Δ[9]-Tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, has been reported to modulate immune responses; however, its effects on complex innate immune signaling pathways and inflammation remain incompletely understood. Here, we investigated the immunomodulatory effects of THC on lipopolysaccharide (LPS)-induced inflammation across cellular and in vivo models.

Neuropathic pain, characterized by dysfunction in the somatosensory system, is prevalent among palliative care patients, often resulting from conditions such as cancer, neurodegenerative diseases, and diabetes. Effective management of neuropathic pain is crucial for enhancing patient comfort and quality of life. This review explores the efficacy of dronabinol, a synthetic delta-9-tetrahydrocannabinol (THC), in managing neuropathic pain in palliative care. A comprehensive review of neuropathic pain mechanisms, treatment options, and the role of the endocannabinoid system was conducted. Clinical evidence supporting use of dronabinol for neuropathic pain was analyzed, including its pharmacological action, safety profile, and potential advantages over traditional analgesics. Dronabinol modulates pain pathways through CB1/CB2 receptor activation, reducing nociceptive transmission and neuroinflammation. Clinical studies indicate that dronabinol provides modest analgesic effects, improves associated symptoms such as nausea and sleep disturbances, and exhibits opioid-sparing potential. Dronabinol may represent a potential therapeutic option for neuropathic pain in palliative care. Its reported multimodal effects, generally favorable safety profile, and possible role in reducing opioid requirements should be considered potential advantages; however, these findings are supported by limited and heterogeneous evidence. Further research is needed to better define optimal dosing, assess long-term safety, and compare its efficacy with established treatments for neuropathic pain.

Adolescent cannabis exposure has been associated with an increased risk of schizophrenia; however, how genetic vulnerability shapes the long-term consequences of adolescent cannabinoid exposure remains poorly understood. Δ[9]-Tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis and the predominant cannabinoid in the THC-rich cannabis extract used here, primarily activates cannabinoid type 1 receptors (CB1). In parallel, reduced availability of D-serine, an endogenous co-agonist of N-methyl-D-aspartate receptors (NMDARs), has been implicated in the pathophysiology of schizophrenia. Here, we investigated whether adolescent exposure to a THC-rich cannabis extract modulated long-term behavioral, neurochemical, and glial outcomes in serine racemase mutant (SrrY269*) mice, a genetic model characterized by reduced D-serine levels and schizophrenia-relevant phenotypes. Mice received escalating oral doses of the THC-rich cannabis extract during adolescence and were evaluated in adulthood using behavioral assays, amino acid quantification, and glial morphometric analyses. Adolescent exposure to the THC-rich cannabis extract prevented deficits in prepulse inhibition and spatial object recognition memory in adult SrrY269* mice, while transiently impairing sensorimotor gating in wild-type animals. Irrespective of genotype, mice exposed to the THC-rich cannabis extract spent more time in the center of the open field in adulthood. In behaviorally tested SrrY269* mice, reduced hippocampal microglial branching was attenuated following adolescent treatment. In an independent behavior-naïve cohort, SrrY269* mice exhibited marked astrocytic morphological alterations, several of which were also attenuated by adolescent exposure to the THC-rich cannabis extract. In contrast, the same treatment induced a distinct astrocytic phenotype in wild-type mice. Adolescent exposure to the THC-rich cannabis extract did not alter hippocampal or prefrontal cortical levels of D-serine or other amino acids involved in NMDAR signaling in adulthood. These findings indicate that adolescent exposure to a THC-rich cannabis extract produces genotype-dependent long-term effects, preventing specific behavioral deficits and attenuating independently assessed microglial and astrocytic alterations in SrrY269* mice, while producing adverse behavioral and astrocytic outcomes in wild-type animals. Genetic background may therefore be an important determinant of the long-term neurodevelopmental consequences of adolescent exposure to THC-rich cannabis extracts.

