Cannabimimetics

Drug interactions may result from chemical reactions between different  components or modifications by certain components of certain biochemical  pathways involved in the action or metabolism of related drugs.  According to Drugs.com, drug interactions can be affected by various factors including disease  and patient conditions, as well as the nature of the compounds involved.  A drug interaction may lead to an enhanced drug response or modified or unexpected adverse reactions.  Use of medical cannabis or cannabis preparations is generally considered  safe and is devoid of common major adverse reactions, although rare  cardiovascular adverse effects and stroke have been noted. Tolerance and  dependence have been documented. Major adverse reactions with  recreational cannabis use occur more with increasing dosages and include  cardiovascular effects, cannabinoid hyperemesis syndrome, psychosis,  and others. 

This paragraph describes CBD interaction with general (drug)-metabolizing enzymes, such as those belonging to the cytochrome P450 family. This might have an effect for coadministration of CBD with other drugs.7 For instance, CBD is metabolized, among others, via the CYP3A4 enzyme. Various drugs such as ketoconazol, itraconazol, ritonavir, and clarithromycin inhibit this enzyme.  This leads to slower CBD degradation and can consequently lead to higher CBD doses that are longer pharmaceutically active. In contrast, phenobarbital, rifampicin, carbamazepine, and phenytoin induce CYP3A4, causing reduced CBD bioavailability.  Approximately 60% of clinically prescribed drugs are metabolized via CYP3A4. 

 Given CBD effects on common biological targets implicated in drug metabolism (e.g., CYP3A4/2C19)  and excretion (e.g., P-glycoprotein), the potential for DDIs with  commonly used medication is high. General clinical recommendations of  reducing substrate doses, monitoring for ADEs, and finding alternative  therapy should be considered, especially in medically complex patients. CBD is implicated as both a victim and perpetrator of DDIs and has its own  ADE profile. These effects should be considered in the risk-benefit  assessment of CBD therapy and patients and consumers made aware of potential safety issues with CBD use. 

CBD is generally safe and has few, if any, minor side effects. But  there’s one big caveat: CBD does have the potential to interact with  some medications. The concern has to do with how the body metabolizes  certain substances.  Before trying CBD, it’s crucial to talk to  your doctor about all of the vitamins, supplements, and prescription and  over-the-counter medications you’re taking. 

 Contraindications have not been identified. There is a risk of  hypersensitivity to CBD's or other constituents of the plant. The  benefits versus risks of cannabinoid use should be carefully weighed in  individuals with psychosocial disorders.  According to Drugs.com a total of 521 drugs are known to interact with cannabidiol.  CBD can also interact with other medications you're taking, such as blood thinners. 

View most common interaction reports for CBD and the medicines listed below.

• Alcohol (contained in alcoholic beverages) (ethanol)
• Aspirin Low Strength (aspirin)
• Benadryl (diphenhydramine)
• Claritin (loratadine)
• CoQ10 (ubiquinone)
• Cymbalta (duloxetine)
• Fish Oil (omega-3 polyunsaturated fatty acids)
• Flonase (fluticasone nasal)
• Lyrica (pregabalin)
• Metoprolol Succinate ER (metoprolol)
• Omega-3 (omega-3 polyunsaturated fatty acids)
• Probiotic Formula (bifidobacterium infantis / lactobacillus acidophilus)
• Singulair (montelukast)
• Tylenol (acetaminophen)
• Vitamin B12 (cyanocobalamin)
• Vitamin C (ascorbic acid)
• Vitamin D3 (cholecalciferol)
• Zofran (ondansetron)
• Zoloft (sertraline)
• Zyrtec (cetirizine)

Drug interactions can occur when two or more drugs/substances with  similar or different actions (including herbal substances) are  co-administrated, such as warfarin with aspirin, and cyclosporine A with  St John’s Wort. Drug interactions may result from chemical reactions  between different components or modifications by certain components of  certain biochemical pathways involved in the action or metabolism of  related drugs.  There are early studies or case reports indicating potential drug  interactions with warfarin, oxymorphone, pentobarbital, cocaine,  sympathomimetic amines, disulfiram, disulfiram etc., but further  research is needed. Interestingly, Russo (2016) mentioned that in  extensive clinical application including complex drug regimens with  opioids, tricyclic antidepressants, anticonvulsants etc, no drug  interactions have been observed that would contraindicate or preclude  the use of nabiximols with any specific pharmaceutical, although  additive sedative effects are always possible. 

