Cannabidiol use and effectiveness: real-world evidence from a Canadian medical cannabis clinic
Cannabidiol (CBD) is a primary component in the cannabis plant; however, in recent years, interest in CBD treatments has outpaced scientific research and regulatory advancement resulting in a confusing landscape of misinformation and unsubstantiated health claims. Within the limited results from randomized controlled trials, and lack of trust in product quality and known clinical guidelines and dosages, real-world evidence (RWE) from countries with robust regulatory frameworks may fill a critical need for patients and healthcare professionals. Despite growing evidence and interest, no real-world data (RWD) studies have yet investigated patients’ reports of CBD impact on symptom control in the common expression of pain, anxiety, depression, and poor wellbeing. The objective of this study is to assess the impact of CBD-rich treatment on symptom burden, as measured with a specific symptom assessment scale (ESAS-r).
This retrospective observational study examined pain, anxiety, depression symptoms, and wellbeing in 279 participants over 18 years old, prescribed with CBD-rich treatment at a network of clinics dedicated to medical cannabis in Quebec, Canada. Data were collected at baseline, 3 (FUP1), and 6 (FUP2) month after treatment initiation. Groups were formed based on symptom severity (mild vs moderate/severe) and based on changes to treatment plan at FUP1 (CBD vs THC:CBD). Two-way mixed ANOVAs were used to assess ESAS-r scores differences between groups and between visits.
This retrospective observational study suggests CBD-rich treatment has a beneficial impact on pain, anxiety, and depression symptoms as well as overall wellbeing only for patients with moderate to severe symptoms; however, no observed effect on mild symptoms. The results of this study contribute to address the myths and misinformation about CBD treatment and demand further investigation.
Cannabidiol (CBD) is one of the primary cannabinoids found in significant but variable concentrations in cannabinoid-based medicines (CBM). While structurally similar to Δ9-tetrahydrocannabinol (THC), CBD does not cause intoxication or euphoria (Russo 2017) and has showed considerable tolerability in humans with a low abuse potential (Chesney et al. 2020). This favorable safety profile has led to the recent mitigation of legal and regulatory barriers surrounding purified CBD products in several countries and recent increased interest in CBD treatments. While recent rulings clarified that CBD is not a drug under the 1961 United Nations as Single Convention on Narcotic Drugs, regulatory status in the USA remains extremely confusing. When derived from cannabis, CBD is a schedule 1 drug but when derived from “industrial hemp” plants it may be lawful federally (Corroon and Kight 2018; Corroon et al. 2020). In Canada, CBD is controlled under the Cannabis Act as are all cannabinoids, cannabis, and cannabis-derived products (Canada Go 2021). This regulatory status imparts restrictions and access obstacles for researchers.
CBD is widely touted as a panacea for a wide range of health problems and has been marketed as a dietary and “wellness” product (Russo 2017; Khalsa et al. 2020; Eisenstein 2019). CBD’s potential effects as an add-on therapy have been studied for social anxiety disorders, schizophrenia, non-motor symptoms in Parkinson’s disease, and substance use disorders (Bergamaschi et al. 2011; Crippa et al. 2019; McGuire et al. 2018; Millar et al. 2019; Prud’homme et al. 2015; Thiele et al. 2019; Leehey et al. 2020). However, the evidence of its effectiveness for indications other than drug-resistant pediatric epilepsy conditions remains very limited (Larsen and Shahinas 2020; Franco et al. 2020) and safety considerations such as drug-drug interactions associated with unsupervised use remain (Chesney et al. 2020; Freeman et al. 2019). Randomized controlled trials (RCTs) are limited in their rigorous design, population sample, and duration of observation making generalization of results and long-term data scarce. Therefore, real-world evidence (RWE) provides valuable insights and supplemental information about the use, safety, and effectiveness of CBD-based treatments (Graham et al. 2020).
