Studies are showing that CBD can reduce itching — but can this symptom also be the result of an allergic reaction to CBD oil? Let’s explain why some people claim that CBD oil can cause itching. CBD is known to have very few side effects, but can it cause itching? We take a look at whether CBD can cause allergies and itchy skin. Cannabidiol (CBD) is a nonpsychotomimetic constituent of the Cannabis plant, with potential therapeutic properties for many physical and neuropsychiatric conditions. Isolated CBD has been suggested to have favorable safety and tolerability profile. Although CBD-related rash is described, few case reports are well documented in the literature, and usually, CBD was used concomitantly with other medications. Thus, we report four females who presented a skin rash after ongoing CBD use. Other causes of these skin rashes were ruled out after conducting an extensive viral and serological detection panel, and three patients had their lesions biopsied. Two patients were re-exposed to the vehicle (MCT) without developing a new skin rash. Therefore, clinicians must be aware of this potential adverse effect of CBD use.
Can CBD Oil Cause Itching?
According to many experts and official reports from international health agencies, CBD has an excellent safety profile, with only a few benign side effects.
However, for some patients, CBD may cause reactions that aren’t experienced by other people — such as itching.
Is it a coincidence, or does CBD oil really cause itching?
In this article, we leave no doubt behind potential allergic reactions to CBD products — and how to avoid them.
Can CBD Cause Itching?
One of the main reasons CBD has become so popular is that it generally doesn’t have serious adverse effects. In a 2017 review published in the journal Cannabis and Cannabinoid Research, the authors concluded that CBD is safe and well-tolerated by humans in comparison to many pharmaceuticals that are prescribed for the same conditions ( 1 ).
That said, there are a few side effects that you might experience when taking large doses of CBD oil. The most common side effects of CBD include dry mouth, changes in appetite, dizziness, and — in extreme cases — diarrhea.
According to the report issued by the Medicines and Healthcare Products Regulatory Agency (MHRA), CBD might cause itching in some individuals. The MHRA is an agency that provides consumers with the opportunity to report adverse reactions after taking certain supplements.
The report stated that there were at least two cases of itching after taking CBD oil. One person took CBD orally and experienced a severe skin reaction known as urticaria. Another used both oral and topical forms of CBD — and also experienced itching .
Whether these side effects were caused by CBD alone, some other compounds of hemp oil, or by impurities is unknown.
So, how common is itching after CBD oil, and does it have any other alarming symptoms?
Itching and Other Allergic Reactions to CBD Oil
The information on CBD oil and allergies is scarce. However, it seems that people can develop allergies to cannabis in general.
The Annals of Asthma, Allergies, and Immunology conducted a study in 2013, where they reported cases of hypersensitivity and even anaphylaxis after using marijuana ( 3 ).
Anaphylaxis, also known as anaphylactic shock, is a severe allergic reaction that causes the swelling of the airways and makes people unable to breathe. The reaction can even be fatal.
The symptoms of allergies to cannabis include:
- Rhinitis (nasal inflammation)
- Sore throat
- Shortness of breath
- Dry eyes
- Shortness of breath
- Nasal congestion
Some studies also suggest that high doses of cannabis could result in asthma and bronchitis. However, the results are conflicted, as there are at least a few studies suggesting that cannabis can be used for the treatment of asthma — being part of the medical cannabis program in many states.
Again, we’d need to consider the purity of cannabis and its derivatives in the studies that indicated the risk of allergic reactions to the plant. Cannabis grown on illegal sites can be contaminated with pesticides, heavy metals, synthetic cannabinoids, and blends of drugs that are used to potentiate its psychoactive effects by black market vendors.
The authors of the study also found that workers in hemp processing facilities may have higher rates of respiratory disorders. They point that cannabis allergies occur due to inhaling and direct handling, although edibles could also potentially cause allergies.
Since CBD is derived from cannabis, it’s within reason to assume that people with cannabis allergies can also be sensitive to CBD.
More research is required to draw definitive conclusions, especially with the purity of cannabis products in mind.
Can CBD Oil Trigger a Skin Rash?
As mentioned earlier in this article, the reports of skin rashes and itching after CBD oil are few and far between — at least when it comes to hemp-derived CBD oil. This side effect might be more common with a synthetic form of CBD known as Epidiolex.
