Abstract. Cytochrome P450 is a family of isozymes responsible for the biotransformation of several drugs. Drug metabolism via the cytochrome P450 system has emerged as an important determinant in the occurrence of several drug interactions that can result in drug toxicities, reduced pharmacological effect, and adverse drug reactions.
Then your sample is sent to a lab where your DNA is analyzed for specific genes. It usually takes several days to a week to get the results of cytochrome P450 tests. You and your doctor can discuss the results and how they might affect your treatment options.
These are the most important factors that will affect your THC levels and overall marijuana potency: Your plant’s genes are hands-down the most important aspect of cannabis potency when it comes to growing! Your plant genetics set the “upper limit” of how much THC and other cannabinoids your plant will ever be able to produce.
Many medical marijuana growers desire high THC levels for the relief of nausea, certain types of pain, spasticity, certain symptoms of multiple sclerosis, etc. Many of the things you do to increase THC levels will also increase your overall cannabis yields.
Evidence from the few systematic clinical studies that have been conducted suggests that THC and CBD can inhibit metabolism of other drugs, via interactions with cytochrome P450 (CYP) enzymes, a large family of enzymes involved in the metabolism of numerous drugs and foreign chemicals in the body.
THC is the main psychoactive compound in marijuana. It's what makes people feel "high." We have two types of cannabinoid receptors in our bodies. THC binds with receptors -- mostly in the brain -- that control pain, mood, and other feelings.
When cannabis or CBD is taken along with certain prescription drugs, THC and CBD can inhibit or induce the metabolic process. For example, CBD is a potent inhibitor of CYP3A4 and CYP2D6 enzymes, while THC is an inducer of CYP1A2.
The half-life of THC for an infrequent user is approximately 1.3 days. For heavy users, the half-life can be 5-13 days.
Abstract. Cytochrome P450 is a family of isozymes responsible for the biotransformation of several drugs. Drug metabolism via the cytochrome P450 system has emerged as an important determinant in the occurrence of several drug interactions that can result in drug toxicities, reduced pharmacological effect, and adverse drug reactions.
Cytochrome P450 represents a family of isozymes responsible for biotransformation of many drugs via oxidation.
In the elderly, decreases in hepatic blood flow, enzyme activity, and liver mass result in reduced metabolic activity. CYP3A4 ISOZYME INTERACTIONS. Studies on the CYP3A4 isozyme and drug-drug/drug-food interactions are becoming an integral part of drug research.
A greater degree of interaction predictability has been achieved through the identification of P450 isozymes and some of the drugs that share them. Six different P450 isozymes—CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP2E1, and CYP3A4—that play important roles in drug metabolism have been identified (1, 2). Of these 6 isozymes, shared metabolism by the ...
The enzymes are heme-containing membrane proteins, which are located in the smooth endoplasmic reticulum of several tissues. Although a majority of the isozymes are located in the liver, extrahepatic metabolism also occurs in the kidneys, ...
When the serum levels of these drugs reach a toxic state, the toxicity can manifest itself with serious medical consequences.
Factors contributing to interpatient variability in biotransformation include genetic polymorphism, disease, age, and gender.
CYP450 and other genetic tests (genotyping tests) are becoming more common as doctors try to understand why antidepressants help some people and not others. While the use of these tests might be increasing, there are limitations.
It usually takes several days to a week to get the results of cytochrome P450 tests. You and your doctor can discuss the results and how they might affect your treatment options.
CYP450 testing isn't useful for all antidepressants, but it can provide information about how you're likely to process a number of them. For example: 1 The CYP2D6 enzyme is involved in metabolizing antidepressants such as fluoxetine (Prozac), paroxetine (Paxil, Pexeva), fluvoxamine (Luvox) and venlafaxine (Effexor XR), as well as tricyclic antidepressants such as nortriptyline (Pamelor), amitriptyline, clomipramine (Anafranil), desipramine (Norpramin) and imipramine (Tofranil). Some antidepressants, such as fluoxetine and paroxetine, can cause the CYP2D6 enzyme to slow down. 2 The CYP2C19 enzyme is involved in metabolizing citalopram (Celexa) and escitalopram (Lexapro).
Your doctor may use cytochrome P450 (CYP450) tests to help determine how your body processes (metabolizes) a drug. The human body uses cytochrome P450 enzymes to process medications. Because of inherited (genetic) traits that cause variations in these enzymes, medications may affect each person differently.
CYP450 tests are generally used only when initial antidepressant treatments aren't successful. Genotyping tests are also used in other areas of medicine. For example, the CYP2D6 test can help determine whether certain cancer medications, ...