RWE from retrospective analyses and patient registries shows that CBMs are used for pain (chronic, neuropathic), mental health conditions, cancer-related symptoms (nausea, fatigue, weakness), HIV/AIDS, and neurological conditions (Bonn-Miller et al. 2014; Gulbransen et al. 2020; Lintzeris et al. 2020; Lucas and Walsh 2017; Sexton et al. 2016; Waissengrin et al. 2015). Symptom control is the primary reason for use of CBM, with most patients looking to address unalleviated symptoms, perceived symptom intensity, and burden on health-related quality of life independently of primary diagnosis (Sexton et al. 2016; Waissengrin et al. 2015; Baron et al. 2018; Purcell et al. 2019; Swift et al. 2005; Webb and Webb 2014). The Edmonton Symptom Assessment Scale-revised version (ESAS-r) is a validated scale to assess symptom burden developed for use in oncology and palliative care (Hui and Bruera 2017), it has relevance to medical cannabis care as patients are often treated for similar symptom management (Good et al. 2019; Pawasarat et al. 2020). Specifically, studies showed self-perceived improvement in ESAS-r emotional symptoms (anxiety and depression) scores following CBM treatment in oncology patients, while pain and wellbeing symptoms showed no improvement (Good et al. 2019; Pawasarat et al. 2020). Yet, RWE on CBD-rich products is scarce (Goodman et al. 2020; Shannon et al. 2019). In addition, although careful titration and treatment adjustment after initiation is critical to symptom improvement and adverse effects care, current literature has failed to address this issue.
In this study, we investigated treatment with CBD-rich products within a dedicated clinical setting in Quebec, Canada, and the effects on a very common clinical symptom expression of pain and comorbid anxiety and depression symptoms, as well as the effect on overall wellbeing. We also examined the relevant clinical effects that were observed when CBD-rich treatments were replaced by THC:CBD-balanced products at subsequent follow-up visits.
This study is a retrospective examination of patients who were prescribed CBD-rich products by physicians at a clinic dedicated to CBM treatments operating at four locations across Quebec, Canada. All data are collected as part of standard clinical procedures during the initial visit and during 3 (FUP1) and 6 (FUP2) month follow-up visits and extracted from electronic medical records (EMR) (Prosk et al., 2021). All data were anonymized following extraction from the EMR and no identifiers linking to original data were maintained. A waiver of consent was required and approved by Advarra Ethics Committee, who also approved the study protocol, and by the provincial privacy commission (La commission d’accès à l’information du Quebec).
Adult patients, at least 18 years of age, who were initially treated exclusively with CBD-rich products from 1 October 2017 to 31 May 2019 and for whom outcome scores and product information were recorded at FUP1 were included in this study. Patients were generally referred by primary-care physicians and specialists for an assessment on the suitability of medical cannabis to treat refractory symptoms. A complete medical history, including primary and secondary diagnoses, was collected at baseline visit. Medical cannabis treatment decisions are determined at the discretion of a clinic physician according to a standardized clinical procedure, including symptom identification, selection of product format, cannabinoid profile, and dosage based on existing evidence (MacCallum and Russo 2018; Cyr et al. 2018), but also to minimize risk of adverse effects. Patient and physician preference may also indicate initiation with products that have higher CBD and lower THC concentration in order to limit use of THC and its inherent potential adverse events. The follow-up visits serve to assess treatment compliance, safety, and effectiveness.
CBD-rich products in Canada
CBD-rich products are administered in various methods and formats, but most commonly as oral plant-derived extracts or oils and as inhaled dried flowers. In the Canadian medical cannabis program, CBD-rich cannabis oils contain approximately 0.5–1 mg of THC/mL and 20–25 mg of CBD/mL depending on the product manufacturer. Table 1 provides cannabinoid content and THC:CBD ratio for the three most common oil products (over 85% of patients) authorized at the clinic. Furthermore, product details in this study sample are described in Table 3. The clinic procedure dictates that all products with a ratio of CBD (mg) to THC (mg) higher than 10 are considered CBD-rich products.
Table 1 THC and CBD contents and associated THC:CBD ratio for the three most common oil products authorized at the clinic
Treatment adjustments occur at follow-up visits as a result of lack of effectiveness, presentation of adverse effects, or social or economic barriers. Adjustments may include a change of the recommended CBD-rich product, method of administration, dosage, or a change in product formulation such as the introduction of THC:CBD-balanced or THC-rich products. We investigated the change from CBD-rich to THC:CBD products during FUP1 by forming two groups based on their product adjustment at FUP1 (CBD-rich vs THC:CBD). Products at FUP1 reflect those recommended at the visit. Therefore, the adjusted treatment affects only the evaluation at FUP2.
