Medical Cannabinoids Research Articles

The State of Synthetic Cannabinoid Medications for the Treatment of Pain.

Synthetic cannabinoids are compounds made in the laboratory to structurally and functionally mimic phytocannabinoids from the Cannabis sativa L. plant, including delta-9-tetrahydrocannabinol (THC). Synthetic cannabinoids (SCs) can signal via the classical endogenous cannabinoid system (ECS) and the greater endocannabidiome network, highlighting their signalling complexity and far-reaching effects. Dronabinol and nabilone, which mimic THC signalling, have been approved by the Food and Drug Administration (FDA) for treating nausea associated with cancer chemotherapy and/or acquired immunodeficiency syndrome (AIDS). However, there is ongoing interest in these two drugs as potential analgesics for a variety of otherclinical conditions, including neuropathic pain, spasticity-related pain, andnociplastic pain syndromes including fibromyalgia, osteoarthritis, and postoperative pain, among others. In this review, we highlight the signalling mechanisms of FDA-approved synthetic cannabinoids, discuss key clinical trials that investigate their analgesic potential, and illustrate challenges faced when bringing synthetic cannabinoids to the clinic.

PARKINSON'S DISEASE AND ENDOCANNABINOID SYSTEM: A BRIEF UPDATE

In Parkinson's disease, dopaminergic neurons located in the substantia nigra of the brain are destroyed, affecting the patients' motor function. The endocannabinoid system is responsible for controlling neuronal homeostasis and its alteration is related to neurodegenerative diseases, such as Parkinson's. A literature review regarding the relationship between the endocannabinoid system and Parkinson's disease was carried out through a search in the Pubmed database. Complete publications from the last year were included, using 15 papers. Treatment with cannabinoid medications for Parkinson's patients should not be the first choice, being restricted to adjuvant therapy as they are elderly and vulnerable. Cannabis extracts have shown in experimental studies neuroprotective and inflammation modulating actions. Pure cannabidiol is safe, with few side effects. Computational analyzes demonstrated that the binding of cannabidiol to the CB1 and CB2 receptors induced structural changes in them. Levels of CB1 receptors were lower in specific areas of the brain of Parkinson's patients and the decline in these receptors was correlated with worse severity of motor symptoms. Selective CB2 receptor agonists have neuroprotective and immunomodulatory actions, reducing inflammation and the formation of defective proteins. Hyperpolarized current-induced inhibition of CB1 receptors improved muscle stiffness but worsened symptoms of depression and anxiety in animals. The use of exogenous cannabinoids in patients with Parkinson's disease is not yet consolidated, and more clinical studies are needed to confirm the safety of the interaction with the endocannabinoid system.

Cannabinoid receptors as new targets for HTLV-1 associated myelopathy (HAM/TSP) treatment

Background/AimThe roles of endocannabinoids are described in immune modulation and neuroprotection. HTLV-1-associated myelopathy (HAM/TSP) is an inflammatory neurodegenerative disease. Therefore, in this study, the interactions of HTLV-1 regulatory factors and host cannabinoid receptors (CBRs) were evaluated in HAM/TSP. MethodsNineteen HAM/TSPs, 22 asymptomatic carriers (ACs), and 18 healthy controls (HCs) were enrolled. RNA was extracted from PBMCs and then reverse-transcribed to cDNA. The gene expression of CB1R and CB2R, as well as HTLV-1 proviral load (PVL), Tax and HTLV-1 basic leucine zipper factor (HBZ) were assessed by RT-qPCR. ResultsThe mean expression of CB1R in ACs (8.51 ± 2.76) was significantly higher than HAMTSPs (1.593 ± 0.74, p = 0.05) and also HCs (0.10 ± 0.039, p = 0.001). The CB2R gene expression level in ACs (2.62±0.44) was significantly higher than HAM/TSPs (0.59 ± 0.15, p = 0.001) and HCs (1.00 ± 0.2, p = 0.006). Meanwhile there was a strong correlation between CB1R and CB2R gene expression levels in the HCs and HAM/TSPs (p = 0.001). HTLV-1-Tax expression in HAM/TSPs (386 ± 104) was higher than ACs (75 ± 32) and statistically significant (p = 0.003). While HTLV-1-HBZ was only expressed in three AC subjects and five HAM/TSPs, thus it cannot be analyzed. ConclusionThe up-regulation of CB2R has immunomodulatory effects in inflammatory reactions. While CB1R as a neuroprotective agent may suppress inflammatory reactions in ACs, preventing HAM/TSP. It seems that, like multiple sclerosis (MS), cannabinoid medications are beneficial in HAM/TSP.

