Cannabinoids are a psychoactive compound found in Cannabis sativa. The THC is one of the 64 different cannabinoids found in the plant; and the degree of impairment caused by the drug is dependent on its concentration in the plasma. Yet, the associated peak plasma concentration for achieving desired symptoms of marijuana has no clear demarcation from its noxious effects.
Various factors affect the associated peak plasma of a human cell after the intake of marijuana. These are the route of exposure, the strength of cannabinoids, the smoking method (when smoked), and the dose consumed. Clinical toxicological analysis of cannabinoids helps determine drug safety and concentration levels that can be considered safe and medically appropriate.
In an acute real-time setting, blood helps in correlating symptoms with drug concentration. The blood specimen collection suits:
- Patient on dialysis/those producing dilute urine
- Correlating dose or symptom with drug concentration
- Malabsorption cases (ex- gastric bypass)
- Evaluation aspects of pharmacokinetics.
Performing single-dose toxicity studies before performing regulated repeated dose toxicity studies is common. Dose range finding (DRF) and MTD (maximum tolerated dose) studies run parallel. These help in determining dosing margins. Acute toxicity of the drugs is performed with repeated dose toxicity. It determines the dose accumulation process on the first and last day of dosing. The results aid in designing non-GLP study dosing for 28 days at least.
TK analysis data interpret the dose-exposure relationship for cannabinoids generated during studies. It helps in understanding whether an increased dose results in saturable metabolism. Toxicology studies in drug development also determine whether multiple doses cause accumulation.
The THC is known to be very lipophilic, and on absorption, it distributes in the body, particularly to the CNS, liver, lungs, and adipose tissues. Generally, THC is metabolized into an active metabolite, 11-OH-THC. This is then metabolized into 11-COOH-THC1. It is a more persistent and non-active metabolite. Researchers use the metabolite for confirming cannabinoids in blood.
Further, IND enabling studies and evaluation of cannabinoids are performed. These assess pulmonary, cardia, reproductive health effects & the drug’s potential for mutations, and carcinogenicity.
The toxicokinetic analysis determines systemic exposure, metabolic imitation of cannabinoids. The non-GLP toxicology study of these TK parameters helps in deciding the correct drug dosage. It also helps in understanding systemic toxicity. The non-GLP studies also include discovery bioanalysis, drug range-finding toxicity, DMPK, plasma protein binding of the cannabinoid.
Clinical toxicological studies of cannabinoids in the blood facilitate:
- Therapeutic drug monitoring
- Trace element toxicity
- Drug testing
- Emergency toxicology.
Further, Cannabidiol usage can result in positive THC results, if pure. Quantitative urine THC metabolite testing helps to interpret an unexpected positive cannabis IA.
As many challenges are there with pose clinical toxicological analysis of drugs in blood, non-GLP research and development help in target identification and validation. It also aids assay development and lead optimization. It also ensures safe and effective therapy. Monitoring for abstinence from non-prescribed drugs can be established through toxicological analysis or studies.
These become the basis of many research projects carried out by pharma companies and drug research laboratories.