Cannabinoid Disposition After Human Intraperitoneal Use: An Insight Into Intraperitoneal Pharmacokinetic Properties in Metastatic Cancer

Lucas, Catherine; Galettis, Peter; Song, Shuzhen; Solowij, Nadia; Reuter, Stephanie E; Schneider, Jennifer; Martin, Jennifer

doi:10.1016/j.clinthera.2017.12.008

Cited by 17 publications

(10 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Different routes of administration and dosing formulations give rise to a varied bioavailability of constituent compounds. Specifically, it is well established that cannabinoids are absorbed differently and have variable effects, dependent upon whether cannabis is inhaled or ingested . It logically follows that the bioavailability of contaminants may be contingent on the administration route with the pyrolytic effect of heating contaminants an important issue.…”

Section: Resultsmentioning

confidence: 99%

Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects

Dryburgh

Bolan

Grof

et al. 2018

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

There has been a resurgence in interest and use of the cannabis plant for medical purposes. However, an in-depth understanding of plant contaminants and toxin effects on stability of plant compounds and human bioavailability is needed. This systematic review aims to assess current understanding of the contaminants of cannabis and their effect on human health, leading to the identification of knowledge gaps for future investigation. A systematic search of seven indexed biological and biomedical databases and the Cochrane library was undertaken from inception up to December 2017. A qualitative synthesis of filtered results was undertaken after independent assessment for eligibility by two reviewers. The common cannabis contaminants include microbes, heavy metals and pesticides. Their direct human toxicity is poorly quantified but include infection, carcinogenicity, reproductive and developmental impacts. Cannabis dosing formulations and administration routes affect the transformation and bioavailability of contaminants. There may be important pharmacokinetic interactions between the alkaloid active ingredients of cannabis (i.e. phytocannabinoids) and contaminants but these are not yet identified nor quantified. There is significant paucity in the literature describing the prevalence and human impact of cannabis contaminants. Advances in the availability of cannabis globally warrant further research in this area, particularly when being used for patients.

show abstract

Section: Resultsmentioning

confidence: 99%

Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects

Dryburgh

Bolan

Grof

et al. 2018

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

show abstract

“…lung, heart, brain, liver) , with subsequent equilibration into less vascularized tissue . Distribution may be affected by body size and composition, and disease states influencing the permeability of blood–tissue barriers .…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…Estimates of the elimination half‐life of THC vary . A population pharmacokinetic model has described a fast initial half‐life (approximately 6 min) and long terminal half‐life (22 h) , the latter influenced by equilibration between lipid storage compartments and the blood .…”

Section: Pharmacokineticsmentioning

confidence: 99%

The pharmacokinetics and the pharmacodynamics of cannabinoids

Lucas

Galettis

Schneider

2018

Brit J Clinical Pharma

Self Cite

520

512

View full text Add to dashboard Cite

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. Cannabis medicines contain a wide variety of chemical compounds, including the cannabinoids delta-9-tetrahydrocannabinol (THC), which is psychoactive, and the nonpsychoactive cannabidiol (CBD). Cannabis use is associated with both pathological and behavioural toxicity and, accordingly, is contraindicated in the context of significant psychiatric, cardiovascular, renal or hepatic illness. The pharmacokinetics of cannabinoids and the effects observed depend on the formulation and route of administration, which should be tailored to individual patient requirements. As both THC and CBD are hepatically metabolized, the potential exists for pharmacokinetic drug interactions via inhibition or induction of enzymes or transporters. An important example is the CBD-mediated inhibition of clobazam metabolism. Pharmacodynamic interactions may occur if cannabis is administered with other central nervous system depressant drugs, and cardiac toxicity may occur via additive hypertension and tachycardia with sympathomimetic agents. More vulnerable populations, such as older patients, may benefit from the potential symptomatic and palliative benefits of cannabinoids but are at increased risk of adverse effects. The limited availability of applicable pharmacokinetic and pharmacodynamic information highlights the need to initiate prescribing cannabis medicines using a 'start low and go slow' approach, carefully observing the patient for desired and adverse effects. Further clinical studies in the actual patient populations for whom prescribing may be considered are needed, to derive a better understanding of these drugs and enhance safe and optimal prescribing.