While oral fluid (OF) is increasingly used in forensic and roadside toxicology, measured drug concentrations remain highly dependent on pre-analytical conditions. This study investigated the impact of buccal-cell content and sample fractionation on concentrations of delta 9-tetrahydrocannabinol (THC), cocaine, benzoylecgonine (BZE), and ecgonine methyl ester (EME). Oral-fluid specimens were collected using FLOQSwabs®. Following elution, sonication, and vortex mixing, various fractions (homogenate, pellet, and expressed swab) were analyzed via liquid chromatography-tandem mass spectrometry. For THC (n = 102), median buccal epithelial cell counts and THC concentrations were significantly higher in the cell-rich pellet than in the homogenate (P < .001), with median enrichment ratios of 4.40 and 3.93, respectively. The association between cellular and THC enrichment was strong to very strong (r = 0.77-0.88) for concentrations above 5 ng/mL. Notably, four specimens were below the limit of detection in the homogenate but detectable in the pellet. In contrast, cocaine and its metabolites showed comparable concentrations between the homogenate and pellet, though the expressed swab fraction consistently yielded the highest levels. In 52 specimens, median expressed swab-to-homogenate ratios were 1.16 for cocaine, 1.28 for BZE, and 1.14 for EME. These findings demonstrate that pre-analytical effects are analyte-dependent: buccal cells act as a reservoir for THC, whereas cocaine-related analytes are primarily affected by incomplete release from the swab. These results identify analyte-dependent pre-analytical sources of variability that may affect oral-fluid concentration measurements obtained with this collection device.

Opioid use disorder (OUD) remains a major public health crisis despite evidence-based medications, including methadone, buprenorphine, and naltrexone. Persistent challenges with treatment retention, access, stigma, and incomplete response highlight the need for adjunctive pharmacotherapies targeting neurobiological systems beyond the mu-opioid receptor.

Cancer remains a highly complex and heterogeneous disease, causing major morbidity and mortality worldwide despite advances in diagnosis and treatment. The hallmarks of cancer enlighten the biological mechanisms supporting tumourigenesis and malignant evolution, while helping to identify potential therapeutic targets. Medical cannabis has mostly been used in oncology for supportive care, but increasing preclinical evidence suggests interference with cancer-related signalling pathways. This narrative review summarizes the current evidence on cannabinoids, in particular the phytocannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), framing their prospective anticancer effects in the hallmarks of cancer. Preclinical studies imply that CBD exerts antiproliferative effects by modulating oncogenic signalling pathways, including EGFR, PI3K/AKT, RAS/RAF/ERK, mTOR and Wnt/β-catenin, while also influencing tumour suppressor pathways involving p53, p21 and p27, causing cell cycle arrest. CBD has additionally been shown to promote programmed cell death via mitochondrial dysfunction and autophagy, altering cancer metabolism as well. Furthermore, CBD has shown anti-invasive and antiangiogenic properties and also appears to modulate immune responses and interactions with the tumour microenvironment, including emerging links with the microbiome. Overall, cannabinoids exhibit biologically plausible antitumour activity across multiple cancer hallmarks and may present promising candidates for combination therapeutic strategies. Nonetheless, the current evidence remains predominantly preclinical, and robust translational studies and clinical trials are needed to clarify their pharmacokinetic and pharmacodynamic profiles, determine their clinical efficacy and safety while assessing their potential integration into multimodal cancer treatment.

