 years) were white (88.4 %), female (79.7 %), and college-educated (78.5 %). Significant improvements (p < 0.001) were observed at 12-months on all PROMIS-29 measures, PSS-4, and PAM. At 12 months, clinically meaningful improvements were found for 38 % and 28 % on PROMIS-29 Mental and Physical Health Summary scores respectively. CONCLUSIONS: PRIMIER is the largest study to assess the real-world effectiveness of integrative medicine. Results indicate a statistical and clinical improvement across all measures at 12 months. Future research could explore whether dosing, timing or combinations of integrative medicine interventions have differential impacts on quality of life.

Backgrounds and Trainings in Cannabis Therapeutics of Dispensary Personnel.

PURPOSE: A growing body of scientific research indicates that oncology teams tend to offer individuals with cancer little clinical advice regarding medicinal cannabis (MC) and that individuals with cancer instead turn to cannabis dispensaries for MC guidance. Our objective was to investigate dispensary personnel's backgrounds and trainings in MC advising. METHODS: The study design was semistructured interviews across 13 states with cannabis dispensary personnel in managerial or client-facing positions. Of 38 recruited, 26 (68%) completed interview. The primary outcome was training in MC advising. Researchers targeted thematic saturation and adhered to Consolidated Criteria for Reporting Qualitative Research. RESULTS: Of 26 participants, 54% were female, with an average age of 40 (range: 22-64) years. Half worked in client-facing roles; half worked in managerial ones. Study participants endorsed passionate commitment to their profession, often motivated by personal experience with MC therapeutics. Cannabis dispensaries often privileged sales skills over cannabis therapeutics knowledge when hiring, resulting in uneven baseline levels of cannabis therapeutics expertise among staff. Most participants reported workplace cannabis therapeutics training to be unstandardized and weak. They described dispensary personnel as resourceful in pursuing cannabis knowledge, self-financing learning in off-hours, sampling dispensary products, and exchanging knowledge. Nearly half the participants called for quality, standardized cannabis therapeutics training for dispensary personnel. CONCLUSION: The many oncology teams who defer to dispensary personnel regarding MC advising rely on a workforce who views themselves as unevenly trained. Further research should include a national survey of cannabis dispensary personnel to learn whether these findings hold true in a larger sample. If so, the oncology community must determine the best approach to clinically advising individuals with cancer about MC.

Cannabis, Cannabinoids and Cannabis-Based Medicines in Cancer Care.

As medical cannabis becomes legal in more states, cancer patients are increasingly interested in the potential utility of the ancient botanical in their treatment regimen. Although eager to discuss cannabis use with their oncologist, patients often find that their provider reports that they do not have adequate information to be helpful. Oncologists, so dependent on evidence-based data to guide their treatment plans, are dismayed by the lack of published literature on the benefits of medical cannabis. This results largely from the significant barriers that have existed to effectively thwart the ability to conduct trials investigating the potential therapeutic efficacy of the plant. This is a narrative review aimed at clinicians, summarizing cannabis phytochemistry, trials in the areas of nausea and vomiting, appetite, pain and anticancer activity, including assessment of case reports of antitumor use, with reflective assessments of the quality and quantity of evidence. Despite preclinical evidence and social media claims, the utility of cannabis, cannabinoids or cannabis-based medicines in the treatment of cancer remains to be convincingly demonstrated. With an acceptable safety profile, cannabis and its congeners may be useful in managing symptoms related to cancer or its treatment. Further clinical trials should be conducted to evaluate whether the preclinical antitumor effects translate into benefit for cancer patients. Oncologists should familiarize themselves with the available database to be able to better advise their patients on the potential uses of this complementary botanical therapy.

Cancer Treatment: Preclinical & Clinical.

