Pharmacokinetics and Pharmacodynamics of Cannabinoids

  title={Pharmacokinetics and Pharmacodynamics of Cannabinoids},
  author={Franjo Grotenhermen},
  journal={Clinical Pharmacokinetics},
AbstractΔ9-Tetrahydrocannabinol (THC) is the main source of the pharmacological effects caused by the consumption of cannabis, both the marijuana-like action and the medicinal benefits of the plant. However, its acid metabolite THC-COOH, the non-psychotropic cannabidiol (CBD), several cannabinoid analogues and newly discovered modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoids exert many effects through… 

Pharmacology of cannabinoids.

There is evidence that besides the two cannabinoid receptor subtypes cloned so far additional cannabinoid receptorSubtypes and vanilloid receptors are involved in the complex physiological functions of the cannabinoid system that include motor coordination, memory procession, control of appetite, pain modulation and neuroprotection.

The pharmacokinetics and the pharmacodynamics of cannabinoids.

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.

Pharmacokinetics of cannabinoids.

Clinical trials have found that nabilone produces less tachycardia and less euphoria than THC for a similar antiemetic response, and the pharmacokinetic-pharmacodynamic modelling with plasma THC versus cardiac and psychotropic effects show that after equilibrium is reached, the intensity of effect is proportional to the plasma THC profile.

Mechanisms of Action and Pharmacokinetics of Cannabis.

Cannabinoids produce more than 100 naturally occurring chemicals, the most abundant of which are Δ-9-tetrahydrocannabinol, cannabidiol (CBD), terpenes, and flavonoids, which are present in the brain and many organs.

REVIEW-THEMED ISSUE The pharmacokinetics and the pharmacodynamics of cannabinoids

The pharmacokinetics of cannabinoids and the effects observed depend on the formulation and route of administration, which should be tailored to individual patient requirements.

Human Cannabinoid Pharmacokinetics

  • M. Huestis
  • Biology, Chemistry
    Chemistry & biodiversity
  • 2007
The cardiovascular and subjective effects of cannabis are blocked by rimonabant, the first CB-1 cannabinoid-receptor antagonist, documenting thatCB-1 receptors mediate these effects of smoked cannabis in humans.

Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol.

  • M. Huestis
  • Biology, Chemistry
    Handbook of experimental pharmacology
  • 2005
Cannabinoid pharmacokinetic research has been especially challenging due to low analyte concentrations, rapid and extensive metabolism, and physicochemical characteristics that hinder the separation of drugs of interest from biological matrices and lower drug recovery due to adsorption of compounds of interest to multiple surfaces.

Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy

Preliminary results from a recently completed controlled trial indicate that efficacy of CBD extends to the treatment of seizures associated with the tuberous sclerosis complex and to precipitation of some adverse effects, particularly somnolence.

The Endocannabinoid System and Synthetic Cannabinoids in Preclinical Models of Seizure and Epilepsy.

This research demonstrates that many SCs do reduce seizure severity in rodent models and may have both positive and negative pharmacodynamic and pharmacokinetic interactions with clinically used antiepilepsy drugs.



Cannabis: pharmacology and toxicology in animals and humans.

The advent of highly potent analogs and a specific antagonist may make possible the development of compounds that lack undesirable side effects, thus limiting therapeutic usefulness of cannabinoid-derived drugs on the market today.

Physiological and Pharmacological Interactions of Marihuana (THC) with Drugs and Anesthetics

The existing data indicate that marhuana or THC is not an acceptable adjunct to anesthesia, and preoperative marihuana smoking exacerbates perioperative tachycardia.

Cardiovascular actions of cannabinoids and their generation during shock

Recent studies indicate that a peripheral endogenous cannabinoid system in circulating macrophages and platelets is activated in hemorrhagic and septic shock and may contribute to the hypotension associated with these conditions via activation of vascular cannabinoid receptors.

Effect of cannabidiol pretreatment on the kinetics of tetrahydrocannabinol metabolites in mouse brain.

CBD pretreatment resulted in large increases in AUC and t1/2 of all THC metabolites in brain, with a modest increase in A UC of THC.

Cannabinoid pharmacology.

  • W. Dewey
  • Biology, Medicine
    Pharmacological reviews
  • 1986

Interactions of Marihuana and THC with Other Drugs

Although medical marihuana is not officially approved, it has been tried empirically for treating a variety of medical disorders, such as nausea and vomiting associated with cancer chemotherapy, wasting syndrome associated with AIDS, and spasticity from neurological diseases.

The Cannabinoids as Potential Antiepileptics

The anticonvulsant nature of cannabidiol suggests that it has a therapeutic potential in at least three of the four major types of epilepsy: grand mal, cortical focal, and complex partial seizures.

Evidence that cannabidiol does not significantly alter the pharmacokinetics of tetrahydrocannabinol in man

The pharmacokinetics of Δ9-tetrahydrocannabinol administered intravenously was evaluated in four subjects after oral administration of placebo and 1500 mg of cannabidiol (CBD) according to a crossover design, and there may have been minimal effect on the formation and excretion of metabolites.

Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716.

These findings confirm, for the first time in humans, the central role of CB1 receptors in mediating the effects of marijuana.