MacCallum & Russo (2018) recently pointed out that there is no drug that cannot be used with cannabis, if necessary.

This entourage effect  is the concept that the different compounds in cannabis—such as terpenes, tetrahydrocannabinol (THC) and cannabidiol (CBD)—could interact with each other to produce synergistic effects.  Much like a musical instrument that joins with other instruments begin to form a symphony that creates a unique sound.  In addition to being found in cannabis, terpenes are found in many plants, including fruits and vegetables. As fragrant compounds, they’re responsible for the aromas in essential oils and different cannabis strains.  Terpenes are found in both food and cannabis, some have speculated that consuming certain terpenes could change the cannabis “symphony,” leading to a different type of medicine and feeling/high.

Grapefruit and certain other citrus fruits represent  examples of foods generally considered to be healthful, but with the  potential for a pharmacokinetic interaction causing greatly enhanced  oral drug bioavailability. The current trend of increasing numbers of  newly marketed grapefruit-affected drugs possessing substantial adverse  clinical effects necessitates an understanding of this interaction and  the application of this knowledge for the safe and effective use of  drugs in general practice.

Key points

• Currently,  more than 85 drugs have the possibility of interacting with grapefruit;  of these drugs, 43 have interactions that can result in serious adverse  effects.
• Drugs  that interact with grapefruit have all of the following characteristics:  they are administered orally, they have very low to intermediate  absolute bioavailability, and they are metabolized by the cytochrome  P450 3A4 enzyme (CYP3A4).
• All  sources of grapefruit and certain related citrus fruits can irreversibly  inhibit CYP3A4 in the gastrointestinal tract; to prevent this  interaction, affected drugs should not be consumed with any of these  fruits during the treatment period, or noninteracting alternative  medications should be prescribed.
• Older  patients have the greatest possibility of ingesting grapefruit and  interacting medications and are the most vulnerable to the adverse  clinical consequences.

Cannabidiol is POSSIBLY SAFE when taken by mouth or sprayed under  the tongue appropriately. Cannabidiol in doses of up to 300 mg daily  have been taken by mouth safely for up to 6 months. Higher doses of  1200-1500 mg daily have been taken by mouth safely for up to 4 weeks.  

Some reported side effects of cannabidiol include dry mouth, low blood pressure, light headedness, diarrhea, changes of appetite/weight and drowsiness. Signs of liver injury have also been reported in some patients, but this is less common.

Along with its needed effects, cannabidiol may cause some unwanted  effects. Although not all of these side effects may occur, if they do  occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking cannabidiol:

More common 

• Agitation
• chills
• cough
• fever
• hoarseness
• irritability
• lower back or side pain
• painful or difficult urination
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Less common 

• Aggression
• anger
• blue lips, fingernails, or skin
• confusion
• diarrhea
• difficult or troubled breathing
• dizziness
• fast heartbeat
• irregular, fast or slow, or shallow breathing
• loss of appetite
• nausea
• stomach pain

Some side effects of cannabidiol may occur that usually do not need medical attention.  These side effects may go away during treatment as your body adjusts to  the medicine. Also, your health care professional may be able to tell  you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common 

• Decreased appetite
• lack or loss of strength
• rash
• trouble sleeping

Less common 

• Change in walking and balance
• clumsiness or unsteadiness
• decreased weight
• drooling
• increased saliva

Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived  from Cannabis sativa that have become very popular over the past few  years. Patients report relief for a variety of conditions, particularly  pain, without the intoxicating adverse effects of medical marijuana.   The chemical compound THC [tetrahydrocannabinol] is the part of the  cannabis plant that most people are familiar with because that is the  part that makes people “high.” Most effects of marijuana that people  think of are caused by THC.

Most recreational marijuana has very little CBD in it. CBD products  are available through dispensaries, health food and convenience stores,  and the internet. It's a widely used product that's not regulated—and is  not legal to sell for its largely unproven health benefits.