Prevalence and Characteristics of Medicinal Cannabis Use among Chronic Pain Patients; A Post- Legalization Study in a Tertiary Care Setting in Thailand

Objective: Cannabinoid products have been applied for numerous medical conditions, including chronic pain. Thailand was the first country in South East Asia to legalize medical cannabinoids. This study aims to explore prevalence, characters, attitude, side effects of medical cannabinoid use, and pain-related outcome among the chronic cancer and non-cancer pain population at Siriraj Hospital. Materials and Methods: 200 chronic cancer pain and 670 chronic noncancer pain patients were collected by questionnaires and interviews. Data included demographic data, clinical diagnosis, pain treatment, knowledge, attitude, pattern of use, side effects and quality of life of cannabinoid extracts. Results: Prevalence of active cannabis user was 15% in chronic cancer pain and 3.1% in noncancer pain. Oil extract sublingual was the most common form. Pain control was the most common initial reason for usage. No serious side effects were reported. Common side effects were dry oral mucosa, drowsiness, and headache. The most common source was obtained from friends. 36% of the patients believed they had enough understanding of medical cannabis, while 68.5% agreed that it is appropriate to use in Thailand. In cancer patients, the Edmonton Symptom Assessment System (ESAS) subscale for lack of appetite, anxiety, and subscale for a brief pain inventory (BPI) for enjoyment of life were higher among active users. In patients with noncancer pain, only the mood subscale BPI was lower among active users. Conclusion: Medical cannabis usage is common compared with general population in Thai patients with chronic pain and may be associated with increased pain interference and cancer-related symptoms. Nonmedical license prescription and nonmedical license cannabis products were common in Thailand.

Prescription Practices of Cannabinoids in Children with Cerebral Palsy Worldwide-A Survey of the Swiss Cerebral Palsy Registry.

Cannabinoids are prescribed to children with cerebral palsy despite limited evidence. We aimed to assess cannabinoid prescribing practices in children with cerebral palsy, focusing on indications, types of preparations used, and tolerability. Furthermore, we investigated how physicians acquire knowledge about cannabinoid medication. We asked physicians with expertise in the care of children with cerebral palsy about their prescribing practices for cannabinoids. Data were collected through an online survey, which was distributed by email. In addition to the demographic information of participants, we also inquired about the indications for the prescription of cannabinoids, experiences regarding efficacy, and observed side effects of the therapy. Seventy physicians from Europe, North America, and Australia completed the survey. Forty-seven participants were experienced in treating of children with cerebral palsy with cannabinoids. The most common indication was epilepsy (69%), followed by spasticity (64%) and pain (63%). The preparations and doses prescribed varied considerably. Half of the participants evaluated the effect of the cannabinoids as moderate. Twenty-nine physicians reported side effects, most frequently, drowsiness (26%), somnolence (19%), fatigue (13%), and diarrhea (13%). Despite the lack of evidence to date, cannabinoids are used to treat children with cerebral palsy in a wide variety of indications. Randomized controlled trials in this vulnerable patient group are therefore of utmost importance.

Does the "Entourage Effect" in Cannabinoids Exist? A Narrative Scoping Review.

