What Is CBD Oil?
This cannabis extract may help treat nerve pain, anxiety, and epilepsy
Cathy Wong is a nutritionist and wellness expert. Her work is regularly featured in media such as First For Women, Woman’s World, and Natural Health.
Verywell Health articles are reviewed by board-certified physicians and healthcare professionals. These medical reviewers confirm the content is thorough and accurate, reflecting the latest evidence-based research. Content is reviewed before publication and upon substantial updates. Learn more.
Meredith Bull, ND, is a licensed naturopathic doctor with a private practice in Los Angeles. She helped co-author the first integrative geriatrics textbook, “Integrative Geriatric Medicine.”
Cannabidiol (CBD) oil is an extract from hemp plants called Cannabis indica and Cannabis sativa . You might be more familiar with cannabis plants because they are grown for marijuana. However, CBD is not the same thing as marijuana.
CBD oil contains CBD that’s mixed with a base (carrier) oil, like coconut oil or hemp seed oil. These are called tinctures. You can get tinctures in different concentrations. The oil can also be put into capsules, gummies, and sprays.
People who support using CBD oil say that it can treat pain and anxiety; can help stimulate appetite and may help manage some types of seizures.
This article goes over what CBD is used for, the possible side effects, and what you should look for if you choose to buy CBD.
CBD vs. Marijuana
CBD is one component (called a cannabinoid ) that’s found in a hemp plant. Marijuana is a separate plant but it’s from the same species that hemp belongs to. Marijuana has CBD and hundreds of other compounds in it.
The main difference between hemp plants and marijuana plants is how much of a compound called tetrahydrocannabinol (THC) is in them. Hemp is grown to have less than 0.3% THC, while marijuana has more.
THC is what’s responsible for the psychoactive effects of cannabis—in other words, it’s what makes you feel “high.”
CBD oil generally does not have THC in it; however, a very small (trace) amount might be in products sold in certain states.
What Is CBD Oil Used For?
We’re not sure exactly how CBD works. Unlike THC, CBD doesn’t have a strong connection with the molecules in the brain that THC binds to create psychoactive effects. These are called cannabinoid receptors.
Instead, CBD works on other receptors, like the opioid receptors that help control pain. It also affects glycine receptors that control a brain chemical called serotonin which helps control your mood.
People that support the use of CBD claim that CBD oil can treat a variety of health problems, including:
- Chronic pain
- Drug use and withdrawal
- High blood pressure
- Muscle spasms
- Poor appetite
As CBD has gained popularity, researchers have been trying to study it more. Still, there has not been a lot of clinical research to look for evidence in support of these health claims.
CBD is not a safe option for everyone. Talk to your healthcare provider if you want to try it for managing a health condition.
A 2015 review of research that was published in the journal Neurotherapeutics suggested that CBD might help treat anxiety disorders.
The study authors reported that CBD had previously shown powerful anxiety-relieving effects in animal research—and the results were kind of surprising.
In most of the studies, lower doses of CBD (10 milligrams per kilogram, mg/kg, or less) improved some symptoms of anxiety, while higher doses (100 mg/kg or more) had almost no effect.
The way that CBD acts in the brain could explain why this happens. In low doses, CBD might act the same as the surrounding molecules that normally bind to the receptor that “turns up” their signaling.
However, at higher doses, too much activity at this receptor site could produce the opposite effect.
There have not been many trials to look at CBD’s anxiety-relieving effects in humans. However, one was a 2019 study published in the Brazilian Journal of Psychiatry.
For the study, 57 men took either CBD oil or a sugar pill with no CBD in it (placebo) before a public-speaking event.
The researchers assessed the participants’ anxiety levels using measures like blood pressure and heart rate. The researchers also used a reliable test for mood states called the Visual Analog Mood Scale (VAMS).
The men who took 300 mg of CBD oil reported less anxiety than the men who were given a placebo; however, the men who took 100 mg or 600 mg of CBD oil did not experience the same effects.
CBD oil might help people with substance use disorder, according to a 2015 review published in the journal Substance Abuse.
The review looked at the findings from 14 published studies. Nine of the studies looked at the effects of CBD on animals, and five studies looked at the effects on humans.
The researchers reported that CBD showed promise for treating people with opioid, cocaine, or psychostimulant use disorders.
However, the effects of CBD were quite different depending on the substance. For example, CBD without THC did not decrease withdrawal symptoms related to opioid use.
On the other hand, it did reduce drug-seeking behaviors in people using cocaine, methamphetamine, and other similar drugs.
Some experts suggest that CBD could help treat cannabis and nicotine dependence, but more research is needed to provide this theory.
