CBD: Things to Consider

Learn about the potential concerns relating to CBD, how you can help mitigate them, and whether or not this fascinating cannaboid is right for you.

| August 2019

cbd-cautions
Getty Images / Syahrir Maulana

MEDICAL DISCLAIMER: The following information is intended for general information purposes only. Individuals should always see their health care provider before administering any suggestions made in this book. Any application of the material set forth in the following pages is at the reader’s discretion and is his or her sole responsibility

CBD has very few known adverse side effects at any dose. THC in high doses can make a person feel very weird for a while, but there are no known fatalities from overdosing on cannabis, as there are for many pharmaceutical drugs.

Many studies prove the effectiveness of CBD treatment of various conditions, and most conclude that it is safe and virtually free of side effects. A 2011 review paper concluded that, although further testing is needed, controlled cannabidiol administration appears to be relatively safe and nontoxic in humans and animals, without affecting food intake or physiological parameters like heart rate, body temperature, or blood pressure. According to the research review, high doses of up to 1,500 mg/day of CBD seem to be well tolerated in humans.



Cannabis products containing THC, the compound responsible for the “high” associated with cannabis, have more contraindications and cautions associated with them. We will cover these below as well, since most products contain at least a small amount of THC, and some have higher ratios. It’s important to note that, while most people do not experience the side effects

CBD associated with THC when taking CBD-dominant products (defined in this book as 20:1 ratio or higher), some patients may be sensitive to small amounts. For this reason, it is recommended to always start with a micro dose and go up from there until symptoms subside.

Keep in mind that all cannabinoids are nontoxic, non-lethal medicine. Researchers have failed to find a lethal acute dosage of cannabis and have found that the doses of long-term cannabis required to produce toxicity and death in animals were so high it would be nearly impossible for a human to consume such quantities via ingestion or inhalation.

Cautions and Side Effects

CBD and other plant cannabinoids can potentially interact with many pharmaceuticals, decreasing their effectiveness by inhibiting the activity of cytochrome P450, a family of liver enzymes. This key enzyme group metabolizes many commonly prescribed medications.

Most medications list a range of potential adverse side effects, and some of those lists are quite horrifying. The most commonly reported side effects of cannabis (mostly associated with high amounts of THC) are dizziness, dry mouth, nausea, fatigue, sleepiness, euphoria, depression, vomiting, diarrhea, disorientation, anxiety, confusion, impaired balance, impaired short-term memory, hallucination, and paranoia. Most people report that cannabis temporarily lowers body temperature slightly, though some report the contrary effect—we discuss more on this bidirectional quality of cannabinoids later in this section.

Cannabis strains that are high in THC can temporarily raise the heart rate for fifteen to twenty minutes. This condition, called tachycardia, subsides on its own, and does so faster when the patient stays calm. Indica strains appear to cause less tachycardia effects than sativa strains. CBD does not have this effect, and there is evidence that CBD is of benefit to patients with certain heart conditions. It is currently being studied for use in treating atherosclerosis, clogging of the arteries, which leads to cardiovascular disease.

Driving while using high-THC cannabis has been shown to significantly increase the risk of accidents, especially in new users. While CBD is not usually associated with these risks, it is advisable to avoid driving or using heavy machinery when starting the medication or adjusting the dose. Use caution when taking any cannabis medicine until you have sufficient experience with the medication that you feel comfortable engaging in activities.

Drinking alcohol while using cannabis-based products is not recommended. The combination of alcohol and cannabinoids can cause dizziness, drowsiness, and impaired judgment. In addition, cannabis products can increase the side effects of other drowsiness-causing drugs, including antidepressants, antihistamines, sedatives, pain relievers, anxiety medicines, seizure medicines, and muscle relaxants.

Some research shows that heavy chronic use of high-THC products can cause a short-term decrease in concentration levels, memory, and certain types of thinking and decision making. Most results showed that these effects are no longer significant after a few weeks of cessation, though some research demonstrated a long-term impact with adolescent onset of heavy use (see more on adolescent use later in this section).

Bidirectional Effect

Many of the adverse effects reported are curiously the same as the symptoms that can be relieved by cannabis. This interesting phenomenon, known as the bidirectional effect, is related to the function of the endocannabinoid system. Because its role is connected to the maintenance of homeostasis, or cellular balance, it has the capacity to influence physiology in opposite directions depending on dose, individual body chemistry, and other factors. For example, a small minority of individuals tends to report the opposite of the majority in terms of the effect of a particular cannabinoid on appetite, mood, body temperature, or sleep.



“By over stimulating the ECS [endocannabinoid system], patients can accidentally trigger or worsen the same symptoms cannabis would otherwise relieve when used correctly,” reports Dustin Sulak, a licensed osteopathic physician with experience in cannabinoid medicine.