Patients age, sex, and diagnosis were recorded at baseline. Patients completed the ESAS-r (Edmonton Symptom Assessment System-revised version) at each visit. The ESAS-r is a self-administered scale, rating the severity of symptoms from 0 (absence of symptom) to 10 (worst possible severity) at the time of assessment (Hui and Bruera 2017). Symptoms evaluated include six physical- (pain, tiredness, nausea, drowsiness, lack of appetite, and shortness of breath), two emotional- (depression, anxiety), and one overall wellbeing-related symptoms. ESAS scores can be categorized as mild (score 0 to 3) moderate (score 4 to 6) or high (score 7 and above) (Butt et al. 2008) and the threshold for clinically significant improvement is a decrease of 1 point (Hui et al. 2015). Since pain and mental health issues represent the most common symptoms for patients and physicians seeking medical cannabis treatments, we investigated effects on pain, depression, and anxiety symptoms as well as overall wellbeing. For each symptom, two groups of patients were formed: moderate-severe severity group in which a baseline score of 4 or more was recorded and a mild severity group with baseline score of 0 to 3.
Mean scores and standard deviation (SD), as well as percentage, where appropriate are presented for each variable. All analyses were performed on each ESAS-r symptom separately through the data analytics software R v4.0.2. An initial analysis compared the overall ESAS-r scores between each visit no matter the severity of the group, and looked at the role of product group (CBD/THC:CBD vs CBD/CBD group) (between-factor). Tukey HSD post hoc test was used to confirm where the differences occurred between groups.
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).
CBD-rich products characteristics
The baseline average daily doses for CBD and THC are presented in Table 3. The maximum initial CBD dose recorded (156 mg) was prescribed for the treatment of pain of one patient. The maximum THC dose recorded at FUP1 (90 mg) was prescribed for two patients for the treatment of pain.
Table 3 Details of the THC and CBD component of the CBD-rich, the THC:CBD 1:1, and the THC-rich formulations
Outcome of CBD treatment
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.
Table 4 Mean and standard deviation (SD) scores of ESAS-r scales for each severity group (mild or moderate/severe) and for each product group (CBD/CBD or CBD/THC:CBD)
CBD-rich treatment effectiveness on pain, anxiety, depression symptoms, and on overall wellbeing in 279 patients. FUP1, follow-up visit at 3 month; FUP2, follow-up visit at 6 month. Mixed ANOVAs revealed a significant effect of visit on symptom reduction between baseline and FUP1 but not between FUP1 and FUP2
All average ESAS-r scores decreased between baseline and FUP1 and FUP2. This was further demonstrated by ANOVAs which revealed a significant effect of visit on mean ESAS-r scores for each symptom assessed (pain: F(2,634) = 4.9, p < 0.008; anxiety: F(2,624) = 8.36, p < 0.001, depression: F(2,629) = 5.36, p < 0.004; wellbeing: F(2,613) = 8.31, p < 0.001; all η 2 p between 0.008 and 0.02). In all assessed symptoms, no significant main effect of adding THC at FUP1, nor visit-by-product interaction, were observed (all ps > 0.2). Post hoc tests revealed ESAS-r mean scores significantly decreased between baseline and FUP1 (all ps < 0.003) for all symptoms, between baseline and FUP2 for anxiety and wellbeing (both ps < 0.03), but not between FUP1 and FUP2 for any symptoms (all ps >0.5). This suggests statistical improvement recorded at FUP1 is still present at FUP2 in all symptoms independently from treatment adjustment at FUP1.
CBD treatment impact according to symptom severity
From Table 2, moderate or severe scores at baseline were most common for pain (205 patients, 73.5%) and poor wellbeing (202 patients, 72.4%).
Clinical effect (difference of 1.3 to 2.5 points) observed in all symptoms for patients with moderate/severe symptoms between baseline and FUP1; however, there was no clinical effect for patients with mild symptoms (from − 0.3 to − 1.8) (Fig. 2). No clinical effect was observed in any symptoms between FUP1 and FUP2 for patients with moderate/severe symptoms (− 0.4 to 0.5) as well as for patients with mild symptoms (from − 0.7 to 0.4).
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
The ANOVA revealed that all main and interaction effects were significant at the 0.001 level with effect sizes large for severity (η 2 p = 0.29), medium for visit (η 2 p = 0.06), and small for the interaction (η 2 p = 0.03). Post hoc tests revealed a significant score difference between baseline and FUP1 and FUP2 (both ps < 0.05) but not between FUP1 and FUP2 (p = 0.98). Patients with moderate/severe symptoms on pain experienced important improvement at FUP1 (t(194) = 7.61, p < 0.001) whereas ESAS-r scores for patients with mild symptoms actually increased (t(64) = − 2.03, p < 0.05) (Fig. 2a).