High Blood Pressure
A 2017 study found that CBD oil may reduce the risk of heart disease because it can lower high blood pressure in some people.
For the study, nine healthy men took either 600 mg of CBD or the same dose of a placebo. The men who took CBD had lower blood pressure before and after experiencing stressors like exercise or extreme cold.
The study also looked at the amount of blood remaining in the heart after a heartbeat (stroke volume).
The stroke volume in the men who took CBD was lower than in was in the placebo group, meaning their hearts were pumping more efficiently.
The study suggested that CBD oil could be a complementary therapy for people with high blood pressure that is affected by stress and anxiety.
However, there is no evidence that CBD oil can treat high blood pressure on its own or prevent it in people at risk. While stress can complicate high blood pressure, it does not cause it.
In June 2018, the U.S. Food and Drug Administration (FDA) approved a CBD oral solution called Epidiolex.
Epidiolex is used to treat two rare forms of epilepsy in children under the age of 2: Dravet syndrome and Lennox-Gastaut syndrome. These are very rare genetic disorders that cause lifelong seizures starting in the first year of life.
Other than for these two disorders, CBD’s effectiveness for treating seizures is not known. Even with Epidiolex, it’s not clear if the anti-seizure effects are from CBD or another factor.
However, there is some evidence that CBD interacts with seizure medicines like Onfi (clobazam) and raises their concentration in the blood. That said, more research is needed to understand the link.
Possible Side Effects
Clinical research has shown that CBD oil can cause side effects. The specific side effects a person has and how bad they are varies from one person to the next and from one type of CBD to another.
Some common side effects people report from using CBD include:
- Changes in appetite
- Changes in mood
- Dry mouth
CBD oil may also increase liver enzymes, which is a marker of liver inflammation.
People with liver disease should talk to their healthcare provider before taking CBD oil. They may need to have their liver enzymes checked regularly if they are using CBD.
Can You Use CBD If You’re Pregnant?
You should not use CBD oil if you’re pregnant or breastfeeding. Even though the effects of CBD are not fully understood, it does pass through the placenta.
The American Academy of Pediatrics (AAP) further states that pregnant people should not use marijuana because of the potential risks to a developing fetus.
Do not drive or use heavy machinery when taking CBD oil—especially when you first start using it or switch to a new brand. Remember that some products do contain THC, even in small amounts.
CBD oil can interact with medications, including many that are used to treat epilepsy. One of the reasons for this has to do with how your body breaks down (metabolizes) drugs.
Cytochrome P450 (CYP450) is an enzyme your body uses to break down some drugs. CBD oil can block CYP450. That means that taking CBD oil with these drugs could make them have a stronger effect than you need or make them not work at all.
Drugs that could potentially interact with CBD include:
- Anti-arrhythmia drugs like quinidine
- Anticonvulsants like Tegretol (carbamazepine) and Trileptal (oxcarbazepine)
- Antifungal drugs like Nizoral (ketoconazole) and Vfend (voriconazole)
- Antipsychotic drugs like Orap (pimozide)
- Atypical antidepressants like Remeron (mirtazapine)
- Benzodiazepine sedatives like Klonopin (clonazepam) and Halcion (triazolam)
- Immune-suppressive drugs like Sandimmune (cyclosporine)
- Macrolide antibiotics like clarithromycin and telithromycin
- Migraine medicine like Ergomar (ergotamine)
- Opioid painkillers like Duragesic (fentanyl) and alfentanil
- Rifampin-based drugs used to treat tuberculosis
Always tell your healthcare provider and pharmacist about all the medicines you take, including prescription, over-the-counter (OTC), herbal, or recreational drugs.
The interactions between these medications and CBD are often mild and you might not have to change your treatment.
However, in some cases, you might have to change medications or space out your doses to avoid a reaction. That said, never change or stop medication without talking to your provider.
Dosage and Preparation
There are no guidelines for using CBD oil. Each product works a bit differently, depending on the form.
For example, putting the oil under your tongue can produce effects more quickly than swallowing a capsule that needs to be digested.
Here are a few ways that you can take CBD oil:
- Placing one or more drops under your tongue and holding it there for 30 to 60 seconds without swallowing. You can also use a spray that is spritz in your mouth/under your tongue.
- Taking a capsule or chewing a gummy
There’s no “correct” dose of CBD oil. How much you take and the form you choose will depend on your needs and what you hope to get for effects. The average dose range is from 5 mg to 25 mg.
Most oils come in 30-milliliter (mL) bottles and include a dropper cap to help you measure.
That said, it’s hard to figure out the exact amount of CBD per milliliter of oil. Some tinctures have concentrations of 1,500 mg per 30 mL, while others have 3,000 mg per mL or more.
