Oral Cannabinoids Research Articles

An Algorithm for Automated Measurement of Kinetic Tremor Magnitude Using Digital Spiral Drawings

Introduction: Essential tremor is a common movement disorder. Numerous validated clinical rating scales exist to quantify essential tremor severity by employing rater-dependent visual observation but have limitations, including the need for trained human raters and the lack of precision and sensitivity compared to technology-based objective measures. Other continuous objective methods to quantify tremor amplitude have been developed, but frequently provide unitless measures (e.g., tremor power), limiting real-world interpretability. We propose a novel algorithm to measure kinetic tremor amplitude using digital spiral drawings, applying the V3 framework (sensor verification, analytical validation, and clinical validation) to establish reliability and clinical utility. Methods: Archimedes spiral drawings were recorded on a digitizing tablet from participants (n = 7) enrolled in a randomized placebo control double-blinded crossover pilot trial evaluating the efficacy of oral cannabinoids in reducing essential tremor. We developed an algorithm to calculate the mean and maximum tremor amplitude derived from the spiral tracings. We compared the digitally measured tremor amplitudes to manual measurement to evaluate sensor reliability, determined the test-retest reliability of the digital output across two short-interval repeated measures, and compared the digital measure to kinetic tremor severity graded using The Essential Tremor Rating Assessment Scale (TETRAS) score for spiral drawings. Results: This algorithm for automated assessment of kinetic tremor amplitude from digital spiral tracings demonstrated a high correlation with manual spot measures of tremor amplitude, excellent test-retest reliability, and a high correlation with human ratings of the TETRAS score for spiral drawing severity when the tremor severity was rated “slight tremor” or worse. Discussion: This digital measure provides a simple and clinically relevant evaluation of kinetic tremor amplitude that shows promise as a potential future endpoint for use in clinical trials of essential tremor.

Feasibility of a Randomized, Interventional Pilot Clinical Study of Oral Cannabinoids in People with HIV on Antiretroviral Therapy: CTNPT 028.

Cannabis-based medicines (CBMs) could help reduce systemic inflammation in people with HIV (PWH). In a prospective, randomized pilot study we enrolled participants from August 2021-April 2022 with HIV, aged ≥18 and on antiretroviral therapy and randomly assigned them to cannabidiol (CBD) ± Δ9-tetrahydrocannabinol (THC) capsules for 12 weeks with the primary objective being to assess safety and tolerability. Here we report on timeliness to study initiation, enrolment, compliance and retention rates. The target sample size was not reached. Two hundred and five individuals were approached, and 10 consented and were randomized; the rest refused (reasons: cannabis-related stigma/discomfort; too many study visits/insufficient time; unwillingness to undergo a "washout period" for three weeks) or were not eligible. The age of those randomized was 58 years (IQR 55-62); 80% were male. Only three met all criteria (30% enrolment compliance); seven were enrolled with minor protocol deviations. Compliance was excellent (100%). Eight (80%) participants completed the study; two (20%) were withdrawn for safety reasons (transaminitis and aggravation of pre-existing anemia). Time to study initiation and recruitment were the most challenging aspects. Ongoing work is required to reduce stigma related to CBMs. Future studies should find a balance between the requirements for safety monitoring and frequency of study visits.

Pharmacokinetics of Oral Minor Cannabinoids in Blood and Brain.

