Thc in drugs

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Corresponding Author Paul T. Although prescribing information PI is often the initial source of information when identifying potential drug-drug interactions, it may only provide a limited of exemplars or only reference a class of medications without providing any specific medication examples. In the case of medical cannabis and medicinal cannabinoids, this is further complicated by the fact that the increased therapeutic use of marijuana extracts and cannabidiol oil will not have regulatory agency approved PI.

The objective of this study was to provide a detailed and comprehensive drug-drug interaction list that is aligned with cannabinoid manufacturer PI. For decades, there has been scientific interest in the involvement of the endocannabinoid system in the physiological regulation of conditions such as pain, nausea and vomiting, seizures, and multiple sclerosis [ 1 ]. Cannabis sativa still remains illegal at the federal level in the USA; however, as of Junethere are 33 States and the District of Columbia that have legalized one or more components of C.

In addition, the Farm Bill rendered CBD oil hemp-derived extract legal as long as its formulation is derived from hemp from a d grower, produced consistently with Federal and State laws, and following specific regulations [ 8 ]. Indeed, in Novemberthe U. Cannabinoid-containing products can be inhaled by smoking cigarettes, pipes, water pipes, and emptied cigars and also inhaled minus the smoke when vaporized, dabbed, and nebulized. Orally, cannabinoids can be administered by a capsule, oil, solution, or tincture.

Additionally, cannabinoids can be mixed in food i. Cannabinoids can also be administered sublingually and through the oral mucosa route with a lollipop, lozenge, or spray. Topically, cannabinoids can be applied as a gel, cream, ointment, patch, or inserted as a suppository [ 1011 ]. During a — online CBD survey, the most common method of CBD administration was sublingual, followed by vaping, oral ingestion of capsules and liquids, smoking, edibles, and topical administration [ 4 ].

Reports on CBD manufacturers that are not being systematically regulated suggest that labeled CBD formulations frequently do not accurately reflect the stated concentration or actual composition [ 4 ]. It is important to take this into consideration whether the cannabinoid-containing products are used to relieve acute symptoms, in the treatment of a routine medical condition, or during recreational use [ 15 ].

The concern for potential drug-drug interactions is of increasing concern and the subject of several recent reviews [ 16 - 21 ]. Although prescribing information PI is often the initial source of information, it may only provide a limited of exemplars or only reference a class of medications without providing any specific medication examples.

In the case of medical cannabis and medicinal cannabinoids, this is further complicated by the fact that the increased therapeutic use of marijuana extracts and CBD oil may not have regulatory agency approved PI. In either event, this still prompts the healthcare provider to conduct further research in order to identify potential drug-drug interactions. In the USA, nabiximols is an investigational drug for polyneuropathy, HIV-associated neuropathy, advanced cancer pain, and palliative care [ 31 ]. While the restricted use of prescription cannabinoids presents a potential concern for drug-drug interactions, another major concern arises from the increased use of cannabis and cannabis extracts as therapeutic agents e.

In addition, the increased use of recreational cannabis presents a ificant concern for healthcare providers in knowing when to be concerned about unintended drug-drug interactions. These concerns arise because these cannabinoid-containing products can interfere with the metabolism of a large of other medications, especially those that are required to be maintained in a narrow concentration range in order to obtain clinical benefit without untoward side effects. Based on the regulatory agency approved PI, CBD, nabiximols, nabilone, and dronabinol are primarily metabolized by 6, 6, 4, and 2 different cytochrome P enzymes, respectively.

Therefore, the ability of the cannabinoids to impact the activity of these enzymes can have dramatic effects on other medications. The UGT enzymes serve to catalyze phase II reactions in which the cannabinoids are conjugated to a sugar to render them more readily excreted.

Moreover, given their shared structures, it is likely that the other cannabinoids are similarly metabolized. Table 2 presents a unified list of NTI medications that will be subject to potential cannabinoid drug-drug interactions of one kind or another. A more complete list of potential drug-drug interactions is provided in the online supplementary material along with detailed specifics of the enzymes involved. List of Narrow Therapeutic Index NTI medications to be closely monitored when coadministered with cannabinoids, either therapeutically or recreationally.

The prescription cannabinoid medications dronabinol, nabilone, CBD, and nabiximols are highly protein bound. That is, they are present in the circulation in tight association with plasma proteins see Table 3. Cannabinoids can displace and hence increase the free fraction of OTHER highly protein-bound medications, especially those that have an NTI and, thus, may require dose adjustments see Table 3.

Thc in drugs

Conversely, other highly protein-bound medications may have an effect on cannabinoid protein binding and availability. More specifically, smoking produces an inter-individual variability in CYP1A2 activity when metabolizing select medications e.

In this case, the healthcare provider will want to question the use of tobacco products, as well as reference the cannabinoid drug-drug interaction list see Table 2. The U. As per the FDA website, these tables provide drug-drug interaction examples and were not intended to be a complete list. See the online supplementary material for a list of FDA defined terms and definitions e.

DrugBank v5. A comprehensive list of these drug-drug interactions is provided in the online supplementary material. In addition to the synergistic effect of alcohol e. When CBD was coadministered with valproate, there was no effect on valproate exposure; however, there is an increased incidence of liver enzyme elevations with a recommendation to discontinue either agent or reduce the dose of either agent [ 28 ].