How to Calculate CBD Dose
To determine an exact dose of CBD, remember that each drop of oil equals 0.05 mL of fluid. This means that a 30-mL bottle of CBD oil will have about 600 drops in it.
If the concentration of the tincture is 1,500 mg per mL, one drop would have 2.5 mg of CBD in it. The math to figure that out looks like this: 1,500 mg ÷ 600 drops = 2.5 mg
What to Look For
CBD oil comes in different forms: isolates, broad-spectrum, and full-spectrum.
- Isolates contain only CBD
- Broad-spectrum oils nearly all of the components of the plan (e.g., proteins, flavonoids, terpenes, and chlorophyll), but does not have THC oils have all the compounds including THC (up to 0.3%)
Alternative medicine practitioners believe that the compounds provide more health benefits, but the is a lack of evidence to support these claims.
Remember that CBD oils are unregulated. There’s no guarantee that a product is what it claims to be on its packaging. You also can’t know for sure that it’s safe and effective.
A 2017 study reported that only 31% of CBD products sold online were correctly labeled. Most had less CBD in them than was advertised, and 21% had significant amounts of THC.
If you are interested in buying CBD products, here are a few tips to keep in mind:
- Buy American: Domestically produced CBD oil might be a safer option than those that have been imported.
- Go organic: Brands certified organic by the U.S. Department of Agriculture (USDA) are less likely to expose you to pesticides and other harmful chemicals.
- Read the product label: Even if you choose a full-spectrum oil, don’t assume that every ingredient on the product label is natural. CBD products can also have preservatives, flavorings, or thinning agents in them. If you don’t recognize an ingredient, ask the dispenser what it is or check online.
Hemp plants can be grown for different purposes. Some species are made for marijuana but others are used to make CBD products.
Unlike marijuana, CBD oil does not “get you high.” Instead, it may help relieve stress, anxiety, drug withdrawals, and nerve pain.
While there are many claims about the health benefits of using CBD oil, the evidence is lacking. A lot of studies were done with animals, not humans.
If you want to try CBD oil, you should learn about the different dosages and preparations first.
You should also know that the products are not regulated, which means you can’t know for sure that a product will work and be safe.
Before you use CBD oil, talk to your provider. If you take certain medications or have a health condition, you may not be able to use these products.
Frequently Asked Questions
It would be hard to overdose on CBD oil. Research has shown that human tolerance for CBD is very high. One study reported the toxic dose would be about 20,000 mg taken at one time.
It depends on where you live, the type of product, how it was sourced (e.g., is it from hemp or marijuana), and its intended purpose (medical or recreational). In many states, you must be 18 or 21 to buy CBD oil. Check your state’s laws.
Not necessarily. While the names are sometimes used interchangeably, hemp oil can also refer to hemp seed oil, which is used for cooking, food production, and skincare products.
CBD oil is made from the leaves, stems, buds, and flowers of the Cannabis indica or Cannabis sativa plant. It should contain less than 0.3% THC.
Hemp oil is made from the seeds of Cannabis sativa and does not have TCH in it.
What You Need to Know (And What We’re Working to Find Out) About Products Containing Cannabis or Cannabis-derived Compounds, Including CBD
The FDA is working to answer questions about the science, safety, and quality of products containing cannabis and cannabis-derived compounds, particularly CBD.
- Cannabis is a plant of the Cannabaceae family and contains more than eighty biologically active chemical compounds. The most commonly known compounds are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the component that produces the “high” associated with marijuana use. Much interest has been seen around CBD and its potential related to health benefits.
- Marijuana is different from CBD. CBD is a single compound in the cannabis plant, and marijuana is a type of cannabis plant or plant material that contains many naturally occurring compounds, including CBD and THC.
- The FDA has approved only one CBD product, a prescription drug product to treat seizures associated with Lennox Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in people one year of age and older.
- It is currently illegal to market CBD by adding it to a food or labeling it as a dietary supplement.
- The FDA has seen only limited data about CBD safety and these data point to real risks that need to be considered before taking CBD for any reason.
- Some CBD products are being marketed with unproven medical claims and are of unknown quality.
- The FDA will continue to update the public as it learns more about CBD.
Potential harm, side effects and unknowns
- CBD has the potential to harm you, and harm can happen even before you become aware of it.
- CBD can cause liver injury.
- CBD can affect how other drugs you are taking work, potentially causing serious side effects.
- Use of CBD with alcohol or other drugs that slow brain activity, such as those used to treat anxiety, panic, stress, or sleep disorders, increases the risk of sedation and drowsiness, which can lead to injuries.