The CYP2C9 test can help determine appropriate dosing of the blood thinner warfarin to reduce the risks of adverse effects. The field of pharmacogenomics is growing and many different types of genotyping tests are available. Tests differ widely by which classes of drugs they examine and how the tests are performed.
For example, results of a CYP2D6 test may show which of these four types applies to you: Poor metabolizers. If you process a certain drug more slowly than normal because of a missing enzyme, the medication can build up in your system. This buildup can increase the likelihood that the medication will cause side effects.
Phytocannabinoids are extensively metabolized by CYPs. The enzymes CYP2C9, CYP2C19, and CYP3A4 catalyze most of their hydroxylations. Similarly, CYP represents a major metabolic pathway for both synthetic cannabinoids used therapeutically and drugs that are abused.
The binding of these substance (s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB 1); cannabinoid receptor 2 (CB 2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer-both in vivo and in vitro clinical trials-has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.
Just over 20 years ago, cannabinoid research focused on single compounds, such as Delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), etc. This is a common research paradigm for compounds which can be inexpensively isolated from their parent material. However, over the last decade, the arc of cannabinoid research has shifted to investigation of full spectrum formulations containing the most abundant phytocannabinoids (CBD and THC), as well as less common cannabinoids like cannabinol (CBN), cannabigerol (CBG), and cannabichromene (CBC) among others. The terpene and flavonoid profiles of cannabis plants have also begun to garner recent interest from researchers. As the scientific community’s understanding of endocannabinoid receptor functionality expands, this research field will continue to grow (Russo 2011; Booth et al. 2017).
Cannabis (marijuana) has been known to humans for thousands of years but its neurophysiological effects were sparsely understood until recently. Preclinical and clinical studies in the past two decades have indisputably supported the clinical proposition that the endocannabinoid system plays an important role in the etiopathogeneses of many neuropsychiatric disorders, including mood and addictive disorders. In this review, we discuss the existing knowledge of exo- and endo-cannabinoids, and role of the endocannabinoid system in depressive and suicidal behavior. A dysfunction in this system, located in brain regions such as prefrontal cortex and limbic structures is implicated in mood regulation, impulsivity and decision-making, may increase the risk of negative mood and cognition as well as suicidality. The literature discussed here also suggests that the endocannabinoid system may be a viable target for treatments of these neuropsychiatric conditions.
Moreover, the Cmax of sildenafil increased by 63% (p < 0.05) and 22% (p > 0.05) in cigarette smokers and cannabis smokers, respectively. Cigarette smoking increases the exposure of sildenafil to a statistically significant level with no effect on its pharmacodynamics, safety and tolerability.
The neuropharmacology of marijuana, including its effects on selective serotonin reuptake inhibitor (SSRI)/antidepressant metabolism and the subsequent response and tolerability in youth, has received limited attention. We sought to (1) review clinically relevant pharmacokinetic (PK) and pharmacodynamic ...
The reaction was inhibited by inhibitors of cytochrome P450 such as SKF 525-A and by cannabidiol. The pretreatment of mice with phenobarbital significantly increased the enzyme activity but not with 3-methylcholanthrene, whereas that with cobaltous chloride significantly decreased the activity.
When exposed to prolonged high temperatures, cannabinoids begin to decarboxylate and/or degrade. THCA will first lose its carboxyl ring in this process, converting it to THC, which can eventually degrade to CBN through prolonged exposure to elevated temperatures.
To summarize, temperature, humidity, airflow, and light are the four major factors that influence the degradation of cannabis. All four variables represent a spectrum that harvested cannabis flowers teeter on.
How UV Light and Oxygen Impact Cannabis Degradation. Where temperature and humidity are both highly influential to cannabis degradation, high exposure to UV light and oxygen can perhaps cause the highest rates of degradation in the shortest time frame.
Cannabis is perishable, meaning that at some point your prized bag of fresh flowers is going to punch out its time card and expire. What was once a vibrant green, fresh-smelling sack of cannabis buds will eventually all but lose those pungent aromas as well as that vibrant hue.
This process can only be slowed by limiting light exposure to cured flowers. Elevated exposure to oxygen can also cause rapid cannabinoid degradation.
For example, temperature has the ability to cause THCA to decarboxylate and become THC (which is highly psychoactive), but heat and light can cause THC to degrade to CBN over time as well.
So as a really rough example, let’s say your strain/plant genetics can only produce 20% THC at most. That means you may get less than 15% THC in your buds if you don’t grow the plant right, but no matter what you do you’ll never be able to increase it above 20%.
