Chronic cannabis exposure is associated with neuroadaptations within the endocannabinoid system, including reduced levels of fatty acid amide hydrolase (FAAH), the primary enzyme responsible for the degradation of anandamide. Whether repeated exposure to cannabinoid receptor agonists is associated with changes in FAAH levels in the human brain remains unknown. The present study examined the effects of repeated administration of nabilone, a synthetic cannabinoid receptor agonist, on brain FAAH levels in healthy volunteers. In this exploratory Phase IV pilot study, ten healthy adults completed two positron emission tomography scans with the FAAH radiotracer [11C]CURB: a baseline scan and a second scan following a 7-day oral nabilone regimen. Nabilone was titrated from 0.25 mg/day to a target dose of 2 mg/day. Brain FAAH levels ([11C]CURB λk3) were quantified using a two-tissue compartment model with irreversible trapping, and regional changes were assessed using repeated-measures analysis of covariance with FAAH genotype (rs324420 C > A; Pro129Thr) included as a covariate. Subjective drug effects and mood measures were assessed before and after nabilone administration. Nabilone produced subjective effects, including increased marijuana-like drug effects (p = 0.004), reductions in self-reported energy (p = 0.02) and clear-headedness (p = 0.01). No detectable mean change in FAAH was observed across brain regions following seven days of nabilone administration (p = 0.357). In this small, uncontrolled pilot study, no detectable mean change in brain FAAH was observed following seven days of nabilone administration. These findings provide preliminary evidence regarding FAAH following repeated cannabinoid receptor agonist exposure and require confirmation in larger, controlled studies. ClinicalTrials.gov Identifier: NCT05885685.
Chronic pain affects more than a quarter of adults worldwide and is frequently inadequately controlled by currently licensed analgesics. Cannabis-based medicinal products are being investigated as an additional or alternative treatment option, but the mechanisms by which different cannabis-derived molecules influence pain signalling are incompletely understood. This review summarises current understanding of the pharmacology of phytocannabinoids and terpenes at peripheral sensory neurons, with emphasis on the lesser known or minor cannabinoids and terpenes that appear to act via mechanisms distinct from those of the classical cannabinoid receptors. Cannabis sativa contains several hundred constituents, including the major cannabinoids Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), more than one hundred minor phytocannabinoids, and a comparable number of terpenes, (including terpenoids) as well. The principal cannabinoid receptors type 1 (CB1) and type 2 (CB2) are present on dorsal root ganglion (DRG) neurons and are coupled to Gi/o proteins, with downstream effects on cyclic adenosine monophosphate (cAMP), TRP channel phosphorylation and neuronal excitability. Recent in vitro work suggests that some minor cannabinoids inhibit calcium influx in nociceptive neurons through activation of inwardly rectifying potassium channels, while certain terpenes appear to inhibit such responses through activation of the Na⁺/K⁺-ATPase. Independent groups have separately attributed terpene-induced antinociception in rodent models to adenosine A₂A receptor activation and to CB2 receptor agonism, indicating that more than one mechanism is likely to be relevant. Clinical translation has been limited by the lack of consistent, clinically significant and high-quality data supporting the use of standardised cannabinoid treatments over placebo for chronic pain in clinical trials. Multiple cannabis-derived molecules influence nociceptive signalling through receptors and pathways that extend beyond the classical CB1/CB2 axis. THC acts principally as a partial agonist at CB1 and CB2 receptors, whereas CBD, minor cannabinoids and terpenes exhibit more complex and incompletely characterised pharmacology. The mechanistic diversity of these constituents provides a biological rationale for studying full-spectrum preparations, but the clinical magnitude of any synergy between cannabinoids and terpenes remains to be established in head-to-head randomised comparisons All data discussed in this review are available from previously published studies, which are cited throughout the manuscript. No primary research results or new datasets were generated.
