The pharmacokinetics and the pharmacodynamics of cannabinoids
Open accessAbstract
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 ʻstart low and go slowʼ 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.
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The primary psychoactive effects of cannabis are thought to be mediated by delta-9-tetrahydrocannabinol, while some nonpsychoactive effects may be mediated by cannabidiol and other minor cannabinoids and terpenes.
“The primary psychoactive effects of cannabis are thought to be mediated by delta-9-tetrahydrocannabinol (THC), while some nonpsychoactive effects may be mediated by cannabidiol (CBD) and other minor cannabinoids and terpenes [106].”
From Consequences of adolescent drug use (2023) · cites this paper as [106]
The paper’s introductory discussion (page not provided) identifies THC as the primary psychoactive cannabinoid and CBD as nonpsychoactive, with several reported therapeutic properties. Our copy does not attribute nonpsychoactive effects to minor cannabinoids or terpenes, so that part of the sentence is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAdditive effects can occur when cannabinoids are combined with sympathomimetics (e.g., tachycardia, hypertension), central nervous system depressants such as alcohol and opioids (e.g., drowsiness, ataxia), and anticholinergics (e.g., tachycardia, confusion).
“Additive effects can occur when cannabinoids are combined with sympathomimetics (e.g., tachycardia, hypertension), central nervous system depressants such as alcohol and opioids (e.g., drowsiness, ataxia), and anticholinergics (e.g., tachycardia, confusion).115”
From Clinical Practice Guidelines for Cannabis and Cannabinoid-Based Medicines in the Management of Chronic Pain and Co-Occurring Conditions (2024) · cites this paper as [115]
The Pharmacodynamics section (page unavailable) describes additive hypertension and tachycardia with sympathomimetics and atropine, and potentiated central effects with CNS depressants. It also reports an interaction with ethanol. It does not specifically describe opioid combinations, ataxia, or confusion from combining cannabinoids with anticholinergics. (LLM, conf=0.86)
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- Authors
- Lucas, C. J., Galettis, P., & Schneider, J.
- Affiliations
- Hunter Medical Research Institute (AU)
- Corresponding author
- Lucas, Catherine J.
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2018-08-07
- Volume
- 84
- Issue
- 11
- Pages
- 2477-2482
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC6177698
- OpenAlex
- W2852302757
- Cited by
- 724
- References
- 74
- Citations by year
- 2026: 85 · 2025: 104 · 2024: 112 · 2023: 126 · 2022: 111 · 2021: 76 · 2020: 66 · 2019: 37 · 2018: 7
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
- Keywords
- cannabinoids, pharmacokinetics, pharmacodynamics, delta-9-tetrahydrocannabinol, cannabidiol, medical cannabis, drug interactions, clobazam, hepatic metabolism, route of administration, central nervous system depressants, cardiotoxicity, elderly patients, symptom management
- MeSH terms
- Cannabidiol, Cannabinoids, Cannabis, Drug Interactions, Humans, Dronabinol
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