The ANOVA showed main effects of visit, severity group (both ps < 0.001 with η 2 p = 0.04 and η 2 p = 0.4, respectively) and a significant group-by-visit interaction (F(2,620) = 34.47, p < 0.001; η 2 p = 0.1). Post hoc tests revealed a significant score difference between baseline and FUP1 and FUP2 (both ps < 0.01) but not between FUP1 and FUP2 (p = 0.85). Specifically, the scores of moderate/severe group decreased notably (t(110) = 9.56, p < 0.001) between baseline and FUP1 but the scores of the group with mild depression symptoms did not (p = 0.07) (Fig. 2c).
This retrospective study explored the use of CBD-rich products in a medical cannabis clinical setting in Canada and associated effectiveness on a common symptom cluster presentation of pain, anxiety, depression, and poor sense of wellbeing, as measured by ESAS-r.
Patients treated with CBD-rich products were mainly women in their sixties, seeking predominantly chronic pain management.
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.
RCTs on CBM and pain symptoms provide inconclusive results; however, several report that treatments of THC and CBD have some benefit for pain management (Häuser et al. 2018; Russo 2008; Prosk et al. 2020). Our results are largely novel as research on the effect of CBD on pain control is very limited (Boyaji et al. 2020). The reduction in reported anxiety may also contribute to the improvement in pain perception.
Discrepancies still exist regarding the anxiolytic effect of CBD. Some RCTs indicate an anxiolytic effect of CBD upon experimentally induced scenarios (Bergamaschi et al. 2011; Zuardi et al. 2017; Bhattacharyya et al. 2010; Skelley et al. 2020); however, these findings are difficult to replicate (Larsen and Shahinas 2020; Hundal et al. 2018; Crippa et al. 2012). This reinforces our findings that CBD may have a differential effect depending on anxiety severity. Regarding the effects of CBD on depression symptoms, further research is required to draw conclusions (Khalsa et al. 2020; Schier et al. 2014; Turna et al. 2017).
The addition of THC to CBD during FUP1 did not produce any effect on ESAS-r scores at FUP2 in this analysis; however, the magnitude of the difference between groups is small. The examination of treatment regimen has been seldom addressed in the literature and further development is required to inform guidelines for prescription and refinement of clinical practice.
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.
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.
The self-reported subjective assessment used may be biased by the patient’s positive expectation of treatment, which could lead to a possible placebo effect. This perceived effectiveness bias may also be increased by social and economic barriers. The current context of medical cannabis access, including social stigma, high cost, and lack of universal insurance coverage can increase the patient selection bias. Self-selection bias is increased by the significant patient interest in medical cannabis as these patients must be motivated to access the non-traditional medication system. This bias limits the generalizability of results but is common across international medical cannabis regimens and should not discount the observed results. The heterogeneity of the patient population with a variety of diagnoses and the diversity of medical cannabis preparations also affects the external validity of the study. However, clinical findings from within Canada’s controlled regulatory program do provide important models for international consideration. Future research is required in controlled clinical settings to examine these factors in order to provide a more complete account of CBD effectiveness.
Also, there was a large drop of sample size (53% loss) due to missing data. Additionally, there was an important loss to follow-up at the 6-month visit (FUP2) due to missed appointment and cost barriers, limiting the power of the findings. The total treatment cost has significant impact on treatment continuation. Improved patient retention and more robust, harmonized data collection methods will improve future observational studies and allow for long-term assessment. Collection of detailed, accurate product information is a challenge, especially with inhaled products (Corroon et al. 2020). There are opportunities for administration devices and other technology advancements to improve this limitation. Lastly, this study did not include safety data assessment, future studies should investigate safety considerations of CBD (Chesney et al. 2020). Collection of high-quality RWD will require improvements in patient retention, data monitoring, and more robust data collection methods within a controlled clinical setting.
This study on CBD-rich products demonstrates the potential of RWE for the advancement of medical cannabis research and practice guidelines, especially in a world where CBD use is exponentially increasing but scientific data are limited. It revealed that CBD-rich treatments have a beneficial impact on patients with self-reported moderate or severe symptoms of pain, anxiety, or depression and overall wellbeing but not in patients with mild symptoms. Further investigation is clearly required, but as of now the hyped, and often illegal, marketed claims of CBD as a wellness product are unsubstantiated. Our findings have important and novel implications to clinical practice, especially the examination of treatment plan adjustment during the first follow-up after initiation with CBD treatments. Improvements in access regimes, oversight, and clarification from regulatory agencies are also needed to improve the validity of RWE and assessment of the use of CBD-rich products.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
CBD Oil: 9 Science-Backed Benefits
Dr. Bindiya Gandhi is an integrative medicine physician with expertise in functional and holistic medicine based in Atlanta, Georgia.