Background: The concept of an "entourage" effect in the cannabis and cannabinoids' field was first introduced in the late 1990s, during a period when most research on medical cannabinoids focused on the effects of isolated cannabinoids, such as cannabidiol and Δ9-tetrahydrocannabinol. Over the past decade, however, with the increased understanding of the endocannabinoid system, the discovery of other phytocannabinoids and their potential therapeutic uses, the term has gained widespread use in scientific reviews and marketing campaigns. Objective: Critically review the application of the term "entourage effect (EE)" in the literature and its endorsement by certain sectors of the cannabis market. Also, explore the perspectives for further interpretation and elaboration of the term based on current evidence, aiming to contribute to a more nuanced understanding of the concept and its implications for cannabinoid-based medicine. Methods: A comprehensive review of the literature was conducted to evaluate the current state of knowledge regarding the entourage effect. Relevant studies and scientific reviews were analyzed to assess the evidence of clinical efficacy and safety, as well as the regulation of cannabinoid-containing product production. Results: The EE is now recognized as a synergistic phenomenon in which multiple components of cannabis interact to modulate the therapeutic actions of the plant. However, the literature provides limited evidence to support it as a stable and predictable phenomenon. Hence, there is also limited evidence to support clinical efficacy, safety, and appropriate regulation for cannabinoid-containing products based on a "entourage" hypothesis. Conclusion: The EE has significant implications for the medical use of cannabinoid-containing products and their prescription. Nevertheless, a critical evaluation of the term's application is necessary. Further research and evidence are needed to establish the clinical efficacy, safety, and regulatory framework for these products. It's crucial that regulators, the pharmaceutical industry, the media, and health care providers exercise caution and avoid prematurely promoting the entourage effect hypothesis as a scientific proven phenomenon for cannabinoids and other cannabis-derived compound combinations.

Medical cannabinoids for painful symptoms in patients with severe dementia: a randomized, double-blind cross-over placebo-controlled trial protocol.

In an observational study in Geneva (Switzerland), we found that administering a standardized THC/CBD oil was feasible, safe, and beneficial in an elderly polymedicated population with severe dementia, behavioral troubles, and pain. Those findings need to be confirmed in a randomized clinical trial. The MedCanDem trial is a randomized, double-blind cross-over placebo-controlled trial to study the efficacy of cannabinoids in improving painful symptoms during severe dementia disorders in patients living in long-term care facilities in Geneva. This manuscript describes the MedCanDem trial protocol. Participants will be patients suffering from severe dementia associated with pain and behavioral troubles and living in long-term care facilities. We selected five facilities specialized in caring for severely demented patients in Geneva (Switzerland). A total of 24 subjects will be randomized 1:1 to the sequence study intervention/placebo or the sequence placebo/study intervention. Patients will receive study intervention treatment or placebo for eight weeks, and then after a one-week wash-out, treatments will be inversed for another eight weeks. The intervention will be a standardized THC/CBD 1:2 oil extract, and the placebo will be a hemp seed oil. The primary outcome is the reduction from the baseline of the Cohen-Mansfield score; secondary outcomes include the reduction in the Doloplus scale, the reduction of rigidity, the monitoring of concomitant drugs prescription and de-prescription, the safety assessment, and a pharmacokinetic evaluation. The primary and secondary outcomes will be assessed at the baseline, after 28 days, and at the end of both study periods. In addition, safety laboratory analysis, pharmacokinetic evaluation, and therapeutic drug monitoring for the cannabinoids will be evaluated through a blood sample analysis conducted at the beginning and the end of both study periods. This study will allow us to confirm the clinical results observed during the observational study. It represents one of the few studies aiming to prove natural medical cannabis efficacy in a population of non-communicating patients with severe dementia, experimenting with behavioral troubles, pain, and rigidity. The trial has Swissethics authorization (BASEC 2022-00999), and it is registered on clinicaltrials.gov (NCT05432206) and the SNCTP (000005168).

Perioperative care for drug abusers in the opioid crisis era

Background: Narcotic abuse and addiction have recently emerged as significant global issues. The consumption of dependence-inducing substances has become increasingly prevalent among younger generations in numerous countries, exacerbating the problem. Until 2015, South Korea had been relatively narcotic-free; however, this is no longer true. Consequently, encountering narcotic abusers in clinical settings, including operating rooms, is becoming more common. It is crucial to be prepared for these phenomena.Current Concepts: Research on managing narcotic abusers during the perioperative period remains insufficient. In 2023, the American Society of Regional Anesthesiologists and Pain Medicine published guidelines for the perioperative management of cannabinoid users. The decision to discontinue or continue medical cannabinoids before surgery remains uncertain. When managing patients with short- or long-term exposure to cannabinoids, anesthetic requirements tend to decrease in cases of acute intoxication and increase among long-term users. Therefore, the duration from the last use should be considered when adjusting the anesthetic dose.Discussion and Conclusion: Punishment is not a viable solution in a reality where narcotic abuse is increasingly common. Preventing addiction in individuals and supporting addicts’ treatment and rehabilitation is essential. There is an urgent need for interest and research focused on narcotic abuse.

