Cannabinoid Therapy: Attitudes and Experiences of People With Chronic Pain.

OBJECTIVE: Clinical trials of cannabinoids for chronic pain have mixed and often inconclusive results. In contrast, many prospective observational studies show the analgesic effects of cannabinoids. This survey study aimed to examine the experiences/attitudes of individuals with chronic pain who are currently taking, have previously taken, or never taken cannabinoids for chronic pain to inform future research. METHODS: This study is based on a cross-sectional, web-based survey of individuals with self-reported chronic pain. Participants were invited to participate through an email that was distributed to the listservs of patient advocacy groups and foundations that engage individuals with chronic pain. RESULTS: Of the 969 respondents, 444 (46%) respondents reported currently taking, 213 (22%) previously taken, and 312 (32%) never taken cannabinoids for pain. Participants reported using cannabinoids to treat a wide variety of chronic pain conditions. Those currently taking cannabinoids (vs previously) more frequently reported: (1) large improvements from cannabinoids in all pain types, including particularly difficult-to-treat chronic overlapping pain conditions (eg, pelvic pain), (2) improvements in comorbid symptoms (eg, sleep), and (3) lower interference from side effects. Those currently taking cannabinoids reported more frequent and satisfactory communication with clinicians regarding cannabinoid use. Those never taken cannabinoids reported a lack of suggestion/approval of a clinician (40%), illegality (25%), and lack of FDA regulation (19%) as reasons for never trying cannabinoids. CONCLUSION: These findings underscore the importance of conducting high-quality clinical trials that include diverse pain populations and clinically relevant outcomes that if successful, could support FDA approval of cannabinoid products. Clinicians could then prescribe and monitor these treatments similarly to other chronic pain medications.

Prevalence and association of non-medical cannabis use with post-procedural healthcare utilisation in patients undergoing surgery or interventional procedures: a retrospective cohort study.

Background: There is paucity of data regarding prevalence and key harms of non-medical cannabis use in surgical patients. We investigated whether cannabis use in patients undergoing surgery or interventional procedures patients was associated with a higher degree of post-procedural healthcare utilisation. Methods: 210,639 adults undergoing non-cardiac surgery between January 2008 and June 2020 at an academic healthcare network in Massachusetts, USA, were included. The primary exposure was use of cannabis, differentiated by reported ongoing non-medical use, self-identified during structured, preoperative nursing/physician interviews, or diagnosis of cannabis use disorder based on International Classification of Diseases, 9th/10th Revision, diagnostic codes. The main outcome measure was the requirement of advanced post-procedural healthcare utilisation (unplanned intensive care unit admission, hospital re-admission or non-home discharge). Findings: 16,211 patients (7.7%) were identified as cannabis users. The prevalence of cannabis use increased from 4.9% in 2008 to 14.3% by 2020 (p < 0.001). Patients who consumed cannabis had higher rates of psychiatric comorbidities (25.3 versus 16.8%; p < 0.001) and concomitant non-tobacco substance abuse (30.2 versus 7.0%; p < 0.001). Compared to non-users, patients with a diagnosis of cannabis use disorder had higher odds of requiring advanced post-procedural healthcare utilisation after adjusting for patient characteristics, concomitant substance use and socioeconomic factors (aOR [adjusted odds ratio] 1.16; 95% CI 1.02-1.32). By contrast, patients with ongoing non-medical cannabis use had lower odds of advanced post-procedural healthcare utilisation (aOR 0.87; 95% CI 0.81-0.92, compared to non-users). Interpretation: One in seven patients undergoing surgery or interventional procedures in 2020 reported cannabis consumption. Differential effects on post-procedural healthcare utilisation were observed between patients with non-medical cannabis use and cannabis use disorder. Funding: This work was supported by an unrestricted philantropic grant from Jeff and Judy Buzen to Maximilian S. Schaefer.

Policy Ahead of the Science: Medical Cannabis Laws Versus Scientific Evidence.

