cannabidiol

Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain

Bethie Seay — Tue, 02 Nov 2021 05:00:00 +0000

Date Added:

November 2, 2021

Journal/Publication:

Agency for Healthcare Research and Quality

Publication Date:

October 27, 2021

Issue:

Volume:

Pages:

EHC036

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.23970/AHRQEPCCER250

This is a summary of the evidence available to date on cannabis and other plant-based treatments for chronic pain.

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Objectives. To evaluate the evidence on benefits and harms of cannabinoids and similar plant-based compounds to treat chronic pain.

Data sources. Ovid® MEDLINE®, PsycINFO®, Embase®, the Cochrane Library, and SCOPUS® databases, reference lists of included studies, submissions received after Federal Register request were searched to July 2021.

Review methods. Using dual review, we screened search results for randomized controlled trials (RCTs) and observational studies of patients with chronic pain evaluating cannabis, kratom, and similar compounds with any comparison group and at least 1 month of treatment or followup. Dual review was used to abstract study data, assess study-level risk of bias, and rate the strength of evidence. Prioritized outcomes included pain, overall function, and adverse events. We grouped studies that assessed tetrahydrocannabinol (THC) and/or cannabidiol (CBD) based on their THC to CBD ratio and categorized them as high-THC to CBD ratio, comparable THC to CBD ratio, and low-THC to CBD ratio. We also grouped studies by whether the product was a whole-plant product (cannabis), cannabinoids extracted or purified from a whole plant, or synthetic. We conducted meta-analyses using the profile likelihood random effects model and assessed between-study heterogeneity using Cochran’s Q statistic chi square and the I2 test for inconsistency. Magnitude of benefit was categorized into no effect or small, moderate, and large effects.

Results. From 2,850 abstracts, 20 RCTs (N=1,776) and 7 observational studies (N=13,095) assessing different cannabinoids were included; none of kratom. Studies were primarily short term, and 75 percent enrolled patients with a variety of neuropathic pain. Comparators were primarily placebo or usual care. The strength of evidence (SOE) was low, unless otherwise noted. Compared with placebo, comparable THC to CBD ratio oral spray was associated with a small benefit in change in pain severity (7 RCTs, N=632, 0 to10 scale, mean difference [MD] −0.54, 95% confidence interval [CI] −0.95 to −0.19, I2=28%; SOE: moderate) and overall function (6 RCTs, N=616, 0 to 10 scale, MD −0.42, 95% CI −0.73 to −0.16, I2=24%). There was no effect on study withdrawals due to adverse events. There was a large increased risk of dizziness and sedation and a moderate increased risk of nausea (dizziness: 6 RCTs, N=866, 30% vs. 8%, relative risk [RR] 3.57, 95% CI 2.42 to 5.60, I2=0%; sedation: 6 RCTs, N=866, 22% vs. 16%, RR 5.04, 95% CI 2.10 to 11.89, I2=0%; and nausea: 6 RCTs, N=866, 13% vs. 7.5%, RR 1.79, 95% CI 1.20 to 2.78, I2=0%). Synthetic products with high-THC to CBD ratios were associated with a moderate improvement in pain severity, a moderate increase in sedation, and a large increase in nausea (pain: 6 RCTs, N=390 to 10 scale, MD −1.15, 95% CI −1.99 to −0.54, I2=39%; sedation: 3 RCTs, N=335, 19% vs. 10%, RR 1.73, 95% CI 1.03 to 4.63, I2=0%; nausea: 2 RCTs, N=302, 12% vs. 6%, RR 2.19, 95% CI 0.77 to 5.39; I²=0%). We found moderate SOE for a large increased risk of dizziness (2 RCTs, 32% vs. 11%, RR 2.74, 95% CI 1.47 to 6.86, I2=0%). Extracted whole-plant products with high-THC to CBD ratios (oral) were associated with a large increased risk of study withdrawal due to adverse events (1 RCT, 13.9% vs. 5.7%, RR 3.12, 95% CI 1.54 to 6.33) and dizziness (1 RCT, 62.2% vs. 7.5%, RR 8.34, 95% CI 4.53 to 15.34). We observed a moderate improvement in pain severity when combining all studies of high-THC to CBD ratio (8 RCTs, N=684, MD −1.25, 95% CI −2.09 to −0.71, I2=50%; SOE: moderate). Evidence on whole-plant cannabis, topical CBD, low-THC to CBD, other cannabinoids, comparisons with active products, and impact on use of opioids was insufficient to draw conclusions. Other important harms (psychosis, cannabis use disorder, and cognitive effects) were not reported.

