Jul 12, 2018 however, unlike most clinically available drugs, little information on the pharmacokinetics and pharmacodynamics of cannabinoids is available to guide prescribers, and further research is needed to address the major gaps in the knowledge required for optimal prescribing of these medicines. Cannabinoids as neuroprotectants against ischemia 101 aidan hampson introduction 101 cannabinoids and ischemia 102 cannabinoid receptors and presynaptic calcium channels 102 cannabinoid receptors and postsynaptic calcium channels 104 the cannabinoid system as an. The cannabinoid cb1 receptor was originally discovered in the central. Pharmacokinetics and pharmacodynamics of cannabinoids franjo grotenhermen novainstitut, hurth, germany contents abstract. Tobacco smoke contains a large number of compounds in the form of metals, volatile gases and insoluble particles, as well as nicotine, a highly addictive alkaloid. Delta9tetrahydrocannabinol thc and cannabidiol are pharmacologically active cannabinoids in marijuana that are metabolized by cytochrome p450 cyp3a4. Cannabinoid pharmacokinetics were examined to characterize differences in plasma concentrations between the two forms of administration. The inal effect may be the result of either the pharmacodynamic or the pharmacokinetic interactions of. Improvements to our existing technique based on gcms with metastable ion monitoring for quantification of delta9thc and its major metabolites with the aim of developing, for the first time, a method sensitive enough to define fully the pharmacokinetics and accumulation of the drug in humans. The intended effects of the drug, at a concentration that minimizes potential adverse effects, are determined by the intricate balance between pk and pd. Pharmacology, psychoactive agents and drug interactions. Pharmacodynamic effects, pharmacokinetics, and metabolism. The effects of cannabinoids on the pharmacokinetics of.
About 50% of the thc in a joint of herbal cannabis is inhaled in the mainstream smoke. Plasma cannabinoid pharmacokinetics following controlled oral. Pharmacodynamics and pharmacokinetics of synthetic. Cannabis medicines contain a wide variety of chemical compounds, including the cannabinoids delta9tetrahydrocannabinol thc, which is psychoactive, and the. The above will hopefully give you a good, brief overview of what is going on but there is still plenty to read for those wanting to learn more. The pharmacodynamics and pharmacokinetics of the benzodiazepines are discussed and differences which may be important in the clinical situation are stressed. Pharmacokinetic drug interactions with tobacco, cannabinoids. Jan 01, 2011 nine cannabis smokers completed all 5 dosing sessions.
Cannabinoids administered via inhalation exhibit similar pharmacokinetics to those administered intravenously 20. Abstract our knowledge of the pharmacodynamics of cannabinoids, that is, the study of the biochemical and physiologic effects of drugs and their. The pharmacokinetics of cannabinoids and the effects observed depend on the formulation and route of administration, which should be tailored to individual patient requirements. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. Pharmacokinetics refers to the sum of the processes the body is conducting on the drug. It may be of benefit in future study to either put in place more stringent exclusion criteria and measure subject fat content or assess the possible accumulation of cbd in fatty tissue. Articles older than 10 years were included only if the study was not. As you can see, there is a lot to learn about cannabinoids and how they interact with our bodies.
Pharmacokinetic and pharmacodynamic characterization of. A search using electronic databases pubmed, cinahl, idis, and medline was conducted limiting date ranges to 1990november 2014. Cannabis and cannabinoids pharmacology, toxicology, and therapeutic potential franjo grotenhermen ethan russo editors the haworth integrative healing press an imprint of the haworth press, inc. Sep 30, 2012 pharmacokinetics and pharmacodynamics of cannabinoids pharmacokinetics and pharmacodynamics of cannabinoids grotenhermen, franjo 20120930 00. Sep 30, 2012 natural cannabis products and single cannabinoids are usually inhaled or taken orally.