Epidiolex is the only form of CBD that has received full approval from the Food and Drug Administration (FDA). Therefore, researchers have investigated it in terms of both potential benefits and side effects.
The information on the drug’s prescription lists rashes as one of the most common side effects of Epidiolex.
It also notes that the drug can trigger liver problems. One of the symptoms of this reaction is itching.
Other signs of liver problems include:
- Pain in the upper-right abdominal area
- Yellowing of the skin and eyes
- Dark urine
- Reduced appetite
It’s worth noting that the above reactions refer to synthetic forms of CBD. There have been no such issues with hemp-derived CBD oil that has been tested for potency and purity by an independent laboratory. So, when buying products online, make sure to check and read these lab test results to know the potency of the products you are going to purchase and their contents.
Anyone experiencing the above side effects after Epidiolex should seek medical attention immediately.
Can CBD Oil Make Your Eyes Itch?
Itchy eyes are an obvious indicator of allergies. Pollen allergies often make our eyes dry, red, watery, and itchy. In other words, if you’re allergic to hemp and get into contact with the plant’s pollen, this could trigger itchy eyes.
Marijuana users may be familiar with the tell-tale effect of red eyes after consumption. However, this side effect is not to be confused with the dryness caused by allergies. Dry and red eyes after consuming marijuana result from its effects on the blood capillaries surrounding the ocular nerves; when THC enters your system, the capillaries get dilated, resulting in increased blood flow — and giving you the ruby eyes.
There are no reliable reports of itching caused by CBD oil. However, this doesn’t mean it’s impossible. Let us know in the comments if you have experienced itching after taking CBD products.
CBD and Itching: The Cause or the Solution?
Although some people have experienced itching after taking CBD products, it seems that this side effect only affects a very small percentage of users. In fact, some studies suggest that CBD could offer relief from itching in skin conditions such as psoriasis or eczema.
CBD works in the body by interacting with the endocannabinoid system (ECS). The ECS has cannabinoid receptors all over the body, including the central nervous system, peripheral nervous system, and all organs. The ECS has been found to regulate many essential biological processes — such as immune function.
When you take CBD oil for itching, it interacts with the CB2 cannabinoid receptors that modulate the activity of immune cells. CBD can both improve the communication between these cells — ensuring the healthy functioning of the immune system — and reduce inflammation by inhibiting the release of pro-inflammatory proteins called cytokines.
Lower inflammation markers have been associated with an anti-inflammatory response, including a reduction in pain, swelling, redness, and itching.
On top of that, CBD indirectly signals the ECS to release more of its endocannabinoids. It also slows down their breakdown by blocking the enzyme called Fatty Acid Amide Hydrolase (FAAH) Once released, they also bind to cannabinoid receptors, bolstering the immunomodulatory effects of cannabidiol.
In a 2006 German study published in the journal Der Hautarzt , the research team tested a compound called N-palmitoyl ethanolamine (PEA) on 22 patients with various skin conditions. The compound is a cannabinoid agonist, meaning it activates the receptors of the ECS ( 4 ).
Of the 22 participants, 14 experienced relief from itching, with an average reduction score of 86.4%.
Unfortunately, the study had a very small sample size; therefore, more large-scale studies are necessary to confirm these results with greater confidence.
Nevertheless, the preliminary findings are very promising, suggesting that CBD is more likely to solve the problem of itching rather than to cause it.
So… Can CBD Oil Cause Itching?
Although some individuals reported itching after using CBD oil, this adverse reaction might affect only a small percentage of users. Moreover, itching doesn’t have to be caused by CBD itself; instead, it may result from contamination with toxic compounds that can irritate the skin and trigger allergies.
The reaction can also be caused by other hemp compounds that are present in full-spectrum and broad-spectrum CBD oils. Natural ingredients are known to cause allergies in sensitive users, so if you suspect that CBD oil causes itching in your case, opt for isolate-based products, as they only contain CBD.
There are two things you can do to avoid experiencing itching after taking CBD oil. First, always make sure to buy CBD products from a reputable manufacturer that provides relevant and up-to-date lab reports for every batch. We also suggest that you consult a doctor and run allergy tests if you believe that you’re allergic to any of the ingredients found in whole plant extracts.
