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cbd oil clinical studies

CBD may offer an option for treating different types of chronic pain. A study from the European Journal of Pain showed, using an animal model, CBD applied on the skin could help lower pain and inflammation due to arthritis. Another study demonstrated the mechanism by which CBD inhibits inflammatory and neuropathic pain, two of the most difficult types of chronic pain to treat. More study in humans is needed in this area to substantiate the claims of CBD proponents about pain control.

Some CBD manufacturers have come under government scrutiny for wild, indefensible claims, such that CBD is a cure-all for cancer, which it is not. We need more research but CBD may be prove to be an option for managing anxiety, insomnia, and chronic pain. Without sufficient high-quality evidence in human studies we can’t pinpoint effective doses, and because CBD is currently is mostly available as an unregulated supplement, it’s difficult to know exactly what you are getting. If you decide to try CBD, talk with your doctor — if for no other reason than to make sure it won’t affect other medications you are taking.

Side effects of CBD include nausea, fatigue and irritability. CBD can increase the level in your blood of the blood thinner coumadin, and it can raise levels of certain other medications in your blood by the exact same mechanism that grapefruit juice does. A significant safety concern with CBD is that it is primarily marketed and sold as a supplement, not a medication. Currently, the FDA does not regulate the safety and purity of dietary supplements. So, you cannot know for sure that the product you buy has active ingredients at the dose listed on the label. In addition, the product may contain other (unknown) elements. We also don’t know the most effective therapeutic dose of CBD for any particular medical condition.

Is CBD safe?

CBD is commonly used to address anxiety, and for patients who suffer through the misery of insomnia, studies suggest that CBD may help with both falling asleep and staying asleep.

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?

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CBD has been touted for a wide variety of health issues, but the strongest scientific evidence is for its effectiveness in treating some of the cruelest childhood epilepsy syndromes, such as Dravet syndrome and Lennox-Gastaut syndrome (LGS), which typically don’t respond to antiseizure medications. In numerous studies, CBD was able to reduce the number of seizures, and, in some cases, it was able to stop them altogether. Videos of the effects of CBD on these children and their seizures are readily available on the Internet for viewing, and they are quite striking. Recently the FDA approved the first ever cannabis-derived medicine for these conditions, Epidiolex, which contains CBD.

Furthermore, a significant discrepancy is observed between the recorded dosages of oral CBD in RCTs and dosages in real-world settings. The average daily CBD dosage authorized at our clinic (11.5 mg) is closer to other observational studies (Gulbransen et al. 2020) compared to what is seen in RCTs (up to 1000 mg for a single dose) (Larsen and Shahinas 2020). The presence of THC and other cannabinoids in CBD-rich products may affect the outcomes in this study. The majority of RCTs investigated single-dose administration of CBD making it difficult to compare observed treatment outcomes with chronic dosing clinical settings. Importantly, medical cannabis products are generally not covered by most insurers and patients rely on out-of-pocket payments. The cost of CBD remains very high globally, approximately $CAD 5–20 per 100 mg (Canada Go 2021; Eisenstein 2019; Canada 2020). Availability of reliable cannabinoid testing in certain international jurisdictions is also limited. The gap between effective doses demonstrated in RCTs and the actual affordable doses demonstrated by RWE mandate the need for a precise pricing and marketing strategy at the initiation of any drug development process.

To determine whether CBD-based treatments have different effectiveness based on the severity of patient symptoms, two-way mixed ANOVAs with severity group as between-factor and visit as a within-factor were conducted to assess the change in ESAS-r scores between visits. Paired t-tests were subsequently performed to assess the difference in mean scores within each severity group between baseline and FUP1. Significant p value was set at 0.05 and all analyses were two-tailed. Partial eta-squared (η 2 p) are reported to indicate magnitude of differences between groups.

A total of 1095 patients were seen at the four clinic sites during the study period. Out of those, 715 were eligible for the study (at least 18 years old and initially treated exclusively with CBD-rich products). A total of 279 patients with ESAS-r scores and product information at FUP1 were analyzed (190 (68%) female, mean age = 61.1, SD = 16.6). The analyzed sample did not differ from the study-eligible group in terms of age, sex, or THC and CBD initial doses (all ps > 0.4). Table 2 outlines patient sample size and demographic information for each symptom and treatment group. Two hundred and ten (75%) patients were prescribed CBD-rich products to treat chronic pain, 19 (7%) for cancer-related symptoms, 21 (7.5%) to treat neurological disorders (Parkinson’s disease, multiple sclerosis, and drug-resistant epilepsy among others), 8 patients for inflammatory disease (arthritis), 10 for gastrointestinal disorders (Chron’s disease, inflammatory bowel syndrome, ulcerative colitis), 2 for anxiety, 1 for depression, 2 for headaches, and 6 unclassified. The chronic pain category included all medical indications for which pain was the main symptom such as but not limited to fibromyalgia, spinal stenosis, and chronic low back pain. Overall, 116 (41.6%) patients adjusted their prescription by adding THC at FUP1 (either to a THC:CBD-balanced combination or a THC-rich treatment). Two hundred and three (73%) patients had moderate/severe ESAS-r scores on at least 2 of the examined symptoms, 57 (20%) on three, and 75 (27%) on all four symptoms. Twenty-nine (10%) patients report no moderate/severe symptoms; these people may use CBD for other ESAS-r symptoms not examined here (shortness of breath, tiredness, nausea, drowsiness, appetite). There was no statistical difference on either age, sex, or THC and CBD initial doses between the patients who completed one FUP versus those who completed two FUP (all ps > 0.1).

