Today’s article seeks to answer a simple query. What are the side effects of CBD in humans? To answer this query successfully, we need to first understand what CBD is and briefly understand what it’s currently being used for. From there, we’ll look at the results of three clinical reviews that investigated the safety and side effect profile of CBD in humans and animals. In saying that, this article will only focus on human results. Hopefully, this will dispel any myths and misinformation surrounding cannabis therapy. But first, let’s start with the basics.

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What Is Cannabidiol (CBD)?

Cannabidiol (CBD) is a component of the Cannabis Sativa, Indica, or Ruderalis plant. It makes up about 40% of the herb extracts derived from one of the aforementioned variants. CBD is a non-psychotropic component of the Cannabis plant. This means CBD won’t get you ‘high‘ unlike THC, which will. CBD has multiple therapeutic actions, which include but are not limited to:

• Anxiolytic i.e. reduces/prevents anxiety
• Antipsychotic i.e. reduces/prevents delusions, hallucinations, paranoia, and disordered thought
• Antiemetic i.e. reduces/prevents vomiting
• Anti-inflammatory i.e. reduces/relieves inflammation, redness, and swelling
• Analgesic i.e. reduces/relieves pain
• Antiepileptic i.e. reduces/prevents seizures
• Neuroprotective i.e. protects/preserves nerve cells against damage, degeneration, and impairment of function
• Sedative i.e. promotes calmness and induces sleep

CBD was first isolated in 1940. Its chemical structure was identified 23 years after it was first isolated. Since then, a lot of published articles have come out dealing with its chemistry, biochemistry, pharmacology, and clinical effects. However, its safety and side effect profile in humans is mostly assumed to be safe without any clinical data backing the assumption. This article seeks to provide a clear and data-backed answer regarding the safety and side effect profile of CBD in humans.

What Is The Safety And Side Effect Profile Of CBD?

CBD is clinically considered safe in humans (and animals) based on the advances made in its administration. Multiple studies suggest that CBD is well tolerated and safe in humans at high doses, and even with chronic use. However, many studies have also shown that CBD has a strong potential for metabolic drug interactions. This indicates that there is a need to be careful when administering CBD to human patients, especially when other drugs are involved.

In order to support the answer above, we need to look at the results of three clinical studies. The studies to be reviewed include a 2011 Review of the Safety and Side Effects of CBD, a 2017 Update Review of the Safety and Side Effects of CBD, and a 2020 Meta-Analysis of the Adverse Effects of CBD.

2011 Review Summary: Safety And Side Effects Of CBD On Humans.

In 2011, researchers set out to investigate the safety and side effects of CBD in humans and animals. The researchers reviewed medical papers published where only CBD was used. The researchers excluded medical papers that included other cannabinoids such as THC for example. In total, the researchers ended up reviewing 132 medical papers to zero in on the side effect and safety profile of CBD.

The researchers found that in human studies, CBD administration across a wide range of dosages did not induce side effects, and tolerance of CBD did not develop in patients. The studies reviewed were conducted on both acute and chronic dose regimens, which means short and long-term time frames. What proceeds from here is a detailed summary of the researcher’s findings in humans.

Detailed Summary Of Findings: 2011 CBD Safety And Side Effect Review

In human acute studies, CBD taken either orally (15 – 160 mg), inhaled (0.15 mg/kg of body weight), or via injection (5 – 30 mg) did not show an onset of negative or ill side effects. Instead, the researchers found that CBD does not interfere with several psychomotor and psychological functions in humans. They also found that CBD does not affect your heart rate, blood pressure, or learning and memory performance at doses as high as 600 mg. In addition, antipsychotic studies where CBD was utilized did not report any side effects after CBD intake.

In human chronic studies, CBD taken orally at 10 mg daily for 21 days did not induce any changes in neurological, clinical, psychiatric, blood, or urine examinations. In healthy participants and epileptic patients, CBD administered daily over 30 days and 135 days respectively was well tolerated. No signs of toxicity or serious side effects were detected in either group when undergoing weekly neurological and physical examinations, blood and urine analysis, and other clinical examinations.

CBD’s safety and effectiveness to relieve symptoms were evaluated in 15 patients with Huntington’s Disease who were neuroleptic-free. Being neuroleptic-free means you do not take meds to depress nerve function in order to reduce nervous tension. The patients were split into two groups. Group one was administered with CBD at 10 mg/kg of body weight per day for 6 weeks. Group two was administered with sesame oil for 6 weeks as a placebo. CBD showed no significant clinical differences in the Cannabis side effect category, clinical lab tests, or safety outcome variables compared to sesame oil.

In a single patient case report, a teenager diagnosed with schizophrenia experienced severe side effects after receiving treatment with conventional antipsychotics. The patient was hospitalized and received 4 weeks of CBD treatment at increasing doses of up to 1,500 mg per day. The patient showed significant symptom improvement with no adverse side effects.