Forty-one US jurisdictions (37 states) have legalized comprehensive medical cannabis programs since 1996. The number of qualifying conditions per jurisdiction varies from 5 to 29. Five (12%) of 42 qualifying conditions have conclusive or substantial evidence of efficacy and are listed in more than half of all jurisdictions. Half (50%) of qualifying conditions have no or insufficient scientific evidence of benefit from medical cannabis; 9% of qualifying conditions have limited evidence of harm from medical cannabis. The mean number of qualifying conditions per jurisdiction and the proportion of conditions with and without evidence of benefit have not changed since 1996.

Review of potential psychedelic treatments for PTSD.

Post-traumatic stress disorder (PTSD) is a debilitating mental illness with limited treatment options and a high treatment dropout rate. Psychedelics, often in combination with psychotherapy, are now under investigation as a potential treatment option for a variety of psychiatric conditions including PTSD. This paper reviews the proposed mechanism of action for 3,4-Methylenedioxymethamphetamine (MDMA) and classical psychedelics such as psilocybin in treating PTSD, along with available clinical evidence, safety and side effects. MDMA-assisted psychotherapy is in FDA phase III clinical trials for PTSD and is purported to work by way of increased empathy and decreased amygdala activation during the therapeutic encounter and trauma processing. Classical psychedelics may create change by a subjective transformative experience along with an observable process of brain network alterations, though these substances have not been clinically studied in the context PTSD. In recent human-subject studies MDMA-assisted therapy resulted in significant improvement in PTSD symptoms with a good safety and side effect profile. There is not yet direct clinical evidence for classical psychedelics in treating PTSD, but the evidence supports such a trial. The studies to date have been relatively small, and participants are wellscreened for potential co-morbidities which could increase the risks of psychedelic treatment. Nonetheless, the data is promising for psychedelic-assisted treatment to become a much-needed treatment option for PTSD.

Buprenorphine in safety-sensitive positions.

The permissibility of buprenorphine in safety-sensitive positions is a controversial topic. As an opioid medication, concerns have arisen regarding the potential for impairment and any effects that this would have on an employee's ability to safely perform job duties. While there are no definitive guidelines on the use of buprenorphine for those employed in safety-sensitive lines of work, most employers do not permit its use under any circumstance due to the potential risk of harm to the public. In addition to overlooking the fact that buprenorphine is a well-established and life-saving treatment for opioid use disorder (OUD), there are many flaws in making this determination. For one, buprenorphine is a partial mu opioid agonist which makes it inherently unique in comparison to other opioids. Most studies on impairment have examined acute use of full agonist opioids instead of chronic dosing of buprenorphine. Furthermore, assessments of impairment are not tailored to the tasks required of specific positions. Importantly, policies banning buprenorphine may contribute to treatment discontinuation and stigma, which can lead to relapse and overdose. Considering the morbidity and mortality associated with OUD, along with the surge in overdose deaths during the COVID19 pandemic, buprenorphine policies should be considered carefully. Given the lack of evidence showing definitive and specific impairments as a result of chronic buprenorphine use, coupled with the consequences of universal bans on its use, determinations on the permissibility of buprenorphine treatment for safety-sensitive positions should be made on a case-by-case basis.

Workplace Cannabis Policies: A Moving Target.

Introduction: This article proposes a workplace cannabis policy paradigm that encompasses rapidly changing laws and regulations, legally defensible drug testing policies, and the needs of particular workplaces. Numerous states have now decriminalized medical or recreational use of cannabis, although U.S. federal law still defines cannabis as a Schedule I substance with no currently accepted medical use and a high potential for abuse. For employers and employees, the confusion generated by this contradiction is exacerbated by the widely varying effects of the available cannabis delivery systems, the primitive and cumbersome drug testing protocols often used in workplace settings, difficulties in measuring cannabis-related workplace impairment, and a rapidly changing cultural ethos regarding cannabis. Although other articles have addressed many of the broad theoretical constructs, there exists little practical guidance on how workplace drug programs should address cannabis use by employees, both on the job and during off-hours. Materials and Methods: Research for this review was performed in the PubMed/National Library of Medicine database. Discussion: Cannabis use is associated with cognitive deficits, motivation problems, and perceptual distortions, so employers have a legitimate interest in preventing on-the-job impairment related to cannabis use. Similarly, employees have a legitimate interest in behaving as they wish outside of the workplace, as long as that behavior does not affect their job performance. Relevant statues and case law on the subject of cannabis in the workplace reflect different legal models across jurisdictions, in addition to legislators and judges' attempts to manage this tension between employer and employees. Conclusion: An effective workplace cannabis policy must fit into a larger workplace drug and alcohol policy. It should be constructed with a collaborative effort of addiction professionals, labor attorneys, and human resource professionals. Only then can the ultimate workplace cannabis policy comply with relevant laws, protect workplace safety and productivity, and support employees while remaining flexible enough to adapt to changes in the legal environment.