According to the NIH: Nobody really knows what is responsible for the mental and physical  health benefits that have been attributed to it. CBD affects the body's  serotonin system, which controls our moods. It also affects several  other signaling pathways, but we really don't understand its mechanisms  of action yet. 

Despite a lack of robust evidence, cannabinoids — such as CBD — are  often assumed to be safe and effective in managing pain and used for  such purposes in real-world settings.   Minor cannabinoids (those other than THC, the high-inducing component of  marijuana) and certain terpenes found in the cannabis plant may have  analgesic properties, but there has been little research on these  substances to understand their effects and underlying mechanisms. The  cannabis plant contains more than 110 cannabinoids and 120 terpenes, but  the only compound that’s been studied extensively is THC. 

Marijuana and hemp are two different varieties of cannabis that come  from the same species of plant (Cannabis sativa L). In general, CBD is  found abundantly in both.  However, it’s important to note that CBD is typically found in the seeds  and stem of marijuana - not in the flowering buds (which is the part  that you smoke). The hemp plant is an entirely different strain of  cannabis that contains high quantities of CBD throughout (stem, buds,  etc), and practically zero traces of THC. If a hemp plant contains more  than 0.3% THC, it is then technically a “marijuana” plant. Most all  CBD-based products come from the industrial hemp plant.  

THC affects the brain by binding to naturally-occurring CB-1 receptors  in the central nervous system. CBD is a differently-shaped molecule that  binds to CB-2 receptors in cell and body tissues outside the central  nervous system.  

No, CBD will not get you high. It's non-intoxicating. Like we just said  THC is the molecule that binds to receptors in our brain and is the one  responsible for the psychoactive effects of marijuana.  In fact, CBD is antagonistic to the marijuana high; some research  expresses its potential to prevent THC molecules from binding to the  brain’s receptors (hence the reason why it’s often used to subdue the  ‘paranoia’ effects of super-potent THC strains).  

CBD functions by binding to cannabinoid receptors in the body’s  endocannabinoid system. These receptors have been found in virtually  every cell and tissue type in the human body (hence the seemingly  endless array of CBD uses).  

CBD doesn’t fit the scientific definition of a drug in a sense that it doesn’t attach to a specific receptor (or set of receptors) in the brain to trigger the release of dopamine.  Instead, CBD actually works to help curb addiction by balancing the levels of neurotransmitters like glutamate and dopamine in the brain.

The endocannabinoid system (ECS) is a biological system first discovered in the late ’80s and early ’90s, although much remains unknown about the system today.  The ECS is largely comprised of endocannabinoids, receptors, and enzymes that are believed to help regulate a variety of functions in human including sleep, mood, memory, appetite, reproduction, and pain sensation. Scientists still have plenty of questions about the human endocannabinoid system and how it functions.  The reason that plant cannabinoids have psychoactive and medicinal effects within the body is, in large part, because we have an endocannabinoid system (ECS) that they can interact with. For example, THC gets you high because it activates the CB1 receptor within the brain. Endocannabinoids like anandamide also activate CB1.  CBD is also interesting because it can affect overall levels of endocannabinoids in the brain, referred to as “endocannabinoid tone.” CBD inhibits the FAAH enzyme, which breaks down anandamide. Thus, CBD can increase anandamide levels by preventing FAAH from breaking it down. Inhibiting the FAAH enzyme has been shown to be a useful strategy for treating anxiety disorders, and some of CBD’s anti-anxiety properties may come from its ability to inhibit this enzyme and thereby increase endocannabinoid tone.

Cannabis plants contain more than 120 different phytocannabinoids. These phytocannabinoids act on your endocannabinoid system, which works to keep your body in homeostasis, or balance.

Cannabidiol (CBD) and tetrahydrocannabinol (THC) are two of the more well-researched and popular phytocannabinoids. People take CBD and THC in a variety of ways, and they can be consumed separately or together.

However, some research suggests that taking them together — along with smaller organic compounds in the cannabis plant, known as terpenes or terpenoids — is more effective than taking CBD or THC alone.

This is due to an interaction between phytocannabinoids and terpenes called “the entourage effect.” 

CBD and other cannabinoids are non-toxic, with no fatal overdose cases ever reported. It's also impossible to overdose on CBD oil. According to a study from 2011, chronic use and high doses up to 1,500 mg of CBD per day are well tolerated in humans.