Similarly, 3 patients with treatment-resistant schizophrenia received CBD monotherapy treatment. Monotherapy means only one drug or medication is being used, which in this case was CBD. The patient started treatment at 40 mg per day and increased to about 1,280 mg per day for up to 4 weeks. At that time no side effects were reported. Not even at the high dosage levels.

Two patients with bipolar disorder mirrored the aforementioned results. The bipolar patients were administered CBD dosages ranging between 600 – 1,200 mg per day for up to 24 days. They did not report any adverse side effects.

In a separate double-blind study, 42 patients with schizophrenia demonstrated that CBD administered at 800 mg reduced psychotic symptoms significantly after 2 – 4 weeks of treatment. At that time, fewer side effects were induced compared to amisulpride. Amisulpride is an antiemetic and antipsychotic drug meaning it’s used to help reduce vomiting, delusions, hallucinations, paranoia, and disordered thought. The fewer side effects that were induced included extrapyramidal symptoms, increased prolactin levels, and weight gain.

In a 4-week open clinical trial, the safety and effectiveness of CBD were studied in patients with Parkinson’s disease who also showed psychotic symptoms. A flexible oral dose of CBD was administered ranging from 150 – 400 mg per day in the final week of the trial. The patients showed a reduction in psychotic symptoms, and cognitive and motor symptoms were not affected by CBD. And, no serious side effects were reported during the trial.

Lastly, a 19-year-old female patient with a cannabis addiction received CBD as a treatment to eliminate her addiction. The patient received 300 mg of CBD on day 1, and 600 mg per day split into two doses from day 2 to day 10. On day 11, the patient received only 300 mg of CBD. During the treatment, the patient did not report any marijuana withdrawal symptoms. The patient did not experience any anxiety symptoms, dissociative symptoms, or improved sleep quality.

There’s more information the study goes into regarding the effects of CBD on certain bodily functions as well as animal study results. However, those details are not the focus of today’s article. Our focus is to highlight the safety and side effect profile of CBD in humans. In 2001, the researchers concluded that CBD is well tolerated and safe in humans at high doses as well as with chronic use.

However, their data also showed potential drug metabolic interactions, cytotoxicity, and decreased receptor activity. Cytotoxicity is the quality of a substance being toxic to body cells such as immune cells or snake venom. This then highlights the need to carefully monitor CBD use in clinical practices. Specifically in cases such as psychiatric disorders or drug abuse treatment for example.

2017 Review Summary: Update On The Safety And Side Effects Of CBD On Humans

In 2017, researchers set out to update the findings discovered in the 2011 CBD safety study. This time around, the focus was on clinical studies that documented CBD’s interactions with other drugs. The majority of the studies reviewed were performed based on patients with epilepsy and psychotic disorders. According to the researchers, CBD has a better side effect profile compared to the current drugs used to treat these medical conditions. This may improve patient compliance and adherence to medical treatment.

In their update, the researchers found that CBD was used mostly as an adjunct therapy. This means CBD was used as an add-on treatment to the primary treatment the patient was already on. The most commonly reported side effects as a result of adding CBD to the current treatment were tiredness, diarrhea, and appetite/weight changes. The researchers stated that more clinical research is warranted on CBD action on liver enzymes, drug transporters, and interactions with other drugs to see if they lead to mainly negative or positive effects.

Detailed Summary Of Findings: 2017 CBD Safety And Side Effect Update Review

In a double-blind, placebo-controlled crossover study, 17 patients were co-administered CBD with fentanyl via an IV. Blood samples were obtained before and after the 400 mg or 800 mg CBD pre-treatment followed by 0.5 or 1.0 μg/kg of fentanyl IV dose. Multiple vital signs were measured during the course of the treatment such as blood pressure, respiratory heart rate, oxygen saturation, EKG, and respiratory function. The researchers found that CBD did not worsen the adverse effects of fentanyl. Co-administration was safe and well tolerated by the patients. This result paves the way for CBD to be utilized as a treatment for opioid addiction.

In a well-known fear-conditioning anxiety study, 48 participants received 32 mg of CBD. This amount of CBD is below levels known to provide anti-anxiety effects. CBD was administered either before or after the extinction event of the fear-conditioning experiment. Multiple means were utilized to measure the participant’s levels of anxiety such as the Mood Rating Scale, and the Bond & Bodily Symptoms Scale. The study found that CBD enhanced the participant’s ability to overcome the stressful memory the fear-conditioning study was created for them. CBD also showed a trend toward protecting against reinstating the stressful memory the fear-conditioning study created. And, on top of that, no side effects were reported during the study.

In a small double-blind pilot study, individuals addicted to opioids either received CBD at 400 or 800 mg orally or a placebo. The administration occurred over 3 consecutive days. Opioid craving was induced via specific cues 1-hour after CBD administration. The researchers found that subjective opioid craving was reduced after a single administration of CBD. This effect lasted for 7-days after the last CBD administration, which was the length of the study. Another effect that was reported was that participants’ anxiety levels were reduced after treatment with CBD. However, no adverse side effects were reported in the study.