Introduction: Minor cannabinoids are increasingly being consumed in oral formulations (i.e., edibles, tinctures) for medical and nonmedical purposes. This study examined the pharmacokinetics (PKs) of cannabinoids tetrahydrocannabivarin (THCV), cannabichromene (CBC), cannabinol (CBN), and delta-8-tetrahydrocannabinol (D8-THC) after the first and last oral dose during a 14-day administration period. Materials and Methods: Sprague-Dawley rats (N=6 animals/dose, 50% female) were given an assigned dose of one of four cannabinoids (THCV=3.2-100 mg/kg, CBC=3.2-100 mg/kg, CBN=1-100 mg/kg, or D8-THC=0.32-10 mg/kg) or vehicle (medium-chain triglyceride oil) through oral gavage once daily for 14 days. Blood was collected 45 min and 1.5, 3, and 24 h following the first dose (day 1) and the last dose (day 14) of repeated oral cannabinoid treatment for PK analysis. Outcomes of interest included time to maximum concentration (Tmax), maximum concentration (Cmax), and area under the concentration versus time curve (AUClast). Dose-normalized (DN) Cmax and DN AUClast were also calculated. Brain tissue was collected 24 h post-administration of the first (day 1) and the last (day 14) dose of each cannabinoid to determine concentrations in brain. Results: All cannabinoids tested were detectable in plasma after single and 14-day repeated dosing. DN Cmax and DN AUClast were highest for D8-THC, followed by CBC, CBN, and THCV. There was no sex difference observed in cannabinoid kinetics. Accumulation of D8-THC in plasma was observed after 14 days of administration. THCV levels in plasma were lower on day 14 compared to day 1, indicating potential adaptation of metabolic pathways and increased drug elimination. Cannabinoids were detected in brain tissue 24 h post-administration of the first and the last dose of 17-100 mg/kg THCV, 3.2-100 mg/kg CBC, 10-100 mg/kg CBN, and 10 mg/kg D8-THC. Conclusions: THCV, CBC, CBN, and D8-THC produced detectable levels in plasma and translocated to brain tissue after the first dose (day 1) and the last dose (day 14) of repeated oral dosing. Examination of PKs of these minor cannabinoids in blood and brain provides a critical step for informing target dose ranges and dosing schedules in future studies that evaluate the potential effects of these compounds.

Effects of Oral Cannabinoids on Systemic Inflammation and Viral Reservoir Markers in People with HIV on Antiretroviral Therapy: Results of the CTN PT028 Pilot Clinical Trial.

Chronic HIV infection is characterized by persistent inflammation despite antiretroviral therapy (ART). Cannabinoids may help reduce systemic inflammation in people with HIV (PWH). To assess the effects of oral cannabinoids during HIV, ten PWH on ART were randomized (n = 5/group) to increasing doses of oral Δ9-tetrahydrocannabinol (THC): cannabidiol (CBD) combination (2.5:2.5-15:15 mg/day) capsules or CBD-only (200-800 mg/day) capsules for 12 weeks. Blood specimens were collected prospectively 7-21 days prior to treatment initiation and at weeks 0 to 14. Plasma cytokine levels were determined via Luminex and ELISA. Immune cell subsets were characterized by flow cytometry. HIV DNA/RNA were measured in circulating CD4 T-cells and sperm by ultra-sensitive qPCR. Results from both arms were combined for statistical analysis. Plasma levels of IFN-γ, IL-1β, sTNFRII, and REG-3α were significantly reduced at the end of treatment (p ˂ 0.05). A significant decrease in frequencies of PD1+ memory CD4 T-cells, CD73+ regulatory CD4 T-cells, and M-DC8+ intermediate monocytes was also observed (p ˂ 0.05), along with a transient decrease in CD28-CD57+ senescent CD4 and CD8 T-cells. Ki-67+ CD4 T-cells, CCR2+ non-classical monocytes, and myeloid dendritic cells increased over time (p ˂ 0.05). There were no significant changes in other inflammatory markers or HIV DNA/RNA levels. These findings can guide future large clinical trials investigating cannabinoid anti-inflammatory properties.

A Phase I Dose Escalation and Expansion Study of Epidiolex (Cannabidiol) in Patients with Biochemically Recurrent Prostate Cancer.