Cannabis sativa trichomes produce hundreds of therapeutic compounds. However, progress in understanding trichome function and chemistry has been hindered by the absence of a unified and consistently applied trichome nomenclature, as well as by limited characterization of trichome diversity, organ-specific distribution, and their relationship to organ chemotype. In this study, we examined the trichome features of different organs in unfertilized female plants of the medical cannabis cultivar ‘NB120’ using light and electron microscopy, energy-dispersive X-ray spectroscopy (EDX) to assess trichome biomineralization, and chemical analyses of THC and CBD content. All investigated organs exhibited defensive pointed non-glandular trichomes and several types of glandular trichomes. Vegetative fan leaves additionally displayed cystolithic trichomes on the upper leaf side, and completely lacked long-stalked glandular trichomes. The flowers and the margins of inflorescence leaves were densely covered with long-stalked glandular trichomes. THC and CBD concentrations were highest in the flowers, about 50
Consumer- and patient-facing cannabis products are commonly labeled “indica,” “sativa,” or “hybrid” to signal expected composition or effects. We systematically reviewed whether these labels predict cannabis composition, animal effects, or human outcomes. We last searched PubMed/MEDLINE, Europe PMC, PubPsych, OpenAlex, and ClinicalTrials.gov, supplemented by Elicit coverage checking and citation searching; records were then screened for peer-reviewed empirical reports published from June 1, 2011, through June 1, 2026. Eligible reports directly compared consumer-facing indica, sativa, or hybrid labels, or included such labels in statistical/model-based analyses. Methodological concern and evidence directness were appraised using stream-specific domains. Twenty-eight peer-reviewed reports were included: 12 plant/product-database/composition reports, one animal marketed-preparation report, and 15 human treatment, symptom-relief, or proximal-outcome reports. Plant/product reports showed limited concordance between labels and genetic structure or major cannabinoid profiles. Terpene findings were compound-specific and inconsistent, with some label-associated signals but no stable label-to-terpene rule. The animal report described preparation-specific cognitive-effort differences between two oils marketed as indica or sativa. Across human reports, label associations with symptom relief, subjective effects, behavioral or neurophysiological outcomes, and side effects were inconsistent. Significant associations were reported for selected outcomes, including insomnia relief and low-arousal effects, but adjustment for delta-9-tetrahydrocannabinol (THC) content and other potential confounders varied. Comparisons without THC adjustment could not establish whether label-associated outcome differences were independent of differences in product potency. The evidence does not support using indica, sativa, and hybrid labels as reliable guides to cannabis composition or therapeutic effects. More defensible descriptors include measured chemistry, product form, route, dose, and patient-specific safety considerations. Current terpene-effect evidence remains preliminary and does not justify terpene-based or label-based prescribing rules. Open Science Framework DOI: https://doi.org/10.17605/OSF.IO/W6PUX
The commercial availability of cannabidiol (CBD)-based products has increased exponentially, often without adequate regulation, raising concerns about product integrity and consumer safety. The analgesic and anxiolytic properties of CBD occur via the endocannabinoid system, which is also active in the skin, where CBD acts directly on sebum-producing sebocytes. Sebum has shown potential as a non-invasive diagnostic tool for diseases, but its applicability for cannabinoid monitoring remains unexplored. This study aimed to develop and validate an analytical method for the quantification of six cannabinoids in commercial products and to explore its application to human sebum samples. Eight over-the-counter (OTC) products, including oils, tablets, gummies and teas, obtained from the UK market were analysed to quantify cannabidiol (CBD), ∆9-tetrahydrocannabinol (THC), cannabidiolic acid (CBDA) and ∆9-tetrahydrocannabinolic acid (THCA) by liquid chromatography-mass spectrometry (LC-MS/MS). Matrix effects were accounted for by using either an internal standard (IS) or a standard addition approach. Sebum samples from the forehead of participants (n = 10) following single dose oral or sublingual CBD consumption were analysed to detect CBD, THC, 7-carboxy-cannabidiol (7-COOH-CBD) and 11-nor-9-carboxy-∆9-tetrahydrocannabinol (11-COOH-THC). Validation parameters of the six cannabinoids included linearity with R² > 0.99, limits of detection of 0.02–0.34 ng/mL, limits of quantification of 0.07–1.2 ng/mL, recoveries between 82.9