Introduction to pharmacokinetics and pharmacodynamics. Metabolismidentification of in vitro metabolites of jwh015, an aminoalkylindole agonist for the peripheral cannabinoid receptor cb2 by hplcmsms. The aim of this article is to provide an overview of the efficacy, pharmacokinetics pk, pharmacodynamics pd, and safety of oral cannabinoids for patients with cinv. Cellular actions of cannabinoids in pain pathways 93 summary 95 chapter 9. In the pharmacokinetic interactions, some of the plant components may improve the. It suggests dissolving cbd in sulphuric acidacetic acid and leaving it for anywhere from 3 hours to 3 days to obtain delta9thc and delta8thc. Thus, it is important to understand cannabinoid pharmacokinetics and the disposition of cannabinoids into biological fluids and tissues. Clinical pharmacokinetics of cannabinoids article pdf available in journal of cannabis therapeutics 31 january 2003 with 8,562 reads how we measure reads. This study evaluated the safety, pharmacokinetics, and pharmacodynamics of taranabant 5, 7. Pulmonary assimilation of inhaled thc causes a maximum plasma concentration within minutes, psychotropic effects start within seconds to a few minutes, reach a maximum after 1530 minutes, and taper off within 23 hours.
Thc is known to be extensively metabolized to a large number of compounds, even though most of the compounds are inactive 7377. Lucas, hunter medical research institute, locked bag, new lambton, nsw, australia, 2305. Because of the paucity of human data with synthetic cannabinoid compounds, future animal studies should compare the effects of dose and route of administration on the pharmacodynamics and pharmacokinetics of these compounds as they emerge in the recreational drug marketplace. Nabilone is well absorbed and the pharmacokinetics, although variable, appear to be linear from oral doses of 1 mg to 4 mg these doses show a plasma elimination halflife of approximately 2 h. There are various ways for thc to enter the bloodstream. Pharmacodynamics is affected by receptor binding and sensitivity, postreceptor effects, and chemical interactions. A phase 1a study eloneisenberg,miriogintz,andshlomoalmog.
Agurell and mats halldin and j e lindgren and agneta ohlsson and m. Our knowledge of the pharmacodynamics of cannabinoids, that is, the study of the biochemical and physiologic effects of drugs and their mechanisms of action the merck manual, has considerably increased within the past decade due to the detection of an endogenous cannabinoid system with specific receptors and their endogenous ligands. Natural cannabis products and single cannabinoids are usually inhaled or taken orally. The first part deals with cannabinoids as cyp substrates, the second summarizes current knowledge on the influence of various cannabinoids on the metabolic activity of cyp, and the third outline a. Of 792 articles retireved, 24 included pharmacokinetic parameters in humans. Pdf human cannabinoid pharmacokinetics marilyn huestis. Introduction cannabis or marijuana is the most commonly used illegal substance in the world and approximately four percent of the worlds population has used cannabis at least once in the past year leggett. Dose pharmacokinetics of oral cannabidiol following. The nonpsychotropic cannabidiol cbd, some analogues of natural cannabinoids and their metabolites, antagonists at the cannabinoid receptors and modulators of the endogenous cannabinoid system are also prom ising candidates for clinical research and therapeutic uses. As both thc and cbd are hepatically metabolized, the potential exists for pharmacokinetic drug interactions via inhibition or induction of enzymes or transporters. It is wellknown that cannabinoids are highly lipophilic compounds and accumulate in fatty tissue which can then be released gradually gunasekaran et al. Pulmonary assimilation of inhaled thc causes a maximum plasma concentration within minutes, while psychotropic effects start within seconds to a few minutes, reach a maxi.
Pharmacokinetics and pharmacodynamics of cannabinoids pharmacokinetics and pharmacodynamics of cannabinoids grotenhermen, franjo 20120930 00. The pharmacologic response depends on the drug binding to its target. Clobazam, one of a new generation of benzodiazepines, is discussed in relation to the 1,4. Metabolism and pharmacokinetics of the cannabinoids. Cannabinoid levels can be increased by other medications. The pharmacokinetics of delta9thc were computed using standard noncompartmental methods following multiple dose administration using winnonlin software version 2.
Marijuana is the most widely used illicit drug of abuse in the world, with a. Department of pharmacology toxicology, inserm u1173. Absorption and metabolism of tetrahydrocannabinol thc vary as a function of route of administration. Both pharmacodynamics and pharmacokinetics explain the drugs effects, which is the relationship between the dose and response. The pharmacokinetics of thc vary as a function of its route of administration.