Cannabinoids (CBD) have anti-tumor activity against prostate cancer (PCa). Preclinical studies have demonstrated a significant decrease in prostate specific antigen (PSA) protein expression and reduced tumor growth in xenografts of LNCaP and DU-145 cells in athymic mice when treated with CBD. Over-the-counter CBD products may vary in activity without clear standardization, and Epidiolex is a standardized FDA-approved oral CBD solution for treatment of certain types of seizures. We aimed to assess the safety and preliminary anti-tumor activity of Epidiolex in patients with biochemically recurrent (BCR) PCa. This was an open-label, single center, phase I dose escalation study followed by a dose expansion in BCR patients after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy). Eligible patients were screened for urine tetrahydrocannabinol prior to enrollment. The starting dose level of Epidiolex was 600 mg by mouth once daily and escalated to 800 mg daily with the use of a Bayesian optimal interval design. All patients were treated for 90 days followed by a 10-day taper. The primary endpoints were safety and tolerability. Changes in PSA, testosterone levels, and patient-reported health-related quality of life were studied as secondary endpoints. Seven patients were enrolled into the dose escalation cohort. There were no dose-limiting toxicities at the first two dose levels (600 mg and 800 mg). An additional 14 patients were enrolled at the 800 mg dose level into the dose expansion cohort. The most common adverse events were 55% diarrhea (grade 1-2), 25% nausea (grade 1-2), and 20% fatigue (grade 1-2). The mean PSA at baseline was 2.9 ng/mL. At the 12-week landmark time-point, 16 out of 18 (88%) had stable biochemical disease, one (5%) had partial biochemical response with the greatest measurable decline being 41%, and one (5%) had PSA progression. No statistically significant changes were observed in patient-reported outcomes (PROs), but PROs changed in the direction of supporting the tolerability of Epidiolex (e.g., emotional functioning improved). Epidiolex at a dose of 800 mg daily appears to be safe and tolerable in patients with BCR prostate cancer supporting a safe dose for future studies.

Safety and Tolerability of Oral Cannabinoids in People Living with HIV on Long-Term ART: A Randomized, Open-Label, Interventional Pilot Clinical Trial (CTNPT 028).

With anti-inflammatory properties, cannabinoids may be a potential strategy to reduce immune activation in people living with HIV (PLWH) but more information on their safety and tolerability is needed. We conducted an open-label interventional pilot study at the McGill University Health Centre in Montreal, Canada. PLWH were randomized to oral Δ9-tetrahydrocannabinol (THC): cannabidiol (CBD) combination (THC 2.5 mg/CBD 2.5 mg) or CBD-only capsules (CBD 200 mg). Individuals titrated doses as tolerated to a maximum daily dose THC 15 mg/CBD 15 mg or 800 mg CBD, respectively, for 12 weeks. The primary outcome was the percentage of participants without any significant toxicity based on the WHO toxicity scale (Grades 0-2 scores). Out of ten individuals, eight completed the study. Two from the CBD-only arm were withdrawn for safety concerns: phlebotomy aggravating pre-existing anemia and severe hepatitis on 800 mg CBD with newly discovered pancreatic adenocarcinoma, respectively. Seven did not have any significant toxicity. Cannabinoids did not alter hematology/biochemistry profiles. CD4 count, CD4/CD8 ratio, and HIV suppression remained stable. Most adverse effects were mild-moderate. In PLWH, cannabinoids seem generally safe and well-tolerated, though larger studies are needed. Screening for occult liver pathology should be performed and hepatic enzymes monitored, especially with high CBD doses.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Are Cannabis and Cannabinoids Effective for Symptomatic Treatment in People With Multiple Sclerosis?: A Cochrane Review Summary With Commentary.

Are Cannabis and Cannabinoids Effective for Symptomatic Treatment in People With Multiple Sclerosis?: A Cochrane Review Summary With Commentary.

The Efficacy of Cannabis on Multiple Sclerosis-Related Symptoms.