show abstract

“…After reaching a peak (125-150 ng/ml) within minutes of inhalation, THC concentrations decline rapidly to approximately 10-20 ng/ml within 60-90 minutes (mostly via redistribution), followed by a much slower elimination phase, with a half-life of approximately 24 hours [15][16][17]. In addition, THC is sequestered in body fat and there is the potential for redistribution from fat back to the bloodstream [18]. The pharmacokinetics of orally administered THC are signifi cantly different from smoked marijuana, with a much lower peak concentration (5-10 ng/ml for 20 mg oral) and a later onset to peak concentration of 1-2 hours [16,17,19].…”

Section: Introductionmentioning

confidence: 99%

Marijuana and alcohol increase crash avoidance reaction time in a driving simulator test at blood concentrations below commonly-used per se ‘Cut-offs’ for Intoxication

Alali¹,

Stewart²,

Taneja³

et al. 2020

J Addict Med Ther Sci

View full text Add to dashboard Cite

The present study demonstrates marijuana-and alcohol-induced impairment of a driving-relevant measure in a driving simulator task at (estimated) blood alcohol and THC concentrations that are below the per se cutoff for impaired driving in several states. The subject was an adult male with a history of occasional alcohol use (2-3 times/week for the past 6 months) and past but very infrequent use of marijuana, i.e., less than once/month for the past 6 months. The testing procedure was a crash avoidance test using a fi xed base driving simulator. In this procedure, while driving at 55 mph, the subject was required to make an 'emergency' steering maneuver to avoid crashing into a 'stalled car' that appeared on the roadway immediately (40 meters) ahead. In the absence of any drug treatment, after training the subject effectively made this avoidance maneuver in >98% of trials (20 trials/session), with a crash avoidance response latency of approximately 450-475 msec from the onset of the car ahead until an abrupt crash avoidance steering response of >10 degrees. On two test days separated by 14 days, the subject was tested for crash avoidance reaction time following oral alcohol (beer consumption) use and, on another occasion, following oral marijuana use (approximately 10 mg in a 'candy'). The testing involved a predrug test and several post-treatment tests, and one fi nal post-treatment test 24 hours later. On both test days, blood samples were collected at various times after drug administration and throughout behavioral testing. Both alcohol and marijuana treatment signifi cantly increased crash avoidance reaction time (from approximately 475 msec to > 550 msec). Plasma alcohol concentrations of 42 mg/dl, 79 mg/dl and up to 99 mg/dl (corresponding to BAC values of 39, 67 and 86 mg/dl, respectively) were associated with alcohol impaired driving over the time period from 45 minutes to 175 minutes after the onset of drinking. On the marijuana test day, plasma concentrations of THC were 4.7 and 2.4 ng/ml (corresponding to blood THC concentrations of 2.9 and 1.5 ng/ml, respectively) at times when signifi cant impairment of driving was observed. This is the fi rst study to demonstrate dramatic driving simulator performance impairment at a THC blood concentration less than 3 ng/ml, which is the below the 5 ng/ml cutoff for marijuana-impaired driving in several states (e.g., Washington, Colorado). These data further suggest that the crash avoidance reaction task might be useful in further studies on the effects of marijuana, alcohol and other drugs (prescription, non-prescription and also drugs of abuse) on driving performance.

show abstract

Cannabinoid Disposition After Human Intraperitoneal Use: An Insight Into Intraperitoneal Pharmacokinetic Properties in Metastatic Cancer

Cited by 17 publications

References 14 publications

Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects

Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects

The pharmacokinetics and the pharmacodynamics of cannabinoids

Marijuana and alcohol increase crash avoidance reaction time in a driving simulator test at blood concentrations below commonly-used per se ‘Cut-offs’ for Intoxication

Contact Info

Product

Resources

About