Patient Experiences With Prescription Cannabinoids in Germany: Protocol for a Mixed Methods, Exploratory, and Anonymous Web-Based Survey.

Medical cannabinoids are controversial. Their use is comparatively rare, but it is rising. Since 2017, cannabinoids can be prescribed in Germany for a broader range of indications. Patient surveys on these drugs are hampered by the stigmatization of cannabinoids and their (still) low prevalence in medical contexts. Against this background, patients' willingness to provide information is limited. Moreover, it is logistically challenging to reach them with a survey. A thorough knowledge of currently ongoing therapies and their effects and side effects, however, is important for a more appropriate and effective use of cannabinoids in the future. This study is an exploratory data collection using a representative sample. The main goal is to provide a detailed picture of the current use of medical cannabinoids in Germany. It is intended to identify subgroups that may benefit particularly well or poorly. We are conducting a representative, anonymous, cross-sectional, one-time, web-based survey based on mixed methods in 3 German federal states. Health conditions under cannabinoid therapy and before are documented with validated, symptom-specific questionnaires. This allows an estimation of the effect sizes of these therapies. The selection of parameters and questionnaires was based on the results of independent qualitative interviews in advance. Representative samples of the hard-to-reach study population are obtained by cluster sampling via contracted physicians of the statutory health insurance companies. Recruitment was ongoing until the end of June 2022, with 256 enrolled participants. Validated questionnaires on pain, spasticity, anorexia or wasting, multiple sclerosis, nausea or vomiting, depression, and attention deficit hyperactivity disorder (ADHD) were selected. Symptom scores are being assessed for both current conditions under cannabinoid therapy and conditions prior to this therapy (in retrospect). Validated questionnaires are also used for treatment satisfaction and general quality of life. These are supplemented by existing diagnoses, a detailed medication history, any previous experiences with cannabis or illegal substances, experiences with the prescription process, and sociodemographic data. Based on the results of the previous qualitative interviews, questions were added regarding prior experience with relaxation methods and psychotherapy, personal opinions about cannabinoids, pre-existing or symptom-related psychological trauma, and different experiences with different cannabis-based therapies. The exploratory mixed methods approach of this project is expected to provide valid and relevant data as a basis for future clinical research. The study design may be representative for a large proportion of outpatients treated with cannabinoids in the German federal states studied. It may have less bias toward social desirability and may provide valuable information in addition to existing studies. Due to the observational and cross-sectional nature of this study, various limitations apply. Causal relations cannot be drawn. German Clinical Trials Register DRKS00023344; https://drks.de/search/en/trial/DRKS00023344. DERR1-10.2196/38814.

Cannabis and cannabinoid medications for the treatment of chronic orofacial pain: A scoping review