Multiple sclerosis (MS) is known as an autoimmune disease that damages the neurons in the central nervous system. MS is characterized by its most common symptoms of spasticity, muscle spasms, neuropathic pain, tremors, bladder dysfunction, dysarthria, and some intellectual problems, including memory disturbances. Several clinical studies have been conducted to investigate the effects of cannabis on the relief of these symptoms in MS patients. The efficacy of Cannabis sativa (C. Sativa) in the management of MS outcomes such as spasticity, pain, tremors, ataxia, bladder functions, sleep, quality of life, and adverse effects were assessed in this review. Most clinical studies showed the positive effects of cannabinoids with their different routes of administration, such as oromucosal spray and oral form, in reducing most MS symptoms. The oromucosal spray Nabiximols demonstrated an improvement in reducing MS spasticity, pain, and quality of life with a tolerated adverse effect. Oral cannabinoids are significantly effective for treating MS pain and spasticity, while the other symptoms indicate slight improvement and the evidence is quite inconsistent. Oromucosal spray and oral cannabis are mainly used for treating patients with MS and have positive effects on treating the most common symptoms of MS, such as pain and spasticity, whereas the other MS symptoms indicated slight improvement, for which further studies are needed.

A phase I does-escalation and expansion study of epidiolex (cannabidiol) in patients with biochemically recurrent prostate cancer.

257 Background: There is a need for a low toxicity option for men with prostate cancer with biochemical recurrence (BCR) following primary curative therapy. Cannabinoids (CBD) have anti-tumor activity in preclinical studies, but products may vary in activity without clear standardization. As epidiolex is a standardized FDA approved oral CBD solution for treatment of certain types of seizures, we studied epidiolex in patients with BCR of prostate cancer to determine safety and dosing of this therapy to support future studies. Methods: We present an open-label, single center, phase I dose escalation study followed by a dose expansion. Patients with BCR prostate cancer after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy) were eligible. Majority of our patients’ prostate-specific antigen (PSA) doubling time was ≤ 12 months. All patients were screened for urine tetrahydrocannabinol (THC) prior to enrollment. With use of a Bayesian optimal interval design, patients received escalating doses of epidiolex starting at 600mg daily and up to 800mg daily. All patients were treated for 90 days followed by a 10 day taper. The Primary endpoints were safety and tolerability. Patients were monitored for both acute (30 days) and chronic (90 days) treatment-related toxicities. Secondary endpoints included change in PSA levels and testosterone levels from baseline throughout the treatment period. Results: A total of 21 patients were enrolled but four withdrew from the study (one patient was hospitalized with COVID-19 and three patients requested to stop due to grade 2 adverse events (AEs). There were seven patients included in the dose escalation phase. Four patients received 600mg daily; two of the four in this phase did not finish the first 30 days (one with COVID-19 and one withdrew). The other three patients received 800 mg daily. No dose-limiting toxicities were observed at any dose level so an additional 14 patients were enrolled at the 800mg dose. Treatment-related chronic AEs occurring in >10% of patients were grade 1 or 2 diarrhea (47.6%), grade 1 or 2 nausea (23.8%) and grade 1 or 2 fatigue (19%). The mean PSA at baseline was 2.9 ng/ml. One patient developed oligo-metastasis disease, two patients progressed after the study period, and one patient died from a non-treatment or disease-related cause. Conclusions: Epidiolex at a dose of 800mg daily appears to be safe and tolerable in patients with BCR of prostate cancer, supporting a safe dose for future studies to determine if there is clinical activity to delay development of hormone refractory metastatic disease. Clinical trial information: NCT04428203.

Medical cannabis and cannabinoids for impaired sleep: a systematic review and meta-analysis of randomized clinical trials.