Have you ever experienced itching after taking CBD oil? Share your stories in the comment section!
- Iffland, K., & Grotenhermen, F. (2017). An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis and cannabinoid research , 2 (1), 139–154. https://doi.org/10.1089/can.2016.0034
- Food.gov.uk. (2019) Committee on Toxicity of Chemicals in Food, Consumer Products, and the Environment. Available at: https://cot.food.gov.uk/sites/default/files/tox2019-32.pdf
- Nayak AP, Green BJ, Sussman G, et al. Characterization of Cannabis sativa allergens. Ann Allergy Asthma Immunol . 2013;111(1):32-37. doi:10.1016/j.anai.2013.04.018
- Ständer, S., Reinhardt, H. W., & Luger, T. A. (2006). Topische Cannabinoidagonisten. Eine effektive, neue Möglichkeit zur Behandlung von chronischem Pruritus [Topical cannabinoid agonists. An effective new possibility for treating chronic pruritus]. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete, 57(9), 801–807. https://doi.org/10.1007/s00105-006-1180-1
Nina created CFAH.org following the birth of her second child. She was a science and math teacher for 6 years prior to becoming a parent — teaching in schools in White Plains, New York and later in Paterson, New Jersey.
Can CBD Oil Cause Itching? [Explained]
Most experts consider cannabidiol (CBD) to have an excellent safety profile and minimal risk of side effects. However, some patients have reported experiencing itching after using CBD oil. Could this be a CBD side effect or merely a coincidence?
In this article, we’ll answer the question, “can CBD oil cause itching?” Read on to learn more.
Does CBD Make You Itch?
One of the reasons CBD has become so popular is that it generally causes very few adverse effects.
A 2017 review for Cannabis and Cannabinoid Research investigated the safety and side effects of CBD. It concluded that CBD has a favorable side effect profile in comparison to many pharmaceuticals that treat the same conditions.
That said, side effects did occur, with the most common being tiredness, diarrhea, and appetite/weight changes. The report makes no mention of itching as a potential CBD oil side effect.
However, in the UK, the Medicines and Healthcare Products Regulatory Agency (MHRA) had different findings. The MHRA runs the Yellow Card Scheme, which provides consumers with an opportunity to report adverse reactions after using a specific medicine or supplement.
The 2019 report suggests that there were at least two cases of rashes and itching after using CBD oil. One patient took CBD orally and experienced urticaria, a severe skin reaction involving red welts, swelling, and intense itching. Another used CBD both orally and topically and also experienced itching.
It seems that the most likely explanation for these adverse effects is an allergic reaction to CBD oil. So, how common is this problem, and are there any other symptoms?
Exploring the advantages and d…
Itching and Other CBD Oil Allergic Reaction Symptoms
There is little information available on CBD oil allergies. However, there is some research into cannabis allergies in general. The Annals of Asthma, Allergies, and Immunology conducted a study in 2013. It concluded that there had been cases of hypersensitivity and even anaphylaxis after using marijuana.
Anaphylaxis, or anaphylactic shock, is an extreme allergic reaction. It results in swelling of the airways and an inability to breathe and can potentially be fatal. Other cannabis allergy symptoms include:
- Sore throat
- Rhinitis (nasal inflammation)
- Nasal congestion
- Shortness of breath
- Watery eyes
Furthermore, the report states that workers in hemp processing facilities may experience higher rates of respiratory problems. The authors point out that most cannabis allergies occur due to smoking and direct handling. However, consuming edibles could also potentially cause a reaction.
The AAAAI (American Academy of Allergy, Asthma, and Immunology) says that cannabis allergy can develop due to “inhaling, smoking, touching, and eating marijuana.” It states that touching the plant could cause rashes, hives, and swelling in sensitive individuals.
Since CBD comes from cannabis plants, it is reasonable to assume that those with cannabis allergies could also be sensitive to CBD. However, more research is necessary to confirm how many people are allergic to CBD oil and to what extent.
Can CBD Oil Cause a Skin Rash?
As we have already mentioned, there have been isolated reports of CBD causing a skin rash. This side effect may be more widely reported with a particular form of CBD known as Epidiolex.
Epidiolex is the only form of CBD with full approval from the Food and Drug Administration (FDA). Therefore, scientists have tested it rigorously for both potential benefits and side effects. The drug’s prescribing information lists rashes as one of the most common side effects of Epidiolex.
