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According to a new study in the Journal of Clinic Medicine, the use of Tetrahydrocannabinol (THC) could have adverse drug effects when combined with other medications due to drug-drug interactions.
Cannabis Sativa, a.k.a “marijuana” is the one of the most popular illicit substances in the world. Its psychoactive ingredient, THC, has made cannabis a highly used recreational drug for millennia.
Over the past few decades, there has been an increased interest in leveraging cannabis and cannabinoids for medicinal purpose. And with the legalization of cannabis in Canada and legislation in 33 US states allowing for some kind of marijuana use (recreational or medicinal), the popularity of cannabis has been on the rise.
There is a strong belief that the plant is relatively benign because of the amount of recreational use in the younger generations. But as an older user-base with more complicated medical conditions continue to grow, it is important to understand how THC could adversely impact other co-administered medications.
This study summarizes potential adverse drug events related to THC when combined with other medications
Medicinal Use of Marijuana
Cannabis has been used widely across North America in various state or provincial medical marijuana programs. In 2018, ProCon.org has estimated well over 3.5M Americans have some kind of medical marijuana card or prescription.
Medical cannabis is typically prescribed for patients with severe conditions including inflammatory conditions (e.g., Crohn’s), chronic pain, appetite loss, issues with sleep, immune system disorders, thermoregulation problems, cancer and more.
While there have been significant studies done over the years, only chronic pain, antiemesis, multiple sclerosis, and sleep have any level of evidence of cannabis effectiveness.
However, in some cases, the risks may outweigh even the proven benefits.
2 Types of THC Impact
THC has broad pharmacological spread which means there are many opportunities for is to cause adverse Drug Events or unpredictable drug-drug interactions.
There are 2 types of impact that THC can have with other medications:
- Pharmacokinetic – How it effects the way a drug is absorbed, metabolized or excreted
- Pharmacodynamic – How it impacts the mechanics of how the drug is supposed to work
Pharmacokinetic Impacts of THC
How medicine is absorbed, metabolized and excreted can have an important impact on the body and dosage.
Diminished Efficacy of Cannabinoid Receptors
Cannabinoid (CB) receptors are part of our nervous system and are responsible for desired effects of cannabis (CB1 – the neuropsychiatric adverse effects and CB2 – the anti-inflammatory, appetite, sleep, and pain receptors).
THC is a agonist of BC receptors and chronic use of Cannabis may lead to tolerance of these receptors. Diminishing efficacy of these receptors over time should be considered for proper treatment.
Increase or Decrease in Effect Metabolism of THC
During the study, 36 healthy adults were given THC/CBD along with other interacting drugs.
When drug Rifampicin (an antibiotic) was used, there was a 87% decrease in 11-hydroxy-THC, the main active metabolite of tetrahydrocannabinol (THC). This metabolite is formed in the body after decarboxylated cannabis is consumed and is what gets excreted through the urine.
When cannabis is combined with Ketoconazole (an antifungal drug used to treat serious fungal infection) there was a 27% increase in THC bio-availability and 204% increase in 11-hydroxy-THC
This shows clearly the potential of drug-drug interactions and how this can change how the body metabolizes THC. This could have major unexpected adverse effects.
Pharmacokinetic Impacts of THC
There are many things that can impact the pharmacodynamic effects of THC.
Not all cannabis is created equal and variation in the specific dispensary, manufacturer, farm, and batch can have an impact. Additionally, there are variations based on the patients at a physiology, route of administration, and administration practices level. Finally, vaping and smoking of products introduces the chance of oxidizing some cannabis compounds.
Neuropsychiatric side Effects
THC has shown to pronounce pre-existing anxiety, schizophrenia, and depression. THC must be used cautiously in patients with these conditions and should not be missed with other drugs with similar effects.
In this study individuals that were given Dronabinol (man-made cannabis) compared to comparator group, had three times the odds of psychiatric or nervous system disorder side effects.
THC is known to alter cognitive functions, including impaired motor skills and heavy sedation. Medicines with similar effects such as opioids, benzodiazepines need to be very carefully managed.
Reported adverse effect in many clinical trials included amnesia, impaired balance, disturbed attention, dizziness, lethargy, and somnolence.
Many people take cannabis for its anti-inflammatory properties which is managed through the endocannabinoid system. But like many other anti-inflammatory products on the market, there is a trade off with the host’s immune system.
THC clearly reduces the body’s response to infections. This increases change of viral infections especially caused by smoke and vapor inhalation.
THC has sympathomimetic properties which increases risk of hypertension, hypotension, syncope and tachycardia. This can have dramatic impact on individuals with pre-existing heart disease. And considering nearly half of US adults have some sort of heart disease, THC should be reconsidered.
Anecdotal evidence suggests that medical marijuana is a relatively benign product with the potential to treat a large number of conditions with few side effects. In reality, there is little evidence supporting its efficacy for many conditions however does create additional safety concerns that must be considered.
Directly from article
Tetrahydrocannabinol (THC) is the primary psychoactive ingredient in cannabis. While the safety of THC and cannabis has been extrapolated from millennia of recreational use, medical marijuana programs have increased exposure among medically complex individuals with comorbid conditions and many co-prescribed medications. Thus, THC should be recognized as a pharmacologically complex compound with potential for drug–drug interactions and adverse drug events. This review summarizes potential adverse drug events related to THC when combined with other medications.
Metabolic drug–drug interactions are primarily due to THC conversion by CYP3A4 and CYP2C9, which can be impacted by several common medications. Further, CYP2C9 polymorphisms are highly prevalent in certain racial groups (up to 35% in Caucasians) and increase the bioavailability of THC. THC also has broad interactions with drug-metabolizing enzymes and can enhance adverse effects of other medications. Pharmacodynamic interactions include neurological effects, impact on the cardiovascular system, and risk of infection.
General clinical recommendations for THC use include starting with low doses and titrating to desired effects. However, many interactions may be unavoidable, dose-limiting, or a barrier to THC-based therapy. Future work and research must establish sufficient data resources to capture medical marijuana use for such studies. Meanwhile, clinicians should balance the potential risks of THC and cannabis and the lack of strong evidence of efficacy in many conditions with patient desires for alternative therapy
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