It is wellknown that cannabinoids are highly lipophilic compounds and. Pharmacology, psychoactive agents and drug interactions ureh nena lekwauwa, m. Ld 1 is the dose where one observes 1% of the ss dying the threshold dose for lethal effects note. Delta9tetrahydrocannabinol thc is the main source of the pharmacological effects caused by the consumption of cannabis, both the marijuanalike action and the medicinal benefits of the plant.
The mechanism of action of cannabinoids is best investigated for. Absorption of a compound, such as thc, means entering of a compound into the bloodstream. Aspects of the pharmacokinetics and pharmacodynamics of. Cannabinoids pharmacokinetics and drug analysis natural. S agurell, m halldin, j e lindgren, a ohlsson, m widman, h gillespie and l hollister. Synthetic cannabinoids sc interact with cb 1 and cb 2 cannabinoid receptors and elicit cannabimimetic effects similar to. Other cannabis compounds of possible pharmaco logical interest are terpenes about 120 which are responsible for the specificsmelloftheplant, flavonoids 21, andnitrogenouscompounds 27 including two spermidine type alkaloids. The pharmacodynamics of cannabinoids is a complex and very deep subject.
Clinical pharmacokinetics of cannabinoids franjo grotenhermen abstract. Mar 06, 2012 pharmacodynamics and pharmacokinetics of synthetic cannabinoids 1. In addition to these phytocannabinoids synthetic agonists and antagonists at the cannabinoid receptor and other modulators of the endogenous cannabinoid system are under investigation for potential therapeutic uses. The compound is responsible for the main psychotropic effects of cannabis and use of synthetic, highaffinity analogues led to the discovery of its cns targets and identification of. Search terms included at least one of the following. Understanding the pharmacokinetics of a drug is essential to understanding the onset, magnitude, and duration of its pharmacodynamic effects, maximizing therapeutic and minimizing negative side effects. Reviewthemed issue the pharmacokinetics and the pharmacodynamics of cannabinoids correspondencedr catherine j. Sc were developed as research tools to explore the endocannabinoid system and as potential therapeutics pertwee, 2006. Pharmacokinetics and pharmacodynamics of cannabinoids. After inhalation, peak plasma concentrations of both thc and cbd are attained rapidly within 310 min 20, 21 and maximum concentrations are higher relative to oral ingestion 16, 22. There is increasing interest in the use of cannabinoids for disease and symptom management, but limited information available regarding their pharmacokinetics and pharmacodynamics to guide prescribers. Pharmacokinetics and metabolism of delta 1tetrahydrocannabinol and other cannabinoids with emphasis on man.
May 08, 2019 0 the pharmacodynamic interactions may occur if some of the components have the same or at least similar inluence on activities of the endocannabinoidome receptors. Pharmacodynamics and pharmacokinetics of synthetic cannabinoids. Pharmacology of cannabinoids in the treatment of epilepsy. The mechanism of action of cannabinoids is best investigated for d9thc thc, dronabinol. General pharmacokineticpharmacodynamic concepts of mood. The pharmacokinetics and the pharmacodynamics of cannabinoids. As with thc, there is a high firstpass effect, and the feces to urine ratio of excretion is similar to other cannabinoids. In contrast, refers to the pharmacodynamics physiologic and biochemical effects of the drug on the body. Cannabinoids exert many effects through activation of gproteincoupled cannabinoid receptors in the brain and peripheral tissues. A phase i, open label, fourway crossover study to compare the pharmacokinetic profiles of a single dose of 20 mg of a cannabis based medicine extract cbme administered on 3 different areas of the buccal mucosa and to investigate the pharmacokinetics of cbme per oral in healthy male and female volunteers gwpk0112. Our knowledge of the pharmacodynamics of cannabinoids.
1193 1082 613 1407 476 1187 464 1530 168 960 861 512 484 1297 1580 243 322 1500 737 1413 385 402 333 1150 642 416 299 1073 94 371 345 646 203 1448 51 129