The idea is that a cannabis plant needs to remain in the vegetative stage for at least 8 weeks before being switched to the flowering stage in order to reach its maximum THC levels when it starts budding.
Your plant’s genes are hands-down the most important aspect of cannabis potency when it comes to growing! Your plant genetics set the “upper limit” of how much THC and other cannabinoids your plant will ever be able to produce. Although you can use grow methods to maximize the THC within that limit, you will never be able to overcome ...
Cannabis uses light to power the growth of buds, along with the THC and cannabinoids contained inside. Outdoors your plant needs direct sunlight 8+ hours a day to produce to its fullest, and indoors you need strong, bright grow lights (like LEDs or MH/HPS grow lights) to produce the highest levels of THC.
For many growers, including both medical marijuana and recreational cannabis growers, a common goal is to maximize the amount of THC and other cannabinoids produced when growing cannabis (ie increase the “potency” of your buds). ...
These techniques and methods are considered “unknowns” because there hasn’t been a whole lot of scientific testing to see what works and what doesn’t work as far as increasing THC.
Many cannabis growers don’t realize they are harvesting their buds too early, dramatically reducing yields and potency! There is a 2-3 week period during the flowering stage when plants are “mature” and buds are at the highest levels of THC.
After a week of THC exposure, the THC injections stopped, and the rate of recovery was measured. Behavior normalized in less than two weeks, and tolerance to THC’s sedative effect recovered quicker than its effect on pain.
Once THC is gone, this activity usually returns to normal. But if you repeatedly expose the brain to THC over a couple days or weeks, the brain takes action to minimize the increase in CB1 receptor activity; the brain fights back so that normal CB1 activation patterns are preserved.
Mice who were given twice daily injections of THC at 10 mg/kg developed tolerance to THC’s pain-relieving and sedative effects after 36 hours (i.e., 3 THC injections). Tolerance to THC’s sedative effects were stronger than to its pain-relieving effects, suggesting that different brain regions or brain cells are more susceptible to tolerance ...
To do so, CB1 receptors are reduced, their effects weakened, or genetic expression altered. These mechanisms work to dampen the impact of THC so that in order to achieve the initial high, one must consume more. This is tolerance.
Desensitized CB1 receptors are detected by components within the cell that tag the receptor with a phosphate group. This is like the pitcher telling the coach to take them out of the game. This phosphate group signals to additional components within the cell to remove the receptor from the cell’s surface.
Repeated activation of CB1 receptors initiates events inside the brain cell that at first leads to desensitization, which is the weakening of the response to THC, followed by internalization, which is the removal of CB1 receptors from the cell’s surface.
When you compare it to alcohol, cannabis doesn’t seem so bad. Excessive alcohol consumption can be toxic to the brain, causing injury or death to the brain cells themselves. Abstaining from alcohol can lead to some recovery, but it takes longer than cannabis and is often less complete.
For example, the induction of CYP3A4 by rifampicin takes around six days to develop and 11 days to disappear 11. Induction normally results in a decrease in the effect of the medicine.
Foetal levels of CYP3A4 expression, content and activity are very low, but appear to reach adult levels at around one year of age 1 . Clinical studies indicate that women metabolise drugs which are substrates of CYP3A4 more quickly than men (20–30% increase) 4.
Inducers of CYP3A4 include phenobarbital, phenytoin, rifampicin, St. John’s Wort and glucocorticoids. Cytochrome P450 enzymes are essential for the metabolism of many medicines and endogenous compounds. The CYP3A family is the most abundant subfamily of the CYP isoforms in the liver. There are at least four isoforms: 3A4, 3A5, ...
There are at least four isoforms: 3A4, 3A5, 3A7 and 3A43 of which 3A4 is the most important 1 . CYP3A4 contributes to bile acid detoxification, the termination of action of steroid hormones, and elimination of phytochemicals in food and the majority of medicines 2, 3 .
Key Messages. CYP3A4 is responsible for the metabolism of more than 50% of medicines. CYP3A4 activity is absent in new-borns but reaches adult levels at around one year of age. The liver and small intestine have the highest CYP3A4 activity.
Some medicines which are substrates of CYP3A4 have low oral (but not intravenous) bioavailability due to intestinal metabolism. The bioavailability of these substrates is dramatically changed by inhibition, induction or saturation of CYP3A4 5.
This is used for its antidepressant activity. The active substance is hyperforin, the most potent known activator of PXR 12. Clinical studies have demonstrated that products containing less than 1% hyperforin are less likely to produce interactions 12. However, most products contain 3% hyperforin 12 .