It also states that the drug could cause liver problems. One of the symptoms of this is itching. Other signs of liver issues include:
- Reduced appetite
- Jaundice (yellowing of the skin and eyes)
- Dark urine
- Pain in the upper-right abdominal area
Anyone experiencing these side effects after taking Epidiolex or CBD oil should seek medical advice immediately.
Can CBD Oil Cause Itchy Eyes?
Itchy eyes are a common allergy symptom. Pollen allergies often cause the eyes to become red, watery, and itchy. Therefore, someone allergic to cannabis coming into contact with cannabis or hemp pollen could experience these effects.
Those who use marijuana regularly may be familiar with the tell-tale side effect of red or bloodshot eyes. However, this is not due to CBD but the intoxicating compound in cannabis, THC.
Red eyes result from THC causing the blood vessels to relax and widen. Many believe that, for the same reason, marijuana could be a useful glaucoma treatment.
We couldn’t find any reliable reports of CBD oil causing itchy eyes, but that does not mean it is impossible. Let us know in the comments at the end of the article if you have experienced this.
CBD and Itching: The Problem or the Solution?
Although some people have experienced itching after using CBD oil, this reaction only affects a minority of users. In fact, some research suggests that CBD could offer a solution to itching in skin conditions such as psoriasis and dermatitis.
CBD impacts the body by interacting with the endocannabinoid system (ECS). This system is present in most of the body’s tissues, including the skin. Experts believe that it regulates the growth and development of skin cells and influences their immune function.
The ECS is also present in the skin’s nerve endings and plays a role in sensory perception, including pain and itching. These effects are under the control of numerous cell receptors, including cannabinoid receptors (CB1 and CB2). These receptors become active when they bind with chemicals called endocannabinoids that our bodies naturally produce.
It seems that CBD works primarily by increasing the levels of these endocannabinoids to enhance ECS function. This effect means that CBD could be more likely to relieve itching than cause it.
A 2006 study for the German journal Der Hautarzt tested a compound called N-palmitoyl ethanolamine (PEA) in 22 patients with itching due to various skin conditions. The chemical is a cannabinoid agonist, meaning that it stimulates receptors in the ECS. Of the 22 participants, 14 experienced reductions in itching, and the average reduction was an impressive 86.4%.
This study, unfortunately, had a very small sample size, and more research is necessary to confirm its results conclusively. However, these preliminary findings suggest that, unless you have a CBD allergy, the compound is more likely to act as a solution to itching than a cause.
Can CBD Oil Cause Itching? Final Thoughts
It seems that CBD oil may cause itching in a small number of consumers. This reaction is most likely the result of a CBD allergy or sensitivity to other ingredients in the product. The latter could be especially true when using topical CBD products, as these contain a variety of components that could potentially irritate the skin.
We advise anyone considering using CBD skin creams to look for a product containing all-natural ingredients and as few of them as possible. This precaution is especially important if you have sensitive skin or other allergies.
As always, we only recommend buying CBD from reputable brands that publish third-party lab reports on their websites. Products that have not undergone testing may contain contaminants and increase the risk of adverse reactions like itching.
And finally, if you do experience itching after taking CBD, we suggest that you stop using it immediately. Make an appointment with a physician who will be able to run tests and advise you further.
Case Report: Cannabidiol-Induced Skin Rash: A Case Series and Key Recommendations
José Diogo S. Souza 1 *, Maíra Fassoni-Ribeiro 2 , Rayssa Miranda Batista 3 , Juliana Mayumi Ushirohira 1 , Antonio W. Zuardi 1,4 , Francisco S. Guimarães 4,5 , Alline C. Campos 5 , Flávia de Lima Osório 1,4 , Daniel Elias 3 , Cacilda S. Souza 3 , AndRea A. Fassoni 6 , Jaime E. C. Hallak 1,4 and José Alexandre S. Crippa 1,4
- 1 Department of Neurosciences and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- 2 Department of Dermatology, São Paulo Federal University, São Paulo, Brazil
- 3 Division of Dermatology, Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- 4 National Institute of Science and Technology—Translational Medicine, Ribeirão Preto, Brazil
- 5 Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- 6 Anatomed Laboratory, Bauru, Brazil
Cannabidiol (CBD) is a non-psychotomimetic constituent of the Cannabis plant, with potential therapeutic properties for many physical and neuropsychiatric conditions. Isolated CBD has been suggested to have favorable safety and tolerability. Although CBD-related rash is described, few case reports are well documented in the literature, and usually, CBD was used concomitantly with other medications. Thus, we report four women who presented a skin rash after ongoing CBD use. Other causes of these skin rashes were ruled out after conducting an extensive viral and serological detection panel, and three patients had their lesions biopsied. Two patients were re-exposed to the vehicle (MCT) without developing a new skin rash. Therefore, clinicians must be aware of this potential adverse effect of CBD use.
Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid with potential therapeutic properties across many physical and neuropsychiatric conditions (Crippa et al., 2018). CBD is generally well tolerated and has few serious adverse effects (Chesney et al., 2020). There is an increasing requirement in many countries for patients to legally use this cannabinoid to treat sleep disorders, addiction, pain, and anxiety and, more broadly, promote their health and wellbeing (Crippa et al., 2018). However, only the isolated CBD Epidiolex® (GW-Pharm, United Kingdom) has been licensed for two rare childhood epilepsies in some Western countries. Some of the most common side effects of Epidiolex® include sleepiness, decreased appetite, diarrhea, increase in liver enzymes, sleep problems, and cutaneous rash (EPIDIOLEX, 2022). Although this skin condition is documented as a common side event, the trials that reported it had used CBD formulations as an adjuvant treatment to other drugs (Devinsky et al., 2018).
We report here four women, three patients without comorbidities and one with diabetes using daily medications, who presented a skin rash between 6 h and 11 days after starting CBD use. The subjects were volunteers in the Brazilian clinical trial and follow-up study to evaluate the anxiolytic effects of CBD in healthcare frontline workers during the current COVID-19 pandemic, between June and November 2020. Part of these results has been published (Crippa et al., 2021). The subjects received isolated oral CBD (99.6% purity with no other cannabinoid; PurMed Global; United States) dissolved in medium-chain triglyceride oil (150 mg/ml) at a daily dose of 300 mg (150 mg twice per day) for 4 weeks. To the best of our knowledge, these are the first case reports with multiple individuals not using other medications, with an extensive investigation to exclude other clinical causes (Pettit et al., 2018; Singh and Antimisiaris, 2020). Half of the patients were exposed only to the vehicle (medium-chain triglyceride (MCT) oil) to confirm that the adverse effect was specifically related to CBD use.
A 34-year-old woman, without comorbidities or medication use, after 6 h of CBD use, noticed the emergence of a skin rash in the cervical region, trunk, and abdomen, with progression to the upper and lower limbs (Figure 1A). She reported an associated feeling of abdominal distension that improved after taking symptomatic medication, Simethicone. She had no fever or any other systemic symptoms. She presented a morbilliform exanthem on the face, neck, trunk, abdomen, upper limbs, and thighs, sparing the face and palmoplantar region, without mucosal lesions. There were no abnormalities in the blood count, and the broad investigation of viral infections and syphilis by RT–PCR or serology was negative for recent or active infections (Table 1). CBD withdrawal resulted in the involution of all lesions after 5 days, without any topical or systemic therapy. The patient voluntarily agreed to be exposed to the CBD vehicle (medium-chain triglyceride (MCT) oil). After 5 days of use, there was no recurrence or emergence of new rashes.
FIGURE 1. (A) Case 1: rash on the inner side of the left thigh after 6 h of CBD use. The disappearance of the lesion on digital pressure is observed. (B) Case 2: confluent erythematous papules on the trunk and left arm after 8 days of CBD use. (C) Case 3: abdominal rash after 5 days of CBD use. The disappearance of the lesion on digital pressure is observed. (D) Case 3: evolution of rash to erythematous papules, surrounded by a hypochromic halo, on the lower limbs, after 10 days of CBD use.
TABLE 1. Laboratory findings for investigation of infections in the four patients with skin rash using cannabidiol.
