“Medicinal cannabis has been trialled for Tourette syndrome in adults, but it has not been studied in adolescents. This open-label, single-arm trial study evaluated the feasibility, acceptability and signal of efficacy of medicinal cannabis in adolescents (12-18 years), using a Δ9-tetrahydrocannabinol:cannabidiol ratio of 10:15, with dose varying from 5 to 20 mg/day based on body weight and response.
The study demonstrated feasibility of recruitment, acceptability of study procedures, potential benefits and a favourable safety profile, with no serious adverse events. Commonly reported adverse events were tiredness and drowsiness, followed by dry mouth.
Statistically significant improvement was observed in parent and clinician reports on tics (paired t-test P = 0.003), and behavioural and emotional issues (paired t-test P = 0.048) and quality of life as reported by the parent and young person (paired t-test P = 0.027 and 0.032, respectively). A larger-scale, randomised controlled trial is needed to validate these findings.”
“Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, with an estimated prevalence of 10%–15%.1 In addition to its reproductive features, that is, hyperandrogenism, anovulation, and polycystic ovarian morphology, PCOS is strongly associated with metabolic disturbances, including obesity, insulin resistance and an elevated risk of metabolic associated steatotic liver disease (MASLD).1 These complications not only worsen the quality of life but also increase long-term morbidity and mortality of women living with PCOS. The coexistence of these metabolic traits complicates clinical management and increases the risk of developing type-2 diabetes and cardiovascular diseases.
Lifestyle modifications are considered first-line interventions in PCOS, but they frequently fail to achieve sustained weight loss or ideal metabolic control, particularly in patients with pronounced hormonal perturbations (e.g., persistent hyperandrogenism) or psychological distress. Pharmacological approaches, such as metformin and GLP-1 receptor agonists, are currently used to handle metabolic complications, but they have limitations regarding efficacy, tolerability and/or accessibility, and are not universally approved for management of PCOS. Moreover, these treatments might overlook the inflammatory and fibrotic dimensions of PCOS, which are increasingly recognized as central contributors to its pathogenesis.
Cannabidiol (CBD), a non-psychotropic phytocannabinoid from Cannabis sativa,5 has garnered attention due to its anti-inflammatory, antioxidant and metabolic regulatory properties. Preclinical studies suggest that CBD acts as a negative allosteric modulator of the cannabinoid CB1 receptor (CB1R),6 and engages additional targets, such as PPARγ7 and the Nrf2 signalling pathway.8 Given these pleiotropic actions, CBD represents an attractive candidate for addressing the complex metabolic profile of PCOS. In this study, we evaluated the metabolic and hepatic effects, including proteomic profiles, of CBD in a validated murine model of PCOS associated with androgenic obesity (AO),9 aiming to provide insights into its therapeutic potential and underlying mechanisms of action.”
“This study provides compelling preclinical evidence that CBD exerts broad metabolic benefits in a murine model of PCOS with androgenic obesity. Treatment with CBD led to significant reductions in weight gain, adiposity, insulin resistance, indices of hepatic fibrosis and systemic inflammation, with prominent favourable actions on MASLD traits. Liver proteomic and circulating biomarker analyses strongly supported the reprogramming of disease-associated molecular pathways caused by CBD, underscoring its potential to mitigate the multifactorial pathophysiology of PCOS.”
“Rett Syndrome (RTT, #312750 – OMIM) is a rare, progressive neurodevelopmental X-linked disorder, caused mostly by mutations in the gene for the methyl CpG binding protein 2 (MECP2). MECP2 is a transcriptional and epigenetic regulator that has been proposed to modulate neuronal development and adult neurogenesis, processes disrupted in both RTT patients and mouse models.
Cannabidivarin (CBDV), a non-psychotropic cannabinoid, has recently been shown to promote adult neurogenesis through a mechanism mediated by transient receptor potential cation channel subfamily V member 1 (TRPV1).
This study aimed to investigate the effects of chronic CBDV administration in a female RTT mouse model.
Pre-symptomatic Mecp2tm1.1Bird/J female mice underwent a chronic CBDV treatment (3 mg/kg/day), followed by behavioral tests to assess potential therapeutic effects.