Conclusions. Low to moderate strength evidence suggests small to moderate improvements in pain (mostly neuropathic), and moderate to large increases in common adverse events (dizziness, sedation, nausea) and study withdrawal due to adverse events with high- and comparable THC to CBD ratio extracted cannabinoids and synthetic products in short-term treatment (1 to 6 months). Evidence for whole-plant cannabis, and other comparisons, outcomes, and PBCs were unavailable or insufficient to draw conclusions. Small sample sizes, lack of evidence for moderate and long-term use and other key outcomes, such as other adverse events and impact on use of opioids during treatment, indicate that more research is needed.

Author/s:

McDonagh, M. S., Wagner, J., Ahmed, A. Y., Morasco, B., Kansagara, D., Chou, R.

Safety and tolerability of natural and synthetic cannabinoids in adults aged over 50 years: A systematic review and meta-analysis

Devin Evans — Wed, 07 Apr 2021 05:00:00 +0000

Date Added:

April 7, 2021

Journal/Publication:

PLos Med

Publication Date:

March 29, 2021

Issue:

Volume:

URL:

Safety and tolerability of natural and synthetic cannabinoids in adults aged over 50 years: A systematic review and meta-analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1371/journal.pmed.1003524

Keywords

PMID (1):

33780450

MeSH

cannabinoids

aged

insulin receptor-related receptor

Drug Combinations

cannabidiol

A systematic review of studies of the use of natural and synthetic cannabinoids in people over 50. James W. Mold, MD, MPH

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Background: Cannabinoid-based medicines (CBMs) are being used widely in the elderly. However, their safety and tolerability in older adults remains unclear. We aimed to conduct a systematic review and meta-analysis of safety and tolerability of CBMs in adults of age ≥50 years.

Methods and findings: A systematic search was performed using MEDLINE, PubMed, EMBASE, CINAHL PsychInfo, Cochrane Library, and ClinicalTrials.gov (1 January 1990 to 3 October 2020). Randomised clinical trials (RCTs) of CBMs in those with mean age of ≥50 years for all indications, evaluating the safety/tolerability of CBMs where adverse events have been quantified, were included. Study quality was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Two reviewers conducted all review stages independently. Where possible, data were pooled using random-effects meta-analysis. Effect sizes were calculated as incident rate ratio (IRR) for outcome data such as adverse events (AEs), serious AEs (SAEs), and death and risk ratio (RR) for withdrawal from study and reported separately for studies using tetrahydrocannabinol (THC), THC:cannabidiol (CBD) combination, and CBD. A total of 46 RCTs were identified as suitable for inclusion of which 31 (67%) were conducted in the United Kingdom and Europe. There were 6,216 patients (mean age 58.6 ± 7.5 years; 51% male) included in the analysis, with 3,469 receiving CBMs. Compared with controls, delta-9-tetrahydrocannabinol (THC)-containing CBMs significantly increased the incidence of all-cause and treatment-related AEs: THC alone (IRR: 1.42 [95% CI, 1.12 to 1.78]) and (IRR: 1.60 [95% CI, 1.26 to 2.04]); THC:CBD combination (IRR: 1.58 [95% CI,1.26 to 1.98]) and (IRR: 1.70 [95% CI,1.24 to 2.33]), respectively. IRRs of SAEs and deaths were not significantly greater under CBMs containing THC with or without CBD. THC:CBD combination (RR: 1.40 [95% CI, 1.08 to 1.80]) but not THC alone (RR: 1.18 [95% CI, 0.89 to 1.57]) significantly increased risk of AE-related withdrawals. CBD alone did not increase the incidence of all-cause AEs (IRR: 1.02 [95% CI, 0.90 to 1.16]) or other outcomes as per qualitative synthesis. AE-related withdrawals were significantly associated with THC dose in THC only [QM (df = 1) = 4.696, p = 0.03] and THC:CBD combination treatment ([QM (df = 1) = 4.554, p = 0.033]. THC-containing CBMs significantly increased incidence of dry mouth, dizziness/light-headedness, and somnolence/drowsiness. Study limitations include inability to fully exclude data from those <50 years of age in our primary analyses as well as limitations related to weaknesses in the included trials particularly incomplete reporting of outcomes and heterogeneity in included studies.

Conclusions: This pooled analysis, using data from RCTs with mean participant age ≥50 years, suggests that although THC-containing CBMs are associated with side effects, CBMs in general are safe and acceptable in older adults. However, THC:CBD combinations may be less acceptable in the dose ranges used and their tolerability may be different in adults over 65 or 75 years of age.

Author/s:

Velayudhan, Latha, McGoohan, Katie, Bhattacharyya, Sagnik

Drug interactions with cannabinoids

John Bayhi — Mon, 02 Mar 2020 18:41:14 +0000

Date Added:

March 2, 2020

Journal/Publication:

CMAJ: Canadian Medical Association Journal = journal de l'Association medicale canadienne

Publisher:

Joule Inc.