Oxycodone is commonly prescribed for moderate-to-severe pain. While efficacious, long-term use can result in tolerance, physical dependence, and opioid use disorder. Cannabis and Δ[9]-tetrahydrocannabinol (Δ[9]-THC) have been reported to potentiate oxycodone-induced antinociception in animals and humans. Whether Δ[9]-THC also facilitates unwanted aspects of oxycodone intake, such as tolerance, dependence, and reward at antinociceptive doses, remains unclear. We evaluated the coadministration of Δ[9]-THC and oxycodone on antinociception, dependence, circadian activity, and reward in male and female mice. Oxycodone and Δ[9]-THC produced dose-dependent antinociception in the hotplate assay, with oxycodone showing lower potency in females. Repeated treatment (twice daily for 5 days) produced antinociceptive tolerance. Δ[9]-THC produced a potentiation-like effect on oxycodone-induced antinociception and delayed antinociceptive tolerance. Repeated oxycodone produced physical dependence and alterations in circadian activity, neither of which was exacerbated by cotreatment with Δ[9]-THC. Combination treatment of oxycodone and Δ[9]-THC produced conditioned place preference at doses that did not produce preference when administered alone. Fiber photometry recordings of nucleus accumbens dopamine release showed that Δ[9]-THC potentiated oxycodone-evoked dopamine release at subeffective oxycodone doses, a candidate mechanism for the behavioral reward potentiation. These data indicate that Δ[9]-THC may facilitate oxycodone-induced antinociception without augmenting certain unwanted features of opioid intake (eg, dependence and circadian rhythm alterations). However, Δ[9]-THC also recruited the rewarding properties of oxycodone at therapeutically relevant doses. These reward-related findings indicate that Δ[9]-THC and oxycodone combinations may carry increased abuse liability, a primary consideration for their therapeutic evaluation. SIGNIFICANCE STATEMENT: In mice, Δ[9]-tetrahydrocannabinol (Δ[9]-THC) produced a potentiation-like effect on oxycodone-induced antinociception and delayed antinociceptive tolerance without exacerbating opioid dependence or circadian disruption, but Δ[9]-THC also produced conditioned place preference and potentiated nucleus accumbens dopamine release at subeffective oxycodone doses. These findings indicate that Δ[9]-THC may enhance oxycodone-induced antinociception, but also that Δ[9]-THC recruits the rewarding properties of oxycodone at doses that are otherwise subeffective. The increased abuse liability of such combinations is a primary consideration for their therapeutic evaluation.

Acute cannabis use and its primary psychoactive constituent tetrahydrocannabinol (THC) can induce postural dizziness, indicating increased risk of orthostatic instability. However, it is unknown if vulnerabilities persist the morning after bedtime THC consumption. This study investigated the influence of bedtime THC consumption on cardiovascular variables during an orthostatic challenge. Nine individuals with no cannabis use and eight individuals who regularly use cannabis participated in a tilt table test associated with a 3-day in-laboratory stay. Participants underwent an acclimatization day, followed by a placebo dosing day, and a 10 mg THC dosing day. Placebo and THC pills were given 1 h before a participant's habitual bedtime, and the tilt table test was performed ~1 h upon awakening. Participants were instrumented with an electrocardiogram and an automated sphygmomanometer. Fluid intake and output were measured throughout the study. The morning after THC administration, individuals with no cannabis use reported a higher frequency of dizziness and exhibited a significant reduction in both diastolic blood pressure and heart rate reactivity to tilt (reactivity = tilt - baseline) compared to the morning after placebo. Our results indicate a potential increased risk for orthostatic instability the morning after cannabis consumption in individuals with no cannabis use history.

Driving under the influence of cannabis is a significant public safety issue. Tetrahydrocannabinol (THC), the main psychoactive compound in cannabis, can impair driving ability and when used in combination with alcohol, the level of impairment can increase. Case studies documenting blood concentrations of THC and associated observations of impairment in individuals suspected of impaired driving continue to provide important contributions to the scientific literature. Retrospective analysis was performed using data from impaired driving investigations in which THC alone, and in combination with alcohol, were the only findings in blood samples submitted to the Centre of Forensic Sciences between 2021 and 2023, inclusive. In cases where only THC was present, blood concentrations ranged from 1.1 to 72 ng/mL (mean 12 ng/mL, median 9.5 ng/mL). When both THC and alcohol were present, the mean blood THC concentration was 13 ng/mL, and the mean blood alcohol concentration was 145 mg/100 mL. The most common driving and drug recognition expert (DRE) observations included collisions, erratic driving, eyelid tremors, poor balance and coordination, and bloodshot eyes. Observations of driving impairment were more frequently observed in cases where both THC and alcohol were detected in the blood. These findings provide additional data to inform the interpretation of blood THC concentrations in the context of DRE observations and suspected impaired driving investigations.