Commissions we earn from partner links on this page do not affect our opinions or evaluations. Our editorial content is based on thorough research and guidance from the Forbes Health Advisory Board.
Cannabidiol, or CBD, is a chemical compound found in the cannabis sativa plant. When applied topically or consumed through smoke inhalation or edible consumption, CBD interacts with neuroreceptors in your endocannabinoid system, which sends signals between your cells to help regulate your movement, mood, homeostasis and immune system.
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CBD is often extracted from the cannabis sativa plant in oil form and mixed with an inert carrier oil like hemp seed oil for consumption. In fact, of the 60% of U.S. adults who report having used CBD before, 55% of them use CBD oils and tinctures specifically, according to a recent Forbes Health survey of 2,000 U.S. adults conducted by OnePoll.
CBD research is growing, too. Here are nine ways studies suggest CBD oil could benefit your health.
1. Offset Anxiety and Depression
CBD’s ability to calm is perhaps its most popular effect and the reason its use is so widespread. A 2017 study in the Brazilian Journal of Psychiatry tested the anxiety levels of 57 men in a simulated public speaking test. Some received a placebo while others received either 150 milligrams, 300 milligrams or 600 milligrams of CBD before their speeches. Those who received 300 milligrams of CBD experienced significantly reduced anxiety during the test compared to those who received the placebo. Interestingly, participants who received either 150 or 600 milligrams of CBD experienced more anxiety during the test than the 300 milligrams group.
Meanwhile, at least one study in mice revealed CBD had effects similar to the antidepressant imipramine. Human trials are needed, though, to confirm whether CBD can induce this same antidepressant reaction in our bodies.
2. Treat Select Epilepsy Syndromes
In some instances, CBD can be used to treat epileptic seizures.
In 2018, the Food and Drug Administration (FDA) approved the use of CBD under the brand name Epidiolex to treat seizures resulting from Lennox-Gastaut syndrome and Dravet syndrome—two rare forms of epilepsy—in patients at least 2 years old.
Three well-vetted studies provide the basis of support for the FDA’s decision. In these trials, 516 patients with Lennox-Gastaut syndrome or Dravet syndrome received either Epidiolex or a placebo. Epidiolex, when taken along with other prescribed medications, decreased the frequency of participants’ seizures compared to the placebo.
3. Reduce PTSD Symptoms
In a small 2018 study in the Journal of Alternative and Complementary Medicine, 11 people with post-traumatic stress disorder (PTSD) received CBD along with routine psychiatric care for eight weeks in an outpatient psychiatric clinic. Ten of the 11 experienced a decrease in their PTSD symptoms. CBD was generally well tolerated, the researchers write.
Margaret Rajnic, a doctor of nursing practice experienced in medical cannabis and CBD, emphasizes the importance of using therapy in tandem with any type of cannabis or CBD for PTSD. “There is an amount of therapy that is needed for PTSD,” she says. “But CBD will give you that little bit of decreased anxiety.”
Four other human trials from 2012 to 2016 suggest CBD reduces PTSD symptoms, although some include THC, or tetrahydrocannabinol, the main mind-altering element in cannabis. When THC and CBD work together, they create what’s called an “entourage effect,” complementing each other’s benefits and potency. For example, taking the same dose of THC and CBD together tempers the “high” from THC, while just a little THC paired with more CBD enhances the effects of the CBD.
4. Treat Opioid Addiction
Some studies—both preclinical animal and human clinical trials—suggest CBD could be used to help treat people who are dependent on opioids.
In one such study, researchers administered CBD to people with heroin use disorder. Over the course of a week, CBD significantly reduced heroin users’ cue-induced cravings, withdrawal anxiety, resting heart rate and salivary cortisol levels. No serious adverse effects were found.
Other studies find CBD helpful in reducing various psychiatric and medical symptoms like anxiety, insomnia and pain in patients with substance use disorders, indicating that CBD may be an effective treatment for opioid addiction. However, further studies are necessary.
5. Alleviate ALS Symptoms
Amyotrophic lateral sclerosis (ALS) is a disease that causes nerve cells in the brain and spinal cord to deteriorate, resulting in loss of muscle control that worsens over time. It’s not yet understood exactly why ALS occurs, although it can be hereditary in some cases. There’s no known cure, and there are only two FDA-approved medications to help treat ALS symptoms.