Publication Date:

March 2, 2020

Issue:

Volume:

192

Pages:

E206

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

Keywords

MeSH

Cytochrome P-450 CYP1A2

cannabinoids

Cytochrome P-450 CYP3A Inhibitors

Cytochrome P-450 CYP3A

Tacrolimus

Trimethoprim

Sulfamethoxazole Drug Combination

Cytochrome P-450 CYP2C9

Cytochrome P-450 CYP2C9 Inhibitors

CYP2C19 protein

Cytochrome P-450 CYP2C19

Benzodiazepines

International Normalized Ratio

Marijuana Use

cholinergic antagonists

A nice one-page review of drug interactions with cannabinoids. James W. Mold, MD, MPH

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No abstract available

Author/s:

Antoniou, T, Bodkin, J, Ho, JMW

Cannabidiol Products Are Everywhere, but Should People Be Using Them?

Brian Desmarais — Thu, 21 Nov 2019 18:13:38 +0000

Date Added:

November 22, 2019

Journal/Publication:

Journal of the American Medical Association

Publication Date:

November 20, 2019

URL:

Cannabidiol Products Are Everywhere, but Should People Be Using Them?

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

https://doi.org/10.1001/jama.2019.17361

Keywords

CBD

MeSH

cannabis

cannabidiol

united states food and drug administration

Here is another concise review on cannabidiol. This one looks like it could be useful to give to patients who have questions about it. James W. Mold, MD, MPH

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Even with pharmaceutical-grade CBD, potentially dangerous adverse events can occur. With unregulated CBD products, the adverse events are unpredictable, in part because their ingredients might not be the same as those listed on the package.

Author/s:

Rubin, R.

Severe Pulmonary Disease Associated with Electronic-Cigarette–Product Use — Interim Guidance

John Bayhi — Fri, 13 Sep 2019 12:52:13 +0000

Date Added:

September 13, 2019

Journal/Publication:

Morbidity and Mortality Weekly Report

Publisher:

U.S. Department of Health & Human Services / Centers for Disease Control and Prevention

Publication Date:

September 13, 2019

Issue:

Volume:

Pages:

787-790

URL:

Severe Pulmonary Disease Associated with Electronic-Cigarette–Product Use — Interim Guidance

Type:

Public Health Announcements

Format:

Article

DOI (1):

10.15585/mmwr.mm6836e2

Keywords

PMID (1):

31513561

MeSH

electronic nicotine delivery systems

volatile organic compounds

Neoplasms

Lung Diseases

centers for disease control and prevention (U.S.)

The latest information from the CDC on lung disease associated with vaping. James W. Mold, MD, MPH

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On September 6, 2019, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr). As of August 27, 2019, 215 possible cases of severe pulmonary disease associated with the use of electronic cigarette (e-cigarette) products (e.g., devices, liquids, refill pods, and cartridges) had been reported to CDC by 25 state health departments. E-cigarettes are devices that produce an aerosol by heating a liquid containing various chemicals, including nicotine, flavorings, and other additives (e.g., propellants, solvents, and oils). Users inhale the aerosol, including any additives, into their lungs. Aerosols produced by e-cigarettes can contain harmful or potentially harmful substances, including heavy metals such as lead, volatile organic compounds, ultrafine particles, cancer-causing chemicals, or other agents such as chemicals used for cleaning the device (1). E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, or other drugs; for example, "dabbing" involves superheating substances that contain high concentrations of THC and other plant compounds (e.g., cannabidiol) with the intent of inhaling the aerosol. E-cigarette users could potentially add other substances to the devices. This report summarizes available information and provides interim case definitions and guidance for reporting possible cases of severe pulmonary disease. The guidance in this report reflects data available as of September 6, 2019; guidance will be updated as additional information becomes available.

Author/s:

Schier, JG, Meiman, JG, Layden, J, Mikosz, CA, VanFrank, B, King, BA, Salvatore, PP, Weissman, DN, Thomas, J, Melstrom, PC, Baldwin, GT, Parker, EM, Courtney-Long, EA, Krishnasamy, VP, Pickens, CM, Evans, ME, Tsay, SV, Powell, KM, Kiernan, EA, Marynak, KL, Adjemian, J, Holton, K, Armour, BS, England, LJ, Briss, PA, Houry, D, Hacker, KA, Reagan-Steiner, S, Zaki, S, Meaney-Delman, D, CDC 2019 Lung Injury Response Group

Clinicians’ Guide to Cannabidiol and Hemp Oils

Brian Desmarais — Wed, 11 Sep 2019 21:41:17 +0000

Date Added:

September 18, 2019

Journal/Publication:

Mayo Clinic Proceedings

Publisher:

Mayo Foundation for Medical Education and Research

Publication Date:

September 1, 2019

Issue:

Volume:

Pages:

1840-1851

URL:

Clinicians’ Guide to Cannabidiol and Hemp Oils

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/j.mayocp.2019.01.003

Keywords

cannabidoil

cannabis

PMID (1):