While CBDV did not prevent deficits in locomotor activity, it mitigated motor coordination impairments in RTT mice. Furthermore, the novel object recognition test suggested that CBDV treatment contributed to the preservation of cognitive function in these animals. Moreover, CBDV administration induced genotype-dependent differences in neural stem cell proliferation, indicating a potential vulnerability in adult hippocampal neurogenesis in Mecp2-deficient contexts.
Taken together, these findings provide new insights into the role of CBDV in RTT and support for future research, highlighting its potential as a repurposed therapeutic agent.”
“The data presented in this manuscript demonstrates the therapeutic potential of CBDV in improving behavioral and phenotypic abnormalities in a female mouse model of RTT. Additionally, CBDV differentially affects adult hippocampal neurogenesis in this model.”
“Cannabinoids, particularly Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have gained popularity as alternative sleep aids; however, their effects on sleep architecture and next-day function remain poorly understood.
Here, in a pilot trial, we examined the effects of a single oral dose containing 10 mg THC and 200 mg CBD (THC/CBD) on objective sleep outcomes and next-day alertness using 256-channel high-density EEG in 20 patients with DSM-5 diagnosed insomnia disorder (16 female; mean (SD) age, 46.1 (8.6) years).
We showed that THC/CBD decreased total sleep time (-24.5 min, p = 0.05, d = -0.5) with no change in wake after sleep onset (+10.7 min, p > 0.05) compared to placebo. THC/CBD also significantly decreased time spent in REM sleep (-33.9 min, p < 0.001, d = -1.5) and increased latency to REM sleep (+65.6 min, p = 0.008, d = 0.7). High-density EEG analysis revealed regional decreases in gamma activity during N2 sleep, and in delta activity during N3 sleep, and a regional increase in beta and alpha activity during REM sleep. While there was no observed change in next-day objective alertness, a small but significant increase in self-reported sleepiness was noted with THC/CBD (+0.42 points, p = 0.02, d = 0.22). No changes in subjective sleep quality, cognitive performance, or simulated driving performance were observed.
These findings suggest that a single dose of cannabinoids, particularly THC, may acutely influence sleep, primarily by suppressing REM sleep, without noticeable next-day impairment (≥ 9 h post-treatment).”
“This study is the first to use high-density EEG to explore the acute effects of oral THC/CBD on objective sleep outcomes in individuals with insomnia. A single oral dose significantly reduced total sleep time and REM sleep, without impairing next-day alertness.”
“Endocannabinoid system is an important contributor to body’s immune responses which are significantly impaired by chronic sleep deprivation (cSD). Although cannabinoids can modulate the endocannabinoid system, most are understudied, especially regarding cSD.
To investigate the therapeutic potential of CBD, CBG, CBC and their combinations, current study analyzed cSD-induced memory impairment, depression, microglial responses, cytokine profile and therapeutic effects of cannabinoid treatments using behavioral test and ELISA. Furthermore, molecular docking of these cannabinoids was performed to deduce the binding affinity with cannabinoid receptors and possible entrouge effects.
The results showed that memory impairment and depression were more evident in cSD groups. Moreover, microglial activation and pro-inflammatory polarization was also more evident and was supported by increased pro-inflammatory cytokine concentrations in cSD groups.
These changes were significantly reversed the cannabinoid groups but the combination of CBD + CBC was more effective than other treatments in reversing these cSD-induced behavioral and neuroinflammatory changes. Whereas, the molecular docking results also corroborated with the neuroimmunological changes observed in the current study, pointing towards the possible therapeutic role.
SIGNIFICANCE STATEMENT: Chronic SD employs microglial activation/polarization, to exert behavioral impairments and neuroinflammation.
This study signifies the therapeutic potential of proper sleep and cannabinoid intake.”
“This study demonstrates the therapeutic efficacy of cannabinoid treatments in ameliorating cSD-induced behavioral and neuroinflammatory alterations. Notably, a multiple-compound treatment of CBD and CBC exhibited superior effectiveness compared to single-compound treatments. These findings suggest potential avenues for developing effective interventions against cSD-induced detrimental changes.”