Discussion

Limitations are common in real-world data (RWD), especially in retrospective studies. In this study, with no control group, no causality effect can be drawn between CBD-rich treatment and symptom improvement. Most patients treated with CBM present with multiple severe symptoms and the analyses presented here are limited to identify the treatment outcomes for such patients. Further studies can investigate the use of CBD to treat several symptoms simultaneously.

CBD-rich treatment effect according to symptom severity: mild or moderate/severe in 279 patients. FUP1, follow-up visit at 3 month; FUP2, follow-up visit at 6 month. a Mean ESAS-r scores for the pain symptom, b mean ESAS-r scores for the anxiety symptom, c mean ESAS-r scores for the depression symptom, and d mean ESAS-r scores for overall wellbeing. According to mixed ANOVAs, patients with moderate/severe symptoms reported symptom reduction whereas patients with mild symptoms reported symptom deterioration from baseline to FUP1. No effect was statistically significant between FUP1 and FUP2

Our findings show that overall effectiveness of CBD treatment is primarily by patients with moderate to severe symptoms. A deficiency in the endocannabinoid system (ECS) may provide a possible explanation for this result (Russo 2016). The ECS could be more deficient in patients with moderate/severe symptoms compared to mild symptoms leading to increased improvement in the first group. The absence of significant improvement for patients with mild symptoms at baseline may be explained by a smaller margin for symptom improvement. In such patients, CBD treatments may have been targeted to other clinical symptoms not assessed in the current study. There is a probable placebo effect; however, there were no differences in initial CBD doses between the severity groups. Furthermore, associated placebo effect would likely be decreased by FUP3M, also considering the significant treatment cost. The distinct beneficial impact of CBD treatment observed for patients with moderate-severe symptoms could elucidate discrepancies found in the literature.

Mean ESAS-r scores of pain, anxiety, depression symptoms, and overall wellbeing at baseline, FUP1, and FUP2 are described in Table 4 and Fig. 1.

Clinical trials inform doctors about the proven safety, efficacy, and dosage of pharmaceutical drugs through double-blind, placebo-controlled studies; however, compounds of the Cannabis plant are used medicinally without undergoing these trials until recently. Although 33 states have approved Cannabis use for medical conditions, the U.S. Drug Enforcement Administration recognizes Cannabis as a Schedule I drug, meaning it has no currently accepted medical use and a high potential for abuse, which also prevented research. Some cannabinoid-containing drugs could be obtained from the University of Mississippi; however, those samples are not chemically or physically representative of the legal Cannabis markets (Vergara et al., 2017). Recently, a CBD formulation, Epidiolex, was approved by the U.S. Food and Drug Administration (FDA) for two conditions, which rescheduled this formulation to a Schedule III drug, a low abuse potential classification, which allows its use in clinical trials (Drug Scheduling, n.d).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Introduction

S-HP was the primary investigator to this research, was responsible for the initial draft, and conceptualized the idea for this review. CP prepared the manuscript. S-HP and CP edited and completed the manuscript. MC assisted in reviewing literature surrounding this subject. S-HP and BH funded this research.

Clinical trial results from Epidiolex-focused studies: The table summarizes the results from the currently completed clinical trials that have tested Epidiolex’s efficacy against various conditions. The % symptom reduction is reported as the percentage of patients in the treatment group to report improvement in the treatment of their condition. Similarly, the % of adverse effects refers to the total percentage of treatment group patients that reported any adverse effect. The sample size describes the number of patients that have completed the clinical trial currently.

From comparing the various clinical trials on CBD, there are also clear incongruencies that need to be addressed in the clinical trial design process. The differences in primary and secondary outcome measurements becomes concerning since there is a lack of comparability that is needed for widely applicable drug-safety. For example, Dr. Leehey’s study evaluated more parameters and collected more comprehensive patient data than the more positive-focused outcomes observed in the GW Pharmaceutical funded studies, as well as using different exclusion criteria. The physical and psychological measurements such as those in Dr. Leehey’s study could act as a model study design for future clinical trials of Epidiolex to ensure safety and efficacy of new CBD-containing drug formulations. Furthermore, it’s notable that nearly 90% of patients in Dr. Leehey’s study had diarrhea; whereas, this wasn’t reported in other Epidiolex studies, which suggests either PD patients have a negative GI response to Epidiolex, or there are potential inconsistencies in the formulations being tested. The latter is supported by the GW Pharmaceutical Epidiolex drug pamphlet, which describes the formulation as “a clear, colorless to yellow liquid”. This color variation could represent a change in chemical composition of one or more of the ingredients that may cause the outcome variations observed between clinical trials (GW Biosciences, 2018).