Pharmacokinetics and pharmacodynamics of cannabinoids pdf

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. Cannabinoid levels can be increased by other medications. The pharmacologic response depends on the drug binding to its target. Abstract our knowledge of the pharmacodynamics of cannabinoids, that is, the study of the biochemical and physiologic effects of drugs and their. The intended effects of the drug, at a concentration that minimizes potential adverse effects, are determined by the intricate balance between pk and pd. The pharmacokinetics of cannabinoids and the effects observed depend on the formulation and route of administration, which should be tailored to individual patient requirements. About 50% of the thc in a joint of herbal cannabis is inhaled in the mainstream smoke. Ld 1 is the dose where one observes 1% of the ss dying the threshold dose for lethal effects note. Sc were developed as research tools to explore the endocannabinoid system and as potential therapeutics pertwee, 2006. The pharmacokinetics of thc vary as a function of its route of administration. Pharmacodynamics and pharmacokinetics of synthetic cannabinoids. 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. Plasma cannabinoid pharmacokinetics following controlled oral. General pharmacokineticpharmacodynamic concepts of mood.

Clobazam, one of a new generation of benzodiazepines, is discussed in relation to the 1,4. There are various ways for thc to enter the bloodstream. Absorption of a compound, such as thc, means entering of a compound into the bloodstream. 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. Jan 01, 2011 nine cannabis smokers completed all 5 dosing sessions. 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. Cannabinoids administered via inhalation exhibit similar pharmacokinetics to those administered intravenously 20. Pharmacology, psychoactive agents and drug interactions. 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. Pharmacology of cannabinoids in the treatment of epilepsy. Pharmacokinetics and metabolism of delta 1tetrahydrocannabinol and other cannabinoids with emphasis on man.

Thus, it is important to understand cannabinoid pharmacokinetics and the disposition of cannabinoids into biological fluids and tissues. Pharmacokinetics and pharmacodynamics of cannabinoids. Mar 06, 2012 pharmacodynamics and pharmacokinetics of synthetic cannabinoids 1. A search using electronic databases pubmed, cinahl, idis, and medline was conducted limiting date ranges to 1990november 2014. As you can see, there is a lot to learn about cannabinoids and how they interact with our bodies. Natural cannabis products and single cannabinoids are usually inhaled or taken orally. Introduction to pharmacokinetics and pharmacodynamics.

Pharmacokinetic drug interactions with tobacco, cannabinoids. Of 792 articles retireved, 24 included pharmacokinetic parameters in humans. In contrast, refers to the pharmacodynamics physiologic and biochemical effects of the drug on the body. Metabolismidentification of in vitro metabolites of jwh015, an aminoalkylindole agonist for the peripheral cannabinoid receptor cb2 by hplcmsms. Dose pharmacokinetics of oral cannabidiol following. It is wellknown that cannabinoids are highly lipophilic compounds and accumulate in fatty tissue which can then be released gradually gunasekaran et al. Pharmacokinetic and pharmacodynamic characterization of. The pharmacodynamics and pharmacokinetics of the benzodiazepines are discussed and differences which may be important in the clinical situation are stressed.

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. Sep 30, 2012 natural cannabis products and single cannabinoids are usually inhaled or taken orally. The mechanism of action of cannabinoids is best investigated for d9thc thc, dronabinol. Department of pharmacology toxicology, inserm u1173.

The cannabinoid cb1 receptor was originally discovered in the central. In the pharmacokinetic interactions, some of the plant components may improve the. Reviewthemed issue the pharmacokinetics and the pharmacodynamics of cannabinoids correspondencedr catherine j. Lucas, hunter medical research institute, locked bag, new lambton, nsw, australia, 2305.

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. S agurell, m halldin, j e lindgren, a ohlsson, m widman, h gillespie and l hollister. Aspects of the pharmacokinetics and pharmacodynamics of. 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. Both pharmacodynamics and pharmacokinetics explain the drugs effects, which is the relationship between the dose and response. The pharmacokinetics of delta9thc were computed using standard noncompartmental methods following multiple dose administration using winnonlin software version 2. 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. 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. Cannabinoids pharmacokinetics and drug analysis natural. Search terms included at least one of the following. 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. Cannabis medicines contain a wide variety of chemical compounds, including the cannabinoids delta9tetrahydrocannabinol thc, which is psychoactive, and the.

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. 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. Absorption and metabolism of tetrahydrocannabinol thc vary as a function of route of administration. Pharmacology, psychoactive agents and drug interactions ureh nena lekwauwa, m. 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. Pdf human cannabinoid pharmacokinetics marilyn huestis.

Pharmacodynamics is affected by receptor binding and sensitivity, postreceptor effects, and chemical interactions. Pharmacokinetics refers to the sum of the processes the body is conducting on the drug. Articles older than 10 years were included only if the study was not. The pharmacokinetics and the pharmacodynamics of cannabinoids. Cellular actions of cannabinoids in pain pathways 93 summary 95 chapter 9. 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. Thc is known to be extensively metabolized to a large number of compounds, even though most of the compounds are inactive 7377. 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. 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. Cannabinoids exert many effects through activation of gproteincoupled cannabinoid receptors in the brain and peripheral tissues. Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. 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. 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. Pharmacodynamics and pharmacokinetics of synthetic.

It suggests dissolving cbd in sulphuric acidacetic acid and leaving it for anywhere from 3 hours to 3 days to obtain delta9thc and delta8thc. Clinical pharmacokinetics of cannabinoids franjo grotenhermen abstract. 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. A phase 1a study eloneisenberg,miriogintz,andshlomoalmog. Sep 30, 2012 pharmacokinetics and pharmacodynamics of cannabinoids pharmacokinetics and pharmacodynamics of cannabinoids grotenhermen, franjo 20120930 00. As both thc and cbd are hepatically metabolized, the potential exists for pharmacokinetic drug interactions via inhibition or induction of enzymes or transporters. Agurell and mats halldin and j e lindgren and agneta ohlsson and m. Clinical pharmacokinetics of cannabinoids article pdf available in journal of cannabis therapeutics 31 january 2003 with 8,562 reads how we measure reads. Metabolism and pharmacokinetics of the cannabinoids. 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. Pharmacodynamic effects, pharmacokinetics, and metabolism. 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.

Synthetic cannabinoids sc interact with cb 1 and cb 2 cannabinoid receptors and elicit cannabimimetic effects similar to. The mechanism of action of cannabinoids is best investigated for. 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. Pharmacokinetics and pharmacodynamics of cannabinoids franjo grotenhermen novainstitut, hurth, germany contents abstract. The effects of cannabinoids on the pharmacokinetics of. Marijuana is the most widely used illicit drug of abuse in the world, with a.

As with thc, there is a high firstpass effect, and the feces to urine ratio of excretion is similar to other cannabinoids. 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. 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. The pharmacodynamics of cannabinoids is a complex and very deep subject. This study evaluated the safety, pharmacokinetics, and pharmacodynamics of taranabant 5, 7. Our knowledge of the pharmacodynamics of cannabinoids. Pharmacokinetics and pharmacodynamics of cannabinoids pharmacokinetics and pharmacodynamics of cannabinoids grotenhermen, franjo 20120930 00. The inal effect may be the result of either the pharmacodynamic or the pharmacokinetic interactions of.