We conducted a systematic review to explore the effectiveness of medical cannabis for impaired sleep. We searched MEDLINE, EMBASE, CENTRAL, and PsychINFO to January 2021 for randomized trials of medical cannabis or cannabinoids for impaired sleep vs. any non-cannabis control. When possible, we pooled effect estimates for all patient-important sleep-related outcomes and used the GRADE approach to appraise the certainty of evidence. Thirty-nine trials (5100 patients) were eligible for review, of which 38 evaluated oral cannabinoids and 1 administered inhaled cannabis. The median follow-up was 35 days, and most trials (33 of 39) enrolled patients living with chronic cancer or noncancer chronic pain. Among patients with chronic pain, moderate certainty evidence found that medical cannabis probably results in a small improvement in sleep quality versus placebo (modeled risk difference [RD] for achieving the minimally important difference [MID], 8% [95% CI, 3 to 12]). Moderate to high certainty evidence shows that medical cannabis vs. placebo results in a small improvement in sleep disturbance for chronic non-cancer pain (modeled RD for achieving the MID, 19% [95% CI, 11 to 28]) and a very small improvement in sleep disturbance for chronic cancer pain (weighted mean difference of -0.19 cm [95%CI, -0.36 to -0.03 cm]; interaction p = .03). Moderate to high certainty evidence shows medical cannabis, versus placebo, results in a substantial increase in the risk of dizziness (RD 29% [95%CI, 16 to 50], for trials with ≥3 months follow-up), and a small increase in the risk of somnolence, dry mouth, fatigue, and nausea (RDs ranged from 6% to 10%). Medical cannabis and cannabinoids may improve impaired sleep among people living with chronic pain, but the magnitude of benefit is likely small.

Tolerability profile of topical cannabidiol and palmitoylethanolamide: a compilation of single-centre randomized evaluator-blinded clinical and in vitro studies in normal skin.

An increasing number of studies have investigated the adverse effect profile of oral cannabinoids; however, few studies have provided sufficient data on the tolerability of topical cannabinoids in human participants. To assess the tolerability profile of several commercial topical formulations containing cannabidiol (CBD) and palmitoylethanolamide (PEA) on the skin of healthy human participants. Three human clinical trials and one in vitro study were conducted. The potential for skin irritation, sensitization and phototoxicity of several products, were assessed via patch testing on healthy human skin. The products assessed included two formulations containing CBD and PEA, one containing hemp seed oil and four concentrations of CBD alone. Ocular toxicity was tested using a traditional hen's egg chorioallantoic membrane model with three CBD, PEA and hemp seed oil formulations. There was no irritation or sensitization of the products evident via patch testing on healthy participants. Additionally, mild phototoxicity of a hemp seed oil product was found at the 48-h time point compared with the negative control. The in vitro experiment demonstrated comparable effects of cannabinoid products with historically nonirritating products. These specific formulations of CBD- and PEA-containing products are nonirritating and nonsensitizing in healthy adults, and further encourage similar research assessing their long-term safety and efficacy in human participants with dermatological diseases. There are some limitations to the study: (i) external validity may be limited as formulations from a single manufacturer were used for this study, while vast heterogeneity exists across unregulated, commercial CBD products on the market; and (ii) products were assessed only on normal, nondiseased human skin, and therefore extrapolation to those with dermatological diseases cannot be assumed.

A systematic review of quantitative analysis of cannabinoids in oral fluid.

Cannabis sativa L. is a substance widely used around the world for recreational and medicinal purposes. Oral fluid has been investigated as an alternative biological matrix for demonstrating the illegal use of cannabis, particularly in situations where its recent use needs to be identified. In the last two decades, many methods have been developed to detect and quantify cannabinoids in oral fluid, especially for Δ9 -tetrahydrocannabinol, the primary psychoactive substance of cannabis. However, some aspects must be considered in the use of these techniques, such as cannabinoids recoveries or extraction efficiency from different oral fluid collection devices/containers. Pharmacokinetic studies have shown that the presence of minor cannabinoids and metabolites in the analysis of oral fluid may be valuable in interpreting tests, which indicates the need to improve the sensitivity of detecting low concentrations. The aim of this review is to summarize and to describe the methodologies for the quantitative analysis of cannabinoids in oral fluid that have previously been investigated. A systematic search for articles was performed of four different databases, using the descriptor "cannabinoids and oral fluid". Forty-seven studies that examined quantitative methods were identified. The analytical data described in these articles, including oral fluid collection, sample preparation, cannabinoids recovery and extraction efficiency, detection instruments, and quantification limits, were analyzed. The discussion of these particular features of cannabinoid analysis in oral fluid could help to improve or to develop methods for use in Forensic Toxicology.