The first evidence that cannabinoids may have in vitro and in vivo antineoplastic activity against tumor cell lines and animal tumor models was published in the Journal of the National Cancer Institute nearly 50 years ago. Cannabinoids appear to induce apoptosis in rodent brain tumors by way of direct interaction with the cannabinoid receptor. They may inhibit angiogenesis and tumor cell invasiveness. Despite preclinical findings, attempts to translate the benefits from bench to bedside have been limited. This session provides a review of the basic science supporting the use of cannabinoids in gliomas, paired with the first randomized clinical trial of a cannabis-based therapy for glioblastoma multiforme. Another preclinical presentation reports the effects of cannabinoids on triple-negative breast cancer cell lines and how cannabidiol may affect tumors. The session's second human trial raises concerns about the use of botanical cannabis in patients with advanced cancer receiving immunotherapy suggesting inferior outcomes.

Challenges for Clinical Cannabis and Cannabinoid Research in the United States.

Significant changes have occurred in the policy landscape surrounding cannabis legalization, production, and use around the globe and across the United States. With widespread availability of novel cannabis and cannabis-based products, there is an urgent need to understand their safety and effectiveness for medical indications. Three primary barriers contribute to the difficulty in initiating research geared toward answering the most pressing public health questions: the US regulatory status of cannabis and cannabinoids, sources for cannabis and cannabinoid study medications, and limited funding and resources to support studies. Despite these hurdles, research is rapidly increasing, and recent changes in the United States have paved the way for exciting new work. Here, challenges and barriers to cannabis and cannabinoid research are described from the perspectives of the National Institute on Drug Abuse, National Institutes of Health; the US Food and Drug Administration; and 2 clinical researchers. Barriers specifically to studying cannabis, cannabinoids, and cancer are emphasized.

Cannabis and the Cancer Patient.

Session 2 of the National Cancer Institute's Cannabis, Cannabinoids, and Cancer Research Workshop opened with testimony from a lymphoma survivor who detailed medicinal cannabis-related improvements in nausea, low appetite, insomnia, and mental health and the limited clinical counsel she received regarding cannabis use. Discussion next turned to the evolution of the legal landscape of cannabis in the United States, one in which state and federal laws frequently conflict and the Controlled Substance Act renders cannabis Schedule I. This legal climate creates conundrums for US medicinal cannabis researchers who contend with limited funding opportunities, avenues to source trial drug, and procedural red tape and for oncology clinicians who recommend medicinal cannabis to patients with some frequency while perceiving themselves as ill equipped to make such clinical recommendations. Ultimately, it creates challenges for cancer patients who find themselves turning to nonmedical and anecdotal information sources. The risks of cannabis use by the cancer patient were discussed next. These include infection, pharmacodynamic and pharmacokinetic drug-botanical interactions, cyclic nausea and vomiting, e-cigarette or vaping product use-associated illness, legal issues, and high cost. The session concluded with a broad survey of the research supporting oncologic cannabinoid use, conclusive evidence for chemotherapy-induced nausea and vomiting, and suggestive evidence for cancer-related pain.

A cannabis oracle? Delphi method not a substitute for randomized controlled trials of cannabinoids as therapeutics.

BACKGROUND: With millions of people using cannabinoids to treat a host of medical conditions, clinicians want guidance on how to utilize cannabinoids as pharmacotherapy in their practices. The Delphi method is a systematic, interactive forecasting method that aims to develop consensus best practices where guidelines are not available. BODY: A multidisciplinary group of global cannabinoid experts utilized a modified Delphi process to develop three protocols for the dosing and administration of cannabinoids to treat chronic pain. Two protocols recommend cannabidiol (CBD), for which there is limited evidence as an analgesic, starting well below doses required for other indications. Guidance on prescribing CBD for pain may demonstrate consensus recommendations based upon suboptimal evidence. CONCLUSION: Consensus processes like the Delphi method are well-meaning, but they are not a substitute for rigorous RCTs with large sample sizes, adequate duration, and standardized outcome measures.

Effect of Inhaled Cannabis for Pain in Adults With Sickle Cell Disease: A Randomized Clinical Trial.