This is impossible provided that you’ve bought a lab-tested and certified CBD oil made from hemp.

CBD is a non-intoxicant, meaning it won’t make you high. In fact, CBD can mitigate and block the psychoactive effects of THC.

The best way to avoid the side-effects of CBD oil is to always check on your vendor’s credibility.

If they can show third-party lab testing results for their products showing less than 0.3% THC — you have nothing to worry about.

According to Drugs.com:  Theoretically, CBD should not show up on a drug test. However,  because most CBD products are classified as a supplement, it is not  regulated for safety and purity. This means that contamination of the  CBD with THC (tetrahydrocannabinol) may and does occur, and this may  show up on a drug test, depending on the cutoff level of the test and  other factors listed below.

This is more likely to happen if the CBD you are buying is  marijuana-derived CBD rather than hemp-derived CBD. Hemp-derived CBD is  required by law to contain less than 0.3% THC, although regular daily  ingestion of high doses of this may still cause THC to accumulate.

Broad-spectrum CBD is also less likely to be contaminated with THC.  This is because all the THC is removed in broad-spectrum CBD as opposed  to full-spectrum CBD which contains all of the compounds that naturally  occur in the plant they were extracted from. CBD isolate is also pure  CBD, and typically comes from hemp so it shouldn’t contain THC.

If you want to pass a drug test, don't take CBD; or if you are taking  it legally within your State's laws, then declare it (however it still  may be contaminated with THC unless brought by a reputable supplier who  guarantees it to be THC-free).

It is difficult to say how much THC needs to be present to cause a  positive drug test because this depends on several drug and  patient-specific variables, and also the cutoff value for the test.

The following variables affect the amount of time that marijuana  (THC) and its metabolites remain detectable in the urine or other  biological samples:

• Frequency of marijuana use (the half-life of THC is 1.3 days for an infrequent user and 5-13 days for frequent users)
• Presence of interacting drugs
• How much is used and the route of administration
• Last time of ingestion.

Several patient factors can also affect the result, such as body  mass, urine pH, urine concentration and other medical conditions such as  kidney or liver disease.

An estimate of the length of time marijuana (THC) is detectable in urine is:

• Single-use: 3 days
• Moderate use (4 times/week): 5 to 7 days
• Chronic use (daily): 10 to 15 days
• Chronic heavy use: More than 30 days.

Federal workplace cutoff values for marijuana metabolites are 50  ng/mL for immunoassay screening tests (one ng is a billionth of a gram).  In a confirmatory test, a metabolite of marijuana is measured, called  delta-9-tetrahydrocannabinol-9-carboxylic acid, and a positive test  result is above 15 ng/mL. However, this can vary depending on the  variables listed above and should not be relied upon to ensure a  drug-free result.

According to Drugs.com:   There is still a lot of confusion over what exactly is CBD, with many  people thinking cannabis, hemp, marijuana, CBD and THC  (tetrahydrocannabinol) are the same thing. They are not.

Cannabis is a plant, and there are two main types; Cannabis Indica and Cannabis Sativa. While marijuana can be derived from both types, hemp is only derived from the Cannabis Sativa family.

This means that even though hemp and marijuana have a few things in  common, there are notable differences, with the most crucial being that  hemp is almost devoid of THC, which is the chemical in marijuana that  gives you a high. In fact, by law, hemp must contain no more than 0.3  percent THC to be considered hemp, otherwise, growers are at risk of  prosecution under federal law.

The main active ingredient in hemp is CBD, and CBD does not have any  psychoactive properties. Instead, CBD has been credited with relieving  anxiety, inflammation, insomnia, and pain, although currently there is  little scientific proof that CBD works, except for epilepsy. Epidiolex  Is a prescription CBD oil that was FDA approved in June 2018 for two  rare and severe forms of epilepsy, Lennox-Gastaut syndrome (LGS) and  Dravet syndrome. Other trials are underway investigating the benefits of  CBD for Parkinson's disease, schizophrenia, diabetes, multiple  sclerosis, and anxiety.

In addition to the medicinal uses of CBD, hemp is also a great  resource for making 100% biodegradable, environmentally friendly  products such as biofuel, building materials, clothing, and paper.