New momentum in exploring marijuana's medical benefits: Marijuana has been lauded and lambasted for its potential effects on the body. In part 1 of a 2-part series, we investigate the accumulating evidence for the effectiveness of cannabis in treating some medical conditions.

New momentum in exploring marijuana's medical benefits: Marijuana has been lauded and lambasted for its potential effects on the body. In part 1 of a 2-part series, we investigate the accumulating evidence for the effectiveness of cannabis in treating some medical conditions.

Oral medicinal cannabinoids to relieve symptom burden in the palliative care of patients with advanced cancer: a double-blind, placebo-controlled, randomised clinical trial of efficacy and safety of 1:1 delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)

BackgroundDespite improvements in medical care, patients with advanced cancer still experience substantial symptom distress. There is increasing interest in the use of medicinal cannabinoids but little high-quality evidence to guide clinicians. This study aims to define the role of a 1:1 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom burden in patients with advanced cancer undergoing standard palliative care.Methods and designOne hundred fifty participants will be recruited from five sites within the Queensland Palliative Care Research Group (QPCRG) and randomly assigned to an active treatment or placebo group. This study is a pragmatic multicentre, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:1 THC/CBD cannabinoid preparation. It will compare efficacy and safety outcomes of a titrated dose (10 mg/10 mg/mL oral solution formulation, dose range 2.5 mg/2.5 mg–30 mg/30 mg/day) against placebo. There is a 2-week patient-determined titration phase, using escalating doses of 1:1 THC/CBD or placebo, to reach a dose that achieves symptom relief with tolerable side effects. This is then followed by a further 2-week assessment period on the stable dose determined in collaboration with clinicians. The primary objective is to assess the effect of escalating doses of a 1:1 THC/CBD cannabinoid preparation against placebo on change in total symptom score, with secondary objectives including establishing a patient-determined effective dose, the change in total physical and emotional sores, global impression of change, anxiety and depression, opioid use, quality of life and adverse effects.DiscussionThis will be the first placebo-controlled clinical trial to rigorously evaluate the efficacy, safety and acceptability of 1:1 THC/CBD for symptom relief in advanced cancer patients. This study will allow the medical community to have some evidence to present to patients wishing to access cannabis for their symptoms caused by advanced malignancy.Trial registrationACTRN, ACTRN12619000037101. Registered on 14 January 2019.Trial Sponsor: Mater Misericordiae Limited (MML) and Mater Medical Research Institute Limited (MMRI)—Raymond Terrace, South Brisbane, Brisbane, QLD, Australia

Complementary and Alternative (CAM) Treatment Options for Women with Pelvic pain.

I.To provide an overview of the current complementary and alternative (CAM) treatment options for women with chronic pelvic pain (CPP). II.Recent studies on chronic pain at cellular, molecular and network level and their interaction with the immune system has unfolded several mechanisms for pain making it promising to explore the alternative paradigm to manage the incredibly complex chronic pelvic pain condition where multifactorial etiology often limits successful outcomes. III.The multifactorial nature and complexity in establishing the underlying diagnosis in CPP limits predictable response to traditional medical and interventional options. Complementary and alternative options have been studied to improve outcomes. Incorporation of exercise-based CAM, pelvic floor physical therapy, acupuncture and cognitive behavioral therapy are suggested to show promising results but well powered randomized studies are needed to draw conclusions on their efficacy. Evidence for non-opioid alternatives such as oral cannabinoids are preliminary and may emerge to be safe and effective.

Cannabinoids in the Management of Acute Pain: A Systematic Review and Meta-analysis.