- Male reproductive toxicity, or damage to fertility in males or male offspring of women who have been exposed, has been reported in studies of animals exposed to CBD.
- CBD can cause side effects that you might notice. These side effects should improve when CBD is stopped or when the amount used is reduced.
- Changes in alertness, most commonly experienced as somnolence (drowsiness or sleepiness).
- Gastrointestinal distress, most commonly experienced as diarrhea and/or decreased appetite.
- Changes in mood, most commonly experienced as irritability and agitation.
- There are many important aspects about CBD that we just don’t know, such as:
- What happens if you take CBD daily for sustained periods of time?
- What level of intake triggers the known risks associated with CBD?
- How do different methods of consumption affect intake (e.g., oral consumption, topical , smoking or vaping)?
- What is the effect of CBD on the developing brain (such as on children who take CBD)?
- What are the effects of CBD on the developing fetus or breastfed newborn?
- How does CBD interact with herbs and other plant materials?
- Does CBD cause male reproductive toxicity in humans, as has been reported in studies of animals?
Unanswered questions about the science, safety, and quality
You may have noticed that cannabidiol (CBD) seems to be available almost everywhere, and marketed as a variety of products including drugs, food, dietary supplements, cosmetics, and animal health products. Other than one prescription drug product to treat seizures associated with Lennox Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in people one year of age and older, the U.S. Food and Drug Administration (FDA) has not approved any other CBD products, and there is very limited available information about CBD, including about its effects on the body.
The FDA recognizes the significant public interest in cannabis and cannabis-derived compounds, particularly CBD. However, there are many unanswered questions about the science, safety, and quality of products containing CBD. The agency is working on answering these questions through ongoing efforts including feedback from a recent FDA hearing and information and data gathering through a public docket.
Despite the 2018 Farm Bill removing hemp — defined as cannabis and cannabis derivatives with very low concentrations (no more than 0.3% on a dry weight basis) of THC — from the definition of marijuana in the Controlled Substances Act, CBD products are still subject to the same laws and requirements as FDA-regulated products that contain any other substance.
The FDA is concerned that people may mistakenly believe that using CBD “can’t hurt.” The agency wants to be clear that we have seen only limited data about CBD’s safety and these data point to real risks that need to be considered. As part of the drug review and approval process for the prescription drug containing CBD, it was determined that the risks are outweighed by the benefits of the approved drug for the particular population for which it was intended. Consumer use of any CBD products should always be discussed with a healthcare provider. Consumers should be aware of the potential risks associated with using CBD products. Some of these can occur without your awareness, such as:
- Liver Injury: During its review of the marketing application for Epidiolex — a purified form of CBD that the FDA approved in 2018 for use in the treatment of two rare and severe seizure disorders — the FDA identified certain safety risks, including the potential for liver injury. This serious risk can be managed when an FDA-approved CBD drug product is taken under medical supervision, but it is less clear how it might be managed when CBD is used far more widely, without medical supervision, and not in accordance with FDA-approved labeling. Although this risk was increased when taken with other drugs that impact the liver, signs of liver injury were seen also in patients not on those drugs. The occurrence of this liver injury was identified through blood tests, as is often the case with early problems with the liver. Liver injury was also seen in other studies of CBD in published literature. We are concerned about potential liver injury associated with CBD use that could go undetected if not monitored by a healthcare provider.
- Drug Interactions: Information from studies of the FDA-approved CBD drug Epidiolex show that there is a risk of CBD impacting other medicines you take – or that other medicines you take could impact the dose of CBD that can safely be used. Taking CBD with other medications may increase or decrease the effects of the other medications. This may lead to an increased chance of adverse effects from, or decreased effectiveness of, the other medications. Drug interactions were also seen in other studies of CBD in published literature. We are concerned about the potential safety of taking other medicines with CBD when not being monitored by a healthcare provider. In addition, there is limited research on the interactions between CBD products and herbs or other plant-based products in dietary supplements. Consumers should use caution when combining CBD products with herbs or dietary supplements.
- Male Reproductive Toxicity: Studies in laboratory animals showed male reproductive toxicity, including in the male offspring of CBD-treated pregnant females. The changes seen include decrease in testicular size, inhibition of sperm growth and development, and decreased circulating testosterone, among others. Because these findings were only seen in animals, it is not yet clear what these findings mean for human patients and the impact it could have on men (or the male children of pregnant women) who take CBD. For instance, these findings raise the concern that CBD could negatively affect a man’s fertility. Further testing and evaluation are needed to better understand this potential risk.