Research suggests people with ALS can benefit from the entourage effect created by the combination of THC and CBD, similar to people with PTSD. In a 2019 study, patients received a combination of THC and CBD in varying doses depending on their needs and preferences. Those with mild, moderate or severe spasticity (muscle tightness and stiffness) due to ALS reported high levels of satisfaction with the treatment, and those with moderate to severe spasticity reported higher satisfaction rates than those with mild spasticity.
6. Relieve Unmanageable Pain
In 2005, Canada approved the use of Sativex, an oromucosal (absorbed in the lining of the mouth) spray with equal proportions of THC and CBD, for the treatment of multiple sclerosis-related central neuropathic pain. In 2007, Canada approved the medicine’s use again for cancer pain that proved unresponsive to other medications.
Meanwhile, continued studies in the U.S. indicate CBD is effective in treating chronic, non-cancer pain. In one 2020 study, researchers administered CBD topically to a group of patients with symptomatic peripheral neuropathy (a result of brain nerve and spinal cord nerve damage) while another group with the same condition received a placebo. Results showed a significant reduction in intense, sharp pains and cold, itchy sensations in those who used the topical CBD compared to those who used the placebo. No participants reported adverse side effects.
When introduced topically, CBD oil doesn’t affect the systemic issue as it might if it were introduced directly into the bloodstream. Instead, topical CBD is more localized and treats pain in a certain area. Since it’s more direct, it may have a more pronounced effect.
7. Ease Diabetic Complications
For starters, tests on human cells found that CBD helps reduce the effects of high glucose levels on other cells in the body, which typically precedes the development of diabetes and various complications. Researchers concluded that with further studies, CBD could have significant benefits when used in patients with diabetes, diabetic complications and plaque buildup in artery walls.
In another small study, 13 patients with type 2 diabetes who weren’t on insulin treatment were given both CBD and a placebo (in lieu of insulin). Researchers found CBD decreased their levels of resistin (which causes resistance to insulin, the protein that regulates sugar levels) and increased their levels of glucose-dependent insulinotropic peptide (a hormone that ensures a sufficient release of insulin from digested food) compared to their baselines before they started the test. These results suggest CBD could be a natural treatment for diabetes by helping the body regulate insulin-related hormone levels.
8. Protect Against Neurological Disease
Preclinical and clinical studies show that CBD has antioxidant and anti-inflammatory properties. Researchers deduce these characteristics can provide significant neuroprotection, or protection against numerous pathological disorders.
Several preclinical studies suggest CBD can produce beneficial effects against Parkinson’s disease, Alzheimer’s disease and multiple sclerosis. Huntington’s disease and cerebral ischemia were also tested, although significant positive results were not recorded. Further clinical studies are needed to confirm CBD’s benefits when used as a treatment for these disorders.
9. Inhibit Arthritis Symptoms
Arthritis involves the deterioration of the tissues in and around your joints. There are several types of arthritis, and symptoms include pain, stiffness and loss of motion. Arthritis treatment usually targets pain relief and improved joint function.
A 2006 study found that Sativex—a CBD-based botanical drug approved in the United Kingdom in 2010—promoted statistically significant improvements in quality of sleep, pain during movement and pain at rest in patients with rheumatoid arthritis when compared to a placebo. It was the first controlled trial of Sativex as a treatment for rheumatoid arthritis, involving 58 patients. CBD was found to have a pain-relieving effect, as well as an ability to suppress disease activity.
In 2018, in a study of more localized treatment, researchers administered a synthetic CBD gel in either 250-milligram or 500-milligram doses daily or a placebo to patients with knee pain due to osteoarthritis. Patients also stopped taking any other anti-inflammatory medications or painkillers, with the exception of acetaminophen, before and during the study period.
The results were interesting, although not entirely conclusive. On one hand, those treated with CBD did not experience much change in pain when compared with placebo patients. On the other hand, there were statistically significant differences between the group receiving the 250-milligram dose and the placebo group when measuring the average weekly improvement of their worst pain levels and their WOMAC (Western Ontario and McMaster Universities Arthritis Index) physical function rating. Additionally, men seemed to benefit from CBD more significantly than women in this test.
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Can CBD help you chill? Here’s what we know so far.
The cannabis and hemp extract can be found in everything from lattes to kids’ vitamins. But doctors are still trying to learn if it’s healthy.