“The American Migraine Foundation estimates that over 39 million Americans and over 1 billion people worldwide suffer from some form of migraine. Treatment of migraine generally falls into two categories: treatment of attacks once they have begun, and prophylactic prevention, including lifestyle changes. The use of phytocannabinoids to reduce both the frequency and severity of migraine is widely documented in scientific, grey, and popular literature. This review provides descriptions of both preclinical and clinical studies involving the treatment of migraines with phytocannabinoids as well as the involvement of endocannabinoids and endocannabinoid-like compounds in migraine pathology, including the receptors and associated mechanisms. Currently unanswered questions and areas for further exploration are discussed.”
“The clinical studies published to date strongly suggest that phytocannabinoids are useful for mitigating migraine pain and for migraine prophylaxis. Further, studies show the potential for endocannabinoid and endocannabinoid-like compounds in migraine treatment.”
“Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.”
“Introduction: Medicinal cannabis has mixed evidence for treating anxiety and depression, yet patients frequently use it as a treatment. This observational study evaluated the effects of medicinal cannabis initiation in adults with clinically significant anxiety and/or depression over a 6-month period.
Methods: Adults with clinically significant anxiety and/or depression initiating medicinal cannabis use in Maryland, USA completed ecological momentary assessment (EMA) and longitudinal follow-up evaluations. Hospital Anxiety and Depression Scale (HADS) assessments were completed at baseline and 1, 3, and 6 months after medicinal cannabis initiation. EMA measures were completed at baseline and daily for 8 weeks after cannabis initiation with measures collected before each cannabis use and at time of expected peak effect. Changes in anxiety and depression were evaluated using linear mixed effect models.
Results: Significant decreases from baseline in anxiety and depression were observed, with mean scores dropping below clinically significant levels within three months of initiation. EMA data indicated that most participants selected THC-dominant cannabis and acute reductions in anxiety, depression, and perceived driving ability along with increased ratings of feeling “high”. Acute effects were dose-dependent: 10-15 mg of oral THC and at least 3 puffs of vaporized cannabis yielded the most robust reductions in anxiety and depression.
Conclusions: Initiation of THC-dominant medicinal cannabis was associated with acute reductions in anxiety and depression, and sustained reductions in overall symptom severity over a 6-month period. Controlled clinical trials are needed to further investigate the efficacy and safety of medicinal cannabis for acute anxiety and depression symptom management.”
“In this prospective, observational study, medicinal cannabis use was associated with significant decreases in self-reported anxiety and depression compared with pre-cannabis use initiation baseline assessments among individuals with clinically significant anxiety and/or depression. Reductions in anxiety and depression were observed acutely following individual episodes of cannabis use and overall symptom reductions were sustained over the six-month period of observation.”
“This study demonstrates the utility of a rat model of chemotherapy-induced peripheral neuropathy (CIPN) to assess the ability of the non-psychoactive cannabinoid cannabidiol (CBD) to modulate the development of this syndrome in vivo. The method utilizes the chemotherapeutic agent paclitaxel to generate an allodynic phenotype in the animals.
This study describes how to handle and solubilize CBD, administer the chemotherapeutic agent, assess mechanical and cold sensitivity, and apply high-speed videography to measure nocifensive behavior in animals.
Using the procedures outlined, the data support that CBD prevents the allodynic phenotype from developing in the treated animals. No difference was observed in the CBD-treated animals from day 0 (pre-paclitaxel baseline) to day 7 (post-sensitization) in mechanical or thermal sensitivity, while the vehicle-treated animals became significantly more sensitive.
This response to treatment is durable up to the latest time point where data were collected (7 weeks). The addition of high-speed videography allows for a more granular and unbiased assessment of this behavioral phenotype (e.g., classification of analgesia and anti-allodynia).
This demonstrates both the utility of this model for cannabinoid drug characterization and the potential role of CBD in mitigating neuropathic pain.”