In addition, CBD can be the cause of side effects that you might notice. These side effects should improve when CBD is stopped or when the amount used is reduced. This could include changes in alertness, most commonly experienced as somnolence (sleepiness), but this could also include insomnia; gastrointestinal distress, most commonly experienced as diarrhea and/or decreased appetite but could also include abdominal pain or upset stomach; and changes in mood, most commonly experienced as irritability and agitation.
The FDA is actively working to learn more about the safety of CBD and CBD products, including the risks identified above and other topics, such as:
- Cumulative Exposure: The cumulative exposure to CBD if people access it across a broad range of consumer products. For example, what happens if you eat food with CBD in it, use CBD-infused skin cream and take other CBD-based products on the same day? How much CBD is absorbed from your skin cream? What if you use these products daily for a week or a month?
- Special Populations: The effects of CBD on other special populations (e.g., the elderly, children, adolescents, pregnant and lactating women).
- CBD and Animals: The safety of CBD use in pets and other animals, including considerations of species, breed, or class and the safety of the resulting human food products (e.g., meat milk, or eggs) from food-producing species.
Unproven medical claims, unsafe manufacturing practices
Some CBD Products are Being Marketed with Unproven Medical Claims and Could be Produced with Unsafe Manufacturing Practices
Unlike the FDA-approved CBD drug product, unapproved CBD products, which could include cosmetics, foods, products marketed as dietary supplements, and any other product (other than Epidiolex) making therapeutic claims, have not been subject to FDA evaluation regarding whether they are effective to treat a particular disease or have other effects that may be claimed. In addition, they have not been evaluated by the FDA to determine what the proper dosage is, how they could interact with other drugs or foods, or whether they have dangerous side effects or other safety concerns.
Misleading, unproven, or false claims associated with CBD products may lead consumers to put off getting important medical care, such as proper diagnosis, treatment, and supportive care. For that reason, it’s important to talk to your doctor about the best way to treat diseases or conditions with available FDA-approved treatment options.
In addition to safety risks and unproven claims, the quality of many CBD products may also be in question. The FDA is also concerned that a lack of appropriate processing controls and practices can put consumers at additional risks. For example, the agency has tested the chemical content of cannabinoid compounds in some of the products, and many were found to not contain the levels of CBD they claimed. We are also investigating reports of CBD potentially containing unsafe levels of contaminants (e.g., pesticides, heavy metals, THC).
CBD products are also being marketed for pets and other animals. The FDA has not approved CBD for any use in animals and the concerns regarding CBD products with unproven medical claims and of unknown quality equally apply to CBD products marketed for animals. The FDA recommends pet owners talk with their veterinarians about appropriate treatment options for their pets.
The FDA’s top priority is to protect the public health. This priority includes making sure consumers know about products that put their health and safety at greatest risk, such as those claiming to prevent, diagnose, treat, mitigate, or cure serious diseases. For example, the agency has warned companies to stop selling CBD products they claim are intended to prevent, diagnose, treat, mitigate, or cure serious diseases such as cancer, Alzheimer’s disease, psychiatric disorders and diabetes. While we have focused on these types of products, we will continue to monitor the marketplace for any product that poses a risk to public health, including those with dangerous contaminants, those marketed to vulnerable populations, and products that otherwise put the public health at risk.
Evaluation of the regulatory frameworks
The FDA is Continuing to Evaluate the Regulatory Frameworks for Products Containing Cannabis and Cannabis-Derived Compounds
The FDA continues to believe the drug approval process represents the best way to ensure that safe and effective new medicines, including any drugs derived from cannabis, are available to patients in need of appropriate medical therapy. The agency is committed to supporting the development of new drugs, including cannabis and cannabis-derived drugs, through the investigational new drug and drug approval process.
We are aware that there may be some products on the market that add CBD to a food or label CBD as a dietary supplement. Under federal law, it is illegal to market CBD this way.
The FDA is evaluating the regulatory frameworks that apply to certain cannabis-derived products that are intended for non-drug uses, including whether and/or how the FDA might consider updating its regulations, as well as whether potential legislation might be appropriate. The information we have underscores the need for further study and high quality, scientific information about the safety and potential uses of CBD.
The FDA is committed to setting sound, science-based policy. The FDA is raising these safety, marketing, and labeling concerns because we want you to know what we know. We encourage consumers to think carefully before exposing themselves, their family, or their pets, to any product, especially products like CBD, which may have potential risks, be of unknown quality, and have unproven benefits.
Our Consumer Update includes a practical summary of what we know to date. As we learn more, our goal is to update you with the information you need to make informed choices about CBD products. Also, as the regulatory pathways are clarified we will take care to inform all stakeholders as quickly as possible.
What Should We Tell Our Patients About Marijuana (Cannabis indica and Cannabis sativa)?