Importance: Sickle cell disease (SCD) is characterized by chronic pain and episodic acute pain caused by vasoocclusive crises, often requiring high doses of opioids for prolonged periods. In humanized mouse models of SCD, a synthetic cannabinoid has been found to attenuate both chronic and acute hyperalgesia. The effect of cannabis on chronic pain in adults with SCD is unknown. Objective: To determine whether inhaled cannabis is more effective than inhaled placebo in relieving chronic pain in adults with SCD. Design, Setting, and Participants: This pilot randomized clinical trial included participants with SCD with chronic pain admitted to a single inpatient clinical research center for 2 separate 5-day stays from August 2014 to April 2017. Participants inhaled either vaporized cannabis (4.4% Δ-9-tetrahydrocannabinol to 4.9% cannabidiol) 3 times daily or vaporized placebo cannabis. Pain and pain interference ratings using the Brief Pain Inventory were assessed throughout each 5-day period. Participants with SCD and chronic pain on stable analgesics were eligible to enroll. A total of 90 participants were assessed for eligibility; 56 participants were deemed ineligible, and 34 participants were enrolled. Of these, 7 participants dropped out before randomization. Of 27 randomized participants, 23 completed both treatment arms of the crossover study and were included in the final per protocol analysis. Data analysis was completed in June 2019, with the sensitivity analysis conducted in April 2020. Interventions: Inhalation of vaporized cannabis plant (4.4% Δ-9-tetrahydrocannbinol to 4.9% cannabidiol) or placebo cannabis plant using a vaporizer 3 times daily for 5 days. Main Outcomes and Measures: Daily pain assessed with visual analog scale and Brief Pain Inventory. Results: A total of 23 participants (mean [SD] age, 37.6 [11.4] years; 13 [56%] women) completed the trial. The mean (SD) difference in pain rating assessment between the cannabis and placebo groups was -5.3 (8.1) for day 1, -10.9 (7.0) for day 2, -16.5 (9.2) for day 3, -8.9 (6.7) for day 4, and -8.2 (8.1) for day 5; however, none of these differences were statistically significant. There was no statistically significant mean (SD) difference in pain interference ratings between cannabis and placebo between days 1 and 5 for interference in general activities (day 1: 0.27 [0.35]; day 5: -1.0 [0.5]), walking (day 1: 0.14 [0.73]; day 5: -0.87 [0.63]), sleep (day 1: 0.59 [0.74]; day 5: -1.3 [0.8]), or enjoyment (day 1: 0.23 [0.69]; day 5: -0.91 [0.48]), but there was a statistically significant mean (SD) difference in decrease in interference with mood (day 1: 0.96 [0.59]; day 5: -1.4 [0.6]; P = .02). No differences in treatment-related adverse effects were observed. Use of concomitant opioids was similar during both treatment periods. Conclusions and Relevance: This randomized clinical trial found that, compared with vaporized placebo, vaporized cannabis did not statistically significantly reduce pain and associated symptoms, except interference in mood, in patients with SCD with chronic pain. Trial Registration: ClinicalTrials.gov Identifier: NCT01771731.

Considering abuse liability and neurocognitive effects of cannabis and cannabis-derived products when assessing analgesic efficacy: a comprehensive review of randomized-controlled studies.

Background: Pain is the most frequent indication for which medical cannabis treatment is sought.Objectives: The clinical potential of cannabis and cannabis-derived products (CDPs) relies on their efficacy to treat an indication and potential adverse effects that impact outcomes, including abuse liability and neurocognitive effects. To ascertain the extent to which these effects impact therapeutic utility, studies investigating cannabis and CDPs for pain were reviewed for analgesic efficacy and assessments of abuse liability and neurocognitive effects.Methods: A comprehensive review of placebo-controlled studies investigating cannabis and CDP analgesia was performed. Methods and findings related to adverse effects, abuse liability, and neurocognitive effects were extracted.Results: Thirty-eight studies were reviewed; 29 assessed cannabis and CDPs for chronic pain, 1 for acute pain, and 8 used experimental pain tests. Most studies ascertained adverse effects through self-report (N = 27). Fewer studies specifically probed abuse liability (N = 7) and cognitive and psychomotor effects (N = 12). Many studies related to chronic and experimental pain (N = 18 and N = 5, respectively) found cannabis and CDPs to reduce pain. Overall, adverse effects were mild to moderate, and dose-related. Studies investigating the impact of cannabis and CDPs on abuse liability and neurocognitive endpoints were mostly limited to inhaled administration and confirmed dose-related effects.Conclusion: Few studies investigating cannabis and CDP analgesia assess abuse liability and cognitive endpoints, adverse effects that impact the long-term clinical utility of these drugs. Future studies should include these measures to optimize research and clinical care related to cannabis-based therapeutics.