What gets resident physicians stressed and how would they prefer to be supported? A best-worst scaling study.

INTRODUCTION: Physician burnout has severe consequences on clinician well-being. Residents face numerous work-stressors that can contribute to burnout; however, given specialty variation in work-stress, it is difficult to identify systemic stressors and implement effective burnout interventions on an institutional level. Assessing resident preferences by specialty for common wellness interventions could also contribute to improved efficacy. METHODS: This cross-sectional study used best-worst scaling (BWS), a type of discrete choice modelling, to explore how 267 residents across nine specialties (anaesthesiology, emergency medicine, internal medicine, neurology, obstetrics and gynaecology, pathology, psychiatry, radiology and surgery) prioritised 16 work-stressors and 4 wellness interventions at a large academic medical centre during the COVID-19 pandemic (December 2020). RESULTS: Top-ranked stressors were work-life integration and electronic health record documentation. Therapy (63%, selected as 'would realistically consider intervention') and coaching (58%) were the most preferred wellness supports in comparison to group-based peer support (20%) and individual peer support (22%). Pathology, psychiatry and OBGYN specialties were most willing to consider all intervention options, with emergency medicine and internal medicine specialties least willing to consider intervention options. CONCLUSION: BWS can identify relative differences in surveyed stressors, allowing for the generation of specialty-specific stressor rankings and preferences for specific wellness interventions that can be used to drive institution-wide changes to improve clinician wellness. BWS surveys are a potential methodology for clinician wellness programmes to gather specific information on preferences to determine best practices for resident wellness.

Risks and Benefits of Cannabis and Cannabinoids in Psychiatry.

OBJECTIVE: The United States is in the midst of rapidly changing laws regarding cannabis. The increasing availability of cannabis for recreational and medical use requires that mental health clinicians be knowledgeable about evidence to be considered when counseling both patients and colleagues. In this review, the authors outline the evidence from randomized double-blind placebo-controlled trials for therapeutic use of cannabinoids for specific medical conditions and the potential side effects associated with acute and chronic cannabis use. METHODS: Searches of PubMed and PsycInfo were conducted for articles published through July 2021 reporting on "cannabis" or "cannabinoids" or "medicinal cannabis." Additional articles were identified from the reference lists of published reviews. Articles that did not contain the terms "clinical trial" or "therapy" in the title or abstract were not reviewed. A total of 4,431 articles were screened, and 841 articles that met criteria for inclusion were reviewed by two or more authors. RESULTS: There are currently no psychiatric indications approved by the U.S. Food and Drug Administration (FDA) for cannabinoids, and there is limited evidence supporting the therapeutic use of cannabinoids for treatment of psychiatric disorders. To date, evidence supporting cannabinoid prescription beyond the FDA indications is strongest for the management of pain and spasticity. CONCLUSIONS: As cannabinoids become more available, the need for an evidence base adequately evaluating their safety and efficacy is increasingly important. There is considerable evidence that cannabinoids have a potential for harm in vulnerable populations such as adolescents and those with psychotic disorders. The current evidence base is insufficient to support the prescription of cannabinoids for the treatment of psychiatric disorders.