With several states allowing medicinal use of marijuana and a growing number decriminalizing recreational use, many of our patients are using this herbal drug. Approximately 43% of US adults have tried marijuana, with 13% using it regularly. These users are seeking help from integrative medicine practitioners regarding safety. They are looking for advice based on research and clinical experience, not politics or philosophical bias. The major health problems caused by marijuana appear to be bronchial irritation, decreased motivation, learning difficulties, and injuries. However, less well appreciated are the toxicity problems caused by contamination with pesticides and solvent residues. We have important guidance to help prevent unnecessary toxicity in our patients who choose to use marijuana. This editorial reviews toxicity and safety. Medicinal use will be addressed in the future.
Long-time readers of IMCJ are well aware of the many editorials I have written on how a growing body of research is showing that toxins have become a major cause of chronic disease. As I study toxicity, my understanding has broadened to include not only environmental metals and chemicals but also endogenously produced toxins such as those from homocysteine, gut bacteria and nonoptimally detoxified hormones. To this list I now add what I call “toxins of choice.” Few of our patients are intentionally exposing themselves to neurotoxic organophosphate pesticides, endocrine disrupting polychlorinated biphenyls (PCBs), insulin receptor site-blocking phthalates, or lung-damaging mold from damp buildings. However, many of our patients are intentionally consuming known toxins such as alcohol and marijuana and are unlikely to realize that at modest dosages, salt, high-fructose corn syrup, phosphates, and nonsteroidal anti-inflammatory drugs (NSAIDs) are toxic as well. Added to this that by also considering genetic susceptibility, even sources of gluten, can be toxic. The huge load of environmental, endogenous, and choice toxins add up to deplete stores of protective glutathione and cause physiological and structural damage in many ways.
Table 1 shows my current list of the many toxins that stress physiology and cause disease in our patients. Where I have written an editorial on the topic, the issue is included in parentheses.
The Many Sources of Toxins
|Exogenous Toxins||Endogenous||Toxins of Choice|
|OTC and prescription drugs (see editorial in IMCJ 7(3))||Catecholamines, if COMT SNP||Alcohol (see editorial in IMCJ 11.(6))|
|Chemicals||Gut-derived toxins||Marijuana (see editorial in IMCJ 15(6))|
|Inorganic||Homocysteine (see editorial in IMCJ 6(4))||Food constituents|
|Organic||Non-end product metabolites||High-fructose corn syrup|
|Fluoride||Poorly detoxified hormones||Phosphates|
|Persistent organic pollutants (see editorial in IMCJ 12(2))||Salt (see editorial in IMCJ 14(1))|
|Metals||Wheat, if zonulin producer (see editorial in IMCJ 12(6))|
|Mercury (see editorial in IMCJ 8(1), 8(2), 9(4))|
|Mold (damp building, 15.2, 15.3)|
|Light at night|
Although the federal government has classified Cannabis as a controlled substance illegal for use, many states have now decriminalized its use. Twenty-four states and the District of Columbia have passed laws allowing medicinal use of marijuana and 14 states have decriminalized its use. The percentage of Americans who say they have tried marijuana has steadily increased from 4% in 1969 to 43% in 2016.1
Cannabis production has become a multibillion dollar industry in the United States, and legal markets for cannabis are projected to reach $11 billion by 2019.2 The federal illegality of Cannabis has resulted in not only limited clinical research but also a production environment with few standards and very little regulation. As most is currently grown indoors, heavy use of agricultural chemicals is common. Toxicity may be due to not only constituents of marijuana itself, but also contaminants such as solvents, pesticides, and heavy metals with most extracts adding solvent residues. This likely helps explain some of the discrepancies in the research.