Improving Access to Integrative Oncology Through Group Medical Visits: A Pilot Implementation Project.

Objectives: This article describes the implementation of a group medical visit (GMV) model to increase access to integrative oncology (IO) care. The most challenging and critical time to access high-quality IO care is while patients are receiving conventional cancer therapy. Often demand for individual IO clinic consultations precludes this from occurring. A three-session GMV program was designed to alleviate barriers to receiving integrative care during active cancer treatment. Design: A consolidated framework was used for implementation research and focused ethnography methods to describe the IO GMV implementation process. Data sources included patient evaluations, participant observation, and brief provider and patient interviews. Setting: A pilot program was created to assess the feasibility and acceptability of implementing IO GMVs at a comprehensive cancer center. Intervention: Each three-session GMV consisted of a didactic session, followed by individual visits with the integrative oncologist. Results: The setting, intervention, and implementation process of the IO GMV program were described. Thirty-two patients participated in the first five cohorts of the program. Twenty-two were women; 24 were White. The median age of participants was 52. Patient evaluations demonstrate high levels of satisfaction with the program with all scored aspects rated >4.0 on a five-point Likert scale. For the medical center, group visits are a financially viable alternative to individual IO visits; revenue from group visits exceeded the revenue potential of 6 h of individual visits by an average of 38%. Conclusion: GMVs are a feasible and promising model for increasing access to IO. Patients in active cancer treatment were able to participate in the program. Future research and implementation efforts could examine health outcomes over time after participation in GMVs, as well as the feasibility of using this model with more diverse patient populations.

Should Oncologists Recommend Cannabis?

OPINION STATEMENT: Cannabis is a useful botanical with a wide range of therapeutic potential. Global prohibition over the past century has impeded the ability to study the plant as medicine. However, delta-9-tetrahydrocannabinol (THC) has been developed as a stand-alone pharmaceutical initially approved for the treatment of chemotherapy-related nausea and vomiting in 1986. The indication was expanded in 1992 to include treatment of anorexia in patients with the AIDS wasting syndrome. Hence, if the dominant cannabinoid is available as a schedule III prescription medication, it would seem logical that the parent botanical would likely have similar therapeutic benefits. The system of cannabinoid receptors and endogenous cannabinoids (endocannabinoids) has likely developed to help us modulate our response to noxious stimuli. Phytocannabinoids also complex with these receptors, and the analgesic effects of cannabis are perhaps the best supported by clinical evidence. Cannabis and its constituents have also been reported to be useful in assisting with sleep, mood, and anxiety. Despite significant in vitro and animal model evidence supporting the anti-cancer activity of individual cannabinoids-particularly THC and cannabidiol (CBD)-clinical evidence is absent. A single intervention that can assist with nausea, appetite, pain, mood, and sleep is certainly a valuable addition to the palliative care armamentarium. Although many healthcare providers advise against the inhalation of a botanical as a twenty-first century drug-delivery system, evidence for serious harmful effects of cannabis inhalation is scant and a variety of other methods of ingestion are currently available from dispensaries in locales where patients have access to medicinal cannabis. Oncologists and palliative care providers should recommend this botanical remedy to their patients to gain first-hand evidence of its therapeutic potential despite the paucity of results from randomized placebo-controlled clinical trials to appreciate that it is both safe and effective and really does not require a package insert.

Pros and Cons of Dietary Strategies Popular Among Cancer Patients.