To collate and summarize existing evidence for the use of cannabis and cannabinoids to treat chronic orofacial pain (COP) by oral and maxillofacial surgeons (OMFS), oral medicine specialists (OMS), and orofacial pain specialists (OPS). We systematically screened for sources including a measure of effect of a cannabinoid compound on pain in COP patients that might be treated by our target specialists. Sources were selected by two authors independently. Sources were summarized by country, publication date, objective(s), COP condition(s) studied, cannabinoid(s) studied, methods, results, limitations, and conclusions. A thematic analysis and word cloud were conducted to elucidate commonalities, emphases, and gaps amongst identified sources. Retrieved from MEDLINE, EMBASE, Web of Science Core Collections, Dentistry and Oral Sciences, DARE, CCRCT, and US National Institute of Health and Controlled Trials Register. Of 705 retrieved titles, 8 met inclusion/exclusion criteria and were included for review. Included sources dealt with COP attributed to: head and neck cancer (3), multiple sclerosis-related trigeminal neuralgia-like symptoms (2), post-herpetic neuralgia (1), temporomandibular dysfunction (1), and primary burning mouth syndrome (1). Cannabinoids studied included: self-administered cannabis (3), topical N-palmitoyle-thanolamine (1), topical cannabis extract (1), cannabis sativa oil (1), nabiximols oromucosal spray (1), and nabilone (1). Most sources concluded their respective cannabinoid treatments to provide some therapeutic benefit for COP (6 of 8) and all concluded their treatments to be safe. Current research is wholistically focused, recording outcome measures for pain, anxiety, depression, quality of life, functional disability. Cannabinoids are most often studied as adjunctive and palliative treatments. Cannabinoids are becoming increasingly accessible and might benefit many COP patients. Patients and clinicians require more and higher quality evidence to make confident and informed decisions regarding treatment of COP with cannabis or cannabinoids. This review summarizes current evidence for patients, clinicians, and future researchers.

Marijuana, Cannabis, and Synthetic Cannabinoid Medications: What Are the Potential Risks and Adverse Effects?

Marijuana, Cannabis, and Synthetic Cannabinoid Medications: What Are the Potential Risks and Adverse Effects?

Correlates of treatment engagement and client outcomes: results of a randomised controlled trial of nabiximols for the treatment of cannabis use disorder

Introduction and aimsThere is increasing interest and evidence for the use of cannabinoid medications in the treatment of cannabis use disorder, but little examination of the correlates of successful treatment. This paper is a secondary analysis of a randomised placebo-controlled trial of nabiximols for the treatment of cannabis use disorder (CUD), aiming to identify which client and treatment characteristics impact treatment engagement and outcomes.MethodBayesian multiple regression models were used to examine the impact of age, gender, duration of regular cannabis use, daily quantity of cannabis, cannabis use problems, self-efficacy for quitting, sleep, mental health, pain measures, and treatment group upon treatment engagement (retention, medication dose, and counselling participation) and treatment outcomes (achieving end-of-study abstinence, and a 50% or greater reduction in cannabis use days) among the 128 clients participating in the 12-week trial.ResultsAmong the treatment factors, greater counselling attendance was associated with greater odds of abstinence and ≥ 50% reduction in cannabis use; nabiximols with greater odds of ≥ 50% reduction and attending counselling, and reduced hazard of treatment dropout; and higher dose with lower odds of ≥ 50% reduction. Among the client factors, longer duration of regular use was associated with higher odds of abstinence and 50% reduction, and lower hazard of treatment dropout; greater quantity of cannabis use with reduced hazard of dropout, greater odds of attending counselling, and higher average dose; greater pain at baseline with greater odds of ≥ 50% reduction and higher average dose; and more severe sleep issues with lower odds of ≥ 50% reduction. Males had lower odds of attending counselling.Discussions and conclusionsThese findings suggest that counselling combined with agonist pharmacotherapy may provide the optimal treatment for cannabis use disorder. Younger clients, male clients, and clients with sleep issues could benefit from extra support from treatment services to improve engagement and outcomes.Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN12616000103460) https://www.anzctr.org.au

Medical Cannabinoids: What Clinicians in Long-Term Care Should Know

Caring for the Ages is the official newspaper of AMDA and provides long-term care professionals with timely and relevant news and commentary about clinical developments and about the impact of health care policy on long-term care medicine.