Almost 500 compounds have been extracted from Cannabis, of which 65 are classified as cannabinoids. The most abundant cannabinoids include delta-9-tetrahydrocannabinoic acid (THCA), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and their decarboxylated derivatives delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol (CBG).3 These compounds are converted into their more active decarboxylated counterparts by heat (smoking, evaporation, baking), light, or natural degradation. THC is the most psychoactive component of cannabis and alters cognition primarily through the activation of CB1 receptors on presynaptic axons, though several other mechanisms have been identified.4,5 The content of THC in marijuana has increased from 3.1% in 1992 to 5.1% in 2002.6,7
THC itself has low toxicity and modest use has shown minimal long-term physical or psychological effects—when not used to excess.8,9 Acute high dose intoxication occurs quickly but is short term. Typical symptoms include nausea, anxiety, paranoia, short-term memory loss, confusion, and disorientation.10 THC impairs gonadal function by blocking gonadotropin-releasing hormone (GnRH) release. This results in lower levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which causes reduced testosterone production by the testicular Leydig cells.11
The research on the toxicity of whole plant marijuana is inconsistent—probably due to lack of control for contaminants, poor assessment of dosage, small sample sizes, limited number of heavy users, mode of use, and not adjusting for other factors such as alcohol, tobacco, and other recreational drugs.12
The method of use significantly affects the toxicity of marijuana. The most common use is inhalation of the smoke of the dried plant. This results in higher risk for adverse effects.13 The whole-plant smoke contains many hazardous compounds such as ammonia, cyanide, heavy metals, carbon monoxide, mutagens, carcinogens, and polycyclic aromatic hydrocarbons.14 Surprisingly, the tar from a Cannabis cigarette contains higher concentrations of carcinogens such as benzanthracenes and benzopyrenes than does tobacco smoke.15
For most of the 20th century, the majority of marijuana produced in the United Sates was grown outdoors. With more aggressive law enforcement, marijuana agriculture moved indoors. Although this provided the benefit of year-round cultivation, it also required the use of agricultural chemicals, typically synthetic fertilizers and pesticides.
Because Cannabis cultivation is illegal, there are no pesticides registered for use on Cannabis in the United States, meaning there is little research on their use for this purpose.16 The limited research suggests that this results in higher chemical residue levels.17 There are apparently no direct studies on how pesticides in Cannabis affects consumers of the product. Table 2 shows a list of the toxic contaminants that have been found in in both medical and recreational marijuana. Research has shown that Cannabis extracts (see Solvents section below) contain considerable amounts of pesticides.18
Toxic Agricultural Chemicals Found in Cultivated Marijuana19,20,21,22
|Pesticides||Bifenthrin, chlorpyrifos, diazinon, methamidophos, teflubenzuron|
|Mosquito repellant||DEET, Malathion|
Abbreviation: DEET, N, N-diethyl-meta-toluamide.
Many methods are used to concentrate the active constituents in Cannabis. The organic solvents benzene, hexane, naphtha, petroleum ether, and butane pose a significant risk of toxic chemical concentration.23 Hexane and benzene are neurotoxic, and naptha and petroleum ether are potential carcinogens. Research has shown significant residues in these products.24 A process called dabbing uses butane to produce higher THC content.25
Safer alternative methods of concentration use ethanol and olive oil. Perhaps best is the use of supercritical CO2 to extract volatile oils from Cannabis as this leaves no residue. Although there is limited research on the efficacy of these methods, nontoxic solvents are clearly preferable.
Cannabis has been shown to be especially effective in absorbing metals such as cadmium and copper from contaminated soils.26 Making matters worse, Cannabis is also intentionally contaminated with metals to increase the market weight. In 2008, 150 people in Germany developed lead poisoning as the result of using adulterated cannabis.27
Indoor growth results in increased susceptibility of Cannabis to contamination by microbes such as fungi, bacteria, and plant viruses. Growing and drying also increase the risk of microbial contamination.28 Penicillium species are the predominant microbe contamination in marijuana grown indoor.29 Cannabis has even been shown to be contaminated with human pathogens such as hepatitis A,30 hepatitis B,31 and salmonella.32 Chronic pulmonary aspergillosis has been found in immunocompromised individuals using medicinal marijuana.33
There is limited research on synthetic cannabinoids (SCBs) such as “Spice,” “K2,” “herbal incense,” and others. Toxicity reports include tachycardia, hypertension, tachypnea, chest pain, heart palpitations, hallucinations, racing thoughts, and seizures.34 The most common clinical signs of toxicity are neurologic including agitation, central nervous system depression/coma, and delirium/toxic psychosis.35 There have been reports of acute renal failure associated with the use of these synthetic analogues.36 These compounds appear significantly more toxic than cannabis and should be avoided.37
The liver metabolizes THC through hydroxylation and oxidation reactions catalyzed by cytochrome P450 enzymes, especially CYP2C9 and CYP3A4.38,39,40 Approximately 65% is excreted in the feces and 20% in urine.41 THC is excreted in the urine primarily as the glucuronic acid conjugate THCCOOH, which has a half-life between 30 and 44 hours.42
Clinical Indications of Toxicity