For this reason, it is essential that you follow dosage recommendations from your physician, combined with suggestions in this book, and start any new cannabinoid-based product at micro dose levels to test for sensitivity.

Potential Risks

When heavily and chronically smoked or vaporized, cannabis may cause irritation to the lungs and an increased risk of developing chronic bronchitis.

Cannabis smoke has not been definitively linked to cancer in humans, including those cancers associated with tobacco use. While it contains many of the same carcinogens as tobacco smoke, including greater concentrations of certain aromatic hydrocarbons such as benzopyrene, it is also high in cannabinoids that demonstrate anti-cancer properties. By contrast, nicotine promotes the development of cancer cells and their blood supply.

In addition, cannabinoids stimulate other biological activities and responses that may mitigate the carcinogenic effects of smoke, such as down-regulating the inflammatory arm of the immune system that is responsible for producing potentially carcinogenic free radicals.

Cannabis vaporization limits respiratory toxins by heating cannabis to a temperature where cannabinoid vapors form but below the point of combustion where noxious smoke and associated toxins occur. See more on p. 49 regarding vaporization and choosing the safest products.

Dependence/addiction: Cannabis use does not carry the risk of physical addiction as most narcotics do. However, it has been shown that cannabis with high levels of THC has the potential for emotional or mental dependence. It is likely (though not proven by research) that appropriate medical use within recommended dosage guidelines does not carry the risk of dependence.

High-THC products can cause withdrawal symptoms when abruptly stopped, including irritability, aggression, decreased appetite, anxiety, restlessness, and sleep difficulties. These symptoms emerge a few days after cannabis cessation and resolve in one to two weeks. Patients have compared the severity of cannabis withdrawal to caffeine withdrawal. CBD has not been associated with these risks according to the most recent research available at press time. In fact, CBD has been shown to be effective in treating nicotine, alcohol, and other drug addictions. Opponents of cannabis use the old propaganda claim that it is a “gateway drug” leading to addiction to harder drugs like methamphetamine and heroin. From our research and experience, CBD can function as a gateway out of addiction, not into it.

Contraindications

While CBD products may have therapeutic value for the conditions described in this section, before using products containing more than a minimum amount of THC (approximately 5 mg), consult a physician if you have been diagnosed with or are at high risk of developing any of the following disorders:

  • Schizophrenia, bipolar disorder, severe depression
  • Heart disease, high blood pressure, angina, or arrhythmia
  • Immune or autoimmune disorder
  • Pregnancy and Breastfeeding
  • Youth and Adolescence

Caution is advised when using products containing THC to treat children, adolescents, and young adults. The effect of THC on the developing brain is different from its effect on the adult brain, and, though there are clearly cases where its use is medically necessary and justified, monitoring dose is essential, and a physician should be consulted before use. Products containing alternative cannabinoids to THC, such as CBD and THCA, are recommended for people under the age of twenty-two (see specific health entries in Chapter 4 for details on treating young people with CBD-dominant products).

Adolescents who use THC are at higher risk for dependence than older users, and a number of studies have looked for correlations between use of high-THC marijuana and reduced academic performance or IQ scores. Some studies have found these links, especially with “heavy use” defined as five or more joints a week, though the effect on global intelligence was not measurable in the long term. Two studies have cited decreased intellectual functioning and loss of brain volume in specific regions of the brain with daily cannabis use in adolescents and adults. Despite being criticized for ignoring socioeconomic status and ongoing alcohol use and abuse, these studies have been cited in legislation in states that restrict medical cannabis use.

In a more recent study done at the University of Colorado in 2015, researchers matched both adult and adolescent daily cannabis users and non-users and screened for alcohol and tobacco use, depression, anxiety, impulsivity, sensation seeking, and education. They compared sophisticated brain imaging showing the brain volumes in areas cited as shrinking in the previous studies and found no difference in the structure, volume, or shape of any of the targeted regions or any other regions of the brain. A 2016 study involving more than 2,200 students concluded that, when factors such as tobacco use are controlled, modest cannabis use in teenagers may have less cognitive impact than epidemiological surveys of previous cohorts have suggested.

Other research has linked heavy use of high-THC cannabis in adolescents to a higher chance of developing schizophrenia.165 The author of a 2016 study wrote: “Adolescence is a critical period of brain development, and the adolescent brain is particularly vulnerable. Health policy makers need to ensure that marijuana, especially marijuana strains with high THC levels, stays out of the hands of teenagers. In contrast, our findings suggest that adult use of marijuana does not pose substantial risk.”

Overdosing on THC?