Care should be taken when prescribing nabiximols with concomitant medications solely metabolized by both or either of these UGT enzymes e. Drug-drug interactions, associated with cannabinoid-containing products, should not be simply limited to the additional dizziness, confusion, sedation, and somnolence when taken concomitantly with alcohol or other central nervous system-sedating medications e.

Additionally, there can be additive cardiac side effects e. If a potential drug-drug interaction is identified, it does not necessarily translate into a contraindicated combination nor a clinically ificant interaction, but an opportunity to evaluate the dose of either the cannabinoid or concomitantly PI. Conversely, metabolism of the cannabinoid-containing medications can be affected by OTHER medications.

These drug-drug interactions can be quite complicated when they involve a of medications, their corresponding metabolizing enzymes, and use within the medically complex patient population e.

Thc in drugs

Additionally, herbal supplements e. Unfortunately, these added herbal supplements themselves also have known drug-drug interactions [ 40 ]. The online supplementary material provides a list of medications that could have a potential drug-drug interaction with a cannabinoid prescription, OTC, or illicit see www. Figure 2 provides a detailed illustration of this online supplementary material. Colors, directional arrows, and capitalization are all utilized to provide visual cues to identify the type of drug-drug interaction.

Thc in drugs

Additionally, the source and date of this information are provided. Although two or more medications may compete for the same enzyme, this may not be clinically ificant when a medication has a broad therapeutic concentration range and with minor fluctuations having minimal clinical impact.

Therefore, in an effort to reduce any potential false alerts, alert fatigue, and to provide a manageable drug-drug interaction list, the medications that only have an NTI are highlighted in this report. The supplementary material list can be viewed online at the Penn State College of Medicine, Department of Pharmacology website. Finally, the source of the drug-drug interaction information e.

While these drug-drug interactions are important for the relatively small patient populations for which the drugs are intended, perhaps the broader importance is derived from the recent deregulation of CBD oil hemp oil and the steady increase in states and countries legalizing recreational and medical marijuana. The use of medical marijuana whether smoked or in extractsCBD oil, or recreational marijuana can deliver a highly variable cannabinoid concentration.

Thc in drugs

Patients may be less likely to accurately report their recreational marijuana frequency and amount of use. Therefore, it is incumbent on the healthcare provider to inquire as to this use. For example, screening for use of cannabinoid-containing products is now advocated for select cardiovascular patient populations [ 43 ]. Finally, plant-derived products may contain myriad other compounds e.

While every attempt has been made to provide the most up-to-date and comprehensive list of drug-drug interactions, there may be OTC, herbal, and prescription medications that are not included within this publication or online supplementary material.

Thc in drugs

Except for selected instances, the medications contained in these lists do not describe their active metabolites and associated metabolizing enzymes. The source of data may, at times, be inherently outdated due to the publication date or revision date of the sourced information e. The DrugBank database [ 23 ], which is updated frequently, was last accessed between November and February The pharmaceutical cannabinoid manufacturer did not, at times, undertake formal drug-drug interaction studies and report only general and nonspecific case reports e.

The withdrawal of a cannabinoid more specific to heavy recreational cannabis use may precipitate the cannabis withdrawal syndrome [ 44 ]. In addition, there have been reports of patients who regularly use recreational cannabis and then require higher doses of propofol for sedation [ 47 ].

There have been various published case reports and journal articles listing P-gp [ 48 ], oncology [ 1749 ], psychotropic [ 16 ], transplant [ 2050 ], and other miscellaneous lists of cannabinoid drug-drug interactions [ 21 ]. Currently, there is not a comprehensive list of medications that is closely aligned with the cannabinoid manufacturer regulatory agency approved PI.

With a paucity of formal drug-drug interaction studies, especially in medically complex patient populations e. While developing these drug-drug interaction data tables, it was evident there can be multiple drug-drug interactions as the result of the many possible combination of medications and their corresponding metabolizing enzymes.

Table 2 provides a starting point for consideration. These lists of potential drug-drug interactions are NOT intended to be a substitute for medical decision making, since individual patient characteristics e. Our sincere appreciation for the feedback received from the Pharmacists of the Medical Marijuana Advisory Workgroup practicing in the Commonwealth of Pennsylvania.

None by P. Additionally, P. While every attempt has been made to provide the most up-to-date and comprehensive list of drug-drug interactions, there may be OTC, herbal, illicit, and prescription medications that are not included. These potential drug-drug interactions are NOT intended to be a substitute for medical decision-making, since all individual patient characteristics e. Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication.

However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor s.

The publisher and the editor s disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Free Supplementary Material. Privacy Policy Terms of Use Imprint. Manage with MyKarger your orders simply and fast, save your favorite articles in your reading list, edit your newsletter profile and benefit from attractive discounts.

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Thc in drugs

Med Cannabis Cannabinoids ;— Abstract FullText PDF References Extras : 7 Abstract Although prescribing information PI is often the initial source of information when identifying potential drug-drug interactions, it may only provide a limited of exemplars or only reference a class of medications without providing any specific medication examples.

Karger AG, Basel Introduction For decades, there has been scientific interest in the involvement of the endocannabinoid system in the physiological regulation of conditions such as pain, nausea and vomiting, seizures, and multiple sclerosis [ 1 ].

Table 1. Hepatically expressed cytochrome P enzymes. Table 2. Table 3. Table 4. Table 5. Related Articles:. Medical use of cannabinoids. First- Preview. Download Figures. Karger AG, Basel. Company People Career Newsroom Contact. E-mail address. Set Your Password.

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Thc in drugs

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