Practices and perspectives on medical cannabis and cannabinoids: A survey of the National Psoriasis Foundation Medical Advisory Board

Practices and perspectives on medical cannabis and cannabinoids: A survey of the National Psoriasis Foundation Medical Advisory Board

Understanding the Evidence for Medical Cannabinoids for the Treatment of Chronic Pain

This paper is an examination of the existing literature on the use of medical cannabinoids for the treatment of adults with chronic pain (CP). The use of medical cannabinoids in the treatment of CP has been a controversial topic due to societal associations with the recreational use of cannabis and the lack of information as to their analgesic effects. This paper analyzes trends in how medical cannabinoids perform as an analgesic treatment for adults with CP, especially in comparison to opioids. Additionally, this paper explores any secondary effects participants may experience as a result of treatment with medical cannabinoids. It will be shown that, while medical cannabinoids have the potential to reduce pain in those suffering from CP, there are numerous factors that must be considered before they become an acceptable treatment option. In addition, there is evidence that the analgesic effects of medical cannabinoids may be primarily due to their intoxicating effect rather than their interaction with neural pain pathways. This review of existing literature acts to guide future research on the use of medical cannabinoids for the treatment of CP.

Cannabinoids reduce opioid use in older patients with pain : Retrospective three-year analysis of data from a general practice

Relevant data for the prescription and therapeutic effects of medical cannabinoids (CAM) are still missing in everyday medicine especially for elderly and geriatric patients. Documentation of prescription (duration, age) of CAM (dronabinol, nabiximols, cannabinoid extracts) and co-medicated opioids in adoctor's office specializing in pain. Analysis of the consumption of opioids (morphine equivalent) and CAM (THC equivalent) for age and gender. In all, 178 patients with chronic pain were treated for aperiod of 366 days (median; range 31-2590 days). Median age was 72years (26-96years); 115 were women (64.8%). Of these, 34were younger than 65years, 42were 65-80years and 40were more than 80years old. Of the 63men, 29were younger than 65years, 24were 65-80years and 10were older than 80years. Indications for CAM were chronic pain and the limitations for opioids because of side effects and worsening of quality of life. To total of 1001 CAM were prescribed, 557 (55.6%) dronabinol as liquid, 328 (32.7%) as full spectrum extracts and66 (6.6%) as oro-mucosal nabiximols spray. 50prescriptions (5%) contained more than one CAM simultaneously. The daily consumption of dronabinol liquor and extracts were 9.6 mg/day (median), and of spray 13.6 mg. The dosage over time did not change in patients older than64; in younger patients, there was anon-significant increasing trend. Women requested lower THCdosages compared to men (8.1 mg vs. 14.8 mg). Furthermore, 10patients (5.6%) stopped CAM because of failing effectivity, 7(3.9%) because of failing cost coverage and only 5because of adverse side effects. 115 patients (65%) with CAM also received opioids a median 65 mg/day morphine equivalents. This opioid dosage was significantly reduced in course of time by 24 mg/day morphine equivalents or 50%. This reduction was independent on CAM dosage, age and gender. Patients with chronic pain profit from long-term CAM which safely and significantly lower the consumption of comedicated opioids, even at low dosages (< 7.5 mg/day). For women, low-dose THC may be sufficient. Older patients benefit from CAM, and adverse effects do not limit the (chronic) use and prescription of CAM in the elderly.