A female subject, 33 years old, diabetic using metformin, sibutramine, and semaglutide, 7 days after starting CBD use, reported the appearance of erythematous and pruritic papules on the trunk, abdomen, and thighs, with an increase in the lesions and progression to the arms after 1 day. She had no fever or other systemic symptoms associated with the skin condition. A physical examination showed coalescing erythematous papules on the limbs, trunk, and abdomen (Figure 1B) without affecting other areas such as the face, and the palmoplantar and mucosal regions. There was a complete remission of the lesions after 6 days of CBD suspension, without the need for any topical or systemic therapy. There was no change in the blood count (before and after CBD use), and the broad investigation of viral infections and syphilis by RT–PCR or serology was negative for recent or active infections (Table 1).
A 34-year-old woman without comorbidities or medication use developed a rash on the abdomen after 5 days of CBD use (Figure 1C). The patient chose to continue using CBD, and after 5 days, the skin condition worsened, with progression to erythematous lesions on the buttocks and limbs, which were not pruritic but sensitive. She presented associated headaches and myalgia without fever or other systemic complaints. On physical examination, monomorphic erythematous papular lesions with a hypochromic halo were observed on the trunk, back, buttocks, lower limbs, and upper limbs (Figure 1D), sparing the face and the palmoplantar region, and without mucosal lesions. Withdrawal of CBD resulted in the involution of all lesions after 7 days, without the need for any topical or systemic therapy. There was no change in the blood count (before and after CBD use), and the broad investigation of viral infections and syphilis by RT-PCR or serology was negative for recent or active infections (Table 1). The patient voluntarily agreed to be exposed to the CBD vehicle (MCT), and after 5 days of use, there was no recurrence or emergence of new rashes.
A female subject, 28 years old, without comorbidities or medication use, reported erythematous and pruritic lesions on the trunk and abdomen with evolution to arms and legs after 9 days of CBD use. She had associated diarrhea but did not present fever or other systemic symptoms. The physical examination showed monomorphic urticarial lesions (Figure 2A) that evolved after 2 days, with coalescence in the trunk, abdomen, and the upper and lower limbs (Figure 2B), even after discontinuing CBD in the period. Lesions spared the face and the palmoplantar and mucosal regions. There was a complete improvement of the lesions after 11 days of discontinuation of CBD, and it was necessary to initiate oral corticosteroid therapy (prednisone 0.5 mg/kg/day). There was no change in the blood count (before and after CBD use). The broad investigation of viral infections and syphilis by RT–PCR or serology was negative for other active or recent infections (Table 1), except for IgM positivity for Epstein–Barr.
FIGURE 2. (A) Case 4: erythematoedematous papules on the left upper limb after 9 days of CBD use. (B) Evolution of the lesions after 2 days, after medication discontinuation, and initiation of oral prednisone.
Adverse drug reactions focus on clinical studies to connect possible side effects and the studied compound. Skin lesions often herald these reactions because this body organ can be quickly evaluated and confirmed to be immunologically active. These aspects make it particularly relevant in this and other clinical contexts. However, the skin condition itself can be highly non-specific, and it is always necessary to rule out other possible clinical causes, especially viral infections and drug vehicle allergies.
These skin reactions can be considered pharmacologically mediated (type A) or allergic or non-allergic hypersensitivity reactions (type B) (Böhm et al., 2018). Type A reactions, as they are generally dose dependent, can be resolved with changes in therapy and allow for the maintenance of treatment. On the other hand, Type B reactions constitute the minority, although they are more unpredictable than type A. Moreover, these responses can lead to severe conditions, such as Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS). In these cases, re-exposure to the potentially causative drug is strictly not recommended.
The most common form of drug rash is morbilliform or maculopapular (Hoetzenecker et al., 2016). Nonetheless, the same drug can cause different patterns of dermatological manifestation since the pathogenesis of pharmacodermia is multifactorial and may involve genetic factors, lymphocyte activation, metabolic enzyme defects, eosinophilia, herpes virus activation, among others. Regarding DRESS cases, it is believed that an allergic immune response to a particular drug can stimulate T cells and induce viral reactivation (Husain et al., 2013). In one of the present study cases, even though it was a mild skin reaction, positive IgM and IgG for Epstein–Barr may suggest a relationship between pharmacodermia and reactivation of herpes virus 7 (HHV-7).