Objective: To synthesize the best evidence surrounding the efficacy of cannabinoids for acute pain in the clinical setting based on subjective pain scores and observed adverse effects. Design: Systematic review with meta-analysis. Data Sources: PubMed, Embase, Cochrane Databases, and Google Scholar. Eligibility Criteria: English-language randomized-controlled clinical trials comparing cannabinoids with placebo in patients with acute pain. Data Extraction and Synthesis: Study quality was assessed using the Cochrane risk of bias tool. All stages were conducted independently by a team of three reviewers. Data were pooled through meta-analysis and stratified by route of administration. Primary Outcomes and Measures: Patient-reported pain and adverse events (AEs). Results: Six trials (678 participants) were included examining oral (5 trials) and intramuscular (1 trial) cannabinoids. Overall, there was a small but statistically significant treatment effect favoring the use of cannabinoids over placebo (-0.90, 95% confidence interval [CI] -1.69 to -0.1, i 2=65%, p=0.03). When stratified by route of administration, intramuscular cannabinoids were found to have a significant reduction in pain relative to placebo (-2.98, 95% CI -4.09 to -1.87, i 2=0%, p<0.0001). No difference in effect was observed between oral cannabinoids and placebo (-0.21, 95% CI -0.64 to 0.22, i 2=3%, p=0.34). Serious AEs were rare, and similar across the cannabinoid (14/374, 3.7%) and placebo groups (8/304, 2.6%). Conclusions: There is low-quality evidence indicating that cannabinoids may be a safe alternative for a small but significant reduction in subjective pain score when treating acute pain, with intramuscular administration resulting in a greater reduction relative to oral. Higher quality, long-term randomized-controlled trials examining whether there may be a role for cannabinoids in treating acute pain are required.

Comparison of Efficacy of Cannabinoids versus Commercial Oral Care Products in Reducing Bacterial Content from Dental Plaque: A Preliminary Observation.

BackgroundDental plaque is a complex biofilm that gets formed on the teeth and acts as a reservoir of different microbes. It is the root cause for the occurrence of several dental problems and diseases, including cavities, bad breath, bleeding gums, tooth decay, and tooth loss. Therefore, it should be regularly removed using suitable oral care aids.ObjectivesThe present study compared the efficacy of oral care products and cannabinoids in reducing the bacterial content of dental plaques.MethodsSixty adults aged 18 to 45 years were categorized into six groups based on the Dutch periodontal screening index. Dental plaques of the adults were collected using paro-toothpick sticks and spread on two Petri dishes, each with four divisions. On Petri dish-A, cannabidiol (CBD), cannabichromene (CBC), cannabinol (CBN), and cannabigerol (CBG) were used, and on Petri dish-B, cannabigerolic acid (CBGA), Oral B, Colgate, and Cannabite F (a toothpaste formulation of pomegranate and algae) were used. The Petri dishes were sealed and incubated, followed by counting the number of colonies.ResultsBy evaluating the colony count of the dental bacteria isolated from six groups, it was found that cannabinoids were more effective in reducing the bacterial colony count in dental plaques as compared to the well-established synthetic oral care products such as Oral B and Colgate.ConclusionCannabinoids have the potential to be used as an effective antibacterial agent against dental plaque-associated bacteria. Moreover, it provides a safer alternative for synthetic antibiotics to reduce the development of drug resistance.

Oral cannabinoid for the prophylaxis of chemotherapy-induced nausea and vomiting-a systematic review and meta-analysis.