Self-Reported Preferences for Help-Seeking and Barriers to Using Mental Health Supports Among Internal Medicine Residents: Exploratory Use of an Econometric Best-Worst Scaling Framework for Gathering Physician Wellness Preferences.

BACKGROUND: Burnout interventions are limited by low use. Understanding resident physician preferences for burnout interventions may increase utilization and improve the assessment of these interventions. OBJECTIVE: This study aims to use an econometric best-worst scaling (BWS) framework to survey internal medicine resident physicians to establish help-seeking preferences for burnout and barriers to using wellness supports by quantifying selections for 7 wellness support options and 7 barriers. METHODS: Internal medicine resident physicians at our institution completed an anonymous web-based BWS survey during the 2020-2021 academic year. This cross-sectional study was analyzed with multinomial logistic regression and latent class modeling to determine the relative rank ordering of factors for seeking support for burnout and barriers to using wellness supports. Analysis of variance with Tukey honest significant difference posthoc test was used to analyze differences in mean utility scores representing choice for barriers and support options. RESULTS: Of the 163 invited residents, 77 (47.2% response rate) completed the survey. Top-ranking factors for seeking wellness supports included seeking informal peer support (best: 71%; worst: 0.6%) and support from friends and family (best: 70%; worst: 1.6%). Top-ranking barriers to seeking counseling included time (best: 75%; worst: 5%) and money (best: 35%; worst: 21%). CONCLUSIONS: Overall, our findings suggest that low utilization of formal mental health support is reflective of resident preferences to seek help informally and that increasing utilization will require addressing pragmatic barriers of time and cost. Assessing physician preferences for wellness-related initiatives may contribute to understanding the low utilization of formal mental health services among physicians, which can be determined using a BWS framework.

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.

Should You Recommend Cannabinoids for This Patient With Painful Neuropathy? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Cannabis includes 140 active cannabinoid compounds, the most important of which are tetrahydrocannabinol and cannabidiol (CBD). Tetrahydrocannabinol is primarily responsible for the intoxicating effects of cannabis; CBD has potential therapeutic effects, including reduction in chronic pain. Recent legislative changes have resulted in the legal availability of cannabinoids in all 50 states, as well as a marked increase in patients' interest in their use. Despite an abundance of data, albeit of varied quality, clinicians may feel poorly prepared to counsel patients seeking advice on the suitability of CBD products for various indications, particularly chronic neuropathic pain. In 2018, on the basis of a systematic review of the literature, a Canadian Evidence Review Group published a guideline with recommendations for clinicians on prescribing cannabinoids in primary care practice. The overall quality of evidence was low to very low. In a meta-analysis of 15 randomized trials of medical cannabis for treating chronic pain, 39% of patients achieved at least a 30% reduction in pain. The corresponding value for placebo-treated patients was 30%; the number needed to treat was 11. More evidence exists for neuropathic pain than for other types of noncancer pain. Here, a general internist with a focus on addiction medicine and an addiction psychiatrist discuss how they would apply the literature to make recommendations for a patient with painful diabetic neuropathy, including counseling on both potential benefits and harms.

Cannabidiol Interactions with Medications, Illicit Substances, and Alcohol: a Comprehensive Review.

Cannabidiol, a non-intoxicating phytocannabinoid, has potential therapeutic effects over a broad range of disorders. Recently, there has been increased interest in CBD, as several studies showed promising anticonvulsant efficacy with few side effects. In 2018, a CBD-based oral solution, Epidiolex®, was approved by the FDA to treat two severe forms of pediatric epilepsy, Dravet syndrome, and Lennox-Gastaut syndrome. Although only these two syndromes are recognized indications for CBD, it has been consumed in an unregulated fashion for a variety of indications including chronic pain, muscle stiffness, inflammation, anxiety, smoking cessation, and even cancer. While CBD legislation in the USA is confusing due to the differences in state and federal laws, CBD has proliferated in the US market in several forms such as CBD oil or capsules, hemp oil/extract, and also as an ingredient in several dietary supplements, syrups, teas, and creams. With the ever-increasing use of CBD and its widespread availability to the general public, it is important to examine and report on possible drug-drug interactions between CBD and other therapeutic agents as well as addictive substances such as alcohol and tobacco. A detailed literature search for CBD's possible interactions was conducted using online databases. As expected, CBD has been reported to interact with anti-epileptic drugs, antidepressants, opioid analgesics, and THC, but surprisingly, it interacts with several other common medications, e.g. acetaminophen, and substances including alcohol. This review provides a comprehensive list of interacting drugs. The possible mechanisms for these drug-drug interactions are presented in table format. Given the growing popularity of CBD as a medication and the dearth of available information on CBD drug-drug interactions, it is critical to be aware of current drug-drug interactions and it will be important to investigate the impact of CBD upon concomitant medication use in future randomized, controlled trials.