We report four women, three patients without comorbidities, and one with diabetes using daily medications, who presented with skin rashes between 6 h and 9 days after starting CBD use. The experimental CBD studied was pharmaceutical grade with no other compound than the MCT oil vehicle. In total, 100 participants (79 women and 21 men) received CBD oil, with four skin reactions related to the medication use (4% of volunteers). Three main patterns were observed: exanthematous, monomorphic erythematous papular lesions, and urticarial pattern, on the trunk and abdomen, with centrifugal progression to the limbs, sparing the face and palmoplantar regions, which were pruritic or sensitive to touch. There was an association with headache and myalgia in one case and abdominal symptoms in two other cases. The suspension of CBD resulted in the involution of the lesions between 5 and 11 days, without any topical or systemic therapy for three of the patients and prednisone 0.5 mg/kg for 5 days for one of the patients. Subsequent re-exposure to CBD vehicle (MCT) for 5 days in two of the patients did not induce a recurrence of the rash.
A broad investigation of viral infections and serology for syphilis and hepatitis was carried out, which were negative, except for one of the patients who had positive serology for the Epstein–Barr virus. The relevance of research on arboviruses is worth noting since they are prevalent in the study region and on SARS-CoV-2, given the context of the COVID-19 pandemic. In addition, lesions were biopsied from three patients (cases 1, 3, and 4). The histopathological pattern showed skin with mild hyperkeratosis, dermal edema, focal vacuolar degeneration of the basal layer, and lymphohistiocytic infiltrate with sparse eosinophils predominantly in the perivascular and periadnexal locations (Figure 3). Given such clinical, laboratory, and anatomopathological findings, the four cases can be diagnosed as skin rashes induced by CBD use. To the best of our knowledge, these are the first case reports with multiple individuals not using other medications, with an extensive investigation to exclude other clinical causes and half of the patients being exposed only to the MCT vehicle afterward (Pettit et al., 2018; Singh and Antimisiaris, 2020).
FIGURE 3. (A) Edema of the papillary dermis and focal area of vacuolar degeneration of the basal layer of the epidermis (arrow), 10x magnification. (B) Details for the presence of eosinophils (arrows), 20x magnification.
An individual analysis of CBD plasma levels was only possible in two of the subjects since the other two withdrew from the trial before measurement. These two subjects showed levels that reached the upper 95% percentile of the whole study (levels of 98 and 179 ng/ml, respectively). This finding suggests that the reported pharmacodermia could be associated with high plasma levels of CBD. However, this possibility should be seen with caution, considering the low number of subjects. Also, the cutaneous rash did not occur in five other subjects that also reached similar high CBD plasma levels. CBD is extensively metabolized by CYP450 isoenzymes. The extent to which genetic polymorphisms in these isoenzymes would affect CBD plasma levels and their side effects remains poorly explored and should be a focus of future research.
Cannabis products are widely employed worldwide, and their use has been illegalized in several countries (Bonomo et al., 2018). After legalizing medicinal and recreational cannabis in some countries, its use highly increased (Wen et al., 2015; Martins et al., 2016; Hasin et al., 2017). In the United Kingdom, for instance, it is estimated that over a million people are using non-legally sourced cannabis for self-medication of diagnosed conditions (Schlag et al., 2021). CBD has gained special attention for its therapeutic potency for several neuropsychiatric and general medical conditions, including a trend as a new ingredient for skincare products. However, apart from epilepsy, much of the available data are from preclinical studies and lack the support of robust human, randomized, placebo-controlled, double-blind studies (Jhawar et al., 2019; Baswan et al., 2020).
While there is a growing demand in many countries for legal CBD use to treat various mental and physical health problems, determining the best regulatory response to these demands is a significant challenge. It occurs because most CBD products come in multiple formulations and routes of administration, and the great majority is prepared in an artisanal manner, without the necessary manufacturing, quality control, labeling, and pharmaceutical-grade production. In addition, there is a paucity of data to support the therapeutic use of many of the indications consumed by this tremendous global demand. The clinical use of CBD needs to be aligned with many other pharmaceutical products to ensure efficacy and safety for patients, given its interactions with other drugs and its potential side effect profile. Therefore, through evidence-based medicine, an exhaustive framework to guarantee the quality and safety of the CBD product is urgently needed to protect the consumers and minimize possible harm.