31447137

MeSH

This is a review of what is known about cannabidiol and other hemp-related oils from the Mayo Clinic. James W. Mold, MD, MPH

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Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have become very popular over the past few years. Patients report relief for a variety of conditions, particularly pain, without the intoxicating adverse effects of medical marijuana. In June 2018, the first CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of rare, severe epilepsy, further putting the spotlight on CBD and hemp oils. There is a growing body of preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction. Care must be taken when directing patients toward CBD products because there is little regulation, and studies have found inaccurate labeling of CBD and tetrahydrocannabinol quantities. This article provides an overview of the scientific work on cannabinoids, CBD, and hemp oil and the distinction between marijuana, hemp, and the different components of CBD and hemp oil products. We summarize the current legal status of CBD and hemp oils in the United States and provide a guide to identifying higher-quality products so that clinicians can advise their patients on the safest and most evidence-based formulations. This review is based on a PubMed search using the terms CBD, cannabidiol, hemp oil, and medical marijuana. Articles were screened for relevance, and those with the most up-to-date information were selected for inclusion.

Author/s:

VanDolah H.J., Bauer, B.A., Mauck, K.F.

Cannabidiol (CBD) - What we know and what we don't

Jeffrey Wilson — Wed, 24 Apr 2019 15:32:45 +0000

Date Added:

April 24, 2019

Journal/Publication:

Harvard Health Blog

Publisher:

Harvard University

Publication Date:

August 24, 2018

URL:

Cannabidiol (CBD) - What we know and what we don't

Type:

Patient Education Materials

Format:

Web Page

Keywords

MeSH

sleep initiation and maintenance disorders

chronic pain

This patient-friendly review of what we currently know about CBD includes a warning that CBD oil reduces the metabolism of warfarin and other drugs metabolized by the CYP450 enzyme system (the same system affected by grapefruit juice) causing elevation of the INR and increased risk of bleeding. James W. Mold, MD, MPH

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Cannabidiol (CBD) has been recently covered in the media, and you may have even seen it as an add-in booster to your post-workout smoothie or morning coffee. What exactly is CBD? Why is it suddenly so popular?

Author/s:

Grinspoon, Peter

Does CBD Actually Work?

Tracy Ashby — Wed, 17 Apr 2019 05:00:00 +0000

Date Added:

April 18, 2019

Journal/Publication:

Quartz

Publication Date:

April 17, 2019

URL:

Does CBD Actually Work?

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

Keywords

MeSH

nebulizers and vaporizers

This lay press article attempts to summarize what is currently known about the efficacy of cannabidiol (CBD) for anxiety, pain, and sleep. James W. Mold, MD, MPH

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Perhaps you’ve heard a lot of people are using CBD.

The chemical compound, naturally occurring in cannabis plants, doesn’t get you high, but does have a wide swath of other purported effects making it very popular. Although clinical studies haven’t necessarily proven those results, many Americans are testing CBD (which stands for “cannabidiol”) for themselves. All over the US, people are rubbing CBD balm onto aching joints, dropping CBD tinctures under tired tongues, popping CBD gummies, and puffing on CBD oil-filled vaporizers in hopes of chilling out.

On Quartz’s behalf, Harris Poll recently surveyed more than 2,000 people in the US about their experience, knowledge, and opinions regarding CBD and found that more than 85% of Americans have heard of CBD, and of those, more than one in five have tried it.

Author/s:

Avins, Jenni

Lack of evidence for cannabis in adults with chronic neuropathic pain

Jeffrey Wilson — Tue, 04 Dec 2018 23:10:18 +0000

Date Added:

December 4, 2018

Journal/Publication:

Pearls

Issue:

597

Type:

Meta-analyses, Reviews, and Guidelines

Keywords

MeSH

There is so far no high quality evidence to support the use of cannabinoids for relief of chronic neuropathic pain.

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Bottom Line:

There was no high-quality evidence for the efficacy of any CBM (herbal cannabis, plant-derived tetrahydrocannabinol (THC) (dronabinol), synthetic THC (nabilone), plant-derived THC/cannabidiol (CBD) com bination) in any condition with chronic neuropathic pain. The studies were two to 26 weeks long and compared an oromucosal spray with a plant-derived combination of THC and CBD (10 studies), a synthetic cannabinoid mimicking THC (nabilone) (two studies), inhaled herbal cannabis (two studies) and plant-derived THC (dronabinol) (two studies) against placebo (15 studies) and an analgesic (dihydrocodeine) (one study). Herbal cannabis was not different from placebo in reducing pain and the number of people who dropped out due to side effects. Some adverse events (particularly somnolence or sedation, confusion, psychosis) might limit the clinical usefulness of cannabis-based medicines.

Author/s:

McAvoy, Brian R.