As many as 48% of cancer patients pursue popular diets, including the alkaline, Paleolithic, ketogenic, vegan, and macrobiotic diets, with the hope that they will improve survival and prevent recurrence. These diets have positive aspects consistent with the dietary guidelines proposed by the American Cancer Society (ACS) and the American Institute for Cancer Research (AICR). All of the diets emphasize eating vegetables, all but the ketogenic diet encourage eating fruit, and all but the vegan diet limit refined grains and alcohol. Both the macrobiotic and the alkaline diets meet the majority of the ACS and AICR guidelines. Negative aspects of these diets include pseudo-scientific rationales for their anti-cancer properties, limited evidence that they improve cancer outcomes, the possibility for nutrient insufficiencies, and elimination of food groups proven beneficial for cancer prevention and general health. Moreover, with nutritional counseling, nutrient insufficiencies and misalignment with cancer clinical guidelines can often be addressed. Clinicians should consider strategies to encourage evidence-based dietary changes that encourage positive features of popular cancer diets, while minimizing negative aspects.

An Integrative Approach to Prostate Cancer.

OBJECTIVES: The mostly indolent natural history and long overall survival associated with a diagnosis of prostate cancer provides a unique opportunity for men to explore diet and lifestyle interventions to alter the trajectory of their disease. As many patients may be appropriate for postponing conventional therapy, the effects of various integrative interventions can be investigated. In addition, treatment of prostate cancer with surgery, radiation, or androgen deprivation therapy, all may produce physical or psychological side effects that could be amenable to complementary therapies. This article serves to review salient information in the published literature. DESIGN: A review of published research was conducted. RESULTS: A plant-based antioxidant-rich diet with an emphasis on cruciferous vegetables, tomatoes, soy, pomegranate, and marine omega 3 fatty acids while avoiding saturated fats, including dairy products is the best option. Supplementation with vitamin D3, omega 3, and some nutraceutical-based preparations may be advised. It is likely prudent to avoid vitamin E and selenium supplements. Physical activity has been shown to have multiple benefits in men diagnosed with all stages of prostate cancer from strengthening bones, improving body habitus, and enhancing overall wellbeing. Yoga, combining physical activity with a mind-body component, has been shown to have a salutogenic effect in both prostate cancer patients and their caregivers. Traditional Chinese Medicine may be particularly useful in managing side effects of conventional treatments, especially the hot flashes associated with androgen deprivation therapy. Although the long natural history, availability of a useful blood marker of disease progression and prolonged survival are overall positive features, they also combine to allow men to live for a long time with diagnosed cancer, fear of progression, or recurrence and fixation on changes in their prostate-specific antigen level. The resultant stress can be deleterious to general health as well as possibly the natural history of their disease. Mind-body interventions to reduce stress, including mindfulness-based stress reduction and support groups may be useful adjunctive therapies. CONCLUSION: Men with prostate cancer may benefit from lifestyle and complementary interventions integrated with their conventional care.

The therapeutic effects of Cannabis and cannabinoids: An update from the National Academies of Sciences, Engineering and Medicine report.

The National Academies of Sciences, Engineering and Medicine conducted a rapid turn-around comprehensive review of recent medical literature on The Health Effects of Cannabis and Cannabinoids. The 16-member committee adopted the key features of a systematic review process, conducting an extensive search of relevant databases and considered 10,000 recent abstracts to determine their relevance. Primacy was given to recently published systematic reviews and primary research that studied one of the committee's 11 prioritized health endpoints- therapeutic effects; cancer incidence; cardiometabolic risk; respiratory disease; immune function; injury and death; prenatal, perinatal and postnatal outcomes; psychosocial outcomes; mental health; problem Cannabis use; and Cannabis use and abuse of other substances. The committee developed standard language to categorize the weight of evidence regarding whether Cannabis or cannabinoids use for therapeutic purposes are an effective or ineffective treatment for the prioritized health endpoints of interest. In the Therapeutics chapter reviewed here, the report concluded that there was conclusive or substantial evidence that Cannabis or cannabinoids are effective for the treatment of pain in adults; chemotherapy-induced nausea and vomiting and spasticity associated with multiple sclerosis. Moderate evidence was found for secondary sleep disturbances. The evidence supporting improvement in appetite, Tourette syndrome, anxiety, posttraumatic stress disorder, cancer, irritable bowel syndrome, epilepsy and a variety of neurodegenerative disorders was described as limited, insufficient or absent. A chapter of the NASEM report enumerated multiple barriers to conducting research on Cannabis in the US that may explain the paucity of positive therapeutic benefits in the published literature to date.