We report four cases who presented with a skin rash between 6 h and 11 days after starting CBD use. Considering the clinical, laboratory, and anatomopathological findings, the four cases can be diagnosed as skin rashes induced by this cannabinoid. This finding reinforces the proposal that CBD use should be guided by evidence-based medicine, being necessary to balance the benefits with potential adverse and undesired effects when making decisions regarding its use.
Data Availability Statement
The raw data supporting the conclusions of this article will be made available by the authors if requested, without undue reservation.
The studies involving human participants were reviewed and approved by the research ethics committee of the Ribeirão Preto Medical School University Hospital and the National Council on Research Ethics as part of the ‘Burnout and Distress Prevention With Cannabidiol in Front-line Healthcare Workers Dealing With COVID-19 (BONSAI)’ trial. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
Assessment and support of study patients: JS, RB, JU, and JC. Drafting of the manuscript: JS, MF-R, and RB. Critical revision of the manuscript: JS, MF-R, RB, JU, AZ, FG, AC, FO, DE, CS, AF, JH, and JC. Anatomopathological analysis: AF. Funding: JH and JC. Supervision: AZ, FG, DE, CS, and JC.
This work was supported by a grant (2020/12,110-9) from the Fundação de Amparo à Pesquisa do Estado de São Paulo and a grant (2008/09,009-2) from the Instituto Nacional de Ciência e Tecnologia Translational em Medicina.
Conflict of Interest
AZ reported receiving grants from the National Institute of Translational Science and Technology in Medicine and personal fees from the National Council for Scientific and Technological Development during the conduct of the study, being a co-owner of a patent for fluorinated cannabidiol compounds (licensed to Phytecs), and having a patent pending for a cannabinoid-containing oral pharmaceutical composition outside the submitted work. FG reported receiving grants from Prati-Donaduzzi, being a co-owner of a patent for fluorinated cannabidiol compounds (licensed to Phytecs), and having a patent pending for a cannabinoid-containing oral pharmaceutical composition outside the submitted work. AC reported having a patent pending for a cannabinoid-containing oral pharmaceutical composition outside the submitted work. CS is a consultant and/or has received speaker fees and/or sits on the advisory board and/or receives research funding from Abbvie, Novartis, Janssen-Cilag, and Boehringer Ingelheim. JH reported receiving grants from Prati-Donaduzzi, travel support and personal fees from BioSynthesis Pharma Group, being a co-owner of a patent for fluorinated cannabidiol compounds (licensed to Phytecs), and having a patent pending for a cannabinoid-containing oral pharmaceutical composition outside the submitted work. JC reported receiving grants from the São Paulo Research Foundation and the National Institute of Translational Science and Technology in Medicine and personal fees from the National Council for Scientific and Technological Development and receiving travel support and personal fees from BioSynthesis Pharma Group; serving as a member of the international advisory board of the Australian Centre for Cannabinoid Clinical and Research Excellence, National Health and Medical Research Council; being a co-owner of a patent for fluorinated cannabidiol compounds (licensed to Phytecs); and having a patent pending for a cannabinoid-containing oral pharmaceutical composition outside the submitted work.
The remaining 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.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors, and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
The authors thank PurMed Global (Delray Beach, Florida) for donating cannabidiol and ANATOMED Laboratory (Bauru, Brazil) for their anatomopathological analysis at no cost.
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Keywords: cannabidiol, drug interaction, side effects, skin rash, case report, case series
Citation: Souza JDS, Fassoni-Ribeiro M, Batista RM, Ushirohira JM, Zuardi AW, Guimarães FS, Campos AC, Osório FL, Elias D, Souza CS, Fassoni AA, Hallak JEC and Crippa JAS (2022) Case Report: Cannabidiol-Induced Skin Rash: A Case Series and Key Recommendations. Front. Pharmacol. 13:881617. doi: 10.3389/fphar.2022.881617
Received: 22 February 2022; Accepted: 25 March 2022;
Published: 19 May 2022.
Gustavo Gonzalez-Cuevas, Idaho State University, United States
Robert B. Laprairie, University of Saskatchewan, Canada
Franjo Grotenhermen, Nova Institut GmbH, Germany
Copyright © 2022 Souza, Fassoni-Ribeiro, Batista, Ushirohira, Zuardi, Guimarães, Campos, Osório, Elias, Souza, Fassoni, Hallak and Crippa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.