“Co-administration of CBD with paclitaxel prevents the development of chemotherapy-induced peripheral neuropathy in rats. This protocol describes cannabinoid handling, inducing an allodynic phenotype in rats via chemotherapeutic administration, assessing mechanical and thermal allodynia, and using high-speed videography to distinguish allodynia and hyperalgesia.”
“Endocrine therapy for estrogen receptor-positive (ER+) breast cancer has significantly improved over the last decades. However, it presents some limitations that make the search for novel therapeutic options mandatory.
Several studies have been conducted to understand the anti-tumor potential of cannabinoids in breast cancer. Yet, most of them are focused on the major phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). However, Cannabis has other minor phytocannabinoids whose anti-cancer properties are still to be elucidated.
Here, we investigated the mechanisms of action of four minor cannabinoids, cannabigerol (CBG), cannabidivarin (CBDV), cannabinol (CBN), and cannabichromene (CBC), in 2D and 3D ER+ breast cancer models.
These cannabinoids dysregulate MCF-7aro cell cycle progression, induce apoptosis by different mechanisms, and inhibit the growth of MCF-7aro spheroids. CBG exerts its effects through a down-regulation of both ER and AR protein levels, while CBDV reduces aromatase protein levels. CBN and CBC simultaneously affect the three targets, ER, aromatase, and AR.
In fact, CBN and CBC present an AR-dependent cell death, down-regulate aromatase levels, and act as ER negative regulators impairing cancer cell growth. CBN caused the most pronounced effects.
Overall, this study highlights the anti-cancer properties and the therapeutic potential of these minor cannabinoids in ER+ breast cancer.”
“Cannabinoid regulation of endosomal signalling via innate immune toll-like receptors (TLRs) is understudied. Endosomal cell signalling via TLR7 and TLR8 governs cellular responses to infection with viral and bacterial single-stranded RNA. TLR7/8 activation is associated with neuroinflammation, with inappropriate activation of TLR7/8 linked to the propagation of autoimmune disease. Following activation, TLR7 and TLR8 control the cellular production of cytokines, chemokines and type I interferons (IFNs).
In this study we focused on two clinically relevant plant-derived (phyto) cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), given that cannabinoid-based therapeutics containing these compounds are currently available in the form of sativex® (nabiximols) and epidiolex®. The study aim was to determine the anti-inflammatory effects of CBD and THC, when delivered in isolation and in a sativex-like combination (1:1), on TLR7/8-induced inflammation in immune cells.
We employed the use of CL075 (3M-002), a thiazoloquinolone derivative that acts as an agonist of both TLR7 and TLR8. Using THP-1-derived macrophages and primary peripheral blood mononuclear cells (PBMCs) from healthy control subjects, we demonstrate that TLR7/8 activation promoted the time- and concentration-dependent production of the chemokine CXCL10, cytokine TNFα and type I IFNs in both macrophages and PBMCs. TLR7/8 activation promoted nuclear factor (NF)-κB activation, p38 MAPK phosphorylation and the transcription of interferon regulator factor 7 (IRF7).
We assessed the anti-inflammatory effects of CBD and THC, when delivered alone and in a 1:1 combination, on CL075-stimulated inflammatory mediator production in macrophages/PBMCs. Data presented herein indicate that CBD and THC, particularly when delivered in a 1:1 combination, can act as TLR7/8 immunomodulatory drugs to dampen inflammation in macrophages and PBMCs.
This study provides evidence that phytocannabinoids target TLR7/8-induced viral signalling on endosomal compartments to control inflammation in immune cells.”
“The significant finding is that CBD and THC can differentially ameliorate TLR7/8-induced inflammation in immune cells, depending on whether the cannabinoids are administered alone or in combination. In particular, the 1:1 combination of CBD:THC (at 10 μM) was consistently anti-inflammatory in immune cells stimulated with CL075. The CB1, CB2, PPAR-γ and A2A receptors do not mediate the anti-inflammatory propensity of the phytocannabinoids in our cell models of inflammation.
Overall, data presented herein identifies TLR7/8-mediated inflammation as a phytocannabinoid target, and gives important insight regarding the cellular mechanisms by which CBD and THC regulate inflammation.”