Safety &amp; Efficacy of Medical Cannabinoids in Children

Source: Treves N, Mor N, Allegaert K, et al. Efficacy and safety of medical cannabinoids in children: a systematic review and meta-analysis. Sci Rep. 2021;11(1):23462; doi:10.1038/s41598-021-02770-6Investigators from multiple institutions conducted a systematic review and meta-analysis to assess the efficacy and safety of medical cannabinoids (MC) in children. Studies in which the efficacy and safety of MCs and placebo or other pharmacotherapy were compared in patients ≤18 years old were selected for review. Outcomes of interest included seizure reduction in children treated with cannabidiol (CBD) or CBD-containing products, reduction in vomiting and retching events in patients with chemotherapy induced nausea and vomiting treated with nabilone (synthetic D-9-Tetrahydrocannabinol [THC]), and adverse events in children receiving MCs such as decreased appetite, gastrointestinal hyperactivity (eg, vomiting, diarrhea, nausea, upset stomach), serious adverse events, adverse mental events, infections, and pyrexia. Seizure reduction was assessed as a 50% reduction in seizure rate from baseline, reported seizure events, and Caregiver Global Impression of Change (CGIC). A variety of statistical tests applicable to meta-analysis were used to compare outcomes in children treated with MCs or comparison treatment.Data from 8 studies were included in the review. Of these, 5 studies reported outcomes on seizure control: 3 evaluated CBD treatment for children with Dravet syndrome and 2 studies using CBD-THC extracts for other conditions. Overall, MCs were associated with an increase in achieving 50% reduction in seizures (RR, 1.69; 95% CI, 1.20, 2.36), and a significant reduction in seizure events (RR, 0.59; 95% CI, 0.36, 0.97); however, a statistically significant reduction in seizure events was observed only in studies evaluating pure CBD treatment and not in those assessing CBD-THC extracts. A significant improvement in CGIC scores was associated with MCs in these studies. Similarly, in 2 studies with a total of 48 participants, nabilone was found to be superior to conventional treatment (prochlorperazine or domperidone) as an anti-emetic in children receiving chemotherapy (difference in means, -11.5; P <0.001).There were 6 studies, including 513 patients, in which serious adverse events were assessed; a non-significant increase associated with MCs was found (RR, 1.59; 95% CI, 0.85, 2.98). Treatment with CBD in doses of 20 mg/kg was associated with decreased appetite (RR, 2.40; 95% CI, 1.39, 4.15, compared to placebo), but the overall risk associated with predominant CBD treatments was of borderline significance (RR, 2.10; 95% CI, 0.96, 4.62). CBD treatment also was associated with an increased risk of gastrointestinal hyperactivity (RR, 2.30; 95% CI, 1.28, 4.12). A statistically significant increase in adverse mental events was found in 4 of 8 studies. There was no statistically significant increase in risk of infections or pyrexia associated with MC use.The authors conclude that MCs are effective in the treatment of some conditions in children but may be associated with an increased risk of adverse events.Dr Candee has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The results of the current study build upon a prior systematic review from 2017 that was centered largely around the use of medical cannabinoids for Dravet syndrome, a rare drug-resistant epilepsy, which showed limited and low-quality evidence in support of the use of MC in children and adolescents.1 Beyond the addition of 3 more years of studies from which to choose, the current review is more comprehensive and stringent in its selection criteria, with investigators reaching out to authors for any missing data and combing through the references of any eligible studies to ensure inclusiveness. While the results of more recent studies support the safety and efficacy of long-term use of CBD for the treatment of epilepsy in children, the current study is the first of its kind to focus more broadly on treatment with MCs in the pediatric population.2,3The current study is, however, also thereby limited in its scope, as it includes MCs used for a variety of medical purposes (eg, epilepsy, severe behavioral problems, chemotherapy-induced nausea and vomiting, spasticity, and autism). This reduces the applicability of the findings. Furthermore, the precise outcomes for each data subset (based on pharmacological mechanism or organ system) were not defined during the study design phase but rather during the data extraction process. The observational nature of the study and limited size are weaknesses as well.Medical CBD is effective in reducing seizures in children with Dravet syndrome, and naboline (synthetic THC) decreases vomiting in patients treated with chemotherapy. Safety concerns related to MC use in children include adverse mental events. (See AAP Grand Rounds. 2021;46[4]:40.)4

Pharmacokinetics, Safety, and Tolerability of a Medicinal Cannabis Formulation in Patients with Chronic Non-cancer Pain on Long-Term High Dose Opioid Analgesia: A Pilot Study.