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CBD comes from the same plants as the psychoactive chemical THC. So, what it makes it safer and legal for use?. Deposit Photos
If you’re reading this, you’re probably stressed. Never fear: We’ve dug through the evidence to reveal what science really says about finding zen—and holding onto it through tough times. Want to try meditation? Take better baths? Stop anxiety in its tracks? Welcome to Calm Month.
In 2013, Charlotte Figi made national news by becoming the youngest patient in Colorado to receive cannabidiol (CBD) therapy to soothe her seizures. The five-year-old had struggled with severe epilepsy since infancy, sometimes experiencing 50 or more episodes a day, with little relief from standard drugs and dietary tweaks. By the time her parents started consulting doctors about CBD extracts, she had difficulty walking, talking, and eating without help.
Figi’s neurologist put her on a low dose of a specially bred strain of medical cannabis, later dubbed “Charlotte’s Web.” The effects were almost immediate. The seizures slowed from daily to weekly events, and soon, the kid was living life almost normally. After close to two years of the oral treatment, the doctors decided to wean Figi off other epilectic medications.
Figi’s story represents one of the clearest, most well-documented cases of the healing potential of CBD. (The young pioneer died last year, due to complications of COVID-19.) Though people have used the plant-based chemical to treat migraines and other bodily aches for centuries, the science around its efficacy is still inconclusive because it’s tricky to study its direct effect on the nervous system. Regardless, the industry has boomed in the past decade. Today CBD can be found in a range of products—from lattes to bath bombs to dog treats—and is marketed as a cure-all for pain, anxiety, insomnia, and even AIDS.
So, what should a person who’s buying CBD expect? There’s plenty of information out there, but the bottom line is confusing. Here’s an overview of what medical experts say about the ingredient and whether it lives up to its hype.
What is CBD?
CBD is essentially cannabis, minus the strong psychoactive bits. The carbon-oxygen-hydrogen compound can be found in high concentrations in Cannabis sativa and less-potent hemp plants. Sometimes manufacturers mix it with traces of tetrahydrocannabinol (THC), the cannabis-based chemical that gets people high, but it generally doesn’t carry the same dopamine-heightening and possibly addictive properties.
Like THC, though, CBD works its “magic” by cozying up to the nervous system. From what molecular scientists know so far, it somehow changes proteins found all over the body that are responsible for managing pain, inflammation, mood, appetite, and even memory. It’s still unknown how extensively it affects that internal chemistry, especially when combined with other ingredients, says Johns Hopkins University food scientist Kantha Shelke.
Is it legal?
The Food and Drug Administration (FDA) recently updated its CBD regulations to state that it supports further research on benefits, safety, and use. For now, the extract is considered a controlled substance if it comes from cannabis plants. It’s less restricted when it’s harvested from hemp.
That seems relatively straightforward, but throw local laws into the mix and the standards become a lot more unwieldy. CBD is legal to sell and buy in one form or another around the US, though it’s harder to hawk across state lines because of the federal regulations. In places where it’s lawful, the ingredient can be added to any product as long as it contains less than 0.3 percent THC and is marketed as a cosmetic or supplement. If it’s labeled as a drug or dietary substance it has to undergo clinical tests and win FDA approval before the public can lay hands on it. The agency has only approved one CBD medication so far: Epidolex, which is used to treat the same genetic syndrome that Charlotte Figi had.
Overall, the FDA seems unconcerned with low doses of the extract in food and wellness items. It does, however, caution against giving CBD products to children, pregnant and lactating people, and pets.
What are the proven benefits?
Some of the best research on CBD’s therapeutic effects comes from treating childhood epilepsy (thanks to the Figi family), schizofrenia, sleep deprivation, and anxiety disorders. The chemical has shown strong results in relieving all four of these conditions, with “a clear calming effect,” according to one 2019 analysis. That said, most of the studies exploring this connection don’t include a control group, or a baseline for comparison.
When it comes to looking at CBD for pain relief, the research is even more flimsy. Tests have shown that it can be effective against arthritis in rats, and that it might work as well as opioids for multiple sclerosis and cancer patients. But many of these treatments also included some amount of THC, so it’s hard to say if CBD was the primary cause of relief.