The most common type of accidental cannabis overdose is related to consuming cannabis edibles. It is reassuring to know that even incredibly high doses of cannabis do not produce brain damage, organ damage, or other types of physical toxicity, although they can cause delirium and hallucinations. These effects will pass, normally within three to eight hours. Use of a cytochrome P450 deactivator, such as CBD, or grapefruit, can reduce unwanted effects of a THC overdose. To ease your mind, in five thousand years of recorded history, there are no records of anyone dying from an overdose of cannabis or THC.

Drug Interactions

CBD, when ingested orally at sufficient doses, temporarily alters the activity of cytochrome P450, a family of liver enzymes. This potentially affects the body’s metabolism of a wide range of compounds—even to 60 percent of commonly prescribed pharmaceuticals. The issue is that CBD is metabolized by cytochrome P450 enzymes, occupying the site of enzymatic activity and preventing it from metabolizing other compounds. Interestingly, components of grapefruit can have the same effect, leading some physicians to advise against consuming it when taking certain drugs.

“The extent to which cannabidiol behaves as a competitive inhibitor of cytochrome P450 depends on how tightly CBD binds to the active site of the metabolic enzyme before and after oxidation,” writes Adrian Devitt-Lee, a researcher at Project CBD who has studied the topic of drug interactions extensively. “This can change greatly, depending on how—and how much— CBD is administered, the unique attributes of the individual taking this medication, and whether isolated CBD or a whole-plant remedy is used.”

This means that patients ingesting CBD products should pay close attention to changes in blood levels of important drugs in their protocol and adjust dosage accordingly under a doctor’s supervision. Devitt-Lee points out that, in cancer treatment, the precise dosing of chemotherapy is extremely important, and the goal is often to reach the maximum dose that will not be catastrophically toxic. For patients using CBD, the same dose of chemotherapy may produce higher blood concentrations of the chemo drugs. If CBD inhibits the cytochrome-mediated metabolism of the chemotherapy and dosage adjustments aren’t made, the chemotherapy agent could accumulate within the body to highly toxic levels.

That being said, adverse cannabinoid-drug interactions have rarely been reported among the many cancer patients who use cannabis to cope with the wrenching side effects of chemotherapy. It is possible that whole-plant Cannabis, with its rich compensatory synergies, interacts differently from the isolated CBD that is administered in most research settings. As well, the cytoprotective effects of the cannabinoids may mitigate some of the chemotherapeutic toxicity.

In epilepsy patients, CBD has been shown to elevate the plasma levels and increase the long-term blood concentrations of clobazam, an anticonvulsant, and norclobazam, an active metabolite of this medication. A majority of these patients needed to have their dose of clobazam reduced due to side effects. A 2015 report concluded that CBD is safe and effective for treatment of refractory epilepsy in patients receiving clobazam, but emphasized the importance of monitoring blood levels for clobazam and norclobazam in patients using both CBD and clobazam.

Other research has suggested that CBD can amplify the activity of certain cytochrome P450 enzymes. This evidence suggests that CBD can either increase or decrease the breakdown of other drugs, depending on the drug in question and the dosages used.

“Drug interactions are especially important to consider when using life-saving or sense-saving drugs, drugs with narrow therapeutic windows, or medications with major adverse side effects,” Devitt-Lee reports. “In particular, those patients who utilize high doses of CBD concentrates and isolates should keep these factors in mind when mixing remedies.”

Note that the list below does not necessarily contain every medication that could be affected by CBD, and not every medication in each of the categories listed will cause an interaction. For this reason, consult a medical professional before taking any combination of drugs at the same time, as alternative medications or dosage adjustments may be required. “If you are worried that your cytochrome P450 enzyme system may not be functioning properly,” Devitt-Lee writes, “physicians can test the system to ensure that the medications you take are metabolizing as expected.”

Drugs that use the cytochrome P450 system include:

  • Steroids
  • HMG CoA reductase inhibitors
  • Calcium channel blockers
  • Antihistamines
  • Prokinetics
  • HIV antivirals
  • Immune modulators
  • Benzodiazepines
  • Anti-arrythmics
  • Antibiotics
  • Anesthetics
  • Antipsychotics
  • Antidepressants
  • Anti-epileptics
  • Beta blockers
  • PPIs
  • NSAIDs
  • Angiotension II blockers
  • Oral hypoglycemic agents
  • Sulfonylureas

cbd-cover

More from CBD: A Patient's Guide to Medicinal Cannabis


From CBD by Leonard Leinow and Juliana Birmbaum, published by North Atlantic Books, copyright © 2017 by Leonard Leinow and Juliana Birmbaum. Reprinted by permission of publisher.






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