In an 8-week clinical study, 13 minors with epilepsy were being treated with clobazam and CBD. According to the study, clobazam’s initial average dose was 1 mg/kg of body weight, and CBD’s starting dose was 5 mg/kg of body weight. However, CBD’s dosage was raised to a maximum of 25 mg/kg of body weight. The study found that CBD’s interaction with liver enzymes (CYP3A4 and CYP2C19) caused clobazam to be more bioavailable in the body. This suggests that you can reduce the dosage of clobazam when combined with CBD, which would reduce its side effects. Clobazam’s side effects include:

• Tiredness
• Coordination problems
• Difficulty speaking/swallowing
• Drooling
• Change in appetite
• Vomiting
• Constipation
• Coughing
• Joint pain

On the 15th of September 2015, GW Pharmaceuticals published a press release that described the results of 88 patients with treatment-resistant schizophrenic psychosis. The patients were treated with either CBD or a placebo in addition to their regular meds. The study found that vital clinical parameters improved in the group administered with CBD and the number of mild side effects was comparable to the placebo group. Meaning, the patients administered CBD experienced a positive effect regarding their symptoms and an absence of side effects.

In a separate study, 23 patients with therapy-resistant epilepsy with CBD in addition to their regular epilepsy meds. CBD dosage was raised up to 25 mg/kg of body weight over a 3-month period. The study found that CBD reduced seizure frequency in 39% of the patients and its side effect report was mild to moderate. Side effects reported in this study include appetite changes, weight changes, and tiredness.

A clinical study presented to the American Academy of Neurology in 2015 saw 137 minors and young adults suffering from various and rare forms of epilepsy. The study lasted 3-months and the patients were treated with a CBD drug called Epidiolex. Nearly 50% of the patients experienced a reduction in seizure frequency during the course of the study. The side effects reported from Epidiolex treatment include:

• Tiredness (21%)
• Diarrhea (17%)
• Appetite reduction (16%)

In a few cases, severe side effects were reported. However, the researchers are not clear as to whether they were caused by Epidiolex treatment.

In a clinical study examining 21 patients with Parkinson’s disease, CBD in two groups or placebo was administered. Patients who were administered CBD received either 75 mg per day or 300 mg per day over a period of 60 weeks. The study found that the high-dose CBD group showed a significant improvement in their quality of life-based on PDQ-39 measurement results. PDQ-39 (Parkinson’s Disease Questionnaire) measures the following factors:

• Mobility
• Activities of daily living
• Emotional well-being
• Stigma
• Social support
• Cognition
• Communication
• Bodily discomfort

Side effects from the study were measured with UKU (Udvalg for Kliniske Undersøgelser). This analyzes adverse side effects such as psychic, neurologic, autonomic, and other manifestations. Utilizing the UKU and verbal reports, no significant side effects were recognized in either of the CBD groups.

In a group of 48 cancer patients receiving a stem cell transplant, 300 mg/kg of CBD was administered orally 7-days before and 30-days after the transplant. The stem cell transplant came from an unrelated donor to treat leukemia or myelodysplastic syndrome. This was in combination with measures to avoid GVHD (Graft vs Host Disease). GVHD occurrence was compared with historical data from 108 patients who only received the standard treatment. Patients treated with CBD did not develop short-term GVHD and 16 months after transplantation GVHD incidence was significantly reduced. And, using the CTCAE v.4.0 (Common Terminology Criteria for Adverse Events), no severe adverse side effects were detected.

In Closing…

To quote the meta-analysis conducted in 2020, CBD is safe and well tolerated by humans. It has next to no adverse side effects based on the available data from clinical trials. However, in saying that, interactions with other medications should be closely monitored.

Various areas of CBD research need to be extended. For example, more studies looking into the CBD side effects after chronic (long-term) administration is required. Or research evaluating CBD’s effect on hormones needs to be conducted as they’re scarce. Yet, despite the knowledge gap, CBD’s safety profile has been established as being non-harmful for human consumption. And, this is irrespective of the condition you may be treating for.

If you ever had any doubt regarding CBD’s safety and side effect profile, you now have clinical data to give your peace of mind. It goes without saying that CBD is safe. You only need to be mindful if you’re taking it with other medication. This an act HempNerd does not recommend unless you consult with a pro-cannabis doctor or nurse.

Citations

• Bergamaschi MM, Queiroz RH, Zuardi AW, Crippa JA. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011 Sep 1;6(4):237-49. doi: 10.2174/157488611798280924. PMID: 22129319.
• 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, DOI: 10.1089/can.2016.0034.
• Chesney, E., Oliver, D., Green, A. et al. Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Neuropsychopharmacol. 45, 1799–1806 (2020). https://doi.org/10.1038/s41386-020-0667-2