cannabidiol

Importance The wide use of unregulated cannabidiol (CBD) products among consumers raises safety concerns. Most research on CBD has studied the relatively high doses used by patients taking prescription CBD. However, limited safety data are available at lower doses.

Objective To study the effects of 4-weeks of twice-daily CBD use on the liver and endocrine hormones using a dose within the range consumers are taking with unregulated CBD products.

Design, Setting, and Participants This randomized double-blinded placebo-controlled trial from January to August 2024, using per protocol analysis, included healthy adults recruited from a clinical pharmacology unit (Spaulding Clinical Research in West Bend, Wisconsin).

Interventions Healthy participants were randomized to CBD, 5 mg/kg/d (2.5 mg/kg/d twice daily), or placebo for 28 days with weekly laboratory assessments.

Main Outcomes and Measures The primary end point was the percentage of participants with an alanine aminotransferase or aspartate aminotransferase level elevation greater than 3 times the upper limit of normal during the study.

Results In 201 healthy participants (median age, 36 years [IQR, 30-43 years]; 89 women [44%]), 8 participants (5.6%; 95% CI, 1.8%-9.3%) in the CBD group and 0 participants (0%; 95% CI, 0%-7.6%) in the placebo group had liver enzyme level elevation greater than 3 times the upper limit of normal. Seven participants met withdrawal criteria for potential drug-induced liver injury, detected at day 21 in 2 participants and day 28 in 5 participants. No differences in change from baseline were observed between the CBD and placebo groups for total testosterone and inhibin B in male participants or thyrotropin, total triiodothyronine, and free thyroxine in all participants.

Conclusions and Relevance In this study, the incidence of elevated alanine aminotransferase or aspartate aminotransferase coupled with the finding of increased eosinophilia, underscores the need for further investigation on the long-term effects of CBD use, its impact on various populations, and the safety of lower doses commonly used by consumers.

Trial Registration ClinicalTrials.gov Identifier: NCT06192589

Author/s:

Jeffry Florian, Pablo Salcedo, Keith Burkhart, Aanchal Shah, Lakshmi Manasa S Chekka, Dro Keshishi, Vikram Patel, ShanChao Yang, Melanie Fein, Ryan DePalma, Murali Matta, David G Strauss, Rodney Rouse

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 (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.