Long-term smoking of marijuana leaf has been shown to cause airway obstruction43; squamous metaplasia44; impaired psychomotor performance; increased incidence of schizophrenia45; cancer of the mouth, jaw, tongue, and lung; and leukemia in children of marijuana smoking mothers.46 Although marijuana smoke has been shown to contain carcinogenic compounds, research is unclear about whether a link with lung cancer exists.47
Population studies in adults show that heavy cannabis use increases the risk of accidents, can produce dependence and has been associated with poor social outcomes and mental health.48 Long-term daily use has been associated with decreased motivation, impaired ability to learn, and reduced sexual desire.49,50 Daily heavy inhalation can produce bronchial irritation and may lead to long-term pulmonary damage secondary to the associated hydrocarbon residues.51
As noted previously, marijuana can be considered a “toxin of choice.” This means dosage and toxicity are under the control of the user. Abstinence is, of course, the most effective way to decrease cannabis toxicity. However, for most patients, management to prevent excessive use and education to choose the least toxic forms is more likely. Research has shown little benefit treating cannabis dependence with prescription drugs such as selective serotonin reuptake inhibitor (SSRI) antidepressants, mixed-action antidepressants, atypical antidepressants (bupropion), anxiolytics (buspirone), and norepinephrine reuptake inhibitors.52
N-acetyl-cysteine (NAC) at 1200 mg BID has shown benefits because its induction of glutathione synthesis helps mitigate many of the toxic effects and improve the odds of abstinence.53,54
Vaporization (“vaping”) of extracts appears the preferred method of use as it reduces respiratory exposure to toxic particulates and carcinogens.55 For those smoking the dried plant (buds, leaf, flowers, etc), the type of filtration significant affects toxic chemical residue. Hand-held glass pipes allow the most toxins, unfiltered water pipes are intermediate, and the lowest quantity is found with filtered water pipes.56 Heating may make many of contaminants more toxic.57
Many of our patients are using, and in some cases abusing, Cannabis. Our key clinical responsibility is to help those who choose to use marijuana—for whatever reason—to do so responsibly and as safely as possible. The most common ways of obtaining and using marijuana clearly result in clinical toxicity. Interestingly, most of this toxicity appears to be determined by contaminants and the consumption method.
We need to advise our patients to carefully avoid marijuana which is contaminated with agricultural chemicals, metals, microbes, solvents, etc. In addition, damage can be decreased by recommending the least toxic ways of consuming marijuana. Because the primary psychoactive constituent of marijuana, THC, appears to have little toxicity (though it likely plays a major role in the psychological issues), our guidance should focus on ways to limit exposure to everything else. This suggests recommending organically grown product, CO2 extraction, and vaporization rather than smoking agricultural chemical-laced dried plant.
In This Issue
Associate Editor Jeffrey Bland, p h d , continues his thoughtful commentaries on how personalization is critical to solving the health care system crisis. I especially like this comment: “We cannot solve the kidney disease problem through the building of more dialysis centers or by providing a greater number of kidney transplants.”
Regular columnist John Weeks reminds us of the huge problem of science and policy distortion by the integrative medicine antagonists. Fortunately, there is good news with natural childbirth and home births receiving more recognition. Very sad about the passing of my friend Robert Duggan, ma . We worked together when Hillary Clinton invited us to make recommendations for how to integrate natural medicine into the health care system. He was a visionary who will be sorely missed.
We present the second of the multipart series on probiotics written by master of science nutrition graduates of Elizabeth A. Lipski, p h d : Keren E. Dolan, ms ; Heather J. Finley, ms , rd ; Cathleen M. Burns, ms , rd ; Margaret G. Gasta, ms , rdn ; Crystal M. Gossard, ms ; Emily C. Parker, ms , rd ; Jessica M. Pizano, ms ; and Christy B. Williamson, ms . This part focuses on traditional and modern fermented foods—quite a fascinating read and important for providing our patients food choices for probiotics.
Managing editor, Craig Gustafson, interviewed for this issue Ellen Kamhi, p h d , rn . I think her thoughts on how the gut affects the hypothalamic-pituitary-adrenal (HPA) axis are quite intriguing. Especially interesting is her novel use of several botanical medicines to help normalize HPA function. Also, a very thoughtful discussion on stress and sleep. Well worth the read. Wish we had a flow chart to track all the interactions she covered.
I am very excited that Associate editor, David Riley, md , continues to recruit helpful case reports. Patrick Veerkamp; Nico Mousdicas, md ; and Robert Bednarek, md , provide us an effective integrative medicine approach to rosacea fulminans. The color pictures are quite convincing.
We do not publish much about integrative medicine education as IMCJ focuses on clinical application. Nonetheless, sometimes a submission will catch my attention. In this case, I thought it was useful assessing what works when trying to teach a new class of interventions. Rebecca Boesl, aprn , and Heidi Saarinen, aprn , provide original research on the challenges and successes teaching health care professionals about essential oils.
Associate editor, Bill Benda, md ’s “Rider on the Storm” reminds us of how extremism and fear mongering are so damaging—on both sides of whatever aisle people are congregating.
Joseph Pizzorno, nd , Editor in Chief
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