IntroductionThis phase I open-label study examined pharmacokinetics, safety, and tolerability of escalating doses of a novel combination cannabinoid medication (1:1 tetrahydrocannabinol [THC]/cannabidiol [CBD]) in patients with chronic non-cancer pain (CNCP) on high dose opioid analgesia.MethodsNine people with CNCP and oral morphine equivalent daily dose of 60 mg or higher were recruited. Blood concentrations of THC, 11-hydroxytetrahydrocannabinol (OH-THC), 11-nor-9-carboxy-tetrahydrocannabinol (COOH-THC), and CBD were assayed weekly. Concentrations were measured after a single dose of 2.5 mg THC/2.5 mg CBD on day 1, and daily escalating doses up to a single dose of 12.5 mg THC/12.5 mg CBD on day 29. Follow-up was on day 36 after a 7-day washout. Secondary outcome data encompassed pain, mood, and sleep parameters.ResultsThe parent compounds THC, and CBD, and metabolites OH-THC and COOH-THC were detected at most time points. In general, the concentration of all analytes increased until 2 h post-administration, decreasing to approximately pre-dose concentrations by 8 h. There was considerable inter- and intra-individual variability. The study medication was well tolerated. Eight participants reported at least one adverse event (AE), with a total of 62 AEs; most common were euphoric mood, headache, and agitation, none classified as severe. There was no significant change to pain severity self-ratings, nor use of pain medications. Improvements in pain interference scores, mood, and some sleep parameters were observed.ConclusionThe THC/CBD formulation was tolerated well in a group of patients with CNCP. Between-participant variability supports personalized dosing and “start low–go slow” titration. To validate and quantify improvements in secondary efficacy outcomes a randomized placebo-controlled study is needed.Trial RegistrationAustralian New Zealand Clinical Trials Register (CT-2019-CTN-01224-1).Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00344-y.

Efficacy and safety of medical cannabinoids in children: a systematic review and meta-analysis

Despite the increased use of medical cannabinoids, the efficacy and safety of the treatment among children remain uncertain. The objective was to study the efficacy and safety of medical cannabinoids in children. The search included studies through 11-May-2020. Selection criteria included studies evaluating efficacy and safety outcomes of medical cannabinoids (tetrahydrocannabinol, cannabidiol and other cannabis derivatives) versus control in children, independently assessed by two reviewers. Eight studies were included, all of which are randomized controlled trials. Cannabidiol is associated with 50% reduction in seizures rate (Relative Risk (RR) = 1.69, 95% CI [1.20–2.36]) and caregiver global impression of change (Median Estimated difference = (− 1), 95%CI [− 1.39–(− 0.60)]) in Dravet syndrome, compared to placebo. While cannabidiol was associated with a reduction in reported seizure events (RR = 0.59, 95% CI [0.36–0.97]), no association was found in products contained also tetrahydrocannabinol (RR = 1.35, 95% CI [0.46–4.03]). Higher dose of cannabidiol was associated with decreased appetite (RR = 2.40, 95% CI [1.39–4.15]). A qualitative assessment suggests that medical cannabinoids might be associated with adverse mental events. In conclusion, cannabidiol is associated with clinical improvement in Dravet syndrome. However, cannabidiol is also associated with decreased appetite. Adverse mental events were reported as well, however, more research should be performed to assess well this outcome.

Long-Term Pain Characteristics and Management Following Minimally Invasive Spinal Decompression and Open Laminectomy and Fusion for Spinal Stenosis.

Background and Objectives: To compare the long-term pain characteristics and its chronic management following minimally invasive spinal (MIS) decompression and open laminectomy with fusion for lumbar stenosis. Materials and Methods: The study cohort included patients with a minimum 5-year postoperative follow-up after undergoing either MIS decompression or laminectomy with fusion for spinal claudication. The primary outcome of interest was chronic back and leg pain intensity. Secondary outcome measures included pain frequency during the day, chronic use of non-opioid analgesics, narcotic medications, medical cannabinoids, and continuous interventional pain treatments. Results: A total of 95 patients with lumbar spinal stenosis underwent one- or two-level surgery for lumbar spinal stenosis between April 2009 and July 2013. Of these, 50 patients underwent MIS decompression and 45 patients underwent open laminectomy with instrumented fusion. In the fusion group, a higher percentage of patients experienced moderate-to-severe back pain with 48% compared to 21.8% of patients in the MIS decompression group (p < 0.01). In contrast, we found no significant difference in the reported leg pain in both groups. In the fusion group, 20% of the patients described their back and leg pain as persistent throughout the day compared to only 2.2% in the MIS decompression group (p < 0.05). A trend toward higher chronic dependence on analgesic medication and repetitive pain clinic treatments was found in the fusion group. Conclusions: MIS decompression for the treatment of degenerative spinal stenosis resulted in decreased long-term back pain and similar leg pain outcomes compared to open laminectomy and instrumented fusion surgery.