Chemotherapy-induced nausea and vomiting (CINV) is a burdensome adverse event frequently associated with chemotherapy treatment of cancer. Evidence suggests that cannabinoid CB2 receptors are present in brainstem neurons, and thus, there may exist a role for cannabinoids to counter CINV. The aim of this paper is to conduct a systematic review and meta-analysis of the efficacy and safety of oral cannabinoids compared with other treatments as documented in randomized controlled trials (RCTs). A literature search was conducted using Ovid MEDLINE up until December 31, 2018; Embase Classic and Embase up until 2018 week 53; and Cochrane Central Register of Controlled Trials up until November 2018. Study data were extracted and included in this meta-analysis if they reported on at least one of the following efficacy endpoints: no nausea and no vomiting, no nausea, and no vomiting. The Mantel-Haenszel method and random effects analysis model were used, to generate odds ratio (OR) and accompanying 95% confidence intervals (CI). In the setting of prophylactic treatment against both nausea and vomiting, oral cannabinoid was more efficacious than placebo or other studied antiemetic treatments. When controlling for vomiting, oral cannabinoid was equally as efficacious as others. Against nausea, oral cannabinoid was equally as effective as other treatments. A greater percentage of patients administered oral cannabinoid for CINV experienced dysphoria, euphoria, and sedation. Although there exists some evidence suggesting that oral cannabinoids may have a role in controlling for emesis from a neurophysiological perspective, these conclusions are currently not mirrored in the published RCTs to date. However, there exists only a limited number of RCTs, comparisons with older treatment regimens and a lack of standard reporting practice across published literature. Further RCTs should investigate the efficacy and safety of oral cannabinoids, to secure a better picture of the efficacy of oral cannabinoids against CINV.

Cannabinoids in Chronic Non-Cancer Pain: A Systematic Review and Meta-Analysis

Background:For patients with chronic, non-cancer pain, traditional pain-relieving medications include opioids, which have shown benefits but are associated with increased risks of addiction and adverse effects. Medical cannabis has emerged as a treatment alternative for managing these patients and there has been a rise in the number of randomized clinical trials in recent years; therefore, a systematic review of the evidence was warranted.Objective:To analyze the evidence surrounding the benefits and harms of medical cannabinoids in the treatment of chronic, non-cancer-related pain.Design:Systematic review with meta-analysis.Data sources:Medline, Embase, CINAHL, SCOPUS, Google Scholar, and Cochrane Databases.Eligibility criteria:English language randomized clinical trials of cannabinoids for the treatment of chronic, non-cancer-related pain.Data extraction and synthesis:Study quality was assessed using the Cochrane risk of bias tool. All stages were conducted independently by a team of 6 reviewers. Data were pooled through meta-analysis with different durations of treatment (2 weeks, 2 months, 6 months) and stratified by route of administration (smoked, oromucosal, oral), conditions, and type of cannabinoids.Main outcomes and measures:Patient-reported pain and adverse events (AEs).Results:Thirty-six trials (4006 participants) were included, examining smoked cannabis (4 trials), oromucosal cannabis sprays (14 trials), and oral cannabinoids (18 trials). Compared with placebo, cannabinoids showed a significant reduction in pain which was greatest with treatment duration of 2 to 8 weeks (weighted mean difference on a 0-10 pain visual analogue scale −0.68, 95% confidence interval [CI], −0.96 to −0.40, I2 = 8%, P < .00001; n = 16 trials). When stratified by route of administration, pain condition, and type of cannabinoids, oral cannabinoids had a larger reduction in pain compared with placebo relative to oromucosal and smoked formulations but the difference was not significant (P[interaction] > .05 in all the 3 durations of treatment); cannabinoids had a smaller reduction in pain due to multiple sclerosis compared with placebo relative to other neuropathic pain (P[interaction] = .05) within 2 weeks and the difference was not significant relative to pain due to rheumatic arthritis; nabilone had a greater reduction in pain compared with placebo relative to other types of cannabinoids longer than 2 weeks of treatment but the difference was not significant (P[interaction] > .05). Serious AEs were rare, and similar across the cannabinoid (74 out of 2176, 3.4%) and placebo groups (53 out of 1640, 3.2%). There was an increased risk of non-serious AEs with cannabinoids compared with placebo.Conclusions:There was moderate evidence to support cannabinoids in treating chronic, non-cancer pain at 2 weeks. Similar results were observed at later time points, but the confidence in effect is low. There is little evidence that cannabinoids increase the risk of experiencing serious AEs, although non-serious AEs may be common in the short-term period following use.