Is your patient's cannabis use problematic?

Individuals who do not meet DSM-5 criteria for cannabis use disorder may still have problematic use. The screening tool and 5 interventions detailed here can help.

Care of the Patient Using Cannabis.

The past 2 decades have seen a revolution in legal access to cannabis, driven largely by activists and business interests. As a result, the population of cannabis users nationwide-especially daily users-has grown significantly. An estimated 4.5-7 million persons in the United States now meet criteria for cannabis use disorder annually. This article focuses on the effects of cannabis use, intoxication, and withdrawal while also reviewing the developmental pathways of cannabis use disorder as well as evidence-based pharmacologic and psychosocial treatments.

The Molecular-Container Calabadion-2 Prevents Methamphetamine-Induced Reinstatement in Rats: A Potential Approach to Relapse Prevention?

BACKGROUND: Reexposure to methamphetamine with a single "priming dose" can trigger intense cravings and precipitate relapse in methamphetamine-dependent individuals. The acyclic cucurbit[n]uril "molecular container" calabadion-2 shows a high affinity to bind and sequester methamphetamine in vitro and attenuates its locomotor-stimulating effect in rats. The present study investigates whether pretreatment with calabadion-2 is sufficient to prevent the reinstatement of drug seeking by a priming dose of methamphetamine in rats. METHODS: Male Long-Evans rats were trained to self-administer i.v. methamphetamine (0.06 mg/kg/infusion). Following 10 days of stable self-administration, rats underwent extinction training and were subsequently tested on a multi-phase reinstatement procedure. Drug-primed reinstatement sessions (0.3 mg/kg methamphetamine, i.v.) were preceded by either saline or calabadion-2 (130 mg/kg). Additional reinstatement tests were conducted after administration of yohimbine (1.0 mg/kg, i.v.) to define the pharmacological specificity of calabadion-2. RESULTS: Pretreatment with calabadion-2 significantly attenuated methamphetamine-induced reinstatement of responding. Cal2 did not affect drug-seeking behavior stimulated by the pharmacological stressor yohimbine, indicating a mechanism of action specific to methamphetamine. CONCLUSIONS: These results demonstrate the effectiveness of calabadion-2 in a preclinical model relapse-like behavior. With further structural optimization, molecular containers may provide a novel and efficacious pharmacokinetic approach to relapse prevention for methamphetamine-dependent individuals.

Clinical uses of cannabis and cannabinoids in the United States.

The role of cannabis in medicine is rapidly evolving. Medical cannabis is now legal in a majority of states, and THC and CBD, the prominent cannabinoids found in cannabis, have both been utilized in the development of FDA-approved drugs. Due to the complicated legal status of cannabis and cannabinoids, as well as regulations that vary from state to state, the appropriate use of these substances for both patients as well as clinicians is often unclear. Advancements in the understanding of the pharmacology of cannabis have led to numerous proposed uses of these drugs, including as antidepressant or analgesic agents. However, clinical trial data for these substances suggests that many purported indications of cannabis and cannabinoids are not supported by good clinical data. Furthermore, cannabis and several cannabinoid-based medications have potentially concerning side effect profiles that may limit their use in certain patient populations. As the legal status and clinical database of these medications continue to evolve, physicians will need to continue to balance the real potential of these compounds with their limitations and adverse effects.