There’s also the question of which forms of CBD are safe enough for consumers but strong enough to make a difference. For neurological conditions like anxiety or apnea, the chemical needs to be absorbed into the bloodstream to have maximum impact. That means it needs to be ingested, inhaled, or rubbed in at high concentrations. But as health reporter Sarah Jacoby wrote in Self while vetting her own CBD buys, many of the proteins that trigger pain and inflammation are located between the skin and veins. So, any cream or gel that wants to counter aching joints and tight muscles needs to be able to get through the dermis but not as deep as the blood vessels. That’s a tall order for any drugstore formula.
Overall, doctors are reluctant to call CBD a pain panacea. But companies keep putting it in gels, goos, tinctures, massage oils, and roll-on creams, and people continue to snap them up. (One market report put CBD sales at nearly $5 billion sales in 2020.) It’s clear that the ingredient is somewhat beneficial to human health—science just needs to understand how much.
Are there any bad effects?
Medical researchers haven’t pinpointed any deadly patterns with CBD use yet. A few case studies have mentioned respiratory failure, but in many of those instances, the patients also had THC in their system. People have complained about nausea and gastrointestinal issues after taking high concentrations of CBD. The Mayo Clinic also mentions fatigue, dizziness, and loss of appetite as possible complications.
There are concerns that CBD might interact negatively with other drugs, specifically blood thinners like wafarin. But there’s no specific guidance on which medications to avoid mixing with the extract.
How much should people take?
Unfortunately, there’s no CBD-specific version of the food pyramid. Dosing depends on body weight, desired effect, and the way a person is taking it. CBD products often come with serving suggestions—but those can be misleading, given that the FDA doesn’t test every supplement against its labels and claims. (The agency has issued warnings to dozens of companies who’ve listed incorrect information about CBD and THC levels in their products; see the full list here.)
“With CBD, dosage matters,” Shelke says, as over-indulgence has been associated with ill effects. But without a fundamental understanding of the chemistry of the ingredient, and how the cooking process changes it, it’s hard to come up with scientifically backed dosing recommendations. With the limited information available, Shelke advises to go the “less is better” route with any unregulated CBD products.
Why is CBD so hard to study?
Because CBD is one of hundreds of compounds in hemp and cannabis, it’s tricky to extract and standardize. If the chemical is tainted or alternated in any way during the process, it can have a different set of effects. The way it’s consumed also plays a big part in the reaction. As Figi’s neurologist wrote back in 2014, cooking or smoking CBD means adding heat, which could break down the chemical and make it less beneficial. Pills and edibles, on the other hand, need to be carefully engineered so that they don’t get neutralized by stomach acid.
All that variability, both in the plants and the products that are derived from them, makes CBD more challenging to test for medicinal purposes. It’s also often mixed with THC when treating chronic pain or life-threatening illnesses, so it take many extra layers of research to isolate the purely physical perks from the psychoactive ones.
Is it safe to cook with?
Plenty of companies, restaurants, and cookbook authors are now folding CBD into their recipes. But does the ingredient have the same therapeutic effect when it’s baked in a brownie pan at 360 degrees Fahrenheit or seared in a skillet with sea bass and lemon rinds?
“There are many unanswered questions about the science, safety, quality, and physiological effects of CBD that need to be addressed before one can identify the effects of various chemical reactions on its efficacy,” Shelke says. Part of the issue with cooking with the extract is that the purity and the concentration is often unknown. This makes it even harder to know how it will interact with other ingredients, and whether that combination will help or harm a person. Bottom line: It’s better to avoid highly processed products or prepared meals with CBD, especially if you’re new to the compound.
What’s the best way to see if CBD works for me?
If you’re looking for a supplement to help you go to sleep at night, relieve a light migraine, or unwind after a stressful event, try a low-stakes gummy or topical oil. Be sure to choose a well-reviewed and reputable product, Shelke says: Just because it says it contains CBD doesn’t mean it will live up to its promise.
To treat chronic pain, depressive disorders, or other serious illnesses, get your doctor’s recommendations first. They can take stock of the latest research specific to your needs and also track how CBD works with other prescriptions you’re taking.
As you head into the experience, manage your expectations. Like most wellness products that are backed by tepid evidence, the results can be hit or miss. Stay within the recommended doses on the products’ labels and report any unexpected side effects to your primary-care physician.
The future of CBD seems full of potential, but in present times, there are more questions than answers.
This post has been updated with new information from the Food and Drug Administration.
Purbita Saha (she/her) is the Deputy Editor at Popular Science. She leads the magazine’s science desk and internship program and also edits features, reads book galleys, guest stars on “Weirdest Thing I Learned This Week,” and tweets bad